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Immunology - DVM year 1 > Exam 2: Dr. Pinchuk TCRs and Antigen Recognition > Flashcards

Exam 2: Dr. Pinchuk TCRs and Antigen Recognition Flashcards

1
Q

How are PRRs developed?

A

Germline encoded

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2
Q

What kind of specificity do PRRs have?

A

Broad

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3
Q

What do PRRs recognize?

A

The presence of microbes or tissue damage

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4
Q

How is the PRR immune response mediated?

A

By a variety of cells and molecules that are effective against a wide range of pathogens

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5
Q

How are TCRs and BCRs developed?

A

Gene rearrangement

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6
Q

What kind of specificity do TCRs and BCRs have?

A

High

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7
Q

What do TCRs and BCRs recognize?

A

Specific single molecules

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8
Q

What is the TCR and BCR immune response mediated by?

A

Antigen-specific lymphocytes that are effective against a particular antigen

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9
Q

What does it mean if an immune receptor is germline encoded?

A

Developed during embryogenesis

They don’t change and the don’t recombine

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10
Q

What makes a TCR similar to IgR (BCR)?

A

Heterodimer
Antigen-binding site
V and C domains
The 3D structure of the the extracellular domain resembles the Fab fragment of IgR
The genes encoding the TCR chains have a germline organization similar to BCR light and heavy chains

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11
Q

What makes a TCR different from an IgR (BCR)?

A

No dramatic difference in the size of 2 chains
Always membrane-associated
One antigen-binding site
Antigen recognition function only
No isotype switching of the constant region

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12
Q

What does it mean if a receptor is a heterodimer?

A

It has alpha and beta chains

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13
Q

What contributes to TCR diversity?

A

Gene rearrangement

Small insertion or deletions of nucleotides at the joints between gene segments

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14
Q

What does gene rearrangement of TCRs produce?

A

Sequence variability in the variable regions

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15
Q

Does antigen stimulation promote change in the TCR?

A

No

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16
Q

What is somatic hypermutation?

A

When B cells have a second chance to produce diversity

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17
Q

What is T cell development in the thymus initiated by? What does it do?

A

The assembly of gene segments to make the variable sequence that encodes the V regions of the TCR alpha and beta chains

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18
Q

What is the diversity (D) gene segment involved in?

A

The random rearrangements that produce the TCR beta chain

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19
Q

What happens during recombination in TCR diversity?

A

The DNA between gene segments is deleted from the chromosome

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20
Q

Which is more diverse, immunoglobulin or α:β T-cell receptors?

A

α:β T-cell receptors

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21
Q

Which has more variable segments, immunoglobulin or α:β T-cell receptors?

A

They are both relatively similar, but beta chains have the most

22
Q

Which has more diversity segment, immunoglobulin or α:β T-cell receptors?

A

Immunoglobulin

23
Q

Which has more V gene pairs, immunoglobulin or α:β T-cell receptors?

A

α:β T-cell receptors

24
Q

Which has more junction diversity, immunoglobulin or α:β T-cell receptors?

A

α:β T-cell receptors

25
Q

What do RAG genes provide?

A

The clonal diversity of T and B cell receptors

26
Q

What do recombinase-activating enzymes encoded by genes RAG-1 and RAG-2 initiate?

A

V(D)J recombination by nicking double-stranded DNA

27
Q

What do DNA repair proteins do?

A

Carry out the rejoining process that brings the gene segment of each type together

28
Q

What happens if either of the RAG genes is knocked out?

A

B and T cell development is completely abolished leading to severe combined immunodeficiency

29
Q

Where have mutations in RAG genes been found?

A

Human SCID

30
Q

What do mutations in RAG genes that cause partial enzymatic activity give rise to?

A

An immunodeficiency called Omenn syndrome

31
Q

What is the immunological analysis of Omenn syndrome?

A

Lymphocytes respond poorly to stimulation
No mature B cells and decreased numbers of T cells by FACS analysis
Analysis of genomic DNA from peripheral blood lymphocytes reveals T cell oligoclonality suggesting a defect in RAG genes
RAG-1 and RAG-2 genes were sequenced and a missense mutation was found in RAG-1 gene

32
Q

What is the immunological analysis of SCID in dogs?

A

The RAG-1 and RAG-2 genes were sequenced and a missense mutation was found in the RAG-1 gene

33
Q

What do current approaches to hematopoietic stem cell (HSC) gene therapy involve?

A

The collection and ex vivo manipulation of HSCs

34
Q

What is an alternative approach for correcting blood-related diseases?

A

The direct intravenous administration of viral vectors, AKA in vivo gene therapy

35
Q

What is the immunological analysis for SCID in horses?

A

SCID foals are incapable of V(D)J gene rearrangement

DNA protein kinase gene mutation

36
Q

What does expression of TCR on the cell surface require?

A

Association with additional proteins

37
Q

What is the marker for TCR complex?

A

CD3

38
Q

What is the function of TCR?

A

Antigen recognition

39
Q

What is the function of TCR complex?

A

Antigen recognition and signal transduction

40
Q

What is the difference between alpha-beta chains and gamma-delta chains?

A

Alpha-beta are specific and adaptive

Gamma-delta are innate immune receptor

41
Q

What does gene rearrangement produce?

A

Sequence variability in the variable regions

42
Q

Which produces more diversity, alpha-beta chains or gamma-delta chains?

A

Alpha-beta

43
Q

What is different about gamma-delta chains compared to alpha-beta?

A

Do nor require antigen processing and MHC presentation of peptide epitopes
Express restricted TCR variability
CD4 and CD8 are not commonly expressed
Rarely contribute to functional memory

44
Q

Where are gamma-delta cells well represented?

A

Peripheral blood mononuclear cells

45
Q

Where are gamma-delta cells rarely found?

A

Lymph node parenchyma
Spleen
Peyer’s patches
Thymus

46
Q

What percentage of CD3 cells are TCR gamma-delta?

A

70%

47
Q

What is the diversity of the TCR V region generated by?

A

Gene recombination and combinatorial association in all species examined to date

48
Q

What percentage of blood lymphocytes in humans have gamma-delta TCRs? In ruminants?

A

5-15%

60%

49
Q

Where is the subset of TCRs with more limited receptor diversity found? What kind of role does it have?

A

In the epidermis of the skin and genital tract

Anti-inflammatory and wound healing role

50
Q

Where is the subset of TCRs with higher receptor diversity found? What does it do?

A

Secondary lymphoid organs and gut mucosa

Binds to a diverse array of antigens and forms 2 populations, cytokine/chemokine producing and cytotoxic

51
Q

In immature ruminants and pigs, which T cells are the major circulating population?

A

Gamma-delta

52
Q

Do gamma-delta receptors have MHC restriction? What does this mean?

A

No

They can perform without MHC

Immunology - DVM year 1 (35 decks)

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