Lecture 15_Autoimmunity

Lecture 15_Autoimmunity - Autoimmunity The failure of the...

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Autoimmunity The failure of the adaptive immune system to discriminate between self and non-self Auto-antibodies and auto-reactive T cells are found in circulation Negative selection (central tolerance), continuous and strong stimulation by self antigens and peripheral tolerance (e.g. anergy, Tregs) are mechanisms to avoid autoimmunity. However, none of these mechanisms unequivocally distinguish self from non-self Causes: Non-self activation of weakly self-reactive lymphocytes (such as during infection or injury) may trigger autoimmunity Many molecules of pathogens resemble self antigens in their 3-D structure. Peptides of a pathogen may be similar to host peptides, although the entire protein may be different
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Table 3. Pathogenesis of autoimmune diseases 1 Sex is a key factor in autoimmune disease, ie a number of autoimmune diseases are much more common in women than in men. 2 There is a genetic background to autoimmune diseases and a strong correlation with particular MHC haplotypes . MHC associations differ in different ethnic groups. 3 T helper cells play a major role in autoimmunity through TH1 clones triggering a DTH response. Auto-reactive cytotoxic T cells develop more rarely but are found in IDDM. 4 At least in experimental models and in certain human auto-immune diseases somatic hypermutation is an important process leading to auto-reactive antibodies. 5 Infection by viruses (HCMV, EBV) or bacteria results in polyclonal B cell activation . This may constitute a mechanism for activation of anergic, self reactive B clones. 6 Exposure of segregated antigens can lead to autoimmune diseases. 7 Molecular mimicry , ie the sharing of identical are highly similar antigenic determinants between viral/bacterial antigens and self antigens, may play a role in autoimmunity.
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Each of these systems by themselves do not ensure lack of auto- reactivity. But together, they represent a series of mechanisms that under ‘normal’ circumstances effectively prevent reactions to self
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Central tolerance is made possible by a single transcription factor named AIRE. AIRE turns on many genes in the thymus, expressing non-thymic proteins during T cell selection.
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Expression of AIRE leads to the negative selection of strongly self- reactive proteins in the thymus, and thus these cells never enter the periphery. AIRE deficiency leads to multi-tissue destruction because
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This note was uploaded on 01/03/2012 for the course BI 144 taught by Professor List during the Fall '10 term at Caltech.

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Lecture 15_Autoimmunity - Autoimmunity The failure of the...

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