Innate Immunity (complete) Flashcards Preview

DMD 5244 (Immunity) > Innate Immunity (complete) > Flashcards

Flashcards in Innate Immunity (complete) Deck (205):
1

is innate or adaptive immunity similar in all individuals of a species

innate immunity
(adaptive immunity varies from individual to individual)

2

is innate or adaptive immunity generally enhanced by repeated exposure

adaptive immunity

3

does innate or adaptive immunity have some sort of "memory"

adaptive immunity

4

does innate or adaptive immunity use nonspecific mechanisms to identify invaders

innate immunity
(adaptive immunity is based on the recognition or specific invader)

5

are the mechanisms of innate or adaptive immunity mobilized immediately, and work quickly?

innate immunity
(effector products of adaptive immunity take several days to produce)

6

What happens to the adaptive immune response with each additional exposure to an invader

the response becomes quicker, more specific, and is at a higher level.

7

what are the 6 types of organisms that can grow in vertebrates

1. viruses
2. bacteria
3. fungi
4. parasites
5. protozoa
6. worms

8

What barriers/mechanisms must be overcome by organisms that want to grow in humans

1. Skin
2. mucous membranes
3. ciliary escalator in the respiratory tract

9

which immunity works early in the infection process

innate immunity

10

T/F the adaptive immune response depends on the innate immune response for activation and for most of its effector functions

True

11

why haven't our bodies adapted and evolved enough over time to already destroy these pathogens

because microbes and viruses evolve faster than vertebrates

12

What are PAMPs

pathogen associated molecular patterns.
certain structures that are only found on pathogens

13

What are some examples of PAMPs

1. double stranded RNA
2. LPS (lipopolysaccharide)
3. Lipoteichoic acid
4. peptidoglycan

14

on what type of pathogen do you see the PAMP double stranded RNA

viruses

15

on what type of pathogen do you see the PAMP LPS

gram negative bacteria

16

on what type of pathogen do you see lipoteichoic acid

the cell wall of gram positive bacteria

17

on what type of pathogen do you see peptidoglycan

the cell wall of gram positive bacteria

18

what type of immunity focuses on these PAMPs

innate immune mechanisms

19

why don't these organsims evolve and change their PAMPs so they can't be used to recognize the organism by immune systems

they must be crucial to the organisms and therefor hard to change

20

What are the three possible immune response outcomes

1. normal response (attacks non-self, leaves self)
2. immune hyperactivity (allergies, and autoimmunity)
3. immune hypoactivity (infections, cancer, immunodeficiency)

21

what are in eyes that are barriers against infection

lysozome in tears
washing of the eyes

22

what acts as barriers on the skin against infection

1. physical barrier
2. antimicrobial secretions

23

what acts as a barrier in the respiratory system against infection

1. mucus
2. cilia
3. alveolar macrophages

24

What acts as a barrier in the genitourinary tracts against infection

1. low pH of urine
2. washing of urine
3. lysozyme
4. vaginal lactic acid

25

what acts as a barrier in the digestive tract against infection

1. stomach acidity
2. normal flora
3. bile

26

what are commensals in our body

bacteria that live in our body, that aren't pathogenic.

27

lysozyme does what, and comes from where?

breaks down peptidoglycan
comes from tears, saliva, nasal secretions, body fluids, lysosomal granules

28

lactoferrin and transferrin do what, and come from where?

they bind iron, and compete with microorganisms for it
they come from granules of PMNs

29

Lactoperoxidase does what, and comes from where?

it is inhibitory to many microorganisms
it comes from milk and saliva

30

B-lysin does what, and comes from where?

effective against gram positive bacteria
it comes from thrombocytes and normal serum

31

Chemotactic factors do what and come from where

they induce direct migration of PMNs, monocytes, and other cells
they come from bacteria, products of cell injury, denatured proteins, complement, and cytokines

32

properdin does what, and comes from where?

it activates complement in the absence of the antibody-antigen complex
it is found in normal plasma

33

cationic peptides do what and come from where

they disrupt membranes and block cell-transportation
they come from PMN granules (defensins)

34

What are the three lines of defense of the immune system. and which are non-specific, and which are specific

1. skin, mucus membranes, chemicals
2. phagocytosis, complement, interferon, inflammation, fever
3. lymphocytes and antibodies

1-2 non-specific, 3 - specific

35

What are the roles of phagocytes in an immune response

1. production of cytokines and chemokines
2. Ingulf and destroy the pathogen (with out without antibodies)
3. presentation of antigen fragements to T-cells

