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Immunology PY2 > Lecture 4: Innate Immunity > Flashcards

Lecture 4: Innate Immunity Flashcards

1
Q

what are the key cells of the innate immune response?

A

neutrophils, eosinophils, basophils, mast cells

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2
Q

what are the key cells involved in the early adaptive immune response?

A

NK, NKT, ILC, monocytes, macrophages, dendritic cells

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3
Q

what are the keys cells involved in the primary adaptive response?

A

T and B cells

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4
Q

what are the key cells in the secondary adaptive immune response?

A

T and B cells

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5
Q

the innate and early adaptive immune responses are considered together as the ____ response

A

innate

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6
Q

the primary and secondary adaptive immune responses are referred to as the ___ response

A

adaptive

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7
Q

what are the 2 main roles of the innate immunity?

A
  1. first line of defence to slow infection until adaptive response can take over
  2. mechanism for directing the adaptive immune response (introduce inflammation, activate dendritic cells, produce cytokines that shape the adaptive immune response)
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8
Q

what is the response time of the innate immune system?

A

minutes to hours

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9
Q

what is the response time of the adaptive immune response?

A

days

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10
Q

describe the level of specificty the innate immune response has

A

specific for molecules and molecular patterns that are typically found on pathogens and recognize the molecules typically produced by dead/damaged cells

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11
Q

describe the level of diversity of the innate immune response

A

a limited number of cnserved, germ-line-encoded receptors

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12
Q

describe the level of memory responses of the innate immune response

A

some (has been observed in invertebrate innate responses and mouse & human NK cells)

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13
Q

describe how well the innate immune response can differentiate between self and nonself

A

perfectly bc they only recognize conserved features of pathogens

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14
Q

what are the soluble compenents of blood from the innate immune response?

A

many antimicrobial peptides, proteins, and other mediators

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15
Q

what are the major cell types of the innate immune response?

A

phagocytes (monocytes, macrophages, neutrophils), NK cells, leukocytes, epithelial and endothelial cellls

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16
Q

describe the specificity of the adaptive immune response

A

highly specific, discriminates between tiny differences in molecular structure of microbial and non-microbial molecules

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17
Q

describe the level of diversity of the adaptive immune resposne

A

highly diverse; very large number of receptors arising from genetic recombination or receptors genes in each person

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18
Q

describe the memory responses of the adaptive immune responses

A

persistent memory with faster response of greater magnitude on subsequent exposure

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19
Q

describe the level of self vs nonself discrimination in the adaptive immune response

A

very good, but there are occaisional failures which result in auti-immune diseases

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20
Q

what are the soluble components of the blood of the adaptive immune response?

A

antibodies and cytokines

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21
Q

what are the major cell types of the adaptive immune response?

A

T cells, B cells, and antigen presenting cells

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22
Q

list 2 anatomic barriers to infection

A
  1. skin

2. mucus membranes

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23
Q

t/f the skin (epidermis and dermis) is a mechanical barrier impermeable to most infectious agents

A

t

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24
Q

what is the epidermis?

A

several layers of epithelial cells where the outermost layer contains dead cells filled with keratin (a waterproofing proetin)

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25
Q

what are mucus membranes?

A

epithelium lining the interior surfaces of the body that secrete mucus to trap foreign particles to prevent them from adhereing to epithelial cells

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26
Q

what happens to the foreign particles trapped in the mucus of mucus membranes?

A

expelled by the mechanical action of cilia or by sneezing, coughing, or swallowing

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27
Q

what is the function of commensal (good) gut bacteria?

A

inhibit the growth of pathogenic bacteria; produce protective peptides

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28
Q

what are the special feature of the mucus membranes in the GI tract that prevent infection?

A

enzymes and normal flora

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29
Q

what are the special features of the mucus membranes of the respiratory tract that help prevent infection?

A

mucus, mechanical action of cilia, macrophages in alveoli

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30
Q

what are the special features of the mucus membranes in the urogenital tract?

A

mucus, fluid flow, aggregation of urinary mucins, low pH, antimicrobial peptides, proteins in vaginal secretions

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31
Q

what are 3 physiologic and chemical barriers that the body’s points of entry have to prevent infection?

