Lecture 10 Flashcards
What causes signal 1 in production of effector t cells
Recognition of MHC + peptide + co-receptor (CD4/8)
What causes signal 2 in the production of effector t cells
Recognition of co-stimulatory molecules (CD28 and B7 which are both member of the immunoglobulin super gene family)
What happens to t cells that have been exposed to signal 1 but in the absence of signal 2
They become unresponsive/ tolerised
What causes signal 3 in the production of effector t cells
Cytokines convert activated T cells into different subsets but this depends on what cytokines the antigen presenting cell is making.
What is B7, where is it expressed and what does it interact with
B7 is a co-stimulatory molecule (present on APCs). It’s expressed by dendritic cells, macrophages and B cells.
It interacts with CD28 inducing expression of IL-2 and the IL-2 receptor.
What do different cytokines induce
Activated niave t helper cells (TH0 cells) which in turn differentiate into various t cell effector subsets.
The different t cell subsets differ in the types of cytokines they produce which help ensure pathogen appropriate immunity.
What do TH1 cells produce and what’s their role
They produce interleukin-2 (autocrine fashion). They have a role in activating macrophages in cell-mediated immunity.
They also induce B cells to produce IgG1 and IgG3 (opsonizing antibodies)
How are TH2 cells produced and what do they produce
They’re generated in response to interleukin-4 and respond by producing IL-4, IL-5 and IL-13.
IL-13 plays a role in class switching.
What do TH-2 cells recruit
They recruit eosinophils to combat parasitic infections and can inhibit TH1 proliferation
What do TH17 cells respond to
Responding growth factor beta and TGF
What do TH17 produce
Produce interleukin 17 and 22 (found in the lymphoid tissue near mucosal surfaces). They activate epithelial cells to cause inflammation.
Where are receptors for IL-17 expressed
On fibroblasts, epithelial cells and keratinocytes.
What does contact with IL-17 result in
The production of several cytokines including IL-6 (initiates fever), chemokines such as CXCL8 (recruits neutrophils) and macrophages
What does IL-22 do
It cooperates with IL-77 to induce synthesis of antimicrobial peptides such as beta-defensins
What do TFH cells respond to and where are they found
IL-6. They are found in the lymphoid follicles
What do TFH cells help with and what needs to occur
B cell differentiation into antibody secreting plasma cells. T and B cells have to get close. The co-stimulatory molecules (CD154 and CD40 interact) this results in somatic hypermutation and class switching.
What are Treg cells
T regulatory cells - they’re a heterogenous group that suppress immune responses (important for regulation) by secreting anti-inflammatory cytokines/ IL-10
Where do Treg cells form
In the thymus or can differentiate from TH0 in the lymph nodes.
What functions does IL-10 have
Inhibiting inflammatory cytokine secretion by macrophages, reducing MHC2 expression in macrophages, blocking macrophage activation by IFN-gamma and blocking cytokine IL-2 production from TH1 cells.
How do cytotoxic t cells kill (two ways)
- Proteases (granzymes) from cytotoxic t cells enter target cell via perforin channel inducing activation of caspase cascade resulting in apoptosis.
- Fas ligand induces clustering of fas (“death receptor”) on target cell inducing caspase cascade resulting in apoptosis.
Features of cytotoxic t cell killing (CD8). How do they differ from NK cells?
- SPECIFIC- only infected cells bearing antigen are killed
-EFFICIENT- granzymes are pre-formed: a single cytotoxic t cell can kill 100s of infected targets
-CLEAN - enzymes formed during apoptosis degrade viral DNA and destroy non-viral pathogens.
What is hypersensitivity/ allergy
A disease following an immune response to innocuous antigen (allergen). Mostly IgE- mediated
What’s the “hygiene hypothesis”
Children brought up on farms or from large families are less prone to allergy. Early repeated childhood infections may be protective.
Insufficient exposure to certain types of infection skews the TH1/TH2 balance towards TH2
What’s the “counter regulation” or “old friends” hypothesis
Childhood infections protects against allergy by promoting IL-10 production.
Infection with microbes or larger parasites plays a critical role in driving immunoregulation e.g. promotes formation of Treg, IL-10
What are the role of gamma delta cells
These cells don’t normally express CD4/CD8. They’re generated earlier in development compared to alpha beta cells. They’re often found at mucosal epithelium. They’re less diverse but recognise a broader range of antigens. They may bridge innate and adaptive immunity
Stages of termination of immune responses
Engagement of CD28 on niave t cells with B7 provides the co-stimulatory signal for activation. Once a t cell has been activated, it starts expressing CTLA-4 on surface. CTLA-4 binds with high avidity to B7 instead of activating, switching it off
What does CTLA-4 engagement do
Inhibits T cell activation - occurs in the later stages on an immune response
What happens when FcyRIIB binds to IgG
Instead of activating, it switches it off
