Infection and innate immunity Flashcards
What is innate immunity
First line or immediate response to pathogen invasion.
What are 3 highly developed and interlinked processes that provide you with innate immunity
- complement C
- myeloid cells and phagocytosis (neutrophils and macrophages)
- pattern recognition receptors (PRR)
What is the defence strategy for viruses
Defence relies on antibodies and cellular immunity. It needs to be able to distinguish infected from normal cells
What is the defence strategy for bacteria
Defence primarily mediated by innate mechanisms and phagocytosis
What is the defence strategy for protozoa and parasites
Complex multi-cellular organisms require direct killing by chemical mediators released by specialist myeloid cells.
What do granules contain in relation to degranulation
Granules are filled with cytotoxic chemicals. Degranulation releases these toxic inflammatory chemicals such as histamine.
What is gram positive bacteria
They have a thick peptidoglycan cell wall as a defence mechanism.
How are gram positive bacteria killed (and not killed by)
Requires phagocytosis but not killed directly by complement.
What are gram negative bacteria
Have a think peptidoglcan layer surrounded by an outer membrane. These bacteria can often be lysed directly complement membrane atttack complex.
What is neutrophil extravastion
Where neutrophils first sense an infection on other side of cappilary. They slow down and bind to cappilary walls. The cells here would be actuvated to find neutrophils about infection on other side of the cappilary.
What are the five steps of neutrophil extravastion
- Activation
- Tethering
- Adhesion
- Diapadesis
- Chemotaxins
What is activation of neutrophil extravasation
Chemokines from tissue injury or inflammation activate the local endothelial cells lining an adjacent cappilary wall.
What is tethering in neutrophil extravasation
Neutroophils tethers to the inside cappilary wall. It is mediatd by selectins which are upregulated on endothelial cells and sialyl Lewis X - carbohydrate antigen on neutrophils.
What is adhesion in neutrophil extravasation
Strong binding between neutrophil integrens and ICAM-1 on the endothelium. Neutrophil immobilises and flattens.
What is diapadesis in neutrophil extravasation
The neutrophil squeezes between the endothelial cells into the interstitial space.
What is chemotaxis in neutrophil extravasation
Neutrophil migrates along a chemical gradient to the site of infection.
How do neutrophils phagacytosises
- Chemoattractants such as C5a are being released that radiate away from the bacteria and are sensed by the leading edge of the neutrophil
- Neutrophils migrate up the chemoattractatn gradient, polymerising actin filaments at their leading edge and de-polymerising those filaments at their trailing edge
- Neutrophils have receptors thta bind deposited complement proteins, mainly C3b on the surface.
where are complement receptors found
On the surface of all myeloid cells.
What are complement receptors
Myeloid cell receptors that bind activated complement components deposited on bacteria.
What initiates phagocytosis
Cross-linking of the surface CR’s
What is the main neutrophil receptor that binds to C3b
Cr1
How does FcR (antibody) mediated phagocytosis work
- Antibody (IgM) and IgG) bind to bacterial antigens.
- This exposes the antibody Fc region which the nuetrophil binds to.
- Activates phagoctyosis
- Membrane invaginates forming a phagosome
- fuses with lysosome to form phagolysosome, which acidifies and superoxides kill bacteria.
What is molecular pattern recognition
- Pattern recognition receptors (PRR) bind complex molecules that are unique to microbes
- Activation stimulates a srong innate response through an importatn inflammation pathway.
What is the best known pattern recognition receptor (PRR)
Toll-like receptors, they are leucine rich receptors (LRR) that look like a slinky.
strucutre,
What are pathogen associated molecular patterns (PAMP’s)
- Molecules unique to microbes recognised by PRR’s.
- They are structurally very complex, which enables antibodies and TLR to recognise its unique features.
- stable
What are PAMP’s relationship with adaptive response
PAMP’s stimulate the ‘power’ switch for the adaptive response.
What is LPS
A membrane component of all gram negative bacteria which tiny amounts of it can induce a powerful innate response.
What can release of LPS by gram negative bacterial infections do
Lead to life threatning septic shock.
What does it mean when LPS is described as a pyrogen?
It can cause fever when injected into the bloodstream.
