Antigen Presentation and MHC

Question 1

Macrophages by location

Answer 1

liver- Kupffer cells
brain- microglia
skin- Langerhans’

Question 2

Macrophages by location

Answer 2

liver- Kupffer cells
brain- microglia
skin- Langerhans’

Question 3

Plasmacytoid Dendritic cells

Answer 3

Produce large amounts of interferon in response to viral infections

Question 4

Conventional Dendritic cells

Answer 4

they encounter a foreign antigen they take up the antigen, they become activated in an immature state and then they mature and they traffic to the lymphatics and then the lymphoid tissue. It now has the capacity in the lymph node to present antigen to the t-cells.

Question 5

Conventional Dendritic cells

Answer 5

they encounter a foreign antigen they take up the antigen, they become activated in an immature state and then they mature and they traffic to the lymphatics and then the lymphoid tissue. It now has the capacity in the lymph node to present antigen to the t-cells.

When it takes up antigen it is activated, this activation results in a down regulation of phagocytic activity and an up regulation of MHC class II expression on that cell. (the antigen is taken in and degraded). The amount of MHC Class II increases as you go through the lymphatics. As the dendritic cell matures the MHC load increases and they decrease the phagocytosis. If there is an antigen it will cause the t-cells in the lymph node to multiply and hence this will cause the lymph nodes in the area to get enlarged.

Question 6

Conventional Dendritic cells

Answer 6

they encounter a foreign antigen they take up the antigen, they become activated in an immature state and then they mature and they traffic to the lymphatics and then the lymphoid tissue. It now has the capacity in the lymph node to present antigen to the t-cells.

When it takes up antigen it is activated, this activation results in a down regulation of phagocytic activity and an up regulation of MHC class II expression on that cell. (the antigen is taken in and degraded). The amount of MHC Class II increases as you go through the lymphatics. As the dendritic cell matures the MHC load increases and they decrease the phagocytosis. If there is an antigen it will cause the t-cells in the lymph node to multiply and hence this will cause the lymph nodes in the area to get enlarged.

Question 7

Conventional Dendritic cells

Answer 7

they encounter a foreign antigen they take up the antigen, they become activated in an immature state and then they mature and they traffic to the lymphatics and then the lymphoid tissue. It now has the capacity in the lymph node to present antigen to the t-cells.

When it takes up antigen it is activated, this activation results in a down regulation of phagocytic activity and an up regulation of MHC class II expression on that cell. (the antigen is taken in and degraded). The amount of MHC Class II increases as you go through the lymphatics. As the dendritic cell matures the MHC load increases and they decrease the phagocytosis. If there is an antigen it will cause the t-cells in the lymph node to multiply and hence this will cause the lymph nodes in the area to get enlarged.

Question 8

MHC Class I antigen presenting pathway

Answer 8

1- Virus infects the cell
2- Viral proteins are produced in the cytosol and degraded (normally by the proteasome).
3- Peptide fragments of the viral proteins are transported to the ER by TAP-1 & TAP-2 and loaded on to MHC Class I in the ER
4- MHC Class I with loaded protein is transported to cell surface for presentation

Question 9

MHC Class II antigen presenting pathway via APC

Answer 9

1- Antigen is taken up from the extracellular space into intracellular vesicles (with help of TLR, CLR, etc).
2- Endosome where extracellular antigen is taken up matures and the acidic pH activates proteases that degrade the antigen.
3- Vesicle that contains the degraded peptide fuses with the vesicle that contains MHC Class II and then the vesicle is sent to the membrane after the antigen is loaded.

Question 10

MHC Class II antigen presenting pathway via B Cells

Answer 10

1- Antigen- specific BCR binds the antigen
2- Specific antigen efficiently internalized by receptor-mediated endocytosis
3- High density of specific antigen fragments are then presented.

Question 11

TAP 1 & TAP 2

Answer 11

transport peptides generated in the cytosol into the ER.

Question 12

Calnexin, Erp57, calreticulin

Answer 12

Help MHC Class I assemble in the ER. They associate with TAP-1 and TAP-2 and when the peptides are transported they are trimmed by ERAAP

Calnexin helps the microglobulin beta 2 bind
Erp57 & Calreticulinthe bind the alpha and beta2 chain and the construct can then bind to TAP1 and TAP 2 which then allow for the association of the molecules including the antigen (tapasin).

Question 13

ERAAP

Answer 13

Trims the viral peptides in the cytosol as they are going into the ER via TAP-1 and TAP-2.

Question 14

MHC Class I antigen presenting pathway

Answer 14

1- Virus infects the cell
2- Viral proteins are produced in the cytosol and degraded (normally by the proteasome).
3- Peptide fragments of the viral proteins are transported to the ER by TAP-1 & TAP-2 and loaded on to MHC Class I in the ER
4- MHC Class I with loaded protein is transported to cell surface for presentation

Under normal conditions, MHC Class I are loaded with self-peptides derived from normal cell degradation

Question 15

MHC Class II antigen presenting pathway via APC

Answer 15

1- Antigen is taken up from the extracellular space into intracellular vesicles (with help of TLR, CLR, etc).
2- Endosome where extracellular antigen is taken up matures and the acidic pH activates proteases that degrade the antigen.
3- Vesicle that contains the degraded peptide fuses with the vesicle that contains MHC Class II and then the vesicle is sent to the membrane after the antigen is loaded.

