Chintana Phawong

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Autoimmune Diseases
Chintana Phawong Department of Clinical
Immunology Faculty of Associated Medical
Sciences Chiang Mai University
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?????????????????????????? -Autoimmunity -Mecha
nisms of autoimmunity
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Immunologic Tolerance
Self/nonself discrimination Self-tolerance
Failure of self-tolerance Autoimmune diseases
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Central Tolerance of T cells
Site Thymus Stage CD4CD8 (doubl
e positive) thymocyte Stimuli high-affinity
recognition of Ag in thymus
Mechanisms clonal deletion (apoptosis)
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Peripheral T cell Tolerance
Site Periphery stage Mature T
lymphocyte Stimuli Ag presentation by
APCs lacking costimulators repeated
stimulation by self Ag Mechanisms anergy
activation-induced cell death suppression of T
cells
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Autoimmunity
Autoimmunity any disease in which immune
reactions accompany tissue injury Etiology ??
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General Concepts of Autoimmunity
-Autoimmunity results from a failure or
breakdown of the mechanisms responsible for
maintaining self-tolerance -Multiple interacting
factors contribute to the development of
autoimmunity -Autoimmune diseases may be either
systemic or organ specific -Various effector
mechanisms are responsible for tissue injury in
different autoimmune diseases
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Mechanism of Autoimmunity
-Autoimmunity may result from primary
abnormality of B cells, T cells or
both. -failure of T cell tolerance failure of
central tolerance failure of T cell
tolerance failure of B cell tolerance
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Failure of Central Tolerance
central tolerance the mechanism of selection
of immature autoreactive lymphocytes that
delete cells with high-affinity receptors for
self antigen
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Failure of Peripheral T cell Tolerance
Tolerance in mature self Ag-specific T
lymphocytes is maintained by functional
anergy deletion by apoptosis suppression by
regulatory cells
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Clonal Anergy Aberation Expression of
Costimulator on APCs
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Failure of B Cell Tolerance
Exposure of B cells to polyclonal activators may
activate a large number of these
cells,including some that are specific for self
Ags
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Genetic Factors in Autoimmunity
Autoimmunity -associated with MHC
genes -multiple non-MHC genes IL-2 CTLA-4
Genetic deficiencies of complement
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Other Factors in Autoimmunity
-viral and bacterial infection molecular
mimicry -anatomic alteration in
tissues inflammation injury trauma -Hormonal
influences SLE femalegtmale
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Genetic Factors in Autoimmunity
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Therapeutic Approaches for Immunologic Diseases
- anti-inflammatory drug corticosteroid -antagoni
sts of proinflammatory cytokines and agents
that block WBC migration -inhibit pathologic
reactions antagonist vs costimulators or T cell
effector molecules -induce T cell
tolerance Altered peptide ligand
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Future directions
-develop animal model of various autoimmune
diseases -identify genes that may predispose to
autoimmunity -identify eitiology of most human
autoimmune diseases -drug discovery and specific
therapeutic approaches
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