cell-mediated immunity - block b

Question 1

what is cell mediated immunity

Answer 1

Activating macrophages and NK cells

Stimulating cytokine secretion

Activating antigen-specific cytotoxic T cells (CD8+)

CMI is most effective in destroying cells infected with viruses, intracellular bacteria and cancer.

Third line of defence

Question 2

intracellular pathogens

Answer 2

bacteria -

myobacterium tuberculosis

listeria monocytogenes

viruses -

herpes simplex

parasites -

trypanosoma brucei

toxoplasma gondii

leishmania spp.

Question 3

CMI is controlled primarily by the action of T cells

Answer 3

T-helper cells – help other cells by stimulating immunity. Recognises MHC-II through CD4 receptor.

Cytotoxic T cells (T-killer) – able to directly kill and infected cell. Recognises MHC-1 through CD8 receptor. MHC-I/CD8 complex releases perforins = cell lysis.

T-suppressor – suppresses the actions of activated T cells once the threat has ended. Prevents over reactivity.

T-memory – creates a larger and faster responses upon repeated exposure. Converted into large numbers of T-helper and cytotoxic.

Question 4

MHC recap

Answer 4

MHC-I: aids in differentiation between self and foreign cells or pathogens. CD8

MHC-II: Present on APCs, alongside MHC-I. MHC-I will present antigen, whereas MHC-II with present phagocytosed pathogens. CD4

Question 5

Cytotoxic T cells

Answer 5

Used to lyse body’s own cells – get rid of abnormal cells or pathogen infected cells

Do not lyse pathogen directly

Need close contact with target – immunological synapse
Cause apoptosis of target – no inflammation

Question 6

CD4 Th1 dependent Tc generation

Answer 6

IL-2 drive T-cell proliferation

IFNgamma drives activation of more macrophages/APCs

TNFbeta can be cytotoxic and induces inflammation, is required for NK-cell differentiation

Fas-ligand induces programmed cell death

Question 7

Type IV hypersensitivy (DTH)

Answer 7

Under certain circumstances, an inappropriate inflammatory response can cause significant tissue damage or even death

Certain Ags activate specific populations of Th cells:
secreting cytokines that induce a DTH - Massive inflammatory cell infiltration, in particular macrophages

First called the tuberculin reaction after response to injected tuberculin filtrate - test for Mycobacterium infection

Hallmark: delayed response & macrophage recruitment rather than neutrophils

Delayed-type hypersensitivity responses often generated against pathogens living inside the macrophages themselves
- recruit monocytes to site of infection
- keep monocytes/Mfs at site of infection
- activate monos/Mfs to kill intracellular pathogens

Question 8

DTH response and amplification loop

Answer 8

Macrophages and Th cells stimulate each other (amplification loop, increasing magnitude of DTH response)

TNFa & IL-2 contribute to macrophage activation in the presence of IFNg

Macrophages retained at DTH site by Macrophage Inhibition Factor (MIF), secreted by Th cells

Upon Ag elimination, macrophages no longer stimulate Th cytokine production maintaining

Question 9

DTH responses do not eliminate infection
& become chronic

Answer 9

Granuloma formation

Chronic macrophage stimulation (fibrin deposition, formation of epithelioid cells - Lytic enzymes released from activated macrophages – extensive tissue damage.

Fibrin can “wall-off area” – lack of O2, tissue necrosis, limits spread

Question 10

In summary: Cell-Mediated Immunity

Answer 10

Principal defence against intracellular microbes

Mediated by T lymphocytes

2 effector responses generated to deal with intracellular pathogens:
- Tc production
- DTH responses

Tc provide the best protection against chronic non-lytic viral infections

DTH responses carry the greatest risk of damage to the host