Lecture 12: Differentiation and Functions of CD4+ T Cells Flashcards
What is one of the most prominent T cells changes that occurs with age
Loss of CD28 expression and progressive accumulation of CD28- Tem cells, mainly in the CD8+ T cell population
T cells with reduced CD28 expression are characterized by
Decreased proliferative capacity
Shortened telomeres
Reduced TCR repertoire
Enhanced cytotoxic activity
Th1 cells activate which response and secrete what
Cell mediated immunity
IFN-y
Intracellular microbes
Th2 cells activate which response and secrete what
Ab mediated
IL-4, 5, 13
Helminthic parasites
Th17 cells activate which response and secrete what
Inflammation and anti-bacterial
IL-17a/f, IL-22
Extracellular bacteria/fungi
Tfh cells function
Follicular helper T cells
Remain in LN and help B cells
Th1 cell immune reaction
Macrophage activation
IgG production
Th2 cell immune reaction
Mast cell/eosinophil activation
IgE production
Alternative macrophage activation
Th17 cell immune reaction
Neutrophilic, monocytic inflammation
IL-2 principal action
T cell proliferation
Regulatory T cell survival
IFN-y principal action
Activation of macrophages
IL-4 principal action
B cell switching to IgE
IL-5 principal action
Activation of eosinophils
IL-17 principal action
Stimulation of acute inflammation
IL-22 principal action
Maintenance of epithelial barrier function
TGF-b principal action
Inhibition of T cell activation
Differentiation of regulatory T cells (Treg)
Development of Th1 cells
DCs/Macrophages produce IL-12 which activates STAT4 and T-bet
NK cells release IFN-y which activates STAT1
Together these stimulate the differentiation of naïve CD4+ T cells into the Th1 subset
Th1 cells release IFN-y which
Inhibits the development of Th2 and Th17 cells
Development of Th2 cells
IL-4 produced by Mast cells/eosinophils activates transcriptions factors GATA-3 and STAT6 which stimulate differentiation of naïve CD4+ into Th2
-IL-4 produced by Th2 cells amplifies this response by inhibiting development of Th1/Th17 cells
Development of Th17 cells
IL-1, -6 and TGF-b activate RORyt and STAT3 which stimulate differentiation of Th17
In turn, IL-21 induced by RORyt and STAT3 amplify generation of Th17 cells in autocrine regulatory manner
IL-23 is very important for ACTIVATION of Th17 cells
IL-17 is produced by and does what
Th17 cells
Protects from EC pathogens and is involved in tissue inflammation and autoimmunity
Type of selection resulting from low/medium/high avidity to self antigen
Low- Positive selection
Medium- Treg cell selection
High- Negative selection
What is required for survival of Treg cells
FOXP3
CD40L gene is located on which chromosome
X chromosome
Activation of classical macrophage by Th1 cells induces macrophage to secrete
TNF, IL-1,- stimulate leukocyte recruitment
IL-12- stimulates Th1 differentiation, IFN-y production
Th2 cells secrete what to activate alternative macrophages
IL-4, IL-13
Th2 cells secrete what to active eosinophils and B cells
Eosinophils- IL-5
B-cells- IL-4
Alternative macrophage function
Anti-inflammatory effects, wound repair, fibrosis
Normal vs inflammatory ratio of IL-17/IL-22
Inflammatory: High ratio of IL-17/IL-22
Normal: Low ratio of IL-17/IL-22
CTL differentiation without helper T cells
CD8+ T cells recognize antigen + costimulators on professional APCs (suboptimal response)
y/d T cells can typically be found, they recognize what
On epithelial surfaces
Conserved, Non-peptide antigens
Pre activated status of y/d T cells
Upregulation of memory markers early in their development.
Allows rapid induction of effector functions following detection of tissue stress
Physiological roles of y/d T cells
Protective immunity against EX/IC pathogens
Tumor surveillance
Modulation of innate/adaptive immune responses
Tissue healing and epithelial cell maintenance
Regulation of physiological organ function
y/d TCRs are generated through
Somatic rearrangement of VDJ gene segments
y/d T cells can recognize
MHC-related and unrelated TCR ligands
MHC I polypeptide related sequence A (MICA) which engages NKG2D
DAMPS/PAMPS recognized by TLRs or Dectin-1
Dectin-1
PRR that plays important role in antifungal innate immunity
Specific receptor for beta-glucans (found in fungi)
Nontraditional y/d T cells have and are found where
y/d TCRs and (identical with a/b T cells)-CD3
Intestine, uterus, tongue
y/d cells may be considered component of adaptive immunity because
Rearrangement of TCR genes occurs to produce diversity, however, they are much less diverse than a/b TCRs
y/d cells may be considered part of innate immunity because
Restricted TCR may be used as a PRR
y/d TCRs recognize unpresented Ags
Several y/d T cell subsets have a memory phenotype
NKT cells are
T lineage cells that share functional characteristics with both T cells and NK cells
NKT cells make up how much of hepatic T cells in liver
30-50%
Following activation, NKT cells can immediately
Commence cytokine secretion without first having to differentiate into effector cells
NKT cells are early/late line of defense?
Very fist line of innate defense against some bacterial/viral infections
Cytokines secreted by NKT cells have powerful effect on
a/b T cell differentiation and functions, which links NKT cells to adaptive defense
NKT cell immunological memory
They do not develop memory
NKT cells recognize
Self and foreign lipids and glycolipids
Cytokines produced by NKT cells
IL-10 IL-4 IFN-y TGF-b Th1/Th2 cytokines
Dysfunction or deficiency of NKT lead to
Autoimmunity
Cancers
Asthma progression
TCR on NKT cell recognizes what on DC
CD1d on APC presents lipid/glycolipid antigen
iNKT indirect activation with APC
Recognition of Ag on CD1d of APC will cause release of IL-12 from APC and subsequent release of IFN-y from NKT which will activate NK cells
iNKT indirect activation with immunosuppressive TAM
Recognition of Ag on CD1d of TAM will stimulate killing of the TAM leading to less immunosuppressive environment where tumor infiltrating NK cells can better perform
