Your SlideShare is downloading. ×
0
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Hypersenstivty
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×
Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

Hypersenstivty

2,912

Published on

immune response

immune response

Published in: Education, Business, Technology
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
2,912
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
269
Comments
0
Likes
1
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. Hypersensitivity
  • 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. 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. 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 -&gt;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. 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. 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. 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. Mediators released by mast cells <ul><li>Primary mediators (preformed): heparin, histamine, neutral protease, eo-sinophil &amp; 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. Mechanism of typeⅠhypersensitivity <ul><li>Allergen-&gt;host-&gt;specific B-cell-&gt;IgE-&gt;Fc fragment of IgE binding FcεRⅠon mast cells/ basophils </li></ul><ul><li>Allergen once again enter the host -&gt;binding IgE -&gt;cross-linking of IgE -&gt; cross-linking of FcεRⅠ -&gt; mast cell activation -&gt; degranulation-&gt; mediators release-&gt; anaphylaxis symptoms </li></ul>
  • 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. The mechanism of typeⅠhypersensitivity
  • 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. 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. <ul><li>Food allergies : diarrhea, vomiting, wheal and flare reaction </li></ul><ul><li>Atopic dermatitis : eczema , urticaria. itch, desquamation, pachyderma </li></ul>
  • 15. &nbsp;
  • 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>
  • 17. Atopic allergies and their treatment
  • 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-&gt; im-munity activation-&gt;Ab-&gt;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
  • 19. Mechanism of tissue damage of typeⅡ hypersensitivity
  • 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>
  • 21. Heamolytic diseases of newborn <ul><li>Rh incompatibility: Rh blood groups </li></ul><ul><li>Rh- mother has the first Rh+ baby-&gt; mother sensitized by baby’s erythrocy-tes -&gt;anti-Rh IgG </li></ul><ul><li>Mother has the second Rh+ baby-&gt; IgG enter the fetus through placenta-&gt; destruction of fetal RBC </li></ul>
  • 22. Hemolytic disease of the newborn due to rhesus incompatibility
  • 23. Drug-induced hemolytic anemia <ul><li>Drug adsorb RBC proteins-&gt;Anti-RBC IgG/IgM-&gt;complement, opsonization, ADCC -&gt;RBC lysis, anemia </li></ul>
  • 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>
  • 25. Myasthenia gravis Grave’s disease
  • 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>
  • 27. Mechanism of type Ⅲ hypersensitivity
  • 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>
  • 29. Immune complex-mediated (type Ⅲ) hypersensitivity
  • 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>
  • 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
  • 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-&gt;Ag:MHCⅡ-&gt;effector T-cell-&gt;MCP-1, IFN-γ, TNF, IL-2-&gt;Mφ attraction and activation-&gt;tissue damage </li></ul>
  • 33. Immune pathogenesis <ul><li>CD8+CTL: primed CTL-&gt;Ag:MHCⅠ-&gt; perforin/ Fas-FasL-&gt;target cell death </li></ul>
  • 34. &nbsp;
  • 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
  • 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>
  • 37. &nbsp;
  • 38. &nbsp;
  • 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>
  • 40. Thanks!
  • 41. Clustering of IgE receptors
  • 42. Patholo-gical changes in asthma
  • 43. An atopic eczema reaction
  • 44. ADCC mediated by NK
  • 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
  • 46. Histology of acute inflammatory reaction in type Ⅲ hypersensitivity
  • 47. IgE mediated mast cell activation and degranulation
  • 48. Skin reaction of atopic allergy (Skin prick tests)
  • 49. Deposition of immune complex in the kidney glomerulus
  • 50. Vasculitic skin rashes due to immune complex deposition
  • 51. Granuloma in tuberculosis infection
  • 52. &nbsp;

×