3 damage Flashcards Preview

infectious disease > 3 damage > Flashcards

Flashcards in 3 damage Deck (194):
1

bug mediated mech of damage

-intoxication
-growth outside normal niche
-overgrowth in normal niche

2

collaborative mechanisms of damage

- growth inside host cells
-lytic enzymes
-toxin mediated
-cytokine release

3

host mediated mechanisms of damage

-inflammation
-immune complex deposition
-autoimmunity

4

pseudomonas elastase

enters tissue, chews up elastin, disseminates
-bacterial mediated virulence factor

5

what does elastase chew up

-collagen
-lysozyme
-C3b + C5b (affects immune system)

6

ECM

-collagen
- elastin
-hyaluronic acid

7

example of bacterial mediated factor

elastase from pseudomonas

8

how does elastase help pseudomaonas

helps it get access to cells and disseminate

9

strains lacking in elastase

persist locally in burn wounds but fail to disseminate

10

how is elastase a multitasking enzyme

cleaves elastin, collagen, lysozyme, immunoglobulins, and complements C3B + C5a (inhibits opsonization + chemotactic responses)

11

plasmin

chews up fibrins/clots

12

borelia

retains ability to bind so that plasminogen can make plasmin + eat clots

13

neutrophils

elastase allows it to get into the tissue
-psuedomonas deactivates normal neutrophil elastase, allowing plasminogen to plasmin, and then there's an attack of the host

14

examples of enzymatic virulence factors that are more "collaborative" involve

borrelia hurgdorferi + yesinia pestis

15

nontoxin mediated damage

bug mediated pseudomonas elastase + lytic enzymes

16

non-toxin-mediated damages

collaborative + bug mediated

17

what facilitates borrelia bind human plasminogen and its activator?

spirochetes

18

What does activated plasminogen do?

converts plasminogen to palasmin

19

plasmin

protease that breaks down fibrin clots, eliminating fibrin barriers at wound sites

20

fibrin

protein that form clots during microbial invasion which is triggered by tissue injury

21

pathogens counter fibrin by producing

fibrinolytic enzymes OR subverting host enzymes that dissolve the clots making further dissemination possible

22

dissemination

the act of spreading something, especially information, widely; circulation.

23

Yersinia Pestis

has a pla gene (plasmin activator gene) which has protease activity on its own + can activate host plasmin

24

pla gene

plasmin activator gene from Yersinia Pestis

25

strep pyogenes (collaborative)

makes streptokinase, which binds to and activates plasminogen, converting it to plasmin

26

staph aureus (collaborative)

produces fibrinolysin and a coagulase that lays down a fibrin network that may provide a protected niche

27

what produces hyaluronidase?

strep, staph + clostridia

28

hyaluronic acid

ECM structural component

29

what causes gas gangrene?

clostridia

30

what does clostridia produce?

collagenase, which breaks down tissue supporting collagen matrix, enhancing spread throughout the body

31

what do enzymatic virulence factors that bacteria make, do?

degrade proteins or carbs that maintain tissue integrity, allowing enhanced dissemination

32

lytic enzymes that are multifunctional

modulate immune function
-elastase acting on Ig, C3b, C5a

33

bug mediated growth outside normal niche can occur during

dental treatment

34

bug mediated overgrowth in normal niche occurs with what two organisms?

D. Difficile + candida albicans

35

What collaborative mechanism of damage involves growth inside host cells?

tuberculosis (inside has access to nutrients)

36

lytic enzymes collaborative mechanism of damage

macrophages cause lysis

37

Dental work

-growth outside normal nice
-leads to transient bacteremia, allowing viridans group streptococci to damage heart valves

38

surgery or trauma can lead to

spillage of intestinal contents into peritoneal cavity and subseueny abcess formation by bacteroids fragilis

39

overgrowth in normal niche can lead to

antibiotic therapy can lead to overgrowth of C. difficile in the GI tract and fungus candida albicans on mucosal surfaces

