MCM 2-8 T-Cell Immunity

Question 1

Where is a naive T cell activated?

What 2 signals are required to activate a naive t-cell?

Answer 1

via exposure to an antigen, occurs in a lymph node that is draining an infected tissue.
2 signals required:
- an antigen specific signal - delivered when the T-Cell receptor recognizes the peptide:MHC complex on the dendritic surface
-a costimulatory signal: delivered when cd28 on T-cell surface binds to B7 on dendritic cell surface (B7 is expressed in activated APC’s)

Question 2

What happens if a naive T-cell enters an uninfected lymph node

Answer 2

it will return to circulation and continue to enter and exit unchanged until it enters an infected one

Question 3

What is the only antigen presenting cell that can present to a naive T-cell? why?

Answer 3

dendritic cell. they constitutively express both MHCII and B7

Macrophages must be activated to express MHCII and B7

B cells must be activated to express B7

Question 4

CD28-mediated co-stimulation is not required for the stimulation of which types of cells?

Why is this?

Answer 4

effector T cells and memory t cells.

because they have already been selected for antigen specificity so the stringent requirement for co-stimulation is not necessary.

Do not need to be presented with B7.

Gamma/Delta T cell activation is CD28 independent

Question 5

what drives the activated T-cells differentation and proliferation?

Answer 5

autocrine production and uptake of IL-2.

Naiive T cells - moderate IL2 affinity
Activatated T-cells - strong affinity IL2

uptake of the IL2 they produce can allow them to differentiate into effector or memrory cells

Question 6

structural changes that occur when a T-cell becomes activated?

Answer 6

change in distribution of cell surface molecules/receptors

lose molecules that cause them to remain in lymph node

gain adhesion molecules/receptors on surrface allowing tehm to interact with other cells that express the ligand to those receptors -> helps them interact with other cells and hones them to other tissues where they are needed. You can generate T-Cells that target every tissue in the body this way.

Question 7

CD4+ TH1 cells

Answer 7

activated t-cells become TH1 cells in presence of IFN-Gamma and IL12.

produce transcription factor T-Bet

Produce cytokines IL2 and IFN gamma

function to activate macrophages

Question 8

CD4+ TH2 Cells

Answer 8

become TH2 in presence of IL-4.

PRoduce transcription factor GATA3

Produce cytokines IL4 and IL5

function to activate cellular and antibody responses to parasites

Question 9

describe the balance of TH1 and TH2

Answer 9

balance is important. TH2 can inhibit macrophages, thus preventing the necessary response.

if TH2 is overproduced when TH1 should be produced (as in a bacterial or viral infection), this can lead to disseminated infection.

-This occurs with leprosy. The mild tuberculoid form occurs in those who can mount the proper TH1 response and rally macrophages. the severe leproid form occurs when the patient is unable to mount the proper TH1 response and instead responds with TH2.

Question 10

CD4+ TH1 and TH2 clear pathogens

Answer 10

indirectly by interacting with effector cells that clear pathogens

Question 11

function of CD8+ T-cells

Answer 11

kill infected target or tumor cells directly by apoptosis and cytokine exposure
1. granule exocytosis (fast, predominant) - arrange their organelles to deposit granzymes and perforin towards the infected cell.

2. Apoptosis (slow)
   - caspace actiavtion which causes DNA fragmentation
   - mtochondrial damage causes cytochrome C release

they also secrete INF-Gamma like the TH1 cells do, but CD8+ cells do it not to kill via macrophage but have the macrophage clean up the debris

Question 12

why are CD8+ cells so stringently activated?

Answer 12

they can cause lots of damage, potentially acting on every cell in the body and causing massive tissue damage.

Question 13

The activation of CD8+ t-cells may or may not require..

Answer 13

CD4+ TCell help, which secretes IL2 which causes the CD8 to proliferate

Question 14

how is the immune response “turned off” after an infection is cleared?

Answer 14

Mainly by the expression of CTLA-4 by activated t-cells. this molecule has a higher affinity for B7 than cd28 does. Once bound to the B7 of presenting cells, stops additional activation and sends inhibitory signals to T-cell

Also once antigen is cleared, there is no antigen to present to T-cells and activate them

Question 15

defects in CTLA-4 can lead to

Answer 15

autoimmune diseases such as lupus. T-cells and immune response doesnt shut off correctly.

Question 16

what is belatacept?

Answer 16

a prescription form of CTLA-4. Given to kidney transplant recipients to shut down t-cells that may have been activated by the transplant.

Question 17

anergy

Answer 17

prevention of T-Cell activation, generally via CTLA-4 or prescription form belatacept.

Question 18

Lupus treatment

Answer 18

molecules that target defective CTLA-4.

Question 19

4 ways to turn off immune response

Answer 19

CTLA-4
elimination of antigen
elimination of other stimuli
Tregulatory Effectors
killing by immunoregulatory cells

Question 20

where are dendritic cells found? how can they take up antigen?

