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Undeleted > Lecture 4 II > Flashcards

Lecture 4 II Flashcards

0
Q

opsonization and phagocytosis

A

C3b

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1
Q

C3a

A

inflammation

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2
Q

inflammation 2nd round

A

C5a

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3
Q

after C5a

A

Lysis of microbe

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4
Q

what consists of several plama proteins that work together to opsonize microbes,
to promote the recruitment of phagocytes to the site of infection,
and in some cases to directly kill the microbes

A

the complement system

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5
Q

What are 3 things that can initiate the complement system?

A

Classical pathway
Alternative pathway
lectin pathway

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6
Q

What is the second step of complement activation?

A

C3b and formation of C3 convertase

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7
Q

What does C3b initiate activation of?

A

C5 and the formation of C5 convertase

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8
Q

What is the last step in the complement activation?

A

the formation of membrane attack complex, bc it creates holes in the plasma membrane

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9
Q

An inactive precursor enzyme called a zymogen is altered to become an active protease that cleaves the next complement protein in the cascasde…

A

proteolytic cascade

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10
Q

What does an enzymatic cascade result in?

A

A temendous amplification of the amount of proteolytic products that are generated

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11
Q

What does the proteolytic products that are generated perform?

A

vaious effector functions of the complement system

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12
Q

What does the complement system work in cooperation with?

A

Other medically important proteolytic casesed that include
the blood coagulation pathways
the kinin-kallikrein system that regulates vascular permeability

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13
Q

How does C3 b bind to a microbe?

A

covalent binding which forms C5 convertase

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14
Q

All three complexes of the complement pathways result in?

A

sequential recruitment and assembly of additional complement proteins into protease complexes

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15
Q

What cleaves the central protein of the complemetn system, C3?

A

C3 convertase

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16
Q

What does C3 convertase cleaving C3 produce?

A

C3a and C3b

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17
Q

What happens to the C3b fragment?

A

It becomes covalently attached to the microbial surface

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18
Q

What serves as an opsonin to promote phagocytosis of the microbes?

A

C3b

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19
Q

When the C3b fragment is realeased, it stimulates?

A

inflammation by acting as a chemoattractant for neutrophils

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20
Q

What do C3b binding to other completment proteins form?

A

A protease called C5 convertase, that cleaves C5

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21
Q

What does C5 convertase cleaving C5 produce?

A

a released peptide (C5a) and a larger fragment (C5b) that remains attached to the microbial cell membranes

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22
Q

C5a has a very important chemoattractant role of?

A

changing the permeabilliy of blood vessels

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23
Q

C5b initiates the formation of what complexes?

A

the complement proteins C6, C7, C8, and C9, which are assembled into a membrane pore

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24
Q

What is the membrane pore of C6, C7, C8, and C9 called?

A

the membrane attach complex (MAC)

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25
Q

What causes lysis of the cells where complement is activated/

A

MAC

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26
Q

What binds to the surface of a microbe, where it functions as an opsonin and as a component of C3 and C5 convertase

A

C3b

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27
Q

What stimulates inflammation?

A

C3

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28
Q

What is a serine protease adn the active enzyme of C3 and C5 conertases?

A

factor B

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29
Q

What is a plasma serine protease that cleaves factor B when it is bound to C3b?

A

Factor D

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30
Q

What stablizes the C3 convertase (C3bBb) on microbial surfaces?

A

properdin

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31
Q

What initiates the classical pathway?

A

C1 (C1qr2s2)

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32
Q

What does C1q bind to?

A

Fc portion of antibody

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33
Q

What are proteases that lead to C4 and C2 activation?

A

C1r and C1s

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34
Q

What does C4a stimulate??

A

inflmmation

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35
Q

What activates C4

A

C4b covalently binds to surface of microbe or cell where antibody is bound

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36
Q

C4b binds to C2 for cleavage by

A

C1s

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37
Q

a serine protease functioning as an active enzyme of C3 and C5 convertases

A

C2

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38
Q

What initiates the lectin pathway?

A

Mannose beinding lectin (MBL)- it binds to terminal mannose resideus of microbial carbohydrates.

