TCR and MHC

Question 1

Why do T cells have to be present at the site of antigen, but B cells don;t?

Answer 1

Because T cells can’t secrete their receptors while B cells can (antibodies)

Question 2

When do Th0 cells decide what type of Th to become?

Answer 2

When the correct antigen is brought to them by dendritic cells

Question 3

What’s the main determinant of the precursor T cell’s ultimate progeny?

Answer 3

It all depends on what the dendritic cell experienced - where they were activated, what TLR was used, what cytokines were involved, etc.

Question 4

What two cytokines will induce formation of Th1 cells?

Answer 4

IL-12 and IFN-alpha

Question 5

What important lymphokine is secreted by the Th1 cells which acts as a pro0inflammatory and a chemotatic agent for monocytes?

Answer 5

interferon gamma

Question 6

Monocytes that are activated by interferon gamma become what?

Answer 6

classically activated M1 (angry) macrophages - they ingest and kill bacteria

Question 7

Classically activated M1 macrophages then secrete what two cytokines which intensity inflammation locally?

Answer 7

TNF alpha and IL-1

Question 8

Why are Th17 cells called that?

Answer 8

They secrete IL-17 as a cytokine (among others)

Question 9

What cytokines will induce formation ot Th17 cells?

Answer 9

TGF-beta and IL-21

Question 10

Like Th1 cells, Th2 cells will secrete cytokines to attract and activate macrophages, but in a different way. how? with what cytokines?

Answer 10

Using IL-4 and IL-13, they alternatively activate the macrophages = M2. They’re more involved in healing

Question 11

IL-4 is chemotactic for macrophages and what other WBC?

Answer 11

Eosinophils

Question 12

Th2 cells will also give rise to what other type of T helper cells?

Answer 12

Th2-like follicular cells, which migrate into lymphoid follicles

Question 13

The high levels of IL-4 secreted by the TH2-like follicular cells will cause B cells to do what Ig class switch?

Answer 13

from IgM/IgD to IgE

Question 14

In more general terms, what do the follicular helper T cells do?

Answer 14

They help the B cells become activated and differentiate into plasma cells

Question 15

WHat do T regulatory cells do?

Answer 15

They’re anti-helpers - they secrete cytokines to inhibit all the other helper cells

Question 16

What cytokines do the Treg cells produce?

Answer 16

TGF-beta and IL-10

Question 17

What are the two ways cytotoxic T cells can kill a cell?

Answer 17

Either way, it binds with Fas on the Fas ligand (CD95 and CD95L)

1. cross-linked Fas triggers a latent apoptosis pathway
2. secrete lytic granules with granzymes and perforins

Question 18

What cytokine from the Th1 cells is necessary for T cells to become active cytotoxic T cells?

Answer 18

IL-2

Question 19

What surface markers do we use to distinguish B cells?

Answer 19

CD19 and CD20

Question 20

WHat surface markers do we use to distinguish T cells?

Answer 20

CD3 (they all have), CD4 and CD8

Question 21

What does “MHC-restriction” mean?

Answer 21

T cells are restricted in their recognition to antigen on the surface of cells that have GENETICALLY IDENTICAL MHC molecules as themselves - so my T cells won’t kill one of Chris’s infected cells

Question 22

How do dendritic cells present things on MHC?

Answer 22

The antigen enters the dendritic cell and is broken down to peptides in the endosome.
the endosome fuses with other vesicles that have MHC molecules facing inwards.
Some of the peptides will bind to the MHC molecules
THe bound MHC molecules are recycled back to the surface

Question 23

Can T cells recognize free antigen?

Answer 23

nope - it’s gotta be on MHC

Question 24

What are the two types of MHC molecules and on what cells are they usually located?

Answer 24

type 1 and type 2

type 1 are on all nucleated cells, type 2 are on phagocytes and B cells

Question 25

Which MHC class presents antigens endocytosed by a cell? Which MHC class presents antigens synthesized by a cell?

