Antigen Processing, Presentation, Co-stimulation

Question 1

In general, once an antigen presenting cell (APC) contacts an antigen (Ag) at the site of infection it will move into the ______

Answer 1

lymph circulation/ lymph node

Question 2

CD8+ T cells are _______ restricted and recognize cytosolic proteins

Answer 2

MHC I

Question 3

CD4+ T cells are _____ restricted and recognize extracellular and intravesicular pathogens

Answer 3

MHC II

Question 4

What are naive B and T cells

Answer 4

inactivated B and T cells floating in the circulation

Question 5

when would naive B and T cells move from the circulation into a lymph node ?

Answer 5

when a APC engulfs an antigen and transports it to the lymph node

Question 6

What does it mean when saying antigen presentation is context dependant

Answer 6

Different immune responses under different conditions

Example : MHC I or MHC II

Question 7

Antigen presentation acts as a bridge b/w Ag recognition and what ?

Answer 7

the full blown immune response

Question 8

Is Ag recognition part of the innate or adaptive immune response

Answer 8

adaptive immune response

Question 9

Successful Ag presentation results in ?

Answer 9

Activation of naive B and T cells

Question 10

What are the 3 “professional” APC

Answer 10

• Dendritic cells (Best)
• Macrophages
• B cells (rare)
• These are majority, but more exist*

Question 11

What can ALL nucleated cells do with regards to Ag presentation ?

Answer 11

Present endogenous Ag tagged with MHC I

Question 12

Degradation/break down of cytoplasmic proteins occurs within ?

Answer 12

proteasome

Question 13

Degradation/break down of endocytic proteins occurs within ?

Answer 13

lysosome

Question 14

There are 2 main pathways in Ag presentation. One processes exogenous Ag with aid of _______ molecule, and the other processes endogenous Ag tagged w/________

Answer 14

MHC II (CD4)
MHC I (CD8)

Question 15

What are the names of the 2 pathways of Ag presentation, and what type of Ag do the recognize ?

Answer 15

Cytosolic Pathway - Endogenous Ag

Endocytic Pathway - Exogenous Ag

Question 16

Explain the Cytosolic pathway of Ag presentation starting from the labeling of proteins via ubiquitin.

Answer 16

1 - Ubiquitin tags proteins(Ag) for degradation
2 - degradation (of Ag) occurs in proteasome
3 - TAP transports digested Ag peptides to lumen RER
4 - MHC I binds to Ag peptides
5 - Ag-MHC I complex transport to surface for interaction w/lyphmocytes

Question 17

What are TAP’s

Answer 17

proteins that transport digested fragments of Ag protein into lumen of RER

Question 18

MHC I and MHC II are both synthesized where ?

Answer 18

RER

Question 19

What is the diff. b/w HLA-DM and HLA-DO

Answer 19

HLA-DM loads Ag in endocytic pathway

HLA-DO inhibits the loading of Ag (by blocking HLA-DM)

Question 20

clatherin coated pits are used to engulf/vesiclize Ag in what Ag presentation pathway

Answer 20

Endocytic Pathway (Exogenous Ag)

Question 21

Explain the Endocytic pathway of Ag presentation starting w/ Ag binding to cell surface

Answer 21

1 - Ag binds and internalized via endosomes
2 - digested in lysomes in Ag peptides
3 - HLA-DM triggers loading of Ag to MHC II

Question 22

what is the role of the invariant chain in the endocytic pathway

Answer 22

When bound to MHC II, it keeps MHC II from binding endogenous Ag

Question 23

what triggers the exchange from CLIP (Class II associated invariant chain peptide) to an Ag on the MHC II molecule

Answer 23

HLA-DM (loads the Ag)

Question 24

what is a haplotype

Answer 24

clusters of alternative forms of the same gene closely linked on the same chromosome

Question 25

What 3 things does the MHC haplotype influence

Answer 25

- how individual responds to pathogens - susceptibility to disease - transplant success

Question 26

The MHC genes are highly polymorphic, what does this mean ?

Answer 26

10^13 different allele combinations (broad response) E | -reason why we can recognize so many different specific types of Ag's

Question 27

A self MHC + a foreign Ag will elicit ___________ whereas a self MHC + self Ag will elicit ______

Answer 27

T cell response | NO T cell response

Question 28

All nucleated cells in the body can alert either CD4 or CD8 T cells, which is it ?

Answer 28

CD8 T cells via MHC I

Question 29

What results in a positive selection in MHC restriction and what results in a negative selection

Answer 29

Ag + MHC = positive selection | self + MHC = negative selection

Question 30

In order to get activation of a T cell, there are 2 signals needed in the immunological synapse, what are they ?

Answer 30

1 - MHC-Ag complex binds to TCR (T cell receptor) 2 - Co-stimulatory signal (engagement of CD28 w/B7 molecule) ****NEEDS BOTH SIGNALS to ACTIVATE****

Question 31

what is the role of CTLA-4 on co-stimulatory molecules

Answer 31

Acts as an "OFF" switch for immune response activation of Tcells by binding to B7 (co-stimulatory molecule)

Question 32

what are the 2 ways CTLA-4 can downregulate the immune response

Answer 32

1 - competively inhibit (co-stimulatory molecule) CD28 from binding to B7 2 - Bind to B7 which actively blocks

Question 33

CD28 and CTLA-4 both can bind to B7, what is the difference in signals if either bind

Answer 33

If CD28 binds to B7 = stimulate T cell activation | If CTLA-4 binds to B7 = inhibit T cell activation

Question 34

What is the difference b/w TH1 and TH2 helper T cells

Answer 34

TH1 - involved in cell mediated immunity, pro-inflammatory | TH2 - humoral immunity, anti-inflammatory

Question 35

What is the main generic role of cytokine IL-2

Answer 35

induces T cell proliferation/differentiation

Question 36

After antigen presentation, in order to amplify the T cell response a signal cascade will occurs to activate ______ which will induce IL-2

Answer 36

transcription factors NF-AT and NF-KB

Question 37

IL-2 is a cytokine that amplifies the T cell response by how much

Answer 37

1000 fold

Question 38

IL-2 once produced can cause 3 effects, what are they ?

Answer 38

1 - T cell proliferation 2 - Regulatory T cell development 3- -NK cell proliferation

Question 39

naive T cells can develop into Th1 or Th2 helper t cells, what drives the development of each

Answer 39

IL-12 drives dev. of Th1 | IL-4 drives dev. of Th2

Question 40

what is the most important cytokine produced in response to Th1

Answer 40

IFN-gamma

Question 41

what is the most important cytokine produced in response to Th2

Answer 41

IL-4