Exam 2 Immune Ontogeny and MHC

Question 1

Waldeyer’s ring consists of:

Answer 1

• pharyngeal tonsil (adenoid)
• tubal tonsils
• palatine tonsils
• lingual tonsils

Question 2

Primary and secondary follicles - describe the difference

Answer 2

Secondary follicle has darker staining (more cells) and surrounds germinal center

Question 3

Germinal center is active site of:

Answer 3

• B cell profileration and differentiation
• Class switching
• Affinity maturation

Question 4

Affinity maturation

Answer 4

Highest affinity B cells are selected by binding to antigen on follicular dendritic cells

Question 5

Class I MHC is expressed by:

Answer 5

most somatic cells (except erythrocytes and platelets)

Question 6

What antigens are presented on MHC I, and they are recognized by:

Answer 6

Endogenous; CD8 T-cells

Question 7

Class II MHC is expressed by:

Answer 7

APC only

Question 8

MHC II presents ____ and recognized by ____

Answer 8

Exogenous/found antigens; CD4 T-cells

Question 9

Which part of CD3 specifically is responsible for signal transduction?

Answer 9

Zeta component

Question 10

MHC I is expressed on most somatic cells except:

Answer 10

Erythrocytes

Question 11

HLA stands for

Answer 11

Human leukocyte antigens

Question 12

HLA/MHC genes are on:

Answer 12

Chromosome 6

Question 13

MHC I genes

Answer 13

A, B, C

Question 14

MHC II genes

Answer 14

DM, DP, DQ, DR

Question 15

Which MHC gene has the most/least allelic variations?

Answer 15

Most - DP
Least - DR

Question 16

MHC is inherited via:

Answer 16

Mendelian inheritance

Question 17

Most transplant rejections are due to:

Answer 17

mismatched HLA-A (solid tumors), HLA-DR (BMT)

Question 18

Mismatched MHC molecules can mediate:

Answer 18

transplant rejection or Graft vs host disease (GVHD)
- look for HLA-A (most common reason for solid tumor rejection) - must all be the same for a transplant to have less likelihood of being rejected

Question 19

For a bone marrow transplant, look at:

Answer 19

HLA-DR

Question 20

For a solid transplant, look at:

Answer 20

HLA-A

Question 21

In MHC I, the peptide-binding groove is found between:

Answer 21

Alpha-1 and alpha-2

Question 22

Some tumors over-express ____, which inhibits the NK response

Answer 22

HLA-E

Question 23

Non-classical MHC 1B genes

Answer 23

HLA-E, HLA-G, HLA-F

Question 24

In MHC II, peptide-binding groove is found between:

Answer 24

Alpha-1 and beta-1

Question 25

Most T cells are within which TCR subset?

Answer 25

TCR2 (have alpha/beta subunits)

Question 26

TCR subset intraepithelial cells have what subunits?

Answer 26

gamma, delta

Question 27

T cell antigen receptor components

Answer 27

Variable domain (antigen binding domain) Constant domain (transmembrane)

Question 28

There are variable genes for alpha/beta chains of TCRs, which allow for:

Answer 28

somatic recombination

Question 29

In TCR gene rearrangement, gene segments are flanked by conserved ____

Answer 29

Recombination signal sequences (RSS)

Question 30

TCR gene rearrangement segments are recognized by what enzyme?

Answer 30

VDJ recombinase (same as BCR)

Question 31

TCR gene rearrangement occurs where?

Answer 31

In the thymus

Question 32

Somatic recombination occurs at:

Answer 32

Hypervariable regions of BCR and TCR

Question 33

Thymus is the site for:

Answer 33

T cell processing and differentiation

Question 34

Why is the thymus so large when you're young?

Answer 34

Because you should be responding to many new antigens

Question 35

T-cells originate in the ____ and move to the _____. They enter as immature _____ and emerge as ______

Answer 35

bone marrow; thymus; thymocytes; mature T cells

Question 36

When thymocytes enter the thymus, they are termed:

Answer 36

Double negative cells

Question 37

Early thymocytes lack:

Answer 37

TCR, CD4, CD8

Question 38

Thymic development begins when thymocytes contact ______ and dendritic cells to create a microenvironment

Answer 38

Epithelial reticular cells

Question 39

ERC provides majority of:

Answer 39

Cytokines

Question 40

Besides ERC, what is another important cell type that participates in T cell selection?

Answer 40

Interdigitating reticular cells (IDC)

Question 41

Hassall's corpuscle is associated with ERC type:

Answer 41

Type 6; DC maturation

Question 42

Medullary and cortical ERC produce thymic hormones such as:

Answer 42

Thymosin, thymulin, thymopoietin

Question 43

In precursor T-lymphocytes, the TCR locus is:

Answer 43

Methylated --> DNA inaccessible

Question 44

Thymic cytokine ____ triggers DNA remodeling

Answer 44

IL-7

Question 45

IL-7 is expressed as a result of:

Answer 45

thymic hormones (microenvironment) - thymosin - thymopoietin - thymulin

Question 46

IL-7 is required for development of

Answer 46

T-cells

Question 47

During chromosomal DNA remodeling, what happens to the TCR locus?

Answer 47

It is moved into a central/active transcriptional position, methylation marks are removed to induce conformational change to euchromatin

Question 48

What is positive selection?

Answer 48

- Double positive T cells have both CD4 and CD8 - TCR binds to MHC I or II - Specific T cells are retained if they can recognize MHC without antigen - lose either CD4 or CD8 depending on what they come into contact with first (become single positive)

Question 49

Negative selection

Answer 49

removes T-cells reacting to MHC+ "self" peptides (self reactive) via apoptosis

Question 50

Difference between positive and negative selection

Answer 50

- positive selection retains T cells that recognize self-MHC - negative selection destroys cells that react with self MHC and self peptide (apoptosis)

Question 51

Final result of mature, single positive T cells

Answer 51

- immunocompetent - self-restricted (can bind MHC) - self-tolerant (does not bind endogenous host antigens)

Question 52

Next generation sequencing for HLA 1

Answer 52

HLA-A*02:101 - many people show different disease predilection/risk

Question 53

High risk oncogenic HPV strains

Answer 53

HPV 16, HPV 18

Question 54

If you have HLA-DR-B1*04:01 and HPV 16:

Answer 54

Cells don't show HPV16 very well so can't make antibodies to HPV16. Increases risk of reinfection

Question 55

Highly increased risk of HPV16 infection is highly concentrated in what population?

Answer 55

Swedish - Scandinavian populations

Question 56

In addition to HPV16, HLA-DR-B1*04:01 also implies highly increased risk of:

Answer 56

wt COVID-19 infection. Can't present antigen well to be able to make antibodies

Question 57

Distribution of HLA-DR-B1*04:01

Answer 57

- highest concentration in Sweden (Scandinavia) -- 6x more deaths than in Germany - densely concentrated in Northern europe

Question 58

Those with HLA-DP-B1*04:01:

Answer 58

- In Chile and Uruguay, highly increased risk of COVID-19 L84S variant - highly increased risk of H1N1 morbidity and mortality

Question 59

HLA-A*02:06 and HLA-A*11:01 HLA-B*07:02 and HLA-B*54:01

Answer 59

Highly decreased risk of wt COVID-19 infection Highest concentrations in Asia (Japan and Korea)