Innate immune system
Encyclopedia
The innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner. This means that the cells of the innate system recognize and respond to pathogens in a generic way, but unlike the adaptive immune system
, it does not confer long-lasting or protective immunity to the host. Innate immune systems provide immediate defense against infection, and are found in all classes of plant
and animal
life.
The innate immune system is thought to constitute an evolutionarily older defense strategy, and is the dominant immune system found in plant
s, fungi, insect
s, and in primitive multicellular organisms.
The major functions of the vertebrate
innate immune system include:
The epithelial surfaces form a physical barrier that is very impermeable to most infectious agents, acting as the first line of defense against invading organisms. Desquamation
of skin epithelium also helps remove bacteria and other infectious agents that have adhered to the epithelial surfaces. In the gastrointestinal and respiratory tract
, movement due to peristalsis or cilia helps removing infectious agents. Also, mucus
traps infectious agents. The gut flora
can prevent the colonization of pathogenic bacteria by secreting toxic substances or by competing with pathogenic bacteria for nutrients or attachment to cell surfaces. The flushing action of tears and saliva helps prevent infection of the eyes and mouth.
is one of the first responses of the immune system to infection or irritation. Inflammation is stimulated by chemical factors released by injured cells and serves to establish a physical barrier against the spread of infection, and to promote healing of any damaged tissue following the clearance of pathogens.
The process of acute inflammation is initiated by cells already present in all tissues, mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells and mastocytes. These cells present on their surfaces certain receptors named pattern recognition receptor
s (PRRs), which recognize molecules that are broadly shared by pathogen
s but distinguishable from host molecules, collectively referred to as pathogen-associated molecular pattern
s (PAMPs). At the onset of an infection, burn, or other injuries, these cells undergo activation (one of their PRR recognize a PAMP) and release inflammatory mediators responsible for the clinical signs of inflammation.
Chemical factors produced during inflammation (histamine
, bradykinin
, serotonin
, leukotriene
s also prostaglandin
s) sensitize pain receptors, cause vasodilation
of the blood vessel
s at the scene, and attract phagocytes, especially neutrophils. Neutrophils then trigger other parts of the immune system by releasing factors that summon other leukocytes and lymphocytes. Cytokines produced by macrophages and other cells of the innate immune system mediate the inflammatory response. These cytokines include TNF, HMGB1
, and IL-1
.
The inflammatory response is characterized by the following symptom:
redness,
heat,
swelling,
pain, and
possible dysfunction of the organs or tissues involved.
is a biochemical cascade
of the immune system that helps, or “complements”, the ability of antibodies to clear pathogens or mark them for destruction by other cells. The cascade is composed of many plasma proteins, synthesized in the liver
, primarily by hepatocytes. The proteins work together to:
Elements of the complement cascade can be found in many nonmammalian species including plant
s, bird
s, fish
and some species of invertebrate
s.
All white blood cells (WBC) are known as leukocytes. Leukocytes are different from other cells of the body in that they are not tightly associated with a particular organ or tissue; thus, they function similar to independent, single-celled organisms. Leukocytes are able to move freely and interact with and capture cellular debris, foreign particles, or invading microorganisms. Unlike many other cells in the body, most innate immune leukocytes cannot divide or reproduce on their own, but are the products of multipotent hematopoietic stem cells present in the bone marrow.
The innate leukocytes include: Natural killer cells, mast cells, eosinophils, basophils; and the phagocytic cells including macrophages, neutrophils and dendritic cells, and function within the immune system by identifying and eliminating pathogens that might cause infection.
and anaphylaxis
. When activated, mast cells rapidly release characteristic granules, rich in histamine
and heparin
, along with various hormonal mediators, and chemokine
s, or chemotactic cytokine
s into the environment. Histamine dilates blood vessel
s, causing the characteristic signs of inflammation, and recruits neutrophils and macrophages.
which merges with a lysosome
. The lysosome contains enzymes and acids that kill and digest the particle or organism. Phagocytes generally patrol the body searching for pathogens, but are also able to react to a group of highly specialized molecular signals produced by other cells, called cytokines. The phagocytic cells of the immune system include macrophages, neutrophils, and dendritic cells.
Phagocytosis of the hosts’ own cells is common as part of regular tissue development and maintenance. When host cells die, either internally induced by processes involving programmed cell death
(also called apoptosis
), or caused by cell injury due to a bacterial or viral infection, phagocytic cells are responsible for their removal from the affected site. By helping to remove dead cells preceding growth and development of new healthy cells, phagocytosis is an important part of the healing process following tissue injury.
vessels and entering the areas between cells in pursuit of invading pathogens. In tissues, organ-specific macrophages are differentiated from phagocytic cells present in the blood called monocyte
s. Macrophages are the most efficient phagocytes, and can phagocytose substantial numbers of bacteria or other cells or microbes.
The binding of bacterial molecules to receptors on the surface of a macrophage triggers it to engulf and destroy the bacteria through the generation of a “respiratory burst
”, causing the release of reactive oxygen species
. Pathogens also stimulate the macrophage to produce chemokines, which summons other cells to the site of infection.
Neutrophils, along with two other cell types; eosinophils and basophils (see below), are known as granulocyte
s due to the presence of granules in their cytoplasm, or as polymorphonuclear cells (PMNs) due to their distinctive lobed nuclei
. Neutrophil granules contain a variety of toxic substances that kill or inhibit growth of bacteria and fungi. Similar to macrophages, neutrophils attack pathogens by activating a respiratory burst
. The main products of the neutrophil respiratory burst are strong oxidizing agent
s including hydrogen peroxide
, free oxygen radicals and hypochlorite
. Neutrophils are the most abundant type of phagocyte, normally representing 50 to 60% of the total circulating leukocytes, and are usually the first cells to arrive at the site of an infection. The bone marrow of a normal healthy adult produces more than 100 billion neutrophils per day, and more than 10 times that many per day during acute inflammation.
(where they are often called Langerhans cell
s), and the inner mucosal lining of the nose
, lung
s, stomach
and intestine
s. They are named for their resemblance to neuronal dendrite
s, but dendritic cells are not connected to the nervous system
. Dendritic cells are very important in the process of antigen presentation
, and serve as a link between the innate and adaptive immune system
s.
are important in defense against parasites, and play a role in allergic reactions (such as asthma
). Upon activation, eosinophils secrete a range of highly toxic proteins and free radicals that are highly effective in killing bacteria and parasites, but are also responsible for tissue damage occurring during allergic reactions. Activation and toxin release by eosinophils is therefore tightly regulated to prevent any inappropriate tissue destruction.
cells or virus-infected cells, recognizing such cells by a condition known as "missing self." This term describes cells with low levels of a cell-surface marker called MHC I (major histocompatibility complex
) - a situation that can arise in viral infections of host cells. They were named "natural killer" because of the initial notion that they do not require activation in order to kill cells that are "missing self."
s (TCRs), such as CD1d
-restricted Natural Killer T cell
s, γδ T cells exhibit characteristics that place them at the border between innate and adaptive immunity. On one hand, γδ T cells may be considered a component of adaptive immunity
in that they rearrange TCR genes
to produce junctional diversity and develop a memory phenotype. However, the various subsets may also be considered part of the innate immune system where a restricted TCR or NK receptors may be used as a pattern recognition receptor
. For example, according to this paradigm, large numbers of Vγ9/Vδ2 T cells respond within hours to common molecules
produced by microbes, and highly restricted intraepithelial Vδ1 T cells will respond to stressed epithelial cells.
