Extracellular Pathogens

Question 1

What does QALY and DALY stand for in terms of disease burden?

Answer 1

Quality-adjusted life years

disability-adjusted life years

Question 2

Name some soluble mediators and give examples

Answer 2

lysozyme - N-acetylmuramide glycan hydrolase
Iron chelator - lactoferrin
Antimicrobial peptides - defensins, cathelicidin
Classical/Alternative and Lectin complement
Collectins - MBL, surfactant proteins SP-AD
Ficolins

Question 3

What are natural antibodies?

Answer 3

constantly produced by CD5+b-1a cells in gut
poylreactive
low affinity
germline encoded
IgM

Question 4

What do innate and adaptive defences entail?

Answer 4

Innate - phagocytic recogntion (PRR and opsinisation) and concomitant antimicrobial mechanisms
binding to modified lips
Adaptive - T and B cells

Question 5

What is the difference between Th1 and Th2 T cell defence?

Answer 5

Th1 = intracellular pathogens - cytotoxic response
Th2 = extracellular pathogens (Th17 helper cells)

Question 6

Briefly describe the production of Th2 cells in the T cell response

Answer 6

Naive Th0 cels differentiate into Th2
process driven by IL-4 and GATA3 which mediate transcription
APCs and DCs have germline-encoded receptors
Th2 cells secrete various factors to turn on B cells

Question 7

What kind of non-B cells do Th2 mediate?

Answer 7

IL-5 (increase eosinophilpoeisis, bone marrow release/activation and survival)
eosinophils
IL-2
IgE

Question 8

What is Th17 essential for?

Answer 8

Extracellular immunity
Inflammatory response (neutrophil recruitment)
Driven by IL-23, TGF-beta, IL-6, ROR gamma
production of pro-inflammatory cytokines for neutrophil activation and recruitment

Question 9

What are some virulence factors of Group A Streptococcus?

Answer 9

(i) bacterial adhesins/invasins bind the host cell
(ii) complex capsule prevents phagocytosis
(iii) surface M proteins inactivate C3b
(iv) secretes C5a protease, CD11b homologue
(v) streptolysins
(vi) pyrogenic exotoxin B (speB) degrades IL-1
(vii) protein G

Question 10

What are some of the consequences on infection by Group A Streptococcus?

Answer 10

(i) tissue necrosis e.g. hyaluronidase
(ii) rheumatic fever - due to molecular mimicry
(iii) glomerulonephritis - immune complex
(iv) toxic shock - non specific T cell activation

Question 11

How can the commensal E. coli become pathogenic?

Answer 11

Obtains a genetic element containing virulence factors by horizontal transfer
e.g. O157:H7 shiva-like toxin
plasmid with >100 ORFs causing hemorrhagic disorders
uropathogenic E.coli obtained adhesins

Question 12

What does infection with helicobacter pylori cause?

Answer 12

chronic inflammation
gastric ulcer/stomach cancer
80% of carriers are asymptomatic
outer membrane proteins include putative adhesins

Question 13

How can the commensal helicobacter pylori become pathogenic?

Answer 13

obtains pathogenicity island, CagPAI
contains approx. 40 genes not in commensal e.g. superoxide dismutase
VacA disruption of endosomal compartments causing apoptosis of cell and reducing acidity in the gut
targeting of mitochondria, release of cyt c

Question 14

Give a few examples of fungal infections from commensals

Answer 14

Tinea corporis-ring worm
Melassezia furfur
Candida albicans

Question 15

What are the main fungal recognition receptors?

Answer 15

Lectin 1 (recognise non self sugars e.g. beta-glucan)
skew Th17 immune response

Question 16

What can defects in fungal immunity cause?

Answer 16

neutropenic patients and promoter polymorphisms in dectin-1 cause increased susceptibility to C. albicans
CGD patients infected with aspergillum fumigatus
AIDS patients infected with pneumocystis carinii/P jiroveci