Hypersensitivity

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Hypersensitivity

  1. 1. Hypersensitivity Reactions FE A. BARTOLOME, MD. FPASMAP Department of Microbiology Our Lady of Fatima University
  2. 2. <ul><li>Exaggerated or misdirected immune response </li></ul><ul><li>Results in tissue injury or other pathophysiological changes </li></ul><ul><li>Occurs when an already sensitized individual is re-exposed to the same foreign substance </li></ul><ul><li>May be immediate or delayed </li></ul>
  3. 3. <ul><li>Ensuing tissue injury may be caused by: </li></ul><ul><ul><li>Release of vasoactive substances </li></ul></ul><ul><ul><li>Phagocytosis or lysis of cells </li></ul></ul><ul><ul><li>Activation of inflammatory & cytolytic components of complement system </li></ul></ul><ul><ul><li>Release of cytokines, proteolytic enzymes and other mediators of tissue injury or inflammation </li></ul></ul>
  4. 4. <ul><li>Immediate/Anaphylactic type </li></ul><ul><li>IgE-mediated </li></ul><ul><li>Occur within minutes </li></ul><ul><li>Provoked by re-exposure to the same antigen (by contact, inhalation, ingestion or injection) </li></ul><ul><li>Local or systemic </li></ul>Type I Hypersensitivity
  5. 5. TYPE I Source: Robbins PATHOLOGIC BASIS OF DISEASE 6 th ed
  6. 6. <ul><li>LOCAL ANAPHYLAXIS </li></ul><ul><li>Atopy  genetically determined predisposition to develop localized anaphylactic reactions to inhaled or ingested allergens </li></ul><ul><li>(+) family history  chr. 5q31 </li></ul><ul><li>With higher serum IgE levels compared to general population </li></ul>Type I Hypersensitivity
  7. 7. <ul><li>LOCAL ANAPHYLAXIS </li></ul><ul><li>Two phases: </li></ul><ul><ul><li>Initial response </li></ul></ul><ul><ul><ul><li>Vasodilation, vascular leakage, smooth muscle spasm or glandular secretions </li></ul></ul></ul><ul><ul><ul><li>5-30 min. after exposure  subside in 60 minutes </li></ul></ul></ul>Type I Hypersensitivity
  8. 8. <ul><li>LOCAL ANAPHYLAXIS </li></ul><ul><li>Two phases: </li></ul><ul><ul><li>Late-phase reaction </li></ul></ul><ul><ul><ul><li>2-8 hrs. later without additional exposure to antigen </li></ul></ul></ul><ul><ul><ul><li>More intense infiltration of tissues with eosinophils, neutrophils, basophils, monocytes & CD4+ T cells </li></ul></ul></ul><ul><ul><ul><li>With mucosal epithelial damage </li></ul></ul></ul>Type I Hypersensitivity
  9. 9. <ul><li>SYSTEMIC ANAPHYLAXIS </li></ul><ul><li>Occur after administration of heterologous proteins (e.g. antisera), hormones, enzymes, polysaccharides & drugs </li></ul><ul><li>Exposure  itching, hives & skin erythema  contraction of resp. bronchioles + resp. distress </li></ul><ul><li>(+) laryngeal edema </li></ul>Type I Hypersensitivity
  10. 10. <ul><li>CLINICAL EXAMPLES: </li></ul><ul><li>Atopic disorders </li></ul><ul><ul><li>Allergic rhinitis, hay fever, asthma, atopic dermatitis, urticaria </li></ul></ul><ul><li>Anaphylaxis </li></ul>Type I Hypersensitivity
