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IMMUNOLOGY SIMPLIFIED —from AIDS to ZZZZZZ Barb Bancroft, RN, MSN, PNP

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Presentation on theme: "IMMUNOLOGY SIMPLIFIED —from AIDS to ZZZZZZ Barb Bancroft, RN, MSN, PNP"— Presentation transcript:

1 IMMUNOLOGY SIMPLIFIED —from AIDS to ZZZZZZ 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 MHC (major histocompatibility complex) A small section on chromosome 6 containing a group of genes that produce molecules that mark a cell as “self” Histocompatibility testing, or tissue typing, involves matching these molecules (antigens) Because tissue typing is usually performed on White Blood Cells (WBCs), or leukocytes, these self-antigens are called HLA-antigens

4 HLA antigens… They were first studied on our WBCs by renal transplant surgeons in the 1960s All tissues have HLA antigens on them except red blood cells with ABO antigens 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 All body cells (except RBCs) have HLA-A, HLA-B, HLA-C—known as Class I antigens HLA-DP, HLA-DQ, HLA-DR—Class II antigens

6 Class II antigens Class II antigens are the immune response antigens and are located on only on monocytes (in blood), macrophages (in tissues—APCs*), dendritic cells (in tissues just beneath the epithelial cells—APCs*), B lymphocytes (effector cells of the immune system), activated T lymphocytes (effector cells of the immune system) *Antigen processing cells—process the “foreign” substance to present to the immune system

7 Class II HLA antigens These antigens are essential for immune function and survival They determine which foreign antigens an individual responds to as well as the strength and type of response These are also “secreted” in body fluids in lower forms of animals—you want to select a mate based on “strength” of the immune system—how do lower forms of animals meet? Clonal selectivity

8 They stick their nose where the “sun don’t shine” and say… “You’re the one for me…” Why don’t humans do that? Well, we kind of do…

9 When the immune system attacks “self”…specific HLAs are associated with autoimmune disease For example…Type 1 diabetes—HLA-DR3 (5% risk), HLA-DR4 (6% risk), both? (20% risk)—more prevalent in Scandnavians Blonde-hair, blue-eyed with… Polyuria (excessive urination), Polydipsia (excessive drinking), polyphagia (excessive eating), weight loss, fatigue Named…

10 Over 80 autoimmune diseases Most autoimmune diseases associated with specific HLA-antigens include: Rheumatoid Arthritis (HLA-DR1, HLA- DR4) Multiple sclerosis (HLA-A8, B8, DR3— 10x greater risk) Celiac Disease (DQ2, DQ8) What about narcolepsy?

11 Narcolepsy Narcolepsy—HLA-DR2 Stanford University and a breed of Doberman’s

12 Other HLA and disease associations Inflammatory diseases such as ankylosing spondylitis and other postinfectious arthropathies (Reiter’s syndrome—HLA-B27 (90-100%) Inherited errors of metabolism—HLA-A and hereditary hemochromatosis

13 One more interesting note about autoimmune disease One in 20 Americans have an autoimmune disorder; 10 times more likely to be female (75%) RA (7:1); Sjögren’s (9:1); SLE (9:1); MS (3:1); Hashimoto’s (10:1) Presentation tends to be between 25-45 Men have an overall increased risk of infectious disease, women have an increased risk of autoimmune disease Any theories as to why?

14 Autoimmune disease—loss of self- tolerance MS—antibodies attack myelin basic protein in the CNS Guillain-Barré—antibodies attack peripheral nervous system myelin Systemic Lupus Erythematosus—antibodies attack nuclear proteins—tested by measuring anti-nuclear antibodies (ANAs) Celiac disease—antibodies attack microvilli of small intestine (especially the duodenum)

15 Triggers for genetically-predisposed individuals Some type of trigger – from the outside? (exogenous agent); from the inside? (endogenous agent) Lack of vitamin D for certain autoimmune diseases (T1 DM, MS?) Inside triggers? Colonic bacteria and Crohn’s disease/ulcerative colitis? Outside triggers? Viruses for T1 DM? Outside triggers? Bacteria (Campylobacter pylori) for Guillain-Barre syndrome?

