Lecture 3: Hematopoiesis

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Immunotechnology
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What is the content of macrophages and monocytes? i) Oxygen radicals: O2-, H2O2 etc. ii) NO's iii) Lysozyme: degrades the cell wall, mainly gram positive bacteria iv) Monocytes and neutrophils have MPO: myeloperoxidase v) Cytokines: IL-12, IL-6, TNF-alpha, IL-1 vi) Antigen presentation via MHC class II
Describe the overall process of phagocytosis i) bacteria encountered ii) phagosome iii) phagosome + lysosome iv) phagolysosome v) contents released and presented by class II MHC
What can activate macrophages? i) humoral factors ii) microorganisms iii) TLR iv) plastic: decent adjuvant! v) Lymphokines vi
What is the content of neutrophils? i) Oxygen radicals ii) Hypohalide ions iii) Granule content: lysozyme, defensins, BPI, lactoferrin and serine proteases
Describe the recruitment of neutrophils, the interractions i) Rolling adhesion: S-Le(x) interraction with E-selectin ii) Tight binding: interaction with ICAM-1 iii) Diapedesis iv) migration
What promotes opsonization and phagocytosis? i) C3bi ii) IgG coating IgG+C3 induce strong neutrophil activation. C5a induce lysosomal release and chemotaxis. Phagocytosis is induced by IgG+C3 and IgG and C3 (but not C5!).
Describe the characteristic of C5 i) 77 aa protein ii) action on: neutrophils, eosinophils, macrophages
Describe the characteristics of FMLP Tripeptide with a blocked N terminus. Acts on neutrophils, eosinophils and macrophages.
Describe the characteristics of LTB4. Arachidonic acid. Acts on neutrophils, eosinophils and macrophages.
What does IL-8 act on? Acts on neutrophils and basophils!
How can neutrophils be activated?
Describe the contents of eosinophils? i) oxygen radicals ii) hypohalide ions: generated by the ezyme EPO iii) granule content: EPO, MBP
Mast cells and basophilic contents Granule content: i) histamