IMMUNOLOGY SIMPLIFIED Barb Bancroft, RN, MSN, PNP www.barbbancroft.com [email protected] 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 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 selfantigens.) These are referred to as HLA (human leukocyte antigens) because HLA antigens They were first studied on our WBCs by transplant surgeons Of course, the HLA antigens werent put
on tissues solely for the convenience of transplant surgeons General principles HLA antigens help the immune system to recognize pathogens and to mount an immune response HLA-A, HLA-B, HLA-CClass I antigens
HLA-DP, HLA-DQ, HLA-DRClass II antigens Class II antigens are the immune response antigens Autoimmune disease Certain diseases are immune based and the risk is associated with specific HLA antigens
For exampleType 1 diabetesHLA-DR3, HLA-DR4 Scandinavian background, Blonde-hair Blue-eyed with Polyuria (excessive urination), polydipsia (excessive drinking), polyphagia (excessive eating), weight loss, fatigue Named
General principles Autoimmune diseases associated with specific HLAantigens: 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, cows milk
2 general principle nd SELECTIVITY and SPECIFICITY The immune system is highly selective and
specific for each pathogen 1 pathogen=1 response 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
2 general principle nd How many types of strep are there? Over 200 (Group A thru O + hemolytic properties alpha, beta, gamma) GABHS (Group A beta hemolytic strepthe bad guy)Antistreptolysin O titers (ASO
titers) RHD, Streptococcal TSS, and the flesheating disease (necrotizing fasciitis) 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. So, how do you acquire memory? You either suffer the infection OR VACCINATE, VACCINATE, VACCINATE!
Vaccines Kids receive a plethora of oral or parenteral vaccines prior to the age of 2 to prevent a plethora of childhood diseases In the future Shampoos as vaccines
In the future?? using foods as vaccines
Potatoes Tomatoes Bananas Spinach Why do we need booster vaccines? To boost the immune systems memory
Pneumococcal vaccine at age 50-65; repeat in 5-7 years Tdap is recommended nowAdacel (11-64); Boostrix (10-18) (acellular pertussis) Tetanus boostersevery 10 years, dont forget! Highest risk group for tetanusover 40 Fishing and gardening in the elderlybig risks
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? HSV-1 Cold sores Usually above the belt
The Herpes family HSV-Type 2below the belt (STD vs. VD) The Herpes family VZVvaricella zoster virus ShinglesHells fire
Can shingles be prevented by administering the varicella vaccine to the elderly? Zostavax (Merck)-a stronger version (14x) of Varivax (for kids) The Herpes family EBV (Epstein-Barr **virus) MONO, Lymphoma
? MS (Dr. Tony Epstein and his lovely assistant, Ms. Yvonne Barr) The Herpes family And dont forget: CMV (cytomegalovius)gastroenteritis, retinitis, pneumonitiswreaks havoc in
immunocompromised patients HHV-6 (Roseola)(?MS) HHV-7 (??) The Herpes family HHV-8 (1995) Kaposis Sarcoma Herpes Virus (KSHV)
OTHER EXCEPTIONS TO THE RULE.. Tuberculosis Exceptions to the rule HPV Vaccine for HPV-16 and 18
Gardasil (Merck) Exceptions to the ruleHepatitis 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 Guys tattoosout there, everywhere Gals are a bit more subtle
Exceptions to the ruleHepatitis 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? INNATE IMMUNE RESPONSEBarrier defense mechanisms
Skin and mucous membranes Open wounds/ulcerative lesions Bleeding gums, sores or lesions in mouth Salivaprotective factorsIgA, low
salinity ph of body fluids Estrogen plays a role in maintaining the healthy pH of the vagina4.5 Vaginal lactobacillus as normal microflora Teenagers and sex Menses
Exocervix vs. endocervix You have a yeast infection. Yeast infections When the estrogen levels are low or nonexistent Young girls Elderly women Antibiotics change the normal flora
pH of body fluids Urine pH4 (estrogen receptors on the urethra) E. Coli and UTIs Young gals, and old gals pH of body fluids semen (pH7); anything with an H_V
lives in italkaline to alkaline transmits disease Do condoms protect? YES But not the natural feel condoms You want to do what with my intestines?