16 Cook your chicken! White meat—170° F Dark meat -- 180° F Whole chicken – 180

17 2 nd general principle—selectivity and specificity The immune system is highly selective and specific for each pathogen 1 pathogen=1 response “monoclonal”

18 For example… How many types of strep are there? Over 200 (Group A thru O + hemolytic properties— alpha, beta, gamma) GABHS (Group A beta hemolytic strep— (anti-streptolysin O titers are antibodies made to group A strep) ASO titers and strep throat

19 Rheumatic heart disease and molecular mimicry Some infections share epitopes with self- antigens, an immune response against such microbes may produce tissue –damaging reactions that cross react with self-antigens; group A beta hemolytic strep cross reacts with cardiac glycoproteins (myosin-like); takes 7 to 21 days to make antibodies; acute rheumatic heart disease usually occurs 2 to 3 weeks after strep throat—murmur, joint pain, rash

20 Monoclonal antibodies made in the laboratory— “magic bullets” Trastuzumab—Herceptin targets the HER/2neu gene in breast cancers; this gene amplifies the growth of the tumor Rituximab—Rituxan targets a specific protein on B lymphocytes; used for non-Hodgkin’s lymphoma, MS, DM Cetuximab (Erbitux)—targets epidermal growth factors (Martha Stewart) Bevacizumab (Avastin)—inhibits angiogenesis (TAF— tumor angiogenesis factor) Infliximab (Remicade)—targets an inflammatory protein (TNF-a)—Crohn’s disease, rheumatoid arthritis, more…

21 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.

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

23 You can’t kill herpes…you can “live with it”… 3 herpes viruses live in the dorsal root (sensory root) of the peripheral nerves “What’s the difference between herpes and love?”

24 Herpes simplex virus--type 1 HSV-1 typically lives in the dorsal root of the trigeminal nerve Cold sores Usually above the belt

25 Herpes simplex virus—type 2… HSV- 2—below the belt (STD vs. VD) “Hey nurse, can I get hairpiece from a toelet seat?”

26 Varicella zoster virus— (chickenpox/shingles) VZV—varicella zoster virus Primary infection is chickenpox—crawls up the sensory nerve and lives in dorsal root of the trigeminal nerve (V) If your immune system is “competent”, the virus remains dormant in the sensory root

27 Immunocompromised? Shingles is the secondary manifestation Hematologic malignancy; rate of HZ is 5-25% Lupus—3.2-21% HIV/AIDS increases risk by 12-17 fold (T cell deficiency)—multidermatomal shingles Depression and significant stress within past 6 months increases risk The elderly

28 Shingles and the elderly population With aging population, the absolute # of herpes zoster cases is increasing dramatically; Why? Because the type of immunity that keeps latent herpes in a “latent” state wanes with aging—this type of immunity is called cell- mediated immunity (CMI); killer T cells are responsible for CMI and their action decreases with age

29 FYI: Percent of individuals with shingles, by age 10—0.5% 20—1.3% 30—2.7% 40—4.8% 50—7.5% 60—11.9% 70—19.7% 80—31.8% 90—46.1% Donahue JG, et al. Archives of Internal Medicine, 1995.

30 Locations of Herpes Zoster or “shingles” 4% sacral 11% cervical 13% cranial 13% lumbar 56% thoracic 3% other Ophthalmic complications 10-25% (keratitis, iritis, retinitis, optic neuritis with vision loss and blindness) AIRBONE precautions for disseminated herpes zoster

31 Herpes Zoster Acyclovir (Zovirax)—800 mg/day po 5x/day x 7-10 days; significant reduction in severity, duration and relative risk of postherpetic neuralgia Famciclovir (Famvir)—500 mg po 3x/day x 7 days—as effective as Zovirax in reducing acute pain and preventing PHN Valacyclovir HCl (Valtrex)—1000 mg/po 3x/d x 7 days provides an improved benefit over acyclovir in reducing the severity and duration of PHN in patients over 50 Start treatment within 48 to 72 hours of rash onset; nerve block? What about Prednisone?

