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IMMUNOLOGY Exam #1- Lo > Lec 05- Innate Immunity (Part 2) > Flashcards

Lec 05- Innate Immunity (Part 2) Flashcards

1
Q

What are the 3 pathways of initiation of complement activation?

A
  • alternative pathway
  • classical pathway
  • lectin pathway
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2
Q

What are the 3 effector junctions of the complement system?

A
  • C3a: Inflammation
  • C3b: Opsonization and phagocytosis
  • C5a: Inflammation
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3
Q

What is the complement system?

A

consists of several plasma proteins that work together to:

  • opsonize microbes
  • promote recruitment of phagocytes to infection site
  • directly kill the microbes (sometimes)
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4
Q

What is the 2nd step in the complement pathway?

A

production of C3b&raquo_space; formation of C3 convertase

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5
Q

What happens when C3b initiates the activation of C5?

A

formation of C5 convertase

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6
Q

What is the last step in the complement pathway?

A

formation of membrane attack complex

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7
Q

What does the membrane attack complex do?

A

creates holes in plasma membranes

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8
Q

What kind of cascades does the complement activation involve?

A

proteolytic cascades

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9
Q

What does the proteolytic cascade do?

A

alters a zymogen (inactive precursor enzyme) to become an active protease

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10
Q

What does an active protease do in complement system activation?

A

cleaves the next complement protein in the proteolytic cascade

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11
Q

What is the result of enzymatic cascades in the complement system?

A

tremendous amplification of the amount of proteolytic products that are generated

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12
Q

What other medically important proteolytic cascades does the complement system work in cooperation with?

A
  • blood coagulation pathways

- kinin-kallikrein system

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13
Q

What does the kinin-kallikrein system do?

A

regulates vascular permeability

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14
Q

What does C3 convertase do?

A

cleaves the central protein (C3) of the complement system into C3a and C3b

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15
Q

Which is a chemoattractant, C3a or C3b?

A

C3a

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16
Q

Which fragment (C3a or C3b) becomes covalently attached to the microbial surface?

A

C3b

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17
Q

Which fragment (C3a or C3b) serves as an opsonin to promote phagocytosis of the microbes?

A

C3b

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18
Q

What happens when the C3a fragment is released?

A

stimulates inflammation by acting as a chemoattractant for neutrophils

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19
Q

What does C5 convertase do?

A

cleaves C5 forming C5a and C5b which remains attached to the microbial cell membranes

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20
Q

C5a is a very potent chemoattactant that also ________

A

induces changes in the permeability of blood vessels

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21
Q

What does C5b initiate?

A

formation of membrane attack complex (MAC)

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22
Q

What is MAC made of?

A 
Complement proteins:
C6
C7
C8
C9
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23
Q

What does MAC do?

A

causes lysis of the cells where the complement is activated

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24
Q

What is the serum concentration of C3?

A

1000-1200

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25
Q

What is the function of C3b?

A
  • binds to microbe surface to function as oposin
  • component of C3 convertase
  • component of C5 convertase
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26
Q

What is the function of C3a?

A

stimulates inflammation

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27
Q

What is the serum concentration of Factor B?

A

200

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28
Q

What is the function of Factor B?

A

Bb= serine protease

-the active enzyme of C3 and C5 convertases

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29
Q

What is the serum concentration of Factor D?

A

1-2

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30
Q

What is the function of Factor D?

A

Plasma serine protease

-cleaves factor B when it is bound to C3b

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31
Q

What is the serum concentration of Properdin?

A

25

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32
Q

What is the function of Properdin?

A

stabilizes C3 convertase (C2bBb) on microbial surfaces

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33
Q

What is the serum concentration of C4?

A

300-600

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34
Q

What is the function of C4a?

A

Stimulates inflammation

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35
Q

What is the function of C4b?

A
  • covalently binds to surface of microbe or cell where antibody is bound and where complement is activated
  • binds to C2 for cleavage by C1s
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36
Q

What is the serum concentration of C2?

