Extracellular Immunity II

Question 1

yeast

Answer 1

candida albicans, Saccharomyces
asexual reproduction - budding
single celled

Question 2

mould

Answer 2

aspergillus, fuasarium

hyphae

Question 3

innate immune defences

Answer 3

skin/musosal surfaces: urinary tract flushes, musocillary escalator
pH - hostile for fungal growth
antimicrobial peptides: skin - dermicidines, cathelicidins, b defensins
gut - b defensins
neutrophils - a defensins, lysosyme.
complemement cascade, - yeast cell wall activates alternative pathway - opsonisation
phagocytosis

Question 4

candida albicans

Answer 4

activates all 3 complement cascades

promotes phagocyte killing

Question 5

aspergillus

Answer 5

requires complement cascade

less complement deposition, more pathogenic

Question 6

cryptococcus neoformins

Answer 6

polysaccharide capsule activates complement

enhances phagocytosis and induces cytokines, depletes complement system

Question 7

neutropenia

Answer 7

reduced number or functional problems with neutrophils (chronic granuloma)
predisposing factor to fungal infection
Mild neutropenia (1000 <= ANC < 1500): minimal risk of infection
Moderate neutropenia (500 <= ANC < 1000): moderate risk of infection
Severe neutropenia (ANC < 500): severe risk of infection.
(normal level is 1500 to 8000 cells per microliter (µl) of blood. )

Question 8

phagocyte - fungal interactions

Answer 8

Phagocyte PRRs - dectins, LTR, lectins, ficolins
fungal PAMPs - chitin, glucans, mannosylated proteins
for candida, neutrophil is best at killing (monocyte > DC)
interaction induces phagocytosis, killing, cytokine production, cytokine release, presentation to T cells

Question 9

neutrophil attack

Answer 9

oxidative mechanisms: respiratory bursts, ROS and RNI
hydrogen peroxide for candida
nitric oxide for cryptococcus
nutrient deprivation - sequester zinc and iron
hydrolases
a defensins

Question 10

adaptive host defences

Answer 10

Cell mediated - T cells
Th1 - protective driven by Il-12
Th2 - harmful, unwanted, chronic infection of aspergillus and candida. driven by Il-4
Th17 - important in mucotanious candidosis
need T reg cells, driven by Il-10
Th17 recruits neutrophils

Question 11

antibody functions

Answer 11

limited
complement activation for opsonisation 
reduced biofilm 
inhibit adhesion
seen in C albicans, C neoformans, A. fumingatis

Question 12

haemotogical malignancy

Answer 12

reduced neutrophils/DCs
due to cancer or to chemotherapy 
leukemia decreases DC maturation
In CLL, more Treg
In myeloid leukemia - impaired T cells

Question 13

HSCT and chemo to treat

Answer 13

decreased neutrophils
steroids supress immune system
suppressed migration of neutrophils
gluticorticoids impairs DC presentation
Retuximab targets B cells
chemotherapy disrupts cytokine network

Question 14

HIV

Answer 14

abnormal phagocytosis
reduced neutrophils
decreased CD4
impaired DC maturation

Question 15

solid organ transplant - T cell defects - immunosuppression

Answer 15

no affect on neutrophils
reduced T cell
reduced DC presentation

Question 16

immunosuppressed patients

Answer 16

at risk of infection 
neutropenia (may be caused by drugs/familial)
HIV
diabetes 
burns 
ICU
malignancy 
HSCT