Lecture 23 Flashcards
What are the key cytokines (Signal 3) involved in the differentiation of TH17 cells?
TGF-β, IL-6, and IL-23
What are the main effector cytokines produced by TH17 cells?
IL-17 and IL-22
What is the master transcriptional regulator of TH17 cells?
RORγT, (a transcription factor) gets activated by STAT3 signaling
When were TH17 cells discovered, and what earlier discovery led to their identification?
TH17 cells were discovered in 2005, following the 2003 discovery that IL-23 is important for autoimmunity.
How did the discovery of TH17 cells change the understanding of T cell differentiation?
It led to a rethinking of the classic TH1 vs TH2 paradigm.
What type of immune response do TH17 cells enhance?
They enhance neutrophil responses and mucosal immunity.
What types of pathogens do TH17 cells help protect against?
Extracellular bacteria and fungi
What kind of immune response are TH17 cells involved in, and what disorders are they linked to?
They drive a pro-inflammatory response and are involved in many autoimmune disorders.
Which transcription factor gets activated in TH17 cell signaling?
STAT3
What effector cytokines are secreted by TH17 cells?
IL-17 and IL-22
What are the main effector cytokines secreted by TH17 cells, and what is their effect on other cells?
IL-17 and IL-22 → Stimulate other cells to secrete more cytokines, chemokines, and antimicrobial peptides
What immune cells are recruited by TH17 cells?
Neutrophils
What type of pathogens do TH17 cells help target?
Extracellular bacteria and fungi
What type of cytokine is IL-17, and what is its role in inflammation?
IL-17 is a pro-inflammatory cytokine involved in promoting inflammation.
What inflammatory diseases are TH17 responses involved in? (Name at least three)
Psoriasis
Inflammatory Bowel Disease
Asthma
Rheumatoid Arthritis
Multiple Sclerosis
Are there therapies targeting IL-17 for inflammatory diseases?
Yes, therapies targeting IL-17 are being studied, and some have already been approved for clinical use.
What effector function do IL-17 and IL-22 have on epithelial cells?
They induce epithelial cells to produce antimicrobial peptides, which help kill or slow bacterial replication.
How does IL-22 affect epithelial turnover, and why is this beneficial?
IL-22 increases division and shedding of epithelial cells, which can hinder bacterial growth.
How does IL-17 stimulate neutrophil production through G-CSF?
IL-17 acts on stromal and myeloid cells → They secrete G-CSF → G-CSF enters circulation and signals bone marrow precursors to produce neutrophils.
What does IL-17 induce stromal and epithelial cells to produce, and what is the outcome?
IL-17 induces them to produce chemokines → Chemokines attract neutrophils.
What are the main functions of neutrophils in response to TH17 signaling?
- Phagocytosis
- Forming NETs (Neutrophil Extracellular Traps)
- Releasing granules to kill bacteria and fungi
How do TH17 cells promote their own recruitment?
TH17 cells secrete a chemokine that attracts more TH17 cells.
How does IL-17 enhance the pro-inflammatory response through macrophages?
IL-17 induces macrophages to secrete IL-1β and TNF-α (pro-inflammatory cytokines).
How is IL-17 targeted as a treatment for psoriasis? (Include the disease, treatment type, and approaches)
- Psoriasis is an autoimmune disease causing scaly red and white patches on the skin.
- Treated with monoclonal antibodies (identical antibodies from a single B cell clone) that bind specifically to IL-17.
- Two approaches:
(1) IL-17 receptor antagonist → Blocks IL-17 receptor signaling
(2) Anti-IL-17 neutralizing antibodies → Bind to IL-17, preventing receptor interaction
How are ILCs (innate lymphoid cells) activated, and what do they target?
ILCs are activated by cytokines, and different groups target different pathogens.
What cytokines do ILC2 and TH2 cells produce, and what is their function?
IL-4, IL-5, IL-13 → Generate IgE and promote granulocyte degranulation to kill and clear helminth infections.
How do ILC3 and TH17 cells cooperate, and what is the result?
ILC3 and TH17 both produce IL-17 to defend against bacterial infections.
What is the signal and master transcriptional regulator for TFH cells?
- Signal 3: IL-6
- Master transcriptional regulator: Bcl-6
What transcription factor is activated in TFH cells?
STAT3 protein
What effector cytokines do TFH cells secrete?
IL-21
How do TFH cells help B cells produce antibodies?
TFH cells secrete IL-21 and other cytokines → Signals to B cells → B cells produce specific types of antibodies.
How do TFH cells recognize B cells?
TFH cells recognize pMHCII on B cells, and the nature of the signal determines the type of antibody produced.
Are NKT cells more like NK cells or T cells?
NKT cells have characteristics of both NK and T cells but are of lymphoid lineage.
What characteristics of NKT cells are similar to T cells?
Express TCR
Develop in the thymus
Undergo antigen receptor gene rearrangement
Recognize specific lipids and glycolipids on CD1
What characteristics of NKT cells are similar to NK cells?
- Kill target cells using activating and inhibitory receptors
- Release cytotoxic granules
- Secrete large quantities of cytokines
- Do not form memory cells
