Humoral immunity
Encyclopedia
The Humoral Immune Response (HIR) is the aspect of immunity
that is mediated by secreted antibodies (as opposed to cell-mediated immunity
, which involves T lymphocytes) produced in the cells of the B lymphocyte
lineage (B cell
). B Cells (with co-stimulation) transform into plasma cells which secrete antibodies. The co-stimulation of the B cell can come from another antigen presenting cell, like a dendritic cell
. This entire process is aided by CD4+ T-helper 2 cells, which provide co-stimulation. Secreted antibodies bind to antigen
s on the surfaces of invading microbes (such as viruses or bacteria), which flags them for destruction. Humoral immunity is so named because it involves substances found in the humours
, or body fluids.
The study of the molecular and cellular components that comprise the immune system
, including their function and interaction, is the central science of immunology
. The immune system is divided into a more primitive innate immune system
, and acquired or adaptive immune system
of vertebrates, each of which contains humoral and cellular components.
Humoral immunity refers to antibody production and the accessory processes that accompany it, including: Th2 activation and cytokine
production, germinal center
formation and isotype
switching, affinity maturation
and memory cell
generation. It also refers to the effector
functions of antibody, which include pathogen and toxin neutralization, classical complement
activation, and opsonin
promotion of phagocytosis and pathogen elimination.
, were shown to be the soluble components of the innate response that lead to a combination of cellular and humoral immunity, and bridged the features of innate and acquired immunity.
Following the 1888 discovery of diphtheria
and tetanus
, Emil von Behring and Kitasato Shibasaburō
showed that disease need not be caused by microorganisms themselves. They discovered that cell-free filtrates were sufficient to cause disease. In 1890, filtrates of diphtheria (later named diphtheria toxin
s) were used to immunize
animals in an attempt to demonstrate that immunized serum contained an antitoxin
that could neutralize the activity of the toxin and could transfer immunity to non immune animals. In 1897, Paul Ehrlich showed that antibodies form against the plant toxins ricin
and abrin
, and proposed that these antibodies are responsible for immunity. Ehrlich, with his friend Emil von Behring, went on to develop the diphtheria antitoxin, which became the first major success of modern immunotherapy
. The presence and specificity of compability antibodies became the major tool for standardizing the state of immunity
and identifying the presence of previous infections.
Activation of this system leads to cytolysis
, chemotaxis
, opsonization, immune clearance, and inflammation
, as well as the marking of pathogens for phagocytosis. The proteins account for 5% of the serum
globulin
fraction. Most of these proteins circulate as zymogen
s, which are inactive until proteolytic cleavage.
Three biochemical pathways activate the complement system: the classical complement pathway
, the alternate complement pathway, and the mannose-binding lectin pathway.
The classical complement pathway typically requires antibodies for activation and is a specific immune response, while the alternate pathway can be activated without the presence of antibodies and is considered a non-specific immune response. Antibodies, in particular the IgG1 class, can also "fix" complement.
An antibody is used by the acquired immune system to identify and neutralize foreign objects like bacteria and viruses. Each antibody recognizes a specific antigen unique to its target. By binding their specific antigens, antibodies can cause agglutination
and precipitation of antibody-antigen products, prime for phagocytosis by macrophages and other cells, block viral
receptors, and stimulate other immune responses, such as the complement pathway.
An incompatible blood transfusion
causes a transfusion reaction, which is mediated by the humoral immune response. This type of reaction, called an acute hemolytic reaction, results in the rapid destruction (hemolysis
) of the donor red blood cell
s by host antibodies. The cause is usually a clerical error (i.e. the wrong unit of blood being given to the wrong patient). The symptoms are fever and chills, sometimes with back pain and pink or red urine
(hemoglobinuria
). The major complication is that hemoglobin
released by the destruction of red blood cells can cause acute renal failure
.
and terminal differentiation
into plasma cell
s).
Naïve B cells can be activated in a T-cell dependent or independent manner, but two signals are always required to initiate activation.
B cell activation depends on one of three mechanisms: Type 1 T cell-independent (polyclonal) activation, Type 2 T cell-independent activation (in which macrophages present several of the same antigen in a way that causes cross-linking of antibodies on the surface of B cells), and T cell-dependent activation. During T cell
-dependent activation, an antigen presenting cell (APC) presents a processed antigen to a helper T (Th) cell, priming it. When a B cell processes and presents the same antigen to the primed Th cell, the T cell releases cytokine
s that activate the B cell.
Meltzer, S. J. and Charles Norris (1897) The Bactericidal Action of Lymph Taken From the Thoracic Duct of the Dog. (Full Text-pdf) Journal of Experimental Medicine Vol. 2, Issue 6, 701-709.
