Cell-Mediated Immunity

Question 1

What cells are involved in cell mediated immunity?

Answer 1

CD4+ T cell

CD8+ T cell

Question 2

What is the difference between inflammation between CD4 effector cells (TH1) vs CD4 cells (TH17)?

Answer 2

TH1- activate macrophage to kill ingested microbe

TH17- induce neutrophils, a lot more destruction, kills microbes

Question 3

What T cells deal with phagocytes with ingested microbes in vesicles? who deals with microbes in cytoplasm?

Answer 3

vesicles - CD4 T cells

cytoplasm- CD8 T (CTL) cells

Question 4

Reactions of CD4 T cells in cell mediated immunity process?

Answer 4

1. TCR engaged
2. costimulatory molecule engaged
3. provide cytokines
4. express CD40 L
5. naive T cells differentiate
6. T cells exit, into systemic circulation
7. TH1 pair with macrophages, activate
8. TH17 migrate to site of infection, call in neutrophils

Question 5

What CD4+ effector cells stay in secondary lymph tissue?

Answer 5

• T follicular helper cells remain associated with B cells, augment plasma cell function
• some will be set aside as memory cells

Question 6

What occurs in secondary lymph tissue to T cells?

Answer 6

activation

proliferation

differentiation

-antigen carried from peripheral tissues by dendritic cells are primary stimulus

Question 7

Upon clearance of infection, what population wanes and what remains?

Answer 7

• effector cells wane
• memory cells remain
• more CD8 memory cells than CD4

Question 8

What is important in the contraction (homeostasis) phase of clonal expansion?

Answer 8

CD40L and CTLA4 (regulation of immune responses) on cell surface

-safeguards prevent immune response from continuing

Question 9

Major T cell subpopulations involved in cell mediated immunity?

Answer 9

CD4 (TH1, TH2, TH17)

CD8

Question 10

What influence the differentiation of adaptive immunity cells (CD4 T cells) and activate them? how?

Answer 10

• innate immune cells (macrophages)
• when macrophages process and present antigen via class 2 MHC

Question 11

What is the major role of TH1 cells? how?

Answer 11

induce macrophage activation

-macrophages have receptors that bind to bacteria and other pathogens which facilitate phagocytosis, destruction, and intracellular degradation

Question 12

Activation of macrophage induces what effects?

Answer 12

synthesis of reactive molecules:

• O2 radicals
• Nitric Oxide
• proteases

Question 13

What signals are required for the macrophage activation from the TH1 cell?

Answer 13

1. IFN-gamma
   - primary signal
   - made by TH1 (also NK cells, possibly macrophages)
2. CD40L
   - secondary signal
   - makes the cells responsive to IFN-gamma

Question 14

Macrophage activation by TH1 cells induce expression of what?

Answer 14

• class 2 MHC
• B7
• CD40
• TNF-R

Question 15

Classically activated macrophage (M1) lead to what?

Answer 15

ROS, NO, lysosomal enzymes:

• microbial actions
• phagocytosis and killing of bacteria and fungi IL1, IL12, IL23, chemokine:
• inflammation

Question 16

Alternatively activated macrophage (M2) lead to what?

Answer 16

IL10, TGF-beta

• anti inflammatory effects
• wound repair
• fibrosis

Question 17

What chemokine lead to production of TH17 cells? what does TH17 produce?

Answer 17

• IL6 from dendritic cells
• TGF-beta from many sources

TH17 produce IL17 mainly (also IL22)

Question 18

Function of TH17 cells?

Answer 18

• stimulate production of chemokine that recruit neutrophils and other leukocytes
• increase production of antimicrobial peptides (defense’s)
• promote epithelial barrier functions

Question 19

What is the role of helper T cells in the differentiation of CD8+ T cells? how?

Answer 19

promote CD8+ cell development:

-secrete cytokines that act directly on CD8 cells by activating antigen presenting cells to become more effective at stimulating the differentiation of CD8 T cells

Question 20

IL-2 function?

