Innate immunity

Question 1

What are the 3 components of the innate immune system?

Answer 1

1) Barriers - physical, chemical, biological

2) Cells (effector cells): phagocytes, NK cells, lymphocytes

3) Soluble molecules: complement proteins, cytokines (inflammatory mediators)

Question 2

Which effector cells fall in the myeloid lineage and the lymphoid lineage?

Answer 2

Myeloid lineage:
- Phagocytes: macrophages, monocytes, neutrophils, dendritic cells
- Other cells: basophils, eosinophils, mast cells

Lymphoid lineage:
- NK cells
- Innate lymphoid cells
- Lymphocytes (b and t cells)

Question 3

What are 3 functions of the NK cells?

Answer 3

1) Recognise infected cells and kills them (virus infected and tumour cells)

2) Express cytotoxic enzymes (lyse target cell)

3) Produce interferon- gamma/ IFN-y (antiviral)

Question 4

How to NK cells collaborate with macrophages?

Answer 4

After macrophages undergo phagosytosis they prouce IL-12 –> activates NK cells

Nk cells produce IFN-y –> activate macrophages –> better killing

Question 5

What are the 2 receptors on the NK cells and what types of cells do they recognise?

Answer 5

• Inhibitory receptors recognise ligands (MHC class I) on healthy cells
• Activating receptors recognise infected/stressed cells

Question 6

Which cells down-regulate MHC I and what is its effect?

Answer 6

• Virus infected cells
• Malignant cancer cells
• Inhibitory receptors on NK cells are not ligated by MHC 1 so will kill virus infected/tumour cells

Question 7

What are the 2 ways NK cells kill target cells?

Answer 7

1) Perforin: forms pores –> delivery of granzymes

2) Granzymes A, B, C: activate caspases –> apoptosis

Delivered at the site of contact between NK cell and target to prevent killing of neighbouring healthy cells

Question 8

What are innate lymphoid cells (ILC)?

Answer 8

• Similar to T cells but don’t express T cell receptors
• 3 different types producing different cytokines
• Faster responses (innate immunity)
• No clonal expansion/ differentiation

Question 9

What are lymphocytes with limited diversity?

Answer 9

• Combined features of T/B lymphocytes and innate cells
• Express Ag receptors but recognise limited number of Ags
• Respond in early stages of infection

Question 10

What are the 3 phagocyte defects/disease?

Answer 10

1) Chronic granulomatous disease - mutation in NADPH component, defect in oxidative burst

2) Chediak-Higashi syndrome - defective phagosome-lysosome fusion, decreased number of neutrophils

3) Leucocyte adhesion defects (LADs) - decreased integrins, defective neutrophil chemotaxis, impaired clearance of pathogens

Question 11

What are the different types of complement deficiencies?

Answer 11

• C2, C4, C1q deficiency: SLE-like syndrome
• C3 deficiency: pyogenic bacteria infections
• C5-C9 deficiency: neisseria infections
• C1 INH deficiency: Oedema in skin/mucosa
  abdominal pain, vomiting, diarrhoea, airway obstruction
• DAF, CD59 deficiency: paroxysmal nocturnal haemoglobinuria

Question 12

What are some defects in NK cells?

Answer 12

• As part of broader immunodeficiencies e.g. Chediak Higashi
• Complete absence of circulating NK cells

-Functional NK cell deficiencies (normal numbers)
Patients have fatal viral infections (herpes viruses)