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Lecture 4 Flashcards

0
Q

What is the reaction of innate immunity?

A

eliminates damaged cells and initiates the process of tissue repair:
-recognizes and responds to host molecules related to stressed, damaged, and dead host

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1
Q

innate immunity

A

initial host defense response to pathogens that prevents, controls, or eliminates infection:
-may keep the infection in check until more specialiezed adaptive immune repsonses are activated

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2
Q

What clears cell debris?

A

phagocytosis

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3
Q

What stimulates and controls tissue remodeling?

A

innate immunity

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4
Q

Innate immunity controls?

A

adaptive responses

  • intracellular vs extracellular pathogens
  • provides the danger signals that alert the adaptive immune system to response
  • reacts in distint ways to different microbes thereby influcencing the type of adaptive immune response
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5
Q

cellular and chemical barriers

A

skin, mucosal epithelia, antimicrobial molecules

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6
Q

blood proteins

A

complemetn, acute phase proteins, cytokines, others

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7
Q

cells

A

phagocytes(macrophages, neutrophils), dendritic cells, natural killer cells, innate lymphoid cells

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8
Q

Liver is major responder to these acute phase proteins

A

components

T cells were-natural killer cells, innate lymphoid cells,

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9
Q

innate immunity

A

inflammation, physical barriers, anti viral responses

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10
Q

leukocytes and plamsa proteins

A

inflammation

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11
Q

skin and epithelial cells

A

physcial barriers

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12
Q

inhibition of viral replication

A

anti-viral reponses

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13
Q

innate immunity specficity

A

pathogen-assocaited mollecular patterns (PAMPs)

damage-associated mollecular patterns (DAMPs)

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14
Q

adaptive immunity specificity

A

Fine structures of microbial and non microbial Ags

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15
Q

Innate immunity receptors

A

patterna recognition receptors (PRRs)

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16
Q

Adaptive immunity receptors

A

greater diversity of BCRs and TCRs generated by somatic recombination

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17
Q

Distribution of receptors innate immunity

A

nonclonal: identical receptors on vaious cell

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18
Q

Distribution of receptors with adaptive immunity

A

clonal: identical on a single cell, but different btw two cells

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19
Q

innate immunity discrimination of self and non self

A

Yes

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20
Q

adaptive immunity discrimination of self and non self

A

Yes

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21
Q

Nucleic Acids

  • ssRNA
  • dsRNA
  • CpG- unmethylated CpG DNA seuqneces
A
  • Virus
  • Virus
  • Virus, bacteria
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22
Q

Protiens
Pilin
Flagellin

A
  • bacteria

- bacteria

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23
Q 
Cell wall lipids
Lipoplysaccharides (LPS)
Lipoteichoic acid (LTA)
A
  • Gram negative bacteria

- gram positive bacteria

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24
Q

Carbohydrates
mannan
glucans

A

fungi, bacteria

fungi

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25
Q

Damage Assocaited molecular patterns

Stress induced proteins

A

HSPs

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26
Q

crystals

A

monosodium urate

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27
Q

nuclear proteins

A

HMGB1

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28
Q

innate immunity inducers inflammation

A

pathogens sd

Exogenous ligands (PAMPs)

  • nucleic acid
  • Lipid
  • Proteins
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29
Q

Sensors Pattern Recognition receptors inflammation

A

Toll-like receptors
NOD-like receptors
C-type lectin and so forth

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30
Q

mediators inflamation

A

TNF alpha
IL-6
IL-1Beta

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31
Q

Homeostatic inflammation Cell/ECM-derived molecules

inducers

A

Nuclecic Acids (ATP)
Lipid
Protein

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32
Q

inflammation causes

A

a lot of macrophages, it is unable to get rid of them.

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33
Q

Where can microbial PRRs be located?

A

extracellular in endososoems or cytosol

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34
Q

5 families of microbieal PRRs

A 
TLR family: surface, endosomal
CLRs family
NOD-like receptors (NLRs) family
RIG-like receptors (RLRs) family
Cytosolic DNA sensors (CDS) family
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35
Q

Which cell expresses toll like receptor 9??

A

macrophages

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36
Q

What bind pathogen assocaited molecular patterns from extracellular pathogens?

A

PRRs on the cell surface

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37
Q

What recognize nucleic acids of phagocytized microbes?

