Fungal Infections Flashcards
unicellular fungi
Candida
filamentous fungi
mould
endemic mycoses
stick to a geographical region with distinct climatic conditions, e.g. Histoplasma
Candida albicans
part of commensal fungus that colonises oral, GI and urogenital. Thrush. & Candida esophagitis are opportunistic with HIV.
Candida albicans dimorphic switching
Without serum, grows as budding yeasts. Add serum, switch to filamentous form. Pathogenicity.
Host recognition of fungi
Fungal-specific PAMPs (galactan, mannans, glucans). Detected by Dectin-1 (key receptor foudn on DC and macro) = particularly recognise beta-glucans.
Dectin-1
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
ITAM
immunoreceptor tyrosine-based activation motif
Dectin-1 and TLR
work synergistically to induce production of inflammaotyr cytokines and chemokines and ROS
TLR
usually signal down MyD88 to activate NFkB
MyD88
myeloid differentiation factor 88
NFkB
nuclear factor kB. function as transcriptional activators.
MASPs
mannose-binding lectin-associated serine proteases
Complement and MBL
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.
Dectin-1 experiment
KO mice. Challenge with fungal spores.
Mincle experiment
KO Mincle. Treat with TLR2 agonist. Measure TNF production. Need both to work synergistically.
Chromoblastomycosis and Fonsecaea pedrosoi
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.
Parasites - Helminths
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).
Nematodes
Roundworms. e.g. Hookworms, Ascaris lumbricoides.
Cestodes
Flatworms and tapeworms . e.g. Taenia solium
Trematodes
Flukes. e.g. Schistosoma mansoni, Schistosoma japonicum, Schistosoma hematobium.
Schistosoma
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.
Cercariae
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.
Type 2 granuloma
Organised circumferential infiltrate of Th2 cells, eosinophils, macrophages and fibroblasts within a dense collagen-rich matrix
