Review of The Innate Immune System

Question 1

Resolution of infection requires what

Answer 1

Resolution of infection requires both adaptive and innate immune responses

Question 2

Compare specificity of adaptive/innate immunity

Answer 2

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 3

List the components to innate immunity

Answer 3

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

Question 4

Phagocytosis - where and by what

Answer 4

Carried out in vertebrates by Dendritic cells, macrophages and neutrophils

Question 5

Phagocytosis - purpose

Answer 5

Phagocytosis clears pathogens but also presents peptides on MHCs – this promotes development or reactivation of the adaptive immune response

Question 6

Macrophages have two distinct roles in innate immunity - describe

Answer 6

Phagocytosis; material is destroyed in lysosomes

Captured material can trigger macrophage activation - activated macrophages produce cytokines and chemokines

=

to stim innate/adaptive immune responses = inflammatory response + can promote a local anti-microbial state

Question 7

The Inflammatory Response - purpose

Answer 7

A generic defence mechanism whose purpose is to localize and eliminate injurious agents and to remove damaged tissue components

Question 8

The Inflammatory Response - effects

Answer 8

Enhanced permeability and extravasation
Neutrophil recruitment
Enhanced cell adhesion
Enhance clotting

Question 9

Cytokines - function and examples

Answer 9

Act to modify the behaviour of cells in the immune response

Most of these are called interleukins (eg. IL-1)

Question 10

Chemokines - function

Answer 10

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 11

How do Phagocytes know what to eat?

Answer 11

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 12

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

Answer 12

Molecules present only on pathogens and not on host cells

Question 13

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

Answer 13

Essential for survival of pathogens

Question 14

Examples of Pathogen-associated Molecular Patterns (PAMPs)

Answer 14

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 15

Pattern recognition receptors (PRRs) - define + describe function

Answer 15

Host factors that specifically recognise a particular type of PAMP

They are germ-line encoded

Question 16

There are several classes of PRR, but functionally they are either:

Answer 16

There are several classes of PRR, but functionally they are either:

Extracellular – they recognise PAMPs outside of a cell and trigger a co-ordinated response to the pathogen

Intracellular (cytoplasmic) – they recognise PAMPs inside a cell and act to co-ordinate a response to the pathogen

Secreted – they act to tag circulating pathogens for elimination

Question 17

Receptor - lectin receptors

• describe the:

Ligand (PAMP)
Outcome

Answer 17

Lectin receptors

Ligand (PAMP) = Terminal mannose and fucose

Outcome = phagocytosis

Question 18

Receptor - Scavenger receptors

• describe the:

Ligand (PAMP)
Outcome

Answer 18

Ligand (PAMP) = Bacterial cell walls
Modified low-density lipoproteins

Outcome = phagocytosis

Question 19

Receptor - Toll-like receptors (TLRs) (surface and endosomal)

• describe the:

Ligand (PAMP)
Outcome

Answer 19

Ligand (PAMP) = LPS (together with CD14)
Lipoproteins
Unmethylated CpG
Flagellin
dsRNA; ssRNA (in endosomes)

Outcome = Inflammation: cytokine release (TNF, IL-1, IL-12)
enhanced killing: reactive oxygen species, NO);
phagocytosis

Question 20

Receptor - NOD-like receptors (NLRs) (cytoplasm)

• describe the:

Ligand (PAMP)
Outcome

Answer 20

Ligand (PAMP) = Peptidoglycan from Gram-positive and Gram-negative bacteria

Outcome = Inflammation: cytokine release (IL-1, IL-8)

Question 21

Receptor - RIG-like receptors (RIG-1 and MDA5) (cytoplasmic)

• describe the:

Ligand (PAMP)
Outcome

Answer 21

Ligand (PAMP) = dsRNA and 5’-triphospho-RNA

Outcome = Type I interferon production
Apoptosis

Question 22

The Complement System - describe

Answer 22

Originally described as a heat-sensitive component of serum that could augment the ability of antibodies to inactivate antigen

Question 23

The Complement System - function

Answer 23

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)

Question 24

The Complement System - role in action of pattern recognition receptors

Answer 24

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”

Question 25

Interferons - define, distribution, induced by what and function

Answer 25

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 26

Anti-microbial peptides (AMPs) | (e.g. Defensins) - define and describe function

Answer 26

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 27

Intrinsic defences – “the hostile cell” - list

Answer 27

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

Question 28

``` Natural Killer (NK) cells (Large granular lymphocytes) - define and describe function ```

Answer 28

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 29

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

Answer 29

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 30

Innate immunity, describe the: ``` Cell types Speed Memory Specificity Receptors ```

Answer 30

Innate first: Cell types Macrophages, Neutrophils, DCs Speed Fast Memory No Specificity Low Receptors Pattern Recognition

Question 31

Adaptive immunity, describe the: ``` Cell types Speed Memory Specificity Receptors ```

Answer 31

Innate first: Cell types Lymphocytes Speed Slow Memory Yes Specificity High Receptors Ig, TCR

Question 32

Innate immunity, describe the: Pattern recognition

Answer 32

Small number of microbial ligands that are highly conserved between pathogens; Germ-line encoded receptors evolved by natural selection

Question 33

Adaptive immunity, describe the: Receptor system

Answer 33

Billions of possible antigens. | Receptors generated randomly within individual; cannot be inherited