Cell-Mediated Immune Responses

Question 1

Where do intracellular microbes replicate?

Answer 1

In the cytoplasm of host cells where they are protected from microbicidal activities

Question 2

What do T cell responses require?

Answer 2

Interactions with other cells

Question 3

What does the TCR mediate?

Answer 3

Signal 1

Question 4

How does the TCR complex divide the labor of signaling?

Answer 4

The TCR variable region detects antigenic peptide

The presenting MHC molecule directs the T cell response

Conserved CD3 and zeta complexes signal to the T cell

Question 5

Why is adhesion important in T cell signaling?

Answer 5

T cells respond weakly to antigens
The T cell-APC interaction must be stabilized by integrins. LFA-1 will bind to ICAM-1 on APCs

Question 6

What does exposure to chemokines do to LFA-1?

Answer 6

It converts LFA-1 to a high affinity state that clusters within minutes
So, T cells bind aPC strongly and thus activation of the TCR is strengthen

Question 7

What does further signaling do to the affinity of LFA-1 for ICAM-1?

Answer 7

It strengthens the affinity of LFA-1 for ICAM-1 which will increases the strength of the T cell - APC interactions and further stabilizes T cell signaling

Question 8

What happens at the same time as peptide presentation?

Answer 8

Microbial PAMPs stimulate expression of costimulators on APCs so that T cells that respond to MHC-microbial antigen complexes also receive a second signal

Question 9

What is the three-signal hypothesis?

Answer 9

Signal 1 = antigen-specific TCR engagement of MHC and peptide

Signal 2 = contact with costimulatory ligands

Signal 3 = cytokines directing T-cell differentiation into distinct effector cell types

Question 10

Define differentiation

Answer 10

The process by which a cell becomes distinct of specialized, acquiring functionality lacking in naive cells

Question 11

What does TCR signaling result in?

Answer 11

Changes in gene expression will lead to the differentiation of naive T cells into CD4 and CD8 T cells

Question 12

What does differentiation coincide with?

Answer 12

Clonal expansion and leads to the generation of large numbers of differentiated effector cells

Question 13

What do type 1 CD4 T cells (TH1) respond to?

Answer 13

Intracellular pathogens inducing cell-mediated immunity

Question 14

What do type 2 CD4 T cells (TH2) respond to?

Answer 14

Pathogens inducing humoral immunity particularity extracellular parasites

Question 15

What do CD4 effector cells produce?

Answer 15

Surface molecules and cytokines that mainly activate macrophages and B cells

Question 16

What do active CD4 T cells express and why?

Answer 16

They express the surface molecule CD40L which bind to CD40 on macrophages, B cells, and dendritic cells
This binding activates macrophages and B cells

Question 17

What do dendritic cells increase the expression of?

Answer 17

Costimulators which further activates CD4 T cells

Question 18

What is the most important cytokine produced by type 1 helper cells and what does it do?

Answer 18

IFN-gamma

It is a potent activator of macrophages - enhances microbial killing

Stimulates B cells to produce antibody isotypes that promote the phagocytosis of microbes

Question 19

What does CD8 differentiation (TH1) support?

Answer 19

The activation and differentiation of CD8 cytotoxic T cells

Initially there is a lot of clonal expansion but as the infection clears that population dies off or differentiates into a smaller population of CD8 memory cells

Question 20

How do CTLs kill target cells?

Answer 20

Up close to avoid damage to non-target cells
Perforin in the synapse between a CTL and a target cell perforates the target cell membrane allowing apoptosis inducers inside

Question 21

How are T cells activated?

Answer 21

Activated T cells produce cytokines that drive clonal expansion
Some of the activated T cells differentiate into effector cells to destroy microbes, other become memory cells

Question 22

What are memory T cells?

Answer 22

They are functionally inactive, long-lived, and respond rapidly to the same microbe

Question 23

What are cytokines produced by and how do they act?

Answer 23

Produced by macrophages and T cells (CD4 in particular)
Production is transient to regulate immune responses and they act in paracrine or autocrine manners to stimulate multiple arms of the immune response

Question 24

Are there more CD8 cells or CD4 cells?

Answer 24

CD8

Question 25

Where do memory T cells reside?

Answer 25

In lymphoid tissues
Mucosal barriers
Circulation

Question 26

Why are memory T cells functionally inactive?

Answer 26

They do not continue to produce cytokines or kill infected cells but may do so rapidly upon reinfection

Question 27

Why might a T cell become anergic?

Answer 27

An MHC molecule presented a peptide but the T cell does not receive a second signal

Question 28

What do anergic T cells provide protection to?

Answer 28

Auto-reactive lymphocytes in the periphery

Question 29

What is the solution to this barrier?

T cells must encounter antigen

Answer 29

APCs concentrate antigens in the lymphoid organs

Question 30

What is the solution to this barrier?

T cells must determine the appropriate response (CD4 or CD8)

Answer 30

Class I and Class II MHC molecules direct the specificity of the response

Question 31

What is the solution to this barrier?

T cells must encounter antigen long enough for T cell signaling to occur

Answer 31

Adhesion molecules tighten interactions between T cells and APCs

Question 32

What is the solution to this barrier?

The T cell response must be directed against microbial antigens and not harmless proteins

Answer 32

2nd signal ensures responses are elicited against microbial antigens

Question 33

What is the solution to this barrier?

A small number of T cells have to mediate the initial response

Answer 33

Amplification mechanisms boost the T cell response

clonal expanision, cytokine production