Guest lecture Flashcards
what does this guy study
host pathogen interaction: innate immunity (mast cells) - fattern recognition receptors
- flavivirues (zika - causes neurological impairment, dec in head circumfrance)
- when virus is introduced to population that is nieve can create small outbreaks
infectious diseases are cuased by microorganisms - what does the body do
- microorganisms are competeing for a niche to eist
- over
two branches of innate immune
- immediate and induced response
- immediate - has rpefomed soluble molecules like compleemnt and resident effector cells
- effector cells are already localaized at cite of infection, response occurs 4 hours after infection
what are teh potential outcomes of the innate immune response
- gets ris of pathogen with minor tissue damage
- does ont get rid and the induced immune response must help
what is complement
- system of plasma proteins that marks pathogens for destruction
- if pathogen penetrates epithelial barrier one of the first weapons are soluble proteins called complement
*made in liver, found in blood, lymph and ECM
- circulate in an inactive enzyme form (zymogen)
- once activated proceed by protease mechanism, they coat bacteria and virus to facilitate phagocytosis
what are the 3 compliemnt pathways and what do they lead to
- alternative, lctin and classical pathway. all lead to activtion of C3a and C3b
- cause recruitment of inflammatory cells, opsonization (more specific phagocytosis which is enhanced by presence of complement - acts like a flag to signal to immune system to check out)
why is Ce importnat
- most importnat complement protein
- those without C3 suffer successive severe infections, those missing other components have minor immunodeficiencies
when complemnt system is activated C3 breaks into C3a and C3b fragment
what is compliment fixation?
- occurs when C3b attached to a pathogen
- tags pathogen for destrcution
- can organize the formation of protein complexes to damage the pathogen membrane
*C2a deosnt bind to pathogen but recuits other cells
how does complement enhace bacterial phagocytosis
- by macrophages- tissue resident white blood cells (arent actually in blood they sit in conective tissue)
- macrophages have CR1 receptors which bind to C3b on bacteria
- stimulates endocytosis by macrophage
*opsonization (coating pathogen to faciliate phagocytosis
- macrophage membrane fuse creating a membrane-bound vasicle -the phagosome
- lysosomes fuse with the phagosomes forming phagolysosome
describe the membrane attack complex
- uses C5 - another complement protein
- C5 can be cleaved into C5a and C5b
- membrane attakc complex initiated by C5b, goal to form holes in pathogen
- CC6 and C7 bind to C5b - exposes a hydrophobic site on C7 that gets inserted into the lipid bilayer
- C8 (also has hydrophobic site) then comes and bind complex
- C8 initiates polymerization of C9, multiple C9 comes to make channel
small peptides released during complement activation induce ____
- local inflammation
- C3a and C5a are anaphylatoxins
- small soluble cleavage fragments - physiologically active
- drivers of innate inflammatory repsonse (anaphylactic shock)
- interact with specific receptors on phagocytes, endothelial cells, mast cells to activate these cells
*mast cells when activated degranulate - release preformed histamine which will increase blood flow and vascular permeability
- C5a is more potent than C3a, enhances neutrophil and monocyte bindign to blood vessel walls - acts as a chemoatractang
- *enhance phagocytic function and expression of CR1 and CR3
rapid response on immediate innate immune system si teh result of
- complement
- fact that effector cells like macrophages are already positioned in the tissues to respond to infection
what is mast cell
- dont know precurser but do know it is in the tissue in a mature form
- prepackaged with a bunch of granules inside - can go trhough degranulation releasing them
- main function: eliminate parasites by inducing powerful physiological responses (vomitng, diahhrea, coughing)
- exist in connective tissue of skin - immediate innate immume
- C3a and C5a anaphlatoxins activate mast cells
- can increase permeability by releasing histamine
mast cell localization
- reside just outside of blood vessel
- mast cells my have significant role in mosquito born viral infection
- mosquito poked trhough skin and searches for blood vessels, release stuff increase blood flow
- body releases neutrophils to site
*question is are mast cells protective or susceptible to virus
compare gendue virus and zika virus
- both transmitted be aedes aegypti
Dengue: mild to sever symptoms, causes hemorrhagic fever (results in internal bleeding
Zika: mild to moderate, can have vertical transmision (mother to child) and horizontal (sexual contact
*dengue was able to replicate thorugh mast cell to amke more dengue particles, question is then can zika also replicate through mast cell - replication of virus in body can cause problems but deosnt cause hemorrhagic fever
*zika doesnt appear to replicate in mast cells
describe mast cell infection in his lab
- exposed mast cell to zika for 1 hours
- during ifnection the virus will bidn to susceptible cells and vika virus particles will be internalized in cell
- separate a cellualr faction, as vrius replicates it ends up in supernatant and cells get pelleted at bottom of tube
- can quanity virus particles hat were replicated in mast cells
