First Aid, Chapter 1 Immune mechanisms: T-cell receptors and signaling Flashcards

1
Q

Briefly outline the steps the T-lymphocyte takes from bone marrow to blood and lymph? What do they do in the lymph?

A

1) T-lymphocyte progenitors arise in the bone morrow and travel to the thymus as double-negative (CD4– and CD8–) and CD3+ cells.
2) Once in the thymus, they are educated and screened for reactivity
3) Then single-positive CD4+ or CD8+ T lymphocytes enter the blood and lymph system as naïve T lymphocytes.
4) Naïve T lymphocytes recirculate through the lymph nodes looking for their unique protein antigen as displayed in the context of an HLA molecule, class I for CD8+ T cells and HLA class II for CD4+ T cells.

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2
Q

What does a TCR-antigen HLA complex need to become activated?

A

A second signal or costimulation.

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3
Q

What is the most important cytokine produced during T lymphocyte activation?

A

The survival signal is provided by IL-2 and its receptor CD25.

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4
Q

What does IL-2 stimulate once the T-lymphocyte is activated?

A

Clonal proliferation. This preserves the specificity of the T lymphocyte for its particular antigen.

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5
Q

What do T lymphocytes become after they are activated?

A

Effector or memory T lymphocytes. CD4 effector cells induce differentiation of the T lymphocyte response to Th1, Th2, Treg, and Th17. The CD8 cells become cytolytic.

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6
Q

1) What costimulators does CD 28 interact with?
2) Is the expression constitutive or inducible? 3) What is the effect of the interaction?
4) Where is CD 28 located?
5) Where are the costimulators located?

A

1) B7-1 (CD 80), B7-2 (CD 86), 2) constitutive,
3) Activation of naïve cells Induction of CD40L, OX40, CXR5, ICOS, CTLA-4
4) T cell
5) APC DC/Mø/B cells

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7
Q

1) What costimulators does CTLA4 (CD152) interact with?
2) Is CTLA4 stimulatory or inhibitory? How?
3) Is it constitutive or inducible?
4) And what is the effect?
5) Where CTLA4 (CD152) located?
6) Where are the costimulators located?

A

1) B7-1 (CD 80), B7-2 (CD 86), 2) inhibitory through ITIM,
3) inducible
4) T-lymphocyte tolerance Th1 development
5) T cell
6) APC DC/Mø/B cells

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8
Q

1) What costimulators does ICOS interact with?
2) Is it constitutive or inducible?
3) And what is the effect?
4) Where is ICOS located?
5) Where is the costimulator located?

A

1) ICOS-L
2) inducible
3) Costimulation of effector T lymphocytes, implicated in Ab class switching
4) T cell
5) APC DC/Mø/B cells

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9
Q

1) What costimulators does CD40L interact with?
2) Is it constitutive or inducible?
3) And what is the effect?
4) Where is CD40L located?
5) Where is the costimulator located?

A

1) CD40
2) Inducible
3) APC activation, germinal center development, class switching
4) T cell
5) APC DC/Mø/B cells

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10
Q

1) What costimulators does PD-1 interact with?
2) Is it inhibitory or stimulatory? how?
3) Is it constitutive or inducible?
4) And what is the effect?
5) Where is PD-1 located?
6) Where is the costimulator located?

A

1) PD-L1/PD-L2
2) inhibitory through ITIM
3) T, B, myeloid cells/inducible
4) Negative regulation, cell death
5) T cell
6) APC DC/Mø/B cells

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11
Q

What two forms does the TCR come in?

A

αβ and γδ

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12
Q

Do αβ TCRs have higher or lower affinity than antibodies?

A

lower affinity

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13
Q

Do αβ TCRs have a signalling receptor attached?

A

No, they need accessory molecules to signal

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14
Q

What is the structure of the αβ TCR?

A

It is a heterodimer of an α and β chain, each with two Ig-like domains

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15
Q

What are the domains of the of the chains of the αβ TCR?

A

One is the variable domain, antigen contact, and HLA contact. The second Ig-like domain is the constant domain.

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16
Q

What is the binding site for superantigen?

A

The particular variable β or Vβ region of the TCR is the binding site for superantigen.

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17
Q

Describe the structure of the chains of the αβ TCR.

A

Both chains have an extracellular region, constant region, transmembrane region, and a short cytoplasmic tail with no signaling molecules

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18
Q

What is the site of recognition of the peptide-HLA complex on the αβ TCR?

A

The CDRs.

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19
Q

What does CD3 deficiency produce?