. For example, beta-lysine
, a protein produced by platelets during coagulation
, can cause lysis
of many Gram-positive bacteria by acting as a cationic detergent. Many acute-phase proteins of inflammation
are involved in the coagulation system.
Also increased levels of lactoferrin
and transferrin
inhibit bacterial growth by binding iron, an essential nutrient for bacteria.
is a prototypical neural circuit that controls cytokine production in spleen. Action potentials transmitted via the vagus nerve to spleen mediate the release of acetylcholine, the neurotransmitter which inhibits cytokine release by interacting with alpha7 nicotinic acetylcholine receptors (CHRNA7
) expressed on cytokine-producing cells. The motor arc of the inflammatory reflex is termed the cholinergic anti-inflammatory pathway
.
Evasion strategies that circumvent the innate immune system include intracellular replication, such as in Salmonella
, or a protective capsule that prevents lysis by complement and by phagocytes, as in Mycobacterium tuberculosis
. Bacteroides
species are normally mutualistic bacteria, making up a substantial portion of the mammalian gastrointestinal flora
. Some species (B. fragilis, for example) are opportunistic pathogens
, causing infections of the peritoneal cavity
. These species evade the immune system through inhibition of phagocytosis by affecting the receptors that phagocytes use to engulf bacteria or by mimicking host cells so that the immune system does not recognize them as foreign. Staphylococcus aureus
inhibits the ability of the phagocyte to respond to chemokine signals. Other organisms such as M. tuberculosis, Streptococcus pyogenes
and Bacillus anthracis
utilize mechanisms that directly kill the phagocyte.
Bacteria and fungi may also form complex biofilm
s, providing protection from the cells and proteins of the immune system; recent studies indicate that such biofilms are present in many successful infections, including the chronic Pseudomonas aeruginosa
and Burkholderia cenocepacia
infections characteristic of cystic fibrosis
.
(and perhaps other prokaryotic organisms), utilize a unique defense mechanism, called the restriction modification system
to protect themselves from pathogens, such as bacteriophage
s. In this system, bacteria produce enzyme
s, called restriction endonucleases, that attack and destroy specific regions of the viral DNA
of invading bacteriophages. Methylation
of the host's own DNA marks it as "self" and prevents it from being attacked by endonucleases. Restriction endonucleases and the restriction modification system exist exclusively in prokaryotes.
s do not possess lymphocytes or an antibody-based humoral immune system, and it is likely that a multicomponent, adaptive immune system arose with the first vertebrates. Nevertheless, invertebrates possess mechanisms that appear to be precursors of these aspects of vertebrate immunity. Pattern recognition receptor
s are proteins used by nearly all organisms to identify molecules associated with microbial pathogens. Toll-like receptor
s are a major class of pattern recognition receptor, that exists in all coelomates (animals with a body-cavity), including humans. The complement system
, as discussed above, is a biochemical cascade of the immune system that helps clear pathogens from an organism, and exists in most forms of life. Some invertebrates, including various insects, crab
s, and worm
s utilize a modified form of the complement response known as the prophenoloxidase (proPO) system.
Antimicrobial peptides
are an evolutionarily conserved component of the innate immune response found among all classes of life and represent the main form of invertebrate systemic immunity
. Several species of insect
produce antimicrobial peptides known as defensin
s and cecropin
s.
cascades that degrade proteins and control many of the mechanisms of the innate immune system of invertebrates—including hemolymph
coagulation and melanization. Proteolytic cascades are important components of the invertebrate immune system because they are turned on more rapidly than other innate immune reactions because they do not rely on gene changes. Proteolytic cascades have been found to function the same in both vertebrate and invertebrates, even though different proteins are used throughout the cascades.
s, a gel-like fluid surrounds pathogen invaders, similar to the way blood does in other animals. There are various different proteins and mechanisms that are involved in invertebrate clotting. In crustaceans, transglutaminase
from blood cells and mobile plasma proteins make up the clotting system, where the transglutaminase polymerizes 210 kDa subunits of a plasma clotting protein. On the other hand, in the horseshoe crab species clotting system, components of proteolytic cascades are stored as inactive forms in granules of hemocytes, which are released when foreign molecules, like lipopolysaccharides enter.
. As with animals, plants attacked by insects or other pathogens use a set of complex metabolic responses that lead to the formation of defensive chemical compounds that fight infection or make the plant less attractive to insects and other herbivore
s. (see: plant defense against herbivory
).
Like invertebrates, plants neither generate antibody or T-cell responses nor possess mobile cells that detect and attack pathogens. In addition, in case of infection, parts of some plants are treated as disposable and replaceable, in ways that very few animals are able to do. Walling off or discarding a part of a plant helps stop spread of an infection.
Most plant immune responses involve systemic chemical signals sent throughout a plant. Plants use pattern-recognition receptors to identify pathogens and to start a basal response, which produces chemical signals that aid in warding off infection. When a part of a plant becomes infected with a microbial or viral pathogen, in case of an incompatible interaction triggered by specific elicitors, the plant produces a localized hypersensitive response
(HR), in which cells at the site of infection undergo rapid programmed cell death
to prevent the spread of the disease to other parts of the plant. HR has some similarities to animal pyroptosis
, such as a requirement of caspase
-1-like proteolytic activity of VPEγ, a cysteine protease
that regulates cell disassembly during cell death.
"Resistance" (R) proteins, encoded by R gene
s, are widely present in plants and detect pathogens. These proteins contain domains similar to the NOD Like Receptors and Toll-like receptor
s utilized in animal innate immunity. Systemic acquired resistance
(SAR) is a type of defensive response that renders the entire plant resistant to a broad spectrum of infectious agents. SAR involves the production of chemical messenger
s, such as salicylic acid
or jasmonic acid
. Some of these travel through the plant and signal other cells to produce defensive compounds to protect uninfected parts, e.g., leaves. Salicylic acid itself, although indispensable for expression of SAR, is not the translocated signal responsible for the systemic response. Recent evidence indicates a role for jasmonates in transmission of the signal to distal portions of the plant. RNA silencing
mechanisms are also important in the plant systemic response, as they can block virus replication. The jasmonic acid
response, is stimulated in leaves damaged by insects, and involves the production of methyl jasmonate.
Adaptive immune system
The adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogenic growth. Thought to have arisen in the first jawed vertebrates, the adaptive or "specific" immune system is activated by the “non-specific” and evolutionarily older innate...
