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Microorganisms + Disease > Complement and Inflammation L6 > Flashcards

Complement and Inflammation L6 Flashcards

1
Q

what is the innate immune response for

A

recognition

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2
Q

what happens in the innate immune resposne

A

bacterial cell surface induces cleavage, complement activation
a complement covalently bonds to bacterium, other attracts effector cell
complement receptor on effector cell binds to complement on bacterium
effector engulfs bacterium, kills it

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3
Q

what is the complement system

A

Complement pathways need C3 molecule
All three pathways lead to lysis of C3 they then all expand out to different potential ways that they can have effect, depending what the immune system requires

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4
Q

what are the effects that the complement system lead to

A

Recruitment of inflammatory cells
Opsonization of pathogens
Killing of pathogens

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5
Q

how is the classical pathway - complement activation classical pathway

A

C3b bind to pathogen surface causing optimisation effect, so pathogen can be recognised by the innate immune system

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6
Q

how does the classical pathway in complement activation begin

A

engagement of C1q globular heads to the antibodies

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7
Q

what are the antibodies that bind to C1q

A

IgM - five of them stick together via the constant region to form a pentamer
IgG - when two or more in close proximity bound to the surface through dimer formations

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8
Q

how does IgM bind to pathogens

A

IgM binds to several epitopes on the surface of the pathogen, it is bent into the staple conformation, allowing the C1q globular heads to bind to the Fc regions of IgM
Bending where globular heads can bind to
Conformational change – c1q bind to surface

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9
Q

how does the IgM structure change

A

pentameric form is a flat planar like structure

turns to staple structure

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10
Q

how does IgG bind to pathogens

A

C1q can bind to two or more IgG molecules which have bound to epitopes on the pathogen surface, then can get activation of the complement cascade

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11
Q

what happens in the mannose binding lectin pathway

A

Mannose Binding Lectin (MBL) recognises
carbohydrates present at the surface of pathogens
Sugars bound on pathogen surface, mannose binding lectin recognizes
Can get activation of the pathway

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12
Q

C3 function in the complement cascade

A

Activation of complement cascade
takes C3 and breaks into C3b and C3a
C3b binds to the surface of the pathogens
C3a activate other parts of immune system

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13
Q

what does C3 convertase do

A

There is a slightly different variant of C3 convertase that can break and cleave C3 into C3a and C3b

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14
Q

what happens after C3 is bound to the pathogen surface

A

Activate more parts in complement cascade

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15
Q

what does the C3 convertase do

A

The two C3 convertases generated through the three pathways of complement activation can form a complex with C3b to generate a C5 convertase

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16
Q

what does C5 convertase do

A

cleave C5 into C5a and C5b

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17
Q

what does C5 cleavage cause

A

leads to the formation of the membrane attack complex

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18
Q

how is a membrane attack complex formed

A

C5 cleaves then c5b bind too c6 c7
C5b67 forms a complex that bind to surface via C7
C8 then binds to this complex and inserts into cell membrane

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19
Q

how do membrane attack complexes form holes in the membrane

A

C9 then can form a pore in the membrane - osmosis
So the cell dies
Complement cascade – kill the pathogen

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20
Q

what happens after the C3b is bound

A

opsonization of pathogens

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21
Q

how do macrophages recognise material

A

through opsonic and non-opsonic receptors

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22
Q

what is used in direct recognition

A

non-opsonic

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23
Q

what is used in indirect recognition

A

opsonic
Antibody-Fc receptor
Complement-Complement receptor

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24
Q

what does the pathogen bind to

A

the complement

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25
Q

how can clearance be enhanced

A

tagging the microbes

recognised by complement receptors in immune system

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26
Q

what happens after C3b is bound

A

recruitment of inflammatory cells = inflammation

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27
Q

what receptor do cells for innate immunity have

A

Cells relevant for innate immunity have receptors for the soluble cleavage products C3a and C5a

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28
Q

what contributes to inflammation initiation

A

Once C3a and C5a bind to their receptors cells become activated. This effect contributes to the initiation of inflammation

29
Q

what happens when complement activation occurs to immune system

A

Other parts of the immune system are activated

30
Q

what are the regulations in complement activation

A

Inactivation of the C3 convertase
Inactivation of C5 convertase
No formation of membrane-attack complex

31
Q

what are the features of gram negative bacteria

A

Long polysaccharide chains in cell wall (LPS)

32
Q

what are the features of gram positive bacteria

A

Layer of peptidoglycan in cell wall

33
Q

what may some pathogens do to subvert complements

A

Proteins that mimic complement regulatory proteins

34
Q

how do gram negative bacteria affect complements

A

LPS forms a barrier around e.g.E. coli so cant get the formation of MAC complex, so no pore formation

35
Q

how do gram negative bacteria affect complements

A

Prevents insertion of MAC

36
Q

how do some pathogens affect complements

A

Inhibit complement cascade

37
Q

what is an inflammatory response

A

Complex response to local injury or trauma

38
Q

what does vasodilation do

A

increase in the diameter of blood vessels, responsible for tissue redness and increase tissue temperature