40

when macrophages are infected by mycobacterium

lysosomes leak and cause cellular damage with granulomas

41

growth inside cells

-mycobacterium tuberculosis
-legionella pneumophila
-salmonella typhii

42

tuberculosis

-survive in alveolar macrophages
-when macrophages are killed by intracellular bacteria, the lysozomal enzymes and other material released from dying cells contribute to chronic infection and granuloma formation

43

legionella pneumophila

survive in alveolar macrophages, subvery normal phagocytic pathway

44

salmonella typhii (typhoid mary)

gall bladder infection (asymptomatic carrier) that sheds bacteria into the intestinal tract and feces

45

after patient is exposed to broad spectrum antibiotics

pseudomembranous colitis

46

granuloma formation

-macrophage eats bug
-bug replicates
-cell lysis
-activated macrophages and T cells recruited walling off of bugs and cell debris

47

persistent infections induce persistant immune responses which in addition to failing to eliminate the infectious microorganism

cause pathological changes

48

old thinking granuloma

was hosts means of walling off bacteria

49

new thinking granuloma

bacteria induce granuloma to recruit naive macrophages they can then use for dissemination

50

immune complex deposition e.g. post streptococcal glomerulonephritis

1 strep infection is presented
2 anti strep antibody formation
3immune complex formation (antibody + strep fragments + complements)
4 immune complex deposition in glomeruli, leading to inflammation and kidney disfunction= BAD

51

what can lead to glomerulonephritis

microbial antigen in blood that lead to an immune complex function, leading to pathological changes

52

what is the major disease process that leads to glomerulonephritis?

immune complex formation

53

glomerulonephritis

painful kidney disease

54

strep pyogenes

group A strep/ strep throat

55

what complexes form in the bloodstream during strep throat

streptococcal Ag-Ab complexes that lodge in the glomeruli, causing inflammation of the kideny

56

glomeruli

filtration membranes of kidneys

57

nephritis

inflammation of the kidney

58

diseases that cause infection triggered autoimunity

strep + lyme disease

59

infection triggered autoimmunity

1 infection
2 generation of immune response against pathogen copmonents
2 cross reactivity against self antigens

60

how do autoimmune disorders occur from microbial infections?

microbial products somehow alter or unmask self components OR modulate the processes that normally maintain tolerance to self components

61

what helps in microbial evasion

similarities between microbial molecules (often surface) + host molecules
-the host immune response instead of protecting, elicits cross reactivity

62

autoimunity

rheumatic fever
scarlet fever
lyme disease

63

toxin

a protein that kills or alters the function of a host cell

64

exotoxin

a toxin that is secreted into the extracellular milieu by the bacteria

65

enterotoxin

a toxin that works in or is produced in the GI tract

66

endotoxin

the lipopolysaccharide component of the gram-negative outer membrane; NOT a true toxin

67

enterotoxin

an exotoxin that acts on the small intestine causing changes in intestinal permeability that lead to diarrhea

68

endotoxin

we will not consider this a true toxin

69

what causes death through hemorrhagic shock and tissue necrosis?

endotoxin= lipid A portion of LPS in large enough doses

70

pyrogens

endotoxin stimulates host cells to release proteins called pyrogens (cause fever)

71

medical supplies that are non-pyrogenic indicate

no LPS contamination

72

which toxicity is higher: endotoxins or exotoxins?

exotoxin

73

toxin that kill cells

streptolysin O +diphtheria toxin

74

toxin that act at cell surface

streptolysin O

75

toxin that act inside cells

diptheria toxin

76

toxin that disrupt function

toxic shock syndrome toxin (does NOT KILL cell)
+ cholera toxin (type AB toxin)

77

streptolysin O kills cells at the surface

a pore former toxin that binds to cholesteral in host membrane and forms pores upon oligimerization

78

diptheria toxin kills cells and act inside cells

A/B toxin (single polypeptide) that ADP ribosylates host EF2, stopping protein synthesis

79

staph aureus= disrupts cell physiology/function and act at cell surface

TSST-1 (Toxic shock syndrome)
-strep pryogenes, streptococcal pyrogenic exotoxins such as SPE A.
-specific for T cells