, it does not confer long-lasting or protective immunity to the host. Innate immune systems provide immediate defense against infection, and are found in all classes of plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...
and animal
Animal
Animals are a major group of multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and...
life.
The innate immune system is thought to constitute an evolutionarily older defense strategy, and is the dominant immune system found in plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...
s, fungi, insect
Insect
Insects are a class of living creatures within the arthropods that have a chitinous exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae...
s, and in primitive multicellular organisms.
The major functions of the vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
innate immune system include:
- Recruiting immune cells to sites of infection, through the production of chemical factors, including specialized chemical mediators, called cytokineCytokineCytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s. - Activation of the complement cascade to identify bacteria, activate cells and to promote clearance of dead cells or antibody complexesImmune complexAn immune complex is formed from the integral binding of an antibody to a soluble antigen. The bound antigen acting as a specific epitope, bound to an antibody is referred to as a singular immune complex....
. - The identification and removal of foreign substances present in organs, tissues, the blood and lymph, by specialized white blood cells.
- Activation of the adaptive immune systemAdaptive immune systemThe adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogenic growth. Thought to have arisen in the first jawed vertebrates, the adaptive or "specific" immune system is activated by the “non-specific” and evolutionarily older innate...
through a process known as antigen presentationAntigen presentationAntigen presentation is a process in the body's immune system by which macrophages, dendritic cells and other cell types capture antigens and then enable their recognition by T-cells....
. - Acting as a physical and chemical barrier to infectious agents
Anatomical barriers
| Anatomical barrier | Additional defense mechanisms |
|---|---|
| Skin Skin -Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat... |
Sweat, desquamation, flushing, organic acids |
| Gastrointestinal tract Gastrointestinal tract The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. .... |
Peristalsis Peristalsis Peristalsis is a radially symmetrical contraction and relaxation of muscles which propagates in a wave down the muscular tube, in an anterograde fashion. In humans, peristalsis is found in the contraction of smooth muscles to propel contents through the digestive tract. Earthworms use a similar... , gastric acid Gastric acid Gastric acid is a digestive fluid, formed in the stomach. It has a pH of 1 to 2 and is composed of hydrochloric acid , and large quantities of potassium chloride and sodium chloride... , bile acid Bile acid Bile acids are steroid acids found predominantly in the bile of mammals. Bile salts are bile acids compounded with a cation, usually sodium. In humans, the salts of taurocholic acid and glycocholic acid represent approximately eighty percent of all bile salts. The two major bile acids are cholic... s, digestive enzyme Digestive enzyme 'Digestive enzymes' are enzymes that break down polymeric macromolecules into their smaller building blocks, in order to facilitate their absorption by the body. Digestive enzymes are found in the digestive tract of animals where they aid in the digestion of food as well as inside the cells,... , flushing, thiocyanate Thiocyanate Thiocyanate is the anion [SCN]−. It is the conjugate base of thiocyanic acid. Common derivatives include the colourless salts potassium thiocyanate and sodium thiocyanate. Organic compounds containing the functional group SCN are also called thiocyanates... , defensin Defensin Defensins are small cysteine-rich cationic proteins found in both vertebrates and invertebrates. They have also been reported in plants. They are, and function as, host defense peptides. They are active against bacteria, fungi and many enveloped and nonenveloped viruses. They consist of 18-45 amino... s, gut flora Gut flora Gut flora consists of microorganisms that live in the digestive tracts of animals and is the largest reservoir of human flora. In this context, gut is synonymous with intestinal, and flora with microbiota and microflora.... |
| Respiratory airways and lungs | Mucociliary elevator, surfactant Surfactant Surfactants are compounds that lower the surface tension of a liquid, the interfacial tension between two liquids, or that between a liquid and a solid... , defensins |
| Nasopharynx Nasopharynx The nasopharynx is the uppermost part of the pharynx. It extends from the base of the skull to the upper surface of the soft palate; it differs from the oral and laryngeal parts of the pharynx in that its cavity always remains patent .-Lateral:On its lateral wall is the pharyngeal ostium of the... |
Mucus, saliva, lysozyme Lysozyme Lysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase, are glycoside hydrolases, enzymes that damage bacterial cell walls by catalyzing hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between... |
| Eye Human eye The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth... s |
Tears |
The epithelial surfaces form a physical barrier that is very impermeable to most infectious agents, acting as the first line of defense against invading organisms. Desquamation
Desquamation
Desquamation , also called skin peeling, is the shedding of the outermost membrane or layer of a tissue, such as the skin.-Skin:Normal, nonpathologic desquamation of the skin occurs when keratinocytes, after moving apically over about 14 days, are individually shed unnoticeably...
of skin epithelium also helps remove bacteria and other infectious agents that have adhered to the epithelial surfaces. In the gastrointestinal and respiratory tract
Respiratory tract
In humans the respiratory tract is the part of the anatomy involved with the process of respiration.The respiratory tract is divided into 3 segments:*Upper respiratory tract: nose and nasal passages, paranasal sinuses, and throat or pharynx...
, movement due to peristalsis or cilia helps removing infectious agents. Also, mucus
Mucus
In vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. Mucous fluid is typically produced from mucous cells found in mucous glands. Mucous cells secrete products that are rich in glycoproteins and water. Mucous fluid may also originate from mixed glands, which...
traps infectious agents. The gut flora
Gut flora
Gut flora consists of microorganisms that live in the digestive tracts of animals and is the largest reservoir of human flora. In this context, gut is synonymous with intestinal, and flora with microbiota and microflora....
can prevent the colonization of pathogenic bacteria by secreting toxic substances or by competing with pathogenic bacteria for nutrients or attachment to cell surfaces. The flushing action of tears and saliva helps prevent infection of the eyes and mouth.
Inflammation
InflammationInflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
is one of the first responses of the immune system to infection or irritation. Inflammation is stimulated by chemical factors released by injured cells and serves to establish a physical barrier against the spread of infection, and to promote healing of any damaged tissue following the clearance of pathogens.
The process of acute inflammation is initiated by cells already present in all tissues, mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells and mastocytes. These cells present on their surfaces certain receptors named pattern recognition receptor
Pattern recognition receptor
Pattern recognition receptors are a primitive part of the immune system. They are proteins expressed by cells of the innate immune system to identify pathogen-associated molecular patterns , which are associated with microbial pathogens or cellular stress, as well as damage-associated molecular...
s (PRRs), which recognize molecules that are broadly shared by pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
s but distinguishable from host molecules, collectively referred to as pathogen-associated molecular pattern
Pathogen-associated molecular pattern
Pathogen-associated molecular patterns, or PAMPs, are molecules associated with groups of pathogens, that are recognized by cells of the innate immune system. These molecules can be referred to as small molecular motifs conserved within a class of microbes...
s (PAMPs). At the onset of an infection, burn, or other injuries, these cells undergo activation (one of their PRR recognize a PAMP) and release inflammatory mediators responsible for the clinical signs of inflammation.