A

SCID

20
Q

What does the TCR complex consist of?

A

TCR, CD3 and two zeta (ξ) chains, and CD4 or CD8.

21
Q

What are ITAMs? Where are they located?

A

The accessory molecules contain immunoreceptor tyrosine-based activation motifs (ITAMs), which are required for signal transduction.

22
Q

How do αβ TCRs recognize antigen?

A

αβ TCRs recognize a single antigen only in the context of an HLA molecule. The receptor has no signaling ability and requires accessory molecules for signal transduction.

23
Q

How are the αβ TCR chains analagous to the immunoglobulin Fab fragment?

A

These molecules undergo recombination for their diversity. Both chains have complementaritydetermining regions (CDRs), and like in an immunoglobulin, the αβ CDR3 region of the TCR imparts the most significant sequence variability.
Flash

24
Q

Mutations in SLAM-associated protein (SAP) cause which disease?

A

X-linked lymphoproliferative syndrome XLPS

25
Q

What enzyme does CD40 ligand: CD40 stimulate? What is this crucial for?

A

It stimulates activation induced cytosine deaminase (AID), which is crucial for somatic mutation and isotype switching.

26
Q

How do NKT cells recognize lipids?

A

In the context of CD1.

27
Q

What disease is ZAP-70 deficiency associated with? And what cells are present and what cells are deficient?

A

ZAP-70 deficiency is a SCID with no CD8 cells and no T-lymphocyte function, but normal B lymphocytes and NK cells.

28
Q

What molecules are required for signal transduction for γδ T lymphocytes?

A

CD3 and the ζ chain

29
Q

Do γδ T lymphocytes have CD4 or CD8?

A

No, most do not. They are not HLA restricted.

30
Q

Do γδ T lymphocytes require antigens to be processed?

A

No, some antigens do not need to be processed.

31
Q

How are some antigens presented to γδ T lymphocytes?

A

In MHC-like class I molecules.

32
Q

What type of T lymphocytes are thought to be a bridge between innate and acquired immunity?

A

γδ T lymphocytes

33
Q

What molecule does CD4 and CD8 signal through? How is this molecule bound to CD4 and CD8? What is it required for?

A

Lck, which is a Src family tyrosine kinase. It is noncovalently associated with CD4 and CD8 and required for T-lymphocyte activation and maturation.

34
Q

What costimulation interactions are required for activation, survival, and stability of the TCR immune synapse?

A

The interaction between CD28 and both CD80 and 86, CD2 and CD58, and a signaling lymphocytic activation molecule (SLAM)

35
Q

1) What is SLAM?
2) What type of motif does SLAM have?
3) What does SLAM bind? and what does that do?

A

1) Signaling lymphocytic activation molecule (SLAM).
2) immunoreceptor tyrosine switch motif (ITSM).
3) SLAM binds to SLAM-associated protein (SAP), which links SLAM to Fyn.

36
Q

What is Fyn?

A

Fyn is a Src family kinase. It is noncovalently associated with CD3.

37
Q

1) What is ZAP-70?

2) How many domains does it have? What does it bind? What does that result in?

A

1) Syk family kinase.

2) It has two Src homology domains (SH), where ZAP-70 binds to the P on the ξ chain, which results in docking.

38
Q

What does LAT phosphorylation do?

A

LAT phosphorylation recruits adapter proteins that mediate different signaling pathways.

39
Q

What is Sos?

A

GDP/GTP exchanger

40
Q

What is ERK? What does it activate?

A

ERK is one of the MAP kinases which activates the transcription factor activation protein 1 (AP-1).

41
Q

Where is CRAC located?

A

On the cell membrane.

42
Q

What is calmodulin?

A

Calmodulin is an ubiquitous, calcium-dependent regulatory protein that binds calcium and interacts with calcineurin.

43
Q

What is calcineurin?

A

Calcineurin is an activator of nuclear factor of activated T lymphocytes (NFAT) by dephosphorylation, allowing it to travel to the nucleus.

44
Q

What is NFAT?

A

NFAT is an antigen-activated transcription factor for cytokines including IL2, IL4, and TNF.

45
Q

What is Rac-GTP?

A

Rac-GTP is another molecule activated by another GDP/GTP exchanger that activates JNK to phosphorylate Jun, which also turns on AP-1

46
Q

Immunosuppressant cyclosporine binds to which molecule in T-cell signaling pathway?

A

Cyclosporin bind to proteins called immunophilins. Then drug protein complex inhibits calcineurin and therefore NFAT translocation to the nucleus.