Exam 2 Immune Ontogeny and MHC Flashcards

1
Q

Waldeyer’s ring consists of:

A
  • pharyngeal tonsil (adenoid)
  • tubal tonsils
  • palatine tonsils
  • lingual tonsils
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2
Q

Primary and secondary follicles - describe the difference

A

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

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3
Q

Germinal center is active site of:

A
  • B cell profileration and differentiation
  • Class switching
  • Affinity maturation
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4
Q

Affinity maturation

A

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

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5
Q

Class I MHC is expressed by:

A

most somatic cells (except erythrocytes and platelets)

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6
Q

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

A

Endogenous; CD8 T-cells

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7
Q

Class II MHC is expressed by:

A

APC only

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8
Q

MHC II presents ____ and recognized by ____

A

Exogenous/found antigens; CD4 T-cells

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9
Q

Which part of CD3 specifically is responsible for signal transduction?

A

Zeta component

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10
Q

MHC I is expressed on most somatic cells except:

A

Erythrocytes

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11
Q

HLA stands for

A

Human leukocyte antigens

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12
Q

HLA/MHC genes are on:

A

Chromosome 6

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13
Q

MHC I genes

A

A, B, C

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14
Q

MHC II genes

A

DM, DP, DQ, DR

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15
Q

Which MHC gene has the most/least allelic variations?

A

Most - DP
Least - DR

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16
Q

MHC is inherited via:

A

Mendelian inheritance

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17
Q

Most transplant rejections are due to:

A

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

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18
Q

Mismatched MHC molecules can mediate:

A

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

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19
Q

For a bone marrow transplant, look at:

A

HLA-DR

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20
Q

For a solid transplant, look at:

A

HLA-A

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21
Q

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

A

Alpha-1 and alpha-2

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22
Q

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

A

HLA-E

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23
Q

Non-classical MHC 1B genes

A

HLA-E, HLA-G, HLA-F

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24
Q

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

A

Alpha-1 and beta-1

25
Q

Most T cells are within which TCR subset?

A

TCR2 (have alpha/beta subunits)

26
Q

TCR subset intraepithelial cells have what subunits?

A

gamma, delta

27
Q

T cell antigen receptor components

A

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

28
Q

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

A

somatic recombination

29
Q

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

A

Recombination signal sequences (RSS)

30
Q

TCR gene rearrangement segments are recognized by what enzyme?

A

VDJ recombinase (same as BCR)

31
Q

TCR gene rearrangement occurs where?

A

In the thymus

32
Q

Somatic recombination occurs at:

A

Hypervariable regions of BCR and TCR

33
Q

Thymus is the site for:

A

T cell processing and differentiation

34
Q

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

A

Because you should be responding to many new antigens

35
Q

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

A

bone marrow; thymus; thymocytes; mature T cells

36
Q

When thymocytes enter the thymus, they are termed:

A

Double negative cells

37
Q

Early thymocytes lack:

A

TCR, CD4, CD8

38
Q

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

A

Epithelial reticular cells

39
Q

ERC provides majority of:

A

Cytokines

40
Q

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

A

Interdigitating reticular cells (IDC)

41
Q

Hassall’s corpuscle is associated with ERC type:

A

Type 6; DC maturation

42
Q

Medullary and cortical ERC produce thymic hormones such as:

A

Thymosin, thymulin, thymopoietin

43
Q

In precursor T-lymphocytes, the TCR locus is:

A

Methylated –> DNA inaccessible

44
Q

Thymic cytokine ____ triggers DNA remodeling

A

IL-7

45
Q

IL-7 is expressed as a result of:

A

thymic hormones (microenvironment)
- thymosin
- thymopoietin
- thymulin

46
Q

IL-7 is required for development of

A

T-cells

47
Q

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

A

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

48
Q

What is positive selection?

A
  • 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)
49
Q

Negative selection

A

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

50
Q

Difference between positive and negative selection

A
  • positive selection retains T cells that recognize self-MHC
  • negative selection destroys cells that react with self MHC and self peptide (apoptosis)
51
Q

Final result of mature, single positive T cells

A
  • immunocompetent
  • self-restricted (can bind MHC)
  • self-tolerant (does not bind endogenous host antigens)
52
Q

Next generation sequencing for HLA 1

A

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

53
Q

High risk oncogenic HPV strains

A

HPV 16, HPV 18

54
Q

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

A

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

55
Q

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

A

Swedish - Scandinavian populations

56
Q

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

A

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

57
Q

Distribution of HLA-DR-B1*04:01

A
  • highest concentration in Sweden (Scandinavia) – 6x more deaths than in Germany
  • densely concentrated in Northern europe
58
Q

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

A
  • In Chile and Uruguay, highly increased risk of COVID-19 L84S variant
  • highly increased risk of H1N1 morbidity and mortality
59
Q

HLA-A02:06 and HLA-A11:01
HLA-B07:02 and HLA-B54:01

A

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