Antigen Capture and Presentation to Lymphocytes

Question 1

B cell receptors (BCR) can regonize a variety of macromolecules in soluble form or cell surface associated form, these include…

Answer 1

proteins, polysaccharides, lipids, nucleic acids and haptens

Question 2

T cell receptors (TCR) can only recognize peptide fragments of protein Ags, only when the peptides are generated in a host cell and presented on to cell surface with specialized molecules called…

Answer 2

major histocompatibility complex (MHC)

Question 3

T cells protect against intracellular microbes, however, T cells also help to mount a Ab to extracellular pathogens, also known as?

Answer 3

T helper cells

Question 4

T cells cannot recognize unprocessed Ags, they are processed by…

Answer 4

being broken up into linear peptides and displayed by APCs with MHC molecules on the cell surface

Question 5

What do CDH4 T helper cells recognize peptides Ags as?

Answer 5

as presented in complex with MHC class II molecules on DCs, Mø, and B cells

Question 6

CD8 T cells recognize peptides associated with what?

Answer 6

MHC class I (call cytotoxic b/c kill host cells infected with pathogens)

Question 7

CD4 and CD8 attach differently to non-polymorphic part of the MHC class II and MCH class I respectively. CD4 and CD8 are called co-receptors because..?

Answer 7

They involve signaling/activation

Question 8

What else needs to be done besides for Ag presentation to the TCR, in order to activate naive T cells?

Answer 8

APCs with CD4 and CD8 express co-stimulatory molecules which are involved in signaling events

Question 9

What does T cell activation produce, which stimulate clonal expansion of Ag activated T cells?

Answer 9

Cytokine IL-2

Question 10

Activated Th1 cells produce what, that activates macrophages to rid of intracellular microbes as well as develop cytotoxic T cells?

Answer 10

Th1 produces cytokines

Question 11

Activated Th2 cells produce what, which is important for B cell proliferation?

Answer 11

Cytokine IL-4

Question 12

What are the main function of Th2 cells?

Answer 12

help B cells to produce Abs and develop plasma cells (antibody production) and memory cells against extracellular microbes

Question 13

TCR (T cell receptor) is composed of 2 polypeptide chains alpha and beta with weights of 50 and 39 kDa. Each chain has a constant and variable region like Ig. What do the variable sites of the alpha and beta chains make up?

Answer 13

the Ag-binding site

Question 14

What happens when T cells have gamma/sigma characteristics instead of alpha/beta?

Answer 14

They have a broader specificity for unconventional Ags

Question 15

T cells expressing CD4 bind to the nonpolymorphic region of MHC class II on APCs restricting Th cells to recognize what?

Answer 15

To only recognize peptides presented on MCH class II molecules

Question 16

Where does CD8 bind to and what does it restrict?

Answer 16

Binds to nonpolymorphic region of MHC class 1 and restricts killing to ONLY cells presenting MHC class I

Question 17

The TCR complex consists of Ag receptor, AB dimer and CD3 whihch is a signaling complex composed of which polypeptides?

Answer 17

Gamma, sigma, epsilon and zeta chains

Question 18

antigen presenting cell-dendritic cell function?

Answer 18

Naive T cell activation (CD40-CD40L)

Question 19

antigen presenting cell- macrophage cell function?

Answer 19

Effector T cell response- activation (CD40-CD40L)

Question 20

APC B cell function?

Answer 20

Effector T cell response, B cell activation and Ab production (CD40-CD40L)

Question 21

Microbial Ags enter through skin/GI/respiratory where DCs capture and take to LN. Ags that enter the blood stream are capture by…?

Answer 21

APCs in the spleen

Question 22

What are the main differences between tissue resident DCs and activated DCs in regard to function, Expression of receptors, expression of molecules involved in T cell activation and life of Class II MHC?

Answer 22

Residents are to capture antigens, high express receptors (Fc/mannose), low B& ICAM-1 and IL12, short life of class II mHC
Active DCs present ag to T cell, no expression of receptors, high expression of B7, ICAM1 IL12, long half like and surface molecules

Question 23

IFN-gamma stimulates class II MHC expression on APCs and enhance the activation of CD4T cells. What does IFN-G and type I interferons effect?

Answer 23

Express class I MHC and activate CD8 T cells.

Question 24

Human MHC is also call the HLA which stands for?

Answer 24

Human leukocyte antigen

Question 25

Class I and II of polymorphic MHC genes encode human leukocyte AG (HLA) that can bind peptides and are critical to Ag presentation. Only polymorphic chain forms a binding groove for peptides to be recognized by T cells... What do class I genes (HLA-A-B-C) encode?

Answer 25

They encode one polymorphic heavy chain which combines with invariant B2-microglobulin, expressed on all nucleated cells

Question 26

What do class II genes (HLA-D) encode, which contribute to the formation of peptide-binding groove?

Answer 26

They encode HLA-DP,DR,DQ which are composed of two dissimilar polymorphic chains, alpha and beta

Question 27

What length of peptides and class I and class II MHCs bind?

