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, the latter of which is further divided into 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.
Following the 1888 discovery of diphtheria and tetanus, Emil von Behring and Shibasaburo Kitasato 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 toxins) 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 antibodies became the major tool for standardizing the state of immunity and identifying the presence of previous infections.
| Alexin(s) |
| Soluble components in the serum|
that are capable of killing microorganisms
| Buchner (1890),|
|Antitoxins|| Substances in the serum that can neutralize|
the activity of toxins, enabling passive immunization
|von Bhering and Kitasato (1890)|
|Bacteriolysins|| Serum substances that work with the|
complement proteins to induce bacterial lysis
|Richard Pfeiffer (1895)|
| Bacterial agglutinins |
| Serum substances that agglutinate bacteria|
and precipitate bacterial toxins
| von Gruber and Durham (1896),|
|Hemolysins|| Serum substances that work with complement|
to lyse red blood cells
| Belfanti and Carbone (1898) |
Jules Bordet (1899)
|Opsonins|| serum substances that coat the outer membrane|
of foreign substances and enhance the rate of
phagocytosis by macrophages
|Wright and Douglas (1903)|
|Antibody|| formation (1900), antigen-antibody binding|
hypothesis (1938), produced by B cells (1948),
structure (1972), immunoglobulin genes (1976)
|Founder: P Ehrlich|
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 zymogens, 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 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 cells 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.
Naive 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 cytokines 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.