1. Immune Injury Hypersensitivities Autoimmune Disorders

2. Immune Injury Autoimmunity Immature or defective T-cells Exposure to normally sequestered antigens Cross reactions Thyroiditis SLE Rheumatoid Disorders Diabetes Sometimes genetic predispositions to autoimmunity

3. “Hypersensitivities” Why in quotes? Some are truly “hyper” reactions, e.g. allergies. Others are due to non-self although not by their nature harmful agents, e.g. transfusion or transplantation reactions Some may be caused by normal immune reactions to infectious agents

4. Four Types I anaphylactic type II cytotoxic type III immune complex type IV Delayed-type hypersensitivity

5. Three are humoral, immediate types can be transferred with serum “passive” hypersensitivities Type IV is the only cell-mediated type, would require transfer of lymphocytes for “passive” sensitization

6. They all require a sensitization stage and time for immune response to develop Later exposure is called the challenge stage

7. The term “immediate” refers only to the challenge stage. In the first three types, preformed antibodies cause immediate and usually very obvious reactions CMI, DTH: even though T-cells are already activated, they do not travel to site as quickly as humoral antibodies. May take a few days before reaction is observable.

8. Anaphylactic Type local or regional: hay fever, animal dander, food allergies Systemic: insect venoms, injected drugs e.g. radio-opaque dyes, foods allergy shots

9. Sensitization Stage

12. Effects of Systemic Anaphylaxis Vascular changes – dilation and increased permeability lead to shock Effects on smooth muscle – constrict bronchioles Affect heart action

14. Treatments Long-term Allergy Shots – what’s the theory? Testing for and avoidance of allergens Symptomatic: Antihistamines Anti-inflammatories For systemic anaphylaxis, epinephrine

15. Cytotoxic Type HDN Transfusion Reactions Autoimmune Hemolytic Anemias Idiopathic Thrombocytopenia Purpura

16. Which one does not require a sensitization stage???

18. May also be due to a foreign substance that attaches to a cell, e.g. some drugs, some bacteria

19. Complex-Mediated Injury May occur after some infections Autoimmune disorders Serum Sickness Arthus Reaction, a local, deliberately caused response

20. Effects Inflammation especially in small blood vessels, glomeruli, joints Accumulation of neutrophils and macrophages Tissue damage

22. Role of Complement In which types of immune injury is C’ involved? Cytotoxic Type Complex-Mediated Type Although some damage may be done by antibody-antigen alone, even without C’ activation

23. Delayed Type Injury Contact Sensitivity Tuberculin Reaction

24. Sensitization Stage

25. Part of Sensitization Stage and also occurs at beginning of Challenge Stage

26. Activation of Tc may follow Cytotoxic T cell activity is one form of Cell-Mediated Immunity Tuberculin Response is another. This is the one most often called DTH. Contact Hypersensitivity is another

27. Contact Hypersensitivity Formaldehyde, latex gloves, poison ivy, poison oak, material in flea collars Material attaches to skin cells. T-cells are activated and attempt to destroy & remove the altered skin cells Effects: mild erythema to severe inflammation, blister formation. Because of itching, the host causes additional damage

28. DTH or Tuberculin Rx’n Activated T cells Secrete lymphokines Recruit many other lymphocytes & macrophages to the area So only a minority are antigen-specific cells Tissue Build-up Granuloma Formation

29. Conclusions Immune injuries occur under a variety of circumstances The mechanisms must have derived from protective measures. Else they would not have persisted evolutionarily Some agents may cause several of the types of immune injury, e.g. penicillin Autoimmune Disorders may exhibit a variety of immune injuries

30. End of our coverage of Immune Injury