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Host and Defense > EXAM 2 Induced Immunity: Cellular Responses and Cytokines > Flashcards

EXAM 2 Induced Immunity: Cellular Responses and Cytokines Flashcards

1
Q

what are the effector functions of immediate innate immunity?

A
  • barriers
  • antimicrobial peptides
  • opsonization
    • isolation
    • pore formation
    • targeting
  • inflammation
  • cellular recruitment
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2
Q

what are the effector functions of induced innate immunity?

A
  • phagocytosis
  • targeted killing
  • antimicrobial peptides
  • cytokine release
  • inflammation
  • cellular recruitment
  • B and T cell activation
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3
Q

the immediate innate immune response occurs in what time frame?

A

0-4 hours

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4
Q

the induced innate immune response occurs in what time frame?

A

4 hours to 4 days

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5
Q

what are the cells of the innate immune system?

A
  • monocyte
    • macrophage
    • dendritic cell
  • mast cell
  • eosinophil
  • neutrophil
  • basophil
  • NK cell
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6
Q

which cell of the innate immune system is the circulating precursor cell to macrophages and dendritic cells?

A

monocyte

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7
Q

which cell of the innate immune system functions in phagocytosis and killing of microorganisms; activation of T cells and initiation of immune responses

A

macrophage

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8
Q

which cell of the innate immune system is responsible for activation of T cells and initiation of adaptive immune responses?

A

dendritic cells

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9
Q

which cell of the innate immune system functions in the expulsion of parasites from the body through release of granules containing histamine and other active agents?

A

mast cell

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10
Q

which cell of the innate immune system is responsible for the killing of antibody-coated parasites through release of granule contents?

A

eosinophil

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11
Q

which cell of the innate immune system kills cells infected with certain viruses?

A

NK cell

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12
Q

which cell of the innate immune system functions in phagocytosis and killing of microorganisms?

A

neutrophil

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13
Q

which cell of the innate immune system is responsible for controlling immune responses to parasites?

A

basophil

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14
Q

what are the local, tissue resident immune cells that respond in the initiation of the induced immune response?

A

macrophages, dendritic cells, mast cells, and specialized T cells

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15
Q

what are the 4 components involved in the initiation of the induced immune response?

A
  • local, tissue resident immune cells
  • complement system
  • pro-inflammatory signaling
  • infected, damaged, or diseased tissues
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16
Q

what are the 3 pro-inflammatory signals involved in initiation of the induced immune response?

A

cytokines, eicosanoids, and acute phase response

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17
Q

infected, damaged, or diseased tissues can help initiate the induced immune response via ___ and ___

A

interferon response and altered MHC expression

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18
Q

___ detect and phagocytose local pathogens

A

macrophages

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19
Q

most tissues have resident macrophages. what are the resident macrophages of the brain, bone, liver, and skin?

A
  • brain - microglia
  • bone - osteoclasts
  • liver - kupffer cells
  • skin - langerhans cells
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20
Q

macrophages induce and direct ___, and activate the ___ immune system

A
  • inflammation
  • adaptive
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21
Q

what are the 4 effector mechanisms of macrophages?

A
  • phagocytosis
  • cytokine release
  • degranulation
  • antigen presentation
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22
Q

macrophages can function as ___

A

pattern recognition receptors (PRRs)

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23
Q

describe the extracellular process of innate immune cell pattern recognition

A

macrophage receptors recognize the cell-surface carbohydrates of bacterial cells but not those of human cells

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24
Q

describe the intracellular process of innate immune cell pattern recognition

A

NK cell receptors recognize changes at the surface of human cells that are caused by viral infection

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25
Q

Pattern recognition receptors are present on most ___ cells

A

innate

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26
Q

PRRs allow local, direct ___

A

activate

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27
Q

what are the 3 innate phagocytic cells?

A

macrophages, neutrophils, and dendritic cells

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28
Q

describe the steps of phagocytosis

A
  1. bacterium becomes attached to membrane evaginations called pseudopodia
  2. bacterium is ingested, forming a phagosome
  3. phagosome fuses with lysosome, forming the phagolysosome
  4. bacterium is killed and then digested by lysosomal enzymes
  5. digestion products are released from the cell
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29
Q

what are the common macrophage PRRs that are involved in phagocytosis?