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...
that is mediated by secreted antibodies (as opposed to cell-mediated immunity
Cell-mediated immunity
Cell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of macrophages, natural killer cells , antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen...
, which involves T lymphocytes) produced in the cells of the B lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
lineage (B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
). B Cells (with co-stimulation) transform into plasma cells which secrete antibodies. The co-stimulation of the B cell can come from another antigen presenting cell, like a dendritic cell
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...
. This entire process is aided by CD4+ T-helper 2 cells, which provide co-stimulation. Secreted antibodies bind to antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s on the surfaces of invading microbes (such as viruses or bacteria), which flags them for destruction. Humoral immunity is so named because it involves substances found in the humours
Humorism
Humorism, or humoralism, is a now discredited theory of the makeup and workings of the human body, adopted by Greek and Roman physicians and philosophers, positing that an excess or deficiency of any of four distinct bodily fluids in a person directly influences their temperament and health...
, or body fluids.
The study of the molecular and cellular components that comprise the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
, including their function and interaction, is the central science of immunology
Immunology
Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. It deals with the physiological functioning of the immune system in states of both health and diseases; malfunctions of the immune system in immunological disorders ; the...
. The immune system is divided into a more primitive innate immune system
Innate immune system
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...
, and acquired or 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...
of vertebrates, each of which contains humoral and cellular components.
Humoral immunity refers to antibody production and the accessory processes that accompany it, including: Th2 activation and 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...
production, germinal center
Germinal center
Germinal centers are sites within lymph nodes where mature B lymphocytes rapidly proliferate, differentiate, mutate their antibodies , and class switch their antibodies during a normal immune response to an infection...
formation and isotype
Isotype (immunology)
An isotype usually refers to any related proteins/genes from a particular gene family. In immunology, the "immunoglobulin isotype" refers to the genetic variations or differences in the constant regions of the heavy and light chains...
switching, affinity maturation
Affinity maturation
In immunology, affinity maturation is the process by which B cells produce antibodies with increased affinity for antigen during the course of an immune response. With repeated exposures to the same antigen, a host will produce antibodies of successively greater affinities. A secondary response...
and memory cell
Memory cell
Memory cell may refer to:* Memory cell, a building block of computer data storage*Memory B cell, an antibody producing cell*Memory T cell, an infection fighting cell...
generation. It also refers to the effector
Effector (biology)
An effector is a molecule that binds to a protein and thereby alters the activity of that protein...
functions of antibody, which include pathogen and toxin neutralization, classical 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...
activation, and opsonin
Opsonin
An 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...
promotion of phagocytosis and pathogen elimination.
History
The concept of humoral immunity developed based on analysis of antibacterial activity of the components of serum. Hans Buchner is credited with the development of the humoral theory. In 1890 he described alexins, or “protective substances”, which exist in the serum and other bodily fluid and are capable of killing microorganisms. Alexins, later redefined "complement" by Paul EhrlichPaul Ehrlich
Paul Ehrlich was a German scientist in the fields of hematology, immunology, and chemotherapy, and Nobel laureate. He is noted for curing syphilis and for his research in autoimmunity, calling it "horror autotoxicus"...
, were shown to be the soluble components of the innate response that lead to a combination of cellular and humoral immunity, and bridged the features of innate and acquired immunity.
Following the 1888 discovery of diphtheria
Diphtheria
Diphtheria is an upper respiratory tract illness caused by Corynebacterium diphtheriae, a facultative anaerobic, Gram-positive bacterium. It is characterized by sore throat, low fever, and an adherent membrane on the tonsils, pharynx, and/or nasal cavity...
and tetanus
Tetanus
Tetanus is a medical condition characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, rod-shaped, obligate anaerobic bacterium Clostridium tetani...
, Emil von Behring and Kitasato Shibasaburō
Kitasato Shibasaburō
Baron was a Japanese physician and bacteriologist. He is remembered as the co-discoverer of the infectious agent of bubonic plague in Hong Kong in 1894, almost simultaneously with Alexandre Yersin.-Biography:...
showed that disease need not be caused by microorganisms themselves. They discovered that cell-free filtrates were sufficient to cause disease. In 1890, filtrates of diphtheria (later named diphtheria toxin
Diphtheria toxin
Diphtheria toxin is an exotoxin secreted by Corynebacterium diphtheriae, the pathogen bacterium that causes diphtheria. Unusually, the toxin gene is encoded by a bacteriophage...
s) were used to immunize
Vaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...
