Lecture 4 Flashcards Preview

Undeleted > Lecture 4 > Flashcards

Flashcards in Lecture 4 Deck (162):
0

innate immunity

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

1

What is the reaction of innate immunity?

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

2

What clears cell debris?

phagocytosis

3

What stimulates and controls tissue remodeling?

innate immunity

4

Innate immunity controls?

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

5

cellular and chemical barriers

skin, mucosal epithelia, antimicrobial molecules

6

blood proteins

complemetn, acute phase proteins, cytokines, others

7

cells

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

8

Liver is major responder to these acute phase proteins

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

9

innate immunity

inflammation, physical barriers, anti viral responses

10

leukocytes and plamsa proteins

inflammation

11

skin and epithelial cells

physcial barriers

12

inhibition of viral replication

anti-viral reponses

13

innate immunity specficity

pathogen-assocaited mollecular patterns (PAMPs)
damage-associated mollecular patterns (DAMPs)

14

adaptive immunity specificity

Fine structures of microbial and non microbial Ags

15

Innate immunity receptors

patterna recognition receptors (PRRs)

16

Adaptive immunity receptors

greater diversity of BCRs and TCRs generated by somatic recombination

17

Distribution of receptors innate immunity

nonclonal: identical receptors on vaious cell

18

Distribution of receptors with adaptive immunity

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

19

innate immunity discrimination of self and non self

Yes

20

adaptive immunity discrimination of self and non self

Yes

21

Nucleic Acids
-ssRNA
-dsRNA
-CpG- unmethylated CpG DNA seuqneces

-Virus
-Virus
-Virus, bacteria

22

Protiens
Pilin
Flagellin

-bacteria
-bacteria

23

Cell wall lipids
Lipoplysaccharides (LPS)
Lipoteichoic acid (LTA)

-Gram negative bacteria
-gram positive bacteria

24

Carbohydrates
mannan
glucans

fungi, bacteria
fungi

25

Damage Assocaited molecular patterns
Stress induced proteins

HSPs

26

crystals

monosodium urate

27

nuclear proteins

HMGB1

28

innate immunity inducers inflammation

pathogens sd

Exogenous ligands (PAMPs)
-nucleic acid
-Lipid
-Proteins

29

Sensors Pattern Recognition receptors inflammation

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

30

mediators inflamation

TNF alpha
IL-6
IL-1Beta

31

Homeostatic inflammation Cell/ECM-derived molecules
inducers

Nuclecic Acids (ATP)
Lipid
Protein

32

inflammation causes

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

33

Where can microbial PRRs be located?

extracellular in endososoems or cytosol

34

5 families of microbieal PRRs

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

35

Which cell expresses toll like receptor 9??

macrophages

36

What bind pathogen assocaited molecular patterns from extracellular pathogens?

PRRs on the cell surface

37

What recognize nucleic acids of phagocytized microbes?

endosomal TLRs

38

NOD

nucleotide-binding oligomerization domain

39

CLR

C type lectin receptor

40

RIG

retinoic acid inducible gene

41

TLR's location

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

42

NLRs llocation

cytosol of phagocytes, epithelial cells and others

43

NLR's example NOD1/2

bacterial cell wall peptidoglycans

44

NLRP family (inflammasomes)

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

45

RLRs location

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

46

CDSs location

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

47

CLRs location

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

48

homodimers or heterodimers

TLRs

49

evolutionalrily conserved family of PRRs expressed on many cell types

TLRs

50

What do TLRs recognize?

PAMPs and DAMPs

51

Whare TLRs are express on the cell surface?

1,2,4,5,6

52

What TLRs are expressed in endosomes?

3,7,8,9

53

DNA containing un methylated ctyosine-guanosine dinucleotides

CpG

54

receptor homology domain

TIR, TOLL/IL-1

55

TLR1;TLR2

bacterial lipopeptides

56

TLR2

bacterial peptidoglycans

57

TLR4

LPS

58

The only anti inflammatory cytokine is?

L10 not dependent on

59

TLR5

bacterial flagelin

60

TLR2;TLR6

bacterial lipopeptides

61

TLR3

dsRNA

62

TLR7

ssRNA

63

TLR8

ss RNA

64

TLR9

CpG DNA

65

TLR structure

Leucine rich repeat motifs
cysteine rich flanking motifs, TIR domain

66

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

MyD88

67

MyD88 activates?

the transcription factors NF-kB and AP-1

68

What adaptor ptoein does TLR3 use/

TRIF

69

What does TRIF activiate?

IRF3 and IRF7 transcription factos

70

TLRs 7 ad 9 can activate

both pathways

71

TLRs 7 and 9 in the endosome use

MyD88

72

MyD88 activates

NF-KB adn IRF7

73

Major TLF signaling pathways?

MyD88, with expetion of TLR3

74

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

TIRAP

75

How does TLR3 signal?

TRIF

76

What is TRIF used in conjuction with?

TRAM in the TLR4-MyD88-independent pathway

77

What are functional roles of TLRs?

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

78

What is produced in the inflammasome?

secreted form of IL-1B and IL-18

79

What are proinflammatory cytokines?

IL-1B and IL-18

80

What is the main function of caspase-1?

