Cell-Mediated Immunity Flashcards

1
Q

What cells are involved in cell mediated immunity?

A

CD4+ T cell

CD8+ T cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

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

A

TH1- activate macrophage to kill ingested microbe

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

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

A

vesicles - CD4 T cells

cytoplasm- CD8 T (CTL) cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Reactions of CD4 T cells in cell mediated immunity process?

A
  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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What CD4+ effector cells stay in secondary lymph tissue?

A
  • T follicular helper cells remain associated with B cells, augment plasma cell function
  • some will be set aside as memory cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What occurs in secondary lymph tissue to T cells?

A

activation

proliferation

differentiation

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

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

A
  • effector cells wane
  • memory cells remain
  • more CD8 memory cells than CD4
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

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

A

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

-safeguards prevent immune response from continuing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Major T cell subpopulations involved in cell mediated immunity?

A

CD4 (TH1, TH2, TH17)

CD8

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

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

A
  • innate immune cells (macrophages)
  • when macrophages process and present antigen via class 2 MHC
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the major role of TH1 cells? how?

A

induce macrophage activation

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Activation of macrophage induces what effects?

A

synthesis of reactive molecules:

  • O2 radicals
  • Nitric Oxide
  • proteases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

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

A
  1. IFN-gamma
    - primary signal
    - made by TH1 (also NK cells, possibly macrophages)
  2. CD40L
    - secondary signal
    - makes the cells responsive to IFN-gamma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Macrophage activation by TH1 cells induce expression of what?

A
  • class 2 MHC
  • B7
  • CD40
  • TNF-R
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Classically activated macrophage (M1) lead to what?

A

ROS, NO, lysosomal enzymes:

  • microbial actions
  • phagocytosis and killing of bacteria and fungi IL1, IL12, IL23, chemokine:
  • inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Alternatively activated macrophage (M2) lead to what?

A

IL10, TGF-beta

  • anti inflammatory effects
  • wound repair
  • fibrosis
17
Q

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

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

TH17 produce IL17 mainly (also IL22)

18
Q

Function of TH17 cells?

A
  • stimulate production of chemokine that recruit neutrophils and other leukocytes
  • increase production of antimicrobial peptides (defense’s)
  • promote epithelial barrier functions
19
Q

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

A

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

20
Q

IL-2 function?

A

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

21
Q

IL-12 and type 1 IFN function?

A

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

22
Q

IL-15 function?

A

important in development of memory CD8

23
Q

IL-21 function?

A

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

24
Q

What is T cell exhaustion?

A
  • 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
25
Q

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

A

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

26
Q

Steps in CTL mediated lysis in targeted cells?

A
  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
27
Q

How is a naive CD8+ T cell primed?

A
  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
28
Q

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

A

non professional antigen presenting cell:

  • true for virally infected cells
  • tumor cells
29
Q

How does CTL induce apoptosis?

A

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
30
Q

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

A

true

31
Q

Difference between neutrophils and CTLs?

A

neutrophils- very destructive, release debris into extra cell environment

CTL- form tight pore with target, pulls it out, cell dies, very clean cell death

32
Q

What cytokines can CD8+ effector cells produce?

A
  • macrophage activating IFN-gamma
  • similar to TH1
  • inflammatory reactions from environmental chemicals
  • arrive earlier than CD4 cells
33
Q

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

A
  • 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
34
Q

What do NK function? how?

A
  • 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
35
Q

What happens if people lack NK cells?

A

suffer from persistent viral infections

-rare disorder -herpes

36
Q

How do NK cells recognize what to attack?

A
  • 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
37
Q

How can NK cells influence T cell differentiation?

A

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)