32 Vaccine to prevent shingles--Zostavax Vaccine approval May 2006 500,000 to 1 million episodes per year PHN – vaccine reduces incidence of HZ by 51% and decreases incidence of PHN by 66%; decreases morbidity by 61% Patients older than 50 have a 14.7-fold higher incidence of chronic pain 30 days after the onset of rash than patients under age 50

33 The Epstein-Barr* virus (EBV) is a member of the Herpes “family” *Dr. Tony Epstein and his lovely assistant, Ms. Yvonne Barr; Denis Burkitt and Burkitt’s lymphoma Lives in your B lymphocytes MONO B-cell Lymphoma (the boy in the bubble— David Vetter) Nasopharyngeal carcinoma ? MS

34 Cytomegalovirus … CMV (cytomegalovius)—gastroenteritis, retinitis, pneumonitis, adrenalitis, pancreatitis, encephalitis, polyneuritis—wreaks havoc in immunocompromised patients (transplant and HIV+ patients) Crosses the placenta and can cause cytomegalic inclusion disease in developing babies ? Trigger of glioblastoma multiforme?

35 Human herpes virus -6, and Human herpes virus -7 HHV-6—roseola HHV-7--???

36 Human herpes virus-8, or KSHV… HHV-8 (1995) Kaposi’s Sarcoma Herpes Virus (KSHV) STD Rarely found in blood transfusions (only 3 known cases)

37 So let’s go back to the MEMORY of the immune system…how do you acquire memory? You either suffer the infection… OR YOU… Vaccinate, vaccinate, vaccinate

38 How does the immune system develop memory? It meets a pathogen, responds to it, and that response can be measured as a memory response Antibodies are made to some pathogens and we measure those as “titers”— Memory T cells directly respond to certain pathogens

39 How do we test memory? Antibody titers can do a couple of things: 1) tell us if you have EVER been exposed to a specific pathogen—varicella titers, CMV titers 2) tell us if you have responded to a pathogen/vaccine and how strong that response was/or currently is—levels of titers 3) these titers tend to wane as we age—we just can’t remember like we used to…

40 TB skin test Tests whether or not you have been exposed to TB OR you can have a positive test if you have had the BCG vaccine High risk groups for TB are patients and healthcare workers from other countries—India, China are the two top countries Having had the BCG vaccine as a child in another country does NOT mean that you are protected from TB Quantiferon Gold test for TB in BCG+ pts.

41 TB and LTCF (long-term care facilities) All newly admitted residents should receive two-step mantoux/purified protein derivative (PPD) test unless a physician’s statement has been obtained that the resident had a past positive reaction to tuberculin A PPD is considered positive and a chest X-ray is indicated when a resident has:

42 TB and LTCF ≥10 mm of induration ≥ 5 mm for residents with organ transplants, other immunosuppressed conditions, HIV +, recent contact of an active TB case or fibrotic changes on CXR TB requires airborne precautions, Use of N-95 respirators when entering the room

43 Let’s get back to vaccines for a moment…historical highlights Chinese vaccines—11 th century B.C. – “sowing the pox”—injecting pus from the smallpox pustules into a cut on the hand of a healthy person; “snorting” the pox was another way of inoculating against small pox Lady Mary Wortley Montegu, wife of the British ambassador to Turkey in the early 1700s, saw it in action and brought the idea back to England from Turkey

44 Historical Highlights… 1796—English country doctor, Edward Jenner and the milkmaid--cowpox (“vacca” is the Latin word for cow) offering protection against smallpox; “vaccinia”=cowpox His prediction?

45 1976…last case of smallpox in Somalia Small pox Great pox Chicken pox

46 World Health Organization and “herd” immunity Vaccinating 70% of the world’s population against smallpox developed “herd” immunity Why were we able to totally eradicate smallpox from the face of the earth?

47 The smallpox vaccine contained 200 different smallpox specific antigens— had the potential to overwhelm the immune system All vaccines today contain approximately 120 antigens combined

48 Vaccines… Prevention of childhood diseases…(kid receive 28 doses by the age of 2 if they get the complete schedule of immunizations recommended by the CDC) The good news—the prevention of childhood diseases… the bad news? Most of the vaccines are needles, so…in the future… Shampoos as vaccines? Foods as vaccines?