80

cholera toxin = disrupts cell physiology/function and act inside cells

A/B toxin with A/B (5) structure, B part binds GM1 ganglioside and A part acts in cells
-CT leads to increased intracellular cAMP, ion loss to gut lumen and poor ion uptake, rice water diarrhea

81

roles of toxins

-promote bacterial growth
-facilitate dissemination
-interfere with host defenses

82

how to do toxins promote bacterial growth?

by providing access to nutrients sequestered inside host cells

83

how do toxins facilitate dissemination

by breaking down epithelial carriers

84

how do toxins interfere with host defenses

by disrupting actin function in phagocytic cells

85

mechanisms for being active at cell surface

-pore formation
-phospholipase (chew through phospholipids)
-superantigen
-lysins

86

examples of pore formers

aerolysin, staph alpha toxin, streptolysin, listeriolysin O

87

examples of phospholipase

C perfingens alpha

88

examples of superantigen

staph TSST

89

TSST

toxic schock syndrome

90

lysins

hemolysins

91

hemolysins

lyse RBCs

92

pore formers

disrupt target cell membrane by causing formation of unregulated channels

93

how are channel pores formed?

-multimer of one bacterial protein that inserts into membrane
-complex of two or more bacterial proteins that inserts into membrane
-binding to target cell membrane protein leading to unregulated opening of pore

94

phospholipases

-cleave phosphatidylcholine (lecithin) or spingomyelin (all over cell so it will affect lots of cell types)
- due to the abundance of substrate, can affect virtually all cell types
-one or more forms expressed by a large number of bacterial species
-probably facilitate bacterial dissemination and allow bacteria access to nutrients normally found only in the host cell cytoplasm

95

cholera toxin, botox, tetox

high level of target cell specificity

96

phospholipases

promiscuous, low cell specificity

97

alpha toxin of C. perfringens

phoshpolipase

98

beta toxin of staph aureus

sphingomyleinase

99

superantigens

staphylococci

100

what grows if tampons are kept in too long

irritated the vaginal environment to that favoring staph aureus

101

what caused toxic shock syndrome

many strains of staph + strep

102

patients most commonly affected by toxic shock syndrome

-menstruating women
-post surgical, either gender if you allow staph aureus to get through a barrier during surgery/injury

103

clinical features of toxic shock syndrome

-high fever
-hypotension
-chills
-nausea, vomiting, diarrhea
-erythematous rash all over leads to desquamation especially on hands and feet

104

classic pyrogen

LPS

105

pyrogenic

causing fever

106

many strains of strep make SPEs

streptococcal pyrogenic exotoxins such as SpE A + C

107

TSST-1

damage due to superantigen activation of T cells, TSST-1 activates 20 to 25% of T cells

108

superantigens

interact with T cell receptors inappropriately
-they bind to a site on the TCR outside of the AG specific TCR binding site

109

superantigen binds to all TCRs with a

shared structure, and many TCRs share the same structure outside the Ag binding site

110

superantigens binds to class

Class II MHC molecules on APCs

111

cell surface interactions with T cells and APCs during TSST mimic

normal Ag presentation and stimulate large numbers of T cells

112

TSST

toxic shock syndrome toxin

113

Toxic shock syndrome toxin

-superantigen
-activates up to 1 in 5 T cells
-causes massive release of cytokines, TNFa, IL-1, IL-2, IL-6
-contrast to conventional antigen: approximately 1 in 10,000 T cells activated
-made by many staph, strep strains

114

toxic shock syndrome

desquamation of hands and feet

115

A-B toxins

activity + binding domain

116

mechanism of AB toxins active in cytoplasm

-protease
-nuclease
-ADP-robosyl transferase
-adenylate cyclase

117

A-B toxin entry

1. binding
2. receptor mediated endocytosis
3. acidification release of a subunit across membrane

118

A-B toxin entry= diptheria

directly transits cell or it can undergo receptor mediated endocytosis

119

A/B toxins

A is active domain B is binding domain

120

what are exotoxins that act at a distance

A/B toxins- B domain may deliver toxin to host cell surface for damaging effects or may permit internalization of toxin such that it acts inside cells

121

"A" domains

proteases, nucleases, ADP-ribosyl transferases, adenylate cyclases

122

Are A/B toxins homologous?

