Lecture 13 Ch. 10 Flashcards
Specific T cells are made by the immune system “____”
On demand
Approximately 1 in 10^__ T cells has a specific TCR that can recognize a given pathogen.
6
The T cell whose TCR recognizes a given invader does what?
becomes mobilized and activated
Over __-__% of T cells in the circulation have αβ TCRs
90-95
The α/β TCRs recognize (bind to) peptides presented within what?
The MHC molecules and the MHC itself
α/β TCRs also express either ____ or ____ co-receptors.
CD4 or CD8
Ag recognition involves what?
clustering of TCRs
Activation of T cells is initiated by what?
A signaling cascade after TCRs (at least two) recognize specific Ag.
The α and β chains have only a very short _____ _____.
Intracellular domain
Signaling is mediated by other proteins comprising _____ _____.
TCR complex
What have cytoplasmic tail that is long enough to signal?
CD3 proteins γ, δ, ε, and ζ
What is needed to activate a T cell?
TCR, CD4 or CD8, and CD3
CD3 is a marker for counting total numbers of what?
T cells (CD4+ CD8 T cells)
Langerhans’ cells are immature DCs which do not express what?
High levels of B7
Activated DC can “interview” how many naive T cells per hour?
500
Langerhans’ cells enter the lymph node to become what?
Dendritic cells expressing B7
B7-positive dentritic cells stimulate what?
Naive T cells
When the TCR is engaged and activated T cell, what must happen to the T cell?
T cell must receive a co-stimulatory signal
What co-stimulatory molecules are expressed on professional APC?
B7 proteins (CD80/CD86)
B7 molecules plug into what?
CD28 receptor expressed on T cells
Co-stimulation can be considered as what?
an amplifier that improves the signal
With co-stimulation, ~_____-____ fewer of clustered TCRs are needed for activation
100-fold
After activation is completed, what happens to the T helper cell and APC?
They are separated.
After APC activates a T cell it goes on to do what?
Activate other T cells
T cell proliferate in order to do what?
increase their numbers
The proliferation of T cells is driven by what?
IL-2, also called “T cell growth factor”
What do naive T cells not have expressed on their surface?
IL-2 receptor (IL-2R)
Activated T cells produce large amounts of what and express what?
IL-2 and express IL-2R
What does IL-2 enhance?
Resistance of activated T cells to apoptosis
Th1, Th2 and Th17 cells are all ….
CD4-positive helper cells
True or false?
Activated T cell produce cytokines randomly?
False, they do not produce cytokines randomly
Each subset of T helper cells tend to produce a set of what?
Particular cytokines
What is a Th0 cell?
An immature effector T cell that has undergone proliferation
What are the outcomes of Th0 cell activation ?
The generation of various T helper subsets: Th1, Th2 and Th17
What do Th1 cells activate?
A cell-mediated immune response
Macrophage activation and killing of phagocytosed microbes
What do Th2 cells activate?
An Ab-mediated immune response - humoral
Antibody secretion; neutralization and elimination of antigen
What are Th17 cells involved in?
In inflammation and anti-bacterial response
Tho cell activation resulting in T help subsets is a process called what?
Differentiation or commitment of T helper cells
What is an important bridge between innate and adaptive immunity?
Pathogen recognition by immature DCs through PRRs
PRR-signaling causes activation and maturation of what?
Antigen-presenting cell (APC)
APC processed antigen is presented to what cells?
Naive Th0 cells
Secreted IL-12 assist the development and differentiation of what cells?
Th1 cell
TLR1, 2, and 6 recognize what ligand?
Gram-positive LPS
TLR3, recognizes what ligand?
dsRNA
TLR4 recognizes what ligand?
Gram-negative LPS
TLR5 recognizes what ligand?
Flagellin
TLR9 recognizes what ligand?
Unmethylated CpG DNA
Describe the development of Th1 cells
DCs and Mo produce IL-12
NK cells produce IFN-γ
These activate transcription factors T-bet, STAT1, and STAT4
The TFs stimulate the differentiation of naive CD4+ T cells to the Th1 subset
What amplifies the Th1 response and inhibits the development of Th2 and Th17 cells?
IFN-γ produced by Th1 cells
Describe the development of Th2 cells
IL-4 is produced by activated T cells themselves or by mast cells
Eosinophils and IL-4 activate the TFs GATA-3 and STAT6
TFs stimulate the differentiation of naive CD4+ T cells to the Th2 subset
What amplifies the Th2 response and inhibits the development of Th1 and Th17 cells?
IL-4 produced by Th2 cells
note, Th2 cells produce IL-4, 5, and 13
What activates the TFs that stimulate the differentiation of Th17 subset?
IL-1, IL-6 and IL-23
What TFs are activated in the development of the Th17 cell?
RORγt and STAT3
What is the most important cytokine in the differentiation of the Th17 cells?
IL-23
What may promote Th17 respnoses by suppressing Th1 and Th2 cells, both of which inhibit Th17 differentiation?
TGF-β
What amplifies the Th17 response?
IL-21 produced by the Th17 cells
note, they also produce Il-17 and 22
What is the Biologic action of T cell cytokine IL-2?
T cell growth stimulation
What is the Biologic action of T cell cytokine IL-4?
B cell switching to IgE
What is the Biologic action of T cell cytokine IL-5?