49 Using foods as vaccines… Potatoes Tomatoes Bananas Spinach Still working on the possibility…

50 Vaccine miracles…meningitis in kids H. flu meningitis—what are the numbers? 40-100 cases/100,000 of invasive H. flu in 1989; vaccine in 1990— 1.4 cases/100,000 today Strep pneumoniae meningitis—what are the numbers? 77% decline in kids; 60% decline in adults via “herd immunity” Lumbar punctures in kids—before, during, after…too many…

51 Acetaminophen and vaccine response Acetaminophen should not be given prophylactically as a routine practice with vaccination Reduces the antibody response after vaccination However, does this actually increase the susceptibility to the infections that the vaccines protect against? The study did not answer that question (Chen RT et al. The yin and yang of paracetamol and paediatric immunizations. Lancet 2009 Oct 17; 374:1305)

52 Why do we need vaccine boosters? To boost the immune system’s memory… Boosters for kids One shot, two shots or three shots? Depends on the response of the immune system Pneumococcal vaccine at age 65; repeat in 5-7 years Give it earlier in patients with chronic disease

53 Tetanus/diphtheria booster Td (tetanus toxoid, reduced diphtheria toxoid) – every 10 years Why every 10 years? The diphtheria portion wears off in 11 years; the tetanus doesn’t wear off for 19 years…but, since they are given together is better to err on the safe side and give it every 10 What are the two most common causes for tetanus (lockjaw) in the older individual? Tdap (Td + and acellular pertussis)Boostrix (ages 10-18) and Adacel (ages 11 to 64)— one time booster

54 So how does the immune system work? You actually have 2 “immune” systems… 1) Innate and 2) acquired (adaptive) Innate “immune” system—born with certain abilities to fight invading pathogens Acquired or adaptive “immune” system—you learn from experience—you have to meet the pathogen and respond specifically to it, and then…remember it!

55 INNATE IMMUNE RESPONSE…Barrier defense mechanisms and acute inflammation Skin and mucous membranes Open wounds/ulcerative lesions CA-MRSA and open wounds in athletes Toothbrushes and flossing Gotta hole? We’ll put a tube in it…if you don’t have a hole for the tube we’re holding—we’ll make a new hole for ya’! Urinary catheters, Hickman catheters, ports, arterial lines, venous lines, surgical sites, IV sites. Hospital-acquired MRSA, MRSA, MRSA and wound infections

56 Barrier defenses Bleeding gums, sores or lesions in mouth Epidemiological synergy—twofold to fivefold increased risk of HIV infections among persons who have other STDs Saliva—antimicrobial proteins, IgA, low salinity (1/7 th the amount of salt as other body fluids pH of body fluids

57 pH of body fluids—gastric acid acid pH of 2 in the stomach keeps a lot of bugs “out” Therapy with PPIs, H2 blockers, and antacids has been associated with an increased risk of hospital- acquired pneumonia (JAMA 2009;301:2120-2128) The incidence of bacterial gastroenteritis caused by salmonella and Campylobacter may be increased in patients taking PPIs, but no association with H2 blockers has been found (Clin Gastroenterol Hepatol. 2007;5:1418-1423)

58 Urinary pH acid pH of urine keeps E. coli (and the other bacteria that live in the bowel) “out”—age of the woman

59 Vaginal pH acid pH of the vagina keeps yeast “out” and STDs (pre-teens vs. teens vs. 20-40s vs. postmenopausal)

60 “You have a yeast infection.” Yeast infections When the estrogen levels are low or non-existent Antibiotics change the pH and normal flora of the vagina

61 pH of body fluids… semen (pH—7); anything with an H_V lives in it—alkaline to alkaline transmits disease Do condoms protect from STDs? YES, for most STDs; not 100% but better than nothing What about those “natural feel” condoms?