  11. 11. <ul><li>PRIMARY MEDIATORS: </li></ul><ul><li>BIOGENIC AMINES </li></ul><ul><ul><li>Histamine </li></ul></ul><ul><ul><li>Adenosine – enhance mast cell mediator release </li></ul></ul><ul><li>CHEMOTACTIC MEDIATORS </li></ul><ul><li>ENZYMES – proteases, acid hydrolases </li></ul><ul><li>PROTEOGLYCANS – heparin, chondroitin sulfate  package & store other mediators in the granules </li></ul>Type I Hypersensitivity
  12. 12. <ul><li>SECONDARY MEDIATORS: </li></ul><ul><li>LEUKOTRIENES – LTC 4 , LTD 4  most potent vasoactive & spasmogenic agents known; LTB 4 (chemotaxis) </li></ul><ul><li>PROSTAGLANDIN D 2 – most abundant in mast cells </li></ul><ul><li>PAF – release of histamine, bronchospasm, inc. vasc. permeability, vasodilation </li></ul><ul><li>CYTOKINES – e.g. TNF  , IL-1, IL-3, IL-4, IL-5, IL-6 </li></ul>Type I Hypersensitivity
  13. 13. <ul><li>DIAGNOSIS: </li></ul><ul><li>History </li></ul><ul><li>Skin prick test – (+) wheal & flare </li></ul><ul><li>Blood eosinophilia </li></ul><ul><li>RAST (Radioallergosorbent assay) </li></ul>Type I Hypersensitivity
  14. 14. <ul><li>TREATMENT: </li></ul><ul><li>Anti-histamine – acts on first phase only </li></ul><ul><li>Corticosteroids – late phase reaction </li></ul><ul><li>Desensitization – to induce tolerance; no IgE production  deplete already bound IgE </li></ul>Type I Hypersensitivity
  15. 15. <ul><li>Mediated by antibodies directed toward antigens present on the surface of cells or other tissue components </li></ul><ul><li>IgG and IgM </li></ul><ul><li>Antigenic determinants – intrinsic or exogenous </li></ul>Type II Hypersensitivity
  16. 16. <ul><li>MECHANISMS: </li></ul><ul><li>Complement-Dependent Reactions </li></ul><ul><li>Antibody-Complement-mediated lysis </li></ul><ul><li>Antibody (IgM/IgG) + antigen on cell surface  (+) activation of complement system  (+) MAC </li></ul>Type II Hypersensitivity
  17. 17. MECHANISMS: Complement-Dependent Reactions Type II Hypersensitivity Source: Robbins PATHOLOGIC BASIS OF DISEASE 6 th ed.
  18. 18. <ul><li>MECHANISMS: </li></ul><ul><li>Complement-Dependent Reactions </li></ul><ul><li>Transfusion reactions </li></ul><ul><li>Erythroblastosis fetalis </li></ul><ul><li>Autoimmune hemolytic anemia, agranulocytosis, thrombocytopenia – (+) antibodies vs own blood cells </li></ul><ul><li>Pemphigus vulgaris – Ab’s vs. desmosomes </li></ul><ul><li>Drug reactions </li></ul>Type II Hypersensitivity
  19. 19. <ul><li>MECHANISMS: </li></ul><ul><li>Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) </li></ul><ul><li>due to NK activity  non-sensitized cells with Fc receptors </li></ul><ul><li>Ab + Ag  activation of NK cells  bind to Fc fragment of IgG  cell lysis without phagocytosis </li></ul><ul><li>Destruction of targets too large to be phagocytosed (parasites, tumor cells) + graft rejection </li></ul>Type II Hypersensitivity
  20. 20. MECHANISMS: Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) Type II Hypersensitivity Source: Robbins PATHOLOGIC BASIS OF DISEASE 6 th ed.
  21. 21. <ul><li>MECHANISMS: </li></ul><ul><li>Antibody-Mediated Cellular Dysfunction </li></ul><ul><li>Antibodies directed against cell surface receptors  impair or dysregulate function </li></ul>Type II Hypersensitivity Source: Robbins PATHOLOGIC BASIS OF DISEASE 6 th ed.
