Antigen presenting and cell cooperation

Question 1

Where do the antigens shown in MHCII on APC’s come from?

Answer 1

APC’s are constantly ingesting their environment. If there is an infection then foreign antigens are displayed if not then it is just self antigens.

Question 2

What is different about the antigens displayed by MHCI and MHCII?

Answer 2

They are from different sources. MHCI presents antigens from intracellular sources and MHCII presents antigens from extracellular sources.

Question 3

What cell types display MHCI and MHCII?

Answer 3

All cells (except RBC’s) express MHCI and only APC’s express MHCII. MHCII is inducible on both B cells and on endothelial cells.

Question 4

How are proteins destined to be displayed in MHCI processed?

Answer 4

These come from intracellular sources (proteins produced on ribosomes). They are tagged in the cytoplasm (ubiquinated), sent to a proteosome and degraded into peptides that are then transported via TAP (trasporter of antigenic peptides) to the ER to come into contact with MHCI. The MHCI/antigen then goes to the golgi and from there is sent to the cell surface.

Question 5

How are proteins destined to be displayed in MHCII processed?

Answer 5

These are from extracellular sources. APC’s ingest them into endosomes. The endosome merges with a lysosome and the proteins are digested. The peptide is then sent to the surface in MHCII.

Question 6

What peptides are held by MHCI and MHCII even in the absence of infection?

Answer 6

self peptides

Question 7

How could a viral protein be held in MHCII?

Answer 7

A virus is normally intracellular but virions released by infected cells may be released and then ingested by an APC.

Question 8

What cell type is essential for chronic viral infections?

Answer 8

CD8 cytotoxic T cells. These T cells recognize antigens displayed in MHCI molecules and these antigens are from intracellular sources. First the CD8 T cell must be activated. It interacts with a virus infected cell with viral antigens displayed. It then becomes activated, divides and kills virus infected cells.

Question 9

What size peptide does the MHCI hold?

Answer 9

About 8-11 peptides long.

Question 10

Does a cell just have self or just have viral antigens on its surface at one time?

Answer 10

No, there are more than 30,000 MHCI molecules on the outside of all cells except RBC’s. They will either hold self or foreign antigen.

Question 11

What is MHC antigen restriction?

Answer 11

Refers to the fact that a given T cell will recognize a peptide antigen only when it is bound to a host body’s own MHC molecule. Normally, as T cells are stimulated only in the presence of self-MHC molecules, antigen is recognized only as peptides bound to self-MHC molecules. Each CTL needs a match of the same peptide in the same MHCI to kill the virus infected cell.

Question 12

What does MHC antigen restriction mean for viral vaccines?

Answer 12

You can only test an anti-viral vaccine’s effect if you have target cells with the exact same MHCI molecule as the donor of the CTL’s.

Question 13

What size peptide does the MHCII hold?

Answer 13

About 20-30 AA’s long.

Question 14

Desribe the advantages of our immune system’s process of peptide antigen presentation to T cells.

Answer 14

1. generates immunity only to pathogens and not other foreign substances - all living things have protein and CD4 T helper cells only recognize peptides from foreign proteins. Since almost all immune responses require T cell help then the risk for immunity to non-pathogenic substances is reduced.
2. Allows T cells to recognize intracellular pathogens since their proteins are processed and then displayed on the cell surface.

Question 15

What are APC’s?

Answer 15

APC’s are antigen presenting cells.

1. Langerhan’s cells in skin
2. Dendritic cells in lymphoid organs
3. macrophages
4. B-cells

Question 16

Are APC’s only used in innate immunity?

Answer 16

No. They are used in both. APC’s have Toll-like receptors that detect LPS and other PAMPS. Once this occurs they secrete the cytokines IL-1 and TNF-a. These 2 cytokines are essential for both T and B cells to respond to their antigens.

Question 17

Name some viruses that evade MHCI antigen presentation.

Answer 17

1. HIV - it blocks MHCI synthesis
2. Human cytomegalovirus - blocks MHCI surface expression
3. Herpes Simplex - blocks TAP (transporter of antigenic peptides) from activity

Question 18

Describe how CTL’s are generated?

Answer 18

1. CTL’s are not fully functional when they leave the thymus. They need to signals to differentiate into effector cells.
2. First they need specific antigen presented in MHCI on a cell and second they need cytokines secreted by TH1 cells.
3. For example. In the event of a viral infection, APC’s will ingest virus infected cells and present viral antigen in both MHCI and MHCII. Both CD4 TFH cells and CD8 T cells will bind.
4. The TFH release cytokines causing the differentiation of TH0 to TH1. TH1 cells release IL-2 and gIFN. These cytokines plus the binding of CD8 T cells to MHCI/antigen cause CD8 T cells to become CTL’s which can then proliferate into effector cells and memory CTL’s to clear the viral infection.

Question 19

How many cell types are required for the generation of CTL’s?

Answer 19

4 cells are needed

1. TFH cells
2. TH1 cells
3. APC
4. virus infected cell

Question 20

Do B cells need T cell help to become effector cells?

Answer 20

Yes. B cell binds antigens with its BCR (a membrane-bound antibody), which transfers intracellular signals to the B cell as well as inducing the B cell to engulf the antigen, process it, and present it on the MHC II molecules. The latter case induces recognition by antigen-specific Th2 cells, leading to activation of the B cell through binding of TCR to the MHC-antigen complex. It is followed by synthesis and presentation of CD40L (CD154) on the Th2 cell, which binds to CD40 on the B cell, thus the Th2 cell can co-stimulate the B cell. Without this co-stimulation the B cell cannot proliferate further. Activated T-helper cells secrete cytokines that cause activated B cells to proliferate and produce antibodies.

Question 21

What is an interleukin?

Answer 21

Small proteins that are secreted by leukocytes upon stimulation. These proteins promote responses among leukocytes.

Question 22

What are lymphokines?

Answer 22

Interleukins made by lymphocytes.

Question 23

What are cytokines?

Answer 23

Small proteins that are secreted by many cells types upon stimulation. they promote responses by leukocytes and other cells.

Question 24

What do B cells need to respond to antigen?

Answer 24

They need 2 signals

1. Antigen that binds to their B cell receptor
2. Co-stimulatory signal. For B cells this is the binding of CD40 (on Bcell) to CD40L (on T helper cell).

Question 25

What receptors do T cells use for co-stimulation?

Answer 25

T cells use the CD28 receptor that binds to B7 on APC’s.

Question 26

What happens to a B cell that gets signal 1 but not signal 2?

Answer 26

Death or anergy.

Question 27

Where do antigen presentation and T and B cell proliferation take place?

Answer 27

This occurs in regions of the lymphoid organs.
B cells proliferate in germinal centers. T and B cells that are specific for the same antigen meet at the T-B regional interface in lymphoid organs.