Quiz 3 - German - Barriers/Effectors II Flashcards

1
Q

What is the complement system?

A

Immune surveillance system of plasma proteins that act in cascades to selectively kill extracellular pathogens and diseased tissue, promote inflammation, clear tissue damage, and regulate tissue homeostasis

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2
Q

What produces complement?

A

THE LIVER

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3
Q

What 3 pathways are in the complement system?

A

Classical pathway

Lectin pathway

Alternate pathway

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4
Q

The complement proteins act as what?

A

Pattern recognition system

*Also in cardiovascular circulation

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5
Q

What does complement do?

A

Goes around and covers everything

  • If healthy cell - cell removes it and cascade is not initiated
  • If unhealthy cell - it initiates a cascade pathway leading to destruction of that cell

**Complement monitors all cells in the body

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6
Q

____% of plasma globulin protein is complement.

A

15%

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7
Q

What are the initiators?

A

These initiate the complement pathways

  • Classical: Antibody/C1q complexes
  • Lectin: Mannose - binding lectins
  • Alternate: C3, properdin
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8
Q

What are convertases?

A

C3b and C5b
-These are cleaved and function as opsonins (coat surfaces of pathogens)

Label pathogens/antigens

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9
Q

What are opsonins?

A

Coat pathogens/antigens and target for phagocytosis

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10
Q

What are anaphylatoxins?

A

Initiate and promote inflammation

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11
Q

What is the membrane attack complex?

A

Form the MAC pore

Group of peptides that form a pore in the cell surface
-This is how complement directly destroys pathogens

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12
Q

What do complement receptors do?

A

Initiate signaling

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13
Q

What are regulators?

A

Restrict or halt complement activity

  • Proteins
  • Proteases drive pathway progression
  • Missing components cause pathogen susceptibility
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14
Q

What does a convertase do?

A

Protease that continuously cleaves its complement component

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15
Q

There are 3 complement pathways. Name them, what activates them, and put them in order of which one goes 1st.

A

1st - Alternative - pathogen surface creates local environment conducive to complement activation (coats everything)

2nd - Lectin - Mannose-binding lectins binds to pathogen surface

3rd - Classical - C-reactive protein OR antibody binds to specific antigen on pathogen surface

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16
Q

ALL pathways lead to what main event?

A

CLEAVAGE OF C3

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17
Q

When C3 is cleaved, what are the 2 products?

A

C3a and C3b

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18
Q

What does C3a do?

A

Acts as an anaphylatoxin

  • Small fragment
  • NO enzyme activity
  • Signaling activity
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19
Q

What does C3b do?

A

Covalently binds to surface components of pathogen/cell

-Large fragment

-Enzyme activity
—Proteolytically active

  • Opsonin
  • Signaling activity
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20
Q

What is significant about C2?

A

This is the EXCEPTION

When cleaved, C2a binds the surface and C2b acts as the anaphylatoxin

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21
Q

What two antibodies are involved in the classical pathway?

A

IgM

IgG

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22
Q

What is the first component of complement in the classical pathway?

A

C1q

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23
Q

Tell me the beginning stages of the classical pathway.

A

Antibodies (IgM or IgG) bind to surface

C1q then comes down in between two antibodies and creates an activation cascade

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24
Q

What is the main difference b/t IgM and IgG?

A

IgM - PENTOMERIC - More binding sites for C1q (Higher binding affinity than IgG) - Highly concentrated in the blood - BLOODSTREAM PROTECTOR

IgG - Easily go into peripheral tissues

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25
Q

C1q has two subunits. Name them.

A

C1r and C1s

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26
Q

C1q binds to ______ IgM molecule(s).

C1q binds to _______ IgG molecule(s).

A

ONE IgM

TWO IgG

27
Q

The binding of C1q to IgM/G activates ____, which cleaves and citrates the serine protease _______.

A

C1r

C1s

28
Q

What proteolytic cleaves C4?

What is C4 and where is it found?

A

C1r and C1s

Protein floating around in periphery and vasculature

29
Q

When C4 is cleaved, what are the products?

A

C4a and C4b

C4a is an anaphylatoxin

C4b is an opsonin and a protease

30
Q

Once C4b sits down on the plasma membrane, what does it recruit?

A

C2

31
Q

C2 is cleaved and what are the products and what happens?

A

C2a

C2b

*This is the EXCEPTION

C2a - Binds with C4b to create a cluster - THIS IS CALLED C4b2a - THIS CREATES C3 convertase

C2b - acts as the anaphylatoxin, but not a lot of known stuff about it

32
Q

C4b2a is a C3 convertase. What does it do?

A

It continuously cleaves its complement component

It cleaves C3 into C3a and C3b

33
Q

What does C3a do?

*What does C3b do?

A

C3a - Anaphylatoxin

C3b - COATS THE ENTIRE SURFACE OF THE PATHOGEN - Also, it can join the cluster to become: C3b2a3b - AKA: C5 convertase

34
Q

What does the the C5 convertase (C4b2a3b) do?

A

Cleaves C5 into C5a and C5b

C5a - Anaphylatoxin

C5b - Opsonin - Opsonizes whole surface of pathogen

35
Q

At what point in this cascade does actual biologic function occur?

A

Cleavage of C3. Once C3b sits down, a cell can be destroyed

36
Q

Which convertase is shared by the lectin pathway?

A

C5 convertase

*The difference in the pathways is HOW they are inititiated

37
Q

Tell me what pathogens have on their cell surface.