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

81

What does inflammasomes activate?

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

82

a subfamily of 14 NOD-like receptors

NLRP(pyrin-domain-containing protines)

83

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

inflammasomes

84

Caspase

important in apoptosis

85

macrophage mannose receptor (MMR) and DEC-205

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

The scavenger receptor (SR) family

trimeric complexes of type II transmembrane polypeptides

87

Have 3 distince extracellular structural domains

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

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

SRs

89

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

SR-A and CD36

90

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

CD36

91

SRs bind various bacterila constituets based on?

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

92

What are c-type lectin receptors?

receptors for carboydates

93

What is the mannose receptor involved in?

phagocytosis of microbes

94

What do mannose receptors recognize?

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

95

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

microbial mannose, N-acetylglucosamine, and B-glucans

96

Some of the lectins are soluble proteins found in?

the blood an dextracellular fluids

97

Other lectins are integral membrane proteins found on

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

98

What doe receptors for carbohydrates facilitate?

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

99

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

physical barriers for innate immunity

100

What remove debris and pahtogens?

pagocytes

101

destroys absnomal cells

immunological surveillance

102

What immune cells are TLRs expressed on?

mcarophages and dendritic cells

103

What do microbial lipoproteins activate?

mammalian immune cells through TLR2

104

What does LPS activate?

TLR4

105

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

TLR9

106

What does TLR dependent signaling pathways activate?

NF-KB which results in transcription of pro inflammatory genes

107

What controsl the adaptive T cell immune response?

Cytokine IL-12

108

What does activation of TLRs trigger?

antimicrobial pathways that directly kill the pathogens

109

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

-can contribute to tissue injury by inducing apoptosis
-can lead to life thratening symptoms of septic shock

110

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

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

111

small cationic peptides that contain both cationic and hydrophobic regions

defensins

112

What are defensins produced by?

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

113

Why is synthesis of defensins stimulated by?

cytokines and microbial products

114

Defensin A and B are produced by

different cell types

115

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

defensins

116

How do defensisn kill microbes?

By inserting into and disrupting functions of the microbail membranes

117

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

antimicrobial peptides defensins

118

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

antimicrobial peptides cathelicidins

119

What are antimicrobial peptides cathelicidins synthesized as?

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

120

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

cytokinds and microbial products

121

What are the mechanisms of antimicrobial peptides cathelicidins?

direct toxicity to microorganisms and the activation of leukocytes

122

What can bind and neutralize LPS?

C-termal fragment called LL-37

123

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

LL-37

124

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

mast cells

125

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

They can regualte vacular permeability and effector- cell recruitment

126

How can mast cells regulate the behavior of neighboring cells?

Effector cells through the release of mediators

127

What are lipid mediators?

prostaglandins, leukotrienes, platelet-activating factors

128

Mast cells release what preformed mediators?

histamine
heparin
proteases
chondroitin sulfates
TNF
antimicribial peptides

129

What effect does lipid mediators have?

-recruitment and activation of monocytes and macrophages
-migration and activation of dendritic cells

130

What effect do preformed mediators have?

-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

Functions of monocyte/macrophages

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

132

Where do dendritic cells arise from?

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

133

What do Dcs further differentiate into?

classical DCs and plamacytoid Dcs

134

What may arise from monocytes in infalmed tissues?

inflammatory DCs

135

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

Langerhans cells

136

What is the matruation of DCs dependent on?

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

137

Dendritic cells are the most improtant for activation of?

naive T cells

138

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

DCs

139

WHat have long membraneous projections and phagocytic capabilites?

DCs

140

DCs are part of the .... lineage?

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

141

Does to Mo and Dcs express?

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

142

What do activated DCs also secret?

cytokines

143

Where do classical DCs reside?

The skin, mucosa and organ parenchyma

144

Where do cassical DCs micrate upon actiatioini by microbes?

to LNs where they display microbial protein Ags to T lymphocytes

145

What are early cellular repsonders to viral infections?

plamacytoid DCs

146

What does plamacytoid DCs recgonize and produce?

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

147

What have potent antiviral activites?

IFN-ALpha/beta

148

DC may also derive from

ciruclating monocytes

149

What do innate lymphoid cells develop from?

Common bone marrow precursor identified by the Id2 transcription factor

150

What are the 3 major subsets of innate lymphoid cells?

distinguished by expression of distince transcription factors and by cytokines produced

151

ILC1-->

IL-12 and IL-18

defense against viruses

152

ILC2-->

IL-25 and IL-33

allergic inflammation

153

ILC3-->

IL-1 and IL-23

intestinal barrier function; lymphoid organogensesis

154

What is the function of NK cells?

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

155

NK cells kill htos...

infected or stressed host cells

156

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

NK

157

What do NK cells respond too?

IL-12 produced by macrophages and secrete IFN-gamma

158

What activates the macrophages to kill phagocytized microbes?

IFN-gamma

159

When NK cells recognize ligands on targe cells, they?

activate protein tyosine kinases (PTKs)

160

What are NK cell activating receptors called?

killer cell immunoglobulin (Ig) like receptors (KIRs)

161

What do Nk cells not kill?

I MHC expressing healthy cells