The concept of humoral immunity developed based on the analysis of antibacterial activity of the serum components. Hans Buchner is credited with the development of the humoral theory.[2] In 1890, Buchner described alexins as "protective substances" that exist in the blood serum and other bodily fluids and are capable of killing microorganisms. Alexins, later redefined as "complements" by Paul Ehrlich, were shown to be the soluble components of the innate response that leads to a combination of cellular and humoral immunity. This discovery helped to bridge the features of innate and acquired immunity.[2]
Following the 1888 discovery of the bacteria that cause 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 toxins, were used to vaccinate 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.[3] In 1897, Paul Ehrlich showed that antibodies form against the plant toxinsricin and abrin, and proposed that these antibodies are responsible for immunity.[2] Ehrlich, with his colleague von Behring, went on to develop the diphtheria antitoxin, which became the first major success of modern immunotherapy.[3] The discovery of specified compatible antibodies became a major tool in the standardization of immunity and the identification of lingering infections.[3]
Major discoveries in the study of humoral immunity[3]
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 cells by host antibodies. The cause is usually a clerical error, such as 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 kidney failure.
Antibody production
In the humoral immune response, the naive B cells begin the maturation process in the bone marrow, gaining B-cell receptors (BCRs) along the cell surface.[6] These BCRs are membrane-bound protein complexes that have a high binding affinity for specific antigens; this specificity is derived from the amino acid sequence of the heavy and light polypeptide chains that constitute the variable region of the BCR.[7] Once a BCR interacts with an antigen, it creates a binding signal which directs the B cell to produce a unique antibody that only binds with that antigen. The mature B cells then migrate from the bone marrow to the lymph nodes or other organs of the lymphatic system, where they begin to encounter pathogens.
Step 1: A macrophage engulfs the pathogen. Step 2: The macrophage then digests the bacterium and presents the pathogen's antigens. Step 3: A T helper cell binds to the macrophage and becomes an activated T helper cell. Step 4: The activated T helper cell binds to a B cell in order to activate the B cell. Step 5: When the B cells are activated, some B cells turn into plasma cells and are released into the blood, while other B cells become B memory cells that quicken the response to a second exposure. Step 6: Plasma cells then secrete antibodies, which bind to antigens to fight the invading pathogens.
B cell activation
When a B cell encounters an antigen, a signal is activated, the antigen binds to the receptor, and is taken inside the B cell by endocytosis. The antigen is processed and presented on the B cell's surface again by MHC class II (MHC-II) proteins. The MHC-II proteins are recognized by T helper cells (Th cells), which stimulate the production of proteins, allowing B cells to multiply and their descendants to differentiate into antibody-secreting cells circulating in the blood.[8] B cells can be activated through certain microbial agents without the help of T cells and have the ability to work directly with antigens to respond to pathogens present.[8]
B cell proliferation
The B cell waits for a Th cell to bind to the complex. This binding will activate the Th cell, which then releases cytokines that induce B cells to divide rapidly, making thousands of identical clones of the B cell. These daughter cells either become plasma cells or memory B cells. The memory B cells remain inactive here; later, upon reinfection with the same antigen, they divide to form plasma cells. On the other hand, the plasma cells produce a large number of antibodies which are released freely into the circulatory system.
Antibody-antigen reaction
These antibodies will encounter antigens and bind with them. This will either interfere with the chemical interaction between host and foreign cells or may form bridges between their antigenic sites, hindering their proper functioning. Their presence might also attract macrophages or killer cells to attack and phagocytose them.
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 blood 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.[1] The complement system is involved in the activities of both innate immunity and acquired immunity.
The classical pathway is initiated through exposure to free-floating antigen-bound antibodies. This leads to enzymatic cleavage of smaller complement subunits, which assemble to form the C3-convertase.
B cell activation is a large part of the humoral immune response.
This differs from the mannose-binding lectin pathway, which is initiated by bacterial carbohydrate motifs, such as mannose, on bacterial surfaces. After the binding process, the same subunit cleavage and synthesis occur as in the classical pathway. The alternate complement pathway completely diverges from the previous pathways, as it spontaneously initiates in the presence of hydrolyzed C3, which then recruits other subunits that can be cleaved to form C3-convertase. In all three pathways, once C3-convertase is synthesized, complement components are cleaved into subunits that either form a structure called the membrane attack complex (MAC) on the bacterial cell wall to destroy the bacteria or act as cytokines and chemokines, amplifying the immune response.[11]
↑Janeway Jr CA, Travers P, Walport M, Shlomchik MJ (November 21, 2001). "The complement system and innate immunity". Immunobiology: The Immune System in Health and Disease (5thed.). New York: Garland Science – via www.ncbi.nlm.nih.gov.