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39
Q

What activates C4 and C2

A

an MBL associated protease

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40
Q

How does the classical pathway detect Abs bound to the surface of a microbe or other sturucture?

A

a plama protein called C1q

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41
Q

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

A

two associated serine proteases called C1r and C1s become active

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42
Q

What initae a proteiolytic cascade involving other complement proteins C2 and C4?

A

C1r and C1s

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43
Q

What does MBL recognize?

A

terminal mannose residues on microbial glycoproteins and glycolipids, similar to the mannose receptor on phagocyte membranes

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44
Q

What family is MBL a member of?

A

the collectin family

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45
Q

The MBL has what strucutre?

A

a hexamertric structure similar to the C1q component of the ocmplement system

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46
Q

What are activated after MBL binds to microbes?

A

two zymogens MASP1(mannose- associated serine protease 1 or mannan binding lectin associated serine protease) and MASP2 are activated

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47
Q

What functions do MAPS1 and 2 have?

A

Similar to C1r and C1s and initaite downstream proteolytic steps identical to the classical pathway

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48
Q

What three homologous hexameric protines can all initate the complement activation?

A

C1q, MBL and Ficolin

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49
Q

What binds to the Fc region of IgM and activates the serine protease activity of C1r and C1s? microbial surface antigetn

A

C1q

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50
Q

MBL binds to?

A

Mannose on the surface of microbes and acitvates MASP1 and MASP2 assocated with mannose binding lectin

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51
Q

What binds to N-acetylglucosamine(bacterial cell wall) on the surface of microbes and activates MASP1 and MASP2

A

Fibolin

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52
Q

What is the collectin family?

A

A fmaily of trimeric proteins with lectin head

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53
Q

What are soluble effector molecules in the innate immune system part of the sollectins?

A

MBL and pulmonary surfactant proteins (2) SP-A and (3)SP-D

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54
Q

what is a soluble PRR that binds carbohydrates with terminal mannose and fucose and enhances phagocytosis of microbes?

A

MBL

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55
Q

What are low MBL levels associated with?

A

increased susceptibility to a vairety of infections

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56
Q

What are collectins with lipophilic properties and their major functions are to maintina the ability of lungs to expand and as mediators of innate immune repsonses

A

SP-A and SP-d

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57
Q

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

A

Various microoganims and act as opsonins, faciciltating phagocytosis by alveolar macrophages

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58
Q

What direclty inhibit bacterial growht?

A

SP-A and SP-D

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59
Q

What directly activate macrophages?

A

SP-A and SP-D

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60
Q

What are plama protiens that are strucutally similar to collectins but they have a fibrinogen type carbohydrate recognition domain?

A

ficolins

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61
Q

What are humoral molecules of the innate immune system?

A

ficolins

62
Q

What are the molecular ligands of the ficolins?

A

N-acetylglucosamine and the lipoteichoic acid component of the cell walls of gram- POSITIVE bacteria

63
Q

Ficolins have been shown to beind serveral species of….

A

bacteria, opsonizing them and activating complemetn in a manner simlar to that of MBL

64
Q

How does involement in a opsonin dependent phagocytosis effect?

A

limits the infection and concurrently orchestrating the subsequent adaptive clonal immune reponse

65
Q

How is the lectin pathway of complemetn activated?

A

that attached serine proteases MASPs

66
Q

How is the alternative pathway triggered?

A

when a complement protein called C3 directly recognizes certain microbail surface strucuteres such as bacterial LPS

67
Q

What is constitutively activated in solution at a low level and binds to bacterail surfaces?

A

C3

68
Q

What is the spontaneous activation amplified on?

A

microbial surfaces

69
Q

What is the alternative pathway no activated on teh surface of mammalian cells?

A

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

70
Q

What dissociate the complement C3 convertase (C3bBb) from host mammal cells?

A

decay- accelerating factor DAF), complement receptor 1 (CR1) adn factor I

71
Q

What complex binds to membrane vai C7 in the formation of MAC?

A

C5b binds C6 and C7 and C5b67 complex

72
Q

What inserts into the cell membrane in MAC?

