49. Review of Innate Immunity

Question 1

Specificity in immunity

Answer 1

• Adaptive immunity – involves very specific recognition of infectious agent (usually sees a protein = antigen)
• Innate immunity – no specific antigen recognition
• Innate involves recognition of broadly conserved features of different classes of pathogens

Question 2

Components to inate immunity

Answer 2

• Phagocytosis
• The Inflammatory Response
• Cytokines, Interferons and Antimicrobial peptides (AMPs)
• Complement
• Intrinsic Defences – “the hostile cell”
• NK cells

Question 3

Expand on phagocytosis

Answer 3

• Carried out in vertebrates by Dendritic cells, macrophages and neutrophils
• Phagocytosis clears pathogens but also presents peptides on MHCs – this promotes development or reactivation of the adaptive immune response

Question 4

Macrophage role in innate immunity

Answer 4

Phagocytosis; material is destroyed in lysosomes

Captured material can trigger macrophage activation - activated macrophages produce cytokines and chemokines to stimulate both innate and adaptive immune responses – this triggers the inflammatory response and can promote a local anti-microbial state

Question 5

What is involved in the inflammatory response?

Answer 5

• A generic defence mechanism whose purpose is to localize and eliminate injurious agents and to remove damaged tissue components
• Enhanced permeability and extravasation
• Neutrophil recruitment
• Enhanced cell adhesion
• Enhance clotting

Question 6

What are cytokines and chemokines?

Answer 6

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 7

How do Phagocytes know what to eat?

Answer 7

Material to be “eaten” is recognised in a number of ways:

• By detecting phosphatidylserine on exterior membrane surface (cells undergoing apoptosis)
• By Scavenger receptors
• By some Toll-Like Receptors (TLRs)
• By passive sampling

Question 8

What are PAMPs? and give some examples.

Answer 8

Pattern recognition is through Pathogen-associated Molecular Patterns (PAMPs)

• Molecules present only on pathogens and not on host cells
• Essential for survival of pathogens
• Invariant structures shared by entire class of pathogens

EXAMPLES:

• Gram-negative bacteria; lipopolysaccharides (LPSs) found in outer membrane
• Gram-positive bacteria; teichoic acid, lipoteichoic acid, peptidoglycan found in outer membrane
• Bacterial flagellin
• Abnormal protein glycosylation
• Abnormal nucleic acids - viruses

Question 9

What are PRRs?

Answer 9

Pattern recognition receptors (PRRs)

•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:
1) Extracellular – they recognise PAMPs outside of a cell and trigger a co-ordinated response to the pathogen
2) Intracellular (cytoplasmic) – they recognise PAMPs inside a cell and act to co-ordinate a response to the pathogen
3) Secreted – they act to tag circulating pathogens for elimination

Question 10

The Complement System

Answer 10

Originally thought to be a biochemically complex antibody-dependent effector mechanism leading to:

- Opsonisation 
- Recruitment of phagocytic cells, vasoactive 	function
- Punches holes in target membranes (MAC)

• Complement proteins act as secreted Pattern recognition receptors (PRRs) and can be activated by a range of PAMPs, and can also be activated by “altered self”
•There are 3 pathways:
     1. Classical 
     2. Lectin 
     3. Alternative

Question 11

What are interferons?

Answer 11

• Secreted factors (type I and type III)
• Induced by viral infection
• Offer cross-protection
• Widely distributed in evolution, from fish upwards, but species-specific

Question 12

What are AMPs?

Answer 12

Anti-microbial peptides (AMPs)
(e.g. Defensins)

• Secreted short peptides (18-45 amino acids)
• Usually work by disrupting cell wall leading to lysis
• Some are induced by bacterial infection
• Offer broad protection

Question 13

What are intrinsic defences – “the hostile cell”?

Answer 13

• Apoptosis
• Restriction factors/Intrinsic •Immunity
• Epigenetic silencing
• RNA silencing
• Autophagy/Xenophagy

Question 14

Natural Killer (NK) cells 
(Large granular lymphocytes)

Answer 14

• 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 15

NK activation

Answer 15

Natural Killer (NK) cells are activated by loss-of-self

• 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