NO, they contain a great variety of enzymatic activities that are delivered to host cells by a common strategy

123

type III secretion system -dependent intoxication

bacteria bind to host cell, then inject toxin into cytosol

124

legionella

use a lysosomal pathway + keep cells from undergoing apoptosis

125

type III, IV, V, + VI secretion systems deliver non A/B toxins directly into

cytosol of host cells

126

NON A/B toxins

similar to A/B toxins
-enzymes that work in the cytoplasm to subvert host cell phsyiology, protecting themselves from host immune response
-antibiotics are irrelevant to toxin if bacteria grow intracellularly

127

legionella pneumophila

>150 effector molecules
that prevent endosome-lysozomal fusion and lead to the production of a unique compartment where legionella can grow intracellularly
-some effectors prevent programmed cell death

128

vibrio cholerae

gram neg rods

129

what organism causes cholera?

vibrio cholerae

130

what kind of environment is vibrio cholerae found?

aquatic environments

131

how do we acquire vibrio cholerae?

contaminated water or food like uncooked shellfish

132

where does the cholera toxin act in our body?

small intestine

133

Can cholera be self-limiting?

yes, if patient is kept hydrated

134

what leads to rice water diarrhea?

cholera

135

does cholera toxin kill its target cells?

no, it subverts their physiology such that ionic balance is lost and water move from cells into the lumen of the small intestine

136

How many liters of fluid can a patient lose per day?

5 gallons = 20kg= 44 lbs

137

What therapy is used to replace fluid that is lost

oral rehydration solution

138

Oral rehydration solution per liter

20g glucose, 4.2 g NaCl, 4.0 g NaHC03, and 1.8g KCL

139

If cholera patients are not too bad off

replace fluids orally

140

if cholera patient is very ill

get IVs of lactated ringer's solution

141

Cholera's mechanism of action

adenylate cyclase (regulator) is stuck in the "on" due to ADP-ribosylation of bound GTP, which prevents its conversion to GTP which turns it OFF

142

cholera toxin subunits

1A subunit + 5B subunits encoded by separate genes in the CTX phage genome

143

What keeps ADPR (ADP ribosylation of bound GTP) on?

cholera toxin + NAD with help from an activator

144

what occurs when GSAlpha (adenylate cyclase regulator) remains in the ON position

-continued activation of adenlyate cyclase
-dramatically increased cAMP

145

what happens in the intestine when GSalpha is ON and cAMP increases?

-decreased Na+ absorption by villus cells
-increased Cl- secretion by crypt cells
-DRAMATIC WATER LOSS THROUGH LUMEN OF GUT

146

what do cholera patients get when there is RAMATIC WATER LOSS THROUGH LUMEN OF GUT

rice water stool

147

does cholera kill cells?

NO!

148

cholera

-cholera toxin action in small intestine
-toxin A subunit is ADP-ribosyl transferase that alters a regulatory subunit of adenylate cyclase
- results in increased cAMP levels in cells--> decreased Na+ uptake and increased Cl- secretion--> massive water loss and "rice water" stool
-Na+ / glucose symporter is not affected, allowing oral rehydration with solutions containing salts + glucose

149

is cholera self liminting?

yes, if patient is kept hydrated

150

bacillus antracis

-AB toxin
-clear central spores
-gram + spore forming abcterium

151

what helped Koch develop the germ theory of disease and derive "Koch's postulates?"