A

c8 binds to C5b67 complex

73
Q

What forms a pore in MAC

A

up to 19 molecules C9 bind and polymerize

74
Q

What is MAC?

A

It is the cytolitic end complex. Membrane attack complex

75
Q

inflammation

A

C5a, C3a

76
Q

phagocytosis

A

C3b

77
Q

lysis of microbe

A

MAC

78
Q

C3a activation can happen spontaeously, so it has a much lower reaction than

A

C5a

79
Q

Contraction of smooth muscles
C3a
C4a
C5a

A

+
(+)
++++

80
Q

increased permeability of blood vessels
C3a
C4a
C5a

A

+
(+)
++++

81
Q

Degranulation of basophils
C3a
C4a
C5a

A

+
(+)
+

82
Q

Chomtaxis, release of O2 racials and lysosomal enzymes
C3a
C4a
C5a

A

++++

83
Q

What helps kill microbes in phagolysosomes?

A

ROS, NO, and lysosomal enzymes

84
Q

Microbes may be ingested by …. of phagocytes

A

different membrane receptors

85
Q

What are microbes internalized into?

A

phagosomes

86
Q

What fuse with lysosomes to form phagolysosomes?

A

phagosomes

87
Q

How are the microbes killed?

A

Reactive Oxygen and Nitrogen species and proteolyitic enzymes

88
Q

What are monocytes actived by?

A

microbial products such as LPS and by NK cell- derived IFN-gamma

89
Q

What does monocyte activation lead to?

A

The activation of transcription factors, the trancription of vaious genes, and the synthesis of proteins

90
Q

What are monocytes acvited by?

A

the stimuli from T lymphocytes such as CD40 ligand and IFN-gamma
- they may alternatively be acitvated by other signals to rpomote tissue repair and fibrosis

91
Q

What lead to inflammation enhanced adaptive immunity?

A

cytokines TNF, IL-1, IL-6, IL-12

92
Q

What is the principal cell source of tumor necrosis factor (TNF)

A

macrophages, T cells

93
Q

What is the principal celluarl targets for TNF endothelial cells?

A

activation (inflammation, coagulation)

94
Q

TNF neutrophils?

A

activation

95
Q

TNF hypothalaums

A

fever

96
Q

TNF liver

A

syntehsis of acute phase proteins

97
Q

TNF mucsle, fat

A

catabolism (Cachexia)

98
Q

TNF many cell types

A

apoptosis

99
Q

principle cell source for IL-1

A

mcarophages, endothelial cells, some epithlieal cells

100
Q

IL-1 endothelia cells

A

activation (inflammation, coagulation)

101
Q

IL-1 hypothalmus

A

Fever

102
Q

IL-1 liver

A

synthesis of acute phase protines

103
Q

IL-1 T cells

A

Th17 differentiation

104
Q

principal cell source for chemokines

A

macrophages, dendritic cells, endothelial cells, T lymphoctes, fibroblasts, platelets

105
Q

chmokines leukoytes

A

increased integrin affinity, chemotaxis, activation

106
Q

Principal cells for IL-12

A

dendritic cells, macrophages

107
Q

IL-12 NK cells and T cells

A

IFN-gamma production, increased cytotoxic activity

108
Q

IL-12 T cells

A

Th1 differentiation

109
Q

IFN-a/b principal cell sources

A

IFN alpha- Dendritic cells, and macrophages

IFN-beta- fibroblast

110
Q

IFN gama princiapl cell source

A

NK cells and T lymphocytes

111
Q

Target of IFN gamma

A

activation of macrophages

stimulatioin of some antibody responses

112
Q

IFN a/b targets

A 
all cells; antiviral state, increased class I MHC expression
NK cells activation
113
Q

IL-10 principal cell source

A

macrophages, dendirtic cells, T cells

114
Q

IL10 macrophages, dendritic cells

A

inhibition of IL12 production, reduced expression of costimulators and class II MHC molecules