Answer 25

MHC 1 - synthesized | MHC 2 - endocytosed

Question 26

Why are dendritic cells capable to rpesenting to both Cd4 and Cd8 T cells?

Answer 26

They are able to undergo "cross presentation" because they can leak some of its antigen over to it's intrinsic pathway so it will present them on class 1 and class 2 at the same time

Question 27

Why are dendritic cells considered to be more effective at presenting than macrophages and B cells?

Answer 27

1. dendritic cells constitutively express both MHC and costimulatory molecules 2. macrophages must first be activated to express both MHC molecules and costimulatory molecules 3. B cells will constitutively express MHC 2 molecules, but need to be active to express costimulatory molecules

Question 28

Describe the structure of a T cell receptor.

Answer 28

2 chains; alpha and beta OR gamma and delta each chain has a variable region and a constant region it's always membrane bound in the form of a heterodimer

Question 29

Which to T cell receptors undergo: somatic mutation of somatic hypermutation?

Answer 29

only somatic mutation - because T cells that have left the thymus are no longer under any sort of regulation, so if they changed once they left there would be no shutting them off

Question 30

What CD molecule is closely associated with the TCR? What does it do?

Answer 30

CD3 - it transduces TCR signals for the T cell when the TCR binds the appropriate MHC

Question 31

Why are co-receptors necessary for the TCR/MHC interactions?

Answer 31

Because without them the binding is relatively weak

Question 32

There are other co-receptors that add to the binding affinity besides CD4 and CD8, such as...

Answer 32

CD2 binds to LFA-3 LFA-1 binds to ICAM-1 CD28 binds to B7 CD45R binds to CD22

Question 33

What gene segments are present in the alpha chains and beta chains of the TCR? Hint - it's similar to Ig...

Answer 33

alpha: made up of V, J, and constant segments beta: made up of V, D, J, and constant segments

Question 34

What enzyme complex does the gene rearrangement for the TCR?

Answer 34

RAG recombinase again

Question 35

The TCR has an addition strategy for increased diversity that Igs do not, which is...

Answer 35

alternative joining of the D sequences to give VJ, VDJ, or VDDJ chains

Question 36

Why would it be a bad idea to allow somatic hypermutation in T cells?

Answer 36

It could lead to autoimmunity because we wouldn't have a mechanism to get rid of them

Question 37

T cells will produce a single beta chain, but can produce two different alpha chains (one from dad and one from mom), so why do functional T cells only express specificity for one antigen?

Answer 37

Because in order to exit the thymus, they have to 1. recognize self MHC and be 2. self tolerant and 3. not recognize free antigen So it's highly unlikely that even one receptor will pass this inspection, let alone two on one cell.

Question 38

Describe the genetics related to MHC Class 1. How many loci? What additional peptide do all the gene products combine with for class 1? So how many are possible within an individual?

Answer 38

There are three classical Class 1 gene loci: gene A, B, and C (encoding HLA-A, HLA-B, and HLA-C) They all combine with another peptide called Beta2 microglobulin For each of the loci, you inherit one allele from mom and one from dad, so in total an individual can make 6 different MHC Class 1 molecules

Question 39

Describe the genetics related to MHC Class 2. How many loci? What do they combine with? So how many are possible within an individual?

Answer 39

There are three major genes loci again, but each gene locus encodes TWO peptides which can mix and match - an alpha and a beta subunit - to be expressed on the surface Gene DP encodes DP alpha beta Gene DQ encodes DQ alpha beta Gene DR encodes DR alpha beta Since you inherit one allele from mom and one from dad, there are 12 possible MHC class 2 molecules in an indiivdual

Question 40

There are TONS of polymorphisms for the MHC molecules. Where are most of them located within the molecule?

Answer 40

in the cleft region - the antigenic binding site

Question 41

MHC class 1 molecules tend to bind ____ peptides and have an end-___ conformation. MHC class 2 molecules tend to bind ____ peptides and have an end-___ conformation

Answer 41

1: shorter peptides, end-closed conformaton 2: longer peptides, end-open conformation