Fungal Infections

Question 1

unicellular fungi

Answer 1

Candida

Question 2

filamentous fungi

Answer 2

mould

Question 3

endemic mycoses

Answer 3

stick to a geographical region with distinct climatic conditions, e.g. Histoplasma

Question 4

Candida albicans

Answer 4

part of commensal fungus that colonises oral, GI and urogenital. Thrush. & Candida esophagitis are opportunistic with HIV.

Question 5

Candida albicans dimorphic switching

Answer 5

Without serum, grows as budding yeasts. Add serum, switch to filamentous form. Pathogenicity.

Question 6

Host recognition of fungi

Answer 6

Fungal-specific PAMPs (galactan, mannans, glucans). Detected by Dectin-1 (key receptor foudn on DC and macro) = particularly recognise beta-glucans.

Question 7

Dectin-1

Answer 7

Has a C-type lectin carbohydrate recognition domain that mediates the recognition of beta (1,3)-glucan and beta(1,6)-glucan on surface of intact cells. Also recognises soluble components of fungal cell wall- zymosans (consist of chitin, beta-glucans, mannans, mannoproteins).
Tyrosine phosphorylation of its ITAM

Question 8

ITAM

Answer 8

immunoreceptor tyrosine-based activation motif

Question 9

Dectin-1 and TLR

Answer 9

work synergistically to induce production of inflammaotyr cytokines and chemokines and ROS

Question 10

TLR

Answer 10

usually signal down MyD88 to activate NFkB

Question 11

MyD88

Answer 11

myeloid differentiation factor 88

Question 12

NFkB

Answer 12

nuclear factor kB. function as transcriptional activators.

Question 13

MASPs

Answer 13

mannose-binding lectin-associated serine proteases

Question 14

Complement and MBL

Answer 14

Candida express mannoproteins and adhesins on surface - activate alternative and lectin complement pathways. MASPs lack protease activity, then on binding - conformational change induces proteolytic activity to form C3 convertase.
Adhesins bind to C3 convertase –> amplification loop.

Question 15

Dectin-1 experiment

Answer 15

KO mice. Challenge with fungal spores.

Question 16

Mincle experiment

Answer 16

KO Mincle. Treat with TLR2 agonist. Measure TNF production. Need both to work synergistically.

Question 17

Chromoblastomycosis and Fonsecaea pedrosoi

Answer 17

Non fatal disease of skin and tissues. Transucatenous trauma (thorn from bush). American, African and Asian regions - farmers and tribes with little access to healthcare. Chronic and difficult to treat.

Question 18

Parasites - Helminths

Answer 18

large and multicellular. Don’t replicate in mammalian host - intermediate host. reproduce sexually to create larval stages that mediate transmission.
Nematodes (roundworms)
Trematodes (flukes)
Cestodes (flatworms and tapeworms).

Question 19

Nematodes

Answer 19

Roundworms. e.g. Hookworms, Ascaris lumbricoides.

Question 20

Cestodes

Answer 20

Flatworms and tapeworms . e.g. Taenia solium

Question 21

Trematodes

Answer 21

Flukes. e.g. Schistosoma mansoni, Schistosoma japonicum, Schistosoma hematobium.

Question 22

Schistosoma

Answer 22

6 species infecting >200 million people. Life cycle:
Eggs develop into motile miracidia which infect the intermediate host (aquatic snail) and mature. They leave snail as cercariae (infectious and motile) which then infect the human.

Question 23

Cercariae

Answer 23

Penetrate the skin, they shed their tails and only the head infects human. Immature schistosomula migrate via circulation to reach liver, where they mature. Release eggs into the veins draining the bladder and intestines. Eggs are excreted into water.

Question 24

Type 2 granuloma

Answer 24

Organised circumferential infiltrate of Th2 cells, eosinophils, macrophages and fibroblasts within a dense collagen-rich matrix

Question 25

African sleeping sickness

Answer 25

trypanosomas brucei. David Bruce (1903)

Question 26

VATs

Answer 26

Trypanosome Variable Antigen Types.
Trypanosome’s way of escaping the host’s immune defence.
Antigenic variation resulting from the successive dominance of each of a series of variable antigen types over time.

Question 27

VSG

Answer 27

variant-specific surface glycoprotein. Parasite elude destruction by expressing a new VSG –> become a new VAT. only one expressed at a time.