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Microorganisms + Disease > Complement and Inflammation L6 > Flashcards

Complement and Inflammation L6 Flashcards

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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
how can clearance be enhanced
tagging the microbes | recognised by complement receptors in immune system
26
what happens after C3b is bound
recruitment of inflammatory cells = inflammation
27
what receptor do cells for innate immunity have
Cells relevant for innate immunity have receptors for the soluble cleavage products C3a and C5a
28
what contributes to inflammation initiation
Once C3a and C5a bind to their receptors cells become activated. This effect contributes to the initiation of inflammation
29
what happens when complement activation occurs to immune system
Other parts of the immune system are activated
30
what are the regulations in complement activation
Inactivation of the C3 convertase Inactivation of C5 convertase No formation of membrane-attack complex
31
what are the features of gram negative bacteria
Long polysaccharide chains in cell wall (LPS)
32
what are the features of gram positive bacteria
Layer of peptidoglycan in cell wall
33
what may some pathogens do to subvert complements
Proteins that mimic complement regulatory proteins
34
how do gram negative bacteria affect complements
LPS forms a barrier around e.g.E. coli so cant get the formation of MAC complex, so no pore formation
35
how do gram negative bacteria affect complements
Prevents insertion of MAC
36
how do some pathogens affect complements
Inhibit complement cascade
37
what is an inflammatory response
Complex response to local injury or trauma
38
what does vasodilation do
increase in the diameter of blood vessels, responsible for tissue redness and increase tissue temperature
39
what does vasoconstriction do
influx of white cells and fluid (exudate) from the capillaries into the tissue, responsible for swelling (oedema)
40
what happens after injury occurs to the body
Injury then the different inflammations :pain swelling, warmth, redness Recruitment to try clear
41
what happens in the body when injured
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
how are macrophages and dendritic cells 'aware'
‘aware’ of the presence of infection because they express multiple receptors - Pattern recognition receptors - Complement receptors - C5a, C3a and C3b
43
what is macrophages and dendritic cells response to infection
producing cytokines and chemokines
44
how is cytokine production activated by macrophages
activated macrophages secrete cytokines Act as messengers – tell need to clear infection Different cytokines have different effects on different parts of the body
45
what does interleukin - 1beta (IL-1beta) do when cytokines released
activated vascular endothelium activates lymphocytes local tissue destruction increases access of effector cells
46
what does tumour necrosis factor alpha (TNF-alpha) do when cytokines released
activated vascular endothelium increase vascular permeability = more IgG, complement and cells enter tissues increased fluid drainage to lymph nodes
47
what does Interleukin-12 (IL-12) do when cytokines are released
activates natural killer cells | induces differentiation of CD4 T cells into TH1 cells
48
what are chemokines
Small proteins mainly chemo attractant for leukocytes
49
what do chemokines fo
Recruit cells to site of inflammation | Recruit cells to secondary organs
50
how are chemokines released
activated macrophages release range of cytokines
51
in normal epithelium what is the interaction between leukocytes
selectin-mediated adhesion to leukocyte is weak, allows leukocytes to roll along vascular endothelial surface
52
what are the stages when activated epithelium - interaction between leukocytes and epithelium
rolling adhesion tight binding diapedesis migration
53
what happens when infection in body (endothelium)
chemokines(IL-8) high concentration nearest to the site of infection – help tell immune system where the site of infection is
54
what occurs in rolling adhesion
Neutrophil will bind to a E-selectin and the chemokine (IL-8) binds to help hold the neutrophil in the same place
55
what occurs in tight binding
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
what happens in diapedesis
diapedesis of the cell into the capillary to the site of the infection
57
what happens in migration
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
what happens after 24h in inflammatory cells
neutrophil - phagocytosis and activation of bactericidal mechanisms eosinophil - killing of antibody coated parasites
59
what happens after 3-4 days in inflammatory cells
basophil present
60
what are the systematic effects of inflammation when more neutrophils made
help to clear infection | neutrophils formed in bone marrow, different signals from cytokines
61
what are the systematic effects of inflammation when increase body temperature
reduced pathogen replication, boost of immune response (why you get a fever)
62
what are the systematic effects of inflammation - liver
Production of acute phase proteins by the liver. These molecule include MBL and C-reactive protein (CRP) which help to clear infection
63
what can cause septic shock
``` response to an overwhelming inflammatory response ```
64
what happens in a local infection with gram negative bacteria
macrophages activated to secrete TNF-alpha in tissue
65
how is infection removed that is caused by local - gram negative
phagocytosis of bacteria local vessel occlusion plasma and cells drain to local lymph node
66
what does the release of TNF-alpha in the local infection stage cause
increase plasma protein into tissue, increase phagocyte and lymphocyte migration to tissue increase platelet adhesion to blood vessel wall
67
what happens when systematic infection with gram positive bacteria (sepsis) occurs
macrophages activated in liver and spleen secrete TNF-alpha into the bloodstream
68
what happens when TNF-alpha is released into the bloodstream - gram positive infection
systematic edema causing decreased blood volume hypoproteinemia and neutropenia, follwed by neutrophilia decreased blood volume caused collapse of vessels
69
how does death occur due to gram positive bacteria
disseminated intravascular coagulation leading to wasting and multiple organ failure

Microorganisms + Disease (16 decks)

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