Innate Immunity- Hunter Flashcards Preview

Block 6 Week 1 > Innate Immunity- Hunter > Flashcards

Flashcards in Innate Immunity- Hunter Deck (183):
1

What are these a part of:
epithelial barriers
anti-microbial enzymes and peptides
the complement system
macrophages, dendritic cells, and neutrophils (myeloid cells)
patter recognition receptors that are germline encoded
inflammation (rubor, calor, tumor, and dolor)
cytokines, chemokines, adhesion molecules, and acute phase proteins
interferons and NK cells

Innate immunity (first line of defense)

2

What does it mean to be colonized by a microbe?

you have an organism that is on or in your tissues but barriers have not been perturbed and therefore there is not immune response

3

What does it mans to be infected by a microbe?

An organism has penetrated you tissues but the response is subclinical (not presenting readily observable symptoms)


NOTE***disease has observable symptoms*****

4

What is this:
a pathogen that resides on or in the body but causes disease only when the host is immunosuppressed.

opportunistic pathogen

5

What are three sources of pathogens?

environmnt
humans
animals (zoonotic diseases)

6

What is the mode of transmission to be infected by a pathogen in the airways?

inhaled droplets and spores

7

What pathogen can you get by inhalin a droplet and pentrating the mucosal surface of your airway?
What does this cause?

influenze virus
influenza

8

What pathogen can you get via spores that pentrate the mucosal surface of your airway?
What does this cause?

neisseria meningitidis->meningococcal meningitis
bacillus anthracis-> inhalation anthrax

9

What is the mode of transmittion to infect the GI tract?

comtainated food or water

10

What pathogen can you get by eating or drinking contaminated food or water?
What does this cause?

salmonella typhi-> typhoid fever
rotavrius-> diarrhea

11

What is the mode of transmission to infect the reproductive tract?

physical contact

12

What pathogen can you get through physical contact that will affect your reproductive tract?
What does this cause?

treponema pallidum-> syphilis
HIV-> AIDS

13

What are the three mucosal surfaces that are suscpetible to pathogens?

airway
GI Tract
Reproductive Tract

14

What are the three routes of entry into your external epithelia?

external surface
wounds and abrasions
insect bites

15

What is the mode of transmission to infect your external surface?

physical contact

16

What pathogen can you get through physical contact that will affect your external surfae?
What will this cause?

trichophyton-> athlete's foot

17

What is the mode of transmission to infect wounds and abrasions?

minor skin abrasions
puncture wounds
handling infected animals

18

What pathogen can you get through minor skin abrasions?
What does this cause?

bacillus anthracis-> cutaneous anhrax

19

What pathogen can you get through puncture wounds?
What does this cause?

clostridium tetani-> tetanus

20

What pathogen can you get through handling infected animals?
What does this cause?

francisella tularensis-> tularemia

21

What type of insect bites can infect your external epithelia?

mosquito bites (aedes aegypt)
deer tick bites
mosquito bites (anopheles)

22

What pathogen can you get through mosquito bites (aedes aegypti)
What does this cause?

flavivirus-> yellow fever

23

What pathogen can you get through deer tick bites?
What does this cause?

barrelia burgdorferi-> lyme disease

24

What pathogen can you get through mosquito bites (anopheles)?
What does this cause?

pasmodium spp. -> malaria

25

Do all organisms have to penetrate tissues to cause sickness?

no (think cholera)

26

If you have an aborgated immune response such as AIDS or malnutrition, what are these people susceptible to?

opportunistic pathogens

27

the immune system is assisted by what three kinds of barriers?

Mechanical
chemical
microbioloical

28

What kind of barriers are these:
longitudinal flow of air or fluids
movement of mucus by cilia
tears
nasal cilia
EPITHELIAL TIGHT JUNCTIONS

mechanical barriers

29

What kind of barriers these:
fatty acids, Beta defensins, lamellar bodies, cathelicidin

chemical barriers for the skin

30

What kind of barriers are these:
low ph, enzymes (pepsin), alpha-defensins (cryptdins), regIII (lecticidins), Cathelicidin

chemical barriers for the gut

31

What kinds of barriers are these:
pulmonary surfactant, alpha densins, cathelicidin

chemical barriers for the lungs

32

What kinds of barriers are these:
enzymes in tears and saliva (lysozyme), histatins, beta defensins

chemical barriers for eyes/nose/oral cavity

33

What is the microbiological barriers for the skin, gut, lungs, eyes/nose and oral cavity?

