L12- Immune system in action

Question 1

How are extracellular bacteria targeted by the immune system?

Answer 1

Antibody responses such as opsonisation and complement system
Phagocytosis
Neutralisation of toxins
Activation of CD4+ cells to activate humoural immunity, anti-inflammatory cytokines, macrophage cytokines

Question 2

How do extracellular bacteria evade the immune response?

Answer 2

Antigenic variation via mutations, inhibiting TLR recognition and signalling by changing PAMPS.

Secretion of membrane blebs to divert Ab response

Resistance to antimicrobial peptides
Resistance to phagocytosis

Complement inhibition by mimicking host proteins, secreting proteases and evasion molecules.

Question 3

How do intracellular bacteria evade the immune system?

Answer 3

Inhibition of phagolysosome formation
Resistance to degradation by phagolysosome
Escaping the phagolysosome altogether

Question 4

How do viruses evade the immune system?

Answer 4

Antigenic variation
Inhibition of MHC pathway
Production of immunosuppressive products
Infection or death of immune cells (HIV)
Inhibition of complement/virus danger sensors

Question 5

What are cancer cells?

Answer 5

Aging or disrupted cells that no longer follow the cell cycle correctly.

Divide in an uncontrolled manner to create a mass with a tumour microenvironment- low O2 (blood supply) and nutrients so less immune cells can reach

Question 6

What is the Warburg effect in cancer cells?

Answer 6

Cancer cells produce energy via anaerobic respiration in glycolysis even if oxygen is present.

Question 7

What are the consequences of the Warburg effect?

Answer 7

Increased production of lactic acid therefore more acidic conditions
Increased hypoxia and PDL1

Lead to suppression of effector function of immune cells.
Immune cells upregulate CTLA-4 and PD1 (inhibit T cell activation).
M2 polarisation occurs.

Question 8

How do cancer cells respond to the immune system?

Answer 8

Recruitment of anti inflammatory cells (T regs)
Release of anti-inflammatory factors
Inhibition of Ag presentation
Promotion of co-inhibition (PD1,CTLA4)

Question 9

What is immune tolerance (immunopriviledge)?

Answer 9

A state of unresponsiveness of the immune system which needs to be established at times to prevent chronic inflammation (can cause cardiovascular disease, organ rejection etc)

Question 10

How does immune tolerance happen?

Answer 10

1. Anatomy
2. Increased regulatory cytokines like IL10, TGFbeta
3. Decreased effector populations- MHC expression, complement inhibition, immunosuppressive cytokines

Question 11

How is the eye immunopriviledged?

Answer 11

1. Blood eye barrier, little vasculature and no lymphatics
2. Immunosuppressants
   Soluble- neuropeptides, TGFbeta, IDO
   Membrane bound- FAS ligand, PD1

Question 12

How is the brain immunopriviledged?

Answer 12

1. Blood brain barrier and tight junctions
2. Immunosuppressants
   Soluble- neuropeptides (somatostatin)
   Astrocytes- microglia

Question 13

How is the placenta immunopriviledged?

Answer 13

1. Uterus and placenta

2. T regs, low nutrients, complement inhibition, TGFbeta and IL10, Low MHC complexes