Autoimmune diseases

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Autoimmune diseases
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Autoimmune diseases

• Immunity reaction against self antigen
• Autoantibody directed against single organ/ cell
  type
• Autoantibody directed against many tissue/ cell
  type

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Autoimmune diseases

• Autoantibody directed against single organ/ cell
  type
• Hashimoto thyroiditis
• Autoimmune hemolytic anemia
• Autoimmune atrophic gastritis of pernicious
  anemia
• Autoimmune encephalomyelitis
• Autoimmune orchitis
• Goodpasture syndrome
• Autoimmune thrombocytopenia
• Insulin dependent diabetes mellitus
• Myasthenia gravis
• Graves disease

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Autoimmune diseases

• Systemic Autoimmune disease
• Systemic lupus erythematosus
• Rheumatoid arthritis
• Sjogren syndrome
• Reiter syndrome
• Possible
• Inflammatory myopathies
• Systemic scerosis
• Polyarteritis nodosa

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Autoimmune diseases

• Three requirements
• Presence of Autoimmune reaction
• Autoimmune reaction should not be secondary to
  tissue damage but it is of primary pathogenetic
  significance
• Absence of another well defined cause of the
  disease

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Autoimmune diseases

• Loss of self tolerance
• Immunological tolerance
• Is a state in which individual is incapable of
  developing an immune response to a specific
  antigen
• Self tolerance
• Lack of responsiveness to self antigen
• Two mechanism
• Central tolerance
• Peripheral tolerance

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Autoimmune diseases

• Central tolerance
• Clonal deletion of self reactive T B lymphocyte
  during their maturation in the central lymphoid
  organs
• Developing T cells that expresses high affinity
  receptors for self antigens are deleted by
  apoptosis

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Autoimmune diseases

• Peripheral tolerance
• Clonal deletion by activation induced cell death
• Clonal anergy
• Peripheral suppresion by T cells

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Peripheral tolerance

• Clonal deletion by activation induced cell death
• Lymphocytes Fas(CD95)
• Activated lymphocytes ligand for Fas (fas L)
• Self Ag present in peripheral tissue causes
  persistent stimulation of self Ag specific T
  cells
• Engagement of Fas by Fas ligand induces apoptosis
  of activated T cells

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Peripheral tolerance

• Clonal anergy Prolonged or irreversible
  functional inactivation of lymphocyte
• Two signals are required for T cell activation
• MHC associated peptide
• CD28 must bind to their ligand (B7-1, B7-2)
• Costimulatory molecules are not expressed /weekly
  expressed on most normal tissue

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Peripheral tolerance

• Peripheral suppression by T cells
• CD4 T cells of TH2 type down regulate TH1
  response by secreting cytokines IL-4, IL-10
  TGF- ß

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Autoimmune diseases

• Defect / bypass in self tolerance result in
  Autoimmune diseases
• Mechanisms
• Immunologic
• Genetic factors
• Microbilogical agents

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Autoimmune diseases

• Failure of peripheral tolerance
• Breakdown of T cell anergy
• Failure of activation induced cell death
• Failure of T cell mediated suppression
• Molecular mimicry
• Polyclonal lymphocytic activation
• Release of sequestrated antigens
• Exposure of cryptic self epitopic spreading

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Autoimmune diseases

• Breakdown of T cell anergy
• Infection induced expression of costimulatory
  molecules (B7-1) secretion of IL-12 to generate
  TH1 T cells
• Upregulation of B7-1 molecule is seen in CNS of
  Multiple Sclerosis and synovium of Rheumatoid
  arthritis

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Autoimmune diseases

• Failure of activation induced cell death
• Defect in Fas Fas ligand mediated apoptosis
  result in proliferation of autoreactive T cells
• Molecular mimicry
• Some infectious agents share epitopes with self
  antigen
• RHD Ab to streptococcal M protein cross react
  with cardiac glycoprotein

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Autoimmune diseases

• Polyclonal lymphocytic activation
• Bacterial endotoxin can induce mouse lymphocytes
  to produce Anti DNA, Antithymocyte, Anti red
  cells antibodies in vitro
• Release of sequestrated antigens
• Spematozoa orchitis after vasectomy
• Occular antigen- post traumatic uveitis

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Autoimmune diseases

• Exposure of cryptic self epitopic spreading
• Each self antigen has many antigenic determinates
  (epitopes)
• Cryptic self epitopes (masked antigens) can
  produce autoimmunity by proliferation of T cells

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Autoimmune diseases (AI)

• Genetic factors
• Familial clustering of AI diseases
• SLE, AI thyroiditis
• Linkage of several AI diseases with HLA
• HLA B27 Ankylosing spondylitis
• HLA DR4 - RA

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Autoimmune diseases

• Microbial agents Trigger AI
• Microbes share cross reacting epitopes with self
  Ag
• Breakdown of T cell anergy
• Upregulation of costimulatory molecule on the APC
  of tissue
• Super antigens other bacterial products can
  activate large pool of T B cells

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