Antigen processing, presentation & Co- stimulation

Question 1

CD8+ T cells are _______ restricted and recognize ________ proteins.

Answer 1

MHC I

Cytosolic

Question 2

CD4+ T cells are _______ restricted and recognize _______ and _______ pathogens.

Answer 2

MHC II

Extracellular & Intravesicular

Question 3

What are the 4 steps of lymphocyte activation?

Answer 3

1. Microbe infects host
2. microbe is taken up by APC (antigen presenting cell) at site of infection
3. APC enters lymph circulation and into Lymph node
4. Naive T and B cells enter Lymph node from circulation.

Question 4

_______ is central to the development of immune response.

Answer 4

Antigen presentation

Question 5

What is Antigen presentation?

Answer 5

It is the bridge between recognition and full blown immune response.
- Enables T cell-mediated killing, or augments antibody production by B cells.

Question 6

True or false, antigen presentation is context dependent?

Answer 6

True! deploys different immune responses under different circumstances.

Question 7

Antigen presentation is modulated by _________.

Answer 7

Co-stimulatory molecules

Question 8

Successful antigen presentation results in what?

Answer 8

Activation of T cells

Question 9

What are the most effective Antigen presenting cells for initial T cell activation?

Answer 9

Dendritic cells

Question 10

_________ must be activated by phagocytes before presenting antigens.

Answer 10

Macrophages

Question 11

_______ may be the major type of antigen presenting cell for secondary immune response.

Answer 11

B cells

Question 12

What can happen if antigen recognition occurs without antigen presentation?

Answer 12

Tolerance = not good!

Question 13

What is the “professional” APC?

Answer 13

dendritic cell

Question 14

True or false, Dendritic cells, B & T cells are the only APC’s.

Answer 14

False!

- All nucleated cells can present endogenous antigen in association with MHC I molecules.

Question 15

What are the two pathways of antigen presentation?

Answer 15

Pathway 1 = Exogenous antigens presented to T helper cells.

Pathway 2 = Endogenous antigens presented to CD8+ T cells

Question 16

Define antigen processing…

Answer 16

process of antigens being digested and placed of surface with correct MHC molecules.

Question 17

What are the steps of the Endogenous antigen Cytosolic pathway?

Answer 17

• Proteins to be degraded are tagged by ubiquitin
• Degradation of ubiquitin-protein complexes occur within the central channel or proteasome.
• Peptides generated are transported into the Lumen of RER by TAP’s
• Newly synthesized MHC within RER membrane binds to antigen peptide.
• Antigen-MHC I complex released and transported to the cell.

Question 18

What are the steps of the Exogenous antigen Endocytic pathway?

Answer 18

• Antigens are internalized in endosomes
• They are digested first in the endosomes, then in lysosomes to 13-18 aa peptides.
• Class II molecules are produced at RER
• They are associated with the invariant chain protein, preventing their binding to endogenous antigens.
• Class II-Ii complex move into endocytic compartments
• Ii will be digested to a short fragment (CLIP)
• HLA-DM triggers the exchange of CLIP and antigen peptide.
• HLA-DO block the activity of HLA-DM

Question 19

_____ is two distinct polypeptides, an alpha and a beta.

Answer 19

MHC II

Question 20

______ is one alpha peptide.

Answer 20

MHC I

Question 21

What is a haplotype and what does it influence?

Answer 21

a cluster of alternative form of same gene, closely linked on same chromosome. Influences:

• How individual responds to pathogens
• Susceptibility to certain diseases
• Transplant success

Question 22

MHC genes are highly polymorphic…. what does this mean?

Answer 22

• Hundreds of alleys in humans apron. 10^13 combinations (This is why its hard to match ppl for transplants, even 1st relatives often differ.)

Question 23

MHC alleles are _______ expressed.

Answer 23

concomitantly

Question 24

Self MHC + foreign AG = ?

Answer 24

T cell response

Question 25

Self MHC + Self Ag = ?

Answer 25

No response

Question 26

MHC expression can be induced on almost every nucleated cell in the body....True or False?

Answer 26

True

Question 27

______ is a key factor in determining tissue matching for a transplant donor and recipients.

Answer 27

MHC

Question 28

True or false, MHC molecules have very limited specificity.

Answer 28

False, its very broad!

Question 29

MHC molecules have a ______ on/off rate.

Answer 29

slow

Question 30

True or false, MHC molecules discriminate self from foreign peptides.

Answer 30

False, it does not!

Question 31

What determines which peptides bind and how they bind?

Answer 31

The MHC haplotype of an individual

Question 32

What is MHC Restriction?

Answer 32

Allows individual cells to recognize foreign Ag displayed on the surface of an individual APC. *Allows T cells to distinguish between self and non-self & prevents destruction of Non-self.

Question 33

What is the basic definition of Antigen presentation?

Answer 33

Process by which MHC-antigen interact with T helper or T cells.

Question 34

What are the steps of Antigen Presentation?

Answer 34

1. MHC-peptide complex binds to the T cell receptor (TCR) 2. CD4 interacts with both MHC II on APC and TCR on T cell to strengthen antigen-TCR interaction. 3. CD8 interacts with both MHC I on target cell and TCR on T cells. 4. Co-stimulatory molecules B7 on APC binds to its T cell ligand CD28. 5. Adhesion molecule ICAM-1 on the APC binds to its T cell ligand LFA-1.

Question 35

Expression of the ______, _______ and _______ are required for antigen recognition and signaling.

Answer 35

TCR, CD3 and "the squiggly line"

Question 36

CTLA-4 can competitively inhibit ______ binding to _____.

Answer 36

CD28 to CD28

Question 37

CTLA-4 when bound to B7 will actively block signals from the _____ and from _____.

Answer 37

TCR and CD28

Question 38

What happens during the absence of a antigen-TCR interaction?

Answer 38

T cell will not be stimulated.

Question 39

What happens during absence of co-stimulatory molecules?

Answer 39

T cells will not be stimulated.

Question 40

T-cells need the Co-reception of what two signal to become activated?

Answer 40

1. Co-stimulatory molecules | 2. Antigen-TCR interaction

Question 41

What happens (to CD28) at the the termination of the Immune response

Answer 41

CD28 is replaced by CTLA-4 and down regulates T-cell function.

Question 42

What 6 things happen after antigen presentation?

Answer 42

1. activation of tyrosine kinases associated with TCR/CD4(8) complex. 2. Activated Tk phosphorylate cytoplasmic tails of the clustered receptors. 3. Atctivation of kinase cascade follows. 4. Activation of Transcripton factors. 5. Induction of IL-2 and IL2R. 6. Cell division after IL-2 ligation to IL-2R.

Question 43

What role does the IL-2 receptor (IL-2R) have in T cell response?

Answer 43

It amplifies the T-cell response.

Question 44

Before activation the T cells express what?

Answer 44

Beta, gamma IL-2R

Question 45

After activation the T cells, IL-2R takes what form and does what?

Answer 45

Alpha, beta, gamma IL-2R | and enhances the affinity of T-cells by 1000 fold.

Question 46

IL-12 drives the development of ____.

Answer 46

Th1 cells

Question 47

IL-4 drives the development of _____.

Answer 47

Th2 cells

Question 48

Th1 cells do what?

Answer 48

Provide help for cell mediated immune responses.

Question 49

What are 2 of the most important Th1 cytokines?

Answer 49

IFN-gamma & IL-4

Question 50

What do Th2 cells do?

Answer 50

Provide help for humoral immune responses

Question 51

What structure is responsible for the fixation of avian limb structures in a lipid saturated carbohydrate membrane?

Answer 51

The KFC