week 7 - infections and pathogens Flashcards
infection terminology:
superficial
- infections that appear on the skin’s surface and can be caused by numerous external factors
- limited to the stratum corneum and essentially elicit no inflammation
infection terminology:
Cutaneous
- skin
- involve the integument and its appendages, including hair and nails. Infection may involve the stratum corneum or deeper layers of the epidermis
infection terminology:
Subcutaneous
- diffuse infection of the skin and subcutaneous tissues characterized by local spreading erythema, warmth, tenderness and swelling
infection terminology:
systemic
Circulation/CNS/other organs
- When it gets access to entire body (passed the yellow bit into blood vessels)
Primary pathogen
- A microbe able to cause disease in a otherwise healthy host
Opportunistic pathogen
- A microbe only able to cause infection in a immunocompromised host
o E.g. HIV, cancer, steroid therapy, pregnancy, diabetes
o Something else has already weakened the immune system
FUNGAL INFECTIONS
fungi as infectious agents
- Moulds and yeast are widely distributed in the air, dust and normal flora
- Humans are relatively resistant
o Body temp 37: huge bottle neck for things that might cause infection
o Physical barriers - Many fungi are non-pathogenic
o Only approx. 600 species have been linked to disease in animals
Even small when humans specifically
o Many. More fungal plant pathogens
FUNGAL INFECTIONS
fungal disease =
myocsis
FUNGAL INFECTIONS
pathogenesis of Mycoses
- Infectious agents: spores, yeast, hyphal elements
o Part of fungus that causes disease is debated
-
FUNGAL INFECTIONS
pathogenesis of Mycoses
enter the body?
Enter body through respiratory, mucous and cutaneous routes
o Primary fungal pathogens tend to enter via respiratory route
FUNGAL INFECTIONS
pathogenesis of Mycoses
normal human flora?
- Dermatophytes and Candida sp. Part of the human normal flora
o Can be present in healthy amounts
FUNGAL INFECTIONS
pathogenesis of Mycoses
communicable?
- Most mycoses not communicable
o Don’t generally spread person to person, haven’t developed transmission routes
Not part of selective pressure to survive
o EXCEPTION: Dermatophytes and Candid sp. ARE transmissible
E.g. athletes foot, ringworm
FUNGAL INFECTIONS
fungal diseases can be:
- Superficial
o Athletes’s foot (Trichophyton) - Opportunistic (secondary)
o Thrush (Candida)
o Cryptococcosis (Cryptococcus neoformans) - But serious primary mycoses exist
o Coccidioides
FUNGAL INFECTIONS
medically important fungi
Primary
- Coccidioides immitis
Opportunistic
- Cryptococcus neoformans
- Candida albicans
(there is more!! this is what we cover)
FUNGAL INFECTIONS
Cryptococcus neoformans
what
- Opportunistic pathogen
o Associated with people immunocompromised - Basidiomycete encapsulated yeast
o Related to many mushroom forming fungi
FUNGAL INFECTIONS
Cryptococcus neoformans
where from?
- Soil, particular tree species and pigeon droppings
o Associated with eucalyptus trees
FUNGAL INFECTIONS
Cryptococcus neoformans
most cases in?
- Most cases in HIV+ in sub-Saharan Africa
o Highest burden of infections
FUNGAL INFECTIONS
Cryptococcus neoformans
infection
- Infection via lung, then disseminating to CNS – cryptococcal meningitis
o Crossing blood brain barrier
o High cerebral spinal pressures
o Keeps growing in spinal fluid
o Hallucinations
FUNGAL INFECTIONS
Cryptococcus neoformans
chance of survival?
40-60% chance of survival
- How quick found
- How good treatment is
o Of the fungi
o Or of existing disease
FUNGAL INFECTIONS
Cryptococcus neoformans
when in body
Crossed by extracellular or in the macrophage
Although should be being digested
Its not
So in a sense in a protected environment
* In the macrophage
Instead of all the antifungal stuff in the blood
FUNGAL INFECTIONS
Cryptococcus neoformans
Vomocytosis
Can escape from the host cell
Leaving host cell intact
* So immune system isn’t triggered
* Lots of implications if happens at blood brain barrier.
This is vomocytosis
FUNGAL INFECTIONS
Candida albicans
what
- Opportunistic pathogen
o Also part of normal healthy flora
FUNGAL INFECTIONS
Candida albicans
most common infection
- Most common serious fungal infection is candidiasis
FUNGAL INFECTIONS
Candida albicans
where on body
- Commensal on skin/body tracts
FUNGAL INFECTIONS
Candida albicans
disseminating infection involved…
a DIMORPHIC SWITCH (yeast to hyphal)
- inflammatory mechanism
FUNGAL INFECTIONS
Candida albicans
pathogenic process
- adhesion and colonization
- hyphal penetration and invasion
- vascular disemination
- endothelial coloization and penetration
Hyphal advantage to fungus
Can puncture tissue and spread to other parts of the body
Hyphal growth to penetrate
Switch to free moving yeast
Ect.
