"Microbiology/Immunology T Cell Development" MARY Flashcards Preview

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Flashcards in "Microbiology/Immunology T Cell Development" MARY Deck (33)
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1
Q

The _____ is the major site of T-cell development.

A

Thymus

2
Q

When we say that T-cells become lineage committed in the thymus, what does this mean?

A

CD4 and CD8

3
Q

T/F: Each of us has a unique, self-restricted TCR repertoire.

A

True.

4
Q

T-cells are tolerized to what in the thymus during T-cell development?

A

Self antigen

5
Q

Explain the concept of MHC restriction.

A

A few things:

  1. HLA is another way of saying MHC
  2. MHC I is recognized by all nucleated cells.
  3. MHC II are only on APCs.
  4. The TCR must recognize both the antigen (peptide) AND the MHC complex
6
Q

T/F: CD4 and CD8 lineage T-cells recognize different MHC molecules.

A

True. CD8 binds to the alpha-3 domain of MHC I. CD4 binds to the beta-2 domain of MHC II.

7
Q

T/F: TCR development involves gene rearrangements.

A

True

8
Q

DiGeorge syndrome involves what deficiency?

A

Human T-cell immunodeficiency

9
Q

What is a “nude” mouse”

A

Lacks hair AND thymic epithelial cell differentiation bc of loss of transcription factor. Can use to study T-cell immunodeficiency.

10
Q

What forms the thymus in embryonic/fetal development?

A

3rd pair of pharyngeal puch (endoderm) and cleft (ectoderm). 1st hematopoietic precursors are planted in the thymus at 8 weeks gestation. Thymus produces chemotactic factors that attract T-cell precursors.

11
Q

B-cells are born in the bone marrow and grow in the thymus. Presuming they make it out of the thymus, what are their next destinations?

A

Secondary lymphoid tissue, ie GI tract, spleen, lymph nodes.

12
Q

T-cell precursors are also known as:

A

Prothymocytes

13
Q

How do prothymocytes enter and leave the thymus?

A

Enter through the corticomedullary junction, exit through the medulla venules. **Migration is influenced by chemokines and sphingosine 1-phosphate receptors

14
Q

How does flow cytometry use “single cell” technique?

A

A graph plots each cell as a dot, and the clusters represent common populations of cells, for example the graph on page 321. Know how to read these!!

15
Q

T-cells early in development are:

(a) double negative
(b) double positive
(c) single positive

A

(a) double negative, using cell surface markers to identify stage

16
Q

CD2 receptor, found in double negative early T-cells, is for what function?

A

Cell signaling and adhesion

17
Q

Give the steps in lineage commitment, starting with the CD2 + “double negative” (-CD4/-CD8) cells.

A
  1. Cell becomes gamma-delta and leaves thymus (function unknown) OR becomes alpha-beta, the typical T-cell.
  2. If becoming an alpha-beta cell, cell undergoes beta, gamma delta rearrangements and becomes double positive (+CD4/+CD8) - pre-TCR assembly -
    2b. Cell tests beta chain (first checkpoint).
  3. Cell can “short circuit” and still become gamma-delta cell, or can undergo alpha, gamma, delta rearrangements.
  4. If successful, alpha part is done and cell is a committed alpha-beta cell.
18
Q

What is the main reason why most genetic rearrangements in T-cell development fail?

A

Reading frame issues

19
Q

How does a pre-TCR “test” its beta chain?

A

Goes to the surface with a helper molecule because it will not go alone (heterodimer –> superdimer –> pre-T-cell receptor)

20
Q

How many attempts can be made to achieve a productive rearrangement of the beta chain locus? How this different from alpha chain building?

A

Two beta chain attempts. Alpha has more chances because it can try further and further upstream regions, and has 3 or more chances to produce a functional alpha chain.

21
Q

During the alpha chain rearrangements in T-cell receptor development, what region is not used?

A

D region. Once this chain is removed, the piece must become an alpha chain.

22
Q

During what stages of TCR development can RAG-1 and RAG-2 be identified?

A

During the rearrangements of beta and alpha chains.

23
Q

When does a developing T-cell become double positive?

A

At the end of successful beta and alpha chain creation.

24
Q

In what section of the thymus do progenitor cells proliferate?

A

Medulla

*Cells go back into medulla once they are SP committed to test their MHC interactions before leaving the thymus.

25
Q

In what section of the thymus to T-cells commit to being T-cells and undergo beta and alpha chain creation?

A

Cortex

26
Q

What cells are responsible for selecting alpha-beta T-cells in the thymus, once they are DP? How do they test for this?

A

Cortical epithelial cells, by their MHC binding (moderate and strong binding proceed, weak or no binding apoptose)

27
Q

How does positive selection for a single lineage occur?

A

Whichever MHC class on the thymic epithelial cells fits better, CD4 (MHC II) or CD8 (MHC I). Then the T-cell will go on to become an exclusive lineage (single positive thymocyte).

28
Q

What cells are involved in negative selection of T-cells in the thymus? What is going on?

A

Dendritic cells, macrophages, and others. Moderate MHC binding is good - T-cell lives, tight binding is bad, T-cell dies. This is to protect against autoimmunity.

29
Q

T/F: Presentation os self-peptides from hematopoietic cells plays little role in shaping T-cell repertoire.

A

FALSE. This is a very important step to protect against T-cells reacting with self cells.

30
Q

What transcription factor is present in the thymic medulla and helps to protect against autoimmunity, for example, peripheral tissue specific antigens such as insulin?

A

The autoimmune regulator (AIRE) is a protein that in humans is encoded by the AIRE gene. AIRE is a transcription factor expressed in the medulla of the thymus and controls the mechanism that prevents the immune system from attacking the body itself.

31
Q

What is the difference between avidity and affinity?

A

Avidity refers to the accumulated strength of multiple affinities of individual non-covalent binding interactions, such as between a protein receptor and its ligand, and is commonly referred to as functional affinity.

32
Q

What is the avidity model of T-cell selection?

A

The final determination of T-cell survival, whereby T-cells that bind moderately to self-MHC peptides are selected for final maturation.

33
Q

What are regulatory T-cells?

A

A special type of CD4 cells involved in moderating other T-cells and promoting tissue tolerance to self antigen.

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