My Immunology

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My Immunology
2012-01-11 13:50:41
Immunity HIV

Immunity, HIV
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  1. Define neutropenia
    What pathogens are normally found in the neutropenic patient
    • Neutrophil count less than 0.5x109, or less than 1x109 and falling
    • Fever develops in almost all patients
    • S.Aureus, enterococci, E.coli and especially fungi
  2. Define chronic granulomatous disease
    • An X-linked inherited cause of innate deficiency
    • Defect in NADPH oxidase = reduced O2 radical production in macrophages
    • Causes recurrent gram +ve and fungal infections
  3. What is the significance of lymphopenia?
    • It affects humoral immunity as well as adaptive
    • Leads to infection by most types of pathogen
  4. Why does a splenectomy cause immunodeficiency?
    • Splenic macrophages eliminate non-opsonised microbeds, including encapsulated organisms
    • Site of primary Ig response
    • All phagocytic cells impaired
  5. When did HIV arise in the human population?
  6. What is the wordwide and national epidemiology of HIV?
    • Small IVDU population, mainly found in london
    • MSMs largest population in UK
    • Heterosexual disease in other counties, especially africa
  7. Outline common presentations of HIV infection
    • Lymphadenopathy
    • Mucosal ulceration
    • Flu-like symptoms
    • Pseudo-membranous candida
    • Oral hairy leukoplakia (EBV infection)
    • Skin disease
  8. List some characteristics of AIDS?
    • CD4:lymphocyte ratio >0.15
    • Candida
    • Polycystic pneumonia (P.jirovecii)
    • Kaposi's sarcoma
    • Gingivitis
    • Cerebral toxoplasmosis
  9. Outline the genome of HIV virus and its replication in cells
    • Retrovirus, ssRNA
    • Integrated into T4 host lymphocyte chromsome, causing latent infection and incurability. Also infects macrophages and dentritic cells
  10. What processes can HIV antivirals inhibit?
    • Entry into cell via CCR5 receptor
    • Envelope fusion with membrane via GP41
    • Reverse transcription via reverse transcriptase
    • Chromosome entry via integrases
    • Replication via nucleotides
  11. What characteristics of HIV make it difficult to treat?
    • Intracellular replication
    • Most enzymes used for replication are cellular not viral
    • Reverse transcriptase has a high mutability; inhibits treatments
  12. What is HAART?
    • Highly active anti-retroviral therapy
    • A regimen of 3 or more drugs used to treat HIV
  13. What problems imitate HIV drug resistance?
    • Non-compliance
    • Insufficient drug dosage
    • Weak antiviral regimen
    • Drug interactions reducing half life
    • Pregnancy (changes metabolism)
  14. What resistance tests for HIV are available?
    • Phenotypic: Virus grown in changing concentrations of drugs. Expensive and lengthy
    • Genotypic: Multiple RT-PCR primes used to sequence protease, RT, integrase or envelope genes
  15. Give examples of immunosuppresants
    • Glucocorticoids
    • Anti-metabolic agents
    • Celcineurin inhibitors
    • Biologic therapies
  16. What is the mechanism of action of azathioprine? What are its adverse affects?
    • Purine analogue
    • Prevents DNA synthesis, especially in lymphocytes, causing apoptosis
  17. What is the mechanism of action of glycophenolate mofetil? What are its indications?
    • Inhibits purine biosynthesis and so lymphocyte proliferation (other cells can scavenge purines)
    • Transplantation and vasculitis
  18. What is the mechanism of action of methotrexate?
    Inhibit folate synthesis to prevent thymine/purine synthesis
  19. Define a biologic therapy
    A medication tailored specifically to target an immune or genetic mediator of a disease
  20. Give examples of some biologic therapies
    • Anti-TNF
    • Rituximab
    • Herceptin
  21. What is the mechanism of action of rituximab?
    Regulates immunosuppression by inducing B cell apoptosis via CD20 binding
  22. What is the mechanism of action of cyclosporine?
    • Inhibits calceneurin pathway, preventing calcium metabolism and influx into nucleus
    • Prevents IL-2 transcription (lymphocyte chemokines)