fungal infections - medlearn Flashcards
fungi that cause human infection *
candida
aspergillus
cryptococcus
what type of pathogen are fungi *
opportunists - only cause infection and disease when host defences are breached
consequence of the fact that fungi are opportunists *
pts with cancer are at particular risk becasue they are immunocomprimised - either because of the underlying malignancy/treatment for the disease
AIDS pts and transplant pts are at risk - Pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii is associated with AIDS
at highest risk are people with prolongued and profound neutriopenia after treatment with chemo for haematological malignancies and recipients of haematopoietic stem cell transplantation (HSCT)
overview of the immune response to fungal infections *
response varies with respect to the species that is encountered and the anatomical site fo infection
the fungal morphocyte might also be a determinant of host response - yeasts and spores are phagocytosed but the bigger size of the hyphae means they are not ingested effectively
neutrophils, macrophages and monocytes are important antifungal effector cells - phagocytes are a critical 1st line of defence
fungal cell walls are different in their structure from human plasma membranes and are sensed by pattern recognition receptors of innate immunity
what are the ligands on fungi *
1,3 B-glucans
mannans
chitin
receptors for 1,3 B-glucans *
dectin-1
CR3 (CD11c/CD18)
CD5
CD36
SCARF1
receptors for mannans *
mannose receptor (CD206)
DC-SIGN (CD206)
langerin (CD207)
Dectin-2
receptor for chitin *
mannose receptor CD206
role of toll like receptors (TLRs) *
sense other fungal components
describe the sequence of the immune response to fungi *
phagocytes already in the target cells at the time of infection attempt to kill or damage fungi
neutrophils ad monocytes are recruited to sites of infection by the action of inflammatory cytokines, chemokines and complement components
describe fungi and complement *
fungi are potent activators of the complement system - can activate the classical, alternative, and lectin complement pathways
activation of lectin pathway happens when recognition of exposed mannans by mannose-binding lectin (MBL) triggers MBL-associated seriene proteases
resulting in opsonisation due to deposition of C3b on the fungal surface and recruitment of inflammatory cells as a result of Ca and C5a generation
however fungi are resistant to complement mediated lysis, presumably because of their thick cell wall
describe body’s Ab defence against fungi *
normal serum contains Ab to fungal cell wall components, particularly mannans that can initiate classical pathway activaton on binding
the Ab directly opsonise fungi for recognition by phagocytic Fc receptors (FcRs)
consequence of complement deficiency *
makes mice more suseptible to experimental mycoses
describe the effect of chronic granulomatous disease *
pts with CGD have defect in NADPH oxidase - therefore neutrophils are unable to kill ingested pathogens
these patients are suseptible to fungal infections - particularly of the aspergillus species
confirming the role of neutrophils in defence against fungus
role of dendritic cells in fungal infections *
innate and adaptive responses to Aspergillus fumigatus, Cryptococcus neoformans and Candida albicans
the signals transmitted to dendritic cells activated by exposure to fungi vary depending on the fungus and its morphotype - helping to shape the appropriate adaptive immune response
