Lymphocyte interactions - Shaw

Question 1

Why do T cells only recognize antigen bound on self-MHC?

Answer 1

Their development in the thymus requires a weak affinity to self-MHC

Question 2

What is an endogenous vs exogenous antigen?

Answer 2

Endogenous - foreign particles which are SYNTHESIZED in the cell, including tumor antigens

Exogenous - foreign particles derived from outside the cell (can include viral proteins

Question 3

What are dendritic cells called in the skin, liver, and brain?

Answer 3

Skin: Langerhaans cells
Liver: Kupffer cells
Brain: Microglial cells

Question 4

What is the function of DC’s?

Answer 4

First guard against pathogens that break through innate immune system, most potent APC. Highly motile, and express TLR that interact with bacterial and viral moeities

Question 5

What is the function of macrophages, and how do they differ in number from DC’s?

Answer 5

phagocytose large particles, and present antigens less potently than DCs

Far more numerous than DC’s (make up 5-15% of leucocytes in lymph nodes and spleen)

Question 6

What stimulates macrophages to upregulate MHC Class 2 to high levels?

Answer 6

Interferon gamma

Question 7

What type of antigens do B cells bind? Present?

Answer 7

Only SOLUBLE antigens which match their BCR. Whether they can present antigens which do not match their BCR is hotly debated.

Question 8

What is a TAP protein?

Answer 8

Transporter which removes proteins from the proteasome degradation across the rough ER membrane for attachment to MHC Class 1

TAP = transporter associated with antigen processing

Question 9

How do degraded proteins get on MHC Class 1?

Answer 9

There are chaperones for MHC 1 folding which relate closely to TAP in order to bring them directly onto MHC

Question 10

What mediates the antigen moving to MHC 2 in the endocytic pathway?

Answer 10

In the ER, Invariant chain sits in the MHC 2 cleft and stabilizes it. In the lysosome, the remnant CLIP stablizes it.

HLA-DM mediates the exchange of peptides of CLIP for antigen, and MHC Class 2 will be brough to surface to express the peptide.

Question 11

What is CD40L? What upregulates it and what does it do?

Answer 11

It is expressed on T cell, binds the CD40 of antigen presenting cell for costimulation

It is upregulated by the CD40 of APC, then proceeds to upregulate the B7 on the APC for further interactions with CD28 and CTLA4

Question 12

How long do a T cell and APC remain bound?

Answer 12

About 8 hours

Question 13

What is ICOS?

Answer 13

Receptor on T cell which interacts with ICOSL on the B cell.

CD40 Ligand will be on T cell.

Question 14

Why is the interaction between CD40 on B cell and CD40L on T cell so important?

Answer 14

Important for class switching, as well as memory B cell formation

Question 15

What cytokine causes massive clonal expansion of T cells, and what type of feedback is it?

Answer 15

IL-2

Positive feedback T cell growth factor

Question 16

What is the direct effect of B7-CD28 costimulation?

Answer 16

Increases the transcription and halflife of mRNA for IL-2

Also activates the kinase PI3

Question 17

How does CTLA4 function?

Answer 17

Binds B7 with high affinity and sends inhibitory signal to cell, which reduces IL-2

Question 18

How does PD1 work? Why might this be important clinically?

Answer 18

PD1 = programmed death, receptor on T cells.

PD1 inhibitors are being used in cancer patients to enhance immunity by allowing T cells to stay active and fight cancer

Question 19

Where does clonal expansion occur?

Answer 19

In lymph nodes

Question 20

What are two fates of T cells once activated?

Answer 20

1. Differentiation into effector cells or memory cells

2. Migration to sites of inflammation via expression of adhesion molecules and chemokine receptors

Question 21

What is the mechanism of how superantigens work?

Answer 21

React with constant region of beta chain on T cell receptor, can activate up to 20% of T cells. Can either cause death of T cells or massive cytokine storm leading to toxic shock syndrome

Question 22

What is one clinical application of plant proteins Con A and PHA?

Answer 22

They activate all T cells, so they can be used to test for immune function post bone-marrow transplant

Question 23

Where exactly do superantigens bind? How is this different than a mitogen like LPS?

Answer 23

The invariant part of the TCR beta chain

Mitogens like LPS bind a cell surface receptor and trigger polyclonal expansion which is adaptive

Question 24

What is the function of TH1 cells?

Answer 24

Produce IFN-gamma and IL-2 in response to virus or bacteria

Question 25

What is the overall effect of IFN-gamma?

Answer 25

upregulates MHC Class 2 and induces B cells to produce IgG3, a complement-activating isotype.

Also stimulates macrophages, which in turn stimulates NK cells (via IL-12)

Question 26

What is the overall effect of IL-2?

Answer 26

Growth factor for CD4+ and CD8+ T cells, as well as NK cells.

Question 27

What cytokines do Th2 cells produce, and what is their major effector function?

Answer 27

IL4, IL5, and IL-13

Response to worms and allergens

Question 28

What are the functions of IL4/13?

Answer 28

Induce B cell production of IgE / IgG4

Question 29

What is the function of IL5?

Answer 29

Growth factor for eosinophils

Question 30

What cytokines do Th17 cells produce and what is their overall function?

Answer 30

IL-17 and IL-22.

Important for combating fungal infection, but are proinflammatory and may cause autoimmune disease

Question 31

What do IL-17 and IL-22 do?

Answer 31

Stimulate neutrophils and epithelial cells for inflammation. Epithelial cells will even begin to produce IL1, IL-6, and TNF-alpha

Question 32

What cytokines do Treg cells produce? What is their CD marker?

Answer 32

TGF-beta and IL10, downregulating the inflammation response.

They are also CD25 positive.

Question 33

What T cell class does IL-12 stimulate?

Answer 33

Th1 cells

Question 34

What T cell class does IL-4 simulate?

Answer 34

Th2 cells

Question 35

What antibody responds best to carbohydrate moeities?

Answer 35

IgM - hard to form an immune response to just sugars, really need proteins for a good IgG response

Question 36

How are CD8 T cells normally activated?

Answer 36

Dendritic cells show viral derived peptides on their MHC Class 1, but also express B7 to stimulate the CD28 on the T cell. This could be because the DC is infected or just cross-presenting

Question 37

What are the usual targets of CD8 cells?

Answer 37

Virus-infected cells, tumor cells, or foreign tissues

Question 38

How do CD8 cells receive stimulation from CD4?

Answer 38

Full activation is gained by stimulating the CD8 cell with IL-2, produced by Th1 cells

Question 39

What are the two mechanisms of CD8 T cell killing?

Answer 39

1. Release of a pore-forming protein (perforin) and proteases (granzymes)
2. Binding of FasL to Fas receptor on target cell (induces apoptosis)

Question 40

What is the major change of a T memory cell which is becoming dormant?

Answer 40

Decreased need for B7-CD28 costimulation once antigen is encountered. (No longer need a professional antigen-presenting cell for full activation)

Question 41

What happens to the T cell pool following antigen elimination?

Answer 41

Most die by apoptosis, as they express FasL and Fas

Question 42

What is a pneumococcus conjugated vaccine?

Answer 42

Linkage of pneumococcal polysaccharide (normally IgM response with no memory) to a protein (conjugate). The T cell will interact with the protein, B cell reacts with the polysaccharide, giving the “linked recognition” required for heightened immune response.