A
  1. acidic pH of lactic acid and fatty acids present in sweat and sebaceous secretions
  2. acidic pH of the stomach
  3. body temperatire and fever response
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32
Q

antimicrobial (host defence) peptides are short ____ (cationic or anionic) peptides that are usually ____ amino acids in length

A

cationic; 29-35

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33
Q

antimicrobial (host defence) peptides are ____ (hydrophillic or hydrophobic)

A

amphipathic (both hydrophillic and hydrophobic parts)

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34
Q

antimicrobial (host defence) peptides are ____ expressed

A

constitutively

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35
Q

antimicrobial host defence peptides are active against what types of pathogens?

A

bacteria, fungi, enveloped viruses

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36
Q

antimicrobial host defence peptides bind to ____ charged (positive or negative) microbial structures and membranes via what type of interactions?

A

negative; electrostatic

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37
Q

give an example of part of a pathogen that an antimicrobial host defence peptide might bind to

A

LPS

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38
Q

how do antimicrobial host defense peptides work to stop pathogens?

A

disrupt the microbial membrane integrity by introducing bulky hydrophobic amino acids & internalized peptides inhibit DNA/RNA/protein synthesis and activate antimicrobial enzymes

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39
Q

how long does it take antimicrobial host defence enzymes to kill pathogens?

A

rapidly (minutes to hours)

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40
Q

give an example of antimicrobial host defence peptides

A

defensins (alpha and beta)

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41
Q

defensins are secreted by ___ cells and other ___ cells and are stored in ___

A

intestinal epithelial Paneth cells and other epithelial cells; stored in netrophil granules

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42
Q

location of defensins can be found where?

A

skin, mucosal epithelia (mouth, intestine, nasal/respiratory tract, urogenital tract)

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43
Q

how do defensins have antimicrobial activity?

A

disrupt membranes of bacteria, fungi, protazoan parasite and viruses. Have additional toxic effects intracellularly

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44
Q

defensins are able to kill ___ and disable ___

A

bacteria; viruses

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45
Q

how does streptococcus pneumoniae get into the body?

A

airways

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46
Q

how does E.coli get into the body?

A

GI tract

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47
Q

how does HIV get into the body?

A

urogenital

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48
Q

how does staph. aureus get into teh body?

A

cuts in the skin

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49
Q

how does West Nile get into the body?

A

mosquito bites

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50
Q

after penetrating epithelial barriers, pathogens are detected by what 3 innate immune components?

A
  1. soluble innate immune recognition elements
  2. phagocytic and other cells
  3. pattern recognition receptors like toll-like receptors
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51
Q

what are soluble innate immune recognition elements that recognize pathogens?

A

mannose-binding lectin, C-reactive proteins, complement, interferons

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52
Q

what are phagocytes and other cells that act as innate immune resposnes against pathogens?

A

neutrophils, macrophages, dendritic cells, NK cells

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53
Q

pattern recognition receptors (PRRs) like toll-like receptors (TLRs) can be found on what innate immune cells?

A

macrophages, mast cells, dendritic cells that function as sentinel cells

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54
Q

what is the acute phase response?

A

systemic, generic response to infection for containment and mobilization of immune cells and effector proteins

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55
Q

acute phase response creates a ____ response to slow pathogen growth and help immune reactions

A

fever

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56
Q

in the acute phase response, the local acute inflammation sends what cytokines to the hypothalamus?

A

IL-1, TNF-alpha, IL-6

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57
Q

in the acute phase response, the local acute inflammation sends what cytokines to the liver?

A

IL-1, TNF-a, IL-6, LIF, OSM

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58
Q

in the acute phase response, the local acute inflammation sends what cytokines to the bone marrow?

A

IL-6, TNF-a

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59
Q

what is the effect of cytokines being sent to teh hypothalamus in the acute phase response?

A

produce prostaglandins to create the fever; also sends ACTH via the pituitary to teh adrenal cortex which will send corticosteroids to the liver to release acute phase proteins

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60
Q

what is the effect of cytokines being sent to the liver in the acute phase response?

A

acute phase proteins are made; C-reactive protein (CRP), serum amyloid A (SAA), fibronogen, manose-binding protein, complement compoenents

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61
Q

what is the effect of cytokines being sent to the bone marrow in the acute phase response?

