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MIMM 214 > Innate immunity: Complement > Flashcards

Innate immunity: Complement Flashcards

1
Q

What does complement system refer to

A

Group of soluble proteins that cooperate with both innate and adaptive immune systems =
Eliminate pathogens, during cells and immune complexes from body

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2
Q

What is a protease

A

Most make up complement system
>30 in blood and other fluids
Enzyme that performs proteolysis = can break down proteins

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3
Q

Naming proteases

A

Called C followed by number
Some called factor followed by cap letter
Most numbered based on when discovered

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4
Q

What are complement proteins produced by

A

Mostly produced by liver

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5
Q

What do complement proteins do

A

Set off A chain reaction that helps clear pathogens = cascade/chain reaction of events

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6
Q

Describe 3 key mechanisms of action of complement system

A

Increasing vascular permeability and chemo taxis = promote inflammation, vasodilate= more cells to site of infection
Destroy pathogen cells membranes = Poke holes
Increasing reognxiiotn of pathogens and facilitating phagocytosis = opsonization

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7
Q

Define opsonizaton

A

Coating of surface of Pathogen by antibody and/or complement that makes it more easily ingested by phagocytes, make tasty, enhance phagocytosis

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8
Q

Define phagocytosis

A

Receptor of opsonins on Phagocytes
Internalization of a particular matter by cells by a process of engulfment, cell membrane surrounds material, eventually forming intracellular vesicle = phagosome = contains ingested material

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9
Q

How does complement get activated

A

Classical, alternative or lectin pathway
Initially pro proteases then act as cascade = proteolytic cleavage generating 2 fragments

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10
Q

Describe products of proteolytic cleavage of complement

A

One small = a, with specific function
One large = b, with proteolytic activities on new substrate

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11
Q

Name the 2 c3 convertases

A

C4b2a
C3bBb
Both cleave c3 into c3a and c3b

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12
Q

Describe functional categories of complement proteins - gen

A

Group of pro proteases = inactive, circulate in blood until activated= cleaved
Proteins are inactive untill cleaved by proteases
Need initiators first

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13
Q

Describe functional categories of complement proteins - whole cascade generally

A

Initiators = initiate respective complement reactions
Convertase activators and some enzymatic mediators = cleave and activate next member of a complement reaction sequence = cleave other complement proteins, immune cells have receptors for these complement proteins
= 3 outcomes = opsonins, anaphylatoxins and membrane attack complex
Regulators = inhibit formation of Mac on host cells —> always regulated

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14
Q

What’s essential to know about complement activation

A

3 pathways can activate compel T
All 3 generate c3 convertase = cleaves c3–> c3a + c3b
3 main outcomes = downstream effects

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15
Q

What is lectin pathway triggered by

A

Triggered by soluble proteins known as lectins
= prrs that circulate in blood, not membrane bound
Binds polysaccharide antigen

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16
Q

Name lectins

A

Mannose binding lectin
Ficolins

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17
Q

What increases during infection

A

Expression of lectins

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18
Q

Describe lectin pathway prrs

A

Bind surface of pathogens
Triggers signalling cascade on pathogen surface = c3 convertase generated (c4b2a) = cleaves c3

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19
Q

Describe lectin pathway - generally whole process

A

Once binds pamp = change conformation of MASPs (proteases)= starts cleaving complement proteins = triggers cascade = c4b2a

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20
Q

Describe how classical pathway activated

A

C1q binds pathogen surface
Can bind pathogen directly
Can bind antibodies that are bound to pathogen surface

21
Q

What does classical pathway do

A

Connect adaptive to innate
Antibodies produced by B cells - can bind antibodies
Innate immune component helps mediate humoral response

22
Q

What happens when c1q binds

A

Triggers signalling cascade on pathogen surface
Proteases = c1r2r2 switches on and cleaves and makes c4b2a

