ViDih m

V2P3J1E

b TCR-a-chain

Germ line < DNA

1. Rearrangement

T lymphocyte DNA

2. Transkription -►Primary RNA

Vgl Val k Qt

Vol la Ca

VI C

Kayser, Medical Microbiology © 2005 Thieme

All rights reserved. Usage subject to terms and conditions of license.

regions encoding the H chain segments Ci, C8, Cy, Ca, and Ce, in consecutive order. Thus all immunoglobulin production begins with the synthesis of IgM and IgD (resulting from transcription of the VDJ and the Ci or C8 gene segments). This occurs without prior antigen stimulus and is transitional in nature. Antigen stimulation results in a second gene rearrangement—during which the VDJ gene is relocated to the vicinity of Cy, Ca, or Ce by a process of recombination involving deletion of the intervening regions. Following this event, the B cell no longer produces H chains of the IgM or IgD classes, but is instead committed to the production of IgG, IgA, or IgE—thus allowing secretion of the entire range of immunoglobulin types (Table 2.2). This process is known as class switching, and results in a change of the Ig class of an antibody whilst allowing its antigen specificity to be retained. Variability types. The use of different heavy or light chain constant regions results in new immunoglobulin classes known as isotypes. Individual Ig classes can also differ, with such genetically determined variations in the constant elements of the immunoglobulins (which are transmitted according to the Mendelian laws) are known as allotypes. Variation within the variable region results in the formation of determinants, known as idiotypes. The idiotype determines an immunoglobulins antigenic specificity, and is unique for each individual B-cell clone.

Functions. Each different class of antibody has a specific set of functions. IgM and IgD act as B-cell receptors in their earlier transmembrane forms, although the function of IgD is not entirely clear. The first antibodies produced in the primary immune response are IgM pentamers, the action of which is directed largely against micro-organisms. IgM pentamers are incapable of crossing the placental barrier. The immunoglobulin class which is most abundant in the serum is IgG, with particularly high titers of this isotype being found following secondary stimulation. IgG antibodies pass through the placenta and so provide the newborn with a passive form of protection against those pathogens for which the mother exhibits immunity. In certain rare circumstances such antibodies may also harm the child, for instance when they are directed against epitopes expressed by the child's own tissues which the mother has reacted against immunologically (the most important clinical example of this is rhesus factor incompatibility). High concentrations of IgA antibodies are found in the intestinal tract and contents, saliva, bronchial and nasal secretions, and milk—where they are strategically positioned to intercept infectious pathogens (particularly commensals) (Fig. 2.5). IgE antibodies bind to high-affinity Fce receptors present on basophilic granulocytes and mast cells. Cross-linking of mast cell bound IgE antibodies by antigen results in cellular degranulation and causes the release of highly active biogenic amines (his-tamine, kinines). IgE antibodies are produced in large quantities following parasitic infestations of the intestine, lung or skin, and play a significant role in the local immune response raised against these pathogens.

Kayser, Medical Microbiology © 2005 Thieme

All rights reserved. Usage subject to terms and conditions of license.

The Mucosa-Associated Lymphoid Tissue — (MALT) Immune System and "Homing" -

The Mucosa-Associated Lymphoid Tissue — (MALT) Immune System and "Homing" -

Mucosa Associated Lymphoid Tissue

Fig. 2.5 Specialized APCs (M cells in the intestinal wall or pulmonary macrophages in the lung) take up antigens in mucosa and present them in the Peyer's patches or local lymph nodes. This probably enhances T cell-dependent activation of IgA-producing B cells, which are preferentially recruited to the mucosal regions ("homing") via local adhesion molecules and antigen depots, resulting in a type of geographic specificity within the immune response.

Fig. 2.5 Specialized APCs (M cells in the intestinal wall or pulmonary macrophages in the lung) take up antigens in mucosa and present them in the Peyer's patches or local lymph nodes. This probably enhances T cell-dependent activation of IgA-producing B cells, which are preferentially recruited to the mucosal regions ("homing") via local adhesion molecules and antigen depots, resulting in a type of geographic specificity within the immune response.

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