Extracellular immunity I Flashcards
Extracellular prokaryotes
- E.coli
- Strep pyogenes
- Clostridium tetani
- Staph aureus
- Helicobacter pylori
Fungi
Candida albicans
Parasites
- Trypanosoma brucei
- Schistosomiasis
QALYS and DALYS
QALYs (Quality-Adjusted Life Year) and DALYs (Disability-Adjusted Life Year) are common terms used within this framework. QALYs are a measure of years lived in perfect health gained whereas DALYs are a measure of years in perfect health lost. They are the most frequently cited metrics for risk-benefit assessment
Barrier defenses to extracellular infection
Skin, gut, eyes, lungs
Epithelial cells, cilia, low ph in the gut, lysozyme in the eyes and gut normal flora
Pemphigus
Caused by an antibody against desmin and destroys tight junctions
Primary cilia dyskinesia
Heart on the wrong side
Soluble mediators
- Ficolins
- Lysozyme - N acetyl muramide glycan hydrolase - gram positive cell wall
- Lactoferrin - iron chelator - sequesters nutrients
- Defensins, cathelicidins, Reg III (AMPs)
- Innate antibodies in gut
- Phospholipase A2
- Complement
- Collectins - MBL, surfactant
Th2 response
Caused by DCs leading to IL-4, IL-5 and IL-13 production
GATA-3 transcription factor important in leading to the response
Antibody response
Make IgA/IgG/IgE
Class switching of IgA1 to IgA2
Th2 mediators also activate non B cells
- Il-5 leads to increased eosinophils
- Il-9 leads to increased basophils
- IgE binds to basophils and mast cells - produce histamine
Th17 response in extracellular infection
Driven by IL-23, TGF-B, IL-6 and RORy
Mediated by neutrophils
proinflammatory - IL-1, IL-6, IL-8
antiinflammatory - IL-4, IL-10
Strep pyogenes - virulence and evasion of the response
- has bacterial adhesins and invasins
- complex capsules
- surface M proteins inactivate C3b
- secrete C5a protease, CD11b homologue
- Streptolysins
- Protein G
Toxic shock
Superantigen triggers T cells non specifically so any T cell becomes activated leading to a cytokine storm and multiple organ failure
E.coli O157:H7
Uropathogenic E.coli obtained adhesins leading to haemorrhagic diarrhoea
Endotoxic shock from E.coli
Leads to:
- inflammatory damage
- NF-kB
- TNF-a, IL-1, IL-8
- Coagulation, ox and nitric free radicals etc
Helicobacter pylori
Gram negative, causes stomach ulcers and cancer
80% of carriers are asymptomatic
Outer membrane includes putative adhesins, Fe2+ transporters, flagella proteins
Express catalase and urease
CapPAI (40 genes) make it pathogenic - the genes include superoxide dismutase which is involved in Type IV secretion
Fungal infection
- Tinea corpis - ring worm
- Malassezia furfur - dandruff
- Aspergillus fumagatus - asthma
Fungal recognition
Dectin -1 is a receptor that binds to glucans and skews the immune response to a TH17
Defects in fungal immunity
Neutropenic patients and individuals with mutations (promoter polymorphisms) in Dectin-1 - C.albicans
Chronic Granuloma Disease patients - Aspergillus
- defects in producing ROSs
AIDS - p. jirovecii