animals in an attempt to demonstrate that immunized serum contained an antitoxin
Antitoxin
An antitoxin is an antibody with the ability to neutralize a specific toxin. Antitoxins are produced by certain animals, plants, and bacteria. Although they are most effective in neutralizing toxins, they can kill bacteria and other microorganisms. Antitoxins are made within organisms, but can be...
that could neutralize the activity of the toxin and could transfer immunity to non immune animals. In 1897, Paul Ehrlich showed that antibodies form against the plant toxins ricin
Ricin
Ricin , from the castor oil plant Ricinus communis, is a highly toxic, naturally occurring protein. A dose as small as a few grains of salt can kill an adult. The LD50 of ricin is around 22 micrograms per kilogram Ricin , from the castor oil plant Ricinus communis, is a highly toxic, naturally...
and abrin
Abrin
Abrin is a toxalbumin that is found in the seeds of a plant called lucky bean, rosary pea or jequirity pea. Abrin is similar to but far more deadly than ricin, a toxin found in the seeds of the castor oil plant.-Physical Properties:...
, and proposed that these antibodies are responsible for immunity. Ehrlich, with his friend Emil von Behring, went on to develop the diphtheria antitoxin, which became the first major success of modern immunotherapy
Immunotherapy
Immunotherapy is a medical term defined as the "treatment of disease by inducing, enhancing, or suppressing an immune response". Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies. While immunotherapies that reduce or suppress are...
. The presence and specificity of compability antibodies became the major tool for standardizing the state of 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...
and identifying the presence of previous infections.
| Substance | Activity | Discovery |
|---|---|---|
| Alexin(s) 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... |
Soluble components in the serum that are capable of killing microorganisms |
Buchner (1890), Ehrlich (1892) |
| Antitoxins | Substances in the serum that can neutralize the activity of toxins, enabling passive immunization |
von Behring and Kitasato (1890) |
| Bacteriolysins | Serum substances that work with the complement proteins to induce bacterial lysis |
Richard Pfeiffer Richard Friedrich Johannes Pfeiffer Richard Friedrich Johannes Pfeiffer was a German physician and bacteriologist.Pfeiffer was born in Zduny, Province of Posen, and died in Bad Landeck.... (1895) |
| Bacterial agglutinin Agglutinin An agglutinin is a substance that causes particles to coagulate to form a thickened mass . Agglutinins can be antibodies that cause antigens to aggregate by binding to the antigen-binding sites of antibodies. Agglutinins can also be any substance other than antibodies such as sugar-binding... s & precipitin Precipitin A precipitin is an antibody which can precipitate out of a solution upon antigen binding.-Precipitin reaction:The precipitin reaction provided the first quantitative assay for antibody, which has since been rendered obsolete by current diagnostic techniques such as ELISA and RIA... s |
Serum substances that agglutinate bacteria and precipitate bacterial toxins |
von Gruber Max von Gruber Max von Gruber was an Austrian scientist.As a bacteriologist he discovered specific agglutination in 1896 with his colleague Herbert Edward Durham... and Durham (1896), Kraus (1897) |
| Hemolysins Hemolysis (microbiology) Hemolysis is the breakdown of red blood cells. The ability of bacterial colonies to induce hemolysis when grown on blood agar is used to classify certain microorganisms. This is particularly useful in classifying streptococcal species... |
Serum substances that work with complement to lyse red blood cells |
Belfanti and Carbone (1898) Jules Bordet Jules Bordet Jules Jean Baptiste Vincent Bordet was a Belgian immunologist and microbiologist. The bacterial genus Bordetella is named after him.-Biography:Bordet was born at Soignies, Belgium... (1899) |
| Opsonin Opsonin An 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... s |
serum substances that coat the outer membrane of foreign substances and enhance the rate of phagocytosis by macrophages |
Wright and Douglas (1903) |
| Antibody Antibody An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen... |
formation (1900), antigen-antibody binding hypothesis (1938), produced by B cells (1948), structure (1972), immunoglobulin genes (1976) |
Founder: P Ehrlich |
Complement system
The complement system is a biochemical cascade of the innate immune system that helps clear pathogens from an organism. It is derived from many small plasma proteins that work together to disrupt the target cell's plasma membrane leading to cytolysis of the cell. The complement system consists of more than 35 soluble and cell-bound proteins, 12 of which are directly involved in the complement pathways. The complement system is involved in the activities of both innate immunity and acquired immunity.Activation of this system leads to cytolysis
Cytolysis
Cytolysis, 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...
, chemotaxis
Chemotaxis
Chemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...
, opsonization, immune clearance, and 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...
