Cell-mediated effector responses -Thrush

Question 1

What are the various ways of destroying an invading microbe? (4)

Answer 1

1. phagocytosis–> through opsonization of PAMP/PRR
2. antibodies neutralizing the microbe
3. complement cascade
4. cytotoxic activity of various cells (cytotoxic T cells, NK cells, NKT cells, ADCC)

Question 2

What are the different classes of CD4+ T cells and what ares their functions (4)?

Answer 2

• Th (helper) cells produce cytokines to regulate the immune response
• Tdth (delayed type hypersensitive) cells produce cytokines to stimulate an inflammatory response (Th1)
• Tregs (regulatory/suppressive) T cells; autoimmunity
• Th17 (role in inflammation and autoimmunity)

Question 3

What are the different classes of CD8+ T cells and what are their functions?

Answer 3

Tc (cytotoxic) cells produce cytokines that kill target cells. “CTL” will kill target cell

Ts (suppressor) cells produce cytokines to turn off the immune response (??)

Question 4

What determines T cell effector function?

Answer 4

the cell type!
either CD4+ (produce cytokines which help regulate other cells) or CD 8+ T cells (cytotoxic effects)

or Plasma cells in B cells–> antibody production

Question 5

How can you identify effector cells? How can you distinguish a naive T cell from an effector T cell?

Answer 5

you can identify effector cells by their protein expression on the surface of the cell

Naive T cells express CD45RA

Effector T cells express CD45RO

Question 6

How do effector T cells better interact with the cell presenting antigen?

Answer 6

Effector T cells increase the expression of co-stimulatory molecules including CD28 and adhesion molecules (CD2 and LFA-1)

Question 7

What can CD45RO interact with? Does this lead to more or less requirements for effector T cells or naive T cells?

Answer 7

CD45RO expression – interacts with TCR and co-receptors (CD4 or CD8)
effectors (activated T cells) have less stringency for co-stimulation than naive T cells because they do not require CD28:B7 costimulatory signal

CD45RA in naïve T cells – doesn’t interact with TCR/co-receptors as well, need CD28:B7

Question 8

What signals are required for CTL-Ps (naive CTLs) to become CTLs? What kind of infections are these involved in?

Answer 8

Signals required:
(3 instead of 2 because they have the ability to kill target cells–> regulation)
1. TCR: Ag/MHC class 1 interaction (with CD8)
2. CD28: B7
IL2R interaction with IL-2 (from Th1 cell)

intracellular (viral infections, tumors, foreign graft tissue)

Question 9

What are the phases of the cytotoxic response of CTLs?

Answer 9

Phase 1: generation of CTLs (activation of CTL-Ps). requires all 3 signals (including IL-2 from Th1 cells)

Phase 2: destruction of target cells through the delivery of cytotoxic proteins. CTL cytoplasm will rearrange to get the cytotoxic mediators closest to the target cell before being released in order to direct the killing at the CTL: target cell interface

Question 10

What are some cytotoxic mediators at the interface of Tc: target cell?

Answer 10

1. perforin –form pores on the target cell lipid bilayer
   similar to C’ pore formation
2. granzymes – enter target cell through pores
   enzymes that produce DNases within target cell
   = apoptosis
3. FasL on CTL and Fas on target cell
   cascade of events yielding apoptosis
   TNFalpha binds to Fas (can kill tumor cells directly)

Question 11

How does NK cell mediated cytotoxicity work? What are the 3 major differences between CTL and NK function?

Answer 11

1. similar to CTL but no Ag specific recognition
2. NK cells active BEFORE CTLs
   - produce cytokines (ex. IFNgamma) that can increase Mf activity and Th1/Th2 ‘selection’
   - produce perforin and granzymes
3. . don’t need prior activation (constitutive expression of these molecules)

Question 12

How do NK cells recognize their target?

Answer 12

NK cells recognize altered self-cells

two types of receptors (opposing signals model)
1. activation receptors
via cytokine binding
surface receptors on target cell
2. inhibition receptors (MHC class 1)

depending which receptor is recognized determines NK cell activity (or inhibition)

Question 13

How does MHC class 1 expression affect NK cell activation/inhibition?

Answer 13

MHC class 1 proteins are expressed in all nucleated cells. It is an inhibitory signal.

In cells where MHC class 1 expression is reduced (virus-infected, cancer, etc), there is a loss of the inhibitory signal normally sent by MHC class 1.

If there is an activating receptor signal (ex: cytokine production) in addition to the decreased class 1 MHC, then the NK cells will recognize and kill the cell.

Question 14

What are the recognition receptors on NK cells? What do they detect?

Answer 14

killer activation receptors (KARs) and killer inhibition receptors (KIRs)

when stress proteins (MICB and MICA) bind to the KAR, it helps activate the NK cell

KIRs detect MHC class 1 molecules

Question 15

1. What do NKT cells recognize in order to be activated? 2. what aspect of the immune system are they considered to be a part of and why?

Answer 15

1. NKT cells’ alpha-beta TCR recognizes lipids presented with CD1 molecules
2. considered to be a part of innate immunity because they have limited antigen specificity and similar function to NK cells
   - no memory cell formation

Question 16

What is the antibody dependent cellular cytotoxic cell response?

Answer 16

Ab (IgG) serves the specificity to deliver non-specific cells to target cell.

the antibody binds its antigen on a target cell and the Fc region of the antibody brings an effector cell into close proximity (by binding the FcR on the effector cell to the Rc region of the antibody). The cytotoxic mediators can then be released leading to cell death

NK cells, neutrophils, eosinophils, Macrophages
release of granules = cell death

combines antigen-specificity (through antibody molecule) with antigen-non-specific lysis to kill target cells