Assessment of immune function Management of patients with immunodeficiency disorders

1. Assessment of immune functionManagement of patients with immunodeficiency disorders

2. Disorders of Immune System • Defenses against infection • Immune system disorders • Autoimmune diseases • Immunodeficiency

3. Defenses Against Infection • Barriers (non-specific) • Skin • Mechanical removal (coughing, vomiting, diarrhea, skin sloughing) • Normal flora • Antimicrobial secretions • Inflammation (non-specific) • Immunity (specific)

4. Immune Response • Natural vs. Acquired • Active vs. Passive • Primary vs. Secondary • Humoral vs. Cell-Mediated

5. Humoral Immunity • B Lymphocytes (Plasma Cells) • Produced in bone marrow • Make antibodies (immunoglobulins)

6. Antibodies • Protein molecules produced by B-cells • Specific shapes allow binding to specific molecules (antigens) • Allow body to respond defensively to presence of specific potential threats

7. Antibody Types • IgG • IgM • IgA • IgD • IgE

8. IgG • Most common antibody type • Only antibody that crosses placenta • Prime mediator of secondary immune response • Principal defender against bacteria, viruses, and toxins

9. IgM • Macroglobulin • Confined to bloodstream • First antibody to appear in response to presence of antigen • Agent of primary immune response

10. IgA • Secretory antibody • Found in saliva, tears, respiratory secretions, GI tract secretions • Frontline bacterial, viral defense

11. IgD • Role not fully understood • Low serum levels • High concentrations on B-cells • May act as receptors that trigger production of other antibodies

12. IgE • Very low serum levels • Primarily bound to mast cells in tissues • Controls allergic response • Prevents parasitic infections

13. Antigen-antibody binding initiates reactions that: • Neutralize bacterial toxins • Neutralize viruses • Promote phagocytosis • Activate components of inflammatory response

14. Cell-Mediated Immunity • T Lymphocytes • Originate in bone marrow • Altered by passage through thymus • Responsible for mediation of cellular immunity

15. T Lymphocyte Types • Helper cells (T4 cells) • Cytotoxic cells (Killer T cells) • Suppressor cells • Memory cells

16. Helper T-Cells • Master “on-switch” of immune system • Recognize antigens • Secrete lymphokines that activate all other immune system cells • Stimulate B-cells to begin antibody production

17. Cytotoxic (Killer) T-Cells • Respond to presence of antigens and lymphokines produced by T-4 cells • Seek out, bind to, and destroy: • Cells infected by viruses • Some tumor cells • Cells of tissue transplants • Can deliver lethal hits on multiple cells in sequence

18. Suppressor T-Cells • Produce lymphokines that inhibit proliferation of B and T cells • Downregulate or dampen immune response

19. Memory T-Cells • Have previously encountered specific antigens • Respond in enhanced fashion on subsequent exposures • Induce secondary immune response

20. Inflammation • Occurs in vascularized tissue • Nonspecific response to injury • Response is same regardless of agent that initiates it

21. Inflammation: Physiology • Triggered by cellular injury • Injury activates mast cells • Mast cells release chemical mediators: • Histamine • Heparin • Leukotrienes (SRS-A) • Eosinophil chemotactic factor

22. Inflammation: Pathology • Mediators cause: • Vasodilation (redness, heat) • Vascular permeability (swelling) • White cell movement to and infiltration of affected area (pus) • Nerve ending stimulation (pain) “Dolor, Calor, Tumor, Rubor”

23. Inflammation: Purposes • Confines injurious agents • Increases blood cell, plasma movement to injured areas • Enhances immune response • Destroys injurious agents • Promotes healing

24. Inflammation: Cellular Components • Neutrophils • Phagocytic cells • Engulf foreign material/organisms • Arrive early • Short-lived

25. Inflammation: Cellular Components • Macrophages • Phagocytic cells • Engulf foreign material/organisms • Arrive later • Long-lived • Transfer antigens back to T4 cells • Help initiate immune response to specific agents

26. Inflammation: Cellular Components • Eosinophils • Secrete caustic proteins • Dissolve surface membranes of parasites

27. Disorders of Immunity

28. Autoimmune Disease • Clinical disorder produced by an immune response to a normal tissue component of a patient’s body

29. Autoimmune Diseases • Hyperthyroidism • Primary myxedema • Type I diabetes • Addison’s disease • Multiple sclerosis • Myasthenia gravis

30. Autoimmune Diseases • Rheumatic fever • Crohn’s disease • Ulcerative colitis • Rheumatoid arthritis • Systemic lupus erythematosis

31. Systemic Lupus Erythematosis • Primarily occurs in 20- to 40-year old females • Also in children and older adults • 90% of patients are female • Autoimmune reaction to host DNA • Mortality after diagnosis averages 5% per year

32. Systemic Lupus Erythematosis • Signs/Symptoms • Facial rash/skin rash triggered by sunlight exposure • Oral/nasopharyngeal ulcers • Fever • Arthritis

33. Systemic Lupus Erythematosis • Signs/Symptoms • Serositis (pleurisy, pericarditis) • Renal injury/failure • CNS involvement with seizures/psychosis • Peripheral vasculitis/gangrene • Hemolytic anemia

34. Systemic Lupus Erythematosis • Chronic management • Anti-inflammatory drugs • Aspirin • Ibuprofen • Corticosteroids • Avoidance of emotional stress, physical fatigue, excessive sun exposure

35. Disorders of Immunity Immunodeficiency Diseases

36. Immunodeficiency Diseases • Congenital • Acquired

37. Immunodeficiency Diseases: Congenital • B cell deficiency • Agammaglobulinemia • Hypogammaglobulinemia

38. Immunodeficiency Diseases: Congenital • T cell deficiency • IgA deficiency • Severe combined immune deficiency syndrome (B and T cell deficiency)

39. Immunodeficiency Diseases: Acquired • Nutritional deficiency • Iatrogenic (drugs, radiation) • Trauma (prolonged hypoperfusion) • Stress • Infection (AIDS)