normal microbiota

34

endotoxins are caused by what kind of bacteria?

gram negative

35

Vibrio cholera, strep and staph are all what kind of toxin?

exotoxin (meaning they release toxins to allow for the penetration of tissues)

36

E. Coli, salmonella are what kind of toxin?

endotoxins (a toxin that is present inside a bacterial cell and is released when the cell disintegrates. It is sometimes responsible for the characteristic symptoms of a disease)

37

AN endotoxin has a lipopolyscharide toxin found in the (blank) of the organism and will perturb the immune system in massive ways by triggering a bunch of cytokines and a over active immune response

cell wall

38

What kind of mechanism is this: a pathogen gets inside a cell and uses the cells machinery and then destroys the cell and moves on to a new one

direct cytopathic effect

39

What do you call a direct mechanism of tissue damage by pathogens?

microbial pathogenesis

40

What do you call indirect mechanisms of tissue damage by pathogens?

immunopathology

41

What are the three pathogenic mechanisms that cause direct tissue damage?

exotoxin production, endotoxins, and direct cytopathic effects

42

What are immune complexes?

It's when really large antibodies attach to antigens and then you cant get them filitered out of your body
(they get stuck places like blood clots)

43

What are anti-host antibodies?

When your body makes antibodies that attack the self

44

What are the three types of anti-microbial enzymes?

lysozyme
pepsin
secretory phospholipase A2

45

How does lysozyme work?

it chews up the outer petidoglycan layer of the cell wall of gram-positive bacteria.

46

Do gram positive bacteria and gram negative bacteria have the same type of cell wall?

no

47

Do both gram positive and gram negative bacteria have peptidoglycan layers in their cell wall?

yes

48

Which type of bacteria has teichoic acid and lipteichoic acid, gram negative or gram positive bacteria?

gram-positive bacteria

49

What are the four major classes of anti-microbial peptides?

defensins alpha
defensins beta
cathelicidins
histatins

50

Are anti-microbial peptides, short or long?

short

51

Anti-microbial peptides are activated by proteolysis to relases (blank) peptides

amphipathic

52

How do defensins work?

They have a positive charge on one side and a hydrophobic charge on the other which will allow them to enter the lipid membrane and create a pore in the microbial membrane.

53

How do you make an anti-microbial protein?

they are pro hormones that are cleaved into an active form

54

Are antimicrobial proteins a primary or secondary defense

primary defense

55

Pathogens that breach epithelial barriers encounter (blank) that trigger (blank)

Macrophages
inflammation

56

How do macrophages recognize pathogens?

by genome encoded receptors (e.g TLRs)

57

(blank) cause vasodilation, increased vascular permeability, and upregulate expression of adhesion molecules on endothelium

cytokines (e.g TNF-alpha)

58

Activation of the (blank) and (blank) systems cause pain and blood clotting

kinin and coagulation systems

59

(blank) attract neutrophils (CXCL8) and monocytes as a second line of defense

chemokines

60

(blank) an (blank) componenets like complement engage the pathogens and often eliminate them before an adaptive immune response is generated.

phagocytic cells and plasma components

61

What is the most important component of adaptive immunity?

inflammation

62

How do macrophages trigger inflammation?

they trigger cytokines and chemokines, neutrophils and more macrophages

63

What is sepsis?

when the inflammatory process gets out of hand (release of massive amounts of cytokines and you have too high of permeability in your vascularization)

64

What is the most important pro-inflammatory cytokine that causes vasodilation and vascular permeability?

TNF alpha

65

After macrophages tell cytokines to come to the tissues, what do they call next to come help?

neutrophils and other macrophages

66

Which or the stronger phagocytic cells, macrophages or neutrophils?

neutrophils

67

What do macrophages recognize?

pathogen associate molecular patterns

68

Can macrophages recognize common motifs? what is a very common one?

yes
peptidoglycan

69

What do macrophages recognize easily on gram-positive bacteria?

peptidoglycan

70

What do macrophages easily recognize on gram-negative bacteria?

Lipopolysaccharide (LPS)

71

What does endotoxin bind to?