A
  • mannose receptor
  • complement receptors 3 and 4
  • dectin-1
  • macrophage receptor with collagenous structure
  • scavenger receptor A and B
  • lipopolysaccharide receptor
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30
Q

what is the common macrophage PRR that are involved in signaling (production and release of cytokies)?

A

toll-like receptors (TLRs)

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31
Q

what are the 6 antimicrobial mechanisms of phagocytes?

A
  • acidification (macrophage & neutrophil)
  • toxic oxygen-derived products (macrophage & neutrophil)
  • toxic nitrogen oxides (macrophage & neutrophil)
  • antimicrobial peptides (macrophage & neutrophil)
  • enzymes (macrophage & neutrophil)
  • competitors (neutrophil only)
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32
Q

___ activate macrophages

A

TLRs

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33
Q

TLR activation requires ___

A

dimerization; can be heterodimerization or homodimerization

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34
Q

what are the main external TLRs?

A
  • TLR-1
  • TLR-2
  • TLR-4
  • TLR-5
  • TLR-6
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35
Q

what are the main internal TLRs?

A
  • TLR-3
  • TLR-7
  • TLR-8
  • TLR-9
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36
Q

what do internal TLRs detect?

A

nucleic acid combinations

ds viral RNA (TLR-3), ss viral RNA (TLR-7, TLR-8), CpG DNA (TLR-9)

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37
Q

which TLR targets protein?

A

TLR-5 (flagellin)

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38
Q

which TLRs target lipids?

A

TLR-1, TLR-2, TLR-4, TLR-6, TLR-10

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39
Q

the heterodimerization of which two TLRs targets diacyl lipopeptides?

A

TLR-2 and TLR-6

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40
Q

the heterodimerization of which two TLRs targets triacyl lipopeptides?

A

TLR-2 and TLR-1

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41
Q

which TLR targets LPS?

A

TLR-4

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42
Q

NOD receptors detect ___

A

degraded antigens

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43
Q

what are NOD receptors?

A

nucleotide-binding oligomerization domains

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44
Q

NOD receptors recognize intracellular ___ and ___

A
  • PAMPs and DAMPs
    • microbial toxins
    • viruses
    • cell stress proteins
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45
Q

___ induce cytokine expression and release

A

NOD receptors

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46
Q

NOD receptors form the ___

A

inflammasome

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47
Q

NOD receptors cooperate with ___

A

TLRs

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48
Q

___ are signaling molecules of the immune system

A

cytokines

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49
Q

are cytokines soluble?

A

yes, mostly

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50
Q

what is the main nomenclature of cytokines?

A

interleukins, chemokines, and others

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51
Q

what are the six families of cytokines, based on receptor morphology?

A
  • class I
  • class II
  • interleukin 1
  • interleukin 17
  • tumor necrosis factor (TNF)
  • chemokines
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52
Q

cytokines signal predominantly in what two fashions?

A

paracrine and autocrine

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53
Q

cytokines effect ___ and ___ tissues

A

immune and non-immune

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54
Q

what are the common intracellular signaling pathways that cytokines are involved in?

A
  • JAK-STAT
  • MAPK
  • NF-kappa B
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55
Q

activated macrophages secrete which main pro-inflammatory cytokines?

A
  • IL-1 beta
  • TNF-alpha
  • IL-6
  • CXCL8
  • IL-12
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56
Q

which pro-inflammatory cytokine has the following function:

local: activates vascular endothelium, activates lymphocytes, local tissue destruction, increases access of effector cells
systemic: fever, production of IL-6

A

IL-1 beta

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57
Q

which pro-inflammatory cytokine has the following function:

local: activates vascular endothelium, increases vascular permeability, which leads to increased entry of IgG, complement, and cells to tissues and increased fluid drainage to lymph nodes
systemic: fever, mobilization of metabolites, shock

A

TNF-alpha

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58
Q

which pro-inflammatory cytokine has the following function:

local: lymphocyte activation, increased antibody production
systemic: fever, induces acute-phase protein production

A

IL-6

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59
Q

which pro-inflammatory cytokine has the following function:

local: chemotactic factor recruits neutrophils, basophils, and T cells to site of infection

A

CXCL8

60
Q

which pro-inflammatory cytokine has the following function:

local: activates NK cells, induces the differentiation of CD4 T cells into Th1 cells

A

IL-12

61
Q

what are the systemic effects of IL-1 beta, IL-6, and TNF-alpha on the liver?

