Innate Immune System

Question 1

Describe the barriers present in the innate immune system

Answer 1

• physical barriers against invasion e.g., epidermis of skin, eyelids, earwax
• inhospitable environments e.g., stomach acid, mucous, cilia
• microbiome - competes with pathogens for resources

Question 2

Describe the anti-microbials present in tears and saliva

Answer 2

• lyzosomes attack peptido-glycans in gram-positive bacterial cell walls
• leads to holes in the walls

Question 3

Describe defensins

Answer 3

• small proteins
• present in lungs, skin, gut, tears
• attacks lipid bilayers
• effective against viruses, bacteria, fungi
• can be induced after activation

Question 4

How do defensins attack lipid bilayers?

Answer 4

• defensins are positively charged molecules
• form pores in bilayer

Question 5

What are PRRs?

Answer 5

Pattern Recognition Receptors
- innate cell receptors that recognise non-self molecules e.g., lipopolysaccharides are only in gram-negative bacteria
- collectively called Pathogen-Associated Molecular Patterns (PAMPs)
- important in identifying pathogens
- recognise conserved PAMPs
- different PRRs interact with different PAMPs - different responses

Question 6

Describe PAMPs

Answer 6

highly conserved so hard for pathogens to evade recognition

Question 7

Give 4 different PRRs

Answer 7

• Toll-Like Receptors (TLRs)
• NOD-like receptors
• Lectins
• RIG-like receptors

Question 8

Describe Toll-like receptors

Answer 8

• multiple receptors in family
• recognise range of PAMPs
• TLR4-LPS recognise gram negative
• TLR9-CpG DNA recognise viral/bacterial
• some occur at cell surface, some within endosomes

Question 9

Describe the activation of TLRs

Answer 9

• TLRs dimerize and induce signalling via adaptor proteins e.g., TRIF or Myd88
• TLR-initiated signalling activates transcription factors e.g., IRFs or Nf κβ
• these mediate transcription of specific cytokines, activating immune system

Question 10

Describe how TLRs within endosomes are different

Answer 10

recognise nucleic acid structures

Question 11

Describe NOD-like receptors

Answer 11

• NOD 1 & 2 are cytoplasmic receptors
• recognise peptidoglycans from bacteria

Question 12

Describe Lectins

Answer 12

• surface receptors
• mannose receptor recognises terminal mannose - glycan unique to microorganisms

Question 13

Describe RIG-like receptors

Answer 13

• cytoplasmic receptors
• MDA5 recognises dsRNA from viruses

Question 14

What are the 7 major innate immune cell types?

Answer 14

• dendritic cells
• macrophages
• neutrophils
• eosinophils
• basophils
• mast cells
• natural killer cells

Question 15

Describe dendritic cells

Answer 15

• present in skin, lungs, gut etc
• major function mediating immune response
• innate and adaptive
• not an effector cell
• activation leads to inflammation
• pathogen molecules shed/dead internalised via phagocytosis or macropinocytosis
• release of immune molecules

Question 16

Which PRRs are expressed in dendritic cells?

Answer 16

TLR1, TLR2, TLR3, TLR4, NOD1, NOD2, MDA5

Question 17

What is the activated function of dendritic cells?

Answer 17

• antigen uptake in peripheral sites
• antigen presentation

Question 18

Which immune molecules are released from dendritic cells?

Answer 18

• cytokines
• chemokines

Question 19

Describe cytokines

Answer 19

• small, soluble proteins - peptides and glycoproteins
• intercellular messengers of immune system
• binds to specific membrane receptors

Question 20

Describe chemokines

Answer 20

• subset of cytokines
• specialised function - chemoattractants
• mobilise immune cells to move to tissues or within tissues

Question 21

Describe macrophages

Answer 21

• PRR activation on macrophages initiates phagocytosis
• critical for adaptive response
• can kill pathogens

Question 22

What are the activated functions of macrophages?

Answer 22

• phagocytosis
• activation of bactericidal mechanisms
• antigen presentation

Question 23

Which PAMPs are expressed from macrophages?

Answer 23

TLR1, TLR2, TLR3, TLR4, NOD1, NOD2, MDA5

Question 24

Describe the process of inflammation

Answer 24

• bacteria trigger macrophages to release cytokines and chemokines
• vasodilation and increased vascular permeability cause redness, heat, swelling
• inflammatory cells migrate into tissue, release inflammatory mediators that cause pain

Question 25

Describe immune evasion in relation to phagocytosis

Answer 25

• deliberate modulation of a host system to benefit infectious agent
• can prevent phagocytosis on specific bacteria
• can prevent lysosome fusion
• can escape endosome

Question 26

Describe the process of phagocytosis

Answer 26

• PRRs and other receptors bind micro-pathogen
• Transported by phagosomes-
• Fuse with lysosomes
• Pathogen destroyed by lysosome products
• destroyed pathogen used to aid adaptive immune response

Question 27

Describe neutrophils

Answer 27

• earliest responders to any infection
• largest % WBCs in blood of most species
• formed in bone marrow & moves from blood to tissue site of infection
• NETosis

Question 28

Describe the activated function of neutrophils

Answer 28

• phagocytosis
• activation of bactericidal mechanisms

Question 29

Describe NETosis

Answer 29

• neutrophils kill extracellular bacteria, fungi after LPS or CXCR8 activation
• release nuclear antimicrobial contents

Question 30

What are the other effector mechanisms of the innate immune system?

Answer 30

• NK cell killing
• complement
• degranulation