T cells: Th17 & Intro to Tfh Flashcards
Th17 signal 3
Tgf-beta
Il6 and
Il23
Effector cytokine th17
Il17 and il22
Master transcriptional regulator th17
RORyT
When was th17 discovered
DIScovered in 2005 —> following discovery in 2003 that il23 is important for development of autoimmunity
Rethinking of classical th1 vs th2 paradigm
What does th17 do
Enhances neutrophil responses and mucosal immunity - increase neutrophil count = helps respond to extra cellular bacteria and fungi
Proinflam responses and involved in many auto immune disorders - highly inflammatory
Tfs activated th17
Stat3 proteins phosphorylated
What does th17 secrete
Il17 and Il22
What are effector functions of th17
Il17 and 22 stimulates other cells to secrete more cytokines, chemokines and anti microbial peptides
Increases = recruits neutrophils
What does th17 aid in
Targeting extracallular bacteria and fungi
What is il17
Pro inflammatory cytokine
Induces inflammation
What is th17 responses involved in
Number of inflammatory diseases, including auto immune diseases -prolonged inflammation = very bad
Like = psoriasis, inflammatory bowel disease, asthma, rheumatoid arthritis, multiple sclerosis
- therapies targeting il17 = being studied for treatments
What is th17 response to infection
Type 3 response
Th17 effector functions = induce production of anti microbial peptides
Il17 and il22 can induce epithelial cells to produce anti microbial peptides —> will hopefully
Contribute to killing/slowing replication of bacteria (or fungi, extracellular)
Th17 effector functions = Increase epi turnover
Il22 increases division and shedding of epithelial cells
Can hinder bacterial growth of extracellular Bacteria//fungi = stop colonization
Th17 effector functions = Induce other cells to produce g-csf
Il17 acts on stromal (certain ct) and myeloid (lineage) cells
Cells secrete g-csf cytokine
What does g-csf do
Granulocyte colony stimulating factor
Enters circulation and targets bone marrow precursors to differentiate into neutrophils = so increase neutrophil count
Endocrine effect
Th17 effector functions =Induce other cells to secrete chemokines
Il17 acts on stromal and epithelial cells
= secrete chemokines = will attract neutrophils - to site infection
What can neutrophils do
Phagocytosis, form nets, release granules that can kill bacteria and fungi
Th17 effector functions = Attract more th17 cells
Th17 secrete chemokine that recruits addition th17 cells = more of these effects
Ccl20
Th17 effector functions = Induce macrophages to…
To secrete pro inflammatory cytokines like Il-1beta and tnf-alpha = part of acute phase response
= th17 cells have several diff pro inflam effects - direct and indirectly
Disregulation =much inflammation = very bad
What is psoriasis
Autoimmune disease that causes scaly and white patches on skin - can be genetic or stress induced
What is treatment for psoriasis
Il7 targeted using monoclonal antibodies
What is a monoclonal antibody
Antibodies produced by a. Single clone of b lymphocytes = so they are all identical
Bind specifically to target to either activate or inhibit its activity
Name and describe the 2 approaches for targeting il-17 in psoriasis using mabs
Il17 receptor antagonist = binds receptor so il17 cannot bind, blocks signalling from il17 receptor
Anti il17 neutralizing antibodies = binds to il17 and prevents it from interacting with receptor
The immune system is…
Very interconnected
What are ilcs activated by
Cytokines and diff groups target diff pathogens
Ex = ilc2 - what does it produce/do
Ilc2 and th2 cells produce trio of cytokines = il4, il5, and il13
= generate ige and degranulation of Granulocyte and other functions that can kill and clear helminth infection
Ex =ilc3 - what does it produce/do
Cooperate with th17 and produce il17 to defend against bacterial infection
What does Ilc2 work against
Helminths
What does Ilc1 work against
Intracellular bacteria
Virus
What does Ilc3 work against
Fungus
Extracellaulr bacteria
What do Tfh cells do
Help activate B cells
In lymph node
Tfh interact directly with B cells
Signal 3 tfh
Il6
Effector cytokines tfh
Il21 - promote differentiation and proliferation of B cells
EITHER = type 1 (inf-y), or type 2 (il4) or type 3 (il17)
= depends on what infected with, determines which ab generated
Master transcriptional regulator tfh
Bcl-6
What tfs actiavted for tfh
Stat3 phosphorylated
(Diff area stat3 than th17)
What does tfh secrete
Il21 = high amounts
Il4 or il17 of ifny = depends on infection
= signal will activate b cells to produce specific types of abs
When do tfh respond
Response to all types fo pathogens
How does tfh help activate B cells
Tfh recognizes pmhc2 on B cells (profesh apc)
B cell needs diff signals for activation
Nature of signals will inform the type of ab produced = induces certain types abs and inhibit others
Ex = il4 = induces ige and igg1
