Complement Cascade Flashcards
describe the very first response to an infection
macrophages are the first responders and they will recognised pathogen associated molecular patterns on the microorganism using toll like receptors
what happens if the infection cannot be removed by the first responding macrophages
the macrophages will release cytokines to lead to inflammation
what is the important action of cytokines
recruit and activate more cells like macrophages, monocytes and neutrophils
what are the processes that occur during inflammation
vasodilation
increased vascular permeability
mast cell degranulation to release more cytokines
activation of clotting and kinin systems
what is the acute phase response
this is when inflammation stimulates macrophages and neutrophils to release interleukins which leads to a more systemic inflammatory response
what does interleukin 1 do
travels to the brain to produce a fever which leads to high temperatures poorly tolerated by the pathogens
reduced appetite and lethargy to conserve energy to better fight off the infection
what does interleukin 6 do
goes to the liver to trigger acute phase proteins
what does interleukin 8 do
recruits and activates neutrophils
what does interleukin 2 and 12 do
activate natural killer cells
what does tumour necrosis factor do
all the effects the interleukins do as well
what are opsonins
complex molecules that attach themselves to pathogens and make it easier for macrophages and neutrophils to recognise and phagocytose that pathogen
what does the complement system do
works alonside the innate and adaptive immune systems
functions in opsonisation, enhancing inflammation and destroying pathogens
which complement pathway occurs only when there is an adaptive immune response
the classical pathway due to the need for antibodies to bind
describe the shape of antibodies
proteins shaped like a Y.
one end is variable in shape to match different antigens
the other is fixed in shaped and is recognised by many cells of the immune system
what can antibodies do to help the immune system
- attach to viral or bacterial receptors and prevent them from carrying out their function to prevent invasion of the cells
- attach to pathogens and clump together to slow the pathogen down
- attach to enemy toxins that are antigens and neutralise their toxic effects
- act as opsonins to help recognition and destruction of pathogens
what is inflammation
process triggered by tissue injury that sets up vascular, cellular and molecular events to clean up the debris and pathogens to initiate repair
what kind of molecule can an antigen be
glycoprotein
protein
sugar molecule
what two things must a molecule on the surface of a microbe be in order to be an antigen
- immunogenic
- reactive
what does immunogenic mean
activate immune system cells to start proliferating
what does reactive mean
this means the plasma cells are able to produce antibodies against the reactive antigens
what must an antigen initiate to be classed as a complete antigen
proliferation and antibody production
what are incomplete antigens called and when do they become complete
these are haptens that become complete antigens once they bind with skin proteins
what does the mast cell produce via degranulation
- histamines
- leukotrienes
- prostaglandins
what does kallikrein convert kininogen into
bradykinin
how are the phospholipids in the cell membrane of host cells affected by infection
phospholipase A2 can be released to break down the phospholipids to form arachidonic acid, which is worked on by lipoxygenases which cleaves it into specific types of leukotrienes.
cyclooxygenases are used to cleave into prostaglandins
what type of molecule are histamines, prostaglandins, leukotriens and bradykinines
cytokines
what do cytokines do to endothelial cell
- allow p selectins to embed in the endothelial cell membrane
- works on endothelial cell receptors to cause the cells to contract and form spaces between the cells
- allows plasma to leak out and create oedema
- oedema presses on nociceptors and stimulates pain
- nociceptors also activated by bradykinines
- they also bind to smooth muscle cells to create vasodilation caused localised hyperaemia, lead to redness and heat
what process leads to both swelling and pain in inflammation
increased vascular permeability
what do the P selectins on the surface of endothelial cells do
leukocytes circulating in blood have sugar molecules that fit with the P selectins which stops them from circulating any further so they can stay at the site of infection and help with infection
through diapedesis the cells can squeeze through the capillaries into the interstitial space
what process gets the immune cells to the site of infection
positive chemotaxis
what is secreted by the macrophages to alert other cells there is bacteria
interleukin 1
tumour necrotic factor alpha
interleukin 8
how does interleukin 1 stimulate fever production from the brain
it works on the hypothalamus to activate the release of PGE2 which resets the body temperature to initiate fever
what is used as a measurement to see if there is active inflammation in a patient
CRP levels as these are produced by the liver in acute phase reaction due to action from interleukins and tissue necrotic factor
which cytokines act on the liver to procide c reactive peptide
IL1 and Il6 and TNF- alpha
what is leukocytosis
this is when the bone marrow pushes out more white blood cells during inflammation
describe how macrophages consume the pathogen
extend pseudopods formed from their cytoskeleton to change shape and come around the bacteria to latch on and consume it
what happens once the macrophage or neutrophil has engulfed and digested the pathogen
only thing remaining from digestion is the antigens
neutrophil releases into the interstitial fluid by exocytosis
macrophage will present them on their cell surface
what can happen to the neutrophil once it consumes and destroys a pathogen
- release antigens into extracellular space
- undergo oxidative burst if bacteria are extreme
- undergo fragmentation and release chromatin and histone proteins which form NETs
which chromatin is used by macrophages for antigen presentation
chromatin number 6
what produces complement proteins
the liver
how do macrophages present antigens
produce MHC2 molecules which bind to antigens ad express it on the membrane
describe the classical complement pathway
- bacteria present with antigens on surface
- IgG bind to bacterial antigen
- specific FC portion of antibody is attractive to complement proteins and this is what binds the first complement protein
- C1 binds
- C4 binds
- C2 binds
- C3 binds
- C3 convertase splits C3 into C3a and C3b
- C3a breaks off and moves away, C3b stays
- C5b binds to C3b
- C6
- C7
- C8
- C9
- C5a and C3a enhance the inflammatory response
- C5b-C9 complex breaks off to form a pore, called membrane attack complex
- C3b is exposed again and acts as opsonin and binds to C3b receptor on macrophage which will phagocytose the entire thing.
how does membrane attack complex
part of the complement cascade, from C5b to C9, will break off and form a channel which inserts in the cell membrane of the pathogen
there is an influx of sodium and water which makes the cell undergo lysis.
describe the alternative complement pathway
- bacteria has antigen on surface
- binds directly to C3b
- C3a released to enhance the inflammatory response
- C5b binds
- C6,7,8,9 bind
- C5a released alonside C3a to enhance response
- C5b-C9 break off and form membrane attack complex
- C3b exposed again and there is opsonisation for enhanced phagocytosis
describe the lectin complement pathway
- bacteria has antigen on surface
- bacteria has antigen specifically called mannose
- mannose binding lectin is a protein that will bind to it and initiate the pathway
- C4 binds binds to this complex
- C2 binds
- C3b
- C5b,C6,7,8,9 bind and break off to form membrane attack complex
- C3b will bind to macrophage, there is phagocytosis
- release of C3a and C5a to enhance the inflammatory response
how do C3a and C5a enhance inflammation
they are chemotactic agents
when do complement proteins get activated
when there is inflammation
what are toll like receptors
non specific parts of the immune system present on the cell membrane that respond to foreign pathogens
what do interferons do
signal nearby host cells to tell them there is a virus to release antiviral peptides and tell macrophages and natural killer cells to activate and proliferate