Answer 20

mostly in epithelial CT, by pino or phagocytosis

Question 21

dendritic vs macrophage vs b-cell presentation

Answer 21

dendritic cells provide a strong Co-stim, and always have MHCII and B7. They are important in stimulating naiive T-cells

Macrophages and B-cells are important in presentation later on in infection when presenting to mature effector T-cells

b-cells and macrophages express lower levels of MHC and other stimulatory molecules

Question 22

CD4 differntiation in a viral/bacteria infection

Answer 22

first cytokine produced is IFN-gamma and macrophages will express IL12. In the prescence of these two signals, T cells differentiate into TH1

Question 23

CD4 differentiation in parasitic environment

Answer 23

you’ll have production of IL4 from basophils and mast cells, driving differentiation towards TH2

Question 24

TH17

Answer 24

produces IL17, enhances neutrophil response (inflammatory)

Question 25

Tfh

Answer 25

stay in lymph node, unique, activate B-cells and maturation of antibody response including switch response. IL21

Question 26

Treg

Answer 26

produces TGF-Beta cytokine that is suppressive, turns off immune system

expresses FOXP3 - suppresses effector cells and antigen presenting cells

Question 27

for lymphocyte to turn to a plasma cell, what is needed?

Answer 27

interaction with TH2 CD4+ T-cell

cognate interaction between cd40 ligand and cd40 requires production of cytokine and binding of bcell receptors to turn plasma cell and secrete antibody to neurtalize antigen

Question 28

main goal of CD4+ TH1 cells?

Answer 28

bring various cells of immune response into area of infection and remove infection

produce LOTS of different cytokines, mostly inflammatory
-excrete INFgamma and have cd40 ligand to activate macrophages
-can express FAS ligand which leads to killing of infected cells
-produce il2 to induce proliferation of more t-effector cells
Produce il3 to induce macrophage differentiation in bone marrow
Produce TNFalpha and TNFbeta to activate epithelium so macrophages can exit into tissues
Cxcl2 - chemokine causes macrophages to accumulate at site of infection

Question 29

what organizies the cellular components of the CD8+ cell when it wants to align its organelles to kill?

Answer 29

MTOC, microtubules

Question 30

benefit of CD8+ inducing apoptosis?

Answer 30

by having cell self-destruct and not lyse, you prevent spread of pathogen. The nucleases not only degrade the cellular DNA but also degrade the pathogen as well. This process helps contain the infection while it is killed.

Question 31

rate limiting step in CD8 Killing?

Answer 31

time it takes to synthesize granules.

Question 32

antigen presented by dendritic cells?

Answer 32

peptides, viral antigens, allergens

Question 33

antigen presented by macrophages?

Answer 33

particulate antigens, intracellular/extracellular pathogens

Question 34

antigen presented by b-cells?

Answer 34

soluble antigens, toxins, viruses

Question 35

how do naiive t-cells enter the lymph node?

Answer 35

by two routes

• in the blood
• or in the afferent lymph coming from an upstream lymph node

Question 36

what directs activated t-cells to distinct anatomical sites?

Answer 36

differential expression of adhesion molecules

Question 37

what is critical to the ability of CD4+ T-cells to activate other cells?

Answer 37

the CD40 ligand

Question 38

the interaction between a b cell and t-cell with specificity for the same antigen is called

Answer 38

cognate interaction

Question 39

effector functions of CD4+ TH1 cells

IFN-Gamma
FAS ligand+TNF beta
IL2
IL3 + GM-CSF
TNF-A,B
CXCL2

Answer 39

IFN-gamma + cd40 ligand = activates macrophages to destroy engulfed bacteria

FAS ligand + TNF-beta - kills infected macrophages, releasing bacteria to be destroyed by healthy macrophages

IL2 - induces T-cell proliferation, increasing the number of effector T-cells

IL3 +GM-CSF = induces macrophage differentiation in bone marrow (increase macrophage population)

TNF alpha and TNF beta = activates endothelium to induce macrophage adhesion and exit from blood vessel at site of infection

CXCL2 = causes macrophages to accumulate at site of infection

Question 40

At an infection site you measure a large amount of IL-12 and IFN-gamma…what class of effector CD4+ t cell will this induce?

What function will that effector t cell perform?

Answer 40

IL-12 and IFN-gamma induce TH1 cells to form and it will activate macrophages at that site.

Question 41

At an infection site you measure a large amount of IL-4…what class of effector CD4+ t cell will this induce?

What function will that effector t cell perform?

Answer 41

IL-4 induce TH2 cells and they will activate cellular and antibody response to parasites

Question 42

Which characteristic cytokines do TH1 and TH2 cells produce?

Answer 42

TH1 cells produce IL-2 and IFN-gamma

TH2 cells produce IL-4 and IL-5

Question 43

what controls migration of naiive T-cells into and out of lymph nodes?

Answer 43

selectins, integrins, and chemokine receptors expressed on T-cells

if a t-cell encounters pathogen antigens, they are activated and leave as effector cells

Question 44

clonal expansion is driven by

Answer 44

high affinity I2 receptor and autocrine IL2 excretion

Question 45

what directs activated T-cells to distinct anatomical sites?

Answer 45

differential expressions of adhesion molecules

Question 46

what induces T-reg differentiation? what do they make?

Answer 46

TGF-beta

tgf-beta and IL10(to inhibit actiavted T-cells)