Chemical factors produced during inflammation (histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
, bradykinin
Bradykinin
Bradykinin is a peptide that causes blood vessels to dilate , and therefore causes blood pressure to lower. A class of drugs called ACE inhibitors, which are used to lower blood pressure, increase bradykinin further lowering blood pressure...
, serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
, leukotriene
Leukotriene
Leukotrienes are fatty signaling molecules. They were first found in leukocytes . One of their roles is to trigger contractions in the smooth muscles lining the trachea; their overproduction is a major cause of inflammation in asthma and allergic rhinitis...
s also prostaglandin
Prostaglandin
A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....
s) sensitize pain receptors, cause vasodilation
Vasodilation
Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
of the blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s at the scene, and attract phagocytes, especially neutrophils. Neutrophils then trigger other parts of the immune system by releasing factors that summon other leukocytes and lymphocytes. Cytokines produced by macrophages and other cells of the innate immune system mediate the inflammatory response. These cytokines include TNF, HMGB1
HMGB1
High-mobility group protein B1, also known as high-mobility group protein 1 and amphoterin, is a protein that in humans is encoded by the HMGB1 gene.HMG-1 belongs to high mobility group.-Role in Inflammation:...
, and IL-1
IL-1
IL-1 may refer to:* Interleukin 1, a protein* Illinois' 1st congressional district* Illinois Route 1* Building 1 of Infinite Loop , the Headquarters of Apple Inc....
.
The inflammatory response is characterized by the following symptom:
redness,
heat,
swelling,
pain, and
possible dysfunction of the organs or tissues involved.
Complement system
The complement systemComplement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
is a biochemical cascade
Biochemical cascade
A biochemical cascade is a series of chemical reactions in which the products of one reaction are consumed in the next reaction. There are several important biochemical cascade reactions in biochemistry, including the enzymatic cascades, such as the coagulation cascade and the complement system,...
of the immune system that helps, or “complements”, the ability of antibodies to clear pathogens or mark them for destruction by other cells. The cascade is composed of many plasma proteins, synthesized in the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, primarily by hepatocytes. The proteins work together to:
- trigger the recruitment of inflammatory cells.
- "tag" pathogens for destruction by other cells by opsonizingOpsoninAn opsonin is any molecule that targets an antigen for an immune response. However, the term is usually used in reference to molecules that act as a binding enhancer for the process of phagocytosis, especially antibodies, which coat the negatively-charged molecules on the membrane. Molecules that...
, or coating, the surface of the pathogen. - forming holes in the plasma membrane of the pathogen, resulting in cytolysisCytolysisCytolysis, or osmotic lysis, occurs when a cell bursts due to an osmotic imbalance that has caused excess water to move into the cell. It occurs in a hypotonic environment, where water diffuses into the cell and causes its volume to increase. If the volume of water exceeds the cell membrane's...
of the pathogen cell, causing the death of the pathogen. - rid the body of neutralized antigen-antibody complexes.
Elements of the complement cascade can be found in many nonmammalian species including plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...
s, bird
Bird
Birds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...
s, fish
Fish
Fish are a paraphyletic group of organisms that consist of all gill-bearing aquatic vertebrate animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish, as well as various extinct related groups...
and some species of invertebrate
Invertebrate
An invertebrate is an animal without a backbone. The group includes 97% of all animal species – all animals except those in the chordate subphylum Vertebrata .Invertebrates form a paraphyletic group...
s.
Cells of the innate immune response
The innate leukocytes include: Natural killer cells, mast cells, eosinophils, basophils; and the phagocytic cells including macrophages, neutrophils and dendritic cells, and function within the immune system by identifying and eliminating pathogens that might cause infection.
Mast cells
Mast cells are a type of innate immune cell that reside in connective tissue and in the mucous membranes. They are intimately associated with defense against pathogens and wound healing, but are also often associated with allergyAllergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
and anaphylaxis
Anaphylaxis
Anaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
. When activated, mast cells rapidly release characteristic granules, rich in histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
and heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
, along with various hormonal mediators, and chemokine
Chemokine
Chemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...
s, or chemotactic cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s into the environment. Histamine dilates blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s, causing the characteristic signs of inflammation, and recruits neutrophils and macrophages.
Phagocytes
The word 'phagocyte' literally means 'eating cell'. These are immune cells that engulf, i.e. phagocytose, pathogens or particles. To engulf a particle or pathogen, a phagocyte extends portions of its plasma membrane, wrapping the membrane around the particle until it is enveloped (i.e. the particle is now inside the cell). Once inside the cell, the invading pathogen is contained inside an endosomeEndosome
In biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway from the plasma membrane to the lysosome. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for...
which merges with a lysosome
Lysosome
thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...
. The lysosome contains enzymes and acids that kill and digest the particle or organism. Phagocytes generally patrol the body searching for pathogens, but are also able to react to a group of highly specialized molecular signals produced by other cells, called cytokines. The phagocytic cells of the immune system include macrophages, neutrophils, and dendritic cells.
Phagocytosis of the hosts’ own cells is common as part of regular tissue development and maintenance. When host cells die, either internally induced by processes involving programmed cell death
Programmed cell death
Programmed cell-death is death of a cell in any form, mediated by an intracellular program. PCD is carried out in a regulated process which generally confers advantage during an organism's life-cycle...
(also called apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
), or caused by cell injury due to a bacterial or viral infection, phagocytic cells are responsible for their removal from the affected site. By helping to remove dead cells preceding growth and development of new healthy cells, phagocytosis is an important part of the healing process following tissue injury.
Macrophages
Macrophages, from the serbian, meaning "large eaters," are large phagocytic leukocytes, which are able to move outside of the vascular system by moving across the cell membrane of capillaryCapillary
Capillaries are the smallest of a body's blood vessels and are parts of the microcirculation. They are only 1 cell thick. These microvessels, measuring 5-10 μm in diameter, connect arterioles and venules, and enable the exchange of water, oxygen, carbon dioxide, and many other nutrient and waste...
vessels and entering the areas between cells in pursuit of invading pathogens. In tissues, organ-specific macrophages are differentiated from phagocytic cells present in the blood called monocyte
Monocyte
Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...
s. Macrophages are the most efficient phagocytes, and can phagocytose substantial numbers of bacteria or other cells or microbes.
The binding of bacterial molecules to receptors on the surface of a macrophage triggers it to engulf and destroy the bacteria through the generation of a “respiratory burst
Respiratory burst
Respiratory burst is the rapid release of reactive oxygen species from different types of cells....
”, causing the release of reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
. Pathogens also stimulate the macrophage to produce chemokines, which summons other cells to the site of infection.
