Lecture 11 – Innate Immunity

Question 1

Cytokines and Chemokines (4)

Answer 1

• Glycoprotein hormones that affect the immune response.
• Cytokines - Act to modify the behaviour of cells in the immune response.
• Most of these are called interleukins (eg. IL-1).
• Chemokines - Act as chemotactic factors – i.e. they create concentration gradients which attract (or occasionally repel) specific cell types to a site of production/infection.

Question 2

How do macrophages “see” microbes? (3)

Answer 2

• Passive sampling.
• Scavenger receptors.
• Engulfing apoptotic cells.

Question 3

Pattern recognition receptors (PRRs) (4)

Answer 3

• Host factors that specifically recognise a particular type of PAMP.
• They are germ-line encoded.
• There are several classes of PRR, but functionally they are either:
o Extracellular – they recognise PAMPs outside of a cell and trigger a co-ordinated response to the pathogen.
o Intracellular (cytoplasmic) – they recognise PAMPs inside a cell and act to co-ordinate a response to the pathogen.
o Secreted – they act to tag circulating pathogens for elimination.

Question 4

Receptors/Ligands/Outcome (2)

Answer 4

Lecithin receptors / Terminal mannose and fucose / Phagocytosis.

Scavenger receptors / Bacterial cell walls and modified LDLs / Phagocytosis.

Question 5

Complement (5)

Answer 5

Proteins made in liver that tag PAMPs,
• Three ways of activating:
1) Recognition of LPS and other PAMPs by the C1q component of “classical” pathway.
2) Non-host glycosylation is recognised by MBP and other lectins to activate the “lectin” pathway.
3) Membranes that are recognised as “non-self” activate the “alternative” pathway.
• Complement activation involves a proteolytic cascade.

Question 6

Natural iller (NK) cells (Large granular lymphocytes) (4)

Answer 6

• 4% white blood cells.
• Lymphocyte-like but larger with granular cytoplasm.
• Kill certain tumour & virally infected cells.
• Target cell destruction is caused by cytotoxic molecules called granzymes & perforins.

Question 7

NK cells - Activated by loss-of-self (2)

Answer 7

• NK cells possess the ability to recognise and lyse virally infected cells and certain tumour cells.
• Selectivity is conferred by LOSS of “self” MHC molecules on target cell surfaces, AND up-regulation of activating ligands.

Question 8

Inherited diseases associated with Innate Immunity (6)

Answer 8

• Complement – core defects (e.g. C3) linked to development of autoimmune diseases such as lupus.
• Complement – non-core defects linked to suspectibility to specific types of pathogens such as Neisseria.
• Macrophage deficiencies - Chronic granulomatous disease (CGD); No oxidative burst for bacterial killing.
• Macrophage deficiencies – IRF8 mutations linked to susceptibility to TB.
• Aicardi–Goutières syndrome associated with constitutive production of inflammatory cytokines.
• Lack of interferon-responsiveness – sensitivity to viral infection (e.g. measles).

Question 9

Innate vs Adaptive (12) - Table

Answer 9

ON DIAGRAM