Immunity

1. Immunity Trisha Economidis, MS, ARNP Spring, 2012

2. WAR DECLARED….. • We are at war with our environment • Troops are prepared to fight from every sector of the body to keep us safe (and healthy) • Regiments on the ready include: • Antibodies • Immunoglobulins • White Blood cells • Immune Response Teams: Humoral and Cell-Mediated Immunity • And others…….

3. Immune System Review: Public Enemy Number ONE • Antigen – a protein that stimulates an immune reaction, causing production of antibodies. • Viruses • Bacteria • Fungi • Parasites • Etc…..

4. Immune System Review • Antibody – a globulin (PRO) produced by B cells as a defense mechanism against foreign materials. Combines in a lock and key style with antigens

5. First Line of Defense: Primary Defenses • Prevent organisms from entering the body • Skin • Respiratory Tree • Tears/Saliva • Gi Tract – acidic environment, peristalsis • Bile - antimicrobial • GU tract – mucous membranes

6. Secondary Defenses • Phagocytosis • White blood cells • TO THE RESCUE!

7. Secondary Defense #2 • Complement Cascade • Set of proteins called complement that trigger release of chemicals that attack the cell membranes of pathogens causing them to rupture

8. Secondary Defense #3: Inflammation • Begins when histamine and other chemicals are released directly from damaged cells or from basophils in response to complement • Histamine/chemical release Dilation and increased Permeability of blood vessels flow of phagocytes, antimicrobials, O2, & nutrients to area of damage

9. Secondary Defense #4 • Fever • Increases metabolism • Inhibits pathogen multiplication • Triggers specific immune responses

10. Tertiary Defenses: Specific Immunity • Body recognizes and destroys pathogens encountered before • Lymphocytes – WBCs that mature to either T cells or B cells

11. 2 Types of Specific Immunity • 1. HumoralImmunity– B (lymphs) cells stimulated to become plasma cells and produce antibodies (immunoglobulins) to the antigens. • Antibodies bind to and destroy antigens.

12. Specific Immunity No. 2: • Cell-Mediated Immunity: Acts to destroy body cells that have become infected. • T Cells are responsible for cell-mediated immunity: • Cytotoxic (Killer) T cells • Helper T cells • Memory T cells • Suppressor T cells

13. WBC’s – Name, Rank & Serial Number • Reported in the WBC Differential with a CBC • Basophils 0.5-1% - Release histamine and heparin granules • Eosinophils 1-3% - Destroy helminths, mediate allergic reactions • Monocytes – 3-8% - Phagocytize directly • Lymphocytes (20-35%) – T lymphs – recognize, attack and destroy antigens; B lymphs – produce immunoglobulins to attack and destroy antigens • Neutrophils – 55-70%. First to arrive – Phagocytize! • Bands – Immature neutrophils (normally 3-5% of total WBCs) • Segmented (Segs) – Mature neutrophils –( normally 50-65T of total WBCs)

14. Shift to the Left?????? • In an acute infection more lymphocytes are produced • A “shift to the left” occurs when there are more bands (immature or baby neutrophils) in circulation than there are segs (mature or grownup neutrophils)

15. “Shift to the left” • Higher number of bands than segs (usually when bands reach 6%) in circulation called bandemia. • Indicates body is responding to an acute infection, usually bacterial, or to Stress (i.e. women in childbirth)

16. Immunoglobulins (Ig) – the Special Agents of Humoral Immunity • IgM – Goes after “first time offenders” • IgG – most common one. (AKA: Gamma Globulin) – Active against bacteria and viruses • IgE – primarily responsible for allergic response and parasitic infections • IgA – secreted by mucous membranes around body openings. Provides more protection for points of entry. • IgD – found of surface of B cells. Trap potential pathogens

17. What are the “weapons” of the Immunoglobulin Agents??? • Phagocytosis • Neutralization • Agglutination • Activation of complement and inflammation

18. Two Types of Immunity Innate (Native) Adaptive (Acquired) • Present at birth • First line of defense • Non-specific response • Neutrophils first on the site • Cannot be developed or transferred • Body can make it or receive it • Specific response • Results from adaptive response to invasion by an antigen (antibody formation) • Can be passive or active • Can be naturally produced or artificially acquired

19. Adaptive Immunity

20. Assessment of the Immune system • Chief complaint – subjective data • Review biographic data: age, gender, race, ethnic background, family history • Comprehensive health history • Physical Assessment

