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Autoim lecture slides Autoim lecture slides Presentation Transcript

  • Autoimmunity Prof M.I.N. Matee Department of Microbiology and Immunology School of Medicine MUCHS
  • Autoimmunity
    • Immunologic tolerance
      • Body develops a tolerance for own tissue and does not produce a rejection response
    • Autoimmunity
      • Tolerance to own tissues is lost and host produces an immunologic rejection of own tissue
  • AUTOIMMMUNITY & AUTOIMMUNE DISEASES Any body protein and many carbohydrates and lipids, as well as nucleic acids are potential antigens. The body is capable of constructing T-Cell receptors (TCRs) or B-Cell receptors (BCRs) that can recognise these antigens and initiate an immune response against them.
  • Mechanisms & Causes of Autoimmunity The occurrence of autoimmune diseases indicates the presence in the body of autoreactive lymphocyte clones which can, under certain circumstances, become activated. a) Some self molecules are expressed at levels below the sensitivity threshold of lymphocytes.
  • b) Some molecules are protected by a barrier from contact with lymphocytes. c) Some epitopes are normally hidden from the immune system and tolerance towards them is not established.
  • d) Autoreactive clones made tolerant by anergization can be reactivated under some circumstances. e) Some autoreactive clones may be kept in check by regulatory mechanisms involving, for example, the suppressor T cells, and when these mechanisms fail the clones may become active.
  • Autoimmunity - Possible mechanisms
      • Sequestered antigens
        • antigens lack access to antibody forming cells
      • Modified cross-reacting antigens
        • fragmentation and recombination of antigens
      • Forbidden clone/clonal anergy
        • lymphocytes developed in fetus against an autoantigen and not eliminated
      • Immunological deficiency
        • anti-idiotype and T-cell suppression not functioning
  • Molecular Mimicry The main assumption of the molecular mimicry hypothesis is that some epitopes on foreign antigens are sufficiently similar to certain self epitopes to become target of immune response elicited by the former.
  • Uncovering of Sequestered Antigens or Cryptic epitopes An injury or infection may temporarily release molecules normally inaccessible to the immune mechanism, which can then stimulate autoimmune attack on the cell carrying them.
  • Activation of Potentially Autoreactive T-Cell clones by superantigens: Autoimmune reaction can also be triggered by superantigens, produced by some microorganisms.
  • Genetic Factors Familial associations and susceptibility of inbred mouse strains to certain autoimmune diseases indicate that the development of autoimmunity depends on genetic factors.
  • Failure of Immune Regulation Some autoimmune diseases are caused by an impairment of negative regulatory T cells (T-suppressor cells) that normally inhibit potentially autoreactive clones.
  • Causes of Tissue Damage Autoimmunity develops into a disease when components of the immune system begin to damage the body. The mechanisms of tissue damage vary according to the types of autoimmune disease.
  • Examples of Autoimmune Diseases Diseases Caused Mainly by Autoantibodies. SLE: Systemic Lupus Erythematosus, Autoantibodies produced against DNA and other nuclear components.
  • Grave’s disease (Hyperthyroidism) Autoantibodies produced against the thyroid-stimulating hormone (TSH) receptor that mimic the action of TSH and stimulate excessive production of thyroid hormones (T4, T3).
  • Hashimoto’s disease (Hypothyroidism) Autoantibodies produced against thyroid antigens such as thyroglobulin.
  • Pernicious Anemia
    • Caused by autoantibodies against intrinsic factor, a membrane protein of intestinal epithelial cells, which is involved in transport of Vitamin B 12 .
      • Atrophy of the mucosal cells of the stomach and infiltration of lymphoid tissue
  • Diseases caused by autoreactive T cells Insulin-dependent diabetes mellitus. In IDDN, insulin-producing  cells of the pancreatic islets of Langerhans are destroyed by CD8+ Tc cells.
  • Rheumatoid Arthritis. The disease is probably caused by T H 1 CD4+ cells reacting with fragments of joints antigens such as collagen or a heat shock protein bound to MHC class II molecules.
