Innate Immunity

Question 1

NATURAL KILLER (NK) CELLS:
What types of cells does it kill? How does it do this?
→ What are these cytotoxic substances stored in?
→ What does Perforin do?

What do the Granzymes (A/B/C) do?
→ How are they able to only kill the target cell and not the healthy cells nearby?

What else do they produce? What does this do?

What types of receptors do they have? What does each recognise?

What occurs when they recognise MHC I on a healthy cell?
→ How does this differ with a Virus-infected/cancer cell?

What are Intracellular Motifs (ITIM/ITAM)? How are they used in NK cells?

What is NK cell Deficiency?
→ Why can this be Fatal?

What are some examples of Lymphocytes with Limited recognition capacity?
→ When are they used?

Answer 1

• Virus-infected cells and cancer cells using cytotoxic Granzymes (lyse targets cells) and Perforin
  → Granules
  → Makes pores in the target cells for Granzymes to enter
• Activate Caspases, which initiates Apoptosis
  → They’re delivered very close to the target cell
• Interferon-γ to activate Macrophages for better killing and phagocytosis
• • Activating receptors - Recognise infected/stressed cells
  • Inhibitory receptors - Recognise MHC I on healthy cells
• They block the signals from activating receptors = NK cells don’t attack
  → They downregulate MHC I → No blockage of signals from activating receptors = NK cells attack
• They use phosphatases to block the other receptor signalling pathway
• Complete absence of circulating NK cells or Normal numbers with a deficiency in NK cell function
  → Viral infections
• NK-T cells, MAIT cells, Marginal zone B cells
  → Early stages of infection

Question 2

DEFECTS IN INNATE IMMUNITY:
Phagocyte Defects and Disease:
What are the ways Phagocytes can be deficient?

What is Chronic Granulomatous Disease?

What is Chediak-Higashi Syndrome?

With the 2 conditions above, since the phagocytosed microbes can’t be killed, what will it lead to?

Complement Deficiencies:
What does a C2/4/1q deficiency lead to?

What does a C3 deficiency lead to?

What does a C5-9 deficiency lead to?

What does a C1 INH deficiency lead to?

What does a DAF, CD59 deficiency lead to?

Answer 2

• Loss of Number or Function
• Mutation in NADPH component, so phagocyte can’t kill microbe through oxidation
• Defective Phagosome-Lysosome fusion in phagocyte and ↓Neutrophils (Neutropenia)
• Recurrent infections
• Defect in β2-chain Integrins, leading to Defective Neutrophil Chemotaxis = Impaired clearance of pathogen
• SLE-like syndrome
• Frequent bacterial infections
• Disseminated (Systemic) infections with Neisseria (e.g. Meningitis)
• Angioedema
• Paroxysmal (Sudden) Nocturnal Haemoglobinuria