Lecture 10: Hypersensitivity & Autoimmunity PDF

Microbiolog y Hypersensitivity SMS233z reactions & autoimmunity Professor Name : Dr. Zeinab Abdel Khalek Professor title at MSA: Head of department LECTURE OUTLINE Hypersensitivity reactions Autoimmune diseasesand tolerance.. LECTURE ILOs Understand Hypersensitivity react...

Microbiolog y Hypersensitivity SMS233z reactions & autoimmunity Professor Name : Dr. Zeinab Abdel Khalek Professor title at MSA: Head of department LECTURE OUTLINE Hypersensitivity reactions Autoimmune diseasesand tolerance.. LECTURE ILOs Understand Hypersensitivity reactions Understand autoimmune diseases and tolerance.. Immunopathogenes is Hypersensitivity reactions Table 1. Gell and Coombs classification of hypersensitivity reactions. Examples Mechanism Type Anaphylaxis, asthma, hay fever, eczema, food allergies IgE I HTR caused by ABO incompatibility, HDN caused by Rh incompatibility Cytotoxic Ab II Serum sickness, Arthus phenomenon, rheumatoid arthritis Immune complexes III Koch's phenomenon, allograft rejection, contact dermatitis Cell-mediated IV The processes underlying type I Hypersensitivity reactions Skin prick test for diagnosis of allergy Drug hypersensitivity Erythema nodosum lesions on skin of back due to hypersensitivity to antigens of Coccidioides immitis Bite reactions appearing as multiple linearly arranged erythematous nodules with tense blister on the forearm of the patient. Hives (urticaria) Type II cytotoxicity mechanism Immune Complex-Mediated hypersensitivity Mechanism of damage in immune complex hypersensitivity Immune complex hypersensitivity Arthus reaction Rheumatoid nodule Rheumatoid arthritis Cell-mediated hypersensitivity  Delayed hypersensitivity reactions Antigen and site Histology Clinical Reaction Type appearance time epidermal ( organic chemicals, poison lymphocytes, followed by Contact ivy, heavy metals, etc.) macrophages; edema of epidermis eczema 48-72 hr Dermatitis lymphocytes, monocytes, intradermal (tuberculin, lepromin, etc.) macrophages local induration 48-72 hr tuberculin persistent antigen or foreign body macrophages, epitheloid and giant hardening 21-28 days granuloma presence (tuberculosis, leprosy, etc.) cells, fibrosis Atopic dermatitis (Eczema) Tuberculin test  Comparison of Different Types of hypersensitivity type-IV type-III type-II type-I characteristics (delayed type) (immune complex) (cytotoxic) (anaphylactic) None IgG, IgM IgG, IgM IgE antibody tissues & organs soluble cell surface exogenous antigen 48-72 hours 3-8 hours minutes-hours 15-30 minutes response time erythema and erythema and edema, induration necrosis lysis and necrosis weal & flare appearance monocytes and complement and antibody and complement basophils and histology lymphocytes neutrophils eosinophil T-cells antibody antibody antibody transferred with SLE, farmer's lung erythroblastosis tuberculin test, poison disease fetalis, Goodpasture's allergic asthma, hay examples ivy, granuloma nephritis fever Immunopathogenesi TOLERANCE AND AUTOIMMUNITY Definition of Tolerance: The absence of specific immune response against some antigens in an otherwise immunocompetent person Auto-tolerance (natural) Acquired (induced) tolerance to other antigens Autotolerance Tolerance to self-antigens Induced early, in utero Failure → autoimmune disease  Acquired (Induced Tolerance) Definition: Induction of tolerance to an antigen at any time during life Question: When should we try to achieve this? - Allergy - Autoimmunity - Graft rejection Definition: Adaptive immune response to self-antigens Breakdown in autotolerance → production of autoantibodies and/or self-reactive T cells → autoimmune disease Aetiology of autoimmune diseases: 1. Exposure to antigens that are normally sequestered: Lymphocytes not exposed during development to these antigens → not deleted → survive → exposure later on → immune response → autoimmune disease Examples: Sperms: testicular trauma or infection → release of sperm antigens → immune response → ab formation → ↓ spermatogenesis Lens: trauma → release of antigen → immune response → destruction of lens 2. Structural modification of tissue proteins Drugs, chemicals or viruses → alteration of certain tissue proteins → Protein no longer recognized as self → immune response → destruction of tissue Example: Alpha-methyl dopa modifies RBC surface proteins → such protein no longer identified as self →immune response → autoimmune hemolytic anemia 3. Cross-reactivity: Example: Streptococcus pyogenes and heart tissue antigens Infection → ab production → ab produced against Streptococcus pyogenes reacts with heart muscle antigens → damage → rheumatic fever and rheumatic heart disease Ag 1 Ag 2 Cross-reactivity 4. Genetic Predisposition to Autoimmune Disease: Genetic factors appear to play a role Certain autoimmune diseases run in families This is thought to be related to specific MHC antigens which are good at presenting certain self peptides to self reactive T-cells → autoimmune response There is a strong association between several autoimmune diseases and certain MHC(HLA) SLE and DR3, Rheumatoid arthritis & DR4 Mechanisms of Tissue Injury in Autoimmune Diseases Type II: Cytotoxic reactions Example: Autoimmune haemolytic anaemia Mechanisms of Tissue Injury in Autoimmune Diseases (cont) Type III: Immune-complex –mediated Examples: SLE Rheumatoid arthritis Mechanisms of Tissue Injury in Autoimmune Diseases (cont) Type IV: Cell-mediated reaction Example: Ulcerative Colitis Mechanisms of Tissue Injury in Autoimmune Diseases (cont) Excessive Stimulation of Cells: Example: Grave’s disease: Ab against thyroid cells → ↑ secretion of thyroxin → Thyrotoxicosis Laboratory diagnosis of Autoimmune Diseases: Management of Autoimmune Diseases: Anti-inflammatory drugs Immunosuppressive drugs Plasmapheresis Interference with cytokine network