21. Immune System Diagnostics • Allergy testing (will discuss with allergies) • Cd4-T cell counts (Helper T’s) – reflection of immune status (normal: 500-1600 cells/mm3) • Viral Load testing – measures the presence of HIV viral genetic material in the patient’s blood rather than the body’s response to the virus • ELISA/Western Blot • Antibody testing • ANA antinuclear antibody

22. Immune System Diagnostics • Rheumatoid Factor • Serum Complement • ESR (erythrocyte sedimentation rate) • HLA testing – Human Leukocyte Antigen

23. Health Promotion and the Immune System – Boosting your Immunity • Diet – Balanced diet • Exercise – Regular, moderate work-outs • Stress relief • Get enough sleep • Use sun exposure protection • Quit smoking or Don’t Start • Avoid Excess alcohol • Immunizations up-to-date

25. Pharmacologic Management of Immune Disorders • Antibiotics (anti-infectives) • Use: treatment/prophylaxis of bacterial infections • Cautions: Can depress bone marrow; Superinfections • Cephalosporins • Penicillins • Fluoroquinolones • Macrolides • Sulfonamides • Tetracyclines

26. Pharmacological Interventions • Antivirals – Destroy viruses either directly or by inhibiting the ability to replicate • acyclovir (Zovirax); HSV-1, HSV-2, VZV • osetamivir (Tamiflu), zanamivir (Relenza); Influenza Types A & B

27. Pharmacological Interventions • Antifungals • Kill or stop growth of fungal infections of skin, mucus membranes, & systemic • Topical • Clotrimazole, ketoconazole, miconazole, nystatin • Systemic • Amphotericin B, fluconazole, ketoconazole

28. Pharmacological Interventions • Anti-inflammatory • Corticosteroids • Used for anti-inflammatory and immunosuppressive properties • Topical, inhaled, intranasal, opthalmic, IV, PO, IM • Long, intermediate, and short-acting

29. Pharmacological Interventions • Antihistamines • Relief of symptoms associated with allergies, rhinitis, urticaria • 1st generation-sedating • Chlor-trimeton (chlorpheninamine) • Dramamine (dimenthydrinate) • Benadryl (dephenhydramine) • Atarax, Vistaril (hydroxyzine) • 2nd generation-non-sedating • Allegra (fexofenadine) • Claritin (loratadine) • Zyrtec (cetirizine)

30. Pharmacological Interventions • Adrenergic sympathomimetic - Epinephrine • Inhibits release of hypersensitivity mediators • Inhibits reaction from mast cells • Produces bronchodilation, vasoconstriction • Epinephrine (Adrenalin) • 0.3mg-0.5 mg subcutaneously or IM (Adults)

31. Pharmacological Interventions • Immunotherapy • SC injections weekly/biweekly of allergen extracts • Goals of Therapy • Stimulate IgG levels for allergen binding • Decrease IgE levels • ALWAYS EXPECT ADVERSE REACTIONS!!!

32. Pharmacological Interventions • Biologic Response Modifers (BRMs) • Broad class of drugs that alter the body’s response to diseases such as cancer and autoimmune, inflammatory and infections diseases • Immune Modulators – either enhance or reduce immune responses (some can do both) • Interferons • Monoclonal antibodies • Interleukins • Disease-modifying antirheumatoid arthritis drugs

33. Pharmacological Interventions • Immunosuppressant Drugs – Decrease or prevent an immune response • cyclosporine (Sandimmune, Neoral, Gengraf) Used to prevent organ rejection in liver, kidney, and heart transplants; treatment of RA and psoriasis. Off-label use in rejection prevention of pancreas, bone marrow, heart/lung transplants. muromonab-CD3 (Orthoclone OKT3) Only one indicated to treat acute organ rejection in kidney, liver and heart transplant

34. Pharmacological Interventions • Antimalarial (What’s this doing HERE?) • Plaquenil (hydroxychloroquine) – used to decrease joint and muscle pain in early or mild Rheumatoid Arthritis or Lupus (SLE) • Gold Therapy – Rarely used in the U.S. because of toxicities, but may see in patients from other countries. • Antigout – • Acute: colchicine and an NSAID • Chronic: allopurinol (Zyloprim), probenecid (Benemid)

