Exam 3: Immune deviation - TH1, TH2, TH17 Flashcards
Master Transcription Factor for ILC 1 that drives TH1
T-bet
Master Transcription Factor for ILC2 that drives TH2
GATA-3
Master Transcription Factor for ILC3 that drives TH17
ROR-γT
Intracellular; Cell-mediated immunity (T. cell activation); inflammation; viruses, tuberculosis, leishmania
TH1
Extracellular; Humoral immunity; Allergies; WORMS; parasites;
TH2
What cytokines associated with TH1?
IL-12 from APC–> activates T-bet + TH1 cell–> IFN-γ
What cytokines associated with TH2?
IL-4 from various sources–> activated GATA-3 –> IL-4, IL-5, Il-13
Sources of IL-4?
Innate lymphoid cells (ILC2) is main source; Also –> Basophil, Eosinophil, NK T cell
What cytokines associated with TH17?
IL-23 + IL-1 from APC activate ROR-γT –> IL-17
Which type of response?
Tissue inflammation; Fungal immunity; autoimmunity
TH17
How are TH1 and TH17 responses similar?
Both driven by heterodimeric cytokines. TH1 driven by IL-12 (p35 + p40). TH2 driven by IL-23 (p19+p40).
What is special about IL-1
Very potent inflammatory cytokine. Released by caspase-1 which is activated by inflammasome.
Immune Deviation..
IFN-γ travels through ___ to turn on T-bet. T-bet induces ___ and TH1 response. T-bet also turns off IL-_, IL-_,IL-_.
Stat-1; IFN-γ; IL-4, IL-5,IL-13 and ROR-γT (TH17)
Immune Deviation..
IL-4 travels through ___ to turn on GATA-3. GATA-3 induces ___ and TH2 response. GATA-3 also turns off ____
Stat-6; IL-4 + IL-5; IFN-γ and ROR-γT (TH17)
TH17 response recruits what? What do they do?
Polymorphonuclear neutrophils (PMNs); Induce inflammation
Which cytokine(s)? Inflammation; Induce TH17
IL-1
Which cytokine(s)? Induce TH1
TH12
Typical pathogens for TH1 response?
Mycobacterium tuberculosis, mycobacterium leprae, Leishmania donovani
Where do pathogens for TH1 responses such as M. tuberculosis, M. leprae, and Leishmania donovani reside?
Macrophage
Antigen recognition site for TH1 response?
MHC Class II located on APC (macrophage)
Effector action of TH1 response?
Activated macrophage (via nitric oxide)
Typical pathogens for TH2 response?
Staphylococcus aureus; Streptococcus pneumoniae; Poliovirus (WHEN VIRUS INFECTS NEW CELLS AND IS THUS EXTRACELLULAR)
Where do pathogens for TH2 responses reside?
Extracellular fluid
Antigen recognition site for TH2 response?
MHC Class II located on APC (B cell)
Effector action of TH2 response?
Activation of B cell to make antibody
Roles of IFN-γ
- Induce expression of vascular adhesion molecules
2. Activate macrophages –> leads to increased release of inflammatory molecules.
Tb Granuloma (example of inflammation induced by TH1 response to M. tuberculosis) causes what in lungs?
lose ability to exchange gas in alveolar sacs
What are the two different forms of leprosy?
Tuberculoid leprosy; Lepromatous leprosy
Immune Deviation…
Tuberculoid Leprosy
Induce appropriate TH1 response. Low infectivity. Inflammation destroys tissue and induces nerve damage –> Lose sensitivity to touch. Normal serum Ig levels.
Lepromatous leprosy
Unusual form of disease. Wrong TH2 immune response. High infectivity. Can’t control bacterial growth due to wrong response. Leprosy isn’t dangerous but develop other infections.
Which cytokines are prominent in TH1 response to tuberculosis leprosy? Lepromatous?
IL-2, IFN-γ, TNF-β
No IL-2, IFN-γ
Important to know that IL-4,IL5 prominent in TH2 response to Lepromatous but not tuberculoid.
Response to parasite Leishmania?
TH1. Release of IFN-γ kills parasite.
What species of in-bred mouse make a TH2 response incorrectly to Leishmania, leading to detrimental effects?
BALB-C; Make IL-4 instead of IFN-γ; leads to much larger lesions
Another source of IFN-γ
Cytotoxic T Cells
Example of worm infection
Schistosomiasis eggs induce TH2 response in the form of TH2 granulomas
Response to worm infections?
TH2 response
Presence of this lymphocyte allude to worm infection
Eosinophil
What is a granuloma?
Collection of immune cells resulting from inflammation.
Undifferentiated T cell path to TH1
Undifferentiated T cell + IL-12–> TH1 Cell via T-bet –> IFN-γ
(Defense against intracellular pathogens)
Undifferentiated T cell path to TH2
Undif. T cell + IL-4 –> TH2 Cell via GATA-3 –> IL-4
defense against parasites, worms, also allergies
Undifferentiated T cell path to TH17
Undif. T cell + IL-23 + IL-1–> TH17 cell via ROR-γT–> IL-17
(Defense against extracellular bacteria, autoimmunity, yeast, cancer)
Undifferentiated T cell path to Treg
Undif T cell + TGF-β1–> Treg via Foxp3–> TGF-β1
(Immunosuppression) without Treg we get autoimmunity
IL-12 induces
TH1 cell
IL-4 induces
TH2 cell
IL-23 and IL-1 induce
TH17
Where does inducing cytokines come from?
APC sees TLR to induce activated APC to release IL-12
subunits of IL-23
p40/p19
subunits of IL-12
p40/p35
What is IL-1 released thru?
caspase-1 via inflammasome activation
What does IL-1 recruit
PMN to induce inflammation
How are reactive oxygen and nitrogen species produced?
T cell activates macrophage
Why do you lose nerve damage from tuberculoid leprosy
Quick TH1 response facilitating localized inflammation/granulomas
T/F The wrong immune response is seen in Tuberculoid leprosy
F; seen in lepromatous leprosy
IFN-gamma has what effect on macrophages infected by Leishmania?
macrophages kill Leishmania via cell-mediated immunity
Why do BALB/c inbred mice exhibit large lesions from Leishmania major?
They make IL-4 (TH2 response) and not TL-12 (TH1)
Schistosomiasis eggs are what type of antigen?
Worm–> TH2 –> Granuloma
What is the master transcription factor for Treg
Foxp3
What happens without Treg?
Autoimmunity
