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Medical Microbiology I > The Complement System > Flashcards

The Complement System Flashcards

1
Q

3 lines of protection

A
  • Natural barriers
  • Innate, antigen-nonspecific immune defenses
  • Adaptive, antigen-specific immune responses
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2
Q

Natural barriers

A
  • Skin, mucosal surfaces, acid of the stomach

- Prevent invasion by most microbes

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3
Q

Innate, antigen-nonspecific immune defenses

A
  • Soluble Components

- Cellular Components

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4
Q

Soluble components of innate, antigen-nonspecific immune defenses

A
  • Soluble antimicrobial molecules
  • Defensins
  • Complement components
  • Type 1 interferons
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5
Q

Cellular components of innate, antigen-nonspecific immune defenses

A
  • Phagocytes
  • Monocytes
  • Macrophages
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6
Q

Skin barrier defenses

A
  • Dry environment

- Fatty acids – organisms & sebaeous glands

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7
Q

Mucous membrane barrier defenses

A
  • Ciliated epithelial cells

- Alveolar macrophages

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8
Q

Eye barrier defenses

A
  • Tears

- Lysozyme

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9
Q

Acidic environment barriers

A
  • GI tract - bile

- Bladder, kidneys

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10
Q

Lysozyme function

A
  • Catalyzes hydrolysis of bacterial peptidoglycan
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11
Q

Lysozyme source

A
  • Tears, saliva, nasal secretions, body fluids, lysosomal granules
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12
Q

List of soluble factor examples

A
  • Lysozyme
  • Lactoferrin, transferrin
  • Lactoperoxidase
  • B-Lysin
  • Chemotactic factors
  • Properdin
  • Lectins
  • Cationic peptides
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13
Q

Lactoferrin, transferrin function

A
  • Bind iron and compete with microorganisms for it
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14
Q

Lactoferrin, transferrin source

A
  • Specific granules of PMNs
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15
Q

Lactoperoxidase function

A
  • May be inhibitory to many microorganisms
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16
Q

Lactoperoxidase source

A
  • Milk and saliva
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17
Q

B-Lysin function

A
  • Effective mainly against gram-positive bacteria
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18
Q

B-Lysin source

A
  • Thrombocytes, normal serum
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19
Q

Chemotactic factors function

A
  • Induce directed migration of PMNs, monocytes, and other cells
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20
Q

Chemotactic factors source

A
  • Complement and chemokines
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21
Q

Properdin function

A
  • Activates complement in the absence of ab-aq complex
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22
Q

Properdin sources

A
  • Normal plasma
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23
Q

Lectins function

A
  • Bind to microbial carbohydrates to promote phagocytosis
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24
Q

Lectins source

A
  • Normal plasma
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25
Q

Cationic peptides function

A
  • Disrupt membranes, block cell transport activities
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26
Q

Cationic peptides source

A
  • Polymorphonuclear granules (defensins)
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27
Q

Complement system definition

A
  • Collection of circulating and cell membrane proteins

- Play important roles in host defense against microbes

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28
Q

Complement system is part of the innate immune system

A
  • Not adaptable & does not change over time
  • Can be recruited & brought into action by the adaptive immune system
  • Alarm system, weapon against infection (especially bacterial)
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29
Q

Complement system name origin

A
  • Complement = ability of these proteins to assist (complement) the antimicrobial activity of antibodies
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30
Q

Goal of complement system

A
  • Elimination of microbes during innate and adaptive immune responses
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31
Q

Functions of complement system

A
  • Opsonization of microbes
  • Complement-mediation cytolysis
  • Stimulation of inflammatory reactions
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32
Q

Opsonization

A
  • Promotes phagocytosis of microbes for recognition by receptors on phagocytes
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33
Q

Complement-mediation cytolysis occurs by

A
  • Formation of membrane attack complex
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34
Q

3 pathways of complement activation

A
  • Alternative Pathway (alternate, properdin)
  • Lectin Pathway (mannose binding)
  • Classical pathway
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35
Q

Alternate and lectin pathway initiation

A
  • Initiated by microbes and microbe products in the presence of antibody
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36
Q

Classical pathway initiation

A
  • Initiated by certain isotypes of antibodies attached to antigens (antigen-antibody complexes)
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37
Q