  22. 22. <ul><li>MECHANISMS: </li></ul><ul><li>Antibody-Mediated Cellular Dysfunction </li></ul><ul><li>Myasthenia gravis – acetylcholine receptors </li></ul><ul><li>Goodpasture’s syndrome – type IV collagen </li></ul><ul><li>Pernicious anemia – intrinsic factor </li></ul><ul><li>Acute rheumatic fever – antibodies vs. Streptococcal antigens cross-react with heart </li></ul>Type II Hypersensitivity
  23. 23. <ul><li>Immune Complex Mediated </li></ul><ul><li>Formation of immune complexes in circulation  deposit in various tissues  trigger classical pathway of complement activation </li></ul><ul><li>Produce damage as they localize within blood vessel walls or when trapped in filtering structures (e.g. renal glomeruli) </li></ul>Type III Hypersensitivity
  24. 24. Type III Hypersensitivity Source: Robbins PATHOLOGIC BASIS OF DISEASE 6 th ed.
  25. 25. Type III Hypersensitivity Source: Robbins PATHOLOGIC BASIS OF DISEASE 6 th ed.
  26. 26. Type III Hypersensitivity Source: Robbins PATHOLOGIC BASIS OF DISEASE 6 th ed.
  27. 27. Antigens Associated with Immune Complex Disorders Type III Hypersensitivity SLE Rheumatoid arthritis Glomerulonephritis ENDOGENOUS Nuclear antigens Immunoglobulins Tumor antigens Arthritis GN, Infective endocarditis Glomerulonephritis Polyarteritis nodosa Glomerulonephritis Farmer’s lung EXOGENOUS Infectious agents: Bacteria: Y. enterocolitica Streptococci T. pallidum Viruses: Hep. B, CMV Parasites: Plasmodium Schistosoma Fungi: Actinomycetes CLINICAL MANIFESTATION ANTIGEN
  28. 28. <ul><li>SERUM SICKNESS </li></ul><ul><li>Patient forms antibodies to xenogeneic Ig administered during passive immune therapy regimens </li></ul><ul><li>ARTHUS REACTION </li></ul><ul><li>Seen when boosters are administered to individuals who already possess high antibody titers to vaccine molecules </li></ul><ul><li>Localized area to tissue necrosis  edema, hemorrhage, ulceration </li></ul><ul><li>Develop over a few hours </li></ul>Type III Hypersensitivity
  29. 29. <ul><li>Cell-mediated hypersensitivity </li></ul><ul><li>Initiated by sensitized T lymphocytes </li></ul><ul><li>Principal pattern of immunologic response to intracellular microbiologic agents (particularly Mycobacterium tuberculosis ) as well as viruses, fungi, protozoa & parasites </li></ul>Type IV Hypersensitivity
  30. 30. <ul><li>Two forms: </li></ul><ul><ul><li>Delayed-type hypersensitivity </li></ul></ul><ul><ul><ul><li>Mediated by CD4 T cells </li></ul></ul></ul><ul><ul><ul><li>1 st exposure to Ag  CD4 T cells + class II MHC  differentiation of naïve CD4 T cells to T H 1 cells  release of IL-12, IFN-  , IL-2, TNF  & lymphotoxin </li></ul></ul></ul><ul><ul><ul><li>Tuberculin skin test, contact dermatitis, granulomatous inflammation </li></ul></ul></ul>Type IV Hypersensitivity
  31. 31. <ul><li>Two forms: </li></ul><ul><ul><li>T Cell-Mediated Cytotoxicity </li></ul></ul><ul><ul><ul><li>Mediated by CD8+ T cells </li></ul></ul></ul><ul><ul><ul><li>Sensitized CD8+ T cells kill antigen-bearing target cells </li></ul></ul></ul><ul><ul><ul><li>Graft rejection, virus infections, tumor immunity </li></ul></ul></ul>Type IV Hypersensitivity
  32. 32. <ul><li>Two forms: </li></ul><ul><ul><li>T Cell-Mediated Cytotoxicity </li></ul></ul><ul><ul><ul><li>Two mechanisms: </li></ul></ul></ul><ul><ul><ul><ul><li>Perforin-granzyme-dependent killing  cause perforation of plasma membrane </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Fas-FasL-dependent killing  activation of apoptosis </li></ul></ul></ul></ul>Type IV Hypersensitivity

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