A

20

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37
Q

What is the function of C2?

A

C2a = serine protease

active enzyme of C3 and C5 convertases

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38
Q

What is the serum concentration of Mannose-binding lectin (MBL)?

A

0.8 - 1

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39
Q

What is the function of MBL?

A
  • initiates the lectin pathway

- binds to terminal mannose residues of microbial carbohydrates

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40
Q

What does an MBL-associated protease do?

A

activates C4 and C2, as in the classical pathway

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41
Q

What plasma protein does the classical pathway use?

A

C1q

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42
Q

What does C1q do?

A

detects antibodies bound to the surface of a microbe or other structure

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43
Q

What happens once C1q binds to the Fc portion of the antibodies?

A

C1r and C1s become activated

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44
Q

What do C1r and C1s do?

A

initiate a proteolytic cascade involving C2 and C4

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45
Q

What triggers the Lectin pathway?

A

Mannose-binding lectin (MBL)

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46
Q

What is MBL?

A

a plasma protein

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47
Q

What does MBL recognize?

A

terminal mannose residues on microbial glycoproteins and glycolipids

(similar to mannose receptor on phagocyte membranes)

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48
Q

What family does MBL belong to?

A

collectin family

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49
Q

What is MBL’s structure?

A

hexametric structure

similar to C1q component of complement system

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50
Q

What happens after MBL binds to microbes?

A

MASP1 and MASP2 are activated

51
Q

What are MASP1 and MASP2?

A

mannose-associated serene protease

or

mannan-binding lectin-associated serene protease

52
Q

What is the function of MASP1 and MASP2?

A

initiate downstream proteolytic steps

similar to C1r and C1s in classical pathway

53
Q

What are the 3 homologous hexameric proteins?

A

C1q
MBL
Ficolin

54
Q

What do the homologous hexametric proteins do?

A

initiate complement activation

55
Q

What does C1q do?

A
  • bonds to Fc regions of IgM

- activates the serene protease activity of C1r and C1s

56
Q

What does MBL do?

A
  • binds mannose on microbe surface

- activates MASP1 and MASP2 on the mannose-binding lectin

57
Q

What does Ficolin do?

A
  • binds N-acetylglucosamine on microbe surface

- activates MASP1 and MASP2 associated with Ficolin

58
Q

What are collectins?

A
  • a family of trimeric proteins with lectin head

- soluble effector molecules in the innate immune system

59
Q

What are the 3 collecins?

A
  • MBL
  • SP-A (pulmonary surfactant protein)
  • SP-D (pulmonary surfactant protein)
60
Q

What is a soluble PRR that binds carbohydrates with terminal mannose and fructose to enhance phagocytosis of microbes?

A

MBL

61
Q

What are low MBL levels associated with?

A

increased susceptibility to a variety of infections

62
Q

Which collections have lipophilic properties?

A

SP-A

SP-D

63
Q

What are the major functions of SP-A and SP-D?

A
  • maintain ability of lungs to expand
  • mediators of innate immune response
  • act as oposins
  • facilitate phagocytosis by alveolar macrophages
64
Q

What do SP-A and SP-D bind to?

A

microorganisms

65
Q

What do SP-A and SP-D directly do?

A
  • inhibit bacterial growth

- activate macrophages

66
Q

What are Ficolins?

A
  • plasma proteins

- humoral molecules of the innate immune system

67
Q

Ficolins are structurally similar to collectins except that they have a ________________

A

fibrinogen-type carbohydrate recognition domain

68
Q

What have ficolins been shown to do?

A

bind several species of bacteria, opsonizing them and activating complement in a manner similar to MBL

69
Q

How are ficolins similar to MBL?

A
  • their involvement in an opsonin-dependent phagocytosis thus limiting the infection and concurrently orchestrating the subsequent adaptive clonal immune response
  • initiate the lectin pathway of complement activation through MASPs
70
Q

What triggers the start of the alternative pathway?

