Effector responses against infectious agents

Question 1

What do cells of the innate immune response get activated by?

Answer 1

Pathogen Recognition Receptors such as toll like receptors

Question 2

Which cells are phagocytes?

Answer 2

Macrophage, Dendritic cells, Neutrophils

Question 3

Which cells are granulocytes?

Answer 3

Eosinophils, basophils, neutrophils

Question 4

What is the major role of phagocytosis of dendritic cells?

Answer 4

To present pathogenic antigen to T-cells to stimulate adaptive response

Question 5

How does phagocytosis kill the pathogen?

Answer 5

Killing occurs by:

• acidification of phagosome
• contents of phagolysosome (enzymes, toxic oxygen species)
• in neutrophils, fusion of cytoplasmic granules containing enzymes and anti-microbial peptides with the phagosome.

Question 6

How do mast cells work?

Answer 6

Bind IgE on cell surface with high affinity. The mast cell is activated when IgE binds and antigen which releases granules.

Question 7

How do natural killer cells know which cells are abnormal?

Answer 7

All cells express MHCI. Abnormal cell may be under expressing MHCI so NK cell binds. As the inhibitory receptor will not have a ligand the cell is killed.

Question 8

How is complement activated and produced?

Answer 8

Produced in the liver as an inactive precursor. Activated by cleaving into two parts; a mediator of inflammation and another with a binding site for next protein and an active enzymatic site.

Question 9

What 3 pathways can activate complement?

Answer 9

1. Classical pathway- complement binds to antibody bound to pathogen surface.
2. Alternative pathway- complement binds to pathogen surfaces.
3. Lectin pathway- complement binds to mannose binding protein bound to pathogen surface.

All 3 pathways generate a C3 converts which cleaves C3.

Question 10

How does C3 cleavage lead to removal of pathogen?

Answer 10

• Induction of cell lysis in infected cells
• Opsonisation of pathogen
• Induction of chemotaxis and inflammation
• Immune complex clearance

Question 11

What is the function of CD4+ T cells and CD8+ T cells?

Answer 11

CD4+:
-Become helper cells-facilitate activation of other immune responses.

CD8+:
-Become cytotoxic T-lymphocytes-directly kill cells infected with intracellular pathogens.

Question 12

How does a CTL kill other cells?

Answer 12

1. CTL binds loosely to target cell.
2. CTL recognises antigen (presented by MHCI) and T-cell cytoskeleton reorganises to place granules at site of contact.
3. CTL releases cytotoxic granules at the cell-cell contact+ very quick, induces apoptosis.

Question 13

What do cytotoxic granules contain?

Answer 13

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

Question 14

What cytokines do CTLs produce to regulate the immune response?

Answer 14

Interferon gamma
TNF-alpha
LT-alpha

Question 15

How do Th1 cells activate macrophages?

Answer 15

• secretion of IFN-gamma
• CD40 ligand-CD40 interaction

Activated macrophages up regulate MHCII- increase T cell activation.

Question 16

How do Th2 cells activate basophils, eosinophils and mast cells?

Answer 16

• directly via Th2 cytokines

- indirectly via stimulation of B-cells to make IgE.

Question 17

How do Th17 cells regulate immune responses?

Answer 17

IL-17:
acts of several cell types to induce cytokine/chemokine secretion->neutrophil recruitment->stimulation of macrophage and neutrophil production in bone marrow.

IL-22:
induces antimicrobial peptide production

Question 18

How do Th1 cells promote indirect killing of pathogens?

Answer 18

• Macrophage activation
• T-cell proliferation
• Antibody production

Question 19

What 6 mechanisms do a antibody effector mechanisms enhance?

Answer 19

1. Neutralisation
2. Agglutination
3. Opsinisation
4. Antibody-dependent cell-mediated cytotoxicity
5. Activation of complement
6. Specialised responses