Acquired immunity depends upon the immune system recognising a substance as foreign the ?rst time it is encountered, storing this information so that it can mount a reaction the next time the substance enters the body. This is the usual outcome of natural infection or prophylactic IMMUNISATION. What happens is that memory of the initiating ANTIGEN persists in selected lymphocytes (see LYMPHOCYTE). Further challenge with the same antigen stimulates an accelerated, more vigorous secondary response by both T- and B-lymphocytes (see below). Priming the immune system in this manner forms the physiological basis for immunisation programmes.
Foreign substances which can provoke an immune response are termed ‘antigens’. They are usually proteins but smaller molecules such as drugs and chemicals can also induce an immune response. Proteins are taken up and processed by specialised cells called ‘antigenpresenting cells’, strategically sited where microbial infection may enter the body. The complex protein molecules are broken down into short amino-acid chains (peptides – see PEPTIDE) and transported to the cell surface where they are presented by structures called HLA antigens (see HLA SYSTEM).
Foreign peptides presented by human leucocyte antigen (HLA) molecules are recognised by cells called T-lymphocytes. These originate in the bone marrow and migrate to the THYMUS GLAND where they are educated to distinguish between foreign peptides, which elicit a primary immune response, and self-antigens (that is, constituents of the person themselves) which do not. Non-responsiveness to self-antigens is termed ‘tolerance’ (see AUTOIMMUNITY). Each population or clone of T-cells is uniquely responsive to a single peptide sequence because it expresses a surface molecule (‘receptor’) which ?ts only that peptide. The responsive T-cell clone induces a speci?c response in other T-and B-lymphocyte populations. For example, CYTOTOXIC T-cells penetrate infected tissues and kill cells which express peptides derived from invading micro-organisms, thereby helping to eliminate the infection.
B-lymphocytes secrete ANTIBODIES which are collectively termed IMMUNOGLOBULINS (Ig)
– see also GAMMA-GLOBULIN. Each B-cell population (clone) secretes antibody uniquely speci?c for antigens encountered in the blood, extracellular space, and the LUMEN of organs such as the respiratory passages and gastrointestinal tract.
Antibodies belong to di?erent Ig classes; IgM antibodies are synthesised initially, followed by smaller and therefore more penetrative IgG molecules. IgA antibodies are adapted to cross the surfaces of mucosal tissues so that they can adhere to organisms in the gut, upper and lower respiratory passages, thereby preventing their attachment to the mucosal surface. IgE antibodies also contribute to mucosal defence but are implicated in many allergic reactions (see ALLERGY).
Antibodies are composed of constant portions, which distinguish antibodies of di?erent class; and variable portions, which confer unique antigen-binding properties on the product of each B-cell clone. In order to match the vast range of antigens that the immune system has to combat, the variable portions are synthesised under the instructions of a large number of encoding GENES whose products are assembled to make the ?nal antibody. The antibody produced by a single B-cell clone is called a monoclonal antibody; these are now synthesised and used for diagnostic tests and in treating certain diseases.
Populations of lymphocytes with di?erent functions, and other cells engaged in immune responses, carry distinctive protein markers. By convention these are classi?ed and enumerated by their ‘CD’ markers, using monoclonal antibodies speci?c for each marker.
Immune responses are in?uenced by cytokines which function as HORMONES acting over a short range to accelerate the activation and proliferation of other cell populations contributing to the immune response. Speci?c immune responses collaborate with nonspeci?c defence mechanisms. These include the COMPLEMENT SYSTEM, a protein-cascade reaction designed to eliminate antigens neutralised by antibodies and to recruit cell populations which kill micro-organisms.
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