A

acute-phase proteins, activation of complement, opsonization

62
Q

what are the systemic effects of IL-1 beta, IL-6, and TNF-alpha on bone marrow epithelium?

A

neutrophil mobilization, phagocytosis

63
Q

what are the systemic effects of IL-1 beta, IL-6, and TNF-alpha on the hypothalamus?

A

increased body temp, decreased viral and bacterial replication, increased antigen processing, increased specific immune response

64
Q

what are the systemic effects of IL-1 beta, IL-6, and TNF-alpha on fat and muscle?

A

protein and energy mobilization to allow increased body temperature, decreased viral and bacterial replication, increased antigen processing, increased specific immune response

65
Q

what are the systemic effects of IL-1 beta, IL-6, and TNF-alpha on dendritic cells?

A

TNF-alpha stimulates migration to lymph nodes and maturation, initiation of adaptive immune response

66
Q

inflammatory cytokines stimulate the ___ response

A

liver acute phase response

67
Q

which acute-phase proteins, produced by the acute phase response, are involved in pathogen recognition?

A

c-reactive protein, mannose-binding lectin, and lipopolysaccharide-binding protein

68
Q

which acute-phase proteins, produced by the acute phase response, are involved in pathogen elimination?

A

complement components C3, C4, C9, and factor B

69
Q

which acute-phase proteins, produced by the acute phase response, are involved in the inflammatory response?

A

granulocyte colony-stimulating factor, serum amyloid A, secreted phospholipase A2

70
Q

which acute-phase proteins, produced by the acute phase response, are involved in coagulation?

A

fibrinogen, plasminogen, tissue plasminogen factor

71
Q

describe how cytokines initiate leukocyte recruitment

A
  1. cytokines produced by macrophages cause dilation of local small blood vessels
  2. leukocytes move to periphery of blood vessel as a result of increased expresion of adhesion molecules by endothelium
  3. leukocytes extravasate at site of infection
  4. blood clotting occurs in the microvessels
72
Q

cytokine activation:

bacteria induce macrophages to produce ___, which acts on hepatocytes to induce synthesis of ___.

one of two steps are taken next:

  1. ___ binds phosphocholine on bacterial surfaces, acting as an ___, and also activating complement.
  2. ___ binds mannose residues on bacterial surfaces, acting as an ___, and also activating complement.
A
  • IL-6
  • acute-phase proteins
  • c-reactive protein
  • opsonin
  • mannose-binding lectin
  • opsonin
73
Q

extravasation depends on what 3 things?

A

chemokines, adhesion molecules, and proteases

74
Q

chemokines function as ___

A

chemoattractants

75
Q

what are the 4 chemokines?

A

CL, CCL, CXCL, and CX3CL (CXXXCL)

76
Q

adhesion molecules function to ___

A

tether leukocytes

77
Q

what are the 4 types of adhesion molecules?

A
  • vascular addressin (CD34)
  • selectin (l-selectin)
  • integrin (LFA-1)
  • immunoglobulin-like molecule (ICAM-1)
78
Q

proteases function to ___

A

open basement membranes

79
Q

what are 2 types of proteases?

A

matrix metalloproteases and elastases

80
Q

chemokine gradients recruit ___ to tissues

A

cells

81
Q

how do chemokine gradients work?

A

as more chemokines accumulate, cells are drawn closer and closer to that chemokine

82
Q

leukocytes extravasate to sites of ___

A

inflammation

83
Q

describe how leukocytes extravasate to sites of inflammation

A
  • chemokine receptor activation leads to binding
  • binding triggers protease release
  • basement membrane degradation and chemokines induce diapedesis and tissue entry
  • *weak selectin-mediated adhesion allows neutrophils to roll along the endothelium; rolling adhesion, tight binding, diapedesis, and then migration
84
Q

chemokine gradients are an ___ mechanism

A

immune targeting

85
Q

excessive plasma TNF-alpha causes ___

A

septic shock syndrome

86
Q

describe how excessive plasma TNF-a causes septic shock syndrome

A
  • often initiated by blood-borne infection
  • systemic extravasation
  • systemic neutrophil infiltration
  • vascular collapse
  • rapid multi-organ failure
87
Q

what is the primary cell of the induced response?

