Published on

immune response

Published in: Education, Business, Technology
1 Like
  • Be the first to comment

No Downloads
Total Views
On Slideshare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide


  1. 1. Hypersensitivity
  2. 2. Introduction <ul><li>What is hypersensitivity? </li></ul><ul><li>It is excessive immune response which leads to undesirable consequences, i.e. tissue or organ damage/ dysfunction . </li></ul><ul><li>Type: typeⅠ, Ⅱ, Ⅲ, Ⅳ hypersensitivity </li></ul><ul><li>Ab mediated: typeⅠ, Ⅱ, Ⅲ </li></ul><ul><li>T-cell mediated: type Ⅳ </li></ul>
  3. 3. Type Ⅰ hypersensitivity <ul><li>IgE mediated, immediate hypersensitivity/ allergy </li></ul><ul><li>Major features: </li></ul><ul><li>React and disappear quickly on re-exposure to Ag </li></ul><ul><li>Dysfunction rather than severe tissue and cell damage occurs </li></ul><ul><li>Obvious individual difference and genetic correlation </li></ul>
  4. 4. Component and cells <ul><li>Allergen: An antigen that causes allergy. </li></ul><ul><li>Hapten can turn into allergen by carrier effect (hapten +carrier ->immunogen) </li></ul><ul><li>Common allergen: inhalant allergen (grass pollen, animal dander, feces from mites in house dust, etc.), some kinds of food and drugs </li></ul>
  5. 5. Reaginic antibody (IgE) <ul><li>The main anaphylactic Ab in human </li></ul><ul><li>IgE can bind FcεRⅠon mast cells and basophils by its CH4 domain, cause anaphylaxis </li></ul>
  6. 6. Mast cells <ul><li>Express high affinity IgE Fc receptor FcεRⅠ, granules contain mediators. </li></ul><ul><li>Distribution: connective tissues, mucosa, skin </li></ul><ul><li>Anaphylaxis is triggered by clustering of IgE receptors (FcεRⅠ) on mast cells and basophils through cross-linking </li></ul>
  7. 7. IgE-binding Fc recepors <ul><li>FcεRⅠ: high affinity receptor of IgE on mast cell/ basophil, activate mast cell/ basophil </li></ul><ul><li>FcεRⅡ:low affinity </li></ul>
  8. 8. Mediators released by mast cells <ul><li>Primary mediators (preformed): heparin, histamine, neutral protease, eo-sinophil & neutrophil chemotactic factors, provoke early phase(immediate) reaction </li></ul><ul><li>Secondary mediators (newly synthesi-zed) : leukotrienes(LTB4, LTC4 and LTD4), PGD2, PAF, CKs(IL-4, GM-CSF), induce late phase reaction </li></ul>
  9. 9. Mechanism of typeⅠhypersensitivity <ul><li>Allergen->host->specific B-cell->IgE->Fc fragment of IgE binding FcεRⅠon mast cells/ basophils </li></ul><ul><li>Allergen once again enter the host ->binding IgE ->cross-linking of IgE -> cross-linking of FcεRⅠ -> mast cell activation -> degranulation-> mediators release-> anaphylaxis symptoms </li></ul>
  10. 10. <ul><li>Early phase response : short-lived, resolve within 1 hr. Increase of vasopermeability, smooth muscle contraction, gland hypersecretion and vasodilation </li></ul><ul><li>Late phase response : inflammation, peak at around 5 hrs, last for several days. Eosinophils, mast cells, basophils, T-cells and neutrophils infiltration. </li></ul>
  11. 11. The mechanism of typeⅠhypersensitivity
  12. 12. Typical diseases of anaphylaxis <ul><li>Systemic anaphylaxis( anaphylactic shock ): fatal, venom from bee, wasp; drugs such as penicillin, antitoxins, etc. </li></ul><ul><li>Localized anaphylaxis( atopy ): the tend-ency to manifest localized anaphylaxis is inherited and called atopy. typical diseases: asthma, hayfever, eczema, food allergy, etc. </li></ul>
