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IMMUNOLOGY SIMPLIFIED

IMMUNOLOGY SIMPLIFIED. Barb Bancroft, RN, MSN, PNP www.barbbancroft.com BBancr9271@aol.com. Immunology… . Definition: The study of the physiologic mechanisms that allow the body to recognize materials as foreign or abnormal and to neutralize or eliminate those foreign materials.

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IMMUNOLOGY SIMPLIFIED

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  1. IMMUNOLOGY SIMPLIFIED Barb Bancroft, RN, MSN, PNP www.barbbancroft.com BBancr9271@aol.com

  2. Immunology… • Definition: The study of the physiologic mechanisms that allow the body to recognize materials as foreign or abnormal and to neutralize or eliminate those foreign materials.

  3. 3 general principles… • Recognition of self versus non-self • MHC (major histocompatibility complex)—a section on chromosome # 6 containing a group of genes that produce molecules marking our own tissues as “self” (referred to as “self-antigens.”) These are referred to as HLA (human leukocyte antigens) because…

  4. HLA antigens… • They were first studied on our WBCs by transplant surgeons • Of course, the HLA antigens weren’t put on tissues solely for the convenience of transplant surgeons…

  5. General principles • HLA antigens help the immune system to recognize pathogens and to mount an immune response • HLA-A, HLA-B, HLA-C—Class I antigens • HLA-DP, HLA-DQ, HLA-DR—Class II antigens • Class II antigens are the immune response antigens

  6. Autoimmune disease… • Certain diseases are immune based and the risk is associated with specific HLA antigens • For example…Type 1 diabetes—HLA-DR3, HLA-DR4 Scandinavian background, Blonde-hair Blue-eyed with… Polyuria (excessive urination), polydipsia (excessive drinking), polyphagia (excessive eating), weight loss, fatigue Named…

  7. General principles • Autoimmune diseases associated with specific HLA-antigens: Rheumatoid Arthritis (HLA-DR1, HLA-DR4); Multiple sclerosis (HLA-A8, B8, DR3); Celiac Disease (DQ2, DQ8) • What triggers autoimmune disease? 75% are women-- • Something from outside the body? (exogenous agent)—virus, bacteria, sunlight, cow’s milk

  8. 2nd general principle SELECTIVITY and SPECIFICITY— The immune system is highly selective and specific for each pathogen 1 pathogen=1 response

  9. 1 pathogen=1 response=1 antibody=MONOclonal • Monoclonal antibodies as “biological response modifiers” • Infliximab (Remicade) • Adalimumab (Humira) • Rituximab (Rituxan) • Trastuzumab (Herceptin) • Cetuximab (Erbitux)—colon cancer (Martha Stewart) • Bevacizumab (Avastin)—inhibits angiogenesis • Omalizumab (Zolair)—mab to IgE

  10. 2nd general principle • How many types of strep are there? • Over 200 (Group A thru O + hemolytic properties— alpha, beta, gamma) • GABHS (Group A beta hemolytic strep—the bad guy)—Antistreptolysin O titers (ASO titers) • RHD, Streptococcal TSS, and “the flesh-eating” disease (necrotizing fasciitis)

  11. General Principles 3) MEMORY— Once having met a pathogen, the immune system never forgets it. If you are re-challenged with the same pathogen the memory response will recognize it immediately-- and destroy it or neutralize it.

  12. So, how do you acquire memory? • You either suffer the infection…

  13. OR… • VACCINATE, VACCINATE, VACCINATE!

  14. Vaccines… • Kids receive a plethora of oral or parenteral vaccines prior to the age of 2 to prevent a plethora of childhood diseases…

  15. In the future… • Shampoos as vaccines

  16. In the future…?? using foods as vaccines… • Potatoes • Tomatoes • Bananas • Spinach

  17. Why do we need booster vaccines? • To boost the immune system’s memory… • Pneumococcal vaccine at age 50-65; repeat in 5-7 years • Tdap is recommended now…Adacel (11-64); Boostrix (10-18) (acellular pertussis) • Tetanus boosters—every 10 years, don’t forget! • Highest risk group for tetanus—over 40 • Fishing and gardening in the elderly—big risks

  18. With such a fabulous memory we should never get the same disease twice! Exceptions… The Herpes “Family” • HSV-type 1 • HSV-type 2 • VZV (varicella vaccine) • Epstein-Barr • CMV • HHV-6, HHV-7 • KSHV (HHV-8) • HUH?

  19. HSV-1 • Cold sores • Usually above the belt

  20. The Herpes family… • HSV-Type 2—below the belt (STD vs. VD)

  21. The Herpes family… • VZV—varicella zoster virus • “Shingles”—Hell’s fire

  22. Can shingles be prevented by administering the varicella vaccine to the elderly? • Zostavax (Merck)-- a stronger version (14x) of Varivax (for kids)

  23. The Herpes family… • EBV (Epstein-Barr **virus) • MONO, Lymphoma • ? MS • (Dr. Tony Epstein and his lovely assistant, Ms. Yvonne Barr)

  24. The Herpes family… • And don’t forget: • CMV (cytomegalovius)—gastroenteritis, retinitis, pneumonitis—wreaks havoc in immunocompromised patients • HHV-6 (Roseola)(?MS) • HHV-7 (??)