A

neutrophil

88
Q

large reserves of neutrophils are reserved in the ___ and are released when needed to fight infection

A

bone marrow

89
Q

when neutrophils are needed to fight an infection, they travel from the ___ to the ___, where they engulf and kill ___; they then die and are engulfed and degraded by ___

A
  • bone marrow
  • infected tissue
  • bacteria
  • macrophages
90
Q

___ are the primary innate killers

A

neutrophils

91
Q

what are the 4 effector mechanisms of neutrophils?

A
  • phagocytosis
  • degranulation
  • extracellular traps
  • cytokine release - this actually will happen as a result of any of the previous three mechanisms
92
Q

briefly describe neutrophils

A
  • potent pathogen killers
  • innate immunity
  • primary cell of the induced response
  • small and numerous
  • destined to die
93
Q

what are the 4 neutrophil granule types?

A
  • azurophil granules - contain proteases and defensins, respond to pathogens
  • specific granules - respond to pathogens
  • gelatinase granules - response to pathogens
  • secretory granules - respond to tissue damage
94
Q

neutrophil granules serve what dual purpose?

A

phagocytosis and degranulation

95
Q

the neutrophil oxidative burst does what?

A

kills pathogens

96
Q

how does the neutrophil oxidative burst kill pathogens?

A
  • bacterium is phagocytosed by neutrophil
  • phagosome fuses with azurophilic and specific granules
  • pH of phagosome rises, antimicrobial response is activated, and bacterium is killed
  • neutrophil dies
97
Q

what are NETs? what are the two types?

A
  • neutrophil extracellular traps
    • non-lytic - does not directly destroy the neutrophil itself; mobile
    • lytic - directly destroys the neutrophil (turns inside out); immobile
  • can happen in both tissues and vasculature
  • its a way of rapidly stopping an infection from spreading, and keeping it localized
98
Q

dendritic cells initiate ___

A

adaptive immunity

99
Q

are dendritic cells resident in tissue?

A

yes

100
Q

dendritic cells process pathogens into ___

A

antigens

101
Q

dendritic cells present antigens to ___

A

lymphocytes

102
Q

dendritic cells are involved in ___ regulation

A

cytokine

103
Q

dendritic cells have an enormous range of PRRs. why?

A

different PRRs induce different responses

104
Q

activated NK cells target ___ cells

A

infected, diseased, and stressed

105
Q

___ are large, cytotoxic lymphocytes

A

NK cells

106
Q

___ cells target and kill diseased self cells

A

NK cells

107
Q

NK cells have diverse combinations of receptors that can be both ___ and ___

A

activated and inhibited

108
Q

NK cells respond to what 3 things?

A

interferons, MHC class I, and unique stress ligands

109
Q

___ cells regulate the shift from induced innate to the adaptive immune response

A

NK cells

110
Q

do NK cells die after killing other cells?

A

no

111
Q

NK cells undergo a process of bone marrow education to select ___

A

functional receptor patterns

112
Q

viral infections cause the ___ response

A

interferon

113
Q

describe the interferon response

A
  • a virally infected cell releases interferon cytokines (INF-alpha and beta), which directly activate NK cells
    • induce resistance to viral replication in all cells
    • increase expression of ligands for receptors on NK cells
    • activate NK cells to kill virus-infected cells
114
Q

describe interferons

A
  • cytokines
  • released by diseased or stressed cells
    • intracellular infection, cancer
  • released by leukocytes
115
Q

what do interferon cytokines do?

A
  • reduce viral replication
  • prevent cell division
  • induce apoptosis
  • activate NK cells, T cells, and macrophages
116
Q

interferons activate ___ cells

A

NK

117
Q

describe how interferons activate NK cells

A
  • virus ifnection of cells triggers the interferon response
  • type I interferon drive the proliferation of NK cells
  • type I interferon drives the differentiation of NK cells into cytotoxic effector cells
  • effector NK cells kill virus-infected cells by inducing them to undergo apoptosis
118
Q

___ cells regulate dendritic cell recruitment of adaptive immunity

A

NK cells

119
Q

___ cells locally activate NK cells

A

dendritic cells

120
Q

describe how NK cells function as a checkpoint on adaptive immune activation

A
  • if there is a large NK cell response, then dendritic cell presentation is inhibited
  • if there is a small NK cell response, then dendritic cells are activated (adaptive immune response)
121
Q

___ protect local tissues

A

granulocytes

122
Q

what are the 3 granulocytes?

