Biol 371- Cryptococcus neoformans

Properties of yeast cells:

single celled

round/ovaloid

reproduce with blastoconidia

have pseudohyphae

dimorphic

Species of C. neoformans which cause disease:

C. neoformans

C. gatti

Serotypes of C. gatti:

B and C

Ecological niche of C. gatti:

tropics in eucalyptus trees

Serotype of C. neoformans var grubii:

A

Serotype of C. neoformans var neoformans:

D

Ecological niche of C. neoformans:

worldwide in soils with high bird feces/ high nitrogen

Characteristics of C. neoformans:

basidiomycete

bipolar mating

dematiaceous

capsule production

Portal of entry of C. neoformans:

inhalation of spores

What happens to immunocompetent people who inhale spores?

the will clear the spores or had temporary mild respiratory symptoms

What happens to immunocompromised people who inhale spores?

the will develop pulmonary infestations which may spread systemically (CNS, bones, skin)

risk factors in non-AIDS individuals:

prolonged corticosteroid use

lymphoma

immunosuppression

risk factors in AIDS individuals:

low CD4+ T cells

Cryptococcosis diagnosis:

lung x-ray and clinical sample of blood, urine, sputum, or CSF

How does India Ink relate to C. neoformans?

it is a negative stain which detects the capsule

How does latex agglutination relate to C. neoformans?

the beads will clump together in the presence of anti-fungal antibodies

How does Bird See Agar relate to C. neoformans?

it contains catecholamines which can be converted to melanin by phenol oxidase

Virulence factor definition:

molecules or traits which enable a pathogen to be better at causing disease

C. neoformans virulence factors:

capsule

phenol oxidase

D-mannitol

superoxide anion dismutase

phospholipase B

Cir1 protein

Capsule is a polymer of __________.

glucuronoxylomanan

Capsules are resistant to what?

phagocytosis

High CO2 and low ferric oxygen (lung conditions) will __________ capsule production.

upregulate

Methods a capsule uses to aid in survival:

1. suppresses Th1 cytokines TNFa and IL-1 by activating IL-10

2. reduces C5a receptors to block neutrophil chemotaxis

3. induces T cell apoptosis

Phenol oxidase uses ____________ as precursors to melanin.

norepinephrine and dopamine (neurotransmitters)

function of melanin:

protects against R.O.I and R.N.I killing

What did the epinephrine killing system prove?

phenol oxidase is a virulence factor, but it does not use neurotransmitters for food and instead uses them for blocking DNA degradation

D-mannitol function:

alters the osmotic environment to allow fluid to leak into tissues, causing edema

Superoxide anion dismutase function:

converts super anion into a less reactive oxygen species hydrogen peroxide (H2O2)

Phospholipase B function:

cleaves phospholipids to allow for tissue invasion

Cir1 function:

promotes expression of CTF1 gene for better iron affinity of siderophores

alpha to a mating type in wild vs in clinical isolates:

40:1 in wild

30:1 in clinical isolates

which is more virulent alpha or a?

alpha

mice infected with this strain die by 40 days

which is more infective alpha or a?

alpha

only it will grow in the hyphal form when limited N is present (spores must be produces by the hyphal form)

function of iC3b:

produced by C. neoformans to downregulate C3b when the compliment pathway is activated

Which is required to clear C. neoformans, NK cells, cell mediated immunity, or both?

both

Why are both CMI and NK cells requires for clearance?

NK cells hold the infection at bay until 21 days, when the CMI response kicks in to completely clear the pathogen

Nu/Nu mice are …

NK positive but negative for CMI

Nu/+ mice are …

NK negative and CMI positive

neutrophils will only kill _______ C. neoformans

opsonized

_________ facilitate the travel of C. neoformans around the body

macrophages

the fungi can escape the phagosome unharmed

macrophages are activated by ___ which is secreted by ________

IFNgamma/ NK cells

treatment of invasive cryptococcosis:

Amphotericin B and fluconazole

treatment of cryptococcosis for those with low CD4+ t cells:

prophylactic