  25. The Herpes family… • HHV-8 (1995) Kaposi’s Sarcoma Herpes Virus (KSHV)

  26. OTHER EXCEPTIONS TO THE RULE.. • Tuberculosis

  27. Exceptions to the rule… • HPV • Vaccine for HPV-16and 18 • Gardasil (Merck)

  28. Exceptions to the rule…Hepatitis C • How often do adults clear hepatitis C? • Blood transfusions prior to 1992 (July)—1 in 3000 prior to 1992; 1 in 276,000 today • Sharing needles • Multiple sex partners • Intranasal cocaine use • Body piercing • Tattoos

  29. Guy’s tattoos—out there, everywhere • Gals are a bit more subtle…

  30. Exceptions to the rule…Hepatitis B • How often do adults clear Hepatitis B? • How often do infants clear Hepatitis B? • Hepatitis B vaccine • Should patients with hepatitis C get the hepatitis A and B vaccine?

  31. INNATE IMMUNE RESPONSE…Barrier defense mechanisms • Skin and mucous membranes • Open wounds/ulcerative lesions • Bleeding gums, sores or lesions in mouth • Saliva—protective factors—IgA, low salinity

  32. ph of body fluids… • Estrogen plays a role in maintaining the healthy pH of the vagina—4.5 • Vaginal lactobacillus as normal microflora • Teenagers and sex • Menses • Exocervix vs. endocervix

  33. “You have a yeast infection.” • Yeast infections • When the estrogen levels are low or non-existent • Young girls • Elderly women • Antibiotics change the normal flora

  34. pH of body fluids… • Urine pH4 (estrogen receptors on the urethra) • E. Coli and UTIs • Young gals, and old gals

  35. pH of body fluids… • semen (pH—7); anything with an H_V lives in it—alkaline to alkaline transmits disease • Do condoms protect? YES

  36. But not the “natural feel” condoms “You want to do what with my intestines?

  37. To circumcise or not to circumcise…that is the question… • YES! • Not only protect themselves but also their partners • If all men were circumcised around the world--↓ cervical cancer by up to 60%

  38. pH of body fluids… • Gastric pH2 • H. pylori and ulcers • Consider the patient on PPIs and continuous H2 blockade for GERD at high-risk for food-borne illnesses

  39. Innate defense: acute inflammation • Vasodilation • Increased permeability of vascular membranes • Arrival of WBCs—first the segs and then the macrophages

  40. Acute inflammation • Segs are the cells of acute inflammation • Respond to tissue necrosis and bacterial invasion • Also respond to a signal from the specific immune response • Play a major role in destruction of tissues such as the joints in patients with rheumatoid arthritis; the kidneys in patients with lupus

  41. SEGS…normal function and the role of Prednisone • Margination, pavementing, migration and engulfment (degranulation) Yum.

  42. Prednisone and the neutrophil • Inhibits migration and degranulation, hence it’s anti-inflammatory properties • 1st 24 hours after prednisone = neutrophillia • Prednisone also increases blood sugar; high blood sugars can inhibit the function of segs • Diabetes– Blood sugars greater than 180 mg/dL inhibits seg migration • Elderly with decreased migration of segs, increases infection susceptibility • Fever increases the migration of segs—is fever good for you? YES!

  43. Neutropenia • Defined as an absolute neutrophil count of less than 1000 • ANC = % segs + % bands x total WBC • Patient is “leukopenic” with a WBC less than 2,500 • 56% segs + 4% bands = 60% x 2500 WBC = ANC = 1500 (not neutropenic) • 36% segs + 4% bands = 40% x 2,000 WBC = 800 (neutropenia)

  44. Monocyte/Macrophage • Monocyte in blood, macrophage in tissue (Kupffer cell in liver, microglial cell in brain) • CD4 receptor on their cell membranes • Phagocytes that respond much slower than the seg (2-4 days vs. 5-10 minutes for the seg) • Cell of chronic inflammation • The macrophage is the antigen processing and presenting cell • It engulfs the pathogen • Chews it up • Processes it and presents it to the helper T cell (T4 cell) of the immune system • Releases cytokines (IFN-gamma, IL-1, IL-12, TNF-alpha)

  45. What else does IL-1 do? • Increases temperature set point by increasing the production and release of prostaglandins in the hypothalamus • Increases serotonin release from brainstem—vomiting • Increases serotonin release from the duodenum—nausea • Duodenum—the organ of nausea

  46. IL-1 release… • Increases melatonin production and makes you sleepy

  47. IL-1 release also… • Lowers pain threshold—everything hurts • Your hair hurts • Your teeth hurt • Your skin hurts • You’re tired • You’re miserable…

  48. Macrophage is the APC--Antigen processing cell and IL-1 release… T4 cell IL-2 “ON” IL-1 release TNF-a CD4 CD4 macrophage With CD4 receptor T4 or helper T cell

  49. TNF-alpha (tumor necrosis factor) • A cytokine released by the macrophage • In small amounts it is a potent inflammatory mediator • In large amounts it can wreak havoc • Examples: Crohn’s disease Rheumatoid arthritis • TNF-alpha inhibition

  50. Drugs to reduce TNF-alpha • Infliximab (Remicade) • Adalimumab (Humira) • Etanercept (Enbrel)—infusion of TNF-α receptors to bind excess TNF-α

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