21 -T cells IV: Th1 & Th2 cells Flashcards by Fumeng Sun

TH1:
Signal 3 (polarizing cytokines)

IFN-y & IL-12

How well did you know this?

Not at all

Perfectly

TH1:
Transcription factors

STAT 1 & STAT 4 proteins get activated

How well did you know this?

Not at all

Perfectly

TH1:
Master transcriptional regulator

T-bet gene gets activated (also TF lead to effector cytokines)

How well did you know this?

Not at all

Perfectly

TH1:
Effector cytokine

IFN-y

How well did you know this?

Not at all

Perfectly

TH1 activate…

Activate cellular immunity

Macrophage activation
-Activation & differentiation of naïve cytotoxic T lymphocytes precursors into effector CTL –> through CD40L binding

How well did you know this?

Not at all

Perfectly

TH1 Response

Intracellular pathogens (bacteria)
intracellular parasites
viruses

How well did you know this?

Not at all

Perfectly

TH1 secrete

Secrete IFNy at point of interaction & other cytokine and chemokine

How well did you know this?

Not at all

Perfectly

TH1 target

macrophages
-TH1 cell TCR recognizes pMHC-II on macrophage surface

How well did you know this?

Not at all

Perfectly

TH1 aid in killing…

killing of microorganisms that persist in macrophage vesicles

How well did you know this?

Not at all

Perfectly

TH1 cells activate

macrophages

How well did you know this?

Not at all

Perfectly

Some pathogens persist in macrophages

-Inhibit fusion of phagosome & lysosome
-Prevent acidification  lysosomal proteases can’t activate

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Activated M1 macrophage =

classically activated macrophage

when TH1 interact with this macrophage - they get extra boost from TH1

How well did you know this?

Not at all

Perfectly

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)

How well did you know this?

Not at all

Perfectly

…induce classical (M1) macrophage activation

CD40L, TNFa & IFNy from effector CTL

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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