35. Organ Donation/Transplant:One Boy’s Story http://www.youtube.com/watch?v=yA8671CyM7w7 year old, Nicholas Green

36. Nursing Management of Clients with Organ Transplants • Transplant success tied to matching tissue antigens, HLA (Human Leukocyte Antigens) • Autograft • Allograft • Xenograft • Histocompatibility – ability of cells and tissues to survive transplantation without immunologic interference by the recipient

37. Host-versus-Graft Transplant Rejection • Complex process involving both antibody-mediated and cell mediated responses • Hyperacute Rejection – Begins immediately and can’t be stopped once it begins • Acute rejection – occurs 1-3 mo post-transplant. Most common rejection and is treatable. • Chronic rejection – occurs from 4 mos to yrs post-transplant. No cure. Once organ cannot function, another transplant is only course.

38. Treatment of Transplant rejection Maintenance therapy – Ongoing immune suppressants Ex. cyclosporin, Imuran & a corticosteroid (prednisone) Rescue therapy – treats acute rejection. Ex: ALG , murononab-CD3. Most effective during first course of treatment

39. What is an allergy? • Allergy is an exaggerated immune response to an antigen (foreign or allergen) to which the patient has been previously exposed. • Also called hypersensitivity

40. Allergy Terminology • Allergen – an antigen that causes an allergic sensitization • Mast cell – a tissue cell that contains granules filled with chemical mediators such as histamine and heparin. Play a major role in allergies as well as immune system function. • Atopic – relating to a hereditary predisposition toward developing certain allergic reactions

41. Why does an allergic reaction occur? • 1. First time exposure to an allergen, our body responds by making “antigen-specific” IgE • 2. The antigen-specific IgE binds to the surface of mast cells and basophils (both have granules containing chemical mediators including histamine that will be released when stimulated) • 3. Once the IgE is formed, we are sensitized to that allergen

42. Hypersensitivity (allergic) Reactions • Type I reaction – occurs when the already sensitized person (see previous slide) is re-exposed to the allergen (IgE mediated) • Histamine and other chemicals are released from the cells • Inflammatory response occurs from other proteins released from the cells that draw more WBC’s to the area

43. Anaphylaxis – Serious Type I Reaction • Immediate life-threatening systemic reaction • Can occur in seconds to minutes • Not common • Life-threatening and can be fatal • What can cause it: allergy shots, insect bites/stings, foods (peanuts, eggs, shellfish, etc.) medications, blood products, contrast media, exercise, skin testing.

44. Anaphylaxis – What does it look like? • Respiratory – bronchospasm, laryngeal edema, wheezing, cough • Cardiovascular – hypotension, tachycardia, palpitations, syncope • Skin – urticaria, angioedema, pruitus, erythema • GI – N/V/D/, abdominal pain

45. Emergency Care • Recognize symptoms • A, B, Cs • Administer drugs -Epinephrine 1:1000 0.3-0.5 mL SQ or Epi-pen 0.3 mL IM (adults), 0.15 mL IM (children) -Oxygen -Antihistamines -Bronchodilators

46. History of Anaphylaxis? • Obtain Medical Alert Bracelet • Carry Epi-pen

47. Did I inherit my allergies? • Yes, and no…. • The tendency to produce IgE to certain antigen exposure is based on genetic inheritance. • Allergic tendencies are inherited (atopy); specific allergies are NOT inherited

48. Other Hypersensitivity Reactions • Type II: Cytotoxic – involve IgG. Body makes antibodies that attack self cells resulting in death of the cell. • Ex. Hemolytic anemias, hemolytic transfusion reactions (person gets wrong blood type in a transfusion)

49. Hypersensitivity Reactions, cont. • Type III: Immune Complex Reactions – too many circulating antigens form large antigen-antibody complexes that lodge in small blood vessel walls; triggering inflammation and tissue damage. • Type IV: Delayed Hypersensitivity Reactions – Sensitized T cells react to antigens by triggering macrophages to destroy the antigen. • Type V: Stimulatory Reactions - autoantibodies constantly stimulate reaction from normal cells resulting in a “turned on” state continuously

50. Allergy Testing • Method-Apply to arms or back • Cutaneous scratch or prick • Intradermal (the most accurate) • **Patch (for contact dermatitis) • Response • Produces localized response (wheal & flare) • Diagnostic for allergies to specific antigen • Positive reaction within minutes • Lasts 8-12 hours