The three activation pathways of complement coalesce at a common junction point

A
  • Activation of C3 component
38
Q

Chemotactic factors are produced by

A
  • Activation by either pathway

- Initiates a cascade of proteolytic events that produce them

39
Q

Chemotactic factors functions

A
  • Attract phagocytic & inflammatory cells to the site

- Increase vascular permeability to allow access to site of infection

40
Q

Chemotactic factors bind to

A
  • The agent to promote their phagocytosis (opsonization) and elimination
41
Q

Most abundant complement protein in the plasma

A
  • C3

- Plays central role in all pathways

42
Q

The sequence of events of activation

A
  • Similar in all 3 pathways
  • Differ in their requirement for antibody
  • Differ in some of the proteins used in the process
43
Q

Common goal of classical, alternate, and lectin pathways

A
  • Cleavage of C3 and C5
44
Q

C3a and C5a

A
  • Provide chemoattractants and anaphylotoxins
45
Q

C3b

A
  • Resposable for attachement to microbes

- An opsonin that adheres to membranes, and to initiate the membrane attack complex to kill cells

46
Q

Alternate pathway activation

A
  • Activated directly by bacterial cell surfaces and their components (endotoxin, microbial polysaccharides)
47
Q

C3 hydrolyzation

A
  • Spontaneously hydrolyzed in plasma at a low level to C3b

- Products are unstable unless deposited on the surface of a microbe

48
Q

The alternate pathway can be activated before

A
  • Establishment of an immune response to infecting bacteria
  • Does not depend on antibody
  • Does not involve the early complement components (C1, C2, and C4)
49
Q

Initial activation of the alternate pathway is mediated by

A
  • Properdin factor B binding to C3b
50
Q

Properdin factor D

A
  • Splits factor B in the complex which yields the Bb active fragment
  • C3bBb - C3 convertase
51
Q

C3bBb - C3 convertase

A
  • C3b sticks to the cell surface and anchors the complex of proteins
  • Inactive Ba is split from this complex
52
Q

Inactive Ba split from the C3bBb complex leads to

A
  • Cleavage and activation of many C3 molecules (amplification of response)
53
Q

Lectin pathway initiation

A
  • Initiated in the absence of antibody by attachment of plasma mannose-binding lectin (MBL, mannose-binding protein MBP)
54
Q

Mannose-binding protein (lectin)

A
  • Large serum protein

- Binds to non-reduced mannose, fucose, & glucosamine on bacterial, fungal, & other cell surfaces

55
Q

MBL is structurally similar to

A
  • Component of C1q of the classical complement pathway that activates C4
56
Q

MBL binds to bacterial surfaces & activates

A
  • Cleavage of mannose-binding protein-associated serine protease (MASP)
57
Q

MASP cleaves the C4 and C2 components to

A
  • C3 convertase
  • Junction point of the complement cascade
  • Subsequent steps same as other pathways
58
Q

MBP resembles and replaces

A
  • C1q component and on binding to bacterial surfaces

- Activates the cleavage of MASP

59
Q

Classical pathway initiated by

A
  • Binding to the Fc portion of antibody that is bound to cell surface antigens
  • An immune complex with soluble antigens
60
Q

Aggregation of antibody isotypes IgG or IgM (not IgA or IgE) in the classical pathway

A
  • Changes the structure of the heavy chain to allow binding to complement
61
Q

C1 complement protein in classical pathway binds to

A
  • 2 adjacent Fc regions
  • 2 IgG molecules
  • 1 pentameric IgM molecule
62
Q

Classical pathway C1 complex

A
  • Recognition unit composed of 3 proteins (C1q, C1r, C1s)
  • C1q bind to 2 Ig molecules
  • C1r & C1s are serine proteases
63
Q

Active C1s cleaves

A
  • C4 & C2
  • C4 to C4a & C4b
  • C2 to C2a & C2b
64
Q

C4b & C2b

A
  • Active binding portion of protein

- C4b2b – C3 convertase

65
Q

C4b2b – C3 convertase in the classical pathway

A
  • Binds to cell membrane
  • Cleaves C3 to C3a & C3b
  • Amplifies the response by splitting many C3 molecules
  • C3b binds to cell surface to remain active
66
Q

