Wednesday, August 16, 2017

The Immune system pathways in terms of infections on the outside of host cells

Imagine macrophages as the vacuums of the immune system carrying TLRs like butterfly nets trying to identify foreign material on bacteria it needs to consume.

In addition to these "nets" macrophages also look for opsonins.  Opsonins are grab handles your immune system puts on infections for macrophages.

Here are how opsonins are placed on infections:

Most gram positive bacterias have thick peptidoglycan cells which antibodies bind easily.  (staph for example has a very flat surface)  When two antibodies are in close proximity the classical pathway is triggered where opsonins are latched on to the surface of the bacteria. Remember to think of opsonins as macrophage grab handles. (C4b and C3b are opsonins)

The use of antibodies is called the classical pathway.

However some infections like strep have added a layer of lipopolysaccharides to make it more difficult for two antibodies to touch.  Your immune system has developed a sugar binding pathway called the lectin pathway using a mannose binding protein.  This mannose binding protein, MBP, binds the sugar and triggers the opsonins. (instead of 2 antibodies)

Lectin pathway and strep
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300866/

Lectin and candida
https://www.ncbi.nlm.nih.gov/pubmed/26730718

Lectin pathway and spirochetes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170916/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179856/

Now imagine a gram negative bacteria like e.coli.  Gram negative bacterias have evolved a very thin peptidoglycan layer with a crazy thick camouflage layer of varying stuff.  E.coli for example is covered with pili.  The surface of the bacteria is not easily visible or accessible to a macrophage and therefore the opsonins grab handles won't be easily used.

Image of e.coli

http://visualsunlimited.photoshelter.com/gallery-image/E-coli/G0000t5nqL4ZyAkU/I0000kKu0VV1fZb0/C0000.oQ5ArSj2dQ

It is in these circumstances that the opsonins collecting on the surface form C5 and go on to bind with C8 and C9 to form the MAC, the membrane attack complex.  The MAC is literally a pore created by your immune system on the bacteria's membrane with purpose of leaking the guts of the bacteria out.

The alternative pathway would best be described as a short cut path.  If the opsonins are struggling to build up on the surface and remain free floating they can still become the C5 free floating and then attach to the surface...short cutting the path to the MAC pore.








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