  13. 13. Atopy <ul><li>Allergic rhinitis: Hay fever, airborn allergens, symptoms include shedding tears, sneezing, coughing, etc. </li></ul><ul><li>Asthma : airborn/blood-born allergens. Occur in lower respiratory tract </li></ul><ul><li>Cardinal clinic and physiological features: variable airflow obstruction, bronchial hyper-responsiveness. </li></ul>
  14. 14. <ul><li>Food allergies : diarrhea, vomiting, wheal and flare reaction </li></ul><ul><li>Atopic dermatitis : eczema , urticaria. itch, desquamation, pachyderma </li></ul>
  15. 16. Therapy of typeⅠhypersensitivity <ul><li>Allergen avoidance : best if possible, but often impractical. Skin test </li></ul><ul><li>Hyposensitivity : repeated injection of increasing doses of allergen. Allergic rhinitis </li></ul><ul><li>Drug: antihistamines; epinephrine (also called adrenaline), etc. Immediate injection of adrenaline could rescue anaphylactic shock </li></ul>
  16. 17. Atopic allergies and their treatment
  17. 18. <ul><li>Mediated by IgG and/or IgM </li></ul><ul><li>Mechanism : </li></ul><ul><li>Ag present on the surface of cells-> im-munity activation->Ab->tissue damage/ dysfunction </li></ul><ul><li>Tissue damage caused by: </li></ul><ul><li>Opsonic adherence : phagocytosis </li></ul><ul><li>Complement : membrane damage </li></ul><ul><li>ADCC : cell destruction </li></ul>Type Ⅱ hypersensitivity
  18. 19. Mechanism of tissue damage of typeⅡ hypersensitivity
  19. 20. Type Ⅱ associated diseases <ul><li>Transfusion reaction: mismatched blood transfusion cause complement-mediated hemolysis. </li></ul><ul><li>ABO blood group : isohemagglutinins(IgM) </li></ul><ul><li>Prevention: cross-matching between donor and recipient blood </li></ul>
  20. 21. Heamolytic diseases of newborn <ul><li>Rh incompatibility: Rh blood groups </li></ul><ul><li>Rh- mother has the first Rh+ baby-> mother sensitized by baby’s erythrocy-tes ->anti-Rh IgG </li></ul><ul><li>Mother has the second Rh+ baby-> IgG enter the fetus through placenta-> destruction of fetal RBC </li></ul>
  21. 22. Hemolytic disease of the newborn due to rhesus incompatibility
  22. 23. Drug-induced hemolytic anemia <ul><li>Drug adsorb RBC proteins->Anti-RBC IgG/IgM->complement, opsonization, ADCC ->RBC lysis, anemia </li></ul>
  23. 24. Grave’s disease and myasthenia gravis <ul><li>Special class of type Ⅱ hypersensitivity, Autoimmune diseases, tissue/organ dysfunction </li></ul><ul><li>Grave’s disease: anti-TSH receptor </li></ul><ul><li>Myasthenia gravis: anti-acetylcholine receptors </li></ul>
  24. 25. Myasthenia gravis Grave’s disease
  25. 26. Type Ⅲ hypersensitivity <ul><li>Participate by IgG/IgM, induced by de-position of immune complex (IC) </li></ul><ul><li>Formation of IC: Excess of antigen over a protracted period </li></ul><ul><li>Deposition frequently observed: blood-vessel walls, synovial membrane of joints, glomerular basement of kidney </li></ul>
  26. 27. Mechanism of type Ⅲ hypersensitivity
