Exam 2: L14

Question 1

What 3 signals are required for CD4 T helper cells activation and differentiation?

Answer 1

1) TCR- MHC class II with peptide complex, CD4
2) Co stimulation with CD 28 and B7
3) inducer cytokines from APC–> helps generate the right type of effector T cell for the antigen at hand

Question 2

What happens to T cells after clonal expansion?

Question 3

How do effector T cells leave the inductive tissue?

Answer 3

• are able to leave the cortical sinus and enter the efferent lymphatics by: downregulating the lymph node homing receptors CD62L and CCR7; upregulation of sphingosine -phosphate 1 receptor (S1PR1)

Question 4

How do effector T cells enter the target tissue?

Answer 4

• p selectin, E- selectin, VCAM-1, and hyaluronic acid are found on the inflamed endothelium
• T cells surface molecules:
• PSGL-1 is a ligand of P selectin and E selectin of the endothelium (expression)
• VLA-4 is a ligand of VCAM-1 (upregulation)
  -CD44 is a ligand of hyaluronic acid (upregulation)

Question 5

What signals does effector T cells need to carry out effector functions?

Answer 5

• TCR specificity is sufficient
  -don’t need co-stimulation

Question 6

What cytokine plays a vital role in clonal expansion?

Answer 6

IL-2

Question 7

What is cytotoxic T lymphocyte (CTL) effector functions?

Question 8

Name the cytokines released by Th1 effector cells

Answer 8

• Fas
• CD40L
  -IL-2
• IL-3
• GM- CSF
• LT- beta
• LT- alpha
• IFN gamma
• TNF- alpha
• CCL2

Question 9

Name the cytokines released by Th2 effector cells

Answer 9

• IL-3
  -IL-4
  -IL-5
• IL-9
• ## IL13

Question 10

Name the cytokines released by Th17 effector cells

Answer 10

• IL-17
  -IL-22
• IL-21
  -CCL20

Question 11

What are Treg effector cell functions?

Question 12

Th1 effector cells: What happens when IFN gamma and CD40L is released?

Answer 12

• induce and activate M1 macrophages
• enhances macrophage killing of engulfed bacteria

Question 13

Th1 effector cells: What happens when Fas ligand and LT-beta is released?

Answer 13

• induce apoptosis of bacteria laden macrophages
• kills chronically infected cells, releasing bacteria to be destroyed by fresh macrophages

Question 14

Th1 effector cells: What happens when IL-2 released?

Answer 14

• acts on naive CD4 and CD8 T cells
• alters balance of Th1 versus Tfh differentiation to favor Th1
• supports expansion of CD8 CTLs

Question 15

Th1 effector cells: What happens when IL-3 and GM-CSF is released?

Answer 15

• stimulate production of monocytes by bone marrow
• induces monocyte differentiation in the bone marrow

Question 16

Th1 effector cells: What happens when TNF- alpha and LT- alpha is released?

Answer 16

• act on local blood vessels
• activates endothelium to induce macrophage binding and exit from blood vessel at site of infection (diapedesis)

Question 17

Th1 effector cells: What happens when CCL2 is released?

Answer 17

• is a chemoattractant for monocyte
• causes macrophages to accumulate at site of infection

Question 18

Th2 effector cells: What happens when IL-13 is released?

Answer 18

• induces epithelial cell repair and mucus
• increased cell turnover and movement help shedding of parasitized epithelial cells.
• Mucus prevents adherence and accelerates loss of parasite
• increases smooth muscle contractility that enhances worm expulsion
• increased contractility of mucosal smooth muscle enhances worm expulsion

Question 19

Th2 effector cells: What happens when IL-5 is released?

Answer 19

• recruits and activates eosinophils
• eosinophils produce MBP which kills parasites
• mediate ADCC using parasite-specific Ig (IgE)

Question 20

Th2 effector cells: What happens when IL-3 and IL-9 is released?

Answer 20

• drive mast cells recruitment–> specific IgE arms mast cels against helminths
• mast cells produce mediator such histamine, TNF alpha, MMCP. These recruit inflammatory cells and remodel the mucosa

Question 21

Th2 effector cells: What happens when IL-13 and IL-4 is released?

Answer 21

• recruit and activate M2 macrophages
• products of arginase-1 expressed by M2 macrophages increase smooth muscle contraction and enhance tissue remodeling and repair

Question 22

Th17 effector cells: What happens when IL-17 and IL-22 is released?

Answer 22

• induce the production of antimicrobial peptides by epithelial cells
• direct killing or growth inhibition of bacteria attached to epithelium

Question 23

Th17 effector cells: What happens when IL-22 is released?

Answer 23

• increases epithelial cell turnover
• increased epithelial cell division and shedding impairs bacterial colonization

Question 24

Th17 effector cells: What happens when IL-17 is released?

Answer 24

• activates stromal cells and myeloid cells to produce G-CSF, which stimulates neutrophil production in bone marrow
• increases numbers of circulating neutrophils to sustain supply of short-lived innate effectors at infection site
• activates stromal cells and epithelial cells to produce chemokines that recruit neutrophil
• recruit of neutrophils to site infection

Question 25

Th17 effector cells: What happens when CCL20 is released?

Answer 25

- chemoattractant for other Th17 cells - increased recruitment of Th17 cells to site of infection

Question 26

What are the two mechanisms of cytotoxic T lymphocyte effector function?

Answer 26

1) perforin, granzymes, and granulysin --> target cell lysis or apoptosis ; FASL--> engages FAS on target cell.. target cell apoptosis 2) produce IFN gamma, TNF and LT alpha - IFN- gamma--> activate macrophages - TNF can induce target cell apoptosis

Question 27

What are the actions of perforin on target cells?

Answer 27

aids in delivering contents of granules into cytoplasm of target cell

Question 28

What are the actions of granzymes on target cells?

Answer 28

serine proteases, which activate apoptosis once in the cytoplasm of the target cell

Question 29

What are the actions of granulysin on target cells?

Answer 29

has antimicrobial actions ad can induce apoptosis

Question 30

What is hemophagocytic lymphohistocytosis (HLH)

Answer 30

- defect with cytotoxic T cells, which attacks cells infected with viruses - caused by loss of function mutations in the genes encoding CTL and NK cell cytotoxic mediators or those important for granular exocytosis - virus infected or cancer cells cannot be clear - often chronic viral infections: EBV, HSV, CMV, VZV (HHV3) - IL-6 and TNF (pro inflammatory cytokines) can cause tissue damage due to CD8 and NK cells producing IFN gamma to activate macrophages to produce the proinflammatory cytokines

Question 31

What is clonal contraction?

Answer 31

- occurs after antigen clearance for immune resolution - ctla-4 co-inhibitory binding with B7 to inhibit T cells

Question 32

What happens with polymorphism of ctla4?

Answer 32

- you need ctla-4 for self-tolerance - polymorphism of ctla-4 is associated with autoimmune disease in humans - autoimmune diseases are associated with lymphadenopathy and splenomegaly

Question 33

What cytokines are involved in the generation of memory T cells?

Answer 33

- IL-15 - IL7 - save effector/activated T cells from death to generate memory T- cells

Question 34

What is activation induced cell death ?

Answer 34

- IL-2 is involved in AICD of T cells after repeated antigenic stimulation - CD4: IL-2 induced FAS-FASL expression and downregulate survival factors such as FLIP -CD8: IL-2 induces TNFR death receptor