Biochem post midterm- lymphocytes

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  1. 2 branches of immunity, and the two major branches of one of the original branches
    • innate/non-specific
    • adaptive specific (humoral mediate[B-cells], cell-mediated [T-cells])
  2. Two main branches of hematopoietic stem cells?
    • Myeloid progenitor cells
    • Lymphoid progenitor cells
  3. What cells are derived from myeloid progenitor cells
    • platelets
    • neutrophils
    • basophils
    • eosinophils
    • monocyte macrophage
    • RBC
  4. What cells are derived from lymphoid progenitor cells?
    • NK cells
    • T cells
    • B-cells
  5. Which cells are polymorphonuclear/granular? What do each of the cells chiefly do? How What percentage of total leukocytes are they?
    • neeutrophils (50-60%)-phagocytose invading pathogens
    • Eosinophils (1-4%)-destroy parasites, modulate allergic inflammatory rxns
    • Basophils (0.5-2%)- release histamine, serotonin, bradykinin, heparin, cytokine; converts arichodonic acid to Prostaglandins+ leukotrienes
  6. Which cells are mononuclear leukocytes? What does each cell do? Percentage of total leukocytes?
    • Lymphocytes (T and B cells)- 20-40% mediate cytokine release, phagocytose and kill ingested microbes
    • Monocytes + Kupffer cells (2-9%)- macrophages in extravascular tissue, kill virally infected cells+tumour cells, offer natural and adaptive immunity, move via amoeboid movement
    • Megakaryocytes (platelets)- initiate blood clotting- release histamine and serotonin
  7. What do neutrophils do? What percentage of total leukocytes are they?
    • Polymorphonuclear
    • 50-60%
    • Phagocytose invading pathogens
  8. What do eosinophils do? What percentage of total leukocytes are they?
    • Polymorphonuclear
    • 1-4%
    • Destroy parasites, modulate allergic inflammatory reactions
  9. What do basophils do? What percentage of total leukocytes are they?
    • polymorphonuclear
    • 0.5-2 percent
    • release histamine, serotonin, bradykinin, heparin, cytokines
    • convert arachidonic acid to prostaglandins and leukotrienes
  10. What do lymphocytes do? What percentage of total leukocytes are they?
    • 20-40%
    • Mononuclear
    • Mediate cytokine release
    • phagocytose and kill ingested microbes
  11. What do monocytes and natural killer cells do? What percentage of total leukocytes are they?
    • macrophages in extracascular tissue
    • kill virally infected cells + tumour cells
    • offer natural and adaptive immunity
  12. describe the activation of leukocyte NADPH oxidase
    • NOX is found on the vesicle.
    • attached to the vesicle is cytochrome b558
    • when the cytosolic subunits (3) bind the cytochrome b558, nox becomes active and releases superoxide radicals inside the vacuole
    • the vacuole will then fuse with the phagosomal membrane, releasing superoxide anion into the phagosome
  13. NADPH oxidase deficiency leads to what? Describe the disease
    • Chronic granulomatous disease
    • can't kil bacteria that have high catalaze activity or low H2O2 production,
    • can kill bacteria with high H2O2 production and low catalaze activity. 

    leads to higher incidences of pneumonia and sepsis
  14. How many nox enzymes? Describe them, which is most important?
    • 5
    • Nox-1= colon> prostate, uterus, breast, macrophage
    • Nox-2= neutrophils>>hepatocyte, B lymphocye, cardiomyocytes, endothelium
    • Nox 3= inner ear, fetus
    • Nox 4= kidney, bloodvessels, cardiomyocytes, endothelium
    • nox 5- lymphoid tissue, testes
  15. What are some properties of protein isoforms?
    • usually single nucleotide polymorphism
    • varying levels of functionality 
    • resistance to mutation
    • overlapping distributions
    • good for drug therapy (selectively affect an isoform)
  16. What is rheumatoid arthritis?
    • Autoimmune inflammatory disease which principally attacks joints
    • -proliferative synovitis progressing to catilage destruction/ joint akylosis 

    pathogenesis: genetic susceptibilty + joint damage mediated by leukocyte or exogenous arthritogen 

    treated with NSAIDs
  17. Ibuprofen
    • cox-1 inhibitor
    • cox-2 inhibitor
  18. Side-effects of NSAIDs
    GI ulcer formation as a result of stomach cell mitochondrial uncoupling and acidosis

    • Cox-1 inhibition causes: increased tisue unsaturated fatty acid (acidosis)
    • decreased PGE2 levels-> decreased protection of stomach
    • (unsat. fatty acids and prostaglandin synthase attacks protective mucous layer)
    • Cox-2 inhibition cuases inhibition of thromboxane and platelt aggregation
  19. How do eosinophils protect from infection
    • Form hypobromite (as opposed to chlorite) to destroy worms, parasite, tumours, fungi
    • Produc cytokines (Platelet activating factor, Leukotriene C4)
  20. How do macrophages protect the body?
    • 1) endocytosis/exocytosis via specific receptors for IgG and C3 coated on bacteria
    • 2) H2O2 production by NOX to kill mycobacteria
    • 3) arachidonate oxidation to prostaglandin
    • 4) cytokine production- upon activation by: 
    • -lipopolysaccharide (endotoxin)
    • -immune system activation
    • -inflammation or interferon (IFN-y)
    • 5) endocytosis and delivery to lysosomes (via scavenger receptor) of oxidized LDL can result in formation of foam cels (basis of atherosclerosis plaque)
  21. What does TNFa do?
    • Primary trigger for inflammatory response
    • macrophages, lymphocytes, monocyte, kertinocyte

    Is increased in chronic inflammation diseases (rheumatoid arthrirites, encephalitis, tumours)

    Drug therapy: NSAIDS, GLUCORTICOIDS, DMARTDs (disease modifying anti-rheumatic drugs)
  22. Immune mediated drug activated hepatocyte cytotoxicity
    • 1) toxic doses of drugs injure jepatocytes-> releases Kupffer-cell attracting factor
    • 2) additional mononuclear phagocytes also recruited from blood and bone marrow precursors
    • 3) macrophages become activated 
    • 4) activated macrophages and endothelial cells release cytokines (ex. TNFa+ PAF-> activates Kupffer cells (which produce ROS and release more cytokines)
    • 5) Attraction of neutrophils by cytokines
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Biochem post midterm- lymphocytes
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