Toll receptors (TLR

72

What are recognized by their motif F-Met-Leu-Phe?

bacteria

73

What carry mannose receptors?

bacteria, fungi, viruses

74

What carry scavenger receptors?

acetylated lipoproteins on bacteria

75

What carry dectin-1 glucan receptors?

fungi

76

What carry LPS binding proteins, TLR-4 and CD14?

gram negative bacteria

77

What are Toll-Like Receptors?

pathogen recognition and signaling molecules

78

How many human TLR genes are there?

10

79

TLR proteins are (blank) receptors

PAMP (pathoen associated molecular patterns)

80

TLR 5 evolved to recognize what?

flagelin

81

You can find (blank) inside vacuoles inside of macrophages.

TLR

82

In innate immunity (blank) have evovled to create the initial self-non self discrimination of the immune system.

TLR Receptors

83

Where do you find TLR receptors?

on the cell surface and intracellularly

84

TLR activation engages the transcription factor (blank) and induces the production of inflammatory mediators.

NF-kB

85

(blank) are similar in structure to TLR, detect cytoplasmic bacteria, and signal inflammation

Nucleoside Oligomerization Domain (NOD)-like proteins

86

(blank) detect viral RNA in the cytoplasm and signal inflammation

retinoic acid inducible gene -I
(RIG)-like proteins

87

What does TLR 2 and TLR 6 recognize?

diacyl lipopeptides

88

what does TLR2 and TLR1 recognize?

triacyl lipoproteins

89

What does TLR-4 recognize?

LPS

90

What does TLR 3 recgonize?

dsRNA

91

What does TLR7 recognize?

ssRNA

92

What does TLR-9 recognize?

CpG DNA

93

Where do you find NOD proteins? What do they do?

in the cytoplasm
intiate inflammation

94

What do RIG do?

detect viral DNA

95

TLR signaling induces (blank)

gene transcription

96

Give a brief description of how TLR signaling induces gene transcription

PAMP allows for dimerization of TLR which induces intracellular signaling and the gene expression of the transcription factors and cytokines like NF-Kb

97

What is IRAK4?

a danger signal

98

What happns when you dimerize TLR receptors?

you recruit IRAK1 and IRAK4 to create an immune response

99

IRAK-1 deficiency is a rare autosomal (blank) defect.

recessive

100

What is this:
any of a class of proteins present in the serum and cells of the immune system, that function as antibodies

immunoglobulin

101

In detail explain how TLR induces gene transcription

Dimierized TLR-> recruits IRAk1 and IRAK4-> IRAK1 and IRAK4 activate E3 ubiquiting ligase Traf-6-> Traf 6 and NEMO are polyubiquitinated-> create scaffolding-> TAK1 gets together with IKK and phosphorylates IKKB which phsophorlates IKB-> IKB degrades-> releases NFkB into the nucleus to induce expression of cytokine genes-> inflammation

102

What is this:
involving or relating to the production of pus.

pyogenic

103

The (blank) pathway involves the expression of more than 100 genes

NF-kB

104

What are the two major defects in intracellular killing in neutrophils?

abnormal respiratory burst
granule abnormalities

105

What are the two types of abnormal respiratory bursts in neutrophil function?

chronic granulomatous disease
glucose-6-phosphate dehydrogenase deficiency

106

What are the three types of granule abnormalities in neutrophil function?

myeloperoxidase deficiency
specific granule deficiency
chediak-higashi syndrome

107

What is the major defect in adhesion defects in neutrophils

leukocyte adhesion deficiency

108

What are the two types of adhesions defects in neutrophils?

Type 1, integrin deficiency
Type 2, E-selectin ligand deficiency

109

What is the most important means of defense against extracellular bacteria, fungi and protozoan parasites?

phagocytosis and intracellular killing

110

What are the 2 most important phagocytic cells?

neutrophils and macrophages

111

Invagination of cell membrane creates the (blank)

phagosome

112

(blank) filled with antimicrobial substances fuse with phagosomes and create (blank). This is where most microbes are killed and digested

lysosomes
phagolysosome

113

Assembly of the (blank) promotes intracellular microbial killing

NADPH oxidase

114

How do you assemble the NADPH oxidase component in the phagolysosomal membrane?

microbe phagocytosis and G-protein receptor signaling

115

What does NADPH oxidase generate?

antimicrobial superoxide, hydrogen peroxide and other reactive oxygen species ('respiratory burst")

116

How do you activate acid hydrolases and antimicrobial peptides within the phagolysosome so that it can kill microbes?

