Humoral immunity

The concept of humoral immunity developed based on analysis of antibacterial activity of the serum components. Hans Buchner is credited with the development of the humoral theory.[2] In 1890 he described alexins, or "protective substances", which exist in the blood serum and other bodily fluid and are capable of killing microorganisms. Alexins, later redefined "complement" by Paul Ehrlich, 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.[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 toxins ricin and abrin, and proposed that these antibodies are responsible for immunity.[2] Ehrlich, with his friend Emil von Behring, went on to develop the diphtheria antitoxin, which became the first major success of modern immunotherapy.[3] The presence and specificity of compatibility antibodies became the major tool for standardizing the state of immunity and identifying the presence of previous infections.[3]

In humoral immune response, first the B cells mature in the bone marrow and gain B-cell receptors (BCR's) which are displayed in large number on the cell surface.

These membrane-bound protein complexes have antibodies which are specific for antigen detection. Each B cell has a unique antibody that binds with an antigen. The mature B cells migrate from the bone marrow to the lymph nodes or other lymphatic organs, 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 in the blood, while other B cells become B memory cells that quicken response for a second exposure. Step 6: Plasma cells then secrete antibodies, which bind to antigens to fight the invading pathogens.

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.

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.[1] Antibodies, in particular the IgG1 class, can also "fix" complement.

B cell activation is a large part of the humoral immune response.

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.[12] 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 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 renal failure.

• Immune system
• Immunity
• Polyclonal response

• The following article reviews some of the early experiments that laid the foundations of the humoral theory: Orji Theddeus C, 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.