MICROBIOLOGY; Lecture 6 and 7 - Immunity to fungal infections, Parasitic infections Flashcards
How are cells immune to fungal infection?
Opsonization by pentraxin 3 and mannose-binding lectin
- Phagocytes are a critical first line of defense
- NK cells provide early interferon-gamma
- A failure of innate immunity leads to adaptive responses
- Dendritic cells influence T cell differentiation
- Th1 and Th17 play a role Most of these organisms interact with mucosal surfaces -> Asp and Cryptococcus initially in the lung, Candida in the lung.
Detected by all aspects of immune system -> dendritic cells leads to T cell responses and B cell based Ab immunity
What are examples of fungal immune evasion?
▪Candidal dimorphism (yeast/hyphal forms) allows tissue invasion
▪Crytpococcus forms a capsule to evade phagocytosis
▪Aspergillus species inhaled as conidia, invade tissues as hyphae.
Fungi can change shape (morphogenesis)
These can transform
For the immune system this is a problem because at one stage it is trying to detect a single cell infection then at another stage it’s trying to detect a multicellular infection and that has consequences in terms of innate and adaptive immunity
What is an infection?
invasion by and growth of pathogenic microorganisms within the body
What is a disease?
a disordered or incorrectly functioning organ, part, structure, or system of the body resulting from the effect of genetic or developmental errors, infection, poisons, nutritional deficiency or imbalance, toxicity, or unfavorable environmental factors; illness; sickness; ailment.
What is a parasite?
Organism living in or on the host and dependent on it for nutrition - causing damage. Endoparasites (Protozoa: amoeba, coccidiae, ciliate, flagellates Metazoa: roundworms, flatworms, flukes) and ectoparasites
What are protozoa?
Protozoa – single celled organisms Eukaryotes (genome within a nucleus, complex organelles in cytoplasm) Pathogenesis (mechanism of disease) varied Some have insect vectors (eg malaria) No eosinophilia
What are metazoa?
Metazoa – Multicellular organisms (Helminths/worms) Free living, intermediate hosts and vectors Some just inhabit gut (geohelminths), other invade tissues Eosinophilia – if invade blood
Name some examples of protozoa?
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What are amoeba?
Entamoeba histolytica/dispar -> infection occurs by ingestion of mature cysts in food/water, or on hands contaminated by faeces.
• Incubation period may be as short as 7 days; tissueinvasion mostly occurs during first 4 months of infection.
Humans are the only reservoir, and infection occurs by ingestion of mature cysts in food or water, or on hands contaminated by faeces.
Invasive amoebiasis most often causes an amoebic liver abscess, but may affect the lung, heart, brain, urinary tract and skin.
Asymptomatic carriers pass cysts in the feces and the asymptomatic carriage state can persist indefinitely.
Cysts remain viable for up to 2 months.
How can you diagnose amoebiasis?
Use a wet mount -> treat with Nitroimidazole derivatives (act on trophozoite, but not on cysts) + parmomycine or diloxanide furoate
What are coccidia?
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What are the symptoms and complications of malaria?
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What is the treatment and how do you diagnose malaria?
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What is toxoplasma gondii?
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How do you diagnose and treat cryptosporidium?
Causes diarrhea, fever, nausea, vomiting in humans; very common in HIV+ patients presenting with diarrhea. Diagnosis: stool examination. Treatment: fluid rehydration.
What are ciliates?
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What are flagellates and what are the symptoms, diagnosis and treatment?
Giardiasis (Giardia lamblia): commonest, globally distributed, water-borne protozoal infection.
Flagellated trophozooites attach by their suckers to surface of the duodenal or jejunal mucosa
Ovoid cysts are able to survive standard chlorination procedures, filtration is required to exclude them from drinking water
DIARRHOEA
What is trichomonas?
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What are helminths?
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Summarise the different kinds of worms?
• Flukes (Trematodes): Schistosoma • Flatworms (Cestodes): Taenia (Tapeworms) • Roundworms (Nematodes): Ascaris, hookworm, Filaria, Strongyloides
What are the symptoms, treatment and diagnosis of ascariasis?
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What are Ancylostoma duodenale hookworms - symptoms/pathology, diagnosis and treatment?
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What is trichuris thriciuria - symptoms, diiagnosis and treatment?
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What are taenia?
Humans only definitive hosts for T.solium(enters brain and causes epilepsy)/asiatica (in pigs) and T. saginata (in beef)
What are the symptoms, diagnosis and treatment of schistosomiasis - trematode?
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What are examples of ectoparasites - scabies?
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What are lice - ectoparasites?
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What are the signalling pathways in the innate recognition of fungi?
There are a large number of toll receptors
There are toll receptors that lead to transcriptional changes and release of cytokines C-type lectins – these sense organisms and are involved in phagocytosis (important for antigen processing and phagosomal killing of organisms)
What is Dectin 1 and how does it affect mucocutaneous fungal infections?
Dectin 1 is a pattern recognition receptor for a variety of glucans from fungi and plants, playing a role in innate immune response against fungi -> found on dendritic cells, monocytes, macrophages and B cells.
Dectin 1 is important in chronic mucocutaneous candidiasis (this is genetic) causes activation of defensins, phagocytosis, chemokines and cytokines ->
Their mucous tracts are chronically coated with candida.
There is a loss of function mutation in dectin 1
These people can’t make normal cytokine responses in their macrophages when they were challenged with candida albicans
They didn’t bind the candida very well either. Major risk factor for aspergillosis after transplants
What is CARD9 and how does it affect mucocutaneous fungal infections?
Caspase recruitment domain-containing protein 9 = adaptor protein in humans -> mediates signals from pattern recognition receptors (dectin 1) to downstream signalling pathways such as NF-kB and by this activates pro-inflammatory cytokines (TNF, IL-23, IL-6, IL-2) and an anti-inflammatory IL-10;
CARD9 is downstream of dectin 1 and it is also susceptible to mutation leading to chronic mucocutaneous candidiasis If you have a mutation in CARD9 then it also predisposes you to candida meningitis as CARD9 is downstream of several different receptors
What is TLR4 and what happens if it has a mutation?
Major toll receptor involved in sensing gram negative bacteria and fungi -> mutations in TLR4 increase risk of fungal disease
What is the effect of plasminogen alleles in fungal infections?
They influence aspergillosis -> risk factor for susceptibility to aspergillosis
What kind of immunity governs fungal tolerance and resistance?
Mucosal immunity->
Which spores can be commonly found in the air?
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What are the 4 types of hypersensitivity reactions?
Type I, III and IV are the ones associated with fungal infections
What is the damage response framework for microbial pathogenesis?
If immune response is too active then you can get disease through allergy, but too weak and you get disease through pathogen invasion
What is the pathophysiology of allergic bronchopulmonary aspergillosis?
ABPA – sensing of aspergillus at the mucosal surface leads to abnormal dendritic cells responses and alveolar macrophage responses
And generation of inappropriate T cell based profiles
Steroids are the main treatment because it shuts down all components of the immune response (active against T cells, B cells and macrophages(
Omalizumab – monoclonal antibody against IgE In most allergies there is a raised IgE – this is to deplete IgE antibodies
What are the criteria for identifying allergic bronchopulmonary aspergillosis?
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What are the radiological features of ABPA?
Hyper dense mucus sign -> high attenuation mucoid impaction within abnormally dilated bronchi
How do you manage ABPA?
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What is aspergillus rhinosinusitis?
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How do you treat fungal sinusitis?
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