T cells: Th1 & Th2 Flashcards by Misha Gandhi

What do some pathogens do

Persist in macrophages =
Inhibit fusion of phagosomes and lysosome
Prevent acidification —> lysosomal proteases can’t activate

How well did you know this?

Not at all

Perfectly

Summarize th1 cell

Recognize pmhc class 2 on surface
Uses cd40L to bind cd40
Secretes ifny
= boosts macrophage anti microbial activity and production of tnfalpha from macrophage

How well did you know this?

Not at all

Perfectly

Describe activated m1 macrophage

Classically activated macrophage
Function induced in context of th1 and have a boost to their anti microbial mechanisms
Like second wind

How well did you know this?

Not at all

Perfectly

What can induce classical m1 macrophage activation

Tnf alpha
Cd40L
Ifn-y

How well did you know this?

Not at all

Perfectly

Describe tnfalpha - m1 macrophage

Tnf alpha secreted —> autocrine signalling sends survival signal to macrophage

How well did you know this?

Not at all

Perfectly

Describe cd40L - m1 macrophage

Cd40L binding activates macrophages and increases expression of Il-12 = part of signal 3 for th1 cells
Like pos feedback loop

How well did you know this?

Not at all

Perfectly

Describe tnfalpha AND IFNY - m1 macrophage

Together= increase expression of mhc classes 1 and 2, cd40, b7 molecules (more costim), il12 = further activates th1 cells - feed forward loop

How well did you know this?

Not at all

Perfectly

Describe IFNY - m1 macrophage

From effector ctls = can also activate m1 macrophages

How well did you know this?

Not at all

Perfectly

TH1 EFFECTOR functions = killing infected macrophages - when can happen

Can happen in case of chronically infected macrophages

How well did you know this?

Not at all

Perfectly

TH1 EFFECTOR functions = killing infected macrophages - what happens

Th1 cells recognize pmhc2 on infected macrophage
FasL expressed on th1 cell binds fas on infected cells —> triggers apoptosis
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

Th1 cells secrete Il12 and stimulate cd8+ T cell proliferation and differentiation
Would occur in secondary lymphoid organ - lymph node
Ctls can recognize via pmhc 1 binding and kill infected macrophages - if pathogen persisting in them

How well did you know this?

Not at all

Perfectly

TH1 EFFECTOR functions = stimulate increased differentiation of monocytes in bone marrow

Th1 cells secrete il3 and gm-csf = circulate in blood and act on precursors in bone marrow = endocrine effect

How well did you know this?

Not at all

Perfectly

What is gm-csf

Granulocyte macrophage colony stimulating factor

How well did you know this?

Not at all

Perfectly

TH1 EFFECTOR functions= adhesion molecules

Change of expression of adhesion molecules on neighbouring endothelium to recruit more macrophages
Th1 cells secrete cytokines that induce these changes

How well did you know this?

Not at all

Perfectly

TH1 EFFECTOR functions = recruitment

Recruitment of macrophages by chemotaxis
= th1 cells secrete chemokine ccl2 that attracts macrophages to site infection

How well did you know this?

Not at all

Perfectly

Clinical ex = m tuberculosis - gen

Chronic activation of macrophages b th1 cells leads to formation of granuloma s
M tuberculosis infects macrophages in lungs
Often resistant to anti microbial effect of macrophages —> chronic infection

How well did you know this?

Not at all

Perfectly

Clinical ex = m tuberculosis - granuloma formation

Core of infected macrophages
Surrounded by layer of activated macrophages and then layer of th1 cells
Centre often becomes necrotic = cells die in centre from a combo of lack of oxygen and cytotoxic effect of activated macrophages = extreme case, can be surgically removed

How well did you know this?

Not at all

Perfectly

Th2 signal 3

Il4

How well did you know this?

Not at all

Perfectly

Th2 effector cytokines

Il4, 5 and 13

How well did you know this?

Not at all

Perfectly

Th2 master transcriptional regulator

Gata3
Gene gets activated, another tf

How well did you know this?

