Soluble mediators Flashcards
how are defensins and histatins activated ?
by proteolysis to release an amphipathic antimicrobial peptide.
what does the skin contain to protect against pathogen ?
fatty acids
B defensins
lamellar bodies
cathelicidins
how are the epithelial cells joined ?
by tight junctions to try to keep pathogens out
what does the gut contain?
tight junctions by epithelial longitudial flow of air low pH enzyme pepsin alpha defensins such as cryptidins
the gut has regIII , what is this ?
an antimicrobial peptide
what do the lungs contain ?
longitudinal flow of air
epithelial cells joined by tight junctions
cillia to move mucus to be excreted
primary surfactant to produce a sterile environment
what contains lysozyme ?
the tears and saliva stored in lysosomes
what is the function of lysozyme ?
it breaks down carbohydrate chains and breaks the integrity of the bacterial outer membrane . The bacteria then burst under their own internal pressure.
how do defensins work ?
The defensin has a positive charge and this is drawn to the electrostatic attraction of the lipid bilayer and it forms a pore with it’s peptide to disrupt the bilayer.
how do cathelicidins work ?
These are stored in neutrophil granules as inactive precursors (prepropeptides) . They are released when cleaved by neutrophil elastase , this then results in the disintegration of the pathogen cell membrane.
what is a complement ?
a collection of serum proteins that protect against infections / abnormal cells , they initiate a cascade effect which amplifies the initial responses.
the complement proteins interact with the immune complexes , what ones?
IgM and IgG antigen
whats the 2 things that the complement proteins do ?
lysis – complete pathway to produce membrane attack complex.
– act as a bridge with an innate cells to allow close contact – complement-mediated cytotoxicity.
why does the complement pathway have three pathways for activation ?
if we just had one and the pathogen evaded this then it wouldn’t be beneficial to just have one.
in .the complement pathways what is A normally ?
small product except C2 where C2a is big molecule
what do the A products normally initiate ?
inflammatory response by binding to specific receptors such as complement component 3a receptor 1 and complement component 5a receptor 1
in the complement pathway what is b normally ?
BIG product - bind to targets near activation sites
what does b product initiate ?
and they interact with cell surface receptors to promote phagocytosis through osponisation.
what’s the 3 complement pathways ?
Classical
Alternative
Lectin
what does the classical pathway require ?
antibodies IgG and IgM
what is the classical initiated by ?
C1 components
what does the C1q bind to and what occurs next ?
the Fc portion of IgM and IgG which then binds to C1r and C1s to form complex C1
what does the C1 enzyme cleave ?
c4 to make c4a ( inflammation mediatior ) and c4b ( opsonise) as well as C2 to C2a and C2b
what does C4b bind to ?
the pathogen to opzonise it and then binds to C2
what cleaves c3?
the complex c4b2a convertase
what does C3 cleave into ?
c3a and C3b
what does c3a do ?
peptide mediator of inflammation
what does C3b do ?
binds to the pathogen surface and acts as a opsonisation for phagocytosis
what is the C5 convertase ?
c3b
what does C5b bind to ?
the surface of the pathogen and then binds C6 , C7 and C8 and a number of monomers of C9 to form C5b-9 .
what does C5b-9 do ?
it results in cell lysis of gram negative bacteria and pores form .
Inflammation also occurs.
what does the alternative pathway require ?
bacteria
what is alternative initiated by and what happens?
C3 and spontaneous hydrolysis to C3(h20)
when C3 is enzmatically cleaved what does this result in ?
c3b
what does c3b do ?
C3b binds to serum protein called Complement factor B form C3Bb complex. Exposes a site on Factor B that is a substrate for Complement factor D.
what does factor D do ?
cleaves factor B to Ba and Bb
C3Bb and 3b form what ?
C3Bb3b - C5 convertase.
what occurs if no stabilisation occurs to the complement factor properdin when binds to C3Bb ?
then the convertase will break up .
what does C5b bind to ?
C6 , C7 , C8 and C9 to form C5b-p membrane attack complex
what is the lectin pathway initiated by ?
mannose binding lectin ( MBL) binding to the mannose residues on the pathogen surface , this causes MASP 1 and MASP2 to be activated which are proteases.
what does MASP-2 do ?
it cleaves C4 to C4a and c4b and C2 to C2a and C2d. C3 convertase C4b2a forms it cleaves C3 and c5 convertase forms which cleaves C5 to C5b which joins with the C6 , C7,C8 and C9 C5b-9.
do bacteria contain lots of mannose residues on their surface ?
YES