62 To circumcise or not to circumcise…that is the question… YES! Not only protect themselves but also their partners 20% of men with intact foreskin carry HPV; only 6% of circumcised men carry HPV If all men were circumcised around the world-- cervical cancer rates would drop by up to 60%

63 Innate defense: acute inflammation Inflammation is Vasodilation Increased permeability of vascular membranes Arrival of WBCs—first the neutrophils and then the macrophages

64 Acute inflammation Segs (neutrophils) are the cells of acute inflammation— comprise 60% of the total WBC and differential; immature segs are called “bands”—normal bands comprise 0-4% of the total white count Segs and bands respond to acute tissue necrosis and acute bacterial invasion within 5 to 10 minutes of tissue damage or invasion Also respond to a signal from the specific immune response— (more later) In autoimmune disease, the segs play a major role in destruction of tissues such as the joints in patients with rheumatoid arthritis; in the kidneys in patients with lupus

65 SEGS… Margination, pavementing, migration and engulfment and degranulation (release of preformed granules) Marginating segs (measured by WBC count) Pavementing segs (stuck to walls) Yum

66 Prednisone and the neutrophil Prednisone inhibits migration, engulfment and degranulation, hence its potent anti-inflammatory properties Why do we use Prednisone with autoimmune disease? To inhibit the damage caused by one’s own segs attacking various tissues 1 st 24 hours after prednisone = neutrophillia (segs increase in the blood due to recruitment of pavementing cells) Prednisone also increases blood sugar; high blood sugars can also inhibit the function of segs

67 Other conditions with segs Blood sugars greater than 180 mg/dL inhibits seg migration (diabetics, high blood sugars and infections) Elderly with decreased migration of segs, increases infection susceptibility Fever increases the migration of segs—is fever good for you? YES! Neutropenia—an oncologic emergency

68 The cell of chronic inflammation and the cells that process antigens are: Monocytes in blood, macrophages (big eater) in tissues Macrophages have other names in various tissues— microglial cells in the central nervous system, Kupffer cells in the liver, histiocytes in connective tissue Dendritic cells are also specialized antigen processing cells

69 The macrophage (CD4)(cell determinant #4) The macrophage (CD4) is the antigen processing and presenting cell These cells respond much slower than the seg (2-4 days vs. 5-10 minutes for the seg) Cell of chronic inflammation 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, Tumor Necrosis Factor-alpha)

70 Gulp, chew, process, spit, kick… macrophage With CD4 receptor IL-1 release T4 cell T4 or helper T cell IL-2 CD4 “ON” TNF-a IFN-gamma B s, Ts WBCs

71 How do drugs and bugs influence this immune response Prednisone inhibits IL-1 (interleukin-1) release— immunosuppressive Methotrexate inhibits macrophage function Cyclosporine inhibits IL-2—used to reduce tissue transplant rejection Etanercept (Enbrel) binds with excess TNF-a molecules—anti-inflammatory

72 Monoclonal antibodies Adalimumab (Humira), infliximab (Remicade), golimumab (Simponi), and certolizumab pegol (Cemzia) block TNF-a Daclizumab (Zenapax)—blocks IL-2 on activated T cells to prevent organ transplant rejection Basiliximab (Simulect)—prevent organ transplant rejection

73 HIV and the CD4 cells The AIDs virus (HIV) enters via CD4 receptors—kills cells after replicating; The macrophages are primarily “fixed” in tissues—only small numbers circulate (4% of the total white count); HIV is silently destroying the macrophage population in tissues HIV also kills the circulating CD4 cells; as they fall to 350 per cu/mm anti-retroviral therapy will be initiated Methamphetamine increases the entry of HIV into CD4+ cells

74 Vitamin D and the immune system Vitamin D boosts macrophage function In the old days—the treatment for TB was to…“go up on the mountain if you have consumption…”— heliotherapy in 1908 vs. today’s heliotherapy Ultraviolet light (UVB rays) and immune boosting Ultraviolet lights in EDs and internal medicine clinics in high-risk hospitals Homeless vs. shelters

75 More on vitamin D and the immune system Dramatically stimulates antimicrobial proteins from neutrophils, monocytes, NK cells, and epithelial cells lining the respiratory tract Vitamin D deficiency (less than 40 nmol/L) increases the risk of respiratory tract infections Sicker in the winter? Vitamin D deficiency and autoimmune disease— correlates positively with latitude from the equator— MS, Type 1 DM, IBD Vitamin D and prostate cancer

