Lecture 11

Phagocytes are cells of the innate system that engluf and destroy pathogens 3 major classes: Neutrophils, eosinophil and macrophage Neutrophils + eosinophil = granulocytes – because their cytoplasm is granular Macrophages are from an agranulocyte lineage (monocyte) but as they mature they form granules Can see granules when looking under microscope At the top of phagocyte linage tree is multipotent hematopoietic stem cell and can branch off into common myeloid progenitor or common lymphoid progenitor The lymphoid progenitor cells go off to form natural killer cells and cells of the adaptive immune response (B and T lymphocytes)

Myeloid progenitor can go off to form neutrophils and eosinophil and monocyte which forms macrophage Neutrophils Dark pink nucleus made up of different lobes They are the most common type of granual site in blood They phagocytose and destroy pathogens They use granular structures to release stuff chew up and get rid of it Neutrophils are short lived and abundant in blood They not found in healthy tissue They found in damaged tissue When infection, neutrophils recruited in site of infection via activation of macrophages, PAMP etc Neutrophils are very sensitive cells to calls for help Small amount of compliment and neutrophils can detect MacrophagesLarger and live longer Macrophage can recognise damaged cells and remove them Csan tackle large orgnaimss such as protozoa Eosinophils They stain easily with eosin hence the name Help destroy parasite Modulate allergic inflammatory response They work together to destroy and “eat”

All phagocytes do the same thing They have all got surface receptors for PAMPS They have receptors for other chemicals for immune resaponse such as compliment protein They have receptors for antibodies Receptor for C3b protein

Pahgocytes induce actin polymerisation site of infection Actin polymerisation allows change of shqpe of cell Once actin is polimerised, phagocytes can surround membrane and engulf it Granular sites are dense mewmbrane bound lysosomal derivative vesicles They fusre with phagosome embrane and release content We also have NADPH oxidase complexes which is important in respiratory bursts Granular sites trake in large amount sof oixygen and is used by NAPDH oxidase to generate toxic oxidative derivatives Neutrophils don’t survive longer than macrophages Dead neutrophils and pathogens = pus Some bacteria can replicate themselves inside neutrophils (gonorrhoea) Some bacteria can neutralise actin to prevent change in structure Inflammation aids killing in pathogens Vasodilation allows WBC to infiltrate tissue WBC degrade tissue and rebuild them after Activation of TLR in epithelia and activated macrophage contributes to inflammation Macrophage release cytokines which attract WBC Prolonged inflammation can get excessive vasodilation and you have low blood pressure and end up in state of shock Septic shock – significant decrease in blood pressure Viruses invade cells and use our ribosomes to make own viral protein Viruses are intracellular – its hard for immune system to recoginse as a foreign body There is not much opportunity for the cell to display virus-encoded PAMPS at the cell surface Innate immune system relies on CpG motives which are detected by TLR9. The other way biruses are detected via double stranded RNA which viruses have as we have single stranded RNA Doible stranded RNA is dected by TLR9.

Interferon alpha and beta work locally as they have short half life and degraded quickly

• It is autocrine and paracrine   Interferons can be made by all cells in response to double stranded RNA   Interferons limit the way viruses can spread by promoting apoptosis – programmed cell death   Paracrine action also induces cytokine production   Interferons upregulate the display of viral peptides on the outer membrane of the infected cell which provides signals for recognition by activated T cells   They stimulate expression of the immunoproteasome to process and destroy viral proteins   Interferon can convert proteosome to immunoproteosome   Proteosome – has caps at the top and bottom and is a bin for proteins they go in through 19S cap at top at centre there is beta subunits that chew up proetins and fragments are released at the bottom   Interferons change the 19s cap to a regulatory complex which enables degradation of different set of proretins and vchanges beta peptides and get replaced which have different enzymatic activity so the peptide that are formed look different   Interfereons activate macrophages and can call for help   They can also reduce growth of cancers   Interferons can cause inflammation of tounge which can cause loss of taste as taste buds are being restructured

NK cells T cells look at peptides within groove and determine weather cell is infected NK cells don’t look at peptide but look at number of peptides being displayed Not enough peptides and they can attack some viruses can inhibit their peptides making them hard to kill NK cells kill by triggering apoptosis (programmed death) of the infected or transformed cell and the apoptotic bodies that are left behind are engulfed by phagocytes