Lecture 5

Question 1

How is a lymphocyte activated?

Answer 1

1. microbe infects host
2. microbe taken up by antigen presenting cell
3. APC enters lymphatic system (to lymph node)
4. Naive B and T cells enter lymph node from circulation and are activated

Question 2

Effector T-Cell

Answer 2

armed and ready to engage infected cells

Question 3

Memory T-Cell

Answer 3

take up residence in tissues and secondary lymphoid organs waiting for next infection

Question 4

CD8+ T-Cell

Answer 4

MHC 1

recognize cytosolic proteins (viruses)

Question 5

CD4+ T-Cell

Answer 5

MHC 2

recognize extracellular pathogens (bacteria)

Question 6

Why is antigen presentation important?

Answer 6

enables T cell mediated killing

augments antibody production by b cells

Question 7

What happens if an antigen is recognized without being presented?

Answer 7

tolerance

Question 8

Dendritic Cells

Answer 8

most effective cells for initial t cell activation

professional antigen presenting cell (APC)

Question 9

Macrophages

Answer 9

professional antigen presenting cell

must be activated by phagocytosis before presenting

Question 10

B cells

Answer 10

major type of APC for secondary immune response

Question 11

Can all nucleated cells present antigens?

Answer 11

Yes

Ag must be associated with MHC 1

Question 12

What MHC do professional APCs use?

Answer 12

MHC 2

Question 13

What are the two pathways for antigen processing?

Answer 13

Endogenous Pathways

Exogenous Pathways

Question 14

What are the steps of the endogenous (cytosolic) antigen processing pathway?

Answer 14

1. Exogenous antigens are taken into cell
2. Ag are tagged for proteolysis by ubiquitin
3. Ag peptides broken down into small segments in proteasome
4. Ag peptides transported through rough ER by TAP
5. Peptide binds with newly made MHC 1
   * MHC I continuously made, degraded until a peptide is available to bind to it*
6. Ag-MHC I complex released and transported to cell surface

Question 15

What are the steps of the exogenous (bailey calls it endocytic–CONFUSING) antigen processing pathway?

Answer 15

1. Ag is internalized into endosome
2. endosome binds with lysozome, breaks down Ag into small segments
3. MHC II produced in rough ER
4. Invariant chain associates with MHC II to act as a placeholder so MHC II doesn’t degrade
5. Invariant chain - MHC II complex moves to endolytic compartments
6. Invariant chain is digested into shorter CLIP fragments
7. HLA-DM triggers exchange of CLIP and Ag peptides (aka triggers Ag loading onto MHC II)
   * HLA-DO inhibits Ag loading*
8. MHC II-Ag complex to cell surface

Question 16

Why does MHC make organ transplants difficult?

Answer 16

huge polymorphism (10^13 combos)

Question 17

Self MHC + foreign antigen = ?

Answer 17

T-Cell response

Question 18

Self MHC + self antigen = ?

Answer 18

no t cell response

Question 19

If a virus is in the body, what MHC and T cells are critical?

Answer 19

MHC 1 necessary to alert CD8+ t cells

Question 20

immunological synapse

Answer 20

MHC-Ag complex interacting with T cell

Question 21

What are the components of an immunological synapse?

Answer 21

MHC-Ag complex binds to T cell receptor (TCR)

costimulatory molecules necessary for t cell activation

Question 22

What t cell interacts with MHC II at an immunological synapse?

Answer 22

CD4+

Question 23

What t cell interacts with MHC I at an immunological synapse?

Answer 23

CD8+

Question 24

What are the most important costimulatory molecules?

Answer 24

costim molecule B7 on APC binds to t cell CD28 ligand

required for activation

Question 25

What competitively inhibits B7 binding to CD28?

Answer 25

CTLA-4

Question 26

What signals are needed to activate t cells?

Answer 26

Ag-TCR B7-CD28

Question 27

What is a major cytokine in activation of T-cells?

Answer 27

IL-2

Question 28

What happens if you mix an e. coli and a macrophage?

Answer 28

1. binding 2. phagocytosis 3. phagolysozome degrades microbe now antigen presentation is possible yesssssss cytokines/chemokines also produced by macrophage

Question 29

What happens if you mix and e. coli and a t-cell?

Answer 29

NOTHING because a t cell can only recognize Ag fragments

Question 30

What MHC do regular old nucleated cells use?

Answer 30

MHC I because a virus can infect any nucleated cell

Question 31

What recognizes Ag on a t cell?

Answer 31

TCR

Question 32

What signals on a t cell? (not sure what it signals to tbh--other cells?)

Answer 32

CD3 and zeta chain

Question 33

What happens if a Ag-MHC complex are recognized by a t cell, but there is no co-stimulation?

Answer 33

t cell becomes anergic

Question 34

What are the general steps for t cell activate?

Answer 34

1. TCR recognizes Ag 2. CD4+ recognizes MHC II/CD8+ recognizes MHC I 3. CD28 on T cell recognizes B7 molecule on APC 4. LFA-1 on t cell recognizes ICAM-1 on APC

Question 35

What down regulates t cell activation?

Answer 35

CTLA-4 it replaces CD28 from binding to B7

Question 36

Why is B7 important?

Answer 36

it plays a role in activating t cells and terminating their response, depending on if CD28 or CTLA-4 is bound to it