21 -T cells IV: Th1 & Th2 cells Flashcards
TH1:
Signal 3 (polarizing cytokines)
IFN-y & IL-12
TH1:
Transcription factors
STAT 1 & STAT 4 proteins get activated
TH1:
Master transcriptional regulator
T-bet gene gets activated (also TF lead to effector cytokines)
TH1:
Effector cytokine
IFN-y
TH1 activate…
Activate cellular immunity
Macrophage activation
-Activation & differentiation of naïve cytotoxic T lymphocytes precursors into effector CTL –> through CD40L binding
TH1 Response
Intracellular pathogens (bacteria)
intracellular parasites
viruses
TH1 secrete
Secrete IFNy at point of interaction & other cytokine and chemokine
TH1 target
macrophages
-TH1 cell TCR recognizes pMHC-II on macrophage surface
TH1 aid in killing…
killing of microorganisms that persist in macrophage vesicles
TH1 cells activate
macrophages
Some pathogens persist in macrophages
-Inhibit fusion of phagosome & lysosome
-Prevent acidification lysosomal proteases can’t activate
TH1 cell:
Recognizes
uses
secretes
boosts
pMHC class II on surface of macrophages
Uses CD40L to bind Cd40
Secretes IFNy
Boosts macrophage antimicrobial activity & production of TNFa from macrophage
Activated M1 macrophage =
classically activated macrophage
when TH1 interact with this macrophage - they get extra boost from TH1
M1 macrophages =
function induced in context of TH1 & have boost to their antimicrobial mechanisms
TNFa secreted –> autocrine signaling –> send signal to macrophage
CD40L binding –> activate macrophage & increases expression of IL-12
-Part of signal 3 for TH1 cells
TNFa + IFNy –> increase expression of MHC class I & II, CD40, B7 molecules, IL-12 –> further activates TH1 cells (feed-forward loop)
…induce classical (M1) macrophage activation
CD40L, TNFa & IFNy from effector CTL
TH1 effector functions:
-activate macrophages
-Killing infected macrophages
-Help CD8+ T cells
-Stimulate increased differentiation of monocytes in bone marrow
-Change expression of adhesion molecules on neighbouring endothelium, to recruit more macrophages
-Recruitment of macrophages by chemotaxis
TH1 effector functions:
Killing infected macrophages
o Happen in case of chronically infected macrophages
o TH1 cells recognize pMHC-II on infected macrophage
o FasL on TH1 cell binds Fas on infected cells = triggers apoptosis
o Bacteria released can be phagocytosed by freshly recruited macrophages
TH1 effector functions:
Help CD8+ T cells
o TH1 cell can secrete IL-2 & stimulate CD8+ T cell proliferation & differentiation
o Occur in secondary lymphoid organ – lymph node
o CTLs recognize via pMHC I binding & kill infected macrophages
TH1 effector functions:
Stimulate increased differentiation of monocytes in bone marrow
o TH1 cells secrete IL-3 & GM-CSF circulate in blood & act on precursors in bone marrow
-Endocrine effect
TH1 effector functions:
Change expression of adhesion molecules on neighbouring endothelium, to recruit more macrophages
TH1 cells secrete cytokines = induce these changes
TH1 effector functions:
Recruitment of macrophages by chemotaxis
TH1 cells secrete chemokine CCL2 = attract macrophages to site of infection
Main TH1 effector function
activating macrophages to kil intracellular pathogens
-M1 macrophages=classically activated macrophages
Other TH1 effector functions
o Killing infected macrophages
o Provide help to activate CTLs
o Induce differentiation of monocytes in bone marrow
o Recruit macrophages to site of infection
TH2 cells
Signal 3
IL-4
TH2 cells
Transcription factors
STAT 6 protein activated
TH2 cells
Master transcriptional regulator
FATA-3 gene activated (also a TF)
TH2 cells
Effector cytokines
Secrete IL-4, IL-5, IL-13
TH2 cells
Important role in response to
helminths (worms)
TH2 cells acivates:
Activates eosinophils, mast cells, basophils & macrophages
Dysregulated TH2 responses, involved in
Involved in allergies/asthma
TH2 functions
Secrete IL-4, Il-5, IL-13
Targets eosinophils, basophils, mast cells & macrophages
Aid in killing helminths parasites
-Parasitic helminths – multicellular worms (Colonize our guts, often cause chronic infection)
TH2 responses to helminths
Can sometimes clear pathogen
-If not = chronic infection
Reduce worm burden
-Weep & sweep
Facilitate tissue repair
IgE antibodies – important for immune responses against helminths
TH2 effector functions: (6)
-Aid in killing helminths parasites
-Promote cell turnover & mucous production
-Enhance worm expulsion – physical removal
-Recruit & activate M2 macrophages
-Eosinophil activation
-Mast cell activation
TH2 effector functions:
Promote cell turnover & mucous production
o IL-13 an increase mucus production by goblet cells & increase turnover of epithelial tissue
o Weep of the weep & sweep response
TH2 effector functions
Enhance worm expulsion – physical removal
o IL-13 – stimulate smooth muscle cells to contract = can lead to worm expulsion
o Sweep of weep & sweep response
TH2 effector functions
Recruit & activate M2 macrophages
Il-4 & IL-13 = important for M2 macrophage activation
M2 macrophages = alternatively activated macrophages
Aid in tissue repair & participate in worm killing & expulsion
-Increase smooth muscle contraction
Can form granulomas to entrap worms
Can release toxic mediators directly onto worm by ADCC (antibody-dependent cell-mediated cytotoxicity)
-Killing of antibody-coated target cells by cells with Fc receptors-they bind to antibodies
-Most ADCC mediated by NK cells
TH2 effector functions
Eosinophil activation
Il-5=activates, recruits & enhances eosinophil differentiation
Eosinophil granules contain MBP (major basic protein) – can kill parasites
IL-4 & IL-13 = IgE generations (opsonin =enhance opsonization)
-IgE antibodies bind antigens on parasites
-Eosinophils express receptors that recognise the Fc portion of IgE= eosinophils specifically target pathogen & degranulate to kill it
TH2 effector functions
Mast cell activation
Cytokines activate mast cells
Mast cell granules = contain histamine & other molecules
-Increase vascular permeability
-Increase intestinal motility
-Increase recruitment of inflammatory cells
IgE antibodies coat parasite
Mast cells express receptors – recognize Fc portion of IgE
Basophils = secrete
Il-4 & IL-13
-Can activate goblet cells
-Allow vasodilation
-Binds to IgE & release histamines
Type 2 response & Allergy
Allergens – enter host via mucosal tissues
-Induce TH2 response
-Il-4 & IL-13 induce IgE generation
Allergies – initiated by
interaction between IgE antibody & antigen
IgE antibodies bind to mast cell/basophils & induce degranulation
-Granule contents released – include histamine, proteases, chemokines
-Act on surrounding tissues & cells to cause symptoms
Free circulating IgE = very … in concentration in blood serum
low
Healthy individuals make IgE – only
in response to parasitic infections
TH2 cells Impact on: … muscle to…
mucosa & smooth muscle to expel/control parasite
TH2 :
Tissue repair by
M2 macrophages
-Alternatively activated macrophages
