Humoral and cell-mediated immunity Essay
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Humoral immunity (also called the antibody-mediated system) is the aspect of immunity that is mediated by macromolecules (as opposed to cell-mediated immunity) found in extracellular fluids such as secreted antibodies, complement proteins and certain antimicrobial peptides. 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 andisotype switching, affinity maturation and memory cell generation. It also refers to the effector functions of antibody, which include pathogen and toxin neutralization, classicalcomplement activation, and opsonin promotion of phagocytosis and pathogen elimination.
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 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. 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 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 compatibility antibodies became the major tool for standardizing the state of immunity and identifying the presence of previous infections.
Main article: 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, 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. Antibodies
Main article: Antibody
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 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. B cells
Main article: B cell
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 proliferation and terminal differentiation into plasma cells). 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 mature B cells respond to highly repetitive structures causing cross-linking of the B cell receptors 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.
Cell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. Historically, the immune system was separated into two branches: humoral immunity, for which the protective function of immunization could be found in the humor (cell-free bodily fluid or serum) and cellular immunity, for which the protective function of immunization was associated with cells. CD4 cells or helper T cells provide protection against different pathogens. Cytotoxic T cells cause death by apoptosis without using cytokines, therefore in cell mediated immunity cytokines are not always present. Cellular immunity protects the body by:
1. activating antigen-specific cytotoxic T-lymphocytes that are able to induce apoptosis in body cells displaying epitopes of foreign antigen on their surface, such as virus-infected cells, cells with intracellular bacteria, and cancer cells displaying tumor antigens; 2. activating macrophages and natural killer cells, enabling them to destroy pathogens; and 3. stimulating cells to secrete a variety of cytokines that influence the function of other cells involved in adaptive immune responses and innate immune responses. Cell-mediated immunity is directed primarily at microbes that survive in phagocytes and microbes that infect non-phagocytic cells. It is most effective in removing virus-infected cells, but also participates in defending against fungi, protozoans, cancers, and intracellular bacteria. It also plays a major role in Transplant rejection.