L1.2 Innate immunity

Question 1

Immunity

Answer 1

• the ability of an organism to resist a particular infection or toxin by the action of specific antibodies or sensitized white blood cells
• Characterised by: Hyperaemia, oedema, pain, leukocyte infiltration, loss of function

Question 2

Inflammation

Answer 2

• characterised by heart, redness, swelling, pain, loss of function

Question 3

Innate immunity overview

Answer 3

• Always takes effect through pro-inflammatory cytokines
• Quick, No memory
• Slash/Burn → resolves
  
  • Through neutrophils

Question 4

Adaptive immunity overview

Answer 4

• Works together with innate
• Slow, flexible, have memory & recall
• Amplify/kill/clear → Long-term memory

Question 5

Pattern recognition receptors (PRR)

Answer 5

• Toll-like receptors (1-11) - recognise: bacteria/viruses…
  
  • Expressed in sentinel cells (i.e. macrophages/dendritic cells)
• NOD/NLR - recognise: DNA from bacteria
• RLR - recognise: viruses
• CLR (C-type lectin/AKA Dectins) - recognise: fungi
  
  • There are 7 reused domains of PRR.

Question 6

Evolution of the immune system

Answer 6

• The immune system has evolved to discriminate b/w infectious non-self & non-infectious self

Question 7

Mounting an appropriate response

Answer 7

1. Recognise (self from non-self)
2. Kill/Contain (the inflammatory response)
   
   • *contain = putting a fibrous shell around it
3. Resolve (organ protective catabasis)
   
   • Decline of diseases by turning off inflammation

Question 8

Overview of infection + defense

Answer 8

• Bacterial adhesion to epithelium
• Local infection, penetration of epithelium (if skin is broken)
  
  • Induces wound healing
• Local infection of tissues - initiates adaptive immunity through:
  
  • Activation of macrophages
  • Dendritic cells migrating to lymph nodes
• Adaptive immunity

Question 9

Barriers of innate immunity

Answer 9

• Mechanical:
  
  • Movement of mucus by cilia
• Chemical
  
  • FA, enz, HCl
• Microbiological
  
  • Metagenome (our genome + bacteria genome)
    
    • Could defend from other bacteria

Question 10

Signal transduction from PRRs

Answer 10

*IRF = interfereron regulatory factor*

Question 11

TLRs

Answer 11

• Have similar structures, but sense different things → ultimately producing similar effects
• All signals converge to NFK-β and produce type I interferon response
• Can be monomers/complexes/heterodimers
• Evolved to recognise specific molecules
• e.g.
  
  • Toll 4 complex recognises LBP/LPS → NFK-β → produce pro-inflammatory cytokines
  • Toll 3, 7, 9 complexes recognise viruses → NFK-β → produce pro-inflammatory cytokines

Question 12

Important cytokines

Answer 12

Question 13

Activated neutrophils

Answer 13

• Attack & destroy bacteria by slash & burn destructive proteases & oxidants

Question 14

Progressive activation of leukocytes

Answer 14

• Endothelium irritated → produce endothelial chemoattractants → capture leukocytes → roll → *if insult is severe → firm adhesion → transmigration b/w cells (other chemoattractants in tissues)

Question 15

What is the pattern of WBC controlled by

Answer 15

• selectins & integrins

Question 16

Example of specific ligands & R. controlling movement of WBC in the body

Answer 16

• e.g. CCL8 (interleukin 8 - a ligand) works through CCR5.R → mobilises WBC to move from blood to tissues

Question 17

How is apoptosis achieved?

Answer 17

• Cell sustains irreparable damage (e.g. excessive DNA damage) → signaled to undergo apoptosis
  
  • Macrophages eat cell & removes (process kept inside cell)
    
    • Phagocytosis prevents inflammation
    • Is anti-inflammatory, PRO-resolution

Question 18

How is necrosis achieved?

Answer 18

• Serious chronic inflammation
• → overwhelmed by tissues cell death
• → necrotic cell released outside
• → leads to serious inflammation (detrimental) by releaseing toll agents (HMGBP, RAGE) → activates toll R.

Question 19

What are the pro-resolution processes?

Answer 19

• Clearance of pathogens
  
  • ↓ key signals for WBC → cell apoptose
• Efferocytosis (removing apoptic cells)
  
  • Turns on local anti-inflammatory factors to help tissues back to healed state

Question 20

Do steroids affect the innate immunity?

Answer 20

• Do not affect innate immunity