Immunological Tolerance and hyper sensitivity reaction

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Went to talk today • Immunological Tolerance

• IgE-Mediated (Type I) Hypersensitivit

• Antibody-Mediated Cytotoxic (Type II) Hypersensitivity

• Immune Complex–Mediated (Type III) Hypersensitivity

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Contents

Tolerance Definition1

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3 IgE-Mediated (Type I) Hypersensitivity

T-Cell and B-Cell tolenace

What is Immunologic Tolerance?

• Tolerance refers to the specific immunological non-reactivity 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 non-self antigens. When an antigen induces tolerance, it is termed tolerogen

Classification

Immunologic tolerance

Central tolerance Peripheral tolerance

• Central Tolerance - this occurs during lymphocyte development.

• Peripheral Tolerance - occurs after lymphocytes leave the primary organs.

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• 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

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 cell-surface 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.

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• 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

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Advantages & disadvantages of tolerance

• Advantages 1. Self-tolerance is essential for the function of the immune

system2. Tolerance to foreign tissue grafts3. Gene therapy4. Control of damaging immune responses such as:

i. Hypersensitivityii. Autoimmune diseases

• Disadvantages1. Tolerance to certain foreign antigens that cause disease

such as bacterial infections2. Tolerance to some self-antigens associated with cancer

hyper sensitivity reaction• IgE-Mediated (Type I) Hypersensitivity

• Antibody-Mediated Cytotoxic (Type II) Hypersensitivity

• Immune Complex–Mediated (Type III) Hypersensitivity

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Antibody-mediated Hypersensitivity (Hyper123)

IgE-Mediated (Type I) Hypersensitivity

• Role of Mast Cells and IgE in Type One Allergy

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IgE &Mast Cells (MastCell)

See also: Figure 16-3Immunology, 5th Edp. 365

Mediators of Type I hypersensitivityPreformed mediators

1. Histamine2. Heparin3. Eosinophil chemotactic

factor of anaphylaxis (ECF-A)

4. Neutrophil chemotactic factor

5. Serotonin

Newly synthesized mediators6. Prostaglandins 7. Thromboxanes 8. Leukotrienes

• Slow reacting substance of anaphylaxis (SRS-A)

Allergen

• Presentaion made by:• Doaa alhariri

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