Innate Immunity 1: Soluble Effectors Flashcards
Induced innate response is for how long?
4 hours to 4 days
Innate immune memory is called?
Trained immunity
Through epigenetic modifications
Metabolic reprogramming
Long term effects
Altered responsiveness
Which cells show trained immunity?
Monocytes, training happens in haemotpoetic stem cells
Soluble barriers?
Complement Defensins
Collectins
What disrupts bacterial cell walls?
Lysozyme
Lysozyme is found in?
Blood and tears
What do collectins, ficolins and pentraxins do?
Bind to pathogens and target them for phagocytosis (opsonisation) and activate complement
Complements do?
Lyse bacteria, opsonise pathogens and induce inflammation
What is lysozyme secreted by?
Paneth cells phagocytes in small intestine
Lysozyme cleaves?
Bond between alternating sugars that make peptidoglycan, exposes lipid bilayer
Phospholipid a2, then disrupts phospholipids, allowing water to get through—
Most effective in gram positive bacteria
Histatins ?
In oral cavity against pathogenic fungi, Candida albicans
Cathelicidins?
Ll-37 against both gram negative and gram positive bacteria
What secrete antimicrobial peptides?
Neutrophils, epithelial cells and paneth cells
How do antimicrobial peptides work?
Inhibit dna and rna synthesis,
Attack fungi virus and bacteria (minutes)
Defensins are?
Microbial peptides 35 to 40 aa amphipathic
Disulphides bond
Defensins work by?
Creating a pore
Collectins bind to?
Bacterial cell surface sugars
Why do collectins not recognise our mannose antigens?
Masked by sialic acid
Ficolins recognise?
Acylated compounds COCH3 such as bacterial cell wall monosaccharides
Pentraxins are?
Cyclic multimeric proteins in the plasma e.g crp
Crp binds to?
Phosphocholine on bacterial surfaces
C3a and c5a are regarded as?
Anaphalatoxins
Complements are made by?
Liver, monocytes macrophages and epithelial cells
Effects mediated by complement components?
Opsonisation Lysis Membrane attack complex Mast cell degranulation Extravasation Clearance of antibody complexes
C1 is made of?
Q, r ,s
18 polypeptides, collagen like helixes, 6 triple helix
C1 binds?
To 2 FC domains of antibody
Which is most efficient antibody at activating complement?
igM cause it has 5 Fc domains
What happens to igM before binding to c1?
When it binds to antigen changes from planar conformation reveals binding site for c1
Binding of c1q to Fc causes?
Conformation change in c1r, and c1s is cleaved and can cleave c2 and c4
What makes c3 convertase?
C4b and c2a
C3 convertase activates?
Over 200 c3 molecules
Leptin pathway includes?
Antibody independent, activated by mbl and ficolins
Mbl binds to mannose residues on carbohydrates and glycoproteins on bacteria and some viruses
Leptin pathway uses what to cleave c4 and c2?
Mbl forms a complex with masp1 and masp2 (serine protease)
Alternative pathway?
C3 hydrolyses into c3a and c3b.
C3b binds to pathogen membrane and factor b, so cleaved by factor d to c3bBb
C3bBb has a half life of?
5 mins unless it binds to serum protein properdin, extending half life to 30 mins
What is c3 convertase?
C3bBb
C1 inhibitor deficiency?
Hereditary angiodema, classical pathway activated very easily,
Injection of c1 inhibitor
Mbl deficiency causes?
Pyogenic infections in children
Deficiency in c8 cause?
Prone to neisseria meningitis
90% of people deficient in c4 develop?
Systemic lupus erythematousus
C3b bind to?
Immune complexes to be picked up by erythrocytes with cr1 receptor, taken to phagocytes in liver.
Which recognise through their fc receptors and engulf them
What causes trained immunity?
Altered responsiveness
Metabolic reprogramming
Epigenetic modifications
Long term effects
What is action of collectins ficolins and pentraxins?
Opsonise pathogens
And activate the complement pathway
What is c5 convertase?
C3bBbC3b
C4b2a3b
What makes the MAC?
C5b6789
C3a and C5a are important because?
Peptide mediators of inflammation
Phagocyte recruitment
C3b is important in?
Opsonisation of pathogens and removal of immune complexes
MAC?
C5b6789
