Effector T lymphocytes

Question 1

What are dendritic cells and where do they exist and explain their cycle?

Answer 1

MAIN subset of APCs for initiation of a T cell response

• DC exist in tissues and acquire antigen. and then move to lymph nodes (need activation by PAMP/PRR)
• in lymph nodes, DC mature and then present antigen on MHC

Question 2

Why are T cell mediated immunity required

Answer 2

• Some pathogens are intracellular and hide in the cell

- some organisms evolve to avoid antigen recognition

Question 3

What do MHC I and MHC II present to?

Answer 3

MHC I- presents intracellular antigen to CD8+ T cells

MHC II- presents extracellular derived antigen to CD4+ T cells

Question 4

When do T cells migrate and where to?

Answer 4

Once they have encountered the DC bearing the antigen- they can go back into the circulation.
There is a system:
-Chemokine gradient: if the cells express the right chemokine receptors they can follow these gradients
-Adressins and Integrins: allows the cells to move out of the vessels

Question 5

Summarise the relationship of DC and T cell?

Answer 5

• DC recognises the antigen
• Moves to the lymph node
• Meets the T cell
• T cell migrates to the source of infection

Question 6

Describe the stages of T cells?

Answer 6

Start as Naive cells: mature recirculating t cells that have not yet encountered antigen
Then become activated
- effector T cells: encountered antigen, proliferated and differentiated into cells that participate in the host defence.
They fulfil their roles and become memory T cells: ready to respond to future infections

Question 7

What is the difference between necrosis and apoptosis

Answer 7

Necrosis: inflammatory cell death ( classic danger signal)
Apoptosis: programmed cell death ( collapses in on itself)

Question 8

Broadly speaking, how do Cytotoxic T Lymphocytes kill infected cells?

Answer 8

Inducing apoptosis

Question 9

What are the two mechanisms for cell mediated cytotoxicity?

Answer 9

1.CD8+ effector T cells kill target cells that present peptides of cytosolic pathogens (viruses) in context with MHC class I molecules on their cell surface. Effector CTLs secrete granules.

2.Cytotoxic T cells (CTL):
Granzyme + perforin – perforin makes a pore in the cell membrane through which granzyme can enter and trigger apoptosis

Fas ligand on CD8 cell binds to Fas receptor on infected cell
When Fas has been engaged – it releases CASPASES
Both pathways upregulate CASPASES which drives apoptosis

Question 10

What are the effector functions a CD4+ cell can have?

Answer 10

• Macrophage Activation
• B cell Activation
• Delayed Type Hypersensitivity response
• Regulation

Question 11

What do macrophage activation do?

Answer 11

• get activated by CD4 T cells which enable them to engulf and kill pathogens better
• Activated macrophages express increased levels of CD40 and TNF-receptors
• secrete TNF-α which synergises with IFN-γ in the induction of antimicrobial effector mechanisms
• T cells and macrophages cross talk via cytokines

Question 12

What is the MAIN function of delayed type hypersensitivity?

what happens if the antigen isn’t eradicated?

what happens if the antigen is not a microbe?

Answer 12

MAIN ROLE: defence against intracellular pathogens

If antigen isnt eradicated: you get CHRONIC STIMULATION and granuloma ( clumping of macrophages) formed

Not a microbe: delayed type hypersensitivity produces tissue injury without protection = HYPERSENSITIVITY

Question 13

What are the two phases involved in Delayed Type Hypersensitivity and what causes it?

Answer 13

1.Sensitisation – initial exposure to the antigen
You have to be exposed to the antigen first before becoming allergic to it.
2.Effector – on 2nd exposure you can trigger a severe response

• T helper cells due to release of cytokines, these cytokines act as inflammatory mediators and also activate macrophages to secrete their mediators.
• It is independent of antibodies.

Question 14

What causes immediate hypersensitivity?

Answer 14

Caused by mast cell degranulation

Question 15

What are the five T helper cell subsets?

Answer 15

Th1 – macrophages activation, Delayed type hypersensitivity reaction, Help for CD8 cells and down regulation of Th2 responses
Th2 – MHC class II restricted and help B cells to differentiate into antibody secreting plasma cells. B cell proliferation, B cell differentiation and immunoglobin class switch and downregulation of Th1 responses.
Th17 – Protective against some bacterial infections, produce a particular set of inflammatory cytokines and mediate pathogenic responses in autoimmune diseases. 
Follicular T helper cells – essential for generation of isotype-switched antibodies
 Treg (Regulatory T cells) – some T cells may differentiate into regulatory cells in the thymus or in peripheral tissue, regulatory T cells inhibit the activation of naive and effector T cells by contact-dependant mechanisms or by secreted cytokines.

Question 16

What is the main difference between T cell memory and B cell memory?

Answer 16

T cell memory doesn’t undergo isotype switching or affinity maturation

• Once a T cell response has been made, it stays the same. B cell responses improve over the time
• Memory T cells are different from naive T cells- as a memory cell they change the type of cytokine receptor they have on the cell.

Question 17

What happens during T cell exhaustion?

Answer 17

• chronic infections, CD8 pool contracts

- cells start to exhibit PD1 (programmed cell death) which makes it harder to activate T cells

Question 18

Which cells are involved in effector memory cells and central memory cells?

Answer 18

CCR7-CD45RA : EFFECTOR ( memory is local to the site of infection)
CCR7+CD45RA: CENTRAL ( go back to the spleen or lymph nodes - longer lasting but take longer to activate)

Question 19

What is the difference/similiarities between B cells and Dendiritic cell activation?

Answer 19

• B cells only take up antigen that they recognise and DC take up a large variety of antigens.
• The antigen presents by both DC and B cell will the same so they will both present the same peptide-MHC complex which can be recognised by the T cell.
• The T cell will go from naive to the effector state- it will recognise the antigen-MHC complex on the B cell and activate it.

Question 20

Describe the full process of T-B collaboration

Answer 20

Immunoglobulin (Ig)+ B cells bind specific antigen. The Ig-antigen complex is internalised, processed and antigenic peptides are presented on the B cell surface in context with MHC class II molecules. T helper cells with specific TcR recognise antigenMHC complex on the cell surface. The T-B interactions trigger expression of CD40 ligand (CD40L) on T cells. CD40 L will
interact with CD 40 expressed by B cells; T cells secrete cytokines and B cells express cytokine receptors. The activated B cell will differentiate into immunoglobulin (antibody) secreting
plasma cells.