36

which types of phagocytes do the presentation of antigen fragments to T-cells

immature dendritic cells, that have been activated by microbial components and cytokines

37

What happens with the T-cells that have had antigen fragments presented to them by immature dendritic cells

they become effector cells, they create an adaptive immune response (present it to B-cells)

38

What do the cytokines and chemokines secreted by phagocytes do

1. increase vascular dilation
2. increase vascular permeability
3. induce production of proteins that recruit more immune cells

= cause inflammation

39

what does increase vascular dilation and permeability do for an immune response

allows more lymphocytes, antibodies, and complement to enter the site of infection

40

What are antigens

molecules that trigger a specific immune response

41

what are epitopes

the portion of the antigen recognized by the antibody or lymphoocyte

42

how do antigens enter the body

1. through breaks in the skin and mucus membranes
2. direct injection (bite or needle)
3. ingestion or inhalation

43

What is the type of cell from which all cells of the immune system are derived

hematopeotic stem cell (HSC)

44

what does a HSC give rise to each time it divides

another HSC and a progenitor cell that is commited to a certain lineage

45

what are the two lineages of immune cells

myeloid (inflammatory cells)
lymphoid (lymphocytes)

46

which is the only cell that can be formed from both the myeloid and lymphoid lineages

dendritic cells

47

what controls the specific differentiation of progenitor cells

hematopoeitins

48

what cells come through the myeloid lineage

RBCs
platelets
basophils
eosinophils
neutrophils
monocytes (dendritic cells/macrophages)

49

what cells come through the lymphoid lineage

B-cells
T-cells
NK cells (natural killer)

50

do all cells of myeloid lineage complete differentiation in the same location

nope,
bone marrow, peripheral tissues, secondary lymphoid tissue

51

What are the three types of formed elements in blood

1. RBCs (erythrocytes)
2. Platelets
3. WBCs (leukocytes)

52

What is the function of RBCs

carry O2 and CO2 in the blood

53

what is the function of platelets

involved in blood clotting and inflammation

54

what are the two classes of leukocytes

granulocytes
agranulocytes

55

What are the different types of granulocytes

neutrophils
eosinophils
basophils

56

what are the different types of agranulocytes

monocytes
lymphocytes

57

list the leukocytes from most abundent to least

neutrophils
lymphocytes
monocytes
eosinophils
basophils

58

what do neutrophils do

they are major phagocytes and cause accute inflammation

59

what do eosinophils do

perform parasite defense and regulate inflammation

60

what do basophils do

secrete histamine, involved in allergies

61

what can high levels of eosinophils in the blood indicate

allergies or a parasitic worm infection

62

what change in white blood cell count does a bacterial infection cause

increase in all leukocytes, but mostly neutrophils

63

what change in white blood cell count does a viral infection cause

increase in lymphocytes

64

what is diapedesis

the passages of White blood cells through intact capillaries

65

what do lymphocytes do

they are the main cells in adaptive immune response

66

what do monocytes do

mature into macrophages

67

what are the phagocytic cells

neutrophils
macrophages
dendritic cells

68

what role do neutrophils play as phagocytes

short lived, but quick destructive phagocytosis
release of cytokines = acute inflammation

69

what roles do macrophages play as phagocytes

they are found in various tissues, important in their maintenance and repair
long lived = cells of chronic inflammation
release cytokines

70

which phagocytes are activated by T-cells and antibodies

macrophages

71

what is phagocytosis

a receptor-mediated process whereby large particles are engulfed.

72

what can the phagocytic receptors bind

they can bind microbes directly
they can bind opsonized particles

73

do some pathogens use phagocytosis to their advantage

yes

74

what are two ways that pathogens can use phagocytosis to their advantage

1. they can get phagocytosed, then rupture the phagosome and enter the cytoplasm
2. they can block the fusion of lysosomes with the phagosome so they can't be destroyed

75

what bacteria rupture the phagosome after they have been phagocytosed and enter the cytoplasm

listeria monocytogenes
burkholderia pseudomallei

76

what bacteria prevent the fusion of the phagosome and lysosome after being phagocytosed

mycobaterium tuberculosis
salmonella

77

what can overcome the block of fusion of the phagosome and lysosome by salmonella and mycobacterium tuberculosis

IFN-y (T-cell cytokine)

78

what are the receptors of macrophages involved in

1. scavenging tissue debris from apoptotic cells
2. tissue repair and maintenance
3. production of anti-inflammatory responses