lower the pH

117

What does the C5a complement do?

augments phagocytosis (internalization and causes formation of NADPH oxidase)

118

What do these make up:
p67, P10, P17, P22, Gp91

NADPH oxidase

119

What happens if you have defect in Gp91 and how does it happen?

you cant make NADPH oxidase and therefore cannot destroy microbes.... Can be caused by X-linked defects

120

What is respiratory burst?

the production of oxygen species via NADPH

121

WHat all can you find within a phagolysosome?

acid, toxic oxygen species, NO, antimicrobial peptides (cathelicidn, defensins etc.), enzymes, competitors (lactoferrin)

122

What makes lactoferrin and vit B12?

neutrophils

123

What does lysozyme do?

digests cell walls of some gram-positive bacteria

124

Why do granulomas form?

when the immune system cant get rid of something

125

If you cant reduce dihydrorhodamine, what is the problem?

gp91 deficiency and a failed NADPH oxidase system resulting in granulomas or chronic granulomatous disease

126

(blank) lesions in the skin and various internal organs are caused by pyogenic bacteria and fungi

Granulomatous

127

What is pyoderma?

an infection of the skin (all over the outside of the skin)

128

When your lymph nodes interact with microbes they become (blank)

hyperplastic

129

What is the defect in chediak-higashi syndrome and what will you see?

defect in microtuble polymerization (decreases phagolysosomes)
recurrent pyogenic infections, partial albinism, large lysosomal vesicles in neutrophils and eosinophils

130

What is neutropenia?

you have a low level of neutrophils

131

What are the two ways you can get neutropenia?

acquired (common) and hereditary (rare)

132

What are the 2 ways you can get acquired (common) neutropenia?

drug-induced (especially cytotoxic drugs for cancer)
autoimmune (anti-neutrophil antibodies)

133

What are three types of hereditary (rare) ways to get neutropenia?

familial (benign, ethnic) neutropenia
infantile genetic agranulocytosis (severe congenital neutropenia)
cyclic neytropenia

134

T or F
neutropenia induced by cytotoxic anti-cancer drugs is common

T

135

Define neutropenia in terms of cell count

1500 to 2000 cells/mm cubed of blood

136

At what neutrophil count to you have an increase in infections?

below 1500 cells/mm cubed

137

What are the most common pathogens that take advantage of neutropenia?

staph, gram negative bacteria, other encapsulated bacteria, fungi

138

Nearly 15% of sepsis cases are caused by (blank)

candida albicans

139

Neutropenic sepsis can be caused by a variety of (blank)

pyogenic bacteria and fungi

140

How do you get rid of drug-induced neutropenia?

broad-spectrum antibiotics and human recombinant granulocyte colony stimulating factor (hrG-CSF) before subsequent rounds of chemotherapy (increases output of granulocytes of bone marrow)

141

(blank) is a genetically and phenotypically heterogenous group of nehreditary neutropenias seen in infants

severe congenital neutropenia (Kostmann disease)

142

What does this describe:
patients present with recurrent infections of skin, soft tissues, lungs and deep organs; sepsis is common, ANC is often below 200/ uL. Differentials includes a wide variety of conditions that impair myelopoiesis. A diagnosis is supported by characteristic findings of maturation arrent at the promelocyte or myelocyte stage.

sever congenital neutropenia (kostmann Disease)

143

How do you treat Kostmann disease (severe congenital neutropenia)

rhG-CSF or bone marrow transplant

144

What is risky about rhG-CSF?

myelodysplasia (refers to a group of disorders in which the bone marrow does not function normally and produces insufficient number of normal blood cells.)
and acute myeloid leukemia (abnormal leukocyte production)

145

What is the chemokine that macrophages use to call in the neutrophils if they cant handle themselves in the tissues?

CXCL8

146

Explain how you can get a neutrophil to diapedis across the basement mebrane into a tissue?

Neutrophils will roll along the basement membrane until they reach a place of inflammation where they will connect their integrin called LFA1 with its special CD18 component to the ICAM1 adhesion molecule on the basement membrane which will pull it through the cracks of the basememnt membrane

147

What is ICAM-1?

it is an immunoglobulin-like molecule that works as an adhesion molecule

148

What is an immunoglobulin?

any of a class of proteins present in the serum and cells of the immune system, that function as antibodies.