A

endosomal TLRs

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38
Q

NOD

A

nucleotide-binding oligomerization domain

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39
Q

CLR

A

C type lectin receptor

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40
Q

RIG

A

retinoic acid inducible gene

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41
Q

TLR’s location

A

surface and endosomal membranes of DCs, phagocytes, B cells, endotheial cells
Ex TLRs 1-9
Ligands= microbial Ags(LPS, peptidoglycans, viral nucleic acids)

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42
Q

NLRs llocation

A

cytosol of phagocytes, epithelial cells and others

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43
Q

NLR’s example NOD1/2

A

bacterial cell wall peptidoglycans

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44
Q

NLRP family (inflammasomes)

A

intracellular crystals (urate, silica); changes in concentrations of ATP and ions lysosomal damage

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45
Q

RLRs location

A

cytosol of phagocytes and other cells
ex RIG-1, MDA-5
Viral RNA

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46
Q

CDSs location

A

cytosol of many cell types
ex AIM2; Sing assocaited CDSs
bacterial and viral DNA

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47
Q

CLRs location

A

plasma membranes and phagocytes
mannose receptors
microbial carbohydrates w terminal mannose or fructose

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48
Q

homodimers or heterodimers

A

TLRs

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49
Q

evolutionalrily conserved family of PRRs expressed on many cell types

A

TLRs

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50
Q

What do TLRs recognize?

A

PAMPs and DAMPs

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51
Q

Whare TLRs are express on the cell surface?

A

1,2,4,5,6

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52
Q

What TLRs are expressed in endosomes?

A

3,7,8,9

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53
Q

DNA containing un methylated ctyosine-guanosine dinucleotides

A

CpG

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54
Q

receptor homology domain

A

TIR, TOLL/IL-1

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55
Q

TLR1;TLR2

A

bacterial lipopeptides

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56
Q

TLR2

A

bacterial peptidoglycans

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57
Q

TLR4

A

LPS

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58
Q

The only anti inflammatory cytokine is?

A

L10 not dependent on

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59
Q

TLR5

A

bacterial flagelin

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60
Q

TLR2;TLR6

A

bacterial lipopeptides

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61
Q

TLR3

A

dsRNA

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62
Q

TLR7

A

ssRNA

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63
Q

TLR8

A

ss RNA

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64
Q

TLR9

A

CpG DNA

65
Q

TLR structure

A

Leucine rich repeat motifs

cysteine rich flanking motifs, TIR domain

66
Q

What adaptor protein does TLRs 1, 2, 5 and 6 use?

A

MyD88

67
Q

MyD88 activates?

A

the transcription factors NF-kB and AP-1

68
Q

What adaptor ptoein does TLR3 use/

A

TRIF

69
Q

What does TRIF activiate?

A

IRF3 and IRF7 transcription factos

70
Q

TLRs 7 ad 9 can activate

A

both pathways

71
Q

TLRs 7 and 9 in the endosome use

A

MyD88

72
Q

MyD88 activates

A

NF-KB adn IRF7

73
Q

Major TLF signaling pathways?

A

MyD88, with expetion of TLR3

74
Q

TLR4 and the TLR2 subfamily(TLF1, TLR2, TLR6) engage?

A

TIRAP

75
Q

How does TLR3 signal?

A

TRIF

76
Q

What is TRIF used in conjuction with?

A

TRAM in the TLR4-MyD88-independent pathway

77
Q

What are functional roles of TLRs?

A

influence adaptive repsone–>T cells–>cell mediated immunity
direct antimicrobial response–> bacterial death
tissue injury–> apoptosis of host cells or septic shock

78
Q

What is produced in the inflammasome?

A

secreted form of IL-1B and IL-18

79
Q

What are proinflammatory cytokines?

A

IL-1B and IL-18

80
Q

What is the main function of caspase-1?

A

to cleave the inactive ctyoplasmic precursor forms of two homologous ctyokines called IL-IB and IL-18

81
Q

What does inflammasomes activate?

A

the enzyme caspase-1(a protease w cysteine residue in the active site)

82
Q

a subfamily of 14 NOD-like receptors

A

NLRP(pyrin-domain-containing protines)

83
Q

What respond to cytosolic PAMPs and DAMPs by binding other proteins and forming signaling complexes?

