Control of Infectious Disease (Innate) Flashcards
What occurs during phagocyte recruitment
- Resident leukocytes and damaged cells release cytokines / chemical mediators
- Allow communication between WBC
- ## Release of cytokines and chemokines draws macrophages and neutrophils to the area as they leave circulation (extravasation)
What are PRRs
- Membrane bound or soluble proteins that recognise PAMPs
- Secreted molecules (body fluids, acute phase proteins)
- Cell surface receptors (CLR / TLR)
- Intracytoplasmic recognition molecules (intracellular pathogens, NODR, RIG-LR)
- DNA sensors (cGAS / STING)
What are PAMPs and DAMPs
PAMPs
- Pattern recognition receptors
- Shared by related groups of microorganisms
- Essential for pathogen survival
- Structures unite to cell wall components
- Not found in mammalian cells (LPS, flagellin, LTA, dsRNA, peptidoglycan)
- Ligands for host innate receptors
- Presence trigger phagocyte recruitment
DAMPs
- Damage associated molecular pattern
- Recognition of damaged host cells due to presence of non-self pathogen, alarmins / danger responses
- Heat shock proteins, uric acid proteins, heparin sulphate, defensins, neo-antigens
What occurs during signal transduction
- PRRs on leukocytes recognise PAMP
- Initiate phosphorylation cascade to transmit activation signal to the nucleus
- Activate TFs (NFκB) to turn on genes in response
- Transcription of pro-inflammatory cytokines / chemokines
- Leukocyte recruitment and effector response
What two families are involved in cytosolic PRR signalling
NLRs:
- Nucleotide binding and oligomerisation domain
- Recognise bacteria compounds (peptidoglycan)
- Can form part of inflammasome and trigger pyroptosis
RLHs:
- Retinoic acid inducible gene 1 (RIG-1) like helicases
- Recognise nucleic acids (dsRNA)
What are symbiotic bacteria
- Live in symbiosis with host
- Express large number of CHO-degrading enzymes
- Evolutionarily adapted to harvest diverse array of plant polysaccharides from diet
- Pathogens lack repertoire of glycoside hydrolases / saccharolytic enzymes typical of symbionts
- Lack factors that promote EC attachment and subversion of host biocidal mechanisms
What is innate vs adaptive immunity
- Innate: Non-specific ability to recognise and destroy a pathogen, does not require previous exposure
- Adaptive: Specific, acquired ability to recognise and destroy a particular pathogen, dependent on previous exposure to pathogen / antigen
How does stratification of intestinal lumen affect microbiota
- Minimise direct contact between intestinal bacteria and epithelial cell surface
- Goblet Cells: Secrete mucin glycoproteins, thick viscous coating at IEC surface
- Mucous Layers: Distinct outer (commensal bacteria) and inner (mucous, resistant to bacteria) layers
- High fibre thickens mucous, low polysaccharide thins mucous
How does compartmentalisation of intestinal lumen affect microbiota
- Confine penetrant bacteria to intestinal sites
- Limit exposure to systemic immune compartment
What are the cells present in intestinal lumen
- Enterocytes: Absorb nutrients, simple columnar cells lining villi and crypts
- Goblet Cells: Produce mucous, lubricates epithelium
- Enteroendocrine Cells: Secrete hormones, scattered in villi and some crypts
- Paneth Cells: Base of SI crypts, secrete antimicrobial agents (defensins / lysozyme)
Describe role of paneth cells in detail
- Contribute to intestinal homeostasis by delivering a potent cocktail of antimicrobial peptides into intestinal lumen
- Moulds composition of colonising microbiota and protects host from enteric pathogens
- Paneth cell dysfunction linked to IBD / Crohn’s
What antimicrobial peptides are secreted by paneth cells
- α-defensins: Constitutive, against gram +ve and -ve
- β-defensins: Inducible, against gram +ve and -ve
- Lysozyme C: Glycosidase, hydrolyses peptidoglycan, against gram +ve and to lesser extent gram -ve
- Phospholipase: Similar to α-defensins and lysozyme C
- REGIIIγ: Binds peptidoglycan, acts against gram +ve, processed by trypsin, activates binding and bactericidal activity
- ANG4: Enigmatic family of host defence-related RNases, antibacterial / antiviral activities
What are probiotics
- Contribute to food digestion and development of optimal functioning of immune system
- Generally lactobacillus or bifidobacterium spp.
- Exclude / inhibit pathogens
- Modulate host immune responses
- Promote iron / mineral absorption
How can probiotic bacteria modulate PRR signalling and what effect does this have
- Enhance function of intestinal epithelial barrier by modulating signalling pathways
- Induce mucous / defensin production
- Enhance tight junction functioning
- Prevent apoptosis
What role do DCs have in regulating responses to microbiota
- DCs activated by pathogenic bacteria
- DCs interact with B and T cells in the Peyer’s patches (prevent pathogen colonisation)
- DCs induce B cells to produce IgA directed against intestinal bacteria
- IgA move across epithelial cells into inner mucous layer to interact with bacteria