Activation of eosinophils
What is the Biologic action of T cell cytokine IFN-γ?
Activation of macrophages
What is the Biologic action of T cell cytokine TGF-β?
Inhibition of T cell activation
What is the Biologic action of T cell cytokine IL-17?
Protection from extracellular pathogens.
Inflammation and autoimmunity
What do Naive CD4+ Th0 cells recognize?
Peptides that are derived and presented to the cells by DCs in the LNs
Ag-activated effector CD4+ T cells enter what?
The circulation and migrate to the site of Ag
Effector T cells migrate through blood vessels in what?
Peripheral tissues
In the tissue, effector T cells recognize what?
The Ag and respond by secreting cytokines
What do cytokines released by effector T cells do?
Recruit more leukocytes and activate phagocytes to eradicate the infection
What cytokines have a role in leukocyte recruitment (inflammation)?
TNF, IL-1
What do Tfh cells do?
Activate B cells
IL-4 and IL-13 produced by Th2 cells have what role?
Intestinal mucus secretion and peristalsis
If there is a presence of helminths in the body, how do Th2 cells respond?
Produce IL-5 to activate eosinophil
Produce IL-4 and IL-13 for mucus secretion and peristalsis
IL-4 activates B cells to produce antibodies and then mast cell degranulation
What cytokines classically activate macrophages?
Microbial TLR-ligands and IFN-γ
What cytokines alternatively activate macrophages?
IL-13 and IL-4
Classically activated macrophages go on to do what?
Have microbicidal actions: phagocytosis and killingo f many bacteria and fungi (ROS, NO, Lysosomal enzym) And inflammation (IL-1,12, 23)
Alternatively activated macrophages go on to do what?
Anti-inflammatory effects
Wound repair, fibrosis
Inhibit inflammation produced by classic macrophage
IL-17 produced by Th17 goes on to do what?
To aid in inflammation and neutrophil response (chemokines, TNF, IL-1, IL-6, CSFs)
And antimicrobial peptides
IL-22 produced by Th17 cells go on to do what?
Increase barrier function and anti-microbial peptides
What are CD8+ T cells activated by?
Dendritic cells loaded with Ags in the LNs
*Exactly like CD4+ T cells
What do CTLs recognize?
Class I MHC-associated peptides
Activated CD8+ cells proliferate and then…
Leave the LN
CD8+ T cells are activated by mechanisms that involve what?
Cross-presentation of antigens to CD8+ T cells
Cells infected with intracellular microbes, such as viruses, are ingested by what?
DCs
Extracellular Ags are processed and presented within what MHC class?
Class II - this is the classical way
Extracellular Ags are processed and are also presented in association with class I MHC. How??
The mechanism called Ag cross-presentation-some viral Ags are released from phagosome in cytoplasm of DC and then presented within class I MHC
The same cross-presenting APC may display microbial peptides within what MHC class?
Class II MHC for CD4+ T cells
Which cells present Class II MHC?
Professional APCs
CD4+ T cells that recognize a DC with cross-presenting APC have what role?
A role in activation of CTLs
They produce cytokines that stimulate CTL differentiation
And they enhance the ability of APCs to stimulate CTL differentiation
CTLs are activated to release what?
(Exocytose) their granule contents
What do CTL granule contents include?
perforin and granzyme
What is induced in the target cells of CTLs?
Apoptosis
What do CD8+ T cells secrete to activate Mo?
IFN-γ
Nontraditional T cells have what?
γδ TCRs and CD3
Most γδ T cells do not express what?
CD4 or CD8 co-receptors
Nontraditional T cells are abundant where?
The intestine, uterus, and the tongue
It is not known whether γδ T cells are “educated” in the …..
Thymus
The functions of γδ T cells are:
The first line of defense
Regulatory cell
Bridging between innate and adaptive responses
γδ T cells may be considered a component of what immunity?
Adaptive
What produces junctional diversity in γδ T cells?
Rearrangement of TCR genes
In γδ T cells, there is a development of a ______ phenotype
memory
Various subsets of γδ T cells may also be considered part of what immunity?
Innate
A restricted TCR may be used as what?
A pattern recognition receptor
True or False?
The γδ TCRs are much less diverse than αβ TCRs
True
The γδ TCRs recognize what?
Unpresented Ags
*Their mission is still to be understood
It has been postulated that γδ T cells kill cells that have become what?
Stressed as the result of a microbial infection
NKT cells should not be confused with what?
Natural killer NK cells
Natural killer T cells are a ________ group of T cells
Heterogeneous
The heterogeneous group of NKT cells share what?
Properties and CD markers of both T cells and NK cells
What do NKT cells recognize?
Self and foreign lipids and glycolipids
Lipids and glycolipids should be presented within what?
Non-polymorphic CD1d molecule - Ag presenting complex like MHC
NKT cells constitute only ______ of all peripheral blood T cells.
0.2%
Activated NKT cells produce large quantities of what?
IFN-γ, IL-4 and GM-CSF (granulocyte-macrophage colony-stimulating factor), as well as other cytokines and chemokines
NKT cells ____ release cytokines
rapidly
NKT cells can do what to different immune responses?
Promote or suppress
Dysfunction or dificiency of NKT leads to what?
Autoimmunity (diabetes or atherosclerosis)
Cancers
Progression of asthma