23
Q

What do all pathways converge on

A

C3
Classical and lectin = make c4b2a
Alternative = makes c3bBb

24
Q

What does c3 convertase do

A

Cleaves c3–> c3a and c3b

25
Q

What c3a involved In

A

Enhancing inflammation

26
Q

What c3 b involved in

A

Oposonization
And is c5 convertase = c5 —> c5a and c5b

27
Q

Name the 2 ways alternative pathway activated

A

C3b given from lectin or classical pathway
When high conc c3

28
Q

Describe process of alternative pathway - c3b gen

A

Once c3b produced by lectin or classical pathway = amplification loop for c3b formation (depositing more c3b molecules on the pathogen) = requires factor b and protease factor d
C3bBb on surface of pathogen = c3 convertase

29
Q

Describe process of alternative pathway - c3b specifics

A

C3b deposited by lectin or classical on surface pathogen
C3b binds factor b then factor d comes in and cleaves factor b into bb or ba
Bb =gives c3bBb
Pos feedback loop =more c3b s and c3a s

30
Q

Describe when high conc c3 - alt pathway

A

High conc c3= c3 can undergo spontaneous hydrolysis = also involves factors b and d
Binds factor b —> can be cleaved by factor b and ultimately forms c3 convertase

31
Q

Describe c3 convertase of alt pathway

A

C3bBb = v unstable
On surface

32
Q

What stabilizes c3bBb

A

Properdin = factor p, secreted by neutrophils
Stabilize c3 convertases since it can bind to some microbial surfaces

33
Q

Describe which type of proteins complement mainly acts on

A

Extracellular = on surface, phagocytosis not inside cell, Mac =outside on surface =
ALL EXTRACELLULAR

34
Q

What does cleavage of c3 do

A

CASUES MANY DOWNSTREAM EFFECTs

35
Q

Name 3 downstream effects

A

Inflammation
Increased phagocytosis
Pathogen lysis

36
Q

Describe inflammation

A

Additional signalling results in cleavage of other complement molecules

37
Q

What causes inflammation

A

C3a and c5a recruit phagocytes and promote inflammation

38
Q

What happens if too much c3a and c5a

A

Anaphylactic shock

39
Q

What do complement receptors do - downstream effects inflammation

A

Complement receptors connect complement tagged pathogens to effector cells

40
Q

describe receptors on granulocytes for downstream effect of ifnalmmtion

A

C3a R/C5a R
= Stimulates release of pro inflammatory cytokines and granule components from basophils, eosinophils, neutrophils, mast cells
Helps recuiremtn and leads to secreting pro inflammatory cytokines

41
Q

Describe increased phagocytosis downstream effect

A

Phagocytes have receptors for c3b
Opsonization of pathogen = more readily taken up by phagocytosis

42
Q

Describe how opsonization can occur - downstream effects

A

Via complement deposition and/or antibodies (phagocytes Also ahev receptors for antibodies, many initiators lead to opsonization)

43
Q

Describe downstream effect = pathogen lysis

A

Additional complement factors create membrane attack complex (mac)—> cell lysis

44
Q

Describe downstream effect = pathogen lysis = WHAT COMPLEMENT proteins involved

A

C5 and c3 are involved = c5b directly forms Mac and c3b indirectly since converts c5–> c5a and c5b

45
Q

Describe downstream effect = pathogen lysis = WHAT IS THE IMPORTANT PART

A

Cascade leading to formation of MAC = pore in surface of pathogen that lyses pathogen

46
Q

DESCRIBE negative regulation of c activation

A

Do not want Mac on host cells or anaphylactic shock
Complement regulatory proteins in plasma or cell surfaces prevent complement activation from proceeding under normal/basal conditions = downreg

47
Q

What does neg reg of c activation do

A

Prevent appearance of c3 convertase
Promote disappearance of c3 convertase

48
Q

Does only the complement system have regulatory component

A

NAWWWW
Each pathway/process in immune system has a regulatory component

49
Q

Describe ex of negative regulation of c activation

A

CD59 = protectin = inhibits mac formation, prevents c9 binding and polymerization

MIMM 214 (8 decks)

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