39
Q

what does vasoconstriction do

A

influx of white cells and fluid (exudate) from the capillaries into the tissue, responsible for swelling (oedema)

40
Q

what happens after injury occurs to the body

A

Injury then the different inflammations :pain swelling, warmth, redness
Recruitment to try clear

41
Q

what happens in the body when injured

A

innate immune system activated
C3 and C5 cleaved off by the C3 convalutase and C5 convalutase, increase the vascular permeability – vasodilation, more components can come inside the tissue – build complement cascade to help start inflammation response
Cells recruited to site, all have different function - amplification effect to clear infection

42
Q

how are macrophages and dendritic cells ‘aware’

A

‘aware’ of the presence of infection because they express multiple receptors

  • Pattern recognition receptors
  • Complement receptors
  • C5a, C3a and C3b
43
Q

what is macrophages and dendritic cells response to infection

A

producing cytokines and chemokines

44
Q

how is cytokine production activated by macrophages

A

activated macrophages secrete cytokines
Act as messengers – tell need to clear infection
Different cytokines have different effects on different parts of the body

45
Q

what does interleukin - 1beta (IL-1beta) do when cytokines released

A

activated vascular endothelium
activates lymphocytes
local tissue destruction
increases access of effector cells

46
Q

what does tumour necrosis factor alpha (TNF-alpha) do when cytokines released

A

activated vascular endothelium
increase vascular permeability = more IgG, complement and cells enter tissues
increased fluid drainage to lymph nodes

47
Q

what does Interleukin-12 (IL-12) do when cytokines are released

A

activates natural killer cells

induces differentiation of CD4 T cells into TH1 cells

48
Q

what are chemokines

A

Small proteins mainly chemo attractant for leukocytes

49
Q

what do chemokines fo

A

Recruit cells to site of inflammation

Recruit cells to secondary organs

50
Q

how are chemokines released

A

activated macrophages release range of cytokines

51
Q

in normal epithelium what is the interaction between leukocytes

A

selectin-mediated adhesion to leukocyte is weak, allows leukocytes to roll along vascular endothelial surface

52
Q

what are the stages when activated epithelium - interaction between leukocytes and epithelium

A

rolling adhesion
tight binding
diapedesis
migration

53
Q

what happens when infection in body (endothelium)

A

chemokines(IL-8) high concentration nearest to the site of infection – help tell immune system where the site of infection is

54
Q

what occurs in rolling adhesion

A

Neutrophil will bind to a E-selectin and the chemokine (IL-8) binds to help hold the neutrophil in the same place

55
Q

what occurs in tight binding

A

complex is attached to the LFA that is bound to the ICAM-1, through the LFA and ICAM-1 binding is really strong, so stops cell disappearing off

56
Q

what happens in diapedesis

A

diapedesis of the cell into the capillary to the site of the infection

57
Q

what happens in migration

A

once the cell is in the tissue can migrate to the site of infection due to the chemokine gradient, and help to kill pathogen

58
Q

what happens after 24h in inflammatory cells

A

neutrophil - phagocytosis and activation of bactericidal mechanisms
eosinophil - killing of antibody coated parasites

59
Q

what happens after 3-4 days in inflammatory cells

A

basophil present

60
Q

what are the systematic effects of inflammation when more neutrophils made

A

help to clear infection

neutrophils formed in bone marrow, different signals from cytokines

61
Q

what are the systematic effects of inflammation when increase body temperature

A

reduced pathogen replication, boost of immune response (why you get a fever)

62
Q

what are the systematic effects of inflammation - liver

A

Production of acute phase proteins by the liver. These molecule include MBL and C-reactive protein (CRP) which help to clear infection

63
Q

what can cause septic shock

A 
response 
to an 
overwhelming 
inflammatory 
response
64
Q

what happens in a local infection with gram negative bacteria

A

macrophages activated to secrete TNF-alpha in tissue

65
Q

how is infection removed that is caused by local - gram negative

A

phagocytosis of bacteria
local vessel occlusion
plasma and cells drain to local lymph node

66
Q

what does the release of TNF-alpha in the local infection stage cause

A

increase plasma protein into tissue, increase phagocyte and lymphocyte migration to tissue
increase platelet adhesion to blood vessel wall

67
Q

what happens when systematic infection with gram positive bacteria (sepsis) occurs

A

macrophages activated in liver and spleen secrete TNF-alpha into the bloodstream

68
Q

what happens when TNF-alpha is released into the bloodstream - gram positive infection

A

systematic edema causing decreased blood volume
hypoproteinemia and neutropenia, follwed by neutrophilia
decreased blood volume caused collapse of vessels

69
Q

how does death occur due to gram positive bacteria

A

disseminated intravascular coagulation leading to wasting and multiple organ failure

Microorganisms + Disease (16 decks)

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