Lecture 3 Flashcards Preview

Principles immunology > Lecture 3 > Flashcards

Flashcards in Lecture 3 Deck (25):
1

What is the late phase acute inflammation composed of 

  • Neutrophils 
  • Complement 
  • Dendritic cells

2

What are the local effects of pro-inflammatory mediators 

A image thumb
3

Describe endothelial migration 

  1. Endothelial cells express - Selectins for carbohydrates on neutrophils 
  • Week binding - causes rolling of neutrophils

    2. Endothelial cells express iCams for intigrins on neutrophils 

  • Stronger binding causes stable adhesion and agregation of neutrophils 
  • Transendothelial migration 

A image thumb
4

Describe acute inflammaiton 

  1. Macrophages, mast cell -> Histamine, pro-inflammatory cytokines and chemokines
  2. ​Increased vascular permeability
  3. Vasodilation and increased blood flow
  4. Endothelial cell activation, adhesion molecules - Icams and Selectins 
  5. Transendothelial migration - nuetrophils squeez through endothelial cells 

A image thumb
5

How do neutrophils migrate to the site of injury 

Through chemokines produced by macrophages and mast cells 

6

Describe neutrophils 

  • polymorphonuclear cells 
  • phagocytes that circulate in the blood 
  • Charateristic features: Intra-cellular granules and multilobed nucleus 
  • Recuireted by cytokines and proinflammatory mediators 

A image thumb
7

what are the functions of neutrophils 

  • Kill pathogen
  • Release more pro-inflammatory cytokines - TNFa

8

What are the 3 types of neutrophil killing mechanisms 

  • Phagocytosis
  • Degranulation 
  • NETs

A image thumb
9

Describe neutrophil phagocytosis 

After encapsulating the bacteria, neutrophils can kill via 2 mechanisms 

  1. Anti-microbial proteins and enzymes 
  2. Reactive oxygen species

10

Describe the 1st phagocytic mechanism of neutrophils 

  • Encapsulating bacterai into cytoplasm - phagosome formation
  • Phasome fuses with Azurophillic and specific granules 
  • PH of phagosome rises 
  • Antimicrobial responce is activated and bacterium is killed
  • PH Descreases - fusion with lysosomes 
  • Acid hydrolases degrades the phagosome compeletly 

A image thumb
11

Describe the 2nd mechanism of Neutrophil phagocytosis 

  1. Neutrophil activation via pro-inflamamtory mediators
  2. Assembly of NADPH oxidase complex 
  3. Production and release of ROS into phagosome 
  4. NADPH oxydase dependent mechanism 

A image thumb
12

How does neutrophil granulation clear infection

  • Release of anti-microbial proteins directly into extracellular millieu
  • Direct killing of extracellular pathogens 
  • can lead to tissue damage and systemic inflammation

A image thumb
13

How do neutrophils trap extra-cellular pathogens via NETs

  • Activated neutrophils release intracullar structures (DNA HIstones etc) into extracelluar spaceto trap potential pathogens 
  • Imobilize pathogens 
  1. ​prevent them from spreading 
  2. Facilitates their phagocytosis 

A image thumb
14

Main difference between macrophages and neurophils 

Neutrophils are short-lived - Pus

A image thumb
15

Decribe the complement system 

  • Family of 30 proteins 
  • produced by the liver- circulate in blood as inactive precursors - enter infected or inflammad tissue 
  • Activated directly or indirectly by pathogens
  • When activated they cleave each other dowstream in an enzamatic cascade reaction

A image thumb
16

What are the 3 pathways of complement 

  

  1. Classical pathway
  2. Mannose binding lectin pathway
  3. Alternative pathway 

17

whats the function of complement 

  • Pathogen Opsonisation 
  • Pathogen killing 
  • Recruitment of Leukocytes and inflammation
  • Removal of immune complexes 

A image thumb
18

Describe the mannose binding lectin pathway of complement 

 

 

  • Mannose (bacterium) binds to MBL (mannose-binding lectin)  
  • This triggers activation and cleavage of C3
  • C3 is cleaved into C3a and C3b
  • Leads to downstream events and amplification loop 

A image thumb
19

Describe the alternative pathway

  • Spontanous cleavage of C3 into C3a and C3b 
  • C3b is then either rapidly degraded 
  • Or binds to Bactieral carbohydrates/protein ligands to stabalise them
  • Binding to C3b to these ligands then triggers an amplificaiton loop 
  • This results in more cleavage of C3 protein
  • this is also selective because human cells express inhibitory proteins that results in degradation of any bound C3b

A image thumb
20

What happens when theres activation of downstream complment proteins in the 2 pathways

  • Pathogen opsonisation
  • Pathogen killing
  • Recruitment of leukocytes and inflammation 
  • Removal of immune complexes 

A image thumb
21

Describe pathogen killing by complement 

  • Formation of membrane attack complex - defense againts encapsulated bacteria 
  1. C5b binds to surface pathogens
  2. C6, 7, 8, 9 assemble with C5b to form the membrane attack complex
  3. Inserts into pathogen - forms a whole
  4. Osmotic cell lysis

A image thumb
22

Describe opsonisation by complement 

Coating of bacterial by humeral factors to enhance phagocytosis

  • Examples : C3b , CRP, IgG/IgM
  • Phagocytes express opsonine receptors on their surfaces to bind the opsonised pathogen
  • Esp Encapsulated bacteria

A image thumb
23

Describe leukocyte recruitment by conplement 

  • C3a and C5a are known as anaphylatoxins ​​
  1. Activation of mast cells - released of pro-inflammatory mediators and chemokines - Which leads to increased permeanbility - leakage of fluid containing opsosnines and antibodies and recruitment of inflammatory cells
  2. Also can act directly on blood vessels to produce these effects

A image thumb
24

How is the complement system regulated 

1. Only cleaved Complement proteins are active

2. Active Complement proteins have very short half-life

3. Some Complement proteins are only produced during an Acute Phase Response

4. Some Complement proteins do not bind to human cells

5. Complement inhibitors and regulatory proteins limit activation of the system

A image thumb
25

Describe dendritic cell activity 

A image thumb