, as well as the marking of pathogens for phagocytosis. The proteins account for 5% of the serum
Blood serum
In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...
globulin
Globulin
Globulin is one of the three types of serum proteins, the others being albumin and fibrinogen. Some globulins are produced in the liver, while others are made by the immune system. The term globulin encompasses a heterogeneous group of proteins with typical high molecular weight, and both...
fraction. Most of these proteins circulate as zymogen
Zymogen
A zymogen is an inactive enzyme precursor. A zymogen requires a biochemical change for it to become an active enzyme. The biochemical change usually occurs in a lysosome where a specific part of the precursor enzyme is cleaved in order to activate it...
s, which are inactive until proteolytic cleavage.
Three biochemical pathways activate the complement system: the classical complement pathway
Classical complement pathway
The Classical pathway of activation of the complement system is a group of blood proteins that mediate the specific antibody response. The main activators of the Classical Pathway are antigen-antibody complexes.-Initiation:...
, the alternate complement pathway, and the mannose-binding lectin pathway.
The classical complement pathway typically requires antibodies for activation and is a specific immune response, while the alternate pathway can be activated without the presence of antibodies and is considered a non-specific immune response. Antibodies, in particular the IgG1 class, can also "fix" complement.
Antibodies
Immunoglobulins are glycoproteins in the immunoglobulin superfamily that function as antibodies. The terms antibody and immunoglobulin are often used interchangeably. They are found in the blood and tissue fluids, as well as many secretions. In structure, they are large Y-shaped globular proteins. In mammals there are five types of antibody: IgA, IgD, IgE, IgG, and IgM. Each immunoglobulin class differs in its biological properties and has evolved to deal with different antigens. Antibodies are synthesized and secreted by plasma cells that are derived from the B cells of the immune system.An antibody is used by the acquired immune system to identify and neutralize foreign objects like bacteria and viruses. Each antibody recognizes a specific antigen unique to its target. By binding their specific antigens, antibodies can cause agglutination
Agglutination (biology)
Agglutination is the clumping of particles. The word agglutination comes from the Latin agglutinare, meaning "to glue."This occurs in biology in three main examples:...
and precipitation of antibody-antigen products, prime for phagocytosis by macrophages and other cells, block viral
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...
receptors, and stimulate other immune responses, such as the complement pathway.
An incompatible blood transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
causes a transfusion reaction, which is mediated by the humoral immune response. This type of reaction, called an acute hemolytic reaction, results in the rapid destruction (hemolysis
Hemolysis
Hemolysis —from the Greek meaning "blood" and meaning a "loosing", "setting free" or "releasing"—is the rupturing of erythrocytes and the release of their contents into surrounding fluid...
) of the donor red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s by host antibodies. The cause is usually a clerical error (i.e. the wrong unit of blood being given to the wrong patient). The symptoms are fever and chills, sometimes with back pain and pink or red urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
(hemoglobinuria
Hemoglobinuria
In medicine, hemoglobinuria or haemoglobinuria is a condition in which the oxygen transport protein hemoglobin is found in abnormally high concentrations in the urine. The condition is often associated with hemolytic anemia, in which red blood cells are destroyed, thereby increasing levels of free...
). The major complication is that hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
released by the destruction of red blood cells can cause acute renal failure
Acute renal failure
Acute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...
.
B cells
The principal function of B cells is to make antibodies against soluble antigens. B cell recognition of antigen is not the only element necessary for B cell activation (a combination of clonal proliferationCell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
and terminal differentiation
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
into plasma cell
Plasma cell
Plasma cells, also called plasma B cells, plasmocytes, and effector B cells, are white blood cells which produce large volumes of antibodies. They are transported by the blood plasma and the lymphatic system...
s).
Naïve B cells can be activated in a T-cell dependent or independent manner, but two signals are always required to initiate activation.
B cell activation depends on one of three mechanisms: Type 1 T cell-independent (polyclonal) activation, Type 2 T cell-independent activation (in which macrophages present several of the same antigen in a way that causes cross-linking of antibodies on the surface of B cells), and T cell-dependent activation. During T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
-dependent activation, an antigen presenting cell (APC) presents a processed antigen to a helper T (Th) cell, priming it. When a B cell processes and presents the same antigen to the primed Th cell, the T cell releases 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 that activate the B cell.
Further reading
- The following article reviews some of the early experiments that laid the foundations of the humoral theory:
Meltzer, S. J. and Charles Norris (1897) The Bactericidal Action of Lymph Taken From the Thoracic Duct of the Dog. (Full Text-pdf) Journal of Experimental Medicine Vol. 2, Issue 6, 701-709.