Not at all

Perfectly

Th2 - important for when

Response to helminths- worms
= Activates eosinophils, mast cells and basophils and macrophages

What happens when th2 dysregulated

Involved in allergies or asthma

What tfs activated for th2

Stat6 protein activated = phosphorylated

What does th2 secrete

Il 4
Il5
Il13

What does th2 target

Eosinophils, basophils, mast cells and macrophages

What does th2 aid in killing of

Helminth parasites

Describe parasitic helminths

Multicellular worms Colonize gut epi of animals and humans all over world - 1 billion ppl infected - adhere to mucosal layer of gut Often cause chronic infection Th2 = reduces burden helminth but cannot clear it alone

Describe th2 response to helminths

Can sometimes clear the pathogen = if not —>chronic infection Reduce worm burden - weep and sweep Facilitate tissue repair - bc worms big and can damage tissue IgE antibodies

Describe IgE ANTIbodies

Important for immune responses against helminths

Th2 effector fcuntions = promote cell turnover and mucous production

Il13 = increase mucus production by goblet cells and increase turnover epithelial tissue - parasites cannot adhere as easily Weep response (in weep and sweep)

Th2 effector fcuntions = enhance worm expulsion

Il13 = stimulate smooth muscle cells to contract = can lead to worm exclusion Physically remove worm Sweep (in weep and sweep)

Th2 effector fcuntions = what does it do to macrophages

recruit and activate M2 macrophages

What is important for m2 activation

Il4 and il13

What are m2 macrophages

Alternatively activated macrophages

What do m2 macrophages aid in

Tissue repair and participate in worm killing and expulsion = increase smooth muscle contraction

What can m2 macrophage form and release

Form granulomas to entrap worms and kill them Also release toxic mediators directly onto worm by adcc

Describe Adcc

Antibody dependent cell mediated cytotoxicity Killing of antibody coated target cells by fc receptors (bind to abs) Most adcc is mediated by nk cells Macrophages bind Complement c3 and binds antibodies - macrophage has receptors for ab —> intracellular signalling and release toxins

Th2 effector fcuntions = eosinophil activation

Il-5 Il-4 and Il-13

Th2 effector functions = eosinophil activation —> Il-5

Activates, recruits and enhances eosinophil differentiation

Th2 effector functions = eosinophil activation —> Il-4 and il-13

Lead to ige generation Ige antibodies bind ag on parasites, eosinophils expres receptors that recognize fc portion of Ige —> eosinophils can then specially target pathogens and degranulate to kill it —> leads to granules

Th2 effector functions = mast cell activation

Cytokines activate mast cells IgE antibodies Basophils

Th2 effector functions = mast cell activatioN = what do mast cell granules contain + effects

Contain histamine and other molecules = increase vascular permeability- help worms pass through Increase intestinal motility Increase recruitment of inflammatory cells

Th2 effector functions = mast cell activatioN = IgE antibodies

Coat parasite Mast cells express receptors that recognize fc portion of ige

Th2 effector functions = mast cell activation= basophils

Can secrete il4 and il13 = can activate goblet cells - secrete mucus, vasodilation Binds to ige and releases histamines

What can allergen do - type 2 response and allergies

Can enter host via mucosal tissues and induce th2 response Il4, il13 induce ige generation

What are allergies initiated by - type 2 response and allergies

Initiated by an interaction between an ige ab and ag

What do IgE antibodies do - type 2 response and allergies

Bind to mast cells or basophils and induce degranulation Granule contents released induce histamine, proteases, chemokines = inflammatory response Act on surrounding tissues and cells to cause symptoms - why some ppl take anti histamines

Describe free circulating IgE - type 2 response and allergies

Usually v low in concentration in blood serum —> hampered studies on antibody

When do health individuals make IgE

Healthy individuals make ige only in response to parasitic infections

What do eosinophil granules contain

Major basic protein = mbp = can kill parasites