79

which cells are the phagocytotic cells in the second line of defense

macrophages

80

where do macrophages come from

when monocytes leave the blood, they become macrophages in the tissues

81

what are some names for macrophages that stay in a certain area of the body

1. microglial cells (CNS)
2. mesangial cells (kidney)
3. marginal zone (spleen)
4. Kupffer cells (liver)

82

are all macrophages fixed to certain tissues

nope, some are wandering

83

are alveolar macrophages fixed, or wandering macrophages

wandering

84

what makes up the MPS (mononuclear phagocytotic system)

monocytes, macrophages attached to endothelial cells

85

how are microbes killed in a phagocyte

they are absorbed and bathed in free radicals, which destroy them

86

what are the different types of dendritic cells

1. immature
2. mature
3. follicular

87

what do immature dendritic cells do

they phagocytize pathogens, then they become mature

88

what do mature dendritic cells do

they present antigens to T-cells

89

what do follicular dendritic cells do

present immune complexes to B-cells

90

where are dendritic cells very numerous

in epithelia and mucosal surfaces

91

what are langerhans cells

specialized dendritic cells in keratinized epidermis that can remain there for months

92

what are dermal or interstitial dendritic cells

dendritic cells that reside in the dermal layer

93

what are the different dendritic cells that function in the epithelium of the small intestines

1. some sample gut contents directly
2. some wait below the epithelial cells to have samples of lumen transported to them
3. some circulate in the blood and wait for viruses

94

what is the function of the dendritic cells that directly sample the lumen of the small intestine

they prevent inflammatory response against the gut commensial bacteria

95

what are the cells that transfer small intestine lumen to lymphoid tissues

M-cells

96

what are the dendritic cells called that circulate with the blood and wait for viruses

plasmacytoid dendritic cells

97

what do plasmacytoid dendritic cells do when they encounter viruses

produce lots of type 1 interferons

98

what are the primary lymphoid organs

the locations where lymphocytes mature
Bone marrow
thymus

99

what are secondary lymphoid organs

the locations where antigens are trapped, where an immune response takes place
lymph nodes
spleen
MALT (tonsils)
GALT (peyers patches)

100

what are tertiary lymphoid tissues

locations where lymphoid tissues is created at sites of chronic infection

101

what does the spleen do

filters for antigens in the blood

102

where do you find the lymphatic tissue (white pulp) of the spleen

around arterioles

103

where do you find the marginal zone of the spleen

around the white pulp

104

what do you find in the marginal zone of the spleen

metallophilic macrophages
marginal zone macrophages
specialized B cells

105

how do antigens get to the GALT

they are transported there by M cells

106

what is the first type of cell that the antigens sees in GALT

dendritic cells

107

what do sentinal cells do

recognize pathogens and secrete cytokines to initiate an immune response

108

can all epithelial cells tolerate microbes on their surface

nope, some can, but places like alveoli and small intestines don't because they would interfere with their function

109

how do the alveoli and small intestines prevent the build up of microbes on their surfaces

secreting antimicrobial peptides
(defensins and cathelicidins)

110

what are defensins

small antimicrobial peptides with a 3 stranded beta-sheet and 3 disulfide bonds

111

what are cathelicidins

they are small antimicrobial peptides, but differ from defensins in structure (a-helical regions)

112

what are the types of defensins

alpha and beta

113

how do alpha and beta defensins differ

both come from neutrophils, but beta can come from epithelia too
both are antimicrobial, but beta are chemotactic, and induce histamine release

114

what are the paneth cells of the small intestine

cells that produces alpha defensins in response to bacteria

115

what do the a-defensins of paneth cells destroy

giardia, but only one of them (cryptdin-3) kills E. coli

116

how do defensins kill microbes

1. they bind to the acidic phospholipids in the membranes of microbes
2. they enter the membranes and create pores
3. this causes the cells to lyse

117

how do some bacteria combat the pore creation in their membranes by defensins

they modify their membrane lipids with lysine = reduction of negative charge = insensitive

118

what are collectins and ficolins

soluble proteins at mucosal surfaces or in blood that recognize carb configurations on microbes.