76 Let’s go back to the cytokines…interleukin 1 Increases temperature set point by increasing the production and release of prostaglandins in the hypothalamus A fever recruits white blood cells and makes them more active A fever decreases the ability of pathogens to utilize iron

77 IL-1 Increases serotonin release from brainstem— vomiting Increases serotonin release from the duodenum—nausea

78 IL-1 … Increases melatonin production and makes you sleepy

79 IL-1 release also… Lowers pain threshold—everything hurts Your hair hurts Your teeth hurt Your skin hurts You’re tired You’re miserable… Amphotercin B releases IL-1 from macrophages;

80 Tumor necrosis factor - alpha Potent inflammatory mediator In small doses it’s good for you, in systemic doses it wreaks havoc with joints (Rheumatoid arthritis), with intestines (Crohn’s disease), with skin (psoriasis) In AIDS patients it’s responsible for “wasting syndrome”

81 Interferons are also produced by various cells of the immune system Interferon alpha—anti-viral cytokine; prevents the attachment of viruses to cells; blocks viral replication in infected cells Intron-alfa + ribivirin for the treatment of Hepatitis C patients One of the notorious side effects is depression; do immune system cytokines trigger depression? Cytokines can decrease levels of serotonin in the brain

82 Interferon beta Interferon beta is an immunosupressing interferon Used to treat multiple sclerosis--betaseron

83 Interferon gamma Interferon gamma is an immune-boosting interferon NK cells release interferon gamma to stimulate macrophages to destroy ingested microbes

84 CHEMICAL EVENTS INVOLVED IN INFLAMMATION in tissues… “itis” Histamine release—histamine must be a bad guy (anti-histamines )

85 Chemical events involved in inflammation Prostaglandin production—lots of drugs we take are “anti-prostaglandin” drugs—ASA, NSAIDS (celecoxib/Celebrex) Prostaglandins are produced daily in certain tissues as a normal part of their function—i.e., the stomach—prostaglandins boost mucus production in the stomach to protect it from acid

86 Prostaglandins are also produced with tissue damage (inducible prostaglandins) via an enzyme called cyclo-oxygenase 2 COX-2 inhibitor—celecoxib (Celebrex)—causes less gastropathy but over time can cause an NSAID-induced gastric ulcer

87 Complement Activation of complement (also known as complement fixation)—consists of more than 20 inactive proteins, some of which are numbered 1 through 9; most abundant is C3 Triggered by fixation to antibodies IgG or IgM; or by various microbes and proteins including venom responsible for inflammation when they are activated— complement levels can be measured—example, lupus and the kidney-- “lupus nephritis” With active kidney involvement the complement levels will DECREASE as it is being “used up” to cause inflammation

88 Inflammation and Immunity How do the 2 go hand-in-hand? Example: Autoimmune glomerulonephritis Autoimmune means the immune system attacks self antigens; glomerulo (kidney) nephritis (inflammation)

89 Abdominal visceral fat and inflammation Macrophages in the abdomen recognize excess adipose tissue in the viscera as “foreign”—results in an inflammatory response; release IL-6, TNF-a, which in turn trigger the liver to produce hs-CRP (high sensitivity C-Reactive Protein, a marker of systemic inflammation) and a high risk for cardiovascular disease This fat is also insulin resistant—T2 diabetes REDUCE ABDOMINAL/VISCERAL FAT—how?

90 Natural Killer lymphocytes are cells of the innate defense system Kill viruses and cancer cells “naturally”—in other words they are ready to destroy invading viruses and cancer cells without having to “learn” the response These comprise about 4-10 percent of the circulating lymphocytes B and T lymphocytes are the lymphocytes of the specific or aquired immune response—Bs 16% and T’s about 70% of the total circulating lymphocytes

91 Cells of the immune system--lymphocytes

92 Lymphatic tissues Spleen Lymph nodes Cutaneous lymph tissue just beneath the epithelial cells Mucosal lymph tissue—pharyngeal tonsils and Peyer’s patches of the intestine—at any given time, more than half of the body’s lymphocytes are in the mucosal tissues (reflecting the large size of these tissues)

