Notes on Hypersensitivities and Autoimmunity Diseases

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Hypersensitivities:

• Sensitize lymphocytes.

• Second exposure elicits greater damage.

• Response is antigen-specific.

• Class II MHC genes: strongest linkage to autoimmune disease.

Type I (Immediate):

• IgE and mast-cell mediated.

• Manifested within minutes.

• Topic or allergic responses.

• First time: TH2 releases IL4 and stimulates B-cell to produce IgE.

• 2-4 hours later, a late-phase reaction occurs; mediated by arachidonic acid cascade.

Type II (Antibody-Mediated):

• Autoantibodies against tissue.

• Activate complement, neutrophils and macrophages.

• Interfere with cellular function.

Hemolytic Disease of Newborn AKA Erythroblastosis Fetalis:

Cause:

• Rh+ fetal cells enter maternal blood and elicit B cells to produce IgG against RhD.

• During second pregnancy, IgG anti-D antibodies from Rh- mother cross placenta to attack Rh+ fetus.

Treatment:

• Give anti-RhD IgD to mother; anti-RhD IgD binds to RhD, clearing it off before maternal immune system officially mounts an attack against RhD.

• Given at 28 weeks of gestation and 72 hours after birth.

Type III (Immune Complex):

• Self or foreign antigens bound to antibodies.

• Systemic disease; no organ/tissue specificity.

• Eg., SLE: anti-dsDNA and anti-Sm antibodies.

• Rheumatoid arthritis: anti-IgM vs IgG Fc region.

Type IV (T Cell Mediated):

• Initiated by T lymphocytes.

• Delayed hypersensitivity reaction.

• CD4+ TH1 cells and CD8+ cells release cytokines that activate macrophages and induce inflammation.

• Eg., Type I diabetes, multiple sclerosis, tuberculin test.

Strongest association with autoimmune disease: class II MHC genes.

HLA Linked Diseases:

Rheumatoid Arthritis:

• DR4.

Insulin-Dependent Diabetes Mellitus:

• DR3/DR4.

Multiple Sclerosis:

• DR2.

SLE:

• DR2/DR3.

Ankylosing Spondylitis:

• B27.

Celiac Disease:

• DQ2 or DQ8.

Additional Readings:

Basic Immunology

1. Introduction to Immunology
2. Cells of Immunology
3. Selection of Lymphocytes
4. Primary Response to Antigen
5. Antigen Processing and Presentation
6. Humoral Effector Mechanism Generator
7. Cell-Mediated Effector Mechanism Generator
8. Vaccination and Immunotherapy
9. Immunodeficiency Diseases
10. Acquired Immunodeficiency Syndrome
11. Hypersensitivities and Autoimmunity Diseases
12. Immunology of Transplantation
13. Immunology of Cancer
14. Immunology Laboratory Technology
15. Acquired Immunity
16. Type II Hypersensitivity Reaction
17. Hypersensitivity Reactions
18. Primary Immunodeficiency
19. Secondary Immunodeficiency
20. Type III Hypersensitivity Reaction
21. Type IV Hypersensitivity Reaction
22. Type V Hypersensitivity Reaction
23. Tumor Immunology
24. Images of Antibodies
25. Th1 vs Th2 cells

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