A

causes increased CSF by stromal cells and macrophages and induced leukocytosis (making more WBCs)

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62
Q

what are the 3 major pro-inflammatory cytokines that cause vascular permeability, systemic and local effects?

A

IL-1, IL-6, TNF-alpha

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63
Q

what is the anti-inflammatory cytokine?

A

IL-10

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64
Q

what cells produce IL-1?

A

monocytes, macrophages, dendritic cells, keratinocytes, epithelial cells, vascular endothelial cells

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65
Q

what cells does IL-1 act on?

A

lymphocytes, bone marrow, vascular endothelium, liver, hypothalamus

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66
Q

what is the immune response fo IL-1?

A

enhances inflammatory reponse, promotes neutrophil production, activates and increases vascular permeability, induces acute pahse response, fever

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67
Q

what is the immune response of IL-6?

A

regulates activity, promotes hematopeiesis (neutrophils), activates and increases vascular permiability, induces acute phase response, fever

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68
Q

what is the immune response of TNF-a?

A

activates inflammatatory response, activates and increases vascular permeability, fluid loss, local blood clotting, induces acute phase response, fever, cytotoxic for many tumor cells

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69
Q

what cells produce IL-6?

A

monocytes, macrophages, dendritic cells, NK cells, epithelial cells, vascular endothelial cells

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70
Q

what cells does IL-6 act on?

A

lymphocytes, bone marrow, vascular endothelium, liver, hypothalamus

71
Q

what cells produce TNF-a?

A

monocytes, macrophages, dendritic cells, mast cells, NK cells, epithelial cells

72
Q

what cells does TNF-a act on?

A

macrophages, vascular endothelium, liver, hypothalamus, tumors

73
Q

most cytokines are controlled by ___

A

NF-kB

74
Q

collection of cytokines enables comprhensive immune response form _____ to ___

A

anti-pathogen. to de novo differentiation of immune cells

75
Q

giev 3 examples of soluble factors that contribute to immune response

A
  1. various secretions contain substances with anti-bacterial activity
  2. collectins
  3. complement
76
Q

what soluble factor is contained in gastric juice that has anti-bacterial activity?

A

acid

77
Q

what soluble factor is contained in semen that has anti-bacterial activity?

A

spermine and zinc

78
Q

what soluble factor is contained in breast milk that has anti-bacterial activity?

A

antimicrobial peptides; lactoperidase

79
Q

what soluble factors are found in tears, saliva, and nasal secretions that have anti-bacterial activity?

A

lysozyme

80
Q

what are collectins and their role in immunity?

A

small proteins tha are able to kill certain bacteria by disrupting their cell walls, causing bacteria to aggregate, which enhances their phagocytosis, and/or activates the complement by the lectin pathway

81
Q

what is the complement and its contribution to immunity?

A

a feed-forward cascade that enables killing spontaneously or killing after antibodies or mannose-binding lectin binds to the target cells

82
Q

what are the 2 key members of the type 1 (IFN) cytokines?

A

IFN-a and IFN-B

83
Q

what is the function of type 1 IFNs (a and B)?

A

inhibit viral replication and genrate an antiviral state

84
Q

type 1 IFN (a and B) are produced by what cells?

A

IFN-a is made by leukocytes, especially PDC

IFN-B is made by fibrobalsts

85
Q

what is the key type 2 IFN?

A

IFN-y

86
Q

what is the function of IFN-y?

A

enhance killing of virus-infected cells, promote Th1 immunity

87
Q

IFN-y is made by what 2 cell types?

A

NK cells and T cells

88
Q

many cells make a small amount of type 1 IFN, but what typeof cells produce 100-1000x more type 1 IFN than any other cell type upon contact with viruses?

A

plasmacytoid dedritic cells

89
Q

do plasmacytoid dendritic cells need a productive viral infection to upregulate genes coding for type 1 interferons?

