Cell Mediated Immunity II Flashcards Preview

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Flashcards in Cell Mediated Immunity II Deck (17)
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1

describe gene products after CD4+ T cell activation (from naive to effector)

  • immediate genes (1/2 hour of recognition)
    • transcription factors (C-Myc, NFAT, NF-kB)
    • early genes (1-2 hours from recognition)
      • IL-2, IL2R, IL-6, IFN-γ
    • late genes (more than 2 days later)
      • encode adhesion molecules

2

describe what happens during the transition from naive to effector CD4+ T cells

  • naive T cells are stimulated by microbial antigen in the lymph nodes and spleen
    • express adhesion molecule:
      • L-selectin
    • express chemokine receptor CCR7 (selective migration in lymph node)
  • gives rise to effector cell whose function is to eradicate intracellular microbes
  • differentiated effector T cells migrate to the site of infection
    • express: E- and P- selectins, Integrin LFA-1 and VLA-4
      • LFA-1 beta chain = CD18 and alpha chain = C11a
  • phagocytes at the site of infection display antigen

3

describe the development of subsets of CD4+ T cells (Th1, Th2 and Th17 cells)

4

describe the activation and function of Treg cells

5

describe the function of T Follicular B helper cells (Tfh)

6

summarize the function of IFN-γ from Th1 cells

  • production of IFN-γ
    • stimulate phagocyte-mediated ingestion
      • expression of lysosomal proteases
      • synthesis of reactive oxygen species and nitric oxide (deals with organisms that escape the phagosome)
    • stimulate production of antibodies that promote phagocytosis
    • stimulate expression of Class II MHC and B7 on APCs (amplify T cell response)
    • activated macrophages produce IL-12
      • drives CD4+ T cells to Th1 cells (amplification)
    • same reaction: delayed type hypersensitivity (DTH)

7

summarize the function of Th2 cells

  • stimulate phagocyte-independent eosinophil-mediated immunity
  • against helminthic parasites
  • produce IL-4
    • stimulates production of IgE antibodies
    • IgE coats parasites and eosinophils/mast cells release granules enzymes that kill them
  • produce IL-5
    • activates eosinophils
  • IL4, IL-10, IL-13
    • alternative macrophage activation
      • synthesis of extracellular matrix proteins for repair
      • inhibit microbicidal activity of macrophages
        • supresses Th1 cell-mediated immunity

8

describe classically activated macrophages (M1) vs alternatively activated macrophages (M2)

9

summarize the cyotkines secreted by Th1 vs Th2 and their actions

10

describe the balance of Th1 and Th2 and what occurs if one is increased vs decreased

11

describe the balance between Th1 and Th2 as seen in Leishmania major and Mycobacterium leprae

12

describe the function of Th17, the cyotkines secrereted, their functions and Th17 defects

  • Th17 cells induce inflammation
  • stimulate antimicrobial production: defensins
  • destroy extracellular bacteria and fungi
  • most important cytokines:
    • IL-17 and IL-22
      • IL-17 recruits leukocytes (neutrophils)
      • IL-22 important in epithelial barrier integrity
  • Th17 defects: bacterial abscesses and chronic mucocutaneous candidiasis

13

describe memory T lymphocytes

  • found in lymphoid organs:
    • central memory cells: rapid clonal expansion
  • found in peripheral tissue (mucosa and skin):
    • effector memory cells: rapid effector cell
  • require IL-7 to stay alive
  • quiescent; G0 stage
  • last months to years vs. effector cells that last days to weeks
  • responsible for secondary response

14

describe the inhibitory role of PD-1 and CTLA-4

15

describe T cell anergy

  • clonal anergy
    • inability of cells to proliferate in response to engagement with MHC-peptide complex
    • due to absence of appropriate costimulatory signal or by CTLA-4 or other inhibitory signal

16

describe the resistance of microbes to cell-mediated immunity

  • intracellular bacteria (Mycobacterium, Legionella, Listeria) inhibit fusion of phagosomes with lysosomes
    • escape into cytosol
    • escape phagocytic killing
  • many viruses inhibit class I MHC-associated antigen presentation
    • block transport of antigenic peptide from cytosol to ER
    • removing class I from ER
    • result in reduced class I MHC on surface (unstable empty MHC molecules)
      • NK cells recognize and act on low class I MHC on surface of cells
  • other viruses produce inhibitory cytokines or decoy soluble cytokine receptors that neutralize cytokines (e.g. INF-γ)
  • other viruses directly infect T-cells (HIV attack CD4+ T cells)

17

describe the microbe and the evasive mechanism of action within the cell (mycobacteria, HSV, CMV, EBV, pox virus)