Antigen Capture and Presentation

Question 1

TLRs recognize _____

Answer 1

PAMPs

Question 2

What are the 2 signals that allows the innate immune system to initiate the adaptive immune response?

Answer 2

Process and present antigens to T lymphocytes

Generation of surface molecules that function as costimulatory signals with antigen to activate B and T cells

Question 3

What are Major Histocompatibility Complexes Type I and II? Where are each found?

Answer 3

MHC I and II are complexes found on cells that present processed antigens to naive T cells

MHC I is found on all nucleated cells
MHC II is found on APCs: Dendritic cells, Macrophages, B lymphocytes, and thymocytes

Question 4

What are MHC molecules AKA?

Answer 4

HLA- Human Leukocyte Antigen

Question 5

Why do we need MHC/HLA receptors to recognize antigens?

Answer 5

T lymphocytes do not recognize free or soluble antigens

Question 6

What are the 3 classes of MHC/HLAs?

Answer 6

Class I**- B, C, and A (Found on all nucleated cells)
Class II- DP, DQ, DR (Found on APCs)
Class III- Cytokines and complement proteins

Note that class I has 1 letter and class II has 2 letters

Question 7

What is an MHC/HLA Haplotype?

Answer 7

The total set of MHC/HLA alleles that are present on each chromosome.

Most humans have 2 MHC/HLA haplotypes- one from mom and one from dad

Question 8

What is the goal during transplantation?

Answer 8

To find the best match possible between recipient and donor for both class I and class II genes

Question 9

Where on all nucleated cells are class I MHC molecules found? What is its function? (Note that it has 2 functions)

Answer 9

On membrane bound glycoproteins

Function is to present antigens to CD8+ Cytotoxic T lymphocytes

It is also an inhibitory receptor to NK cells

Question 10

Describe the structure of class I MHC/HLA receptors.

Answer 10

Heterodimer of 2 proteins:
Alpha chain (alpha 1, 2, 3)
Beta2- Microglobulin- associates noncovalently with the alpha chain

Question 11

What kind of antigen molecules bind to MHC class I receptors? Where do they bind?

Answer 11

Peptides with 8-10 amino acids

They bind to the peptide groove between alpha1 and alpha 2. Note that the conformation of this groove dictates what peptides can bind.

Question 12

Where are MHC class I and II receptors synthesized?

Answer 12

In the Endoplasmic Reticulum

Note that how the antigen finds the MHC receptors is different for both. Will get to this in later note cards

Question 13

Where are MHC class II receptors found on APCs? What is their function?

Answer 13

Membrane bound glycoproteins

Function is to present antigen to CD4+ T-lymphocyte

Question 14

Describe the structure of MHC class II receptors. Describe the binding site.

Answer 14

Composed of two proteins- alpha and beta chains. Both encoded by the HLA-D gene.

Alpha1 and Beta1 form the peptide groove where antigens bind.

Question 15

How does the peptide binding groove of MHC class II differ from MHC class I?

Answer 15

It allows for larger peptides to bind (13-18 amino acids)

Question 16

For MHC Class I and MHC Class II, which regions of the receptors have the greatest amount of polymorphisms?

Answer 16

MHC Class I- alpha 1 and alpha 2

MHC Class II- alpha 1 and beta 1

Note that these are the peptide binding groove for each MHC

Question 17

What is the dual recognition system that is critical for T-lymphocyte function?

Answer 17

The ability of T-lymphocytes to recognize antigens when associated with the organism’s own MHC/HLA Haplotype.

Question 18

What is the function of MHC class II receptors on Dendritic cells?

Answer 18

To allow dendritic cells to present antigens to naive T cells to allow for “priming” of the T cells

Question 19

What is the function of MHC class II receptors on Macrophages?

Answer 19

For antigen presentation to CD4+ effector T cells in the cell-mediated immune response

Question 20

What is the function of MHC class II receptors on B lypmhocyte cells?

Answer 20

Antigen presentation to CD4+ Helper T cells in the humoral immune response (T cell - B cell interactions)

Question 21

What are the costimulators for MHC class II receptors on APCs such as dendritic cells, macrophages, and B lymphocytes?

Answer 21

CD40-CD40L

Question 22

Antigens entering via the periphery are filtered by the ____.

Antigens in the blood are filtered by the _____.

Answer 22

Ags from periphery are filtered by lymph nodes

Ags from the blood are filtered by the spleen

Question 23

When dendritic cells are activated, they lose adhesion markers allowing them to travel to lymph nodes unaffected. What is the marker they up regulate to allow entry into the lymph nodes?

when they are in the lymph nodes what receptor is up regulated to allow costimulation with T cells?

Answer 23

CCR7

CD80 on the Dendritic cells are upregulated to bind to CD86 on T cells (costimulation) and allow presentation to T lymphocytes

Question 24

Differentiate between the types of pathogens Class I and Class II MHC receptors are used to kill?

Answer 24

MHC class I kills intracellular pathogens

MHC class II kills extracellular pathogens

Question 25

Describe the pathway of MHC class II synthesis.

Answer 25

Exogenous proteins are ingested and degraded in a lysosome and endosome. From the endosome the ER synthesizes MHC class II and the antigen is further degraded in the lysosomes where MHC from the ER migrates to and binds with CLIP.

In the lysosome, CLIP is removed which allows for the processed antigen to enter the MHC class II.

MHC class II with the antigen from the lysosome migrates to the surface of the cell to allow for binding with T cells

Question 26

Describe the pathway of MHC class I synthesis.

Answer 26

Cytosolic antigens are processed in the proteasome via ubiquitin. From the proteasome, the processed antigen enters the ER using TAP and binds to MHC class I.

MHC class I + antigen migrate to the golgi and then to the exocytic vessicle and then leaves the cell to bind to CD8+ T lymphocytes.

Question 27

Describe what cross presentation is?

Answer 27

Extracellular pathogens are taken up and end up getting processed by the proteasome therefore allowing them to be expressed on MHC class I receptors and bind to CD8+ Cytotoxic T lymphocytes

Question 28

T/F: Even in the absence of infection, protein degradation and peptide transport occur constinuously

Answer 28

True

Question 29

What is a major factor that determines the success of transplantation?

Answer 29

HLA/MHC matching from patient to donor

Question 30

Which HLA associated disease occurs in 88% of individuals that express the HLA-B27 allele?

Answer 30

Ankylosing Spondylitis- inflammation of the spine

Question 31

Describe the issue with a rheumatic fever from streptococcus pyogenes and how it causes an HLA associated disease.

Answer 31

The generation of antibodies against the streptococci cross react with cardiac tissue. Patients with the HLA-D4 allele are more prone to develop rheumatic fever.

This is what grandma had

Question 32

What disease occurs from down regulation of the TAP protein, which is used to transport antigens into the ER for MHC class I presentation?

Answer 32

Human Neuroblastoma

Question 33

What are the molecules that are involved in the transport of proteins and loading of MHC class I receptors? Essentially asking what allows for the antigens to move into the ER for each MHC class…

What about for MHC class II receptors?

Answer 33

TAP- MHC Class I

Invariant chain- MHC class II