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Immune System Disorders Hypersensitivities (≈ Allergies) I) Anaphalactic II) Cytotoxic III) Immune Complex IV) Cell-mediated (Delayed) Autoimmune Diseases Transplant Rejection Hypersensitivity results from a second exposure to what could be normally harmless antigen (≈ allergen). The second response is not an appropriate normal one. The immune system goes too far.

Immune System Disorders Hypersensitivities (≈ Allergies) I) Anaphalactic II) Cytotoxic III) Immune Complex IV) Cell-mediated (Delayed) Autoimmune Diseases

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Page 1: Immune System Disorders Hypersensitivities (≈ Allergies) I) Anaphalactic II) Cytotoxic III) Immune Complex IV) Cell-mediated (Delayed) Autoimmune Diseases

Immune System Disorders

Hypersensitivities (≈ Allergies)I) Anaphalactic

II) Cytotoxic

III) Immune Complex

IV) Cell-mediated (Delayed)

Autoimmune Diseases

Transplant Rejection

Hypersensitivity results from a second exposure to what could be normally harmless antigen (≈ allergen). The second response is not an appropriate normal one. The immune system goes too far.

Page 2: Immune System Disorders Hypersensitivities (≈ Allergies) I) Anaphalactic II) Cytotoxic III) Immune Complex IV) Cell-mediated (Delayed) Autoimmune Diseases

I) AnaphalaxisAllergies to pollen, pet dander, insect venoms, fungal spores, dust mites, peanuts, & penicillin.

Localized: (asthma, allergic rhinitis; true food allergies)

Systemic (anaphalactic shock): vasodilation throughout body, BP drops; capillaries become porous; edema; constricts brachioles; fatality.

IgE from first exposure to antigen (≈ allergen) bind to mast cells and basophils; the person is “sensitized”.

Page 3: Immune System Disorders Hypersensitivities (≈ Allergies) I) Anaphalactic II) Cytotoxic III) Immune Complex IV) Cell-mediated (Delayed) Autoimmune Diseases
Page 4: Immune System Disorders Hypersensitivities (≈ Allergies) I) Anaphalactic II) Cytotoxic III) Immune Complex IV) Cell-mediated (Delayed) Autoimmune Diseases

Treatment of Anaphalaxis

• Short-Term:

- anti-histamines; epinephrine

- leukotriene receptor blockers

• Long-Term:

- Controlled repeat exposures; boost IgG

Page 5: Immune System Disorders Hypersensitivities (≈ Allergies) I) Anaphalactic II) Cytotoxic III) Immune Complex IV) Cell-mediated (Delayed) Autoimmune Diseases

II) Cytotoxic• IgG and IgM antibodies bind to foreign antigens on the

surface of otherwise healthy human blood cell types.

• This results in activation of the complement cascade via the classic pathway, which leads to cytolysis of blood cells with the foreign antigen.

• Further antibody and complement C3b binding results in opsonization (i.e. enhanced phagocytosis by phagocytes) of the blood cells with the foreign antigen.

• Which foreign antigens will cause a cytotoxic reaction?– AB red blood cell (RBC) antigens & Rh RBC antigen

– Drugs (haptens) that bind to blood platelets to become antigenic.

Page 6: Immune System Disorders Hypersensitivities (≈ Allergies) I) Anaphalactic II) Cytotoxic III) Immune Complex IV) Cell-mediated (Delayed) Autoimmune Diseases

Transfusion Rh Incompatibility & Hemolytic Disease of the Newbornes

Page 7: Immune System Disorders Hypersensitivities (≈ Allergies) I) Anaphalactic II) Cytotoxic III) Immune Complex IV) Cell-mediated (Delayed) Autoimmune Diseases

Thrombocytopenic purpura

Bruising due to low platelet count; poor clotting favors hemorrhages.

Intracerebral hemorrhaging

Stroke

= thrombocyte

Page 8: Immune System Disorders Hypersensitivities (≈ Allergies) I) Anaphalactic II) Cytotoxic III) Immune Complex IV) Cell-mediated (Delayed) Autoimmune Diseases

III) Immune ComplexThe right proportions of antigen to IgG antibody results in small immune complexes avoid phagocytosis and instead get stuck beneath endothelial cells of capillaries. Damaging to kidney glomeruli (glomerulonephritis).

Page 9: Immune System Disorders Hypersensitivities (≈ Allergies) I) Anaphalactic II) Cytotoxic III) Immune Complex IV) Cell-mediated (Delayed) Autoimmune Diseases

IV) Cell-Mediated (Delayed)Takes days not hours or minutes; requires T cell and macrophage migration to foreign antigen exposure sight.

Allergic Contact Dermatitis:

Latex gloves

Poison ivy

TB skin test is cell-mediated.

Page 10: Immune System Disorders Hypersensitivities (≈ Allergies) I) Anaphalactic II) Cytotoxic III) Immune Complex IV) Cell-mediated (Delayed) Autoimmune Diseases

Autoimmune Diseases• Lymphocytes become involved in attacking the bodies own cells (antigens).

• Self-tolerance of lymphocytes is lost: B cells produce antibodies and Tc cells activate their cytotoxicity.

Causes:• Similarities between viral and self antigens (Hepitius C autoimmunity).

• Cell malfunction due to antibody binding (Grave’s Disease; thyroid gland).

• Immune complex forms (rheumatoid arthritis; joints).

• Cell-mediated destruction of specific cell types (insulin-dependent diabetes mellitus; insulin-secreting cells of pancreas).

• Some individuals are genetically predisposed (higher risk) due to specific human leukocyte antigen (HLA) gene alleles that they possess.

Page 11: Immune System Disorders Hypersensitivities (≈ Allergies) I) Anaphalactic II) Cytotoxic III) Immune Complex IV) Cell-mediated (Delayed) Autoimmune Diseases

Transplant Rejection• Non-self hypothesis: for most tissues if the HLA classes do not match

there will be rejections by T cell, antibody, and complement attack on transplant blood vessels; see graft-versus-host (GVH) disease.

• This does not apply for privileged sites; those that are non-vascular (cornea, heart valves); rare exceptions.

• Grafts are the new tissues transplanted to a target site.– Autographs; – isographs; – allographs; and – xenographs.

• Immunosuppression by cyclosporine to minimize transplant rejection; its action is suppression of IL-2 release. Other IL-2 receptor blockers are also available (rapamycin).