Answer 20

promotes proliferation and differentiation of CD4+ and CD8+ cell into CTLs and memory cells

Question 21

IL-12 and type 1 IFN function?

Answer 21

stimulate the differentiation of naive CD8+ T cells into effector CTLs

Question 22

IL-15 function?

Answer 22

important in development of memory CD8

Question 23

IL-21 function?

Answer 23

induction of CD8+ cell memory and prevention of CD8+ cell exhaustion

Question 24

What is T cell exhaustion?

Answer 24

• over time CD8 T cells stop responding to an antigen because CTLA-4 engagement on surface of CD8 cell by target cells, begin to express costimulatory (B7) molecules that down regulate CD8 responses
• due to chronic infection

Question 25

What happens with CD8 cells in acute infection as opposed to chronic infection, leading to T cell exhaustion?

Answer 25

acute- CD8 cells differentiate in CTLs that eliminate infected cells, antigen is cleared chronic- response of CD8 cells is suppressed by the expression and engagement of PD-1 and other inhibitory receptors, antigen persists, T cell exhaust

Question 26

Steps in CTL mediated lysis in targeted cells?

Answer 26

1. target cell shows MHC class 1 2. endogenous antigen form intracell infection is displayed on surface 3. LFA1 and ICAM1 interact 4. granule exocytosis 5. detachment of CTL 6. target cell death

Question 27

How is a naive CD8+ T cell primed?

Answer 27

1. TCR engages MHC class 1: peptide complex 2. class 1 MHC may also present peptides derived from microbes that have been phagocytksed by dendritic cells: - if they are transported from the phagosomes and into the cytosol - cross priming or cross presentation

Question 28

Once activated, CTLs must be able to recognize antigen as what?

Answer 28

non professional antigen presenting cell: - true for virally infected cells - tumor cells

Question 29

How does CTL induce apoptosis?

Answer 29

Cytotoxins contained in lytic granules: 1. perforin -protein analogous to C9 (membrane attack complex) - polymerizes to create transmembrane channels - allows granzymes to enter 2. Granzymes - family of serine proteases - cleave cell proteins - activate endonuclease (activates effector caspases) - induce apoptosis, inside cell 3. Fas-FasL interaction - induce apoptosis - happens on cell surface receptor in absence of granzymes and perforin

Question 30

T/F CTLs can kill multiple target cells on repetitive fashion.

Answer 30

true

Question 31

Difference between neutrophils and CTLs?

Answer 31

neutrophils- very destructive, release debris into extra cell environment CTL- form tight pore with target, pulls it out, cell dies, very clean cell death

Question 32

What cytokines can CD8+ effector cells produce?

Answer 32

- macrophage activating IFN-gamma - similar to TH1 - inflammatory reactions from environmental chemicals - arrive earlier than CD4 cells

Question 33

What are NK cells? what do they lack? what do they express?

Answer 33

- mononuclear lymphocyte - lacks CD3 - expresses CD56 (adhesion molecule) - most are large granular lymphocytes (LGL)- well developed cytosol containing cytotoxic granules - no rearrangements of TCR or Ig genes - express IL-2Rb and IL-2Rg- allow response to IL-2 - 10-15% PBL

Question 34

What do NK function? how?

Answer 34

- provide innate immunity against intracellular infections, viruses especially - migrate from blood to tissue in response to inflammatory cytokines - act fast, within 6-12 hours - effective against tumors if drops MHC class 1

Question 35

What happens if people lack NK cells?

Answer 35

suffer from persistent viral infections -rare disorder -herpes

Question 36

How do NK cells recognize what to attack?

Answer 36

- if virus expresses MHC class 1, NK cells are inhibited - if virus inhibits the expression of MHC class 1, NK cells are activated, kills by perforin and granzymes

Question 37

How can NK cells influence T cell differentiation?

Answer 37

If NK cells target a virus infection, they produce cytokines (IFN-gamma) which trigger IL-12 secretion from macrophage which will skew immune response to a T cell response (kill with perforin and granzymes)