Neutrophils
Granulocyte
Granulocytes are a category of white blood cells characterized by the presence of granules in their cytoplasm. They are also called polymorphonuclear leukocytes because of the varying shapes of the nucleus, which is usually lobed into three segments...
s due to the presence of granules in their cytoplasm, or as polymorphonuclear cells (PMNs) due to their distinctive lobed nuclei
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
. Neutrophil granules contain a variety of toxic substances that kill or inhibit growth of bacteria and fungi. Similar to macrophages, neutrophils attack pathogens by activating a respiratory burst
Respiratory burst
Respiratory burst is the rapid release of reactive oxygen species from different types of cells....
. The main products of the neutrophil respiratory burst are strong oxidizing agent
Oxidizing agent
An oxidizing agent can be defined as a substance that removes electrons from another reactant in a redox chemical reaction...
s including hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...
, free oxygen radicals and hypochlorite
Hypochlorite
The hypochlorite ion, also known as chlorate anion is ClO−. A hypochlorite compound is a chemical compound containing this group, with chlorine in oxidation state +1.Hypochlorites are the salts of hypochlorous acid...
. Neutrophils are the most abundant type of phagocyte, normally representing 50 to 60% of the total circulating leukocytes, and are usually the first cells to arrive at the site of an infection. The bone marrow of a normal healthy adult produces more than 100 billion neutrophils per day, and more than 10 times that many per day during acute inflammation.
Dendritic cells
Dendritic cells (DC) are phagocytic cells present in tissues that are in contact with the external environment, mainly the skinHuman skin
The human skin is the outer covering of the body. In humans, it is the largest organ of the integumentary system. The skin has multiple layers of ectodermal tissue and guards the underlying muscles, bones, ligaments and internal organs. Human skin is similar to that of most other mammals,...
(where they are often called Langerhans cell
Langerhans cell
Langerhans cells are dendritic cells of the skin and mucosa, and contain large granules called Birbeck granules. They are present in all layers of the epidermis, but are most prominant in the stratum spinosum. They also occur in the papillary dermis, particularly around blood vessels, as well as...
s), and the inner mucosal lining of the nose
Human nose
The visible part of the human nose is the protruding part of the face that bears the nostrils. The shape of the nose is determined by the ethmoid bone and the nasal septum, which consists mostly of cartilage and which separates the nostrils...
, lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s, stomach
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
and intestine
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...
s. They are named for their resemblance to neuronal dendrite
Dendrite
Dendrites are the branched projections of a neuron that act to conduct the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project...
s, but dendritic cells are not connected to the nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
. Dendritic cells are very important in the process of antigen presentation
Antigen presentation
Antigen presentation is a process in the body's immune system by which macrophages, dendritic cells and other cell types capture antigens and then enable their recognition by T-cells....
, and serve as a link between the innate and adaptive immune system
Adaptive immune system
The adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogenic growth. Thought to have arisen in the first jawed vertebrates, the adaptive or "specific" immune system is activated by the “non-specific” and evolutionarily older innate...
s.
Basophils and eosinophils
Basophils and eosinophils are cells related to the neutrophil (see above). When activated by a pathogen encounter, basophils releasing histamineHistamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
are important in defense against parasites, and play a role in allergic reactions (such as asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
). Upon activation, eosinophils secrete a range of highly toxic proteins and free radicals that are highly effective in killing bacteria and parasites, but are also responsible for tissue damage occurring during allergic reactions. Activation and toxin release by eosinophils is therefore tightly regulated to prevent any inappropriate tissue destruction.
Natural killer cells
Natural killer cells, or NK cells, are a component of the innate immune system which does not directly attack invading microbes. Rather, NK cells destroy compromised host cells, such as tumorTumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
cells or virus-infected cells, recognizing such cells by a condition known as "missing self." This term describes cells with low levels of a cell-surface marker called MHC I (major histocompatibility complex
Major histocompatibility complex
Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
) - a situation that can arise in viral infections of host cells. They were named "natural killer" because of the initial notion that they do not require activation in order to kill cells that are "missing self."
γδ T cells
Like other 'unconventional' T cell subsets bearing invariant T cell receptorT cell receptor
The T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is responsible for recognizing antigens bound to major histocompatibility complex molecules...
s (TCRs), such as CD1d
CD1d receptor
CD1d is a member of the CD1 family of glycoproteins expressed on the surface of various human antigen-presenting cells. They are related to the class I MHC molecules, and are involved in the presentation of lipid antigens to T cells...
-restricted Natural Killer T cell
Natural Killer T cell
Natural killer T cells are a heterogeneous group of T cells that share properties of both T cells and natural killer cells. Many of these cells recognize the non-polymorphic CD1d molecule, an antigen-presenting molecule that binds self- and foreign lipids and glycolipids...
s, γδ T cells exhibit characteristics that place them at the border between innate and adaptive immunity. On one hand, γδ T cells may be considered a component of adaptive immunity
Adaptive immune system
The adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogenic growth. Thought to have arisen in the first jawed vertebrates, the adaptive or "specific" immune system is activated by the “non-specific” and evolutionarily older innate...
in that they rearrange TCR genes
V(D)J recombination
VJ recombination, also known as somatic recombination, is a mechanism of genetic recombination in the early stages of immunoglobulin and T cell receptors production of the immune system...
to produce junctional diversity and develop a memory phenotype. However, the various subsets may also be considered part of the innate immune system where a restricted TCR or NK receptors may be used as a pattern recognition receptor
Pattern recognition receptor
Pattern recognition receptors are a primitive part of the immune system. They are proteins expressed by cells of the innate immune system to identify pathogen-associated molecular patterns , which are associated with microbial pathogens or cellular stress, as well as damage-associated molecular...
. For example, according to this paradigm, large numbers of Vγ9/Vδ2 T cells respond within hours to common molecules
Non-peptidic antigen
Non-peptidic antigens are low-molecular-weight compounds that stimulate human Vγ9/Vδ2 T cells. The most potent activator for Vγ9/Vδ2 T cells is -4-hydroxy-3-methyl-but-2-enyl pyrophosphate , a natural intermediate of the non-mevalonate pathway of isopentenyl pyrophosphate biosynthesis...
produced by microbes, and highly restricted intraepithelial Vδ1 T cells will respond to stressed epithelial cells.
Other vertebrate mechanisms
The coagulation system overlaps with the immune system. Some products of the coagulation system can contribute to the non-specific defenses by their ability to increase vascular permeability and act as chemotactic agents for phagocytic cells. In addition, some of the products of the coagulation system are directly antimicrobialAntimicrobial
An anti-microbial is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoans. Antimicrobial drugs either kill microbes or prevent the growth of microbes...
. For example, beta-lysine
Beta-lysine
Beta-lysine is an amino acid produced by platelets during coagulation and is directly antibacterial by causing lysis of many Gram positive bacteria by acting as a cationic detergent....
, a protein produced by platelets during coagulation
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
, can cause lysis
Lysis
Lysis refers to the breaking down of a cell, often by viral, enzymic, or osmotic mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a "lysate"....
of many Gram-positive bacteria by acting as a cationic detergent. Many acute-phase proteins of inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
are involved in the coagulation system.