149

What is CD18?

a special component of the integrin LFA1 that is found on neutrophils

150

What is LFA-1?

the integrin found on neutrophils that binds to ICAM-1

151

WHat is a rare autosomal recessive disorder presenting with recurrent bacterial infections due to defects in neutrophil adhesion?

leukocyte adhesion deficiency (type I)

152

What will adhesion molecule defects result in?

poor neutrophil chemotaxis, phagocytosis, neutrophilia (too many neutrophils in thie blood because they are stuck and cant get into the tissues)

153

Infants who have (blank) will suffer from infections such as omphalitis, pneumonia, ginigivitis, and peritonitis

leukocyte adhesion deficiency (type I)

154

What is the defect in leukocyte adhesion deficiency type I?

beta-2 integrin subunit CDI8

155

How do you determine if someone has leukocyte adhesion deficiency (type I)?
How do you treat it?

you look at CD18 levels
bone marrow transplant

156

The acute phase responses is mediated by (blank)

acute phase proteins

157

Bacteria induce macrophages to produce (blank), which acts on hepatocytes to induce synthesis of acute-phase proteins.

IL-6

158

What is this:
an antibody or other substance that binds to foreign microorganisms or cells, making them more susceptible to phagocytosis.

opsonin

159

(blank) is an opsonin and is used to identify patients with active inflammatory processes

c reactive protein

160

(blank) binds and sequesters iron to inhibit microbial growth

ferritin

161

(blank) is a coagulation factors, its levels correlate w/ erythrocyte sedimentation rate (ESR), an inflammation indicator

fibrinogen

162

(blank) production is downregulated during acute phase response.

albumin

163

What all are involved in the acute phase response induced by IL6?

C-reactive protein (CRP)
ferritin
fibrinogen
albumin
mannose-bindin lectin

164

What does mannose-binding lectin do?

it is an opsonin that activates complements

165

Where does IL6 bind?

the liver

166

Viral RNA induces (blank) gene expression

interferon alpha/beta (a protein that inhibits virus replication)

167

How does Viral RNA induce interferon gene expression in an endosome?

in an endosome TLR3 recognizes viral DNA and recruits TRIF which recruits IRF3 and IRF7 to induce gene expression

168

How does viral RNA induce interferon gene expression in the cytosol?

MDA5, RIG-I, CARDIF get together and recruit IRF3 and IRF7 to induce gene expression

169

How do antiviral type I interferons work?

an infected cell is recognizesby plasmacytoid dendritic cells that produce large amounts of interferon which will induce the interferon response

170

What is the interferon response?

stops virus from replicatng
increases expression of ligands for receptors on NK cells, activates NK cells to kill virus

171

In an interferon alpha/beta primed cell, what does viral dsRNA do?

it activates RNAse L which degrades viral/host mRNA causing apoptosis

172

interferon alpha/beta increases the expression of (Blank) molecules on nucleated cells/

MHC class I (molecules that present cytosolic proteins of cells to T cells to allow for the determination of whether the proteins are foreign or self i.e. they allow for self, nonself recognition)

173

Where do NK cells come from?

from lymphoid progenitor cells

174

How do you activate a NK cell?

with type I interferon and cytokines (tnf alpha and IL -12)

175

What will NK cells produce?

large amounts of IFN-Y

176

What do NK cells do?

kill virus infected cells, cells with intracellular pathogens and tumors by using cytotoxic granules to kill them

177

What are the cytotoxic granules that NK cells use to kill stuff?

perforin and granzymes

178

HOw do NK cells differentiate b/w self and non self?

through MHC class I molecule recognition and stress molecule

179

NK cell deficiency can result in susceptibility to what viruses?

herpes
(varicella (chicken pox and shingles), simplex 1 (oral) and 2 (genital) , epstein barr (mono) and cytomegalovirus)

180

What is antibody dependent cell-mediated cytotoxicity or ADCC?

when NK cells bind and kill antibody coated pathogens

181

Wha t is the quickest response in a viral infection? what is the slowest/

production of interferon,TNF alph and IL2-> NK cell killing-> T cell killing

182

What response lasts the longest in a viral infection?

T cell mediated killing

183

The epithelial surfaces of the (blank), (blank) and (blank), which together with the skin, provide the first lines of defense against infection (chemical, mechanical, and physical barriers)

gastrointestinal, urogenital, and respiratory tracts