microbiology 1: Fungal infections Flashcards
3 main fungus causing infections?
Asperilligus
Cryptococci
Candida (albicans)
usually target immunocompromised organisms
Which cells respond to fungal infections
Opsoninaation
phagoctytosis by macrophages, NK cells provide early interferon gamma
Tcells and B cells also have a role
pretty much all the cells
What is fungal morphogenesis?
lot of funguses can change shapes and function depending on the host /environement they are in
cryptococci-can form many forms, but in humans forms large capsules
What are the main receptors used to innate system recognise fungi? exemples of what deficiencies exist and they can cause?
PAMPs-Tol like receptors, Dectin-1 receptor-> macrophages, etc
Dectin 1 deficiency causes mucocutaneous fungal infections -> fungal infections all the time
Also CARD9-downstream signalling of Dectin 1-if mutated also get those fungal infection
also these patients can make proper Th17-CARD9 needed to differentiate
macrophages cant respond
a lot of other receptors also have role
What is the roll of toll like receptors in fungal infections?
TLR4-important for fungal immunity
lots of SNPs can cause lose of functions-massively increase risk of pulmonary aspriologgis
similar effects to immune stoppers
What is the roll of dectin 1 in fungal infections?
Homozygous loss of function-very sensitive to fungal
heterozygous-as well, not as bad
Transplant fungal infections also increased
What is the role of macrophages in fungal infections? Why?
macrophages have less of a role in fungal-if knocked out then not much more happens
but neutrophils are a lot more important-if knock out->suceptible
In neutropenia, uninterupted growth of fungus in the lungs
Neutrophilas are very good at phagocytosis, but also use of NET (DNA traps)-> binding the fungi and stop it from germinating and replicatin
What is the role of fungal morphogenesis in immune response modulation?
Depending on the form of the fungus-multicellular/unicellular and other-> different response
Unicellular-Th1 response
multicellular-Th2 response (like worms /allergies)
ALso some forms cause more Th17 responses
What is adaptive antifungal immunotherapy? Other forms of immune modulation with fungi?
Lead to engineering of T cells to target fungal infections-adaptive antifungal immunotherapy -very good for patient with transplants (seperate antifungal T cells from patient, then put them back in after transplant (and no other-so no antigraft therapy)
Interferon gamma or adoptive T cell therapy have increasing utility
Gene therapy also used to grow GP91 subunit of NADPH oxidase->increase expression->forms ROS that kill fungus within the lungs –quite effective, and doesnt need working bone marrow (for transplant), or in people with immunodeficiencies
What are forms of response fungi can ellicit?
Immune, allergy, toxic
What are fungi allergies and what are they caused by?
Allergic reactions to air spored-like aspergillius (niger, fumigatus) MAIN DRIVER-many allergic spored per species-cause asthma, sensitise the lungs
Spores can reach deep in the lungs
Excess response can lead to death
What is the damage response framework in immunity?
If immune is weak-infections and die
If immune is too high-allergies and excess response-death
Need a normal one
Its like a upside down bell curve
Which types of hypersensitivity are fungal allergy responses?
Mostyl type 1 (IgE mediated )and type 4 (T cell mediated)
but can see IgG mediated allergic reaction with no underlying fungal infection (type 3)
What is the pathophysiology of bronchopulmonry asprigiliossis?
Abberent DC activation seems to be the issue, leading to TH17 activation instead of Th1/2 -> IgE class switch and sensitisation to the allergy
alawys have baseline serum >1000IU/ml
diagnosis driven by IgE, IgM, skin test
What are the radiological feature of ABPA?
Bronchoestasis, shadowing, opaque (one whole lung whited out)-airway damage and mucus production cause mucus to grow into them, and can lead to airway collapse seen on XRAy
