12: Differentiation and Fxn of Cd4+ Flashcards
how are T cells made
on demand
how many T cells have specific TCR for pathogen
1 in 10^6
TCR who recognize invader means they are
mobilized and activated
how many TCRs are a and B
90-95%
what do a and B TCRs recognize and bind
both peptides in MHC
where does activation of T cell occur
in LM
what are langerhans cells
immature DCs with low levels of B7
where do langerhans reside
skin epithelial
how many T cells can activated DCs interview
500 naive T cells per hour
most efficient APCs
mature, DCs
what is the evolution of DCs
immature Ag capturing to APC and T cell priming cells
what do DCs convert Ags into
immunogens
where do langerhans go after skin
lymphatic system
where do langerhans become DCs and what do they express
lymph nodes and express B7
what type of Ags are recognized by T cells
peptide/ protein Ags
where do activated CD4+ T cells go
enter circulation, remain in LN, migrate to follicles, help B cells make Abs
what happens for TCRs to have Ag recognition
they cluster
what initiates a signaling cascade
2 TCRs recognize an Ag
what do CD4 activate compared to CD8
4= T helper and 8=CTLs
marker for counting total number of T cells
CD3
co-stimulators can also be called
facilitators
how does costimulation alter TCR numbers
100x fewer TCRs needed for activation
what is the Role PI3 kinase in T cell activation
activate PIP3 for AKt and mTOR for increased protein synthesis
what causes clonal expansion of T cells
IL2 to IL2Ra for proliferation
what is the role of effector CD4+ cells
activate macrophages and B cells
what is the role of effector CD8+ cells
kill target cells and activate macrophages
what happens after Th cell activation
separates from APC so APC can bind other T cell
T cell growth factor
IL2
which cells do NOT have IL2R
naive T cells
how are IL2 growth factors
enhance activated T cell resistant to apoptosis
what happens in effector phase of T cell mediated immunity
effector T cells migrate to site of Ag
how do Effector T cells migrate
through blood vessels to peripheral tissue by binding cytokine activated endothelial cells due to infection in tissue
What is the role of CD4 T h cells
recruit and activate phagocytes to destroy microbes
role of CD8+ cytotoxic T lymphocytes
kill infected cells
what is different about the types of T helper cells
produce certain set of cytokines that determine cell phenotype
what is cytokine production from T helper cells called
differentiation or commitment
Th1 activates what type of immune response
cell-mediated
what type of immune response is activated by TH2
Ab mediated
TH 17 activate which immune response
inflammation and anti-bacterial
how do immature DCs recognize Pathogens
PRRS
what do PRRs provide for immunity
A bridge between innate and adaptive
What does PRR signaling cause
activation and maturation of APCs
what is another name for naive T helper cells
TH0
what cytokine produces T H1 cells
IL12
what is produced by TH1 cells
IL2 and IFNy
TLRs for gram+ and LPS
TLR 1,2,6
TLR for dsRNA
TLR3
TLR for Gram - LPS
TLR 4
TLR for flagellin
5
TLR for unmethylated CpG DNA
9
what is another name for PRR
TLR
inducing cytokine for T reg
TGF-B, IL2
produced by T reg
TGF B, IL10, IL35, STAT6, FOXP3
what do T regs do
suppress tumor immunity, promote immune tolerance and maintain homeostasis
TH1 produce
IFNy, TNF or Lta, SAT 4, T-bet
what is role of T helper
promote tumor immunity, intracellular pathogens, autoimmunity
inducing cytokine of TH2
IL4
what does TH2 produce
GATA3, STAT 6, IL 4,5, 13
what are TH2 for
extracellular pathogens, allergy, asthma
inducing cytokines for TH17
TGF-B, IL6, IL 12
IL1B and IL 23
what does TH17 produce
IL17A, 17F, 22,21, CCL20, STAT 3, RORyt
role of TH17
break immune tolerance, ec bacteria, autoimmunity, controversial tumor immunity
immune reaction of TH1
macrophage activation and IgG
role of TH1 in diseases
autoimmune, tissue damage
immune reaction of TH2
mast cell, eosinophil activation, IgE, alternative macrophage activation
host defense of TH2
helminthic parasites
role of TH2 in diseases
Allergies
immune reaction of TH17
neutrophils and monocyte inflammation
host defense of TH17
extracellular bacteria and fungi
what disease uses TH17
autoimmune inflammatory
