Antigen Processing, Presentation, and Lymphocyte Development

Question 1

MCH Restriction

Answer 1

T-cell receptors have specificity for a particular MHC/peptide compex

Question 2

Polyspecificity of MHC receptors

Answer 2

Many different peptides can bind to MHC receptors, but not all peptides

Question 3

Which MHC receptor can accomodate longer peptides?

Answer 3

MHC Class II molecules can accomodate longer peptides

Question 4

MCH I peptide/complexes engage TCRs with ____ co-receptors

Answer 4

CD8+

Question 5

MCH II peptide/complexes engage TCRs with ____ co-receptors

Answer 5

CD4+

Question 6

Which cells express MHC I?

What is the significance of this?

Answer 6

• All nucleated cells express MCH I
• Can present viral peptides when infected

Question 7

What are 2 important properties of MHC genes?

Answer 7

• Polymorphic: many different alleles present in the population
• Co-dominant expression: Both parental alleles of each MHC gene are expressed

This increases the number of microbial peptides that the MHC can present to T-cells

Question 8

How do Dendritic Cells act as specialized activators of naive T-cellls?

Answer 8

Dentric cells:

1. Process foriegn antigen
2. Migrate to lymph nodes where they present the antigen to naive T-cells
3. Provide addtional stimulating signals necessary for T-cell activation

Question 9

What role does the spleen play with regards to blood-borne antigens?

Answer 9

Blood-borne antigens are captured by antigen-presenting cells in the spleed

Question 10

Cytotoxic T-cells present T-Cell Receptors (TCRs) with

CD__ co-receptors which binds to MHC class ___

Answer 10

• CD8+ co-receptors
• MCH Class I

Question 11

Helper T-cells present T-Cell Receptors (TCRs) with

CD__ co-receptors which binds to MHC class ___

Answer 11

• CD4+ co-receptors
• MHC Class II

Question 12

MHC Class I Presentation Process

Answer 12

1. Viral protein in the cytoplasm is cleaved by proteasomes
2. Cleaved products = viral peptides
3. Viral peptides are transported to the endoplasmic reticulum
4. Peptides combine with MHC Class I in the ER
5. MCH Class I/Peptide Complex is then transfered to the cell surface where it is expressed

Question 13

MHC Class II Presentation Process

Answer 13

1. Uptake of extracellular protein antigen via endocytosis or phagocytosis
2. Endosome/Phagosome fuse with Lysosome
3. Protein antigen is processed to form peptides
4. MHC Class II is transported via a vesicle to the endosome/phagosome
5. MHC Class II/Peptide Complex is formed and transfered to be expressed on the cell surface

Question 14

Cross-Presentation

Answer 14

• Endosomal antigen (normally presented by MHC II) is presented by MHC I (when the endosomal antigen is viral instead of bacterial/fungal)
• Occurs as a result of certain viruses only infecting certain cell types, and the immune system (Ex. Dendritic Cells) still needs to be able to present these viral antigens even when the particular virus doesn’t infect Dendritic Cells
• Follows a similar process as normal MHC I Presentation with the only difference being that the antigen source comes from endosomes instead of the cytoplasm

Question 15

Are MHC without peptide presented on the cell surface?

Answer 15

No because MHC without peptide are inherently unstable and undergo degredation while MHC with peptide is very stable

Question 16

Which cells express MHC II?

Answer 16

• Dendtritic Cells
• Macrophages
• B-Lymphocytes
• Thymic Epithelium

Question 17

What are the cell surface antibody associated signaling receptors?

Answer 17

Iga and IgB

Question 18

What are the T-Cell Receptor (TCR) associated signaling receptors?

Answer 18

CD3

Question 19

What does the T-Cell Receptor (TCR) recognize and bind to?

Answer 19

The MHC and peptide within the complex

Question 20

What components make up the MHC Class I peptide-binding cleft?

Answer 20

a1 and a2

Question 21

What components make up the MHC Class II peptide-binding cleft?

Answer 21

a1 and b1

Question 22

What type of molecules do MHC bind?

Answer 22

Peptides only (they do not bind lipids, carbohydrates, nucleic acids, etc.)

Question 23

Where do MHC I peptides originate?

Where do MHC II peptides originate?

Answer 23

• MHC I peptides originate from intracellular viral proteins
  
  • With the exception of cross-presentation where the viral proteins come from endosomes
• MHC II peptides originate from extraceullar pathogens

Question 24

“MHC Restricted Antigen Recognition” refers to the ability of:

Answer 24

T-cells to respond to a given antigenic peptide, only when this antigen is bound to a specific MHC molecule

Question 25

Helper T-Cell Function

Answer 25

Activate macrophages to kill phagocytosed microbes

Question 26

Cytotoxic T-Cell Function

Answer 26

Kill infected cells and eliminate reservoirs of infection

Question 27

Analogy between ab T-Cell receptor and Antibody

Answer 27

* TCR is like the Fab fragment of an antibody * TCR has an a/b chain; antibody has a light/heavy chain * TCR is membrane anchored; antibody can be membrane anchored as a B-cell receptor or secreted

Question 28

Antibody Structure

Answer 28

* 2 light chains and 2 heavy chains * Each chain has one variable domain (V) and at lesat one constant domain (C) * Two V domains (V_L and V_H) make up antigen binding site * The Fc region determines the antibody effector function

Question 29

Generation of combinatorial BCR diveristy

Answer 29

During B-Cell development in the bone marrow: * Multiple different V, D, and J gene segments are selected and combined to form the gene that codes the BCR * Genetic assembly of gene segments is mediated by the enzyme Recombinsase Activating Gene (RAG) Additional diversity is generated by enzymes that semi-randomly add/remove nucleotides at the ends of different gene segments prior to assembly by RAG

Question 30

Negative Selection

Answer 30

* Elimination of self reactive lymphocytes during their development * This leads to central tolerance: the immune system does not attack self

Question 31

Positive Selection of T-Cells

Answer 31

In order to complete development, mature naive T-cells must be able to _weakly_ bind MHC/self-peptide complexes from thymust epithelial or dendritic cells

Question 32

Negative Selection (T-Cells)

Answer 32

If a T-Cell binds _strongly_ to MHC/self-peptide it undergoes apoptosis

Question 33

Death By Neglect (T-Cells)

Answer 33

* Failure of positive selection * If a T-Cell Receptor doesn't bind MHC/self-peptide complexes at all (_no binding_), it undergoes apoptosis

Question 34

How does TCR gene arrangement relate to BCR gene arrangement?

Answer 34

* They are very similar * TCR diversity is also generated by combination of different V, D, and J gene segments

Question 35

Double-Negative T-Cells

Answer 35

Early in development: T-Cells do not express CD4+ or CD8+ co-receptors

Question 36

Double-Positive T-Cells

Answer 36

* Later in development, T-Cells express both CD4+ and CD8+ * After CD4+ or CD8+ co-receptors weakly bind MHC II or MHC I/self-peptide complexes, they stop expressing the other type of CD co-receptor * For example, if during development CD4+ weakly binds to MHC II, that cell will stop expressing CD8+ and become a helper T-Cell * This ensures that after maturation T-Cells only express CD4+ or CD8+, never both

Question 37

Where does the following generally occur: * T-Cell Selection * T-Cell Activation * T-Cell Effector Function

Answer 37

* T-Cell Selection --\>Thymus * T-Cell Activation --\> Lymph Nodes * T-Cell Effector Function --\> Site of Infection