chapter 10 Flashcards
T cells require _______________as a first signal.
antigen presentation
Once activated, T cells differentiate into their ____________________forms.
effector
Successful T cell–APC interactions organize signaling molecules into an ____________________, which consists of TCR/MHC-peptide complexes and adhesion molecules/bound ligands.
immunological synapse
additional signal that is required to induce proliferation of antigen-primed T cells and is generated by interaction of CD28 on T cells with CD80/86 on antigen-presenting cells
costimulatory signal
What is required for optimal T-cell activation and proliferation?
costimulatory signals
costimulatory signal 1:
antigen-specific TCR engagement
costimulatory signal 2:
contact with costimulatory ligands
costimulatory signal 3:
cytokines directing T-cell differentiation into distinct effector cell types
function of positive costimulatory receptors?
facilitate activation
-examples are CD28 ICOS
function of negative costimulatory receptors?
help turn activation off
-examples are CTLA-4, PD-1, and BTLA
describe CD28 and its functions:
-Generally involved in initial activation events in T cells
* 44 kDa glycoprotein homodimer expressed on majority of T cells
* Markedly enhances TCR-induced proliferation and survival
* Binds to B7-1 and B7-2 expressed by APCs
describe ICOS and its functions:
-expressed on memory and effector T cells
-inducible costimulator, binds ICOS-ligand on activated APCs
-may help to maintain activity of already differentiated cells
describe CTLA-4 and its functions:
-Induced within 24 hours after activation, peaks 2–3 days post-stimulation
- Binds to B7-1/B7-2 with higher affinity than CD28 but shuts down signaling pathways (“putting the brakes on”)
What does PD-1 stand for?
program death 1
what does BTLA stand for?
B- and T-lymphocyte attenuator
may help to mediate T-cell tolerance in nonlymphoid tissues
PD-1
may downregulate inflammatory and autoimmune responses
BTLA
-a physiological state in which cells are unable to be activated by antigen
-results if a costimulatory signal is absent
-helps provide tolerance
-if only signal 1 is received, the cell is rendered nonresponsive
clonal anergy
Which signal do cytokines provide?
signal 3
describe how IL-2 is an example of an autocrine type of cytokine response system:
-T cells produce the cytokine and receptor for it
-binding of this ligand induces a very strong proliferation signal during activation stages
what type of characteristic costimulatory properties do APC cells have?
they provide the right signals to activate T cells
Viral/bacterial proteins that bind to specific Vβ regions of TCRs and α chain of class II MHC molecules
superantigen
superantigens non-specifically, effectively “short-circuits” TCR and MHC-peptide, which produces what?
dramatic cytokine secretion by large proportion
of inappropriately activated T cells
Initial activation signals 1 and 2 induce:
-upregulation of prosurvival genes
-transcription of IL-2 and IL-2R genes
-outcome is activation and proliferation
Differentiation of T helper cell subsets is regulated
by_______________________
polarizing cytokines
Factors that are added to a vaccine mixture to enhance
the immune response to antigen by activating innate immune cells
adjuvants
What are the functions of TH1?
-enhances APC activity
-enhances Tc activation
-protects against intracellular pathogens
-involved in delayed type hypersensitivity, autoimmunity
What are the functions of TH2?
-protects against extracellular pathogens
-involved in allergy
What are the functions of TH9?
-protects against extracellular pathogens
-involved in mucosal autoimmunity
What are the functions of TH17?
-protects against fungal and extracellular bacterial infections
-contributes to inflammation, autoimmunity
What are the functions of TH22?
-protects against extracellular pathogens
-involved in inflammatory skin disease
What are the functions of Treg?
-inhibits inflammation
-inhibits antitumor responses
What are the functions of TFH?
B cell help in follicles and germinal centers
TH1 regulate immunity to ________________________.
intracellular bacteria and viruses
TH2 regulate immunity to _____________.
worms
TH17 regulate immunity to_______________________.
extracellular bacteria and fungi
TREG are inhibitory in terminating ___________________ and inhibiting
_________________________
immune responses
autoimmunity
What type of immunity is regulated by TFH?
humoral
-Polarizing cytokines: IL-12, IL-18, and IFN-γ induce TH1
differentiation
-Master gene regulator: T-bet
-Effector cytokines: strong IFN-γ production
» Leads to class switching to IgG classes
» Supports differentiation of antiviral CD8+ killer T cells
Differentiation and function of TH1 cells
-Polarizing cytokines: IL-4 induce TH2 differentiation
-Master gene regulator: GATA3
-Effector cytokines: IL-4, IL-5, and IL-13 production
» IL-4 acts to promote activities of eosinophils against worms
» IL-4 induces class switching to IgE
Differentiation and function of TH2 cells
describe how cytokines achieve cross regulation:
– IFN-γ (Th1) inhibits IgG1/IgE class switching (Th2)
– IL-4 (Th2) inhibits production of IgG2a (Th1)
– IL-10 (Th2) inhibits TH1 responses from APCs
describe how master regulators commit T cells to one subset and against
the other:
– T-Bet (Th1) suppresses TH2 pathway gene expression
– GATA3 (Th2) suppresses TH1 pathway gene expression
-Polarizing cytokines: IL-6 and TGF-β
-IL-23 also plays a role in finalizing the subset commitment
* Master gene regulator: RORγt
* Effector cytokines: IL-17A, IL-17F, and IL-22
– IL-17A produced is associated with chronic inflammatory and
autoimmune responses
– IL-17F and IL-22 produced may play a role in warding off fungal and
extracellular bacterial infections
Differentiation and function of TH17 cells
-Polarizing cytokines: TGF-β
* Master gene regulator: FoxP3
* iTREG cells secrete IL-10 and TGF-β to downregulate inflammation
(by inhibiting APCs) and suppress other T- cell subsets
Differentiation and function of (induced) TREG cells
increases in response to activation signals
CD44
an adhesion protein
CD62L
a chemokine receptor
CCR7
Which of the following conditions would lead to T-cell anergy?
a. A naïve T-cell interaction with a dendritic cell in the presence of CTLA-4 Ig
b. A naïve T cell stimulated with antibodies that bind both the TCR and CD28
c. A naïve T cell stimulated with antibodies that bind only the TCR
d. A naïve T cell stimulated with antibodies that bind only CD28
a & c
