Antigen Presentation and Processing - Diebel

Question 1

Define Anergy

Answer 1

Self-tolerance; T-cell binds to APC without CD28 binding CD80/86 => T-cell inactivated or may die

Question 2

What 3 receptors need to bind for a T-cell to be activated?

Answer 2

TCR = MHC
CD4/8 = MHC
CD28 = CD80/86 (B7-1/2)

Question 3

When a T-cell is activated, what happens next?

Answer 3

IL-2 produced with IL-2R (high affinity) to promote division, differentiation, effector functions

Question 4

What happens to T-cell activation 24 hours after an event?

Answer 4

CTLA-4 binds CD80/86, blocking the stimulatory effects that the T-cell gets from CD80/86; shuts off the signal

Question 5

Which has a higher affinity for the CD80/86 complex?

CD28 or CTLA-4

Answer 5

CTLA-4 will outcompete and bind better to CD80/86 leading to T-cell activation inhibition

Question 6

What is the main function of CTLA-4 (broad picture)?

Answer 6

Prevent overstimulation of T-cells

Question 7

ACP LFA-3 binds to…

Answer 7

CD2 on T-Cell

Question 8

APC MHC II binds to…

Answer 8

TCR-CD3 on T-Cell

CD4 on T-Cell

Question 9

APC CD80/86 binds to…

Answer 9

CD28 on T-Cell (Activating)

CTLA-4 on T-Cell (Inhibiting)

Question 10

APC ICAM-1 binds to…

Answer 10

LFA-1 on T-Cell

Question 11

What is the BCR made up of?

Answer 11

Membrane bound IgM or IgD

Question 12

How do T-cells recognize antigen?

Answer 12

Cannot recognize free antigen - must first be processed and presented on an MHC molecule

Question 13

How many different Class I MHC molecules could each cell express?

Answer 13

6

Question 14

How many different Class II MHC molecules could each cell express?

Answer 14

12 (DP, DQ, DR)

Question 15

What cell type is the most effective professional antigen presenting cell?

Answer 15

Dendritic Cells

Question 16

Describe the MHC presentation on immature and mature dendritic cells.

Answer 16

Immature DCs = LOW MHC II
Mature DCs = HIGH MHC II (primary presenters of antigen via phagocytosis and endocytosis)
- Constitutively express CD80/86

Question 17

How can macrophages express MHC II molecules?

Answer 17

Activated by phagocytosis and cytokines to express MHC II

Activated to express co-stimulatory molecules

Question 18

If B-Cells constitutively express MHC II, how are they activated?

Answer 18

By antigen binding to antibody to express co-stimulatory molecules

Question 19

Describe the types of antigens presented by DCs, Macrophages, and B-Cells.

Answer 19

DCs = peptides, viral antigens, allergens
Macrophages = particulate antigens
B-Cells = soluble antigens, toxins, viruses

Question 20

What is the cytosolic pathway for antigen presentation?

Answer 20

Requires intracellular protein synthesis of the endogenous antigen for presentation on MHC I
* Key for presenting damaged DNA or proteins to receive apoptotic signal from CD8+ T-Cell

Question 21

What is the endocytic pathway for antigen presentation?

Answer 21

Requires the endocytic uptake of exogenous antigen and degradation in phagolysosomes or endosomes for presentation of antigen on MHC II

Question 22

What two ways can cellular proteins be degraded?

Answer 22

Constitutive proteasome: 20S proteasome or 26S proteasome (Ub required 20S proteasome with 19S regulator

Immunoproteasome: stimulated with INF-y or TNF-a to efficiently load peptides into MHC I through better TAP protein complex association

Question 23

What is the TAP protein and what is it used for?

Answer 23

TAP = Transporter Associated with Antigen Processing with affinity for peptides 8-16 amino acids long

A transporter protein heterodimer complex of TAP1 and TAP2 extends across the RER membrane to facilitate the passage of peptides into the lumen of the RER to be loaded onto MHC I

Question 24

What is the optimal binding size of the MHC Class I Molecule?

Answer 24

9 amino acids

Question 25

What enzyme is responsible for the final trimming of the amino acid peptide sequence and where does this trimming occur?

Answer 25

In the ER by ERAAP (ER-associated aminopeptidase) Can also occur in MHC I grove in ER

Question 26

What are DRiPs?

Answer 26

Defective Ribosomal Products are proteins that are synthesized incorrectly

Question 27

What do virus-infected cells contain and how did it get there?

Answer 27

A distinct 20S proteosome induced by INF-y and TNF-a, which degrades and presents viral proteins on MHC I

Question 28

What two ways can CD8+ activated T-cells induce apoptosis?

Answer 28

``` Release of cytotoxic molecules - Perforin - Granzymes - Granulysin Binding of Fas ligand to Fas receptor (death receptor) ```

Question 29

What does chromosome 6 encode?

Answer 29

HLA Class I, II, & III and TAP

Question 30

What does chromosome 15 encode?

Answer 30

Beta2-microglobulin

Question 31

What is the normal ratio of CD4:CD8 T-Cells?

Answer 31

65% CD4+ to 35% CD8+ T-Cells

Question 32

MHC Class II molecules are synthesized in the RER as trimers. What makes up the trimer?

Answer 32

Alpha and Beta chain coupled with an invariant chain, CD74.

Question 33

What is the role of the invariant chain?

Answer 33

Assist in folding of MHC Class II, binds to peptide-presenting site, assists in transport from Golgi to cytoplasmic vesicles

Question 34

What non-classical MHC Class II molecule releases the CLIP invariant chain remnant from the peptide binding site of MHC Class II molecules?

Answer 34

HLA-DM exchanges CLIP for the antigenic peptide, which is regulated by HLA-DO

Question 35

What is the function of Th1 T-Cells?

Answer 35

Recognize peptide bound to MHC Class II to activate macrophages and destroy intravesicular pathogens

Question 36

What is the function of Th2 T-Cells?

Answer 36

Recognize peptide bound to MHC Class II to cause B-Cell proliferation and differentiation to plasma cells and antibody production

Question 37

What is the normal nutrophil and lymphocyte counts in a WBC differential?

Answer 37

Neutrophils: 40-60% Lymphocytes: 22-44%

Question 38

How is MHC Class II deficiency inherited?

Answer 38

Autosomal Recessive with health problems in early infancy

Question 39

What is typically seen in dividuals with a MHC Class II deficiency that are deficient in CD4+ T-Cells?

Answer 39

Moderate to Severe Hypogammaglobulinemia

Question 40

What is the treatment for MHC Class II deficiency?

Answer 40

Hematopoietic Stem Cell Transplant

Question 41

What is the cause of MHC Class II Deficiency?

Answer 41

Defects in the transcription factors required to regulate expression of MHC Class II genes

Question 42

What induces the expression of MHC Class II on APCs in normal people?

Answer 42

IFN-y