Immunological tolerance and hyper sensitivity reaction


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Immunological tolerance and hyper sensitivity reaction

  1. 1. Immunological Tolerance and hyper sensitivity reaction 1
  2. 2. Went to talk today • Immunological Tolerance • IgE-Mediated (Type I) Hypersensitivit • Antibody-Mediated Cytotoxic (Type II) Hypersensitivity • Immune Complex–Mediated (Type III) Hypersensitivity 2
  3. 3. Contents 1 2 3 Tolerance Definition T-Cell and B-Cell tolenace IgE-Mediated (Type I) Hypersensitivity
  4. 4. What is Immunologic Tolerance? • Tolerance refers to the specific immunological nonreactivity to an antigen resulting from a previous exposure to the same antigen. While the most important form of tolerance is non-reactivity to self antigens, it is possible to induce tolerance to nonself antigens. When an antigen induces tolerance, it is termed tolerogen
  5. 5. Classification Immunologic tolerance Central tolerance Peripheral tolerance
  6. 6. • Central Tolerance - this occurs during lymphocyte development. • Peripheral Tolerance - occurs after lymphocytes leave the primary organs. 7
  7. 7. • Central Tolerance • T cells • As we have already seen, during T cell development in the thymus the process of negative selection leads to the deletion of thymocytes whose T cell receptors have 'high affinity' for self. • B cells • During B cell development in the bone marrow when the complete antigen receptor (IgM) is first expressed on 'immature' B cells if those cells encounter their target antigen in a form which can cross-link their sIgM then such cells are programmed to die (deleted from the repertoire). 8
  8. 8. Story discovary • This was discovered many years ago when it was shown that injection of a polyclonal anti-IgM from birth prevented the development of B cells, resulting in a 'B-less' mouse. The requirement for crosslinking means that the antigen has to be polyvalent, the most obvious example of this being cellsurface molecules. This has been directly demonstrated by using transgenic mice expressing rearranged Immunoglobulin genes specific for natural or artificial membrane bound molecules. Presumably other multivalent self antigens to which immature B cells are exposed also induce deletion of self reactive cells. 9
  9. 9. • Peripheral Tolerance • after the immune system has matured there need to be some mechanisms to prevent autoreactivity of lymphocytes after they have emigrated from the thymus/bone marrow. In fact there are several such mechanisms: • Ignorance • Suppression • Anergy • Split Tolerance • 10
  10. 10. Advantages & disadvantages of tolerance • Advantages 1. Self-tolerance is essential for the function of the immune system 2. Tolerance to foreign tissue grafts 3. Gene therapy 4. Control of damaging immune responses such as: i. ii. • Hypersensitivity Autoimmune diseases Disadvantages 1. Tolerance to certain foreign antigens that cause disease such as bacterial infections 2. Tolerance to some self-antigens associated with cancer
  11. 11. hyper sensitivity reaction • IgE-Mediated (Type I) Hypersensitivity • Antibody-Mediated Cytotoxic (Type II) Hypersensitivity • Immune Complex–Mediated (Type III) Hypersensitivity 12
  12. 12. Antibody-mediated Hypersensitivity (Hyper123)
  13. 13. IgE-Mediated (Type I) Hypersensitivity • Role of Mast Cells and IgE in Type One Allergy 14
  14. 14. 15
  15. 15. IgE &Mast Cells (MastCell) See also: Figure 16-3 Immunology, 5th Ed p. 365
  16. 16. Mediators of Type I hypersensitivity Preformed mediators 1. 2. 3. 4. 5. Histamine Heparin Eosinophil chemotactic factor of anaphylaxis (ECFA) Neutrophil chemotactic factor Serotonin Newly synthesized mediators 1. 2. 3. Prostaglandins Thromboxanes Leukotrienes • Slow reacting substance of anaphylaxis (SRS-A) Allergen
  17. 17. • Presentaion made by: • Doaa alhariri 18