immuno pulmonary

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dtminhthu
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37987
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immuno pulmonary
Updated:
2010-09-28 11:42:53
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immuno pulmonary
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immuno pulmonary
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  1. lung dz that are mediated primarily by innate immunity
    acute respiratory distress syndrome
  2. lung Diseases mediated by adaptive mechanisms of immunity
    • Th1 mediated: Hypersensitivity pneumonitis
    • Th2 mediated: Asthma
  3. lung dz mediated by autoimmune mechanisms
    • Wegener’s granulomatosis
    • Goodpasture Syndrome
  4. severe-life threatening respiratory insufficiency caused by diffuse alveolar capillary damage and influx of fluid into the alveoli
    ARDS
  5. collapsed or distended alveoli.
    Many contain dense proteinaceous debris, desquamated cells and hyaline membranes
    ARDS
  6. triggers of ARDS
    Sepsis, Diffuse pulmonary infections (viral, mycoplasma, pneumocystis, pneumonia and military tuberculosis), Gastric aspirations, Mechanical trauma
  7. mechanism of ARDS from infectious insults
    • Antigen (bacteria) LPS binds TLR4 on alveolar macs --> Activation of transcription factors, particularly NF- kB, that control pro-inflammatory gene expression --> Transcription of inflammatory cytokine genes --> TNF, IL-1, IL-12, IL-8 --> strong neutrophil chemoattractant and stimulates their recruitment from the
    • microvasculature, thru the interstitium and into alveolus --> Once in air space, neutrophils produce leukotrienes, ROS and proteases, and platelet activating factor (vasodilation) --> loss of diffusion capacity and both Type I and II cells die & permeability increases
  8. mechanism of ARDS from non infectious insults
    Activation of transcription factors, particularly NF- kB, that control pro-inflammatory gene expression --> Transcription of inflammatory cytokine genes --> TNF, IL-1, IL-12, IL-8 --> strong neutrophil chemoattractant and stimulates their recruitment from themicrovasculature, thru the interstitium and into alveolus --> Once in air space, neutrophils produce leukotrienes, ROS and proteases, and platelet activating factor (vasodilation) --> loss of diffusion capacity and both Type I and II cells die & permeability increases
  9. IFN gamma
    produced by Th1 cells. Activates macs
  10. Macs produce _____ to activate/differentiate more Th1 cells
    IL 12
  11. stimulates monocyte production by bone marrow
    IL3/GM-CSF
  12. cause local tissue destruction, incr expression of local adhesion molecules
    TNF-alpha and TNF-beta
  13. mechanism of granulmatous formation
    Chronic CD4 T cell activation (by persistent antigen) and Th1 cytokine production (IFNg) continually stimulate macs --> macs develop incr cytoplasm & cytoplasmic organelles (epitheloid cells), and may fuse together to form multinucleated giant cells --> Clusters of activated macs surrounding persistent antigen --> granulomas
  14. true granuloma is...
    composed of an aggregation of macs that are transformed into epithelium-like (epithelioid) cells, surrounded by lymphocytes & fibroblasts
  15. pathogenesis of TB
    • Primary Tb infection is characterized by early proliferation of bacteria in pulmonary alveolar macrophages (Lasts about 3 weeks)
    • By 3 wks a Th1 CD4 T cell response is mounted that activates macs to contain the M. Tb, by 1) formation of intracell phagolysosome, 2) production of NO, and 3)orchestrating formation of granulomas.
    • TNFa, produced by activated macrophages, recruits monocytes, which differentiate into epithelioid cells, and in combo w/ formation of Giant cells form granuloma
  16. differ from asthma cuz it involves alveoli instead of airways
    hypersensitive pneumotitis. Farmer's lung and pigeon breeder's lung
  17. caused by inhalation of spores of thermophilic actinomycete found in harvested hay
    Farmer's lung (hypersensitivity pneumotitis)
  18. caused by proteins from serum, excretions, or feathers of birds
    pigeon breeder's lung (hypersensitive pneumotitis)
  19. mechanism of hypersensitivity pneumotitis
    Activated neutrophils release proteases, ROS, and vasodilator substances resulting in damage to alveolar epithelium and edema.

    Activated alveolar macrophages produce IL-12, which promotes Th1 CD4 T cell production of IFNg, that further stimulates inflammatory cytokine production by alveolar macrophages and contributes to granuloma formation
  20. type II hypersensitivity because immune complexes are not tissue bound
    Wegener’s granulomatosus (cANCAs--PR3) and Goodpasture
  21. Noncollagenous protein in basement membrane of lung alveoli and kidney glomeruli is antigen --> complement activation via immune complexes à neutrophil activation and degranulation
    Goodpasture syndrome
  22. high prevalence of certain HLA haplotypes (eg, HLA-DRB1) in a affected patients
    diffuse pulmonary hemorrhage, glomerulonephritis, or both presenting simultaneously, in association with circulating
    Goodpasture syndrome
  23. anti-basement membrane antibodies. bind to type IV collagen. Destruction of alveolar basement membrane
    results in intra-alveolar hemorrhage
    Goodpasture syndrome
  24. mechanism of Goodpasture syndrome
    Bound antibody leads to activation of classical complement pathway and generation of C5a, which recruits neutrophils and monocytes --> Recruited cells bind to deposited antibodies via Fc receptors --> produce enzymes ROS that mediate tissue damage
  25. Rheumatic fever mechanism
    hypersensitivity reaction induced by group A streptococci , where antibodies directed against M proteins of certain strains of streptococci cross-react with glycoprotein antigens in the heart, joints and other tissues
  26. molecular mimicry
    In rheumatic fever. resemblance of pathogen and host antigens that leads to the targeting of host tissues
  27. rheumatic fever is type ___ hypersensitivity rxn
    II and IV

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