Under normal conditions, MHC Class II molecules only contain CLIP in the peptide binding groove.

Question 16

TAP 1 & TAP 2

Answer 16

transport peptides generated in the cytosol into the ER.

Question 17

ERAAP

Answer 17

Trims the viral peptides in the cytosol as they are going into the ER via TAP-1 and TAP-2.

Question 18

invariant chain (Ii)

Answer 18

associated protein that occupies the peptide binding cleft of the newly synthesized MHC Class II molecule which was made in the ER.

Acidification in the endosome cleaves the invariant chain leaving a short peptide fragment, CLIP

Question 19

Class II- Associated invariant chain peptide (CLIP)

Answer 19

bound to the peptide binding groove of MHC Class II and it is a result of a cleaved invariant chain due to the acidifcation of the endosome.

When antigens are endocytosed and degraded, CLIP prevents them from binding to the MHC Class II molecules.

Question 20

HLA-DM

Answer 20

removes CLIP and then places foreign peptides in the groove of MHC Class II.

Question 21

HLA-DM

Answer 21

removes CLIP and then places foreign peptides in the groove of MHC Class II.

Question 22

CD4 T-lymphocytes

Answer 22

can either mediate macrophage activation or act as helper cells in antibody responses by secreting cytokines

Question 23

Th1

Answer 23

Activate macrophages

Question 24

Th2

Answer 24

Induce antibody synthesis by means of cytokines. They bind to MHC Class II on B-cells and activate it by means of cytokines

Question 25

Resting APC vs. Mature APC

Answer 25

Resting APC (dendritic cell/macrophage): phagocytic but don’t present antigen well. Don’t express many co-stimulatory factors or cytokines (i.e. they don’t have B7 on the surface. once the cell engulfs something it will up regulate the presence of B7 on the surface).

Mature APC (dendritic cell/macrophage): Phagocytose more effectively AND EXPRESS ON THE SURFACES CO-STIMULATORY FACTORS i.e. B7 (CD80/CD86) AND CAN PRODUCE MANY CYTOKINES THAT ARE REQUIRED FOR T LYMPHOCYTE PROLIFERATION AND DIFFERENTIATION.

Question 26

Activation of naive T-cell

Answer 26

REQUIRES 2 signals:

1- Presentation of peptide by MHC to a TCR
2- Interaction between B7 on the APC and CD28 on the T-cell surface.

These signals lead to the activation of T-cells and regulate the expression of co-stimulatory molecules to make sure that the t-cell is activated at the right time and place.

Question 27

Activation of naive T-cell

Answer 27

REQUIRES 2 signals:

1- Presentation of peptide by MHC to a TCR
2- Interaction between B7 on the APC and CD28 on the T-cell surface.

These signals lead to the activation of T-cells and regulate the expression of co-stimulatory molecules to make sure that the t-cell is activated at the right time and place.

Question 28

Induction of B7 on the APC surface

Answer 28

T cells that recognize peptides expressed by MHC Class II on the surface are gonna be stimulated to express CD40 ligand (CD40L).

CD40L is going to bind to the CD40 on the surface of the APC and this is going to signal the expression of B7 by the APC which will then bind the CD28 that is already on the t-cell. This is going to induce T-cell proliferation and differentiation.

Question 29

Production of Antibodies

Answer 29

Requires B & T cells.

1- B- cells take up antigen and process it, displaying it on MHC Class II.
2- Activation of B cell to make B7
3- T-cells recognize the MHC Class II and the B-cell B7 binds to CD28 on the surface of the T-cell to activate the naive T-cell.
4- T-cell produces CD40L which then binds CD40 and these ligate and activates the naive t-cell more
5- Activation of the naive T-cell produces cytokines
6- B cell proliferates and differentiates into plasma cells that secrete antibody.

WITHOUT T-CELLS CLASS SWITCHING WOULD NOT HAPPEN. Need them for the CD28 receptor to activate the t-cell when bound to B7 which then induces CD40L which then binds to CD40 and then the cytokines are released from the mature T-cell in order to activate B-cell.

Question 30

Immune synapse

Answer 30

Provides a mechanism for sustained TCR engagement and signaling (Prolonged TCR engagement and signaling allows for T-cell proliferation and more complex functions of the t-cell.)

APC surface: I-CAM1
T-Cell Surface: LFA-1
Intermediate ring: Adhesion molecules that promote efficient TCR-MHC peptide interactions

Question 31

Immune synapse

Answer 31

Provides a mechanism for sustained TCR engagement and signaling (Prolonged TCR engagement and signaling allows for T-cell proliferation and more complex functions of the t-cell.)

APC surface: I-CAM1
T-Cell Surface: LFA-1
Intermediate ring: Adhesion molecules that promote efficient TCR-MHC peptide interactions
Inner circle has TCR, CD4 and co-stimulatory factors (i.e. CD28).

direct interaction allows the T-cell receptor and the MHC peptide to connect and sample. If the T-cell is not specific for the peptide then the t-cell will do nothing and will come off and go to the next cell. If the T-cell is specific for the MHC class II molecule and the peptide, then the TCR is stimulated and will cause a change of the adhesion molecules to the outside periphery and the TCR and MHC Class II move to the center creating a bubble like structure. The t-cell is then ready to proliferate and divide.