which cytokine leads to activation of eosinophils
IL5
what does IL2 do
B cells switch to IgE
role of IL17
acute inflammation
role of IL22
maintenance of epithelial barrier
role of TGFB
inhibit T cell activation and make T reg cells
which cytokines is broduced by both CD 4 and 8 Cells
IFNy
who produces most cytokines
CD4
cytokines produced by NK cells
IFNy and IL22
produced by mast cells
IL4 and 5
cytokines are pleiotrophic meaning
multiple biological fxn
cytokines are redundant meaning
many cytokines have similar fxn
what cause CD4+ to become TH1 cells
IL12 from DC and macrophages and IFNy from NK cells
what does IL12 produce and IFNy produce TFs for CD4 differentiation
12=STAT1 and T bet while IFNy makes STAT4
what does TH1 do to effect TH2 and TH17
IFNy to inhibit them
how are TH2 cells made from CD4+
mast cells and eosinophils produce IL4 that makes TF STAT 6 and GATA 3
what inhibits TH1 and TH17 by TH2
IL4
causes CD4+ to become TH17
IL1, 6 and TGF B that make RORyT and STAT3
role of IL21 for TH17
induced RORyt adn STAT3 amplification by autocrine
what suppresses TH1 and 2 from TH17
TGF-B
important cytokine for TH17 with unknown fxn
IL23
what is IL17 for
produced for TH17 for ec pathogens and tissue inflammation and autoimmunity
what is required for Treg
FOXP3 with high TCR self reactivity
what happens if FOXP3 isn’t on TCR
death of Tcell
what does T reg inhibit
all TH
what antibody produces IgG
IFNy
how do TH1 activate macrophages
binding of CD40L and IFNy
what does activated macrophage secrete
TNF, IL1 and 12, chemokines
IL12 role
TH1 and IFNy production
TNF, IL1 and chemokines cause
inflammation
constitutive activation of macrophages
no CD 40
inducible macrophage activation
CD40L
IL4 from TH2 leads to
B cell production for IGE, intestinal mucus secretion, macrophage activation
IL5 from TH2
eosinophil activttion
what does IgE do
degranulate mast cells
IL13 from TH2
intestines and macrophage activation
macrophage activation from TH2 is for
alternative activation for tissue repair
what does an alternative macrophage do
produce IL10 and TGFB for anti-inflammatory, wound repair and fibrosis
what does alternative macrophage block
inflammation
what does IL17 from TH17 do
produce TNF, IL1,6 CSFs for inflammation and neutrophil response and antimicrobial pepetides
what from IL22 increases barrier fxn and antimicrobial peptides
IL22
how are CD8+ T cells activated
cross presentation of antigens to CD8+ T cells
what do CD4+ helper cells induce for CD8+
potentiated response
2 ways CD4 activate CD8+
DC with CD4+ bound at the same time or bound to CD4 before CD8 with CD40
what do CD4+ celsl use for CTL activation
cytokines
what APCs do CTLs recognize
MHC class I with Ag on DC or infected cells in tissue
activated CTLs do what
release granule content
what is in granules
perforin and granzymes
what do CTLs induce
apoptosis in target cells
what do CD8+ cells release
IFNy that activates macrophages
how do granzymes enter cells
receptor mediated endocytosis
how do granzymes enter cytoplasm
perforin
why are y delta cells nontraditional
no CD4 or 8
where are y delta cells
intestines, uterus and toung
fxn of y delta
first line of defense, immunoregulatory, bridge innate and adaptive
why are y delta bridge between innate and adaptive
work like innate but on adaptive immunity
other bridges between innate and immunity (ADD to
DCs
what makes y delta adaptive
may become memory cell
why can y delta be considered innate
recognize unpresented Ags
what can y delta cells kill
stressed cells
fxn of y delta
cytokine and chemokine production, help B cells and igE production, DC maturation, Prime aB T cells, lysis stressed cells, regulate stromal cells via growth factors
NKT cells are not
NK cells
what are NKT
heterogenous T cells that recognize self and foreign lipids and glycolipids
what presents lipids and glycolipids
non polymorphic CD1d APCs
% of NKT cells
0.2%
what do NKT produce
IFN-y, IL4, and GMCSF
NKT cells cause
rapid release of cytokines
role of NKT
promote or suppress immune
deficiency in NKT means
autoimmunity, cancers, asthma
examples of autoimmunity
diabetes and atherosclerosis
IFNy from NKT activate
B cells, DC, and NK
IL4 from NKT works on
B cells
IL2 from NKt leads to
T reg activation