C43b2b in the classical pathway forms on

A
  • Cell membrane – C5 convertase

- C5 split into C5a & C5b

67
Q

Early steps of complement activation are similar in all 3 pathways

A
  • C3b binds to microbes in the alternate pathway to form C3 convertase complex
  • C4b2b binds to the microbe in the classical and lectin pathways to form C3 convertase complex
  • Cleavage of C3 central to all pathways to form C5 convertase
68
Q

Cleavage of the C3 and C5 components produces important factors that

A
  • Enhance clearance of the infectious agent
  • Promote access to the infection site
  • Attracting the cells that mediate protective inflammatory reactions
69
Q

C3b is an opsonin that promotes clearance of bacteria by

A
  • Binding directly to the cell membrane

- Makes the cell more attractive to phagocytic cells (neutrophils and macrophages that have receptors for C3b)

70
Q

C3b can be cleaved further to generate

A
  • C3d

- Activator of B lymphocytes

71
Q

In humoral immunity, complement activation is the

A
  • Relevant innate immune response

- C3d is the second signal for B lymphocytes, analogous to the co-stimulators of APCs for T lymphocytes

72
Q

B lymphocytes express a receptor

A
  • Type 2 complement receptor (CR2, or CD21)

- Binds C3d

73
Q

B cells that are specific for a microbe’s antigens recognize the antigen by

A
  • Ig receptors
  • Simultaneously recognize the bound C3d by the CR2 receptor
  • This greatly enhances antigen-dependent activation responses of B cells
74
Q

C3a and C5a - powerful anaphylatoxins that stimulate mast cells to

A
  • Release histamine

- Enhances vascular permeability & smooth muscle contraction

75
Q

C3a and C5a also act as attractants for

A
  • Neutrophils

- Macrophages

76
Q

The terminal stage of the classical pathway involves creation of the

A
  • Membrane attack complex (MAC)

- Also called the lytic unit

77
Q

Membrane attack complex

A
  • 5 terminal complement proteins (C5 through C9) associate on target cell membranes to mediate injury
78
Q

The C9 component of MAC

A
  • Similar to perforin, which is produced by cytolytic T cells and natural killer cells
79
Q

Cell lysis by complement

A
  • Activation of C5 initiates the molecular construction of an oil-well-like membrane attack complex (MAC)
  • C9 resembles perforin (natural killer cells and cytotoxic T cells) to promote apoptosis in the target cell
80
Q

Last steps of complement activation (formation of MAC)

A
  • Start after formation of the C5 convertase
  • Identical in all pathways
  • C5a induces inflammation
  • (C5b,6,7,8)1(C9)n complex forms
81
Q

(C5b,6,7,8)1(C9)n complex

A
  • Drills a hole in the membrane

- Leads to the hypotonic lysis of cells

82
Q

Humans have several mechanisms for preventing generation of the C3 convertase to

A
  • Protect against inappropriate complement activation
83
Q

Mechanisms for preventing generation of C3 convertase to prevent inappropriate complement activation

A
  • C1 inhibitor
  • C4 binding protein
  • Factor H
  • Factor I
  • Cell surface proteins (decay-accelerating factor (DAF) and membrane cofactor protein)
84
Q

CD59 (protectin) prevents

A
  • Formation of the membrane attack complex (like a stop sign)
85
Q

Most infectious agents lack

A
  • Protective mechanisms and remain susceptible to complement
86
Q

The complement system is a collection of

A
  • Circulating and cell surface proteins

- Important in host defense

87
Q

The complement system may be activated

A
  • On microbial surfaces without antibodies (alternative and lectin, components of innate immunity)
  • After the binding of antibodies to antigens (classical pathway, component of adaptive humoral immunity)
88
Q

Complement proteins are sequentially cleaved, & active components, mainly C3b, become

A
  • Covalently attached to the surfaces on which complement is activated
89
Q

The late steps of complement activation lead to the formation of the

A
  • Cytolytic membrane attack complex
90
Q

Different products of complement activation

A
  • Promote phagocytosis of microbes
  • Induce cell lysis
  • Stimulate inflammation
91
Q

Mammalian cells express surface and circulating regulatory proteins that

A
  • Prevent inappropriate complement activation on host cells

Medical Microbiology I (8 decks)

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