Cell Mediated Immunity II

Question 1

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

Answer 1

• 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

Question 2

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

Answer 2

• 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

Question 3

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

Answer 3

Question 4

describe the activation and function of Treg cells

Answer 4

Question 5

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

Answer 5

Question 6

summarize the function of IFN-γ from Th1 cells

Answer 6

• 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)

Question 7

summarize the function of Th2 cells

Answer 7

• 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

Question 8

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

Answer 8

Question 9

summarize the cyotkines secreted by Th1 vs Th2 and their actions

Answer 9

Question 10

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

Answer 10

Question 11

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

Answer 11

Question 12

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

Answer 12

• 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

Question 13

describe memory T lymphocytes

Answer 13

• 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

Question 14

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

Answer 14

Question 15

describe T cell anergy

Answer 15

• 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

Question 16

describe the resistance of microbes to cell-mediated immunity

Answer 16

• 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)

Question 17

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

Answer 17