93 Cell determinants CD3 – found on all T cells CD4—found on Helper T cells CD8—found on suppressor/cytotoxic (killer T cells) CD20—found on B lymphocytes; the monoclonal antibody, rituximab/Rituxan), targets this cell determinant—RX for non- Hodgkin’s lymphoma and some autoimmune diseases (lupus) CD21—found on B lymphocytes (Epstein Barr virus enters the B lymphocytes via this cell determinant/receptor) CD16 and CD56 are found on NK cells

94 Cell-mediated immunity (CMI) T4 Helpers—turn the system “on” (there are actually subsets of helper T cells—more later) T8 Suppressors—turn the system “off” T4/T8 ratio is 2:1 CMI fights viruses, fungus’, protozoa, TB, parasites, cancer, transplant tissue

95 What are the diseases observed in AIDS patients? Viruses—herpes (HSV-1,2, VZV, EBV, HHV-8), hepatitis C Fungus’—candida albicans Parasites--toxoplasmosis Protozoa—pneumocystis jirovecii pneumonia TB Cancer—Non-Hodgkin’s lymphoma, Kaposi’s sarcoma

96 HIV (human immunodeficiency virus) and CD4 cells The AIDS virus – enters dendritic cells and macrophages (CD4) and T4s initially; portal of entry? Rectum, blood, vagina It replicates itself by making copies via an enzyme called reverse transcriptase; for every one HIV that enters a cell, it makes 10,000 copies; once the “copy machine” has finished, HIV exits the cell to look for another host cell; as it exits, the cell dies; CD4 cells in the blood continue to decline

97 HIV and the CD4 cells Treatment for HIV/AIDS is usually started when the circulating T4 count falls to 350 cells/ml Treatment targets various processes that occur within the T4 cell to replicate and exit the cell Reverse transcriptase inhibitors were the initial therapies and continue to be used today with a multitude of other drugs

98 HIV and the CD4 cells Another receptor is necessary for HIV to enter CD4 cells CCR5 receptor is one of them Blond-haired, blue-eyed gay men named? New class of drugs called entry inhibitors A few historical highlights about HIV

99 T H 1 and T H 2 Hygiene Hypothesis; the earlier the exposure to dirt, the better the T H 1 system will be T H 1 predominance = cell mediated immunity T H 2 predominance=allergies and autoimmune disease Let them eat dirt!!

100 B lymphocytes (cells) B cell---plasma cell ---antibody (immunoglobulins, gamma globulins) production (7-21 days)(except HIV—can take as long as 1 year) fab Y fc receptor

101 Multiple myeloma Multiple myeloma is an uncontrolled proliferation of plasma cells, also known as a plasma cell dyscrasia Produces an overabundance of antibodies; usually one clone—monoclonal Light chains (Bence-Jones proteins excreted in the urine) and heavy chains Y

102 Immunophoresis IgM, IgG, IgA, IgD, IgE

103 Immunoglobulins IgM—1 st formed to an infection; fixes (activates) complement (inflammation), agglutinates (clumps)— cold agglutinins, warm agglutinins IgG—2 nd formed; memory; crosses placenta; opsonizes (coats); fixes (activates) complement (inflammation); reactivated with latent infection Antibody testing— “acute vs. convalescent titers” IgM? Or IgG? Have you had this disease or vaccine before? IgG testing

104 Plasma cells produce antibodies… IgA—barrier antibody; saliva, tears, urine, breast milk How can you boost IgA levels? Humor, exercise, and a little sex perhaps? IgD--??

105 Plasma cells produce antibodies… IgE—antibody of allergies Drills a hole in the mast cell—releases primary granules full of histamine Histamine is responsible for itchy, sneezy, wheezy, coughy, runny… Localized histamine release? Systemic histamine release? Anaphylactic shock

106 Hay fever, asthma, allergic rhinitis— the allergic salute

107 What are the triggers? Pollen, ragweed and other airborne particles Wasp venom (fire ants have same venom) Animal dander—cats and dogs Roach dander Certain foods—shellfish, peanuts, tomatoes, eggs, strawberries, maple syrup

