chapters 18 & 19: practical applications of immunology immune system disorders

1. chapters 18 & 19: practical applications of immunologyimmune system disorders

2. immunological memory

3. immunological memory movement via circulation memory B  bone marrow secrete Ab continuously effector memory T  tissue space central memory T  lymphatic circulation

4. Ab & TCR affinity • memory cell abundance • 100–1000x 1°response • memory affinity • 1° 1/100000 bind tightly • 2° 1/1000 bind tightly • B cells don’t require TH cells • 1° response 12–14 d • 2° response 1–2 d

5. immunity

7. childhood immunization recommendations

8. case study: Varicellavirus • March 12, 2009 15yo female ER admission • 3d Hx rash, 1d Hx shortness of breath, fever (101.1OF) • Dx: septic shock • hospital stay • Tx: acyclovir, Abx (ciprofloxacin, meropenem, STX, ticarcillin w/clavulanate, tigecycline) &mechanical ventilation • pneumonia & acute respiratory distress • multi-organ dysfunction • pancytopenia • nosocomial infections • LRI: Enterobacter cloacae • UTI: Pseudomonas aeruginosa • sepsis: Stenotrophomonas maltophilia • prognosis: dead on day 21 • Click here to read and here to listen, if you have concerns about a link between autism & vaccinations.

9. immunological identification methods immunological assays • Ag-Ab interaction • direct detect Ag • indirect detect Ab • Sensitivity: probability of false negativeSN-N-OUTSeNsitive when Negative rules OUT • Specificity: probability of false positiveSP-P-INSPecific when Positive rules IN

10. monoclonal antibodies (mAbs) hybridoma: cancerous B cell fused to Ab producing spleen cell  mAb

11. 1896: Gruber-Durham reaction “agglutination” 1896: Widal’s serum diagnosis of Typhoid carriers 1900: Landsteiner: ABO & Rh blood typing Current: various latex agglutination agglutination reactions: naked eye results Figure 18.4 CrypotococcusneoformansAb diagnoses cryptococcalpneumoniae

12. enhancing visibility: fluorescent Abs & FACS direct Lyssavirus rabies test

13. complement fixation

14. enzyme-linked immunosorbent assay (ELISA) direct ELISA indirect ELISA

15. the rapid strep test • 70–85% pharyngitis cases are viral- no Abx, bacterial cases are self-limiting • S. pyogenes causes pharyngitis and long-term sequelae (rheumatic fever, kidney disease) • No symptoms are specific to streptococcal pharyngitis • rapid strep test • 95–98% specificity; 70-95% sensitivity

16. chapter 18 learning objectives • How and when is immunological memory generated? • Where do memory B cells, effector memory T cells and central memory T cells “live?” • Compare and contrast the affinity and speed of the primary vs. the secondary immune response. • Distinguish the four ways that immunity can be acquired. Be able to recognize and give an example of each. • Describe the serological tests discussed in lecture; include direct and indirect versions of each. Understand how to interpret positive and negative results for each. As technology has advanced, how has that made these serological tests more specific? • Define specificity and sensitivity. How do these terms relate to the serological tests you described above. • Describe the GENERAL mechanism for producing monoclonal Abs. Why are they necessary?

17. chapter 19: immune system disorders

18. immune deficiencies

19. Acquired Immune Deficiency Syndrome • ~1930: SIVcpz crosses species barrier • 1959: death in Congo • 1968: HIV in U.S. (Africa  Haiti) • 1981 • MMWR P. carinii • homosexuals, PCP, CMV, Kaposi’s sarcoma • 200,000 people infected • 1983 • discovery of HIV • AIDS in 28 nations • 2012 • >35 million people with HIV/AIDS, 3.3 million <15 YO • 2.3 million infected, 260,000 <15YO • 6,300 new infections daily • 1.6 million people died, 210,000 <15YO • 75 million total infections, 36 million total deaths

20. infected body fluid transmission via: sexual contact (MSM, MSW, WSW, artificial insemination) blood-contaminated needles organ transplants & blood transfusion breast milk transplacental infection of fetus HIV transmission

21. HIV target cells

22. HIV infection in CD4+ T cells active infection latent infection

23. HIV diagnostic methods western blot (not current recommendation) proviral PCR: 1/150,000 cellsRT-PCR: 50 RNA/ml blood ELISA P24 Ag & HIV Ab 0.9996% specificity

24. Treatment: HAARTHighly Active AntiRetroviral Therapy 1987: Retrovir (azidothymidine) (N)NRTIs: (N)Nucleoside analog Reverse Transcriptase Inhibitors PIs: Protease Inhibitors IIs: IntegraseInhibitors FIs: Fusion Inhibitors  CRAs: Chemokine Receptor Antagonists (prevent CD4 binding)

25. the stages of HIV Infection

26. Ab Fluorescence and Fluorescence Activated Cell Sorting (FACS)

27. HIV/AIDS worldwide • 70% of world’s HIV/AIDS (20 million) • 88% of world’s HIV/AIDS children • 1.6 million infected in 2012 • 1.2 million died (75% of deaths worldwide)

28. HIV/AIDS in the US • 1.1 million have HIV/AIDS, 1/5 don’t know they’re infected • 1.7 million have been infected, 650,000 have died • 50,000 new infections per year • MSM: 44x MSW, 40x women • 54% blacks • 20% women • Southerners

29. chapter 19 learning objectives • Contrast congenital and acquired immune deficiencies. How can microbiology aid in the treatment of congenital immune deficiencies? • Describe the origin, modes of transmission, and host cells for HIV. What do each of these host cells have in common? Does HIV behave the same way in all host cells? • How is HIV transmission different in developing vs. developed countries? • How is HIV diagnosed initially? How does this differ from the monitoring that is done to track HIV conversion to AIDS? Why is it necessary that viral RNA and viral DNA is looked for? What does each tell you about HIV? • Generally speaking, AIDS is defined by a drop in a certain body cell and a serum rise in something else. What are these? • Describe why FACS is necessary to track the population of the body cell mentioned above? • Where are the majority of people living with AIDS?