Also increased levels of lactoferrin
Lactoferrin
Lactoferrin , also known as lactotransferrin , is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, such as milk, saliva, tears, and nasal secretions...
and transferrin
Transferrin
Transferrins are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. In humans, it is encoded by the TF gene.Transferrin is a glycoprotein that binds iron very tightly but reversibly...
inhibit bacterial growth by binding iron, an essential nutrient for bacteria.
Neural regulation of innate immunity
The innate immune response to infectious and sterile injury is modulated by neural circuits that control cytokine production. The Inflammatory ReflexInflammatory reflex
The inflammatory reflex is a neural circuit that regulates the immune response to injury and invasion. All reflexes have an afferent and efferent arc. The Inflammatory reflex has a sensory, afferent arc, which is activated by cytokines, and a motor, or efferent arc, which transmits action...
is a prototypical neural circuit that controls cytokine production in spleen. Action potentials transmitted via the vagus nerve to spleen mediate the release of acetylcholine, the neurotransmitter which inhibits cytokine release by interacting with alpha7 nicotinic acetylcholine receptors (CHRNA7
CHRNA7
Neuronal acetylcholine receptor subunit alpha-7 is a protein that in humans is encoded by the CHRNA7 gene.-See also:* Alpha-7 nicotinic receptor* Nicotinic acetylcholine receptor* Acetylcholine receptor...
) expressed on cytokine-producing cells. The motor arc of the inflammatory reflex is termed the cholinergic anti-inflammatory pathway
Cholinergic anti-inflammatory pathway
The Cholinergic Anti-inflammatory Pathway regulates the innate immune response to injury, pathogens, and tissue ischemia. It is the efferent, or motor arm of the Inflammatory Reflex, the neural circuit that responds to and regulates the inflammatory response.- Regulating the Immune Response :For...
.
Pathogen-specificity
The parts of the innate immune system have different specificity for different pathogens.| Pathogen | Main examples | Phagocytosis | complement Complement system The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime... | NK cells |
|---|---|---|---|---|
| Intracellular and cytoplasmic virus Virus A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea... |
|
yes | no | yes |
| Intracellular bacteria Bacteria Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals... |
Legionella Legionella is a pathogenic Gram negative bacterium, including species that cause legionellosis or Legionnaires' disease, most notably L. pneumophila. It may be readily visualized with a silver stain.... Mycobacterium Mycobacterium is a genus of Actinobacteria, given its own family, the Mycobacteriaceae. The genus includes pathogens known to cause serious diseases in mammals, including tuberculosis and leprosy... Rickettsia Rickettsia is a genus of non-motile, Gram-negative, non-sporeforming, highly pleomorphic bacteria that can present as cocci , rods or thread-like . Being obligate intracellular parasites, the Rickettsia survival depends on entry, growth, and replication within the cytoplasm of eukaryotic host cells... |
yes (specifically neutrophils, no for rickettsia) | no | yes (no for rickettsia) |
| Extracellular bacteria Bacteria Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals... |
Staphylococcus Staphylococcus is a genus of Gram-positive bacteria. Under the microscope they appear round , and form in grape-like clusters.... Streptococcus Streptococcus is a genus of spherical Gram-positive bacteria belonging to the phylum Firmicutes and the lactic acid bacteria group. Cellular division occurs along a single axis in these bacteria, and thus they grow in chains or pairs, hence the name — from Greek στρεπτος streptos, meaning... Neisseria The Neisseria is a large genus of commensal bacteria that colonize the mucosal surfaces of many animals. Of the 11 species that colonize humans, only two are pathogens. N. meningitidis and N. gonorrhoeae often cause asymptomatic infections, a commensal-like behavior... |
yes | yes | no |
| Intracellular protozoa Protozoa Protozoa are a diverse group of single-cells eukaryotic organisms, many of which are motile. Throughout history, protozoa have been defined as single-cell protists with animal-like behavior, e.g., movement... |
Plasmodium malariae Plasmodium malariae is a parasitic protozoa that causes malaria in humans. It is closely related to Plasmodium falciparum and Plasmodium vivax which are responsible for most malarial infection. While found worldwide, it is a so-called "benign malaria" and is not nearly as dangerous as that... Leishmania Leishmania is a genus of Trypanosomatid protozoa, and is the parasite responsible for the disease leishmaniasis. It is spread through sandflies of the genus Phlebotomus in the Old World, and of the genus Lutzomyia in the New World. Their primary hosts are vertebrates; Leishmania commonly infects... |
no | no | no |
| Extracellular protozoa Protozoa Protozoa are a diverse group of single-cells eukaryotic organisms, many of which are motile. Throughout history, protozoa have been defined as single-cell protists with animal-like behavior, e.g., movement... |
Entamoeba histolytica Entamoeba histolytica is an anaerobic parasitic protozoan, part of the genus Entamoeba. Predominantly infecting humans and other primates, E. histolytica is estimated to infect about 50 million people worldwide... Giardia lamblia Giardia lamblia is a flagellated protozoan parasite that colonizes and reproduces in the small intestine, causing giardiasis. The giardia parasite attaches to the epithelium by a ventral adhesive disc, and reproduces via binary fission... |
yes | yes | no |
| Extracellular fungi |
Candida (genus) Candida is a genus of yeasts. Many species are harmless commensals or endosymbionts of animal hosts including humans, but other species, or harmless species in the wrong location, can cause disease. Candida albicans can cause infections in humans and other animals, especially in immunocompromised... Histoplasma Histoplasma is a genus of dimorphic fungi commonly found in bird and bat fecal material. Histoplasma contains a few species, including—H. capsulatum—the causative agent of histoplasmosis; and Histoplasma capsulatum var. farciminosum , causing epizootic lymphangitis in horses... Cryptococcus Cryptococcus is a genus of fungus. Species grow in culture as yeasts. The perfect forms or teleomorphs of Cryptococcus species are filamentous fungi in the genus Filobasidiella... |
no | yes | no |
Innate immune evasion
Cells of the innate immune system effectively prevent free growth of bacteria within the body; however, many pathogens have evolved mechanisms allowing them to evade the innate immune system.Evasion strategies that circumvent the innate immune system include intracellular replication, such as in Salmonella
Salmonella
Salmonella is a genus of rod-shaped, Gram-negative, non-spore-forming, predominantly motile enterobacteria with diameters around 0.7 to 1.5 µm, lengths from 2 to 5 µm, and flagella which grade in all directions . They are chemoorganotrophs, obtaining their energy from oxidation and reduction...
, or a protective capsule that prevents lysis by complement and by phagocytes, as in Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
. Bacteroides
Bacteroides
Bacteroides is a genus of Gram-negative, bacillus bacteria. Bacteroides species are non-endospore-forming, anaerobes, and may be either motile or non-motile, depending on the species. The DNA base composition is 40-48% GC. Unusual in bacterial organisms, Bacteroides membranes contain sphingolipids...
species are normally mutualistic bacteria, making up a substantial portion of the mammalian gastrointestinal flora
Gut flora
Gut flora consists of microorganisms that live in the digestive tracts of animals and is the largest reservoir of human flora. In this context, gut is synonymous with intestinal, and flora with microbiota and microflora....