119

what are the structures of collectins

they are a long chain, with a big carb recognizing head

120

what do collectins do

the head binds to a sugar on the microbe, this increases phagocytosis, and activates complement

121

what is the complement system

a series of about 30 proteins that can be activated in 3 ways

122

what happens in the activation of the 30 proteins in the complement system

proteins are cleaved into two substances
beta - stays
alpha - leaves

123

what are the three pathways in activation of the complement system

lectin pathway
classical pathway
alternative pathway

124

what are the four ends of the complement system

1. lysis of bacteria
2. chemotaxis of phagocytes to the bacteria
3. opsonization of bacteria

4. all of which increase inflammation

125

what are the two main players in the lectin pathway of the complement system

MBL
ficolins

126

what are the three main players in the classical pathway of the complement system

IgG, IgM, pentraxins

127

what is the main player in the alternative pathway of the complement system

microbial membranes

128

the early events of all three pathways of the complement system all lead to what

the cleavage of C3 by C3 convertase

129

which complements lead to inflammation, chemoattraction

C3a
C5a

130

which complements lead to induction of phagocytosis

C3b

131

which complements lead to attack on membranes

C5b, C6, C7, C8, C9

132

which complements lead to promotion of antibody production

C3b

133

which complements are the late events

C5-C9

134

how is the classical pathway of the complement system activated

1. C1q/r/s complex couples with pentraxins or antibodies
2. C1s cleaves C4
3. C4b binds to cell surface
4. C2 binds to C4b
5. C1 cleaves C2
6. C4b-C2b = C3 convertase
7. C3 convertase cleaves = C3a, C3b

135

how is the lecthin pathway of the complement system activated

1. MBL or ficolin bind to the microbial surface carbs
2. MASP's bind to MBL/Ficolin
3. MASP2 cleaves C4
4. C4b stays attached
5. C2 binds to C4b
6. C2 is cleaved by MASP-2
7. C4b-C2b = C3 convertase
8. C3 convertase cleaves = C3a, C3b

136

how is the alternative pathway of the complement system activated

1. C3a and C3b bind to the cell surface
2. B binds to C3b
3. D cleaves B
4. C3b-Bb = C3 convertase
5. C3 convertase cleaves = C3b, C3a

137

what happens to C3b that can't find a microbe to bind to

it is bound by factor H, then factor I cleaves the C3b (making it inactive)

138

what does properdin do in the complement pathways

it stabilizes the C3b/Bb complex

139

what happens when C3b attaches to either the C3b/Bb or C4b/C2b complexes

this leads to the cleavage of C5

140

what does C5a do

it is a proinflammatory peptide that acts on endothelial cells and mast cells.
it is a powerful neutrophil chemoattractant

141

what does C5b do

it nucleates the formation of the (MAC) membrane attack complex (this makes large holes in the cell)

142

defects in which components of the complement can cause SLE (systemic lupus erythematosis)

defects in C1 and C4

143

how do defects in C1 and C4 lead to SLE (systemic lupus erythematosis)

they lack the ability to clear apoptotic cell debris and immune complexes

144

the deficiency of which complement component is the most severs

C3

145

what do defects in the late part (C5-C9) cause

severe nisseria infections

146

how do microbes fight against the actions of the complement system

1. make surface proteins that bind factor H (so that it will inactivate C3b)
2. make proteins that bind to C4bp (an inactivator of C4b)
3. take host control proteins with them as they bud

147

what microbes make surface proteins that bind factor H to fight against the complement system

HIV
S. Pyogenes
S. Pneumonia
Neisseria
B. Burgdorferi
gonorrhoeae

148

which microbes make proteins that bind C4bp to fight against the complement system

gonorrhoeae
B. pertussis

149

which microbes take host control proteins with them as they Bud

HIV-1
vaccina

150

which fuse first, primary or secondary granulues

secondary (yep these fuse first)

151

what does NAPDH oxidase create

O2
H2O2
HOCl
OH
ONOO (with NO from iNOS)

152

what does iNOS create

NO
ONOO (with O2 from NAPDH oxidase)

153

which attack first, the toxic O2 intermediates or the toxic nitrogen intermediates

the toxic O2 intermediates are used immediately, the toxic nitrogen intermediates are used later, and last longer

154

what happens when you have defects in any subunit of the NADPH oxidase

you will get a chronic granulomatus disease (CGD)
patients have a hard time clearing infections and get persisting granulomas

155

What are the three types of sentinel immune cells in tissues

1. macrophages
2. Mast cells
3. immature dendritic cells

156

what do sentinel immune cells do

recognize microbial threats and initiate an inflammatory immune response.

