Lecture 10

Question 1

What causes signal 1 in production of effector t cells

Answer 1

Recognition of MHC + peptide + co-receptor (CD4/8)

Question 2

What causes signal 2 in the production of effector t cells

Answer 2

Recognition of co-stimulatory molecules (CD28 and B7 which are both member of the immunoglobulin super gene family)

Question 3

What happens to t cells that have been exposed to signal 1 but in the absence of signal 2

Answer 3

They become unresponsive/ tolerised

Question 4

What causes signal 3 in the production of effector t cells

Answer 4

Cytokines convert activated T cells into different subsets but this depends on what cytokines the antigen presenting cell is making.

Question 5

What is B7, where is it expressed and what does it interact with

Answer 5

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.

Question 6

What do different cytokines induce

Answer 6

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.

Question 7

What do TH1 cells produce and what’s their role

Answer 7

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)

Question 8

How are TH2 cells produced and what do they produce

Answer 8

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.

Question 9

What do TH-2 cells recruit

Answer 9

They recruit eosinophils to combat parasitic infections and can inhibit TH1 proliferation

Question 10

What do TH17 cells respond to

Answer 10

Responding growth factor beta and TGF

Question 11

What do TH17 produce

Answer 11

Produce interleukin 17 and 22 (found in the lymphoid tissue near mucosal surfaces). They activate epithelial cells to cause inflammation.

Question 12

Where are receptors for IL-17 expressed

Answer 12

On fibroblasts, epithelial cells and keratinocytes.

Question 13

What does contact with IL-17 result in

Answer 13

The production of several cytokines including IL-6 (initiates fever), chemokines such as CXCL8 (recruits neutrophils) and macrophages

Question 14

What does IL-22 do

Answer 14

It cooperates with IL-77 to induce synthesis of antimicrobial peptides such as beta-defensins

Question 15

What do TFH cells respond to and where are they found

Answer 15

IL-6. They are found in the lymphoid follicles

Question 16

What do TFH cells help with and what needs to occur

Answer 16

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.

Question 17

What are Treg cells

Answer 17

T regulatory cells - they’re a heterogenous group that suppress immune responses (important for regulation) by secreting anti-inflammatory cytokines/ IL-10

Question 18

Where do Treg cells form

Answer 18

In the thymus or can differentiate from TH0 in the lymph nodes.

Question 19

What functions does IL-10 have

Answer 19

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.

Question 20

How do cytotoxic t cells kill (two ways)

Answer 20

1. Proteases (granzymes) from cytotoxic t cells enter target cell via perforin channel inducing activation of caspase cascade resulting in apoptosis.
2. Fas ligand induces clustering of fas (“death receptor”) on target cell inducing caspase cascade resulting in apoptosis.

Question 21

Features of cytotoxic t cell killing (CD8). How do they differ from NK cells?

Answer 21

• 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.

Question 22

What is hypersensitivity/ allergy

Answer 22

A disease following an immune response to innocuous antigen (allergen). Mostly IgE- mediated

Question 23

What’s the “hygiene hypothesis”

Answer 23

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

Question 24

What’s the “counter regulation” or “old friends” hypothesis

Answer 24

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

Question 25

What are the role of gamma delta cells

Answer 25

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

Question 26

Stages of termination of immune responses

Answer 26

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

Question 27

What does CTLA-4 engagement do

Answer 27

Inhibits T cell activation - occurs in the later stages on an immune response

Question 28

What happens when FcyRIIB binds to IgG

Answer 28

Instead of activating, it switches it off