Cytokines & T helper Cell Mediated Responses Flashcards
What are Costimulatory signals are required for ?
T-cell activation and proliferation
Positive costimulatory receptors facilitate ?
Activation, help turn T cell on e.g. CD28
What is meant by Clonal Anergy ?
The inactivation of immune cells resulting from their interaction with antigen in the absence of a second antigen signal
Negative costimulatory (coinhibitory) receptors help?
Turn activation off. E.g. CTLA-4 & PD-1 (checkpoint blockade)
- These are important for the treatment of chronic immune-
mediated diseases
What are two types of communication in the immune system ?
1. Cell-cell direct receptor communication 2. Cytokine mediated communication - Small, soluble glyoprotein messengers <30 kDa a communication network for the immune system
How can cytokines act specifically ?
- Only cells expressing specific cytokine receptors can be activated
- Short-lived
- High concentrations needed
What happens when adaptive immune cells are stimulated by APCs ?
They proliferate & differentiate into effector cells with a range of functions appropriate for the immunological challenge
Effector T cell differentiation into functionally distinct
subsets depending on the type of infection?
- Th1 cells
- Th2 cells
- Th17 cells
- Tregs
- TFH cells
How does CD4+ T cells help the activity of other immune cells ?
- Releasing a variety of cytokines with direct effector functions
- B cell antibody class switching
- Activation & growth of cytotoxic CD8+ T cells
- Maximizing bactericidal activity of macrophages
What is proliferation and differentiation of naive T cells is driven by ?
Autocrine IL-2
What are Tacrolimus (FK506).. Cyclosporin A and Rapamycin (Sirolimus) and what are they used for ?
Immunosuppressive drugs used to mediated T cell mediated rejection of transplants via
inhibition of IL-2 production/signalling
What can the Helper T cells be divided into at least five distinct subsets ? and explain what each one does?
- Th1 regulate immunity to intracellular bacteria and viruses
- Th2 regulate immunity to worms & are responsible for allergy
- Th17 regulate immunity to extracellular bacteria anf fungi
- Treg are inhibitory in terminating immune responses and inhibiting autoimmunity
- Tfh regulate humoral immunity (B cells and antibodies)
What do the differentiating IL-12 cytokine produce ?
- Transcription factor = T-bet
- Produces the IFN-γ and favours the differentiation of T helper 1
What do the differentiating IL-4 cytokine produce ?
- Transcription factor = GATA-3
- Produces characteristic cytokines IL-4, IL-5 and IL-13
- Produces Th2 cells
What do the differentiating TGF-β, IL-6 and IL-23 cytokines produce?
- Transcription factor = RORγ
- Produces characteristic cytokines IL-17 and IL-22
- Produces Th17 cells
What does only the IL-6 cytokine produce ?
- Transcription factor = Bcl-6
- Produces characteristic cytokines IL-21
- Produces Tfh cells
What do the TGF-β and IL-2 cytokines produce ?
- Transcription factor = FoxP3
- Produces characteristic cytokines TGF-β and IL-10
- iTreg cells
What is the major actions of CD4+ T helper 1 cells ?
- Activate specialised killing mechanisms of macrophages
- Support CD8+ T cell response
What types of infection do CD4+ T helper 1 cells target ?
- Extracellular bacteria & microbes that persist in macrophage vesicles (e.g. Listeria, mycobacteria,
Leishmania donovani, Pneumocystis carinii) - Must be tightly regulated to avoid tissue damage
Chronic activation of
macrophages by Th1 cells
mediates formation of ?
Granulomas to contain pathogens e.g. M. tuberculosis
What is the major actions of CD4+ T helper 2 cells ?
- Promote enhanced barrier function & mediate contraction
of smooth muscle(IL-13) - Activate & recruit eosinophils (IL-5)
- Activate & recruit basophils & mast cells (IL-4).
- Induce antibody class switching to IgE (IL-4)
What types of infection do CD4+ T helper 2 cells target?
Helminths parasites, allergy
What is the major actions of CD4+ T helper 17 cells ?
- Activate barrier epithelial cells to upregulate anti-microbial peptides
- Recruit neutrophils
What types of infection do CD4+ T helper 2 cells target?
Extracellular bacteria (e.g., Klebsiella pneumoniae), Fungi (Candida Albicans)