108 What can you do to reduce allergies? Get rid of the roaches Get rid of the pet? Why?

109 Don’t sleep with the enemy Speaking of sleep…People who sleep less than seven hours are 2.94 times more likely to develop a cold than those who sleep eight or more Sleep deprivation causes a dip in killer T cells and lower interleukin-2 levels

110 Drugs to reduce allergic symptoms Oral anti-histamines--cetirizine (Zyrtec), desloratadine (Clarinex), fexofenadine (Allegra) Nasal antihistamines—fluticasone propionate (Flonase); mometasone furoate (Nasonex); triamcinolone acetonide (Nasacort-AQ) Mast cell stabilizers—cromolyn sodium (Nasalcrom) Anti-leukotrienes—montelukast (Singulair) Anti-IgE monoclonal antibody—omalizumab (Xolair)

111 Immune-mediated hypersensitivity reactives— 4 types Type 1– Immediate hypersensitivity Type II – Antibody-mediated hypersensitivity Type III – Immune complex-mediated hypersensitivity Type IV – Cell-mediated hypersensitivity

112 Type 1 immediate hypersensitivity Prototype – Hay fever; asthma; allergic rhinitis; IgE—immediate release of histamine and other vasoactive substances; late phase reaction 2 to 24 hours after repeat exposure Anaphylactic shock…the systemic release of histamine—vasodilation (bright red), blood pressure drops, bronchoconstriction, may have explosive diarrhea Triggers? Bee stings, penicillin, various foods (shellfish, peanuts), husbands

113 Type 2 – antibody-mediated hypersensitivity Production of IgG, IgM—binds to antigen on target cell or tissue; phagocytosis or lysis of the target cell by activated complement or Fc receptors Autoimmune hemolytic anemia—anti-RBC antibodies (Coomb’s test positive)

114 Type 3 – immune complex hypersensitivity Antigen/antibody complexes land in small vessels and fix complement; trigger inflammation wherever they land Prototype—systemic lupus erythematosus; antigen is the nucleus of cells/antibody formed to it…combines into an Ag/Ab complex (measured as anti-nuclear antibodies or ANAs

115 Type 4—T cell mediated Contact dermatitis such as poison ivy; latex; type 1 diabetes; MS, RA, IBD Latex “allergies” are usually contact dermatitis but can also be type 1 if anaphylaxis is involved

116 Bibliography Chen RT et al. The yin and yang of paracetamol and paediatric immunizations. Lancet 2009 Oct 17; 374:1305) Dantzer R, et al. From inflammation to sickness and depression: when the immune system subjugates the brain.” Nature Reviews Neuroscience. January 2008. Fehervari Z, Sakaguchi. Regulatory cells of the immune system. Scientific American 2006; 57-63. Hoffman RL. What lies behind the vitamin D revolution? The Cinical Advisor 2010 (March); 31-36)

117 Bibliography Garten RJ, et al. Antigenic and genetic characteristics of swine-origin 2009 A (H1N1) influenza viruses circulating in humans. Science 2009 May 22. Maxmen A. Sick and Down. Science News. 2008 (July 19) Report. Arousing the Fury of the Immune System. Howard Hughes Medical Institute. 1998 Rituximab Protects Insulin Producing Cells in Diabetes— www.MedPageToday.com; November 25, 2009. Prymula R et al. Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: Two open-label, randomised controlled trials. Lancet 2009 Oct 17; 374:1339

118 Bibliography Schaffner W, Jones, TF. Immunizing older adults against tetanus and diptheria. Patient Care 2004 (October); 19-22. The Strategies for Management of Antiretroviral Therapy (SMART) Study Group. Major clinical outcomes in antiretroviral therapy (ART)-naïve participants and in those not receiving ART at baseline in the SMART study. J Infect Dis 2008 Apr 15;197:1133. Wejse C et al. Vitamin D as supplementary treatment for tuberculosis; A double-blind, randomised, placebo-controlled trial. Am J Respir Crit Care Med 2009 May 1;179:843.

119 Thank you…and remember, “Support bacteria…they’re the only culture some people have…” Barb Bancroft, RN, MSN, PNP bbancr9271@aol.com www.barbbancroft.com


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