Micro-L14- Host Pathogen Interface

what is the host pathogen interface?

• it is the dynamic cross talking between the pathogen and the host cells that determines infection outcome

• this is where pathogens adhere and is the main battlefield where host immunity fights infection

what are the main innate defences against pathogens? PPACS

• rapid, non specific mechanis

• physical barriers- skin, mucosal membranes

• pattern recognition receptors- TLRs, NLRs

• secretion of AMPs, stomach acid, tears, saliva, mucus

• cellular defenses- neutrophils, macrophages, DCs, NK

• soluble mediations: cytokines chemokines, complement, IFN

what is the role of epidermal and epithelial barrier

• skin: squamous and pathogens fall off

• fibroblasts- EM and supports tissue structure

• resident immune cells: DCs

• cilia in airways: brush off pathogens away from

provides a physical removal and chemical defence to block infection

what is mucus and mucins and their defensive roles? chemical barriers and the 2 types of mucins

• contain glycoproteins that line mucosal surfaces

• provide a physical barrier: prevents pathogens from reaching epithelial cells

• chemical barriers: neg charged and repels neg bacteria

• tethered mucins: anchored to the epithelial surface: MUC1 in the gastrointestinal.

• secreted mucins: MUC5AC- ciliated airways, MUC2 gastrointestinal. extracellular—>trap pathogens

• produce AMPS

how do pathogens interact with mucins?

• use mucins to attach to mucosal surface by binding to tethered or secreted mucin

• some produce mucins to attach and then digest via mucinase to liberate nitrogen and carbon sources for bacterial growth

• allows bacteria to penetrate mucus barrier

what are PRRs and their roles? list the types

• TLR1/26- lipoporteins

• TLR4- LPS- gram neg

• TLR5- flagellin

• TLR9- unmethylated CpG DNA

• TLR11- flagellin

• NOD1/2- detect peptidoglycan

• inflammasome- pyroptosis

NFkB and make pro inflammatory cytokines IL-1/6/8/12, IFN-gamma

steps of phagocytosis? steps

• chemotaxis: move toward pathogen

• attachment: via PAMPs, TLRs interaction or opsonisation

• ingestion of pathogen

• phagolysosome formation- vesicle with lysosome

• destrcution- superoxide, enzymes, H2O2, pH

• expulsion or antigen presentation

what is GALT and its components? PMLPGSM

gut associated lymphoid tissues

• peyers patches: B cells that make IgA

• M cells- transports microbes to Peyers patches

• lamina propria- extracellular matrix under the epithelial

• panted cells- secrete AMPs

• Goblet cells- secrete mucus

• stem cell progentiros- replenish the epithelium

• mesenteric lymph nodes: drain microbes

what is programmed cellular heterogeneity? what is used to study this? why study this?

• in a microbe population in a host- the cells can have different phenotypes: diff growth rates, metabolism and stress response

• FISH- bacteria embedded in agora's and fixed with probes to identify mRNA in individual cells. can look at many traits and sequences

• in cystic fibrosis- some cells exhibit high oxidative stress and others cluster- drug treatment may kill some cells while others survive. need to keep this in mind to combat ALL microbes!! due to programmed cellular hetergenity→some will survive

how do microbes know they are in a cell?

• temperature change

• pH change

• nutrient availability

• they can also detect surface metabolites and change gene expression to change behaviour accordingly

key features of streptococcus pneumoniae? morphology, disease, virulence factors, route of infection, clinical signs, treatment

• morphology: gram pos, forms chains

• diseases: pneumonia, sepsis, meningtiitis

• virulence factors: capsule and pneuomolysin

• route of infection: inhalation and colonises nose and lungs

• clinical signs: lobar pneumonia, alveoli filled with fluid

• treatment: amoxicillin

discuss the pneumoniae capsule? what it does to decrease immune response. also how is it synthesised? WGWWW

• protects against antibiotics, phagocystsos

• decrease IL-8, TNF, IL-6

• protects against complement

synthesised:

o   WchA initial transferase: links first sugar as a sugar phosphate Glc-P to membrane lipid carrier

o   Glycosyl transferase: links further sugarsmake repeat units

o   Wzx flippase: transports this across cytoplasmic membrane

o   Wzy polymerase: links these units to make a lipid linked unit- to make a capsule polysaccharide

o   Wzd translocates the capsular polysaccharide this to the peptidoglycan

specialised defenses to the respiratory tract? CGBCB

1. Ciliated cells- beat at 15 beats per sec

2. Goblet cells- mucus MUC5AC- mostly water- 1.5L per day

3. Basal STEM cells

4. Club cells- make AMPs- lysozyme, glycosaminoglycans and can act as stem cells

5. Brush cells- sensory roll and modulate mucociliary—> more ciliated activity and modulate immune response. first line defense of pathogens

dcesribe the Griffith experiment

-              Rough vs smooth strains. S has a capsule and is virulent, R has no capsule and non virulent

-              When rough R is incoluated with killed Smice died

-              Live R transformed into Sgot a capsule

-              Natural transformation