A

no

90
Q

the recognition mechanism for viral infection of plasmacytoid dendritic cells is via ___ that recogize ___

A

TLR7/8; ssRNA and TLR9 (CpG DNA)

91
Q

t/f plasmacytoid dedritic cells are important in driving immune response against viral infections (ex: NK cell responses)

A

t

92
Q

presence of viral ___ or ____ activates IFNa/B production by stimulating ____ receptors

A

DNA or RNA; pattern recognition receptors like toll-like receptors

93
Q

interferons can induce antiviral responses in neighbouring cells by binding to ____ receptors, leading to ____

A

IFN-a/B; mRNA degradation and inhibition of protein synthesis

94
Q

t/f virus infected cells produce type 1 interferons that act on neighbouring cells (i.e. paracrine signalling), making them refractory to viral groth

A

t

95
Q

genes turned on by IFN are called ____

A

IFN stimulated genes (ISG)

96
Q

the products of IFN stimulated genes typically inhibit ___ and ___ of ALL genes in the cell, which prevents viral genes from being used

A

transcription and translation

97
Q

phagocytosis is initiated by binding to microbes via ____ or ____ receptor and is enhanced by pathogen binding to ____ receptors

A

bound antibodies (opsonization) or scavenger receptors, enhanced by pathogen binding to pattern recognition receptors

98
Q

how does respiratory burst in phagocytosis kill pathogens?

A

generates reactive oxygen and nitrogen intermediates

99
Q

how to activated neutrophils and macrophages kill phagocytosed pathogens?

A

express inducible nitric oxide synthase that produces nitric oxide to kill pathogens; can also kill by hydrolytic enzymes, or antimicrobial peptides

100
Q

give 3 examples of C-type lectin receptors (CLRs) and their ligands

A
  1. mannose receptor–> mannans (bacteria, fungi, parasites)
  2. dectin-1 –> B-glucans (fungi, some bacteria)
  3. DC-SIGN –> mannans (bacteria, fungi, parasites)
101
Q

give 2 examples of scavenger receptors and their ligands

A
  1. SR-A –> LPS, LTS (bacteria_

2. SR-B –> LTA, lipopeptides, diacylglycerides (bacteria), B-glucans (fungi)

102
Q

what are the ligands to opsonin receptors?

A

microbe-binding opsonins (soluble, bind to micribes)

103
Q

what are the ligands for pattern recognition receptors?

A

microbial ligands (found on microbes)

104
Q

give an example of a collagen domain receptor and its ligand

A

CD91/calrectculin –> collectins SPA, SPD, MBL; L-ficolin, C1q

105
Q

give 5 examples of complement receptors and their ligands

A

CR1, CR3, CR4, CRIg, C1qRp –> complement components and fragments

106
Q

give 2 examples of Ig Fc receptors and their ligands

A

FcaR –> specific IgA antibodies bound to antigen

FcyRs –> specific IgG antibodies bound to antigen, & c-reactive protein

107
Q

what are pattern racognition receptors

A

molecular sensors that recognize structural motifs (pathogen-associated molecular patterns; PAMPs) in microbes that are highly conserved and usually needed for their survival AND innate inlammatory reponses

108
Q

what are DAMPs? What is their function?

A

damage-associated molecular patterns like heat shock proteins. Not expressed on healthy cells, so they trigger TLRs and NLRs to cause clearance of dead, dying, and aging cells by macrophage-mediated phagocytosis

109
Q

on what cells are pattern recognition receptors found?

A

myeloid cells, lymphoid subsets, and other cells that are commonly exposed to pathogens such as skin and mucosal epithelial cells, endothelial cells and fibroblasts

110
Q

what are the 3 main classes of pattern recognition receptors?

A
  1. toll-like receptors (TLRs)
  2. Nod-like receptors (NLRs)
  3. C-type lectin receptors (CLRs)
111
Q

what is detected by TLRs?

A

a variety of PAMPs and DAMPs

112
Q

how do TLRs detect PAMPs and DAMPs?

A

bind to their leucine-rich repeat (LRR) domains that make up the extracellular ligand binding structure. Lingand binding caused dimerization of the TLR and signal trnasduction

113
Q

can TLRs promote phagocytosis?

A

no

114
Q

what are Nod-like receptors (NDLs)?

A

intracellular PRRs that are activated by PAMPs and DAMPs

115
Q

how do C-type lectin receptors (CLRs) work?