bacillus anthracis

152

What kind of infection is bacillus anthracis

zoonotic infection, derived from herbivores such as cattle and sheep

153

woolsorter's disease

derived from catle and sheep; bacillus anthracis

154

domestic terrorism via US mail caused 22 cases of anthrax

11 inhalation + 11 cutaneous via envelopes

155

3 ways bacillus anthracis

skin, Gi Tract, Lungs

156

anthrax is a

multi component A +B toin

157

how anthrax gets in the skin

scrape or scratch- scores germinate-anthrax toxin produced-local lesions-tissue necrosis-pustules and ulceres

158

how anthrax is presented in the GI tract

ingested spores germinate-- anthrax toxin produced-local lesions-possible dysentery

159

what is the most common way disease is presented by anthrax?

on the skin

160

how anthrax is presented in the lungs

inhaled spores germinate-septicemia-high mortality

161

B subunit of anthrax

"PA" for protective antigen, binds to type 1 membrane protein causing receptor mediated endocytosis

162

A subunit of anthrax

LF or EF

163

PA + LF anthrax

lethal activity

164

PA + EF anthrax

edema

165

EF+ LF anthrax

inactive

166

LF antrhax

letal factor, a Zn++ dependent protease that induces cytokine formation in macrophages + lymphocytes (A2 + B)

167

EF

edema factor , an adenylate cyclase enzyme that increases levels of cAMP

168

how does EF cause edema + phagocytic response

leads to the formation of ion= increase fluid release, permeable pores in membranes, causing edema and phagocytic response

169

tetanus + botulinum neurotoxins

synthesized as a single polypeptide chains

170

what synthesizes tetanus

clostridium tetani

171

how do tetanus and botulinum neurotoxins lead to disruption of neurotransmission

A subunits cleave proteins involved in docking of synaptic vesicles to plasma membranes

172

BoTox and Tetox

homologos + highly sequence similar toxins that affect neural transmission

173

Tetox is transmitted to cranial nerves by

intraspinal transmission among involved motor neurons (retrograde transport) OR by bloodstream delivery to neuromuscular junctions

174

TEtox is associated with

traumatic wounds/deep puncture (anaerobic)- dreaded "rusty nail". leads to spastic paralysis (lockjaw)

175

vaccine DDT2

tetanus toxoid generated by formalin treatment of TeTox

176

Botox prevents

release of neurotransmitter and acts at peripheral cholinergic synapses leading to flaccid paralysis

177

what toxin is heat labile

C. botulinum

178

heat labile protein

one that can be changed or destroyed at high temperatures.

179

does the C. botulinum toxin grow in the body?

rarely, except in infant botulism where there is colonization of the large intestine

180

how is C. botulinum introduced?

through contaminated food, and the toxin is heat labile

181

does C. botulinum kill targets?

Toxin does NOT act by killing target cells nor does it produce sepsis/fever.

182

How do we treat C. botulinum disease?

antitoxin + supportive care

183

What two toxins can damage at extremely low doses?

Botox and Tetox

184

How much of botox could kill all the people on earh?

.6kg

185

botox (botulinum?) and tetox (tetanus?) attack

same targets but different neurons
-you can take A from botulinum and put on B of tetanums and you can retarget

186

how many kDa are Botox and Tetox proteins

~150lDa

187

Botox and Tetox

Zn++ proteases that cleave proteins in involved in docking of synaptic vesicles to the plasma membrane of neurons

188

What proteins are proteolytically clipped at the hairpin to produce a light chain and a heavy chain that are held by a disulfide bridge

botoxin + tetoxin

189

what two toxins block similar steps in neurotransmission but affect different target neurons due to their B domains?

botox + tetox

190

locked jaw

starts in jaw but then whole body gets rigid

191

how do you die from botulinum neurotoxin

flaccid paralysis- you die of suffocation because you can't breathe

192

tetanus and botulinum neurotoxins A subunits

cleave proteins involved in docking of synaptic vesicles to plasma membrane, leading to disruption of neurotransmission; opposite effects on host due to selection of target neurons by B subunits

193

botulinum toxin

peripheral neurons, blocks release of stimulatory neurotransmitters, flaccid paralysis

194

tetanus toxins

retrograde transport to CNS, blocks release of inhibitory neurotransmitters, spastic paralysis