Answer 27

8-10 and 10-20 respectively

Question 28

The alpha chain, is glycosylated, and B2-microglobulin chains are bound how in mhc class I?

Answer 28

covalently

Question 29

In MHC class II, the polymorphic alpha and beta chains are both glycosylated and bound non-covalently. What would be the name of the structure?

Answer 29

HLA-DR1

Question 30

Listed are some main features of properties of MHCs, list the significance for each? 1. Co-dominant expression 2. Polymorphic genes (many different allels are present) 3. Class II express on DCs,Mø, B cells Class I express on all nucleated cells

Answer 30

1. Increase # of MHC molecules that can present Ags to T cells 2. Different people can respond to different Ags 3. CD4 helper T cells interact 4. CD8 CTL can kill virus infected cell

Question 31

Peptides that bind MHC class I molecules are viruses and intracellular microbes that infected the host cell while peptides that bind to class I MHC are recognize by?

Answer 31

CD8 cytotoxic T lymphocytes

Question 32

Class II MHC recognize APCs that present extracellular pathogens and Ags to activate?

Answer 32

CD4 T helper cells

Question 33

An anchor residue on the peptides bind to residues in the class I and II grooves, holding it in place, and vary for different MHC alleles. A single MHC can bind....

Answer 33

Many different peptides which have the same anchor residue

Question 34

Polymorphic residues of class I and II MHC molecules are located?

Answer 34

in the peptide-binding clefts and the alpha helixes around the clefts

Question 35

The cleft is where peptides lie in the peptide bind clefts. MHC class I clefts are closed while class II are open, this results in?

Answer 35

class II molecules accomodate longer peptides than class I molecules

Question 36

Why do alpha/beta T cells only recognize linear peptides?

Answer 36

Because only peptides bind to MHC molecules and conformation is lost during enzymatic processing of Ags into peptides

Question 37

Why do A/B T cells recognize cell-associated and not soluble Ags?

Answer 37

MHC stably bound peptides stably and complexes are located on the cell surface

Question 38

Why do CD4 T cell recognize extracellular and CD8 T cells receognize intracellular Ags?

Answer 38

CD4 because MHC II display peptides that are taken up from extracellular environment by APCs via pinocytosis CD8 becaue MHCI present peptides from cytosolic proteins including intracellullar pathogens

Question 39

What are the 5 steps involved in the class II mHC pathway?

Answer 39

1. Uptake of extracellular proteins / antigen 2. Processing of proteins in lysosomal vessicle 3. Biosynthesis/transport of class II MHC in ER to endosomes 4. Processed antigens bind to groove in MHC 5. Express antigen/MHCII on cell curface to bind CD4 -> T helper cell

Question 40

The HLA-DM editing mechanism works to ensure the presentation of only the protein fragments most relevant for eliciting an immune response. What are it's three major functions?

Answer 40

1. Causes dissociation of clip from MHC II binding groove 2. Stabilizes and prevents degredation of empty MHCII 3. Helps bind Ag frament to open, stabilized MHCII groove

Question 41

What are the 5 stesp involved in synthesis and protection of class II MHC in the pathway?

Answer 41

1. Class II MHC synthesized in ER 2. Transported with invariant chain (which blocks binding groove) to vesicle 3. HLA-DM removes clip,stabilizes MHCII, facilitates Ag binding 4. Transported to surface 5. Expression of peptide-MHC on cell surface

Question 42

What are the 5 main steps involved in class I MHC pathway?

Answer 42

1. Proteins produced in cytosol with virus 2. Proteolytic degradation of proteins 3. Transport of peptides from cytosol to ER by proteasome 4. Class I MHC chaperone switched with B2micro, activates antigen transporter binds Ag by ERAP, binds to Ag 5. Peptide-MHC I complex brought to surface to activate CD8 and Cytotoxic T cell

Question 43

When fragments of cells infected with intracellular microbes (CD8) are ingested by DCs (use CD4), what can happen?

Answer 43

Cross-presentation of Ags. Some DCs have both MHC 1 and 2. So the DC with bound MHCII, can pick up intracellular virus peices and present to CTL by MHC 1

Question 44

Main difference between class II MHC and class I?

Answer 44

Class II use T helper cells which secrete cytokines to either a) activate marcphages to kill or b) help B cells make antibodies to antigens Class I use cytotoxic T cells kills the presenting cell immediately

Question 45

What are immunodominant peptides?

Answer 45

Peptides of a degraded antigen that are the ones that bind to the to MHC molecules to be recognized by T cells, some may respond and some may not respond to an antigen, just depending on structural constraints

Question 46

B cells differentiate in response to Ags and other signals (cytokines from CD4) into Ab secreting cells. No antigen processing is needed for BCRs and anitbodies to recognize, bind and eliminate. How are the antigens expressed to to B cells?

Answer 46

microbial surfaces (capulsar or envelope Ags) or solube form (secreted toxins)