18 Phagocytosis, Complement, Bacteria (1) Flashcards
how do phagocytes recognise pathogens
Outer surface structures recognised as PAMPS- pathogen-associated molecular patterns by phagocytic immune system cells
where are phagocytes found
different parts of the body such as blood, bone marrow, mucosal tissues
what do phagocytes recognise
recognise surface features of bacteria, sometimes by binding them directly such as Toll like receptors (TLRs) for specific structures such as LPS or flagellin. These are called non-opsonic receptors
what happens if bacterium makes a particular fimbrus type that has been seen in body previously
If a bacterium makes a particular fimbrus type and has been seen in the body before then antibodies may already by circulating that recognise and bind those fimbriae and opsonic receptors recognise that binding
what are the more general marking proteins of host
mannose-binding lectin, can recognise mannose sugars in structures like LPS O antigens of bacterial outer membranes
Complement
what does complement mark
bacterial surfaces, fibronectin or lactadherin are also proteins which are recognised bound to bacterial surfaces by opsonic receptors on phagocytes
effect of macrophage engulfment
Macrophages usually thought of as mounting an inflammatory response to bacteria when then engulf them
what pathways do macrophages enter
can enter pathways associated with healing (called M2) or inflammatory pathways associated with killing/inhibiting bacteria (called M1)
which bacteria can evade complement activation
Some bacteria like spirochaetes can evade complement activation
how does bacteria evade complement activation
proteolysing some essential proteins of complement pathway, directly interfering with complement activation process by binding proteins that take part in it, or by altering membrane surface of the bacterium so that the MAC complex doesn’t assemble on it and damage it
what do receptors do in phagocytsosis
Receptors bind bacteria they signal to inside of phagocyte - changes cytoskeletal machinery under phagocyte plasma membrane so it moves out around bacterium and engulfs it inside a vacuole
what is the early phagosome
Vacuole inside phagocyte, containing still living bacterium
how does phagocyte matures this phagosome
forms by fusing vesicles called endosomes to it that contain enzymes and bacterial damaging compounds that kill and break bacteria, including proteins that pump acid into phagosome and proteins that later attack cell walls e.g. lysozymes
what do mature phagolysosomes do
phagolysosome kills and breaks bacteria and presents some broken materials to adaptive immune system so that more antibodies recognising the bacterial structures are made
what happens if reinfected with same bacteria
So further bacteria of the same type are phagocytosed faster next time because there are more opsonins for that bacterial type already
Avoiding killing by phagocytes is one of the main “aims” of pathogenic bacteria
- Cover up several surface structures that directly bind TLRs on phagocytes to reduce recognition and phagocytic engulfment
- Vary surface structure proteins/sugars
- Fight back against phagolysosomal killing processes once inside phagocyte
examples - cover up several surface structures that directly bind TLRs on phagocytes to reduce recognition and phagocytic engulfment
can be done by producing a capsule that covers the LPS of Gram –ve bacteria for example.
which bacteria is an example of covering several surface structures that directly bind TLRs on phagocytes to reduce recognition and phagocytic engulfment
spirochaetes e.g. Borrelia burgdorferi agent of Lymes disease
example of varying surface structure proteins/sugars so they aren’t always the same
antibodies won’t recognise altered form of surface structure = less opsonisation of bacteria and less recognition of cell surface and less engulfment by macrophages
how can bacteria fight back against phagolysosomal killing processes once inside phagocyte
different bacterial pathogens do this in different ways: some neutralise low pH in the phagolysosome; some resist lysozymes
how does growth affect detection
grow very slowly or not at all inside macrophages and they don’t activate the phagolysosome
where is the flagella in spirochetes
internalize their flagella inside periplasm, only rotate outer membrane, can cross tight junctions in human epithelia
how does spirochates infect
enter human body from a tick bite, can invade into CNS and joints where can cause blindness and lethargy or arthritis
how long do spirochetes persist
Spirochaetes like Borrelia can persist for a long time inside the body without recognition & phagocytosis
how do spirochetes ‘hide’ from immune system
reduce protein content of their outer membrane to have less lipoproteins on their surface and their outer membrane chemistry is different and doesn’t contain usual lipid A and sugar components of LPS- so less immune stimulatory that normal Gram negtive bacteria
effect when borrelia injected into human blood
Borrelia injected in human blood switches off some surface proteins to avoid immune recognition, also switches on some surface proteins that prevent complement system inducing and opsonising spirochaetes
how does borrelia adapt to prevent complement action
- Inhibit alternative complement pathway with binding proteins on their surface that bind complement factor and/or inhibiting lectin or classical pathways by binding C4 binding protein on their surface
- Borrelia have an altered (non LPS) outer membrane composition with slime layer -MAC complex doesn’t assemble
- OspC protein of Borrelia binds tick salivary protein - stops Mac complexes forming