. Some species (B. fragilis, for example) are opportunistic pathogens
Opportunistic infection
An opportunistic infection is an infection caused by pathogens, particularly opportunistic pathogens—those that take advantage of certain situations—such as bacterial, viral, fungal or protozoan infections that usually do not cause disease in a healthy host, one with a healthy immune system...
, causing infections of the peritoneal cavity
Peritoneal cavity
The peritoneal cavity is a potential space between the parietal peritoneum and visceral peritoneum, that is, the two membranes that separate the organs in the abdominal cavity from the abdominal wall...
. These species evade the immune system through inhibition of phagocytosis by affecting the receptors that phagocytes use to engulf bacteria or by mimicking host cells so that the immune system does not recognize them as foreign. Staphylococcus aureus
Staphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
inhibits the ability of the phagocyte to respond to chemokine signals. Other organisms such as M. tuberculosis, Streptococcus pyogenes
Streptococcus pyogenes
Streptococcus pyogenes is a spherical, Gram-positive bacterium that is the cause of group A streptococcal infections. S. pyogenes displays streptococcal group A antigen on its cell wall. S...
and Bacillus anthracis
Bacillus anthracis
Bacillus anthracis is the pathogen of the Anthrax acute disease. It is a Gram-positive, spore-forming, rod-shaped bacterium, with a width of 1-1.2µm and a length of 3-5µm. It can be grown in an ordinary nutrient medium under aerobic or anaerobic conditions.It is one of few bacteria known to...
utilize mechanisms that directly kill the phagocyte.
Bacteria and fungi may also form complex biofilm
Biofilm
A biofilm is an aggregate of microorganisms in which cells adhere to each other on a surface. These adherent cells are frequently embedded within a self-produced matrix of extracellular polymeric substance...
s, providing protection from the cells and proteins of the immune system; recent studies indicate that such biofilms are present in many successful infections, including the chronic Pseudomonas aeruginosa
Pseudomonas aeruginosa
Pseudomonas aeruginosa is a common bacterium that can cause disease in animals, including humans. It is found in soil, water, skin flora, and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also in hypoxic atmospheres, and has, thus, colonized many...
and Burkholderia cenocepacia
Burkholderia cenocepacia
Burkholderia cenocepacia is a species of Gram-negative bacteria that is common in the environment and may cause disease in plants. It is an opportunistic pathogen and human infections are common in patients with cystic fibrosis and chronic granulomatous disease, and are often fatal...
infections characteristic of cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
.
Host defense in prokaryotes
BacteriaBacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
(and perhaps other prokaryotic organisms), utilize a unique defense mechanism, called the restriction modification system
Restriction modification system
The restriction modification system is used by bacteria, and perhaps other prokaryotic organisms to protect themselves from foreign DNA, such as the one borne by bacteriophages. This phenomenon was first noticed in the 1950s. Certain bacteria strains were found to inhibit the growth of viruses...
to protect themselves from pathogens, such as bacteriophage
Bacteriophage
A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid...
s. In this system, bacteria produce enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s, called restriction endonucleases, that attack and destroy specific regions of the viral DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
of invading bacteriophages. Methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
of the host's own DNA marks it as "self" and prevents it from being attacked by endonucleases. Restriction endonucleases and the restriction modification system exist exclusively in prokaryotes.
Host defense in invertebrates
InvertebrateInvertebrate
An invertebrate is an animal without a backbone. The group includes 97% of all animal species – all animals except those in the chordate subphylum Vertebrata .Invertebrates form a paraphyletic group...
s do not possess lymphocytes or an antibody-based humoral immune system, and it is likely that a multicomponent, adaptive immune system arose with the first vertebrates. Nevertheless, invertebrates possess mechanisms that appear to be precursors of these aspects of vertebrate immunity. Pattern recognition receptor
Pattern recognition receptor
Pattern recognition receptors are a primitive part of the immune system. They are proteins expressed by cells of the innate immune system to identify pathogen-associated molecular patterns , which are associated with microbial pathogens or cellular stress, as well as damage-associated molecular...
s are proteins used by nearly all organisms to identify molecules associated with microbial pathogens. Toll-like receptor
Toll-like receptor
Toll-like receptors are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors that recognize structurally conserved molecules derived from microbes...
s are a major class of pattern recognition receptor, that exists in all coelomates (animals with a body-cavity), including humans. The complement system
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
, as discussed above, is a biochemical cascade of the immune system that helps clear pathogens from an organism, and exists in most forms of life. Some invertebrates, including various insects, crab
Crab
True crabs are decapod crustaceans of the infraorder Brachyura, which typically have a very short projecting "tail" , or where the reduced abdomen is entirely hidden under the thorax...
s, and worm
Worm
The term worm refers to an obsolete taxon used by Carolus Linnaeus and Jean-Baptiste Lamarck for all non-arthropod invertebrate animals, and stems from the Old English word wyrm. Currently it is used to describe many different distantly-related animals that typically have a long cylindrical...
s utilize a modified form of the complement response known as the prophenoloxidase (proPO) system.
Antimicrobial peptides
Antimicrobial peptides
Antimicrobial peptides are an evolutionarily conserved component of the innate immune response and are found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for antimicrobial peptides...
are an evolutionarily conserved component of the innate immune response found among all classes of life and represent the main form of invertebrate systemic immunity
Immunity (medical)
Immunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involves both specific and non-specific components. The non-specific components act either as barriers or as eliminators of wide...
. Several species of insect
Insect
Insects are a class of living creatures within the arthropods that have a chitinous exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae...
produce antimicrobial peptides known as defensin
Defensin
Defensins are small cysteine-rich cationic proteins found in both vertebrates and invertebrates. They have also been reported in plants. They are, and function as, host defense peptides. They are active against bacteria, fungi and many enveloped and nonenveloped viruses. They consist of 18-45 amino...
s and cecropin
Cecropin
Cecropins are antimicrobial peptides. They were first isolated from the hemolymph of Hyalophora cecropia, from whence the term cecropin was derived. Cecropins lyse bacterial cell membranes; they also inhibit proline uptake and cause leaky membranes....
s.
Proteolytic cascades
In invertebrates, pattern recognition proteins (PRPs) trigger proteolyticProteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
cascades that degrade proteins and control many of the mechanisms of the innate immune system of invertebrates—including hemolymph
Hemolymph
Hemolymph, or haemolymph, is a fluid in the circulatory system of some arthropods and is analogous to the fluids and cells making up both blood and interstitial fluid in vertebrates such as birds and mammals...
coagulation and melanization. Proteolytic cascades are important components of the invertebrate immune system because they are turned on more rapidly than other innate immune reactions because they do not rely on gene changes. Proteolytic cascades have been found to function the same in both vertebrate and invertebrates, even though different proteins are used throughout the cascades.
