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Hypersensitivity

Hypersensitivity. M. Jurajda. Immune response. Specificity and memory. Immunopathology. Immune system can react: too little – immunodeficiency to wrong target – autoimmunity too much - hypersensitivity. Hypersensitivity reactions. I. Anaphylactic – immediate - AB

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Hypersensitivity

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  1. Hypersensitivity M. Jurajda

  2. Immune response • Specificity and memory

  3. Immunopathology • Immune system can react: • too little – immunodeficiency • to wrong target – autoimmunity • too much - hypersensitivity

  4. Hypersensitivity reactions • I. Anaphylactic – immediate - AB • II. Cytotoxic - immediate - AB • III. Complex mediated - immediate - AB • IV. Cell mediated – delayed - cells • (V. Stimulating antibodies) • Coombs and Gell 1975

  5. Typical course of hypersensitivity reaction • Sensitization = first contact with allergen • Elicitation = repeated contact

  6. Anaphylactic reaction • IgE mediated immediate reaction

  7. 1901 Albert of Monaco cruised Mediterrian sea on board of Princess Alice II • Charles Richet and Paul Portier

  8. Portuguese man-of-war (Physalia physalis)

  9. Dog Neptune died after 3rd nonlethal dose of sea anemone poisson • They expected just opposite! • Well, we do not know what it is. We should name it at least. • Profylaxis → anafylaxis

  10. Charles Richet was awarded by the Nobel prize in 1913 .

  11. 1921 • Otto Prausnitz and Heinz Küstner (alergic) • Mr. Küstner was interested why he had suffed allergic reaction after eating fish. • Mr. Kustner injected Mr. Prausnitz with his serum into the skin. Injection of fish extract followed leading to skin reaction. • PK reaction

  12. IgE • IgE was simultaneously discovered in 1966-7 by two independent groups: Ishizaka's team at the Children's Asthma Research Institute and Hospital in Denver, Colorado, and by Gunnar Johansson and Hans Bennich in Uppsala, Sweden. Their joint paper was published in April 1969.

  13. Anaphylactic shock • Generalized reaction

  14. Local Allergy • Hay fever • Food allergy • Allergic asthma • Urticaria - hives • Atopic dermatitis – more complex reaction comparing to urticaria

  15. Two phases of allergic reaction • 1st phase release of histamin, TNF, PAF, prostaglandin D2, leukotriene C4 • Vasodilatation, vascular leakage, bronchoconstriction, mucus production • 2nd phase 6-12 hours inflamatory response • Enzymes, products of eosinophils

  16. Why people react in this way? • Th2 paradigm • Th1 paradox • Hygiene hypothesis • Atopy

  17. Th2 paradigm

  18. Th1 paradox

  19. Anaphylactoid reaction • Histamin liberators • Selye 1968 • Iodinated contrast media, insect sting • Direct effect on mast cells

  20. Histamine poisoning • It can happen with fish meal. • Conditions required: • (a) fish proteins containing much histidine • (b) sloppy fish cleaning, spilling bacteria that contain histidine decarboxylase • (c) delayed refrigeration. • Symptoms: flushing, headache, racing pulse, vomiting, diarrhea, itching, swelling of the face and tongue, and sometimes wheezing.

  21. Cytotoxic reaction • IgG mediated immediate reaction

  22. Antibody dependent Complement mediated cytotoxicity Cell-mediated cytotoxicity (ADCC) Antibody dependent cellular dyfunction (V.)

  23. Examples • ABO mismatch blood transfusion • Anti A/B antibodies probably generated against the gut bacteria • Rh hemolytic disease of fetus • Antigens bind to normal cell surfaces • Mechanism of early rejection reaction

  24. Complex mediated reaction • Immune complexes antibodies combined with soluble antigens • Complement is activated leucocytes are attracted

  25. Local reaction – Arthus phenomenon

  26. Local reaction – Arthus phenomenon

  27. Examples • Serum sickness – diphteria tratment

  28. Examples immunocomplexes • Glomerulonephritis IgG against basement membrane

  29. Polyarteritis nodosa • Hypersensitivity pneumonitis

  30. Cell mediatedDelayed type hypersensitivity

  31. Contact dermatitis • Hapten • Nickel, latex etc.

  32. Hapten-protein complex is picked up by APC delivered into lymph node and activated Th1 go to the bloodstream

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