In immunology, clonal selection theory explains the functions of cells of the immune system (lymphocytes) in response to specific antigens invading the body. The concept was introduced by Australian doctor Frank Macfarlane Burnet in 1957, in an attempt to explain the great diversity of antibodies formed during initiation of the immune response. The theory has become the widely accepted model for how the human immune system responds to infection and how certain types of B and T lymphocytes are selected for destruction of specific antigens.
The theory states that in a pre-existing group of lymphocytes (both B and T cells
), a specific antigen activates (i.e. selects) only its counter-specific cell, which then induces that particular cell to multiply, producing identical clones for antibody production. This activation occurs in secondary lymphoid organs such as the spleen and the lymph nodes. In short, the theory is an explanation of the mechanism for the generation of diversity of antibody specificity. The first experimental evidence came in 1958, when Gustav Nossal and Joshua Lederberg showed that one B cell always produces only one antibody. The idea turned out to be the foundation of molecular immunology, especially in adaptive immunity.
The clonal selection theory can be summarised with the following four tenets:
Each lymphocyte bears a single type of receptor with a unique specificity (generated by V(D)J recombination).
Receptor occupation is required for cell activation.
The differentiated effector cells derived from an activated lymphocyte bear receptors of identical specificity as the parent cell.
Those lymphocytes bearing receptors for self molecules (i.e., endogenous antigens produced within the body) are destroyed at an early stage.
In 1900, Paul Ehrlich proposed the so-called "side chain theory" of antibody production. According to it, certain cells exhibit on their surface different "side chains" (i.e. membrane-bound antibodies) able to react with different antigens. When an antigen is present, it binds to a matching side chain.
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In immunology, central tolerance (also known as negative selection) is the process of eliminating any developing T or B lymphocytes that are autoreactive, i.e. reactive to the body itself. Through elimination of autoreactive lymphocytes, tolerance ensures that the immune system does not attack self peptides. Lymphocyte maturation (and central tolerance) occurs in primary lymphoid organs such as the bone marrow and the thymus. In mammals, B cells mature in the bone marrow and T cells mature in the thymus.
Immune tolerance, or immunological tolerance, or immunotolerance, is a state of unresponsiveness of the immune system to substances or tissue that would otherwise have the capacity to elicit an immune response in a given organism. It is induced by prior exposure to that specific antigen and contrasts with conventional immune-mediated elimination of foreign antigens (see Immune response). Tolerance is classified into central tolerance or peripheral tolerance depending on where the state is originally induced—in the thymus and bone marrow (central) or in other tissues and lymph nodes (peripheral).
A neutralizing antibody (NAb) is an antibody that defends a cell from a pathogen or infectious particle by neutralizing any effect it has biologically. Neutralization renders the particle no longer infectious or pathogenic. Neutralizing antibodies are part of the humoral response of the adaptive immune system against viruses, intracellular bacteria and microbial toxin. By binding specifically to surface structures (antigen) on an infectious particle, neutralizing antibodies prevent the particle from interacting with its host cells it might infect and destroy.
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