Clotting mechanisms
In the hemolymph, which makes up the fluid in the circulatory system of arthropodArthropod
An arthropod is an invertebrate animal having an exoskeleton , a segmented body, and jointed appendages. Arthropods are members of the phylum Arthropoda , and include the insects, arachnids, crustaceans, and others...
s, a gel-like fluid surrounds pathogen invaders, similar to the way blood does in other animals. There are various different proteins and mechanisms that are involved in invertebrate clotting. In crustaceans, transglutaminase
Transglutaminase
Transglutaminases are a family of enzymes that catalyze the formation of a covalent bond between a free amine group and the gamma-carboxamid group of protein- or peptide-bound glutamine. Bonds formed by transglutaminase exhibit high resistance to proteolytic degradation.Transglutaminases were...
from blood cells and mobile plasma proteins make up the clotting system, where the transglutaminase polymerizes 210 kDa subunits of a plasma clotting protein. On the other hand, in the horseshoe crab species clotting system, components of proteolytic cascades are stored as inactive forms in granules of hemocytes, which are released when foreign molecules, like lipopolysaccharides enter.
Host defense in plants
Members of every class of pathogen which infect humans also infect plants. Although the exact pathogenic species vary with the infected species, bacteria, fungi, viruses, nematodes and insects can all cause plant diseasePhytopathology
Plant pathology is the scientific study of plant diseases caused by pathogens and environmental conditions . Organisms that cause infectious disease include fungi, oomycetes, bacteria, viruses, viroids, virus-like organisms, phytoplasmas, protozoa, nematodes and parasitic plants...
. As with animals, plants attacked by insects or other pathogens use a set of complex metabolic responses that lead to the formation of defensive chemical compounds that fight infection or make the plant less attractive to insects and other herbivore
Herbivore
Herbivores are organisms that are anatomically and physiologically adapted to eat plant-based foods. Herbivory is a form of consumption in which an organism principally eats autotrophs such as plants, algae and photosynthesizing bacteria. More generally, organisms that feed on autotrophs in...
s. (see: plant defense against herbivory
Plant defense against herbivory
Plant defense against herbivory or host-plant resistance describes a range of adaptations evolved by plants which improve their survival and reproduction by reducing the impact of herbivores. Plants use several strategies to defend against damage caused by herbivores...
).
Like invertebrates, plants neither generate antibody or T-cell responses nor possess mobile cells that detect and attack pathogens. In addition, in case of infection, parts of some plants are treated as disposable and replaceable, in ways that very few animals are able to do. Walling off or discarding a part of a plant helps stop spread of an infection.
Most plant immune responses involve systemic chemical signals sent throughout a plant. Plants use pattern-recognition receptors to identify pathogens and to start a basal response, which produces chemical signals that aid in warding off infection. When a part of a plant becomes infected with a microbial or viral pathogen, in case of an incompatible interaction triggered by specific elicitors, the plant produces a localized hypersensitive response
Hypersensitive response
The hypersensitive response is a mechanism, used by plants, to prevent the spread of infection by microbial pathogens. The HR is characterized by the rapid death of cells in the local region surrounding an infection. The HR serves to restrict the growth and spread of pathogens to other parts of...
(HR), in which cells at the site of infection undergo rapid programmed cell death
Programmed cell death
Programmed cell-death is death of a cell in any form, mediated by an intracellular program. PCD is carried out in a regulated process which generally confers advantage during an organism's life-cycle...
to prevent the spread of the disease to other parts of the plant. HR has some similarities to animal pyroptosis
Pyroptosis
Pyroptosis is a form of programmed cell death associated with antimicrobial responses during inflammation. In contrast to apoptosis, pyroptosis requires the function of caspase-1, and has been studied in the context of salmonella-infected macrophages....
, such as a requirement of caspase
Caspase
Caspases, or cysteine-aspartic proteases or cysteine-dependent aspartate-directed proteases are a family of cysteine proteases that play essential roles in apoptosis , necrosis, and inflammation....
-1-like proteolytic activity of VPEγ, a cysteine protease
Cysteine protease
Proteases are enzymes that degrade polypeptides. Cysteine proteases have a common catalytic mechanism that involves a nucleophilic cysteine thiol in a catalytic dyad. The first step is deprotonation of a thiol in the enzyme's active site by an adjacent amino acid with a basic side chain, usually a...
that regulates cell disassembly during cell death.
"Resistance" (R) proteins, encoded by R gene
R gene
Resistance genes are genes in plant genomes that convey plant disease resistance against pathogens by producing R proteins. The main class of R-genes consist of a nucleotide binding domain and a leucine rich repeat domain and are often referred to as R-genes. Generally, the NB domain binds...
s, are widely present in plants and detect pathogens. These proteins contain domains similar to the NOD Like Receptors and Toll-like receptor
Toll-like receptor
Toll-like receptors are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors that recognize structurally conserved molecules derived from microbes...
s utilized in animal innate immunity. Systemic acquired resistance
Systemic acquired resistance
The systemic acquired resistance is a "whole-plant" resistance response that occurs following an earlier localized exposure to a pathogen. SAR is analogous to the innate immune system found in animals, and there is evidence that SAR in plants and innate immunity in animals may be evolutionarily...
(SAR) is a type of defensive response that renders the entire plant resistant to a broad spectrum of infectious agents. SAR involves the production of chemical messenger
Chemical messenger
A chemical messenger is any compound that serves to transmit a message.A chemical messenger may refer to:*Hormone, Long range chemical messenger*Neurotransmitter, communicates to adjacent cells...
s, such as salicylic acid
Salicylic acid
Salicylic acid is a monohydroxybenzoic acid, a type of phenolic acid and a beta hydroxy acid. This colorless crystalline organic acid is widely used in organic synthesis and functions as a plant hormone. It is derived from the metabolism of salicin...
or jasmonic acid
Jasmonic acid
Jasmonic acid is derived from the fatty acid linolenic acid. It is a member of the jasmonate class of plant hormones. It is biosynthesized from linolenic acid by the octadecanoid pathway....
. Some of these travel through the plant and signal other cells to produce defensive compounds to protect uninfected parts, e.g., leaves. Salicylic acid itself, although indispensable for expression of SAR, is not the translocated signal responsible for the systemic response. Recent evidence indicates a role for jasmonates in transmission of the signal to distal portions of the plant. RNA silencing
RNA interference
RNA interference is a process within living cells that moderates the activity of their genes. Historically, it was known by other names, including co-suppression, post transcriptional gene silencing , and quelling. Only after these apparently unrelated processes were fully understood did it become...
mechanisms are also important in the plant systemic response, as they can block virus replication. The jasmonic acid
Jasmonic acid
Jasmonic acid is derived from the fatty acid linolenic acid. It is a member of the jasmonate class of plant hormones. It is biosynthesized from linolenic acid by the octadecanoid pathway....
response, is stimulated in leaves damaged by insects, and involves the production of methyl jasmonate.