115
Q

IL6 principal cell source

A

macrophages, endothelial cells, T cells

116
Q

IL-6 liver

A

synthesis of acute phase proteins

117
Q

IL6 B cells

A

proliferation of antibody producing cells

118
Q

IL15 principal cell source

A

macrophages and others

119
Q

IL15 NK cells

A

porliferation

120
Q

IL15 T cells

A

proliferation

121
Q

IL18 principal cells source

A

macrophages

122
Q

IL18 NK cells and T cells

A

IFN gamma synthesis

123
Q

TGF beta principal cell source

A

many cell types

124
Q

TGF beta inhibition of inflmmation T cells

A

differentiation of TH17, regulatory T cells

125
Q

Local inflammation in endothelia cells

A

TNF, IL-1 act on adhsion molecule TNF increase permability and give off IL-1 chemokines

126
Q

Local inflmmation of leukocytes

A

TNF, IL1 activation… gives IL1 IL6 chemokines

127
Q

systemic protective effects of the brain

A

TNF, IL1, IL6 give fever

128
Q

ststemic protective effects of the liver

A

IL1, IL6 give actue phase protiens

129
Q

ststemic protective effect of bone marrow

A

TNF, IL1, IL6 produce leukocyte production

130
Q

Systemic pahtologic effects on heart

A

TNF… low output

131
Q

systemic pahtologic effects on endothlial cells/ blood vessel

A

TNF becasue of thrombus gives increased permablity

132
Q

systemic pathologic effects on multiple tissues

A

TNF on skeletel muscles insulin resisitance

133
Q

What have multiple local and systemic inflammatory effects?

A

TNF, IL1, IL6

134
Q

what act locally on leukocytes and endothleium to induce acute inflmation/

A

TNF and IL1

135
Q

TNF and IL1 induce?

A

the expression of IL6 from leukocytes and other cell types

136
Q

What mediate protective systemic effects of inflmmation?

A

IL1, IL6 and TNF

137
Q

What induce fever, acute phase protein synthesis by liver, and increased production of leukocytes by bone marrow?

A

TNF IL1 MAIN, IL6

138
Q

TNF can cause septic shock, what are 3 pahtologic abnormalities?

A

decreased cardiac function
thrombosis and capillary leak
metabolic abnormalitites due to insulin resistance

139
Q

several plama protines that recognize microbial structrue and partcipate in innate immunity belong to the

A

pentraxin family

140
Q

What are acute phase protines from the pentraxin

A

C reactive protein (CRP) and serum amyloidP (SAP)

141
Q

What can activate complement by binding C1q and intiaitng the classical pathway?

A

CRP and SAP

142
Q

What do CRP and SAP recognize?

A

phosphorylcholine and phosphatidylethanolamine respectively, which are found on bacteria and apoptotic cells

143
Q

Plasma concentrations of CRP and SAP are very low in helathy individuals but can?

A

Increase up to 1000-fold during infections and in response to other inflammatory stimuli

144
Q

What does the increased levels of CRP and SAP result in?

A

An increased synthesis by the liver induced by cytokines IL6 and IL1, which are produced by phagocytes as part of the innate immune repsone

145
Q

What are acute phase protines from the pentraxin family

A

C-reactive protien (CRP) and serum amyloid P (SAP)

146
Q

opsonize

A

make more susceptible to phagocytosis

147
Q 
Acute phase reactant Dramatic increase in concentration...
C-reactive protine
mannose biding lectin
alpha 1- acid glycoprotein
serum amyloid P component
A

fixes complement, opsonizes
fixes complement, opsonizes
transport protein
amyloid component precursor

148
Q

What are produced by virus infected cells?

A

Type 1 interferons (IFNalpha and IFNbeta)

149
Q

What is the production of IFNa and IFNb triggered by?

A

response to intracellular TLR signaling and other sensors of viral RNA

150
Q

What do IFNalpha and IFN beta bind to?

A

receptors on neighboring unifected cells and activate JAK STAT signaling pathways

151
Q

What does the activation of the JAK STAT pathyway induce?

A

genes whoe products interfer with viral replication

152
Q

IFNA and IFNb bind to receptors on infected cells and?

A

induce expression of genes whoe products enhance the cell’s susceptibility to CTL medicated killing

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