7: Ag Capture And Presentation

Question 1

Two ways innate immunity activates adaptive

Answer 1

1. Presenting Ags to T cells

2. Co-stimulatory signals to T/B cells

Question 2

Path for Ags entering periphery vs blood

Answer 2

Periphery -> filtered by lymph/lymphoid tissue

Blood -> filtered by spleen

Question 3

Three professional APCs

Answer 3

DCs, macrophages, B cells

Question 4

A transient professional APC

Answer 4

Thymic epithelial cells (also have MHC II)

Question 5

Which professional APC is the only one that can activate naive T cells?

Answer 5

DCs

Question 6

Plasmacytoid DCs function and major cytokine

Answer 6

Are anti-viral; produce INF type I

Question 7

What three things are up regulated on DC surface when they become activated?

Answer 7

MHCs, CCR7, CD80 (B7)

Question 8

What does HLA stand for

Answer 8

Human leukocyte Ag

Question 9

Histocompatible tissue

Answer 9

Accepted by self as non-foreign

Question 10

MHC genes

Answer 10

Tight cluster of genes that are highly polymorphic, with more than 150 known alleles

Question 11

HLA gene location

Answer 11

Chromosome 6

Question 12

How many classes of HLA genes are there?

Answer 12

Class I, II, and III

Question 13

HLA haplotype

Answer 13

Total set of HLA alleles present on each chromosome

Question 14

What does each allotype of the HLA gene confer?

Answer 14

The ability to bind different peptides for T cells to respond to

Question 15

What type of expression do we have for our HLA haplotypes?

Answer 15

Heterozygous / co-dominant (one from mom, one from dad)

Question 16

Which HLA class of genes is more diverse? Why?

Answer 16

Class I; they are responsible for self vs non-self recognition

Question 17

Linkage disequilibrium in terms of genes

Answer 17

Certain alleles in a haptotype are found together significantly more frequently than expected by chance

Question 18

What are class I and II HLAs important for?

Answer 18

Class I: intracellular pathogens + self vs non self

Class II: extracellular pathogens

Question 19

Class I HLAs and NK cells

Answer 19

Class I HLA inhibits NK cell killing by engaging the CD94/NKG2A receptors

Question 20

Class I and II genes on the HLA locus

Answer 20

Class I: HLA-A, HLA-B, HLA-C

Class II: HLA-DP, HLA-DQ, HLA-DR

Question 21

Four proteins of class I and class II HLAs

Answer 21

Class I: a1, a2, a3, B2

Class II: a1, a2, B1, B2

Question 22

What encodes the alpha chain and B2-microglobulin of HLA 1?

Answer 22

Alpha chains: HLA locus

B2 microglobulin: non-HLA genes

Question 23

Which chain of class I HLA binds to the T cell? Which on the class II?

Answer 23

Class I: a3 binds T cell

Class II: B2 binds T cell

Question 24

Which two chains form the peptide binding domain for class I and II?

Answer 24

Class I: a1, a2

Class II: a1, B1

Question 25

Size of peptides that can bind to class I and class II HLAs

Answer 25

Class I: 8-10 AAs (closed ends)

Class II: 13-18 AAs (open ends)

Question 26

How many alleles of a and B chains of class II HLA are expressed in a person?

Answer 26

6 alpha chains + 6 beta chains (3 from mom each, 3 from dad each)

Question 27

On/off rates of HLA/peptide interactions

Answer 27

Slow on rate, even slower off rate -> peptide/HLA complex can persist long enough to contact T cells

Question 28

6 Steps in Class I Ag Presentation pathway

Answer 28

1. Proteasome degrades Ag + tags peptides with ubiquitin
2. TAP and tapasin: transport peptide into ER
3. A chains of HLA -> translated into ER with chaperone
4. A chains and B2 globulin combine in ER
5. Peptide is trimmed -> loaded into class I molecule
6. Class 1 HLA - peptide complex transported to cell surface

Question 29

4 Steps in Class II Ag presentation pathway

Answer 29

1. A chains, B chains, and Ii invariant chain -> synthesized in ER -> transported through Golgi
2. Lysosomal enzymes: degrades Ii to CLIP
3. HLA-DM in late endosome: removes CLIP -> adds peptide
4. Class II HLA - peptide complex -> transported to cell surface

Question 30

Cross presentation involving DCs

Answer 30

DCs can display peptides on class I and II HLAs - by injesting virally-infected or transformed cells and displaying those Ags on class I HLAs

Question 31

Do HLAs always carry foreign Ags?

Answer 31

No, without infection, they will carry self Ags that shouldn’t provoke an immune response

Question 32

What two diseases/disorders are related to HLAs?

Answer 32

Autoimmune diseases, susceptibilities

Question 33

Which HLA type I allele is present in 87% of people with Ankylosing Spondylitis?

Answer 33

B27

Question 34

Bare lymphocyte syndrome

Answer 34

Deficiency in HLA class I or II expression on cells

Question 35

Common defects found in neuroblastoma s

Answer 35

Defects of Ag-processing machinery

Question 36

Common defects found in renal cell carcinomas

Answer 36

Class I Ag processing defects, involving TAP