Pathogenesis Flashcards

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1
Q

when are we colonized

A

at birth

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2
Q

our microbiome protects us from

A

disease

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3
Q

how does our microbiome protect us from disease

A

produces inhibitory substances
stimulates appropriate immunity responses
stimulates antibodies
generate essential nutrients

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4
Q

what essential nutrients does our microbiome produce

A

vitamin K production in the colon by E.Coli
and fermenting fiber

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5
Q

types of disease

A

infectious: caused by a pathogen
communicable: transmit between organisms indirect or direct
non-communicable: does not transmit between hosts
contagious: easily spread
iatrogenic: caused by medical procedure
nosocomial: acquired in hospital
zoonotic: human infected by animal
reverse zoonotic: human infecting animal

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6
Q

pathogen

A

an organism that can produce disease

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7
Q

primary pathogen

A

infect any host
establish in a niche, occupied by commensal microbial populations
cross anatomic barriers or overcome other host defenses that limit commensals

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8
Q

opportunistic infections

A

infection when normal host defenses are diminished
weakened immune system: HIV, cancer, chemotherapy
dysbiosis
disruption of physical barriers

caused by primary pathogen or normal commensal bacteria: E.coli is commensal in intestine but can cause UTIs

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9
Q

periods of disease

A

incubation: pathogen has entered the host and multiplies but too few organisms are present to cause disease
prodromal: pathogen continues to multiply, non-specific signs and symptoms of illness, immune activation
illness: pathogen continues to multiply, signs and symptoms are obvious
decline: decrease in pathogen numbers of signs and symptoms of illness
convalescence: return to normal function

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10
Q

virulence

A

the degree that an organism is pathogenic

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11
Q

median infectious dose ID50

A

number of viable organisms required to infect 50% of subjects

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12
Q

if infectious dose is low, it can be difficult to

A

identify the source

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13
Q

koch’s postulates for virulent organisms

A

-bacteria must be present is diseased individuals but not healthy ones
-bacteria must be isolated from host with disease and grown in pure culture
-specific disease must be reproduced when a pure culture of the bacteria is inoculated into a healthy susceptible host
-bacteria from original host and new host must be identical

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14
Q

shortcomings of Koch’s postulates

A

-some disease can be commensals: H. Pylori
-many bacteria cannot be grown in pure cultures: Chlamydia
-not all hosts are equally susceptible to infection: SARS-CoV-2
-ethical issues, some pathogens can only infect humans

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15
Q

falkow’s molecular koch’s postulates: virulence genes

A

-phenotype of the disease should be associated only with pathogenic strain of species
-inactivation of the genes associated with pathogenicity should reduce virulence
-reversion of the mutation, or allelic complementation must restore virulence

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16
Q

virulence genes

A

help pathogens survive and proliferate

adherence/colonization factors
exotoxins
enzymes
immune evasion

17
Q

adherence/colonization factors

A

bind to host cells
-fimbriae
-afimbrial adhesions
-capsule

18
Q

exotoxins

A

secrete proteins to effect host function
-activated by heating

19
Q

enzymes

A

degrade host structures
-proteases: degrades connective tissue
-lipases: lyse host cell membranes

20
Q

immune evasion

A

hide from the immune system
-protective structurers: capsules, antigenic variation
-suppress immune responses
-physically hide from the immune system: bladder, or inside a cell

21
Q

common exotoxins

A

botulism: blocks acetylchonline release, stops muscle contraction
tetanus: prevents release of glycine and GABA, prevents muscle relaxation

22
Q

how does the bacteria know when it is in the host

A

quorum: when bacteria reach a required density - S. Aureus
temperature: 37 C
pH: stomach <3, stimulates gene expression in H. pylori
oxygen tension: normal atmospheric oxygen ~21%, human tissue 3-10%

23
Q

expression of virulence genes is often _____

A

coordinated

genes are co-regulated in response to environmental cues

24
Q

lateral gene transfer

A

spreads virulence factors
help bacteria adapt to new environment
selective pressure
plasmids: large, found in Shigella, Yersinia
phage: smaller pieces of DNA encoding few genes, found in Cholera, STEC

25
Q

STEC

A

shiga-toxin producing E.Coli
central kitchen

26
Q

e.coli: vitamins and dysentery

A

colonize the bowel within 40 h of birth
aids in digestion, produces vitamin B12 and vitamin K
major cause of foodborne illness
extracellular (STEC or EHEC) or intracellular (EIEC) replication

27
Q

shiga toxin

A

contributes to bloody diarrhea and kidney failure

28
Q

STEC serology

A

E.Coli: O157:H7
187 O Antigen: LPS endotoxin
53 H Antigen: Flagella made of flagellin

29
Q

virulence factors of STEC

A

locus of enteric effacement
-attachment to cells
-type III secretion system
TRANSFORMATION- chromosomal pathogenicity island

shiga toxins
-damages host cells, inhibits translation, induces apoptosis
TRANSDUCTION- phage-derived, integrated DNA

plasmid O157
-encodes virulence factors, hemolysin and catalase
-proteins
CONJUGATION- F-like plasmid

RpoS - sigma factor
-RNA polymerase to transcription initiation sites
-master stationary phase and stress regulator: acid, heat, salt resistance

30
Q

1.4 Mb are _________ _________ foreign DNAs

A

horizontally transferred

31
Q

pathogenicity islands

A

chromosomal islands are regions of the chromosome of foreign origin
GC content then the rest of the core genome
associated with tRNA genes
integrase
pathogenicity islands are chromosomal islands with virulence gene of different GC content
promote virulent factors

32
Q

locus of enteric effacement

A

flanked with phage sequences, required for intestinal cell attachment
contains:
-type III secretion system
-section proteins
-regulatory genese
-host-interacting proteins
initial contact stimulates T3SS expression

33
Q

what is T3SS

A

a bacterial needle which penetrates the host membrane to translocate effectors

34
Q

type III secretion systems

A

gram -
spans three membranes
proteins translated can be translocated through the hollow needle
effectors

35
Q

what do effectors do in type III secretion systems

A

remodel and manipulate the host response
-suppress immune responses
-target host proteins for degradation
-alter host cytoskeleton dynamics

enhance association with enterocyte
-stimulate pedestal formation
-adhesion molecules inserted into host membrane

36
Q

exotoxin: shiga toxin type III secretion system

A

A/B toxin
A/B binds to Gb3 receptor
A/B undergoes retrograde transport
A/B cleaved in golgi and reduced in ER
A is extracted from the ER
A subunit is glycosidase, depurinates 28S rRNA
prevents aminoacyl-tRNA from binding with the ribosome
causes apoptosis

37
Q

intracellular invasion

A

-live in a vacuole (Salmonella, Chlamydia, Legionella)
advantages: avoid immune detection
disadvantages: need specialized ways to get nutrients
-escape the vacuole (Listeria, Shigella, Rickettsia)
advantages: cytosol is rich in nutrients
disadvantages: cytoplasm is hostile and full of immune sensors