  • Autoimmune Diseases - Hematological
    • Autoimmune Hemolytic Anemia
      • Two types
        • Warm
        • Cold
      • May be secondary to another immune disease or idiopathic
  • Autoimmune Diseases Hematological
    • Warm Autoimmune Hemolytic Anemia
      • Sometimes minimal but may be life threatening
      • RBC are sensitized with IgG, C’ or both
      • Selective immunodeficiency seems to predispose to the disease - may have other autoimmune conditions - may be associated with other abnormal hematological disorders
      • Transfusion problems
  • Autoimmune Diseases Hematological
    • Cold Autoimmune Hemolytic Anemia
      • Acute and transient or chronic forms
      • Acute often follows an infection from Mycoplasma, viruses, hepatitis, syphillis
      • Chronic form found in older people and the anemia is worse in the winter.
      • Testing - cold agglutinin test
        • dilute patient’s serum and react with patient’s cells
  • Autoimmune Diseases Hematological
    • Paroxysmal Nocturnal Hemoglobinuria
      • C’3 activation and destruction of cells
      • Activation occurs in acidic environment
  • Addison’s Disease
      • Lymphocytic infiltration of the adrenal gland and antibodies to adrenal cells
      • Often associated with thyroid disease, pernicious anemia and diabetes
      • Tests - Complement fixation and immunoflourescent immunologic demonstration of antibodies
  • Autoimmune Diseases Endocrine System
    • Thyroid diseases
      • Hashimoto Thyroiditis
        • lymphoid invasion of thyroid gland and resulting hypothyroidism
        • Antibodies against cellular thyroid elements and thyroglobulins
      • Grave’s Disease
        • Antibody that mimics TSH causes hyperplasia of the thyroid also causes exopthalmus
      • Tests
        • Detection of thyroid antibodies
  • Autoimmune Diseases Gastrointestinal Tract
    • Ulcerative Colitis
      • Inflammatory disease of the colon and rectum/ allergy or cell mediated
      • often associated with other autoimmune diseases
      • Some have antibodies against sterile fetal colon tissue detected with immunoflourescence
  • Autoimmune Diseases Neuromuscular
    • Myasthenia Gravis
      • Acetylcholine is prevented from stimulating muscle to contract
      • Antibodies to acetylcholine receptors and thymus abnormalities
  • Autoimmune Diseases Neuromuscular
    • Multiple sclerosis
      • demyelination of the white matter of the central nervous system
      • presence of lymphocytes in the early lesions and plasma cells, lymphocytes and macrophages in later lesions
      • Testing for increased IgG levels in CSF
  • Autoimmune Diseases Liver
    • Primary Biliary Cirrhosis
      • affects the small intrahepatic bile ducts and eventually leads to liver failure
      • presence of high titer anti-mitochondrial antibody
    • Chronic Active Hepatitis
      • Infiltration of lymphocytes and plasma cells
      • Diminished number and function of suppressor T cells and presence of autoantibodies to different organs
  • Autoimmune Diseases
    • Goodpasture’s Syndrome
      • Glomerularnephritis and pulmonary damage
      • Antibodies against basement membrane
    • Bullous Skin Disease
      • Antibodies against intercellular bridges of the cells in the epidermis
  • GROUP A BETA HEMOLYTIC STREP SEQUELAE
    • Glomerulonephritis
      • often follows infection with Group A types 12, 4, or 49 and occurs approximately 10 days after throat infection and 20 days after skin infections
      • Cause may be due ag-ab immune complex at the glomerular membrane which activates complement and causes destruction
  • GROUP A BETA HEMOLYTIC STREP SEQUELAE
    • Rheumatic Fever
      • Follows multiple infections with different types of Group A Beta Hemolytic Strep
      • Includes inflammation and injury to the joints, heart and central nervous system.
      • Possibility of a cross reacting antibody or modified antigen which results in damage