18 Phagocytosis, Complement, Bacteria (1)

Question 1

how do phagocytes recognise pathogens

Answer 1

Outer surface structures recognised as PAMPS- pathogen-associated molecular patterns by phagocytic immune system cells

Question 2

where are phagocytes found

Answer 2

different parts of the body such as blood, bone marrow, mucosal tissues

Question 3

what do phagocytes recognise

Answer 3

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

Question 4

what happens if bacterium makes a particular fimbrus type that has been seen in body previously

Answer 4

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

Question 5

what are the more general marking proteins of host

Answer 5

mannose-binding lectin, can recognise mannose sugars in structures like LPS O antigens of bacterial outer membranes
Complement

Question 6

what does complement mark

Answer 6

bacterial surfaces, fibronectin or lactadherin are also proteins which are recognised bound to bacterial surfaces by opsonic receptors on phagocytes

Question 7

effect of macrophage engulfment

Answer 7

Macrophages usually thought of as mounting an inflammatory response to bacteria when then engulf them

Question 8

what pathways do macrophages enter

Answer 8

can enter pathways associated with healing (called M2) or inflammatory pathways associated with killing/inhibiting bacteria (called M1)

Question 9

which bacteria can evade complement activation

Answer 9

Some bacteria like spirochaetes can evade complement activation

Question 10

how does bacteria evade complement activation

Answer 10

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

Question 11

what do receptors do in phagocytsosis

Answer 11

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

Question 12

what is the early phagosome

Answer 12

Vacuole inside phagocyte, containing still living bacterium

Question 13

how does phagocyte matures this phagosome

Answer 13

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

Question 14

what do mature phagolysosomes do

Answer 14

phagolysosome kills and breaks bacteria and presents some broken materials to adaptive immune system so that more antibodies recognising the bacterial structures are made

Question 15

what happens if reinfected with same bacteria

Answer 15

So further bacteria of the same type are phagocytosed faster next time because there are more opsonins for that bacterial type already

Question 16

Avoiding killing by phagocytes is one of the main “aims” of pathogenic bacteria

Answer 16

1. Cover up several surface structures that directly bind TLRs on phagocytes to reduce recognition and phagocytic engulfment
2. Vary surface structure proteins/sugars
3. Fight back against phagolysosomal killing processes once inside phagocyte

Question 17

examples - cover up several surface structures that directly bind TLRs on phagocytes to reduce recognition and phagocytic engulfment

Answer 17

can be done by producing a capsule that covers the LPS of Gram –ve bacteria for example.

Question 18

which bacteria is an example of covering several surface structures that directly bind TLRs on phagocytes to reduce recognition and phagocytic engulfment

Answer 18

spirochaetes e.g. Borrelia burgdorferi agent of Lymes disease

Question 19

example of varying surface structure proteins/sugars so they aren’t always the same

Answer 19

antibodies won’t recognise altered form of surface structure = less opsonisation of bacteria and less recognition of cell surface and less engulfment by macrophages

Question 20

how can bacteria fight back against phagolysosomal killing processes once inside phagocyte

Answer 20

different bacterial pathogens do this in different ways: some neutralise low pH in the phagolysosome; some resist lysozymes

Question 21

how does growth affect detection

Answer 21

grow very slowly or not at all inside macrophages and they don’t activate the phagolysosome

Question 22

where is the flagella in spirochetes

Answer 22

internalize their flagella inside periplasm, only rotate outer membrane, can cross tight junctions in human epithelia

Question 23

how does spirochates infect

Answer 23

enter human body from a tick bite, can invade into CNS and joints where can cause blindness and lethargy or arthritis

Question 24

how long do spirochetes persist

Answer 24

Spirochaetes like Borrelia can persist for a long time inside the body without recognition & phagocytosis

Question 25

how do spirochetes ‘hide’ from immune system

Answer 25

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

Question 26

effect when borrelia injected into human blood

Answer 26

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

Question 27

how does borrelia adapt to prevent complement action

Answer 27

1. 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
2. Borrelia have an altered (non LPS) outer membrane composition with slime layer -MAC complex doesn’t assemble
3. OspC protein of Borrelia binds tick salivary protein - stops Mac complexes forming