Immune 3 Flashcards
The inflammatory response
(- broken physical barrier and allowed a way for infectious organisms to get inside the body)
- chemical signals get released from tissue-resident cells and act to attract more myeloid cells to the site of injury or infection
- neutrophils enter blood from the bone marrow (signals can go very quickly into the cells of the bone marrow to release more neutrophils into the blood - up regulate the number of neutrophils in the blood)
(- netophills have entered blood from bone marrow and are moving up the veins until they hit the site where the infection is and they slow down)
- neutrophils cling to the capillary wall (it slows cos there are interactions between receptors on the neutrophil surface and receptors on epithelial cell wall)
- chemical signals from tissue - resident cells dilate blood vessels and make cappillaries ‘leakier’ (blood vessels dilate and get bigger meaning more blood can move into area of inflammation
- neutrophils squeeze through the ‘leaky’ capillary wall and follow the chemical trail to the injury site
Stages of phagocytosis
- Phagocyte adheres to pathogens or debris
- Phagocyte forms pseudopods that eventually engulf the particles, forming a phagosome
- Lysosome fuses with the phagocytic vesicle, forming a phagolysosome
- Toxic compounds and lysosomal enzymes destroy pathogens
- Sometimes exocytosis of the vesicle removes indigestible and residual material
Killing and digestion of phagocytosed microbes
- low pH - acid environment
- reactive oxygen (hydorogen peroxide) and reactive nitrogen intermediates (nitric oxide)
- digested by enzymes
- proteases - protein
- lipases - digest lipids
- nucleases - nucleic material
The complement cascade
complement - 9 major proteins / protein complexes (C1-9) act in sequences to clear pathogens from blood and tissues
(- Inactive enzymes in the plasma form the compliment cascade
- inactive big complexes but when the get triggered they will break and split into active components and amplify as they go in order to do 3 things:)
-label pathogens (opsonisation) (tagging a pathogen to make sure it gets phagocytosed)
-recruit phagocytes (chemotaxis) (cells of the myeliod lineage - phagocytic cells are following a chemical trail)
-destroy pathogens (lysis) (punch holes in it)
3 compliment pathways triggering
CLASSICAL- antibody bound pathogen binds complement (activating enzyme allowing cascade to occur)
ALTERNATIVE - pathogen binds complement to surface / pathogen component (doesn’t involve adaptive immune response - involves innate immune system)
LECTIN - carbohydrate components of microbes bind complement and trigger path activation (don’t require adaptive immune response or antibodies)
Complement pathways converge always
- different triggers start off a little different and involve different molecules in the complement pathway system but they all converge and become the same pathway when they develop a concept called the C3 convertase (enzyme complex) and end up with the same 3 outcomes
3 outcomes from the complement cascade - LABEL
Opsonisation (labels pathogens which bind to complement receptors on phagocytes - triggering phagocytosis)
- the complement molecule the labelling is known as C3b and is a breakdown product of the C3 convertase
3 outcomes from the complement cascade - RECRUIT
Complement protiens (C3a and C5a) act as peptide mediators of inflammation and recruit phagocytes through chemotaxis
3 outcomes from the complement cascade - DESTROY
Membrane attack complex formation (C9 joined with other complements): pores in bacterial cells —-> death
Opsonisation I DONT UNDERSTAND
- can occur with complement
- can also occur directly with antibody
Opsonisation = coating of a microbe with:
- antibody and / or… - like classical????
(Antibody binds pathogen and when they bind it - they trigger it for uptake through receptors on phagocyte) - complement fragment C3b
(When complement fragment C3b binds to bacteria - bacteria gets taken up by macrophage that has compliment receptors on its surface that recognise the C3b fragments)
This leads to immediate protection form invading pathogens
Recruit.
- phagocytes attracted into site
- mast cells degranulated by C3a and C5a
- inflammatory mediators released including proteins that attract phagocytes
Destroy
- microbes coated with C3b are phagocytosed
- assembly of the MAC causes lysis
- Mac is formed by activated compliment components (c5b and c6 and c9) C9 is the major component of the pore