A

mast cells, eosinophils, and basophils

123
Q

___ are predominant in tissues and rare in the blood

A

granulocytes

124
Q

granulocytes express ___, usually as a result of being primed by prior adaptive responses

A

PRRs

125
Q

granulocytes ___ when activated, as a result of cell-type specific granule components

A

degranulate

126
Q

granulocytes respond to ___ organisms

A

parasitic

127
Q

___ are responsible for initiating type I hypersensitivity (allergic reactions)

A

granulocytes

128
Q

macrophages have ___ that bind microbes and their components. bound material is internalized in phagosomes and broken down in ___.

A
  • phagocytic receptors
  • phagolysosomes
129
Q

pattern recognition receptors are present on most ___ cells, and provide ___, ___ activation

A
  • innate
  • local, direct
130
Q

describe how TLR signaling initiates cytokine production through NF-kappaB

A
131
Q

NOD receptor recognition of bacterial cell wall components leads to activation of ___

A

NF-kappaB

132
Q

___ drives the production of cytokines

A

NF-kappaB

133
Q

inflammasomes activate and promote ___ release

A

cytokine

134
Q

what are the chemokines that are released by targets?

A

CXCL

135
Q

what are the chemokine receptors present on immune cells?

A

CSCR

136
Q

cells detect viral infections by recognizing viral ___. ultimately, ___ is activated, which causes synthesis and secretion of ___.

A
  • RNA
  • NF-kappaB
  • inflammatory cytokines
137
Q

describe macrophage and NK cell bidirectional regulation

A
  • macrophage activated by viral infection secretes inflammatory cytokines that recruit and stimulate NK cells
  • NK cell and macrophage form a conjugate pair with a synapse in which IL-12 and IL-15 activate the NK cell
  • NK cells proliferate and differentiate into effector NK cells secreting IFN-gamma
  • IFN-gamma binds to its receptor on macrophages and activates them to increase phagocytosis and secretion of inflammatory cytokines
138
Q

most cytokines are in the ___ form when they are produced (they have little activity, and are not great at signaling).

NOD proteins come together, bind ___, and activate it.

procaspase-1 activates ___ (go from pro form to active form).

this drives and enhances the release of ___ and functions as a ___.

A
  • pro
  • procaspase-1
  • cytokines
  • cytokines
  • checkpoint
139
Q

local infection with gram negative bacteria causes macrophages to secrete ___ in tissue.

this ultimately results in the removal of infection via ___ immunity

A
  • TNF-alpha
  • adaptive
140
Q

systemic infection with gram negative bacteria (sepsis) results in macrophages in the ___ and ___ to secrete TNF-alpha into the blood stream.

this ultimately results in multi organ failure and ___

septic shock syndrome

A
  • liver and spleen
  • death
141
Q

neutrophils produce ___-defensins

A

alpha

142
Q

how do NETs work?

A

neutrophils release NETs (lytic and non-lytic), which are basically chromatin with attached proteases that form a fibrous structure that captures and binds bacteria and pathogens

143
Q

activated NK cells target infected, diseased, and stressed cells:

MHC class I on normal cells is recognized by inhibitory receptors that inhibit ___

NK cell does not kill the ___ cell

A
  • signals from activating receptors
  • normal
144
Q

activated NK cells target infected, diseased, and stressed cells:

altered or absent MHC class I cannot stimulate a ___ signal. the NK cell is triggered by ___.

activated NK cell releases ___ contents, inducing ___ in the target cell

A
  • negative
  • signals from activating receptors
  • granule
  • apoptosis
145
Q

cells detect viral infections:

viral replication in cytoplasm prduces uncapped RNA with a ___

___ binding to viral RNA induces association with ___ and dimerization

dimerization initiates signaling pathways that activate ___ and ___

IRF3 causes synthesis and secretion of type I interferons, and NF-kappaB causes synthesis and secretion of ___

A
  • 5’-triphosphate
  • retinoic-acid-inducible gene (RIG)-I-like receptor (RLR)
  • mitochondrial antiviral signaling protein (MAVs)
  • IRF3 and NF-kappaB
  • inflammatory cytokines

Host and Defense (57 decks)

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