A

bind to carbohydrates on the surface of pathogens and promote phagocytosis

116
Q

______ receptors bind vrial RNAs and are additional important PRRs

A

retinoic acid inducible gene-I-like receptors (RLRs)

117
Q

the u-shaped domain of TLRs is made of ___ rich repeats

A

leucine

118
Q

describe the structure of the TLRs

A

u-shaped, leucine rich extracellular domain and endosomal TIR domain

119
Q

when ligands bind to TLRs, they can dimerize in what 2 ways?

A
  1. homodimerize (TLR3/3) or heterodimerize (TLR2/1)
120
Q

what is the function of the Toll/IL-1 receptor (TIR) domain of the TLR?

A

interacts with adaptor molecules that function as sorting receptors for other adaptor molecules and can initiate early specialization (polarization) of immune responses tailored to pathogens

121
Q

t/f some TLR are found in the cell surface and some are found in the endosomes

A

t

122
Q

which 3 TLR are found in the endosomes?

A

TLR-3, TLR-7 and TLR-9

123
Q

which 6 TLR are found in the plasma membrane?

A

TLR-1, TLR-2, TLR-4, TLR-5, TLR-6

124
Q

TLR-5 in the plasma membrane binds to ____

A

flagellin

125
Q

the combo TLR-2/TLR-1 in the plasma membrane binds to __

A

triacycle lipopeptides

126
Q

the combo TLR-2/TLR-6 in the plasma membrane binds to ___

A

diacyle lipopeptides

127
Q

the TLR-4 in plasma membranes binds to ____

A

LPS (and MD-2?)

128
Q

TLR-3 in the endosome binds to ___

A

dsRNA

129
Q

TLR-7 in the endosome binds to

A

ssRNA

130
Q

TLR-9 in the endosome binds to ___

A

CpG DNA

131
Q

TLR signalling from the plasma membrane relies on the ___ adaptor

A

MyD88

132
Q

what are the 3 major steps in the MyD88-dependent TLR signalling pathway?

A
  1. mitogen-activated protein kinase (MAPK) pathways leading to AP-1 translocation
  2. NK-kB activation and translocation
  3. IFN response factors (IRFs) are activated downstream of endosomal MyD88 activation
133
Q

inflammation-promoting genes regulated by NF-kB include what 5 main categories?

A
  1. inflammatory cytokines
  2. chemokines
  3. adhesions molecules on endothelial cells
  4. immune effector molecules
  5. costimulatory molecules
134
Q

what are the inflammatory cytokines regulated by NF-kB?

A

TNF-a, IL-1, IL-6, IL-12, GM-CSF, IFN-a/B

135
Q

what are the chemokines regulated by NF-kB?

A

IL-8, MCP, RANTES, eotaxin

136
Q

what are the adhesion molecules on endothelial cells that are regulated by NF-kB?

A

ICAM -1, VCAM-1, E-selectin, P-selectin

137
Q

what are the immune effector molecules that are regulated by NF-kB?

A

inducible nitric oxide synthase (iNOS), defensins

138
Q

what are the costimulatory molecules that are rugulated by NF-kB?

A

CD40 and CD80/CD86 on dendritic cells

139
Q

MyD88 can additionally activate ____

A

IRFs

140
Q

TRIF-dependent signalling activates what 3 things?

A
  1. MAPKs and IRFs to induce IFN a/B expression
  2. NF-kB
  3. IRFs
141
Q

Dendritic cells must do what in order to be able to present antigens?

A

must mature from their immature (tissue-resident) form to mature cels

142
Q

what are the hallmarks of dendritic cell maturation?

A

expression of CD80/CD86 and CD40, upregulation of class 2 MHC and production of IL-12 and CCR7 to migrate to lymph nodes

143
Q

what 2 things induce maturation of dendritic cells?

A
  1. TLR binding (most iDCs express most TLRs)

2. acute phase cytokines, TNF and IL-1B

144
Q

what are NOd-like receptors?

