T cells: Th1 & Th2 Flashcards
What do some pathogens do
Persist in macrophages =
Inhibit fusion of phagosomes and lysosome
Prevent acidification —> lysosomal proteases can’t activate
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
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
What can induce classical m1 macrophage activation
Tnf alpha
Cd40L
Ifn-y
Describe tnfalpha - m1 macrophage
Tnf alpha secreted —> autocrine signalling sends survival signal to macrophage
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
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
Describe IFNY - m1 macrophage
From effector ctls = can also activate m1 macrophages
TH1 EFFECTOR functions = killing infected macrophages - when can happen
Can happen in case of chronically infected macrophages
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
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
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
What is gm-csf
Granulocyte macrophage colony stimulating factor
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
TH1 EFFECTOR functions = recruitment
Recruitment of macrophages by chemotaxis
= th1 cells secrete chemokine ccl2 that attracts macrophages to site infection
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
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
Th2 signal 3
Il4
Th2 effector cytokines
Il4, 5 and 13
Th2 master transcriptional regulator
Gata3
Gene gets activated, another tf
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
