Lecture 12- Effector responses against infectious agents

Question 1

How are CD4+ and CD8+ T cells activated?

Answer 1

Activated in similar ways.
Both require recognition of antigen to be activated.
Both require co-stimulation to be activated

Question 2

What are the CD4+ and CD8+ T cell functions?

Answer 2

Cd4+ T cells become T-helper cells- produce cytokines, facilitate activation of other immune response

CD8+ T cells become cytotoxic T lymphocytes (CTLs)- directly kill cells infected with intracellular pathogens

Question 3

How are cd8+ t cells get activated to become CTLs?

Answer 3

Get recognition with MHC class I.
Then signal 2.
CD8+ t cells don’t tend to have signal 3
once

Question 4

When does cd8+ t cells need co-stimulation?

Answer 4

After initial activation, the CTL does not require co-stimulation to kill cell

Question 5

What is the major way that CD8= CTLs kill cells?

Answer 5

By releasing granules

Question 6

How does CTL kill an infected cell?

Answer 6

1. CTL binds to target cell loosely
2. CTL recognises antigen (presented by MHCI) and T-cell cytoskeleton reorganises to place granules at site of contact
3. CTL released cytotoxic granules at the cell-cell contact = allows specific killing-> induces apoptosis

Question 7

why is apoptosis better by CTL?

Answer 7

apoptosis produce less damage than necrosis- less inflammation induced

Question 8

What’s in the CTL cytotoxic granules?

Answer 8

• Granzymes- serine proteases that induce apoptosis in target cell
• Granulysin-antimicrobial and can induce apoptosis
• Perforin- helps deliver granule contents to target cell

Question 9

Why are all our nucleated cells potential targets for CD8+ t cells?

Answer 9

CD8+ cells recognise antigen in association with MHC Class I molecules, and all nucleated cells of body express MHC I

Question 10

How do CTLs kill specifically?

Answer 10

CTL very directed killing of the cells that are expressing the pathogen’s antigens on the surface. Stops spread of virus

Question 11

Apart from directly killing infected cells what do CTLs do?

Answer 11

Produce cytokines to regulate immune response (like CD4+ do)
e.g. interferon gamma which activates macrophages, increases MHCI expression in infected cells, inhibits viral replication

Question 12

Which cytokines do CTLs produce?

Answer 12

1. Interferon gamma which activates macrophages, increases MHCI expression in infected cells, inhibits viral replication
2. TNFalpha and LTalpha- helps IFNgamma activate macrophages, can help directly kill some infected cells

Question 13

what is the major way that CD4+ T helper cells do their jobs?

Answer 13

Production of cytokines-> regulate many different aspects of the immune response

Question 14

How do CD4+ Th1 cells regulate immune response?

Answer 14

Generally mounted against intracellular pathogens-> viruses, some bacteria
In some infections, infection of the macrophage renders it inactive= needs activating to function

Question 15

How do CD4+ Th1 cells activate macrophages?

Answer 15

-secretion of IFN-gamma
-CD40 ligand expressed on T cell-CD40 interaction
Activated macrophage upregulates MHCII- increased T cell activation (crosstalk)

(more slowly than CD8+)
Also produce IL3- induce macrophage differentiation. IL2 induces T cell proliferation
LT-alpha can kill infected cell.

Question 16

In some circumstances what else can cd4+ th1 cells do?

Answer 16

Can stimulate some antibody production- IgG1 in humans and IgG2a in mice. Can opsonise pathogens in extracellular phase

Question 17

what are some similarities between CD4 and CD8?

Answer 17

Both coordinate response against intracellular pathogens

Can activate macrophage via IFN-gamma and macrophage can make IFN-gamma itself

Question 18

What do CD4+ Th2 cells fight?

Answer 18

Deal with extracellular pathogens e.g. worms

too big for cellular response or phagocytosis.

Question 19

How do CD4+ Th2 cells regulate immune response?

Answer 19

1. Help B cells produce antibody

2. Activate basophils, eosinophils and mast cells

Question 20

What is an important antibody to deal with extracellular pathogens which CD4 Th2 activate B cells to produce?

Answer 20

IgE

Question 21

How do CD4+ Th2 cells activate B cells to produce antibody?

Answer 21

interacts with B cell via CD40 then releases cytokines e.g. IL4,5,6 that activate B cell to proliferate, class swithc them to produce IgE

Question 22

How do Cd4+ th2 cells activate basophils, eosinophils and mast cells?

Answer 22

directly via Th2 cytokines or indirectly via stimulation of B cells to make IgE which binds to cells and activates them

Question 23

What do Cd4+ th17 cells fight?

Answer 23

generally against extracellular bacteria and fungi

Question 24

How do CD4+Th17 cells regulate immune responses?

Answer 24

Produce IL17-> acts on several cell types to induce cytokine secretion
Neutrophil recruitment
stimulation of and macrophage and neutrophil production in bone marrow

Produce IL-22-> induces antimicrobial peptide production (at epithelial surfaces) act directly on extracellular pathogen to prevent it proliferating

Question 25

how does an antibody kill the pathogen?

Answer 25

• Not directly toxic
• they facilitate destrcution of antigens by enhancing innate immune mechanisms:
  1. Neutralisation
  2. Agglutination
  3. Opsonisation
  4. Antibody-dependent cell-mediated cytotoxicity (ADCC)
  5. Activation of complement
  6. Specialised responses

Question 26

1.antibody function- Neutralisation

Answer 26

Antibody binds to pathogen or toxin that pathogen’s producing to prevent attachment and entry into cell

Question 27

2.antibody function- Agglutination

Answer 27

Clumping of particles to increase their ability to be taken up. Lattice work formed, more likely to be phagocytosed, can involve complement pathway (removal of immune complexes)

Question 28

3. antibody function- Opsonisation

Answer 28

antibodies coat the bacteria and then certain cells have receptors (e.g. macrophages have fc receptors) antibody binds to receptor and facilitates engulfing of bacteria. Helps macrophage recognise it and engulf.

Question 29

4.antibody function- Antibody-dependent cell-mediated cytotoxicity (ADCC)

Answer 29

antibody binds to an infected cell or a large extracellular pathogen- too large to phagocytose
antibody forms bridge to immune cells via Fc receptors e.g. NK cells, macrophages etc.
mediates death of infected cell/pathogen

Question 30

5. antibody function- complement

Answer 30

trigger activation of the classical complement cascade

Question 31

6. antibody function-specialised response

Answer 31

e.g. IgE-mediated activation of mast cells- release of mast cell granules, lipid mediators and cytokines released
Initiates an inflammatory response- increased vasodilation, increased vascular permeability= accumulation of immune cells at site of infection

Question 32

Summary of antibody actions?

Answer 32

1. NEUTRALISING- pathogen/toxin to stop entry into cell
2. AGGLUTINATING- to facilitate phagocytosis
3. OPSINISING- pathogen/cell to facilitate phagocytosis
4. ADCC- aid killing by immune cells
5. COMPLEMENT- classical cascade activation
6. SPECIALISED RESPONSES- e.g. IgE-mediated activation of basophils/eosinophils/mast cells

Question 33

How have parasites adapted to avoid immune response?

Answer 33

parasitic worms have evolved to secret cytokine-like molecules to regulate host immunity
e.g. produce TGF-beta like molecules to induce Tregs, inhibits immune response against the parasite