First Aid, Chapter 1 Immune mechanisms: T-cell receptors and signaling Flashcards
Briefly outline the steps the T-lymphocyte takes from bone marrow to blood and lymph? What do they do in the lymph?
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.
What does a TCR-antigen HLA complex need to become activated?
A second signal or costimulation.
What is the most important cytokine produced during T lymphocyte activation?
The survival signal is provided by IL-2 and its receptor CD25.
What does IL-2 stimulate once the T-lymphocyte is activated?
Clonal proliferation. This preserves the specificity of the T lymphocyte for its particular antigen.
What do T lymphocytes become after they are activated?
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.
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?
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
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?
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
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?
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
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?
1) CD40
2) Inducible
3) APC activation, germinal center development, class switching
4) T cell
5) APC DC/Mø/B cells
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?
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
What two forms does the TCR come in?
αβ and γδ
Do αβ TCRs have higher or lower affinity than antibodies?
lower affinity
Do αβ TCRs have a signalling receptor attached?
No, they need accessory molecules to signal
What is the structure of the αβ TCR?
It is a heterodimer of an α and β chain, each with two Ig-like domains
What are the domains of the of the chains of the αβ TCR?
One is the variable domain, antigen contact, and HLA contact. The second Ig-like domain is the constant domain.
What is the binding site for superantigen?
The particular variable β or Vβ region of the TCR is the binding site for superantigen.
Describe the structure of the chains of the αβ TCR.
Both chains have an extracellular region, constant region, transmembrane region, and a short cytoplasmic tail with no signaling molecules
What is the site of recognition of the peptide-HLA complex on the αβ TCR?
The CDRs.