A

intracellular complexes that bind to conserved microbial features like flagellin and non-microbial substances like DAMPs

145
Q

some nod-like receptors assemble into ____, which contain proteases to form a complex that converts prescursor forms of ___ and ___ into active inflammation-promoting cytokines via ____

A

inflammasomes; IL-1B and IL-8; caspase-mediated cleavage (acute phase)

146
Q

inflammasomes act in tandem with other ___ in response to ___ or ___ to prime the inflammatory reposne

A

PRRs; PAMPs and DAMps

147
Q

give 3 examples of self-derived sterile activators of inflammasomes

A
  1. atp
  2. glucose
  3. cholesterol crystals
148
Q

give 3 examples of environmentally derived sterile activators of inflammasomes

A
  1. UV radiation
  2. asbestos
  3. skin irritants
149
Q

give 3 examples of bacteria derived pathogen activators of inflammasomes?

A
  1. flagelling
  2. RNA
  3. DNA
150
Q

give 2 examples of virus derived pathogen activators of inflammasomes

A
  1. RNA

2. influenza M2 protein

151
Q

give 3 examples of fungi derived pathogen activators of inflammasomes

A
  1. B glucans
  2. mannan
  3. hyphae
152
Q

give an example of protozoa derived pathogen activators of inflammasomes

A

hemozoin

153
Q

the NLRP3 inflammasome is expressed by what 6 cell types?

A
  1. monocytes
  2. macrophages
  3. neutrophils
  4. dendritic cells
  5. some lymphocytes
  6. epithelial cells
154
Q

In addition to signalling from PAMPs and DAMPs, inflammasomes need a second signal for activation; what are the 3 proposed models?

A
  1. ATP influx secondary to pore formation
  2. crystalline/particulate substances secondary to lysosomal rupture
  3. reactive oxygen species
155
Q

there are at least ___ human c-type lectin receptors (CLRs)

A

15

156
Q

c-type lectin receptors (CLRs) are expressed on what cell types? (6)

A
  1. monocytes
  2. macrophages
  3. dendritic cells
  4. neutrophils
  5. T cells
  6. B cells
157
Q

C-type lectin receptors are responsible for detecting what?

A

carbohydrate components (like glucans) of microbes

158
Q

binding to c-type lectin receptors triggers ___ and sometimes ____

A

intracellular signalling; phagocytsosis

159
Q

____ (distal or proximal) CLR signalling differs from MyD88-dependent TLR signalling, but, ____ (distal or proximal) events are similar

A

proximal; distal

160
Q

what makes distal CLR signalling similar to MyD88 TLR signalling?

A

NK-kB and AP-1 are activated

161
Q

CLR and TLR signalling can occur in the same cell and combine to enhance the production of _____

A

inflammation-promoting cytokines

162
Q

what are the functions of neutrophils?

A

phagocytosis, reactive oxygen & nitrogen species, antimicrobial peptides

163
Q

what are the functions of macrophages?

A

phagocytosis, inflammatory mediators, antigen presentation, reactive oxygen and nitrogen species, cytokines, and complement proteins

164
Q

what are the functions of dedritic cells?

A

Antigen presentation, costimulatory signals, reactive oxygen species, IFN, cytokines

165
Q

what are the functions of NK cells?

A

lysis of viral infected cells, IFN, macrophage activation

166
Q

why are NK cells the first line of defence against viral infections?

A

they have rapid activation by IFN-a and IFN-B and by IL-12 produced by dendritic cells

167
Q

NK cells are important for virus-specific ____ induction

A

CTL

168
Q

why are NK cells important to CTL induction?

A

because of their production og source of CTL-promoting IFN-y

169
Q

what are NK cells?

A

non-specific cytotoxic effector cells that provide early defence against viruses and cancer

170
Q

NK cells make up ___% of peripheral blood lymphocytes

A

5-10%

171
Q

Natural killer cells arise from what pathway?

A

T/NK progenitor downstream from the common lymphocyte progenitor (most closely related to T cells)

172
Q

List 4 functions of NK cells

A
  1. produce IFN-y & respond to type 1 IFN
  2. induce target cell death through receptor-ligand signalling and release of toxic products (ex: perforin and granzyme)
  3. respond to antibodies bound to target cells by inducing antibody-dependent cellular toxicity (ADCC)
  4. NK cell function is regulated by MHC receptors
173
Q

NK function os regulated by ___ receptors

A

MHC

Immunology PY2 (20 decks)

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