A

when C3 directly recognizes certain microbial surface structures (bacterial LPS)

71
Q

Why is the alternative pathway not activated on the surface of mammalian cells?

A

mammals have a regulatory protein that inhibits the activation of the alternative pathway

72
Q

What 3 things dissociate the complement C3 convertase (C3bBb) from the host cell?

A
  • Decay-accelerating factor (DAF)
  • Complement receptor 1 (CR1)
  • Factor 1
73
Q

What happens when C5b binds to C6 and C7?

A

forms C5b67 which binds to the membrane via C7

74
Q

What does C8 bind to?

A

C8 binds to C5b67 and inserts into the cell membrane

75
Q

What happens when 16 molecules of C9 bind?

A

They bind and polymerize to form a pore

76
Q

Phagocytosis and intracellular killing steps

A

1- Microbes bind to phagocyte receptors
2- Phagocyte membrane zips up around microbe
3- Microbe ingested in phagosome
4- Fusion of phagosome with lysosome forms phagolysosomes
5- Activation of phagocyte
6- Killing of microbes

77
Q

What are the 3 ways of killing microbes in phagosomes?

A
  • ROS
  • NO
  • Lysosomal enzymes
78
Q

What are macrophages activated by?

A
  • microbial products (LPS)
  • natural killer cell-derived IFN-y
  • stimuli from T lymphocytes (CD40 ligand and INF-y)
79
Q

What does macrophage activation lead to?

A
  • activation of transcription factors
  • transcription of various genes
  • synthesis of proteins
80
Q

Macrophages may also be alternatively-activated by other signals to promote ________

A

tissue repair and fibrosis

81
Q

What is the principal cell source of TNF?

A
  • macrophages

- T cells

82
Q

What is the principal cell source of IL-1?

A
  • macrophages
  • endothelial cells
  • some epithelial cells
83
Q

What is the principal cell source of chemokines?

A
  • macrophages
  • dendritic cells
  • endothelial cells
  • T lymphocytes
  • fibroblasts
  • platelets
84
Q

What is the principal cell source of IL-12?

A
  • macrophages

- dendritic cells

85
Q

What is the principal cell source of IFN-y?

A
  • NK cells

- T lymphocytes

86
Q

What is the principal cell source of Type I IFN-a?

A
  • macrophages

- dendritic cells

87
Q

What is the principal cell source of Type I IFN-b?

A

-fibroblasts

88
Q

What is the principal cell source of IL-10?

A
  • macrophages
  • dendritic cells
  • T cells
89
Q

What is the principal cell source of IL-6?

A
  • macrophages
  • endothelial cells
  • T cells
90
Q

What is the principal cell source of IL-15?

A
  • macrophages

- others

91
Q

What is the principal cell source of IL-18?

A

-macrophages

92
Q

What is the principal cell source of TGF-b?

A

-many cell types

93
Q

What are the principal cellular targets and biological effects of TNF?

A
  • Endothelial cells: activation (inflammation, coagulation)
  • Neutrophils: activation
  • Hypothalamus: fever
  • Liver: synthesis of acute-phase
  • Muscle, fat: catabolism
  • Many cell types: apoptosis
94
Q

What are the principal cellular targets and biological effects of IL-1?

A
  • Endothelial cells: activation (inflammation, coagulation)
  • Hypothalamus: fever
  • Liver: synthesis of acute-phase
  • T cells: Th17 differentiation
95
Q

What are the principal cellular targets and biological effects of chemokines?

A

Leukocytes:

  • increased integrin activity
  • chemotaxis
  • activation
96
Q

What are the principal cellular targets and biological effects of IL-12?

A
  • NK and T cells: IFN-y production, increased cytotoxic activity
  • T cells: Th1 differentiation
97
Q

What are the principal cellular targets and biological effects of Type I IFNs?