157

what do sentinel cells have to differentiate between

apoptotic bodies and microbial threats

158

what allows sentinel cells to distinguish between apoptotic bodies and microbial threats

TLRs (toll like receptors)

159

what are TLRs (toll-like receptors)

a protein with an extracellular portion with lots of leucine (LRRs) a transmembrane domain, and a Toll/IL-1 receptor (TIR) domain

160

what can TLRs bind

Nucleic acids
Proteins
Lipids
polysaccharides

161

are accessory proteins sometimes used to help things bind to TLRs

yes

162

how do sentinel cells recognize LPS

1. LPS is taken from the cell wall by LBP
2. LBP gives the LPS to CD14
3. CD14 give the LPS to TLR/MD-2 complex
4. this sends a signal into the cell

163

what is required for LPS responsiveness of TLR4

MD-2

164

is CD14 required for LPS response

no, but it helps a lot

165

where do you find TLRs that recognize microbial cell wall components

in the plasma memebrane

166

where do you find TLRs that recognize microbial nucleic acids

in the intracellular membranes (phagosomes or endosomes)

167

What does the Activation of TLRs lead to

production of cytokines
TNF
IFN (alpha and beta)
IL (6 and 12)

168

what do NOD1, NOD2 and Cryopyrin do

recognize parts of peptidoglycan, and activate NF-kB (inflammatory cytokine)

169

when TLRS and sentinel cells recognize microbes, what do they do

release cytokines
release chemokines
release lipid mediators

these lead to a coordinated response by vessels and leukocytes = inflammation

170

what are the 4 main functions of inflammation mediators

1. increase vascular permeability
2. change adhesive properties of the epithelium (increased amounts of leukocytes)
3. activate phagocytes
4. activate NK cells

171

what are the two proteolytic cascades triggered by activation of endothelial cells

kinin cascade
coagulation cascade

172

how does the kinin cascade affect inflammation

increases vas. permeability

173

how does the coagulation cascade affect inflammation

clotting reactions decrease microbial spread

174

Where does TNF come from

macrophages and mast cells

175

what does TNF do

increases:
vascular permeability
endothelial cell adhesiveness
activation of phagocytes
cytoxicity of NKcells

176

what does IL-1 come from

macrophages, mast cells, KC, EC

177

What does IL-1 do

increases chemokine production and endothelial cell adhesiveness

178

Where does IL-6 come from

macrophages, mast cells, FB

179

what does IL-6 do

recruites monocytes, systemic effects

180

what does IL-12 come from

macrophages

181

what does IL-12 do

increases IFN-y production by NK cells
increases NK cytoxicity

182

what does IFN-y come from

NK cells

183

what does IFN-y do

enhances phagocytosis and killing by phagocytes

184

what do chemokines come from

macrophages, mast cells, EC

185

what do chemokines do

attract neurtophils. monocytes, effector T-cells

186

what are the antinflammatory cytokines

IL-10 and TGF-Beta

187

how does arachadonic acid turn into inflammatory mediators

1. a stimulus activates PLA2 and COX-2
2. PLA2 pulls arachadonic acid from phospholipids
3. COX-2 breaks arachadonic acid into PGH2
4. PGH2 is broken down into PGI, PGE, PGF, and thromboxane

188

what are luekotrienes involved in

chronic inflammation

189

what are the steps in getting neutrophils out of the blood and into the tissues

rolling
activation
adhesion
diapedesis

190

what cells dominate acute inflammation

neutrophils

191

what cells dominate chronic inflammation

macrophages and Tcells

192

What mediates the shift from acute inflammation to chronic inflammation

IL-6

193

what effects to proinflammatory cytokines systemically

1. TNF uses fat and muscle cells to mobilize energy stores
2. IL-1 and IL-6 sitmulate the liver to produce proteins to help fight infection
3. IL-1 and IL-6 act on the hypothalamus to induce a fever

194

what is the acute phase response

when IL1 and IL6 stimulate the liver to produce proteins that help fight infection

195

what are antiinflammtory actions

1. glucocorticoids
2. IL10 and TGF-b
3. acetylcholine receptors

196

What are the two types of interferons

type 1 (IFN -a and IFN-b)
type 2 (IFN-y)

197

what is type 1 interferon

IFNa and IFNb
they are produced by infected cells, and by cells sensing viruses through TLR.
they work against virus's
they leave the infected cells and go to nearby cells. they stop the cells from proliferating the virus

198

what is type 2 interferon

they are antiviral and antibacterial (IFN-y)

199

what does type 1 interferon do to cells

1. through PKR they shut off all translation
2. degrade RNA
3. inhibit transcription

200

what does type 2 interferon do to cells

shut off all translation through PKR

201

what cells produce Interferons

macrophages, immature dendritic cells, plasmacytoid dendritic cells

202

which cells produce the most interferons

plasmacytoid dendritic cells

203

what TLR gives rise to IFN-B

TLR 3

204

what TLD gives rise to IFN-a

TLR 7,8,9

205

what is the most potent activator of macrophages

IFN-y