  27. 28. <ul><li>Tissue damage caused by: </li></ul><ul><li>Complement activation and attraction of neu-trophils : release tissue damaging mediators </li></ul><ul><li>Stimulation of Mφ : release proinflammatory cytokines </li></ul><ul><li>Aggregation of plate-lets : cause microthrombi and vasoactive amine release </li></ul>
  28. 29. Immune complex-mediated (type Ⅲ) hypersensitivity
  29. 30. Type Ⅲ associated diseases <ul><li>Localized type Ⅲ reaction: the Arthus reaction , erythematous and edematous, intense neutrophil infiltration </li></ul><ul><li>Generalized type Ⅲ reaction: </li></ul><ul><li>Serum sickness: injection of foreign protein (horse serum) </li></ul><ul><li>SLE: systemic lupus erythematosus , DNA/ anti-DNA/ complement </li></ul>
  30. 31. <ul><li>Rheumatoid arthritis: rheumatoid factor (RF): anti-IgG autoantibodies, usually IgM. IgM-IgG complex deposit in joints </li></ul><ul><li>Immune complex glomerulonephritis : Ag-Ab-C3 deposit glomerular basement membrane </li></ul><ul><li>Others: drug reactions, infectious diseases </li></ul>Type Ⅲ associated diseases
  31. 32. Type Ⅳ hypersensitivity <ul><li>Delayed-type(DTH), T-cell mediated, 24-72 hr after Ag contact, Ab not involve </li></ul><ul><li>Results from excessive CMI, secondary response, chronic granuloma </li></ul><ul><li>Mechanism: </li></ul><ul><li>CD4 + Th1: Tm->Ag:MHCⅡ->effector T-cell->MCP-1, IFN-γ, TNF, IL-2->Mφ attraction and activation->tissue damage </li></ul>
  32. 33. Immune pathogenesis <ul><li>CD8+CTL: primed CTL->Ag:MHCⅠ-> perforin/ Fas-FasL->target cell death </li></ul>
  33. 35. <ul><li>Insulin-dependent diabetes mellitus (IDDM): insulin-producing βcells </li></ul><ul><li>Multiple sclerosis(MS): central nervous system, myelin Ag </li></ul><ul><li>Contact dermatitis : foreign low molecular weight materials, hapten-carrier, topical </li></ul><ul><li>Infectious diseases: tuberculosis </li></ul><ul><li>Others: hashimoto’s thyroiditis, IBD </li></ul>Type Ⅳ associated diseases
  34. 36. Summary <ul><li>Hypersensitivity is excessive immune response which leads to undesirable consequences, i.e. tissue or organ damage/ dysfunction . </li></ul><ul><li>Type: typeⅠ, Ⅱ, Ⅲ, Ⅳ hypersensitivity </li></ul><ul><li>Ab mediated: typeⅠ, Ⅱ, Ⅲ </li></ul><ul><li>T-cell mediated: type Ⅳ </li></ul>
  35. 39. Summary <ul><li>Therapy for typeⅠhypersensitivity: </li></ul><ul><li>Allergen avoidance </li></ul><ul><li>Hyposensitivity </li></ul><ul><li>Drug treatment: antihistamines, adrenaline </li></ul>
  36. 40. Thanks!
  37. 41. Clustering of IgE receptors
  38. 42. Patholo-gical changes in asthma
  39. 43. An atopic eczema reaction
  40. 44. ADCC mediated by NK
  41. 45. The ABO system Phenotype genotype Ag on RBC (agglutinins) Ab to ABO in serum (isohem-agglutinins) A AA, AO A Anti-B B BB, BO B Anti-A AB AB A and B none O OO H Anti-A and anti-B
  42. 46. Histology of acute inflammatory reaction in type Ⅲ hypersensitivity
  43. 47. IgE mediated mast cell activation and degranulation
  44. 48. Skin reaction of atopic allergy (Skin prick tests)
  45. 49. Deposition of immune complex in the kidney glomerulus
  46. 50. Vasculitic skin rashes due to immune complex deposition
  47. 51. Granuloma in tuberculosis infection
  1. A particular slide catching your eye?

    Clipping is a handy way to collect important slides you want to go back to later.