Ch. 6 Effector Mechs of Cell-mediated Immunity

Question 1

Naive T-cell surface expression

Answer 1

L-selectin and and LFA-1 integrin - allows naive cells to enter and stay in lymph nodes

Question 2

Activated T-cell surface expression/ migration of T-cells to site of infection

Answer 2

Activated T-cells lose L-selectin and therefore stay out of lymph nodes (they already know what antigen they need, they just have to go find it.)

• Increase expression of E/P selectin Ligand and LFA-1 and VLA integrin.
• TNF and IL-1 from macrophages at site of infection induce endothelial cells to express E/P selectin and ICAM-1 and VCAM-1 to bind the respective markers on T-cells
• Selectins bind first and a slow roll.
• Integrins lead to tight adhesion
• Macrophages and endothelial cells also release chemokines to attract the T-cells and then T-cells migrate through the vessels and to the infection

Question 3

Th1 Reaction

Answer 3

• CD4+ cells activate macrophages
• Response that occurs in a DTH (to immunized individuals, longer on first exposure)
• delay is result of 24-48 hrs it takes for memory T-cells to be activated to effector cells, find the infection, and induce a response

Question 4

Macrophages bind antigen then…

Answer 4

• phagosome
• phagolysosome
  
  • ROS, NO, Proteases
• display peptides on MHC-II
• present to T-cells
  
  • This activates T-cells

Question 5

T-cells recognize antigen present by macrophage…

Answer 5

• T-cells increase expression of CD40L
• CD40L binds to CD40 on macrophage and activates them
• (Th1) T-cells are express INF-gamma to activate macrophages
• Secrete TNF to make vascular endothelial express more secretins and integrins

Question 6

Macrophages activated by T-cells…

Answer 6

• Activated macrophages release IL-12 to stimulate T-cells to turn into Th1 cells
• IL-12 also Increases the amount of INF-gamma T-cells secrete
• Activated macrophages releases IL-12 and TNF to increase vascular permeability and secretin and integrin expression
• make PDGF to activate fibroblast and endothelial cells\
• increase MHC-II expression

Question 7

Th1 cells secrete..

Answer 7

INF-gamma to stimulate macrophages

Question 8

Actions of Th1 CD4+ cells

Answer 8

• activate macrophages
• stimulate CD8+ cells into active CTLs
  
  • CTLs can also activate macrophages when they present with MHC-1
• Stimulates B-cells into plasma cells - Ig producing

Question 9

TH17 cell function

Answer 9

secrete chemokines to attract neutrophils and monocytes to an infection

Question 10

Th2 reaction + cytokines

Answer 10

• eosinophil based reaction - against helminths
• less tissue damage
• IL-4,5,10,13

Question 11

IL-4

Answer 11

Activates production of IgE - binds to mast cells to cause degranulation and surround helminths

• inhibits microbial activities of macrophages - limits tissue damage and turns on Th1 response
• increases macrophage expression of mannose receptors (complement)

Question 12

IL-5

Answer 12

Activates eosinophils - they bind to the IgE coated helminths and release their granules and kill the parasites

Question 13

IL-4, IL10, IL-13

Answer 13

• inhibitions the microbial activities of macrophages - ending the TH1 response and limiting tissue damage

Question 14

IL-4, Il-13

Answer 14

increases macrophage expression of mannose receptors (complement

Question 15

IL-13

Answer 15

• microbial macrophage inhibition
• mannose receptors on macrophage
• make fibroblasts increase production of collage and leads to fibrosis

Question 16

CD8 CTL’s general role

Answer 16

• they destroy cells that are infected with microbes that exist only in the cytoplasm
• recognize MHC-1and CD8 co-receptor
• kill the reservoire of microbes hiding in the cell that can’t be attacked by macrophages
• do not require co-stimulators to activate it at this point. already differentiated so can kill any cell in any tissue

Question 17

Two main proteins in CTL granules that kill infected cells

Answer 17

• perforin - polymerizes and forms a pore in the membrane of the infected cell. - makes a place for granzymes to enter the cell
• granzymes - cleave pro-caspase into a caspase and initiate the apoptosis cascade
• granzyme and perforin can also both enter via receptor mediated endocytosis
  
  • perforin can then put a pore in the endosome and release granzymes into the cytoplasm

Question 18

Minor CTL Killing pathway

Answer 18

• CTL’s have Fas-L which can bind to Fas receptors on infected cells -> caspase cascade -> apoptosis

Question 19

CTLs produce which cytokine

Answer 19

INF-gamma - activates macrophages also to kill phagocytoized stuff (they clean up after apoptosed cells)

Question 20

Evolution of microbes to avoid cell mediate immunity

Answer 20

• prevent fusion of phagosome and lysosome
• prevent the presentation of peptide on MHC-1
• escape vesicles into the cytoplasm
• release cytokine receptors to sop up all the inflammation and t-cell stimulating cytokines