To circumcise or not to circumcisethat 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%
pH of body fluids Gastric pH2 H. pylori and ulcers Consider the patient on PPIs and continuous H2 blockade for GERD at highrisk for food-borne illnesses Innate defense: acute inflammation
Vasodilation Increased permeability of vascular membranes Arrival of WBCsfirst the segs and then the macrophages 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
SEGSnormal function and the role of Prednisone Margination, pavementing, migration and engulfment (degranulation) Yum. Prednisone and the neutrophil Inhibits migration and degranulation, hence its
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 segsis fever good for you? YES! 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) 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) 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 Duodenumthe organ of nausea IL-1 release Increases melatonin production and
makes you sleepy IL-1 release also
Lowers pain thresholdeverything hurts Your hair hurts Your teeth hurt Your skin hurts Youre tired Youre miserable
Macrophage is the APC--Antigen processing cell and IL-1 release CD4 IL-1 release TNF-a
macrophage With CD4 receptor IL-2 T4 cell CD4
T4 or helper T cell ON 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: Crohns disease Rheumatoid arthritis TNF-alpha inhibition Drugs to reduce TNF-alpha
Infliximab (Remicade) Adalimumab (Humira) Etanercept (Enbrel)infusion of TNF- receptors to bind excess TNF- Chemical events involved in inflammation itis Histamine releasehistamine must be a bad guy
Prostaglandin productionlots of drugs we take are anti-prostaglandin drugs Activation of complement (also known as complement fixation)a series of 9 inactive proteins responsible for inflammation complement levels can be measuredexample, lupus and the kidney-- nephritis
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) Cells of the immune system-lymphocytes Cell-mediated immunity
T4 Helpersturn the system on T8 Suppressorsturn the system off T4/T8 ratio is 2:1
Fights viruses, fungus, protozoa, parasites, cancer, transplant tissue AIDS and the T-cells T-cells release cytokines
(should this be used in your patients with autoimmune disease?) TH1 and TH2 Hygiene Hypothesis; the earlier the exposure to dirt, the better the TH1 system will be TH1 predominance = cell mediated immunity TH2 predominance=
allergies and autoimmune disease Get em dirty!! B lymphocytes (cells) B cell---plasma cell---antibody production (7-21 days)(except HIVcan take as long as 1 year)
Y Flu vaccine 2-4 weeks before it gets here! Immunoglobulins IgM1st formed to an infection; fixes complement (inflammation), agglutinates (clumps) IgG2nd formed; memory; crosses placenta; fixes 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 Plasma cells produce antibodies IgAbarrier antibody; saliva, tears, urine,
breast milk How can you boost IgA levels? Boosting immune system Humor Exercise Sex
What about IgD? No one knows exactly what it does, so you dont have to learn it Plasma cells produce antibodies IgEantibody of allergies Drills a hole in the
mast cell releases primary granules full of histamine Antihistamines Allergies and anaphylaxis What can you do to reduce allergies? Get rid of the pet?
Take drugs Anti-histamines Anti-leukotrienes Anti-IgE (monoclonal antibody) omalizumab (Zolair) How about sleeping with the
enemy? Give em a bath once a week They love it Thanksand remember, Support bacteria theyre the only
culture some people have Barb Bancroft, RN, MSN, PNP [email protected] www.barbbancroft.com
15 states have appropriate TPR codes. Problems still persist. Medical-Industrial Complex (MIC) Authoritarian government. Child-custodybattles. n=35. Figure 2. Disability as a condition for terminating parental rights. Figure 1. Specific disability identified in state TPR codes.
Funding Opportunities at Wellcome Fiona MacLaughlin Heather Chaffey Basic Organisational Structure Key to an innovative healthcare and pharmaceutical industry we must: develop bench to bedside - bedside to bench approaches optimize academia & industry links develop innovative public private partnerships...
Financial Disclosures. Neither I nor any member of my immediate family have had a financial relationship or interest in the last twelve months with a proprietary entity producing health care goods or services referenced in this presentation
Manage or Measure Spillover. Spillover: when the control group, although "untreated", is affected (positively or negatively) by the treatment. Choose unit that contains spillover (ie randomize at school or village rather than individual level) Measure Spillover: TUP (Bangladesh, Honduras, Peru,...
paul nipkow (1884) berhasil mengiriman gambar elektronik menggunakan kepingan logam yg disebut teleskop elektrik dgn reolusi 18 garis, dengan temuannya itu maka dia disebut bapak televisi. sejarah televisi.
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