A

inflammasomes

84
Q

Caspase

A

important in apoptosis

85
Q

macrophage mannose receptor (MMR) and DEC-205

A

a) a cysteine- rich N terminal domain
b) a fibronectin-like domain
c) multiple calcium-dependent (C-type)lectin domains that bind various carbohydrate ligands

86
Q

The scavenger receptor (SR) family

A

trimeric complexes of type II transmembrane polypeptides

87
Q

Have 3 distince extracellular structural domains

A

a) SR cysteine-rich (SRCR) domain (absent in SR-A II)
b) the collagen-like domain, which is implicated in the binding of polyanionic ligands
c) the alpha- helical coiled-coil domain (absent in MARCO), which is believed to assist in receptor trmerization

88
Q

What is a group of receptors mediated the uptake of oxidiezed lipoprotiens into cells?

A

SRs

89
Q

What are expressed on Mo and mediate recognition/phagocytosis of microorganisms?

A

SR-A and CD36

90
Q

What functions as a coreceptor in TLR2/6 recogintion and repsonse to bactrailly derived lipoteichoic acid and diacylated lipopeptides?

A

CD36

91
Q

SRs bind various bacterila constituets based on?

A

negative charges of bacterial LPS, lipoteichoic acid, nucleic acids, B-glucan and proteins…. only bacteria has sugars

92
Q

What are c-type lectin receptors?

A

receptors for carboydates

93
Q

What is the mannose receptor involved in?

A

phagocytosis of microbes

94
Q

What do mannose receptors recognize?

A

terminal D-mannose, L-fucos, and N-acetyl D glucosamine sugars on microbial surface

95
Q

What does carbohydrate receptors contain a conserved carbohydrate recognition domain for?

A

microbial mannose, N-acetylglucosamine, and B-glucans

96
Q

Some of the lectins are soluble proteins found in?

A

the blood an dextracellular fluids

97
Q

Other lectins are integral membrane proteins found on

A

the surfaces of macrophages, dendritic cells, and some tissue cells

98
Q

What doe receptors for carbohydrates facilitate?

A

the phagocytosis of the microbes and the secretion of cytokines that promote subsequence adaptive immune repsones

99
Q

what prevent approach and deny entry of pahtogens at skin and mucous membranes?

A

physical barriers for innate immunity

100
Q

What remove debris and pahtogens?

A

pagocytes

101
Q

destroys absnomal cells

A

immunological surveillance

102
Q

What immune cells are TLRs expressed on?

A

mcarophages and dendritic cells

103
Q

What do microbial lipoproteins activate?

A

mammalian immune cells through TLR2

104
Q

What does LPS activate?

A

TLR4

105
Q

What do bactreial DNA sequences containing unmethylated cytosine-guanomsine dinucleotides(CpGs) work through?

A

TLR9

106
Q

What does TLR dependent signaling pathways activate?

A

NF-KB which results in transcription of pro inflammatory genes

107
Q

What controsl the adaptive T cell immune response?

A

Cytokine IL-12

108
Q

What does activation of TLRs trigger?

A

antimicrobial pathways that directly kill the pathogens

109
Q

In what way can actiavtion of the TLRs be detrimental to the host?

A
  • can contribute to tissue injury by inducing apoptosis

- can lead to life thratening symptoms of septic shock

110
Q

What does epithelia at the portals of entry of microbes provide?

A

physical barriers, produce antimicrobial substances, and harbor intraepithelial lymphocytes that are believed to kill microbes and infected cells

111
Q

small cationic peptides that contain both cationic and hydrophobic regions

A

defensins

112
Q

What are defensins produced by?

A

epithelial cells of mucosal surfaces and by granule containign leukocytes, including neutrophils, NK cells, and CTLs

113
Q

Why is synthesis of defensins stimulated by?

A

cytokines and microbial products

114
Q

Defensin A and B are produced by

A

different cell types

115
Q

What have direct toxicity to microbes, including bacteria, fungi and enveloped viruses?

A

defensins

116
Q

How do defensisn kill microbes?

A

By inserting into and disrupting functions of the microbail membranes

117
Q

What regualted activation of cells involved in the infalmmatory repsonse to microbes?

A

antimicrobial peptides defensins

118
Q

What are produced by neutrophils and barrier epithelial cells in the skin, gastrointestinal tract and respiratory system?

A

antimicrobial peptides cathelicidins

119
Q

What are antimicrobial peptides cathelicidins synthesized as?

A

18-kD two domain precursor protine and is proteolytically cleaved into two protective peptides

120
Q

Whay would synthesis and cleavage of antimicrobial peptides cathelicidins be stimulated by?

A

cytokinds and microbial products

121
Q

What are the mechanisms of antimicrobial peptides cathelicidins?

A

direct toxicity to microorganisms and the activation of leukocytes

122
Q

What can bind and neutralize LPS?