A
  • All cells: antiviral state, increased class I MHC expression
  • NK cells: activation
98
Q

What are the principal cellular targets and biological effects of IL-10?

A

Macrophages and Dendritic cells:

  • inhibition of IL-12 production
  • reduced expression of costimulators
  • reduced expression of class II MHC molecules
99
Q

What are the principal cellular targets and biological effects of IL-6?

A
  • Liver: synthesis of acute-phase

- B cells: proliferation of antibody producing cells

100
Q

What are the principal cellular targets and biological effects of IL-15?

A
  • NK cells: proliferation

- T cells: proliferation

101
Q

What are the principal cellular targets and biological effects of IL-18?

A

-NK and T cells: IFN-y synthesis

102
Q

What are the principal cellular targets and biological effects of TGF-b?

A
  • inhibition of inflammation

- T cells: Th17 differentiation, differentiation of regulatory T cells

103
Q

What is the major cytokine related to septic shock in patients?

A

TNF

104
Q

Which cytokine is the major activator of fibroblasts which causes increased amounts of connective tissue thus causing scarring?

A

IL-18

105
Q

All cytokines of innate immunity have macrophages as a principal cell source except which?

A

IFN-y

106
Q

Which cytokine is the most important when it comes to inducing fever?

A

IL-1

107
Q

What 3 cytokines have multiple local and systemic inflammatory effects?

A

TNF
IL-1
IL-6

108
Q

What 2 cytokines act locally on leukocytes and endothelium to induce acute inflammation and induce the expression of IL-6?

A

TNF

IL-1

109
Q

What 3 cytokines mediate protective systemic effects of inflammation including:

  • induction of fever
  • acute-phase protein synthesis
  • increased production of leukocytes by bone marrow?
A

TNF
IL-1
IL-6

110
Q

What 3 pathologic abnormalities can systemic TNF cause that lead to septic shock?

A
  • decreased cardiac function
  • thrombosis and capillary leak
  • metabolic abnormalities due to insulin resistance
111
Q

Plasma proteins that recognize microbial structures and participate in innate immunity belong to which family?

A

pentraxin family

112
Q

What are the 2 major acute-phase proteins from the pentraxin family?

A

C-reactive protein (CRP)

Serum amyloid P (SAP)

113
Q

How much can plasma concentrations of CRP and SAP increase to during infections and in response to inflammatory stimuli?

A

up to 1000 fold

114
Q

How are CRP and SAP levels increased?

A

1- Innate immune response
2- Phagocytes are produced
3- IL-1 and IL-6 induce increased synthesis of CRP and SAP by the liver

115
Q

What does CRP recognize?

A

phosphorylcholine

found on bacteria and apoptotic cells

116
Q

What does SAP recognize?

A

phosphatidylethanolamine

found on bacteria and apoptotic cells

117
Q

How can CRP and SAP activate complement?

A

by binding to C1q, initiating the classical pathway

118
Q

What produces Type I IFNs?

A

virus-infected cells

119
Q

What triggers the production of Type I IFNs?

A

response to:

  • intracellular TLR signaling
  • other sensors of viral RNA
120
Q

What is the function of Type I IFNs?

A
  • bind to receptors on neighboring uninfected cells

- activate JAK-STAT signaling pathway

121
Q

What happens when JAK-STAT pathway is activated by Type I IFNs?

A
  • induces expression of genes

- gene products interfere with viral replication

122
Q

What happens when Type I IFNs also bind to receptors on infected cells?

A

induce expression of genes whose products enhance the cell’s susceptibility to CTL-mediated killing

123
Q

What does Ag recognition by B cells and T lymphocytes provide?

A

provides signal 1 for the activation of lymphocytes

124
Q

What provides signal 2 in the interface between Adaptive and Innate immunity?

A

molecules induced by innate immunity responses to microbes

IMMUNOLOGY Exam #1- Lo (6 decks)

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