FUNGAL INFECTIONS
Candida albicans
Candodalysin
see notes for diagram
attacks host’s cholesterol-containing membrane
Make Ece1 toxin
Secreted as candidalysin toxin
Makes pores in the membrane (fungal toxin that causes damage)
So not just hyphae physical force rupturing cells
Also chemical
Important for ability to cause disease
has various adhesion molecules so it can better adhere to cells
FUNGAL INFECTIONS
Coccidioides imitis
what
- Primary pathogen
o Can infect to healthy individuals
FUNGAL INFECTIONS
Coccidioides imitis
ascomycete
o Hyphae can segment and every other cell can become a pore
o So a switch to a spherule –> which are full of endospores
o Example of differentiation
FUNGAL INFECTIONS
Coccidioides imitis
found in?
in desert soilds of South-West USA
FUNGAL INFECTIONS
Coccidioides imitis
causes?
- Causes coccidiodomycosis
o Valley / California fever
FUNGAL INFECTIONS
Coccidioides imitis
risk factors
- Construction and severe weather are major risk factors
o Spores become air borne (inhalation)
FUNGAL INFECTIONS
Coccidioides imitis
effects and treatment
- Flu like symptoms
- Rare-CNS/joints/skin lesions
- When becomes chronic treatment can take years (might not even be successful
FUNGAL INFECTIONS
Coccidioides imitis
dimorphic
switches between yeat and hyphae
FUNGAL INFECTIONS
Coccidioides imitis
life cycle
see notes
Spherule too large for phagocytosis
The cells are huge compared to immune cells
* Dimorphic change so resistant to macrophage
PROTISTS INFECTIONS
Trypanosoma (kinetoplastid)
what
- African sleeping sickness
- Chagas’ diseases
Two different species of Trypanosoma causing two different infections
PROTISTS INFECTIONS
Trypanosomiasis
transmission
- Trypanosoma parasite transmitted by an invertebrate vector:
PROTISTS INFECTIONS
T. brucei gambeinse
disease?
African sleeping sickness
PROTISTS INFECTIONS
T. brucei gambeinse
transmitter
Tsetse fly
PROTISTS INFECTIONS
T. cruzi
disease
Chagas’ disease
PROTISTS INFECTIONS
T. cruzi
transmitter
Assassin / kissing bug
PROTISTS INFECTIONS
T. brucei gambeinse vs. T. cruzi
growth
T. brucei gambeinse
- Extracellular growth in bloodstream
T. cruzi
- Intracellular growth
PROTISTS INFECTIONS
T. brucei gambeinse vs. T. cruzi
causes?
T. brucei gambeinse
- Fever, lethargy, mental disturbance (+trouble sleeping), death
T. cruzi
- Acute infection (fever/headaches), chronic >20 yrs, latent/asymptomatic
Some cardiac complications
PROTISTS INFECTIONS
T. brucei gambeinse vs. T. cruzi
area
T. brucei gambeinse
- Sub-Saharan Africa
T. cruzi
- South and central America
PROTISTS INFECTIONS
life stages of Trypanosoma
Epimastigote
- In the Tsetse fly/kissing bug
- Become trypomastigotes in the salivary gland/rectum
Trypomastigote
- In humans
- Can multiply by binary fission
Amastigote
- In humans
- Intracellular replicating form T. cruzi
PROTISTS INFECTIONS
Apicomplexans
what
- Apicomplexans are ALL obligate parasites
- Included malaria
Chosen example - Toxoplasma
PROTISTS INFECTIONS
Apicomplexans
Toxoplasma gondii
who does it affect
Affects a lot of mammals
Most well known for infection in rodents
PROTISTS INFECTIONS
Apicomplexans
Toxoplasma gondii
what does it do?
Manipulates rodents behaviour to make them more likely to be predated on my felines
* More likely to be found
PROTISTS INFECTIONS
Apicomplexans
Toxoplasma gondii
why switch between rodents and felines?
- In rodents can only divide asexually in gut
- In felines and divide sexually in gut and make oocytes
o Felines are the divinitve host
o Need to mix up genes
PROTISTS INFECTIONS
Apicomplexans
Toxoplasma gondii
humans infected?
Humans can be infected
* This is accidently
* No evolutionary benefits
PROTISTS INFECTIONS
Apicomplexans -Toxoplasma gondii
Toxoplasmosis
- Usually asymptomoatic but transmission to foetus is very serious
o Foetus cant protect itself
o Miscarriages - Humans are accidental hosts latent CYSTS form in the brain
- Asymptomatic carriage in humans varies greatly from country to country
PROTISTS INFECTIONS
Apicomplexans -Toxoplasma gondii
Toxoplasma
- Human is an (inadvertent) intermediate host
- But still get some behavioural manipulations
o Higher incidence of mental illness in infected humans
o Higher incidence of infection in drivers who crash - Evidence is patchy
is developing antimicrobial for eukaryotic infection difficult?
why?
yes really difficuly
because:
- Similar to our cells
- Not a lot of options for mechanism of action
o Only a handful that work
- Which first?
o Cells die or fungi die first
summary
fungal infections are most often…
opportunistic with serious complications in immunocompromised people
summary
Protozoan parasitic infection are often (but not always) transmitted by…
a vector and are often primary pathogens