A

C-termal fragment called LL-37

123
Q

What plays an anti inflammatory role by beinding to DNA and blocking AIM2 inflammasome activation?

A

LL-37

124
Q

What are common at sites in the body that are exposed to the external environment, such as the skin?

A

mast cells

125
Q

Why are mast cells found in close proximity to blood vessels?

A

They can regualte vacular permeability and effector- cell recruitment

126
Q

How can mast cells regulate the behavior of neighboring cells?

A

Effector cells through the release of mediators

127
Q

What are lipid mediators?

A

prostaglandins, leukotrienes, platelet-activating factors

128
Q

Mast cells release what preformed mediators?

A 
histamine
heparin
proteases
chondroitin sulfates
TNF
antimicribial peptides
129
Q

What effect does lipid mediators have?

A
  • recruitment and activation of monocytes and macrophages

- migration and activation of dendritic cells

130
Q

What effect do preformed mediators have?

A
  • recruitment and activation of T cells
  • recuritment and activation of neutrophils, basophils and eosinophils
  • phagocytosis and or antimicrobial activity
  • effects on epithelial cells, tight juction protiens, etc..
131
Q

Functions of monocyte/macrophages

A

1.activation
2.chemotaxis, tissue inflammation
3. phagocytosis, scavenger function, tissue repair
4effector function
5. antigen presentation
6. immunomodulation

132
Q

Where do dendritic cells arise from?

A

A common precursor cell of the myeloid lineage in the bone marrow

133
Q

What do Dcs further differentiate into?

A

classical DCs and plamacytoid Dcs

134
Q

What may arise from monocytes in infalmed tissues?

A

inflammatory DCs

135
Q

tissue-redient DCs, the skin, appears early in life and may develop from embryonic precursors

A

Langerhans cells

136
Q

What is the matruation of DCs dependent on?

A

Flt2 ligand, which binds to the Flt3 tyrosine kinase receptor on the precursor cells

137
Q

Dendritic cells are the most improtant for activation of?

A

naive T cells

138
Q

Play a major role in inate responses to infections and in linking innate and adaptive immune repsonses?

A

DCs

139
Q

WHat have long membraneous projections and phagocytic capabilites?

A

DCs

140
Q

DCs are part of the …. lineage?

A

Myeloid and arise from a precursor that can also differentiate into monocytes

141
Q

Does to Mo and Dcs express?

A

receptors that recognize Ags typically made by microbes and no mammalian cells

142
Q

What do activated DCs also secret?

A

cytokines

143
Q

Where do classical DCs reside?

A

The skin, mucosa and organ parenchyma

144
Q

Where do cassical DCs micrate upon actiatioini by microbes?

A

to LNs where they display microbial protein Ags to T lymphocytes

145
Q

What are early cellular repsonders to viral infections?

A

plamacytoid DCs

146
Q

What does plamacytoid DCs recgonize and produce?

A

They recognize nucleic acids of intracellular viruses and produe soluble proteins type I interferons, aka IFN-alpha/beta

147
Q

What have potent antiviral activites?

A

IFN-ALpha/beta

148
Q

DC may also derive from

A

ciruclating monocytes

149
Q

What do innate lymphoid cells develop from?

A

Common bone marrow precursor identified by the Id2 transcription factor

150
Q

What are the 3 major subsets of innate lymphoid cells?

A

distinguished by expression of distince transcription factors and by cytokines produced

151
Q

ILC1–>

A

IL-12 and IL-18

defense against viruses

152
Q

ILC2–>

A

IL-25 and IL-33

allergic inflammation

153
Q

ILC3–>

A

IL-1 and IL-23

intestinal barrier function; lymphoid organogensesis

154
Q

What is the function of NK cells?

A

Recgnize ligands on infected cells or cells undergoing other types of stress

155
Q

NK cells kill htos…

A

infected or stressed host cells

156
Q

what eliminate reservoirs of infection and thus release intracellular pahtoges for phagocytosis?

A

NK

157
Q

What do NK cells respond too?

A

IL-12 produced by macrophages and secrete IFN-gamma

158
Q

What activates the macrophages to kill phagocytized microbes?

A

IFN-gamma

159
Q

When NK cells recognize ligands on targe cells, they?

A

activate protein tyosine kinases (PTKs)

160
Q

What are NK cell activating receptors called?

A

killer cell immunoglobulin (Ig) like receptors (KIRs)

161
Q

What do Nk cells not kill?

A

I MHC expressing healthy cells

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