A

Pathogens express unique cell surface glycoproteins

*N-linked glycoproteins of yeasts contain many terminal mannose residues

**Glycoproteins of vertebrates have terminal sialic acid residues

38
Q

How is the lectin pathway initiated?

A
  • Mannose binding lectins (MBL)

- Ficolins

39
Q

What does the lectin pathway recruit?

A

Mannose binding lectins (MBL) Associated Serine Proteases [MASP]
—MASP-1
—MASP-2

**The MASPs are to the lectin pathway as the C1s/C1r are to the classical pathway

40
Q

Serine proteases (MASPs) cleave complement protein _____.

A

C4

41
Q

MBL binds with high affinity to _____ and fructose residues.

A

Mannose

42
Q

Ficolins bind ___________ containing acetylated sugars.

A

Oligosaccharides

43
Q

Once MASPs are bound, what happens?

A

C4 comes in and is cleaved

THE REST OF THE PATHWAY IS THE SAME AS THE CLASSICAL PATHWAY

44
Q

Third pathway is the alternative pathway. What happens there?

A

C3 is spontaneously hydrolyzed

LOOK AT ONE NOTE FOR DRAWING

45
Q

LOOK AT ONE NOTE FOR PATHWAY DRAWINGS.

A

SERIOUSLY

46
Q

What do anaphylatoxins do?

A

Act on blood vessels to increase vascular permeability and cell-adhesion molecules

Help with inflammation

Increased permeability allows increased fluid leakage
—This allows for migration of macrophages, PMNs, and lymphocytes is increased. Microbicidal activity of macrophages and PMNs are increased

47
Q

What do anaphylatoxins activate?

A

Immune cells

  • Macrophage
  • Neutrophil
  • Basophil
  • Eosinophil
  • Mast cells

*They interact with discrete receptors on innate immune cells

48
Q

How does opsonization neutralize pathogens and target them for phagocytosis?

A

C3b all over bacterium
-Macrophage has C3b and C5a receptors all over

Macrophage binds the C3b on bacterium

WHEN ONLY C3b BINDS TO CR1, BACTERIA ARE NOT PHAGOCYTOSED
-This prevents macrophages from destroying self-cells

When C5a binds, the macrophages have the green light to phagocytose via CR1

49
Q

T/F - C3b and C5a are NECESSARY for macrophage phagocytosis.

A

TRUE

50
Q

Receptor questions

CR1 - Bind what? Functions? Cell types?

CR3 - “

C5a - “

A

CR1

  • C3b, C4bi
  • Stims phagocytosis (req’s C5a)
  • Macrophages, RBCs, WBCs

CR3

  • iC3b
  • Stims phagocytosis
  • WBCs

C5a

  • C5a
  • Binding of C5a activates G protein
  • Endothelial cells, mast cells, phagocytes
51
Q

Tell me how the MAC is formed.

A

C5b recruits C6 and C7

Then, C8 is recruited, and the C5b678 complex is created

Then ~20 C9s are recruited

C9 perforates into the membrane and forms the MAC
-This puts large lesions into the membrane
—With more C5b on the surface, more MAC is formed and pathogen is killed

52
Q

How is the MAC regulated?

A

Human cells have CD59 that binds the C5b678 complex and PREVENTS recruitment of C9 to form the MAC pore

53
Q

Why is opsonization and convertase activity regulated?

A

This is obviously critical since C3b and C5b need to be removed from self-cells to avoid too frequent self-destruction

54
Q

How is C3b opsonizaiton and convertase activity regulated?

Factors H and I

A

Factor H and Factor I (From vasculature)

These cleave off C3b into a number of different sub components which leads to an insoluble/inactive C3b
-When properdin binds, it prevents the binding of Factor H and Factor I

55
Q

How is C3b opsonization and convertase activity regulated?

DAF and MCP

A

DAF and MCP (On healthy human cells)

  • Decay-Accelerating Factor
  • Membrane Co-Factor Protein

DAF - Removes Bb component from C3b, and prevents the C3 pathway from moving on

MCP - Removes Bb component by binding, recruits factor I, and leads to cleavage of iC3b

56
Q

OVERVIEW

Classical Pathway

A

Initiated by C-reactive protein or antibodies

C1q interacts with pathogen surface or antibodies on pathogen surface

C1r and C1s

Pathway starts

57
Q

OVERVIEW

Lectin Pathway

A

Initiated by mannose binding lectin (MBL) or ficolins

These recognize and bind carbs on pathogen surface

MASP-1 and MASP-2

Pathway starts

58
Q

OVERVIEW

Alternative Pathway

A

C3 undergoes spontaneous hydrolysis (via H2O) and C3b is put all over everything

Pathways starts

Leads to MAC

59
Q

C3 convertases:

Classical and lectin - ??

Alternative - ??

A

Classical and lectin - C4b2a

Alternative - iC3Bb, C3bBb

60
Q

C5 convertases:

Classical and lectin - ??

Alternative - ??

A

Classical and lectin - C4b2a3b

Alternative - (C3b)2Bb

61
Q

What do anaphylatoxins do?

A

Vasodilation

Chemotactic factors
-Recruit induced immune system

Drive phagocytosis

Drive degranulation

62
Q

What does C3b do?

A

Targets a cell for destruction

Creates the C5 convertase
-Forms the MAC

63
Q

What is the difference b/t iC3b and C3b?

A
  • C3b sits down on any surface

- iC3b is insoluble and floats around

64
Q

What prevents the MAC complex from forming?

A

CD59