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Clinical Immunology When the Immune System Causes Disease
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Clinical Immunology When the Immune System Causes Disease

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  • 1. Clinical Immunology When the Immune System Causes Disease or Doesn’t Work
  • 2. Immune Deficiencies and Hypersensitivities
  • 3. Allergies and Autoimmunity
    • Allergies are IgE immune responses to harmless antigens
    • The immune response causes the disease = hypersensitivity
    • Other hypersensitivities are caused by IgG or by Th1 or Tc activities
    • Autoimmune reactions occur against self antigens
  • 4. Hypersensitivities
  • 5. Type I Hypersensitivity: Allergy
    • Immediate hypersensitivity
    • Reaction in ~ 30 minutes
    • Inflammation
    • Symptoms depend on where allergen enters
  • 6. Common Allergens
    • Pollens
    • Cat dander
    • Dust mite feces
    • Food antigens
  • 7. Type I (Immediate) Hypersensitivity
  • 8. Effects of Allergic Mediators
  • 9.
    • Systemic anaphylaxis : inflammation throughout circulation  death
  • 10. IgE Effector Function
    • Eosinophils bind an IgE-coated schistosome larva via Fc  receptors
  • 11. Hygiene Hypothesis
    • Asthma rates are increasing in the US
    • Children in day care have lower asthma rates than children kept at home
    • People from areas with high helminth infections have low allergy rates
      • When those people move to the US, their allergy rates increase
  • 12. Strategies for Avoiding Allergic Symptoms
  • 13. Allergy Shots
    • Shots induce IgG formation; IgG binds all the allergen so it can’t reach IgE on mast cells
  • 14. Hypersensitivities
  • 15. Type II Hypersensitivity
    • IgG/IgM antibodies bind RBC antigens
    • Complem e nt is activated, lyses RBC
    • ADCC: macrophages or NK cells bind antibody-coated RBC, kill them
  • 16. Hemolytic Disease of the Newborn
  • 17. Prevention of Hemolytic Disease of the Newborn
  • 18. Other Type II Hypersensitivities
    • Medication allergies
    • Mismatched blood (transfusion rxn)
    • Rheumatic fever (Strep throat)
    • Autoimmune hemolytic anemia
  • 19. Hypersensitivities
  • 20. Immune Complex Disease
  • 21. Type III Hypersensitivities
    • Serum sickness: horse anti-snake venom
    • Lyme arthritis
    • Systemic lupus erythematosis (SLE): autoimmune disease
  • 22. Hypersensitivities
  • 23. Type IV: T-Cell Mediated Poison Ivy
  • 24. Contact Dermatitis
  • 25. Type IV Hypersensitivities
    • TB Skin test
    • Contact dermatitis to nickel
    • Chronic asthma
    • Autoimmune diabetes (Type I)
    • Transplant rejection
  • 26. Transplant Rejection Responses
  • 27. Transplant Rejection
    • Organ grafts: Host T cells kill cells in graft with foreign MHC I and II
    • Bone Marrow Transplant: mature T cells in graft kill cells in host with foreign MHC I and II
  • 28. MHC Inheritance
  • 29. Transplant Rejection
    • We each have ~6 different Class I and ~6 different Class II MHC proteins; each has many alleles
    • Best chance of sharing MHC alleles is between close blood relatives
    • No time for tissue typing in heart transplants; just do blood typing
  • 30. Anti-Rejection Drugs
    • Block inflammation
      • corticosteroids
    • Block T cell activity
      • Cyclosporine A
      • monoclonal antibodies
  • 31. Autoimmunity
    • Often triggered by an infection
    • Molecular mimicry : Immune response to a pathogen antigen generates antibodies and T cells that also bind self antigens
    • Linked to certain MHC alleles
  • 32. Autoimmune (Type I) Diabetes
    • Virus infection (Coxsackie)
    • Anti-virus T cells recognize self peptides on islets
    • Islets destroyed --> insulin dependence
  • 33. Role of MHC in Diabetes ©1999 by Elsevier Science Ltd/Garland Publishing From Immunobiology: The immune system in health and disease by Charles A. Janeway
  • 34. Immune Deficiencies
    • Inborn
      • usually a problem in cell development or mutation in gene for an essential protein
    • Acquired
      • usually due to microbe virulence factors
  • 35. Immune Deficiencies
    • Also deficiencies of innate immunity
  • 36. David the “Bubble Boy”
    • SCID: no T or B cells
    • Kept alive in sterile environment
    • Died from cancer caused by EBV in bone marrow transplant from his sister
  • 37. What You Should Know
    • Mechanisms of hypersensitivities
    • Normal function of IgE
    • Role of MHC in transplant rejection and autoimmunity
    • Molecular mimicry trigger for autoimmunity
    • SCID