Activation of Adaptive Immunity

Question 1

What are the two ways an APC (macrophage or dendritic cell) can activate a T cell?

Answer 1

1. TLR binds a PAMP then produces cytokines (IL12, 6, TNF alpha)
2. takes in pathogen/Ag, chews it up, throws it out on an MHC for TCR to see

Question 2

Where are type 2 HLA found?

Answer 2

APCs: Dendritic cells, macrophages, b cells and T helper

Question 3

Where is HLA controlled from?

Answer 3

Chromosome 6

Question 4

How many haplotypes does a human have for HLA?

Answer 4

2, one from mom, one from dad

Question 5

What are the class 1 HLA genes?

Answer 5

HLA-A, HLA-B, HLA-C

Question 6

Where are class 1 expressed? What do they do?

Answer 6

All nucleated cells, present antigen to CTL and inhibit NK cells

Question 7

What are the parts of HLA 1?

Answer 7

Three alpha units and 1 beta unit

Question 8

What regions of HLA 1 are encoded by HLA?

Answer 8

a1, a2, a3

Question 9

What limits the size of HLA1 peptides?

Answer 9

Closed ends on the protein, limits to 8-10 AA

Question 10

Where is HLA 1 made?

Answer 10

In the ER as a glycoprotein, in the ER the beta subunit associates, then in the ER the peptide binds to the receptor and moves to the cell surface

Question 11

What are the HLA 2 subtypes?

Answer 11

HLA-DP, HLA-DQ, HLA-DR

Question 12

What is the structure of HLA2?

Answer 12

It is made of an alpha and beta unit which are roughly mirrors of each other

Question 13

How many peptides does HLA2 bind?

Answer 13

Between 13-18 because the ends are open

Question 14

What domains of HLA2 have the greatest polymorphism? Where are they from?

Answer 14

a1, b1, they come from DQ

Question 15

What binds to HLA2 in the ER? What does it do?

Answer 15

Invariant chain, it directs the protein to an endosome where the invariant protein is removed and the peptide is allowed to bind

Question 16

How many alpha and beta chains do we have for HLA2?

Answer 16

6a and 6b; you get 3 from each parent and they can combine in any combination of a and b

Question 17

What are the features of peptide binding to HLA

Answer 17

They are slow to bind and even slower to come off because you want T and B cells to be able to recognize the protein as problematic before it is removed

Question 18

What are our antigen presenting cells?

Answer 18

B cells, macrophages, dendritic cells

Question 19

What is the HLA2 pathway for antigen processing?

Answer 19

The protein is taken into the cell-> endosome and lysosome bind and degrade the protein -> HLA2 is made in ER and invariant chain is attached -> endosome carrying degraded protein and HLA2 are fused -> CLIP removes portion of invariant chain -> HLA-DM removes CLIP from HLA2 -> protein binds to HLA2 -> whole complex is transported to cell surface

Question 20

What is the pathway for HLA1 antigen processing?

Answer 20

Protein inside cells is degraded by proteasome -> degraded pieces are taken up by TAP which moves it into the ER lumen -> TAP is connected to HLA1 by tapasin on the lumen -> the complex forms -> moves to golgi -> vesicles dumps complex in cell surface

Question 21

What is cross presentation?

Answer 21

When one thing is recognized by both CD8+ and CD4+ t cells

Question 22

What is Ankylosing spondylitis associated with?

Answer 22

Inflammation of the spine based on overexpression of HLA-B27

Question 23

What is rheumatic fever?

Answer 23

After effect of S. Pyogenes infection; Ab created cross react with the heart

patients with HLA-DR4 allele are more likely to get it

Question 24

What is sjogren’s syndrome?

Answer 24

Associated with HLA-DR3

Defect in salivation and lacrimation

Question 25

What HLA is Type 1 DM associated with?

Answer 25

HLA-DQw8

Question 26

What HLA is psoriasis associated with?

Answer 26

HLA-B3

Question 27

What cancer has an antigen processing defect?

Answer 27

Renal cell carcinoma

Down regulated TAP protein (transports peptides into ER lumen)

Question 28

What is bare lymphocyte syndrome?i

Answer 28

Defect in TAP protein that doesn’t transport peptides in so there are no peptides expressed on the cell surface (no HLA1 on cell surface)

Question 29

What are the symptoms of bare lymphocyte syndrome?

Answer 29

Chronic respiratory infection and poor response to viruses