4) Antigen Presentation and MHC

Question 1

ALL nucleated cells express which MHC molecule?

Answer 1

Class 1

Question 2

What cells express MHC class II?

Answer 2

antigen-presenting cells (APCs)

1) dendritic cells
2) macrophages
3) B cells

Question 3

Do APCs express MHC class I?

Answer 3

yes because they are nucleated as well

Question 4

Do RBCs express MHC molecules?

Answer 4

NO, they are NOT nucleated

Question 5

MHC proteins in humans are called…

Answer 5

HLA (human leukocyted antigens)

Question 6

Total set of MHC genes on each chromosome

Answer 6

MHC haplotype (one from each parent)

Question 7

refers to different genes within each person

Answer 7

polygenic

Question 8

refers to wide variety of genes in the human genome pool

Answer 8

polymorphic

Question 9

A, B, C genes are encoded for which MHC proteins?

Answer 9

MHC Class I

Question 10

DP, DQ, DR genes are encoded for which MHC proteins?

Answer 10

MHC Class II

Question 11

Which characteristics (3) virtually guarantees that two randomly selected individuals will not be identical matches (not related individuals such as siblings)?

Answer 11

1) polygenic
2) polymorphic
3) codominant

Question 12

How many MHC proteins do each individual express?

Answer 12

theoretically 6 different Class I and 6 different Class II (3 different of each from each parent)

Question 13

True or False. Peptides are covalently bound to MHC proteins on cell surface.

Answer 13

FALSE. they are non-covalently bound

Question 14

Which HLA allele is found in patients with narcolepsy? Which class of MHC is this?

Answer 14

HLA-DR2, class II

Question 15

Which HLA allele is found in patients with ankylosing spondylitis? Which class of MHC is this? (possible boards topic)

Answer 15

HLA-B27, class I

Question 16

True or False. Paternity tests are 100% definitive.

Answer 16

No, they can only exclude the alleged father, but cannot 100% definitively determine who the actual father is.

Question 17

Why is matching so difficult for organ transplantation?

Answer 17

patient will reject non-self MHC protein and recognize it as foreign, inducing an immune response to the transplanted organ

Question 18

Which MHC proteins have one big alpha chain and one small beta chain?

Answer 18

MHC class I

Question 19

True or False. The microglobulin beta chain in MHC class I is NOT important for the actual binding of antigens

Answer 19

True. But it is important for getting the MHC molecule to the cell surface

Question 20

What are the three regions of a Class I MHC molecule?

Answer 20

1) peptide-binding
2) transmembrane
3) cytoplasmic

Question 21

Why do infections by Plasmodium go undetected by cytotoxic T cells?

Answer 21

RBCs are not nucleated, thus also lack MHC Class I proteins

Question 22

Which MHC proteins presents antigens to CD8+ T cells (cytotoxic T cells)?

Answer 22

MHC Class I

Question 23

Which MHC proteins presents antigens to CD4+ T cells (T-helper cells)?

Answer 23

MHC Class II

Question 24

The binding region of MHC Class I proteins are for peptides of which size?

Answer 24

small fragments of 9-11 amino acids long

Question 25

Describe the molecular structure of MHC class II proteins

Answer 25

two non-covalently-linked polypeptide chains (same as MHC Class I, but beta chain in class II is just as big as the alpha chain)

Question 26

MHC Class II molecules can bind to longer peptides, why is this possible?

Answer 26

MHC class II have peptide-binding regions for larger peptides (10-30 amino acids long). the ends of the binding regions are open-ended (long hot dog for a regular-sized hot dog bun)

Question 27

CD4+ T cells are also known as…

Answer 27

T helper cells

Question 28

CD8+ T cells are also known as …

Answer 28

cytotoxic T cells

Question 29

CD8+ binds to this MHC class proteins

Answer 29

class I

Question 30

CD4+ binds to this MHC class proteins

Answer 30

class II

Question 31

True or False. T cells can recognize and bind to all kinds of molecules such as peptides, polysaccharides, and lipids.

Answer 31

FALSE. T cells can ONLY bind to peptides presented on MHC molcules

Question 32

Dendritic cells are important in which type of immune response?

Answer 32

primary

Question 33

Macrophages and B cells are important for which type of immune response?

Answer 33

secondary

Question 34

Which of the three APCs is the most potent APC and the best at their job?

Answer 34

dendritic cells are the most professional APCs

Question 35

True or False. dendritic cells are in nearly all organs of the body.

Answer 35

True

Question 36

Where are dendritic cells produced?

Answer 36

bone marrow

Question 37

Where do dendritic cells (DCs) go after they are produced?

Answer 37

circulate in blood then migrate into tissues where they reside as immature DCs and constantly sample the environment through phagocytosis and macropinocytosis

Question 38

What is the most potent activator of macrophages?

Answer 38

IFN-gamma

Question 39

Describe how antigen processing can lead to upregulation of MHC molecules on APCs

Answer 39

1) APC presents antigens to CD4+ and NK cells thus activating them
2) CD4+ and NK cells produce and release IFN-gamma
3) IFN-gamma activates APCs
4) IFN-gamma causes APCs to upregulate MHC class II expression

Question 40

What effects do upregulation of MHC class II have?

Answer 40

high level of MHC class II expression on APCs –> more T cells being presented to by APCs –> more IFN-gamma released –> better and faster immune response

Question 41

What happens when dendritic cells capture antigens?

Answer 41

they become activated, travel to lymph nodes and present antigens to T-helper cells (CD4+)

Question 42

Which pathway do MHC class I molecules process antigens?

Answer 42

endogenously

Question 43

What occurs inside uninfected cells during endogenous antigen processing? Why is this important?

Answer 43

Class I MHC proteins bind to self peptides. It’s a sign to NK cells that they are fine and not infected. This is why cancer cells down-regulate Class I MHC

Question 44

Describe the steps of endogenous antigen processing in response to viral infection

Answer 44

1) virus within the cytoplasm synthesizes viral proteins
2) viral protein is broken down by proteasome into small peptide fragments (9-11 a.a.’s)
3) the peptide fragments are transported to ER where MHC class I is being assembled
4) peptide fragment is attached to MHC class I in the ER
5) the MHC complex is packaged and shipped to the cell surface
6) APC then presents the antigen to CD8+ (cytotoxic T cells)

Question 45

Which pathway do MHC class II molecules process antigens

Answer 45

exogenously

Question 46

How are exogenous antigens obtained?

Answer 46

they are internalized by phagocytosis, receptor-mediated endocytosis or gluid phase pinocytosis

Question 47

Describe the steps of exogenous antigen processing in response to viral infection

Answer 47

1) virus particle is internalized and enters cell as an endosome
2) endosome binds with lysosome and the virus is broken down to peptide fragments
3) Class II MHC (with clip protein) is packaged into exocytic vesicle by the Golgi
4) the vesicle then docks with the phagolysosome (containing peptide fragments of virus)
5) Clip protein falls off class II MHC and peptide binds instead
6) the vesicle is then brought to cell surface where class II MHC presents the antigen to CD4+ (T helper cells)

Question 48

What does the invariant chain, clip protein, do?

Answer 48

it binds to the peptide-binding region to prevent self peptides from binding to it (which would elicit an auto-immune response)

Question 49

Some DCs are even more awesome and can present antigens via BOTH endo- and exogenous pathways. Why is this important?

Answer 49

viral infections can stimulate cytotoxic T cells (CD8+) instead of just T helper cells (CD4+). This leads to a much faster immune response (cells are getting killed faster)

Question 50

Describe how DCs are shunted to endogenous pathway instead of the other route

Answer 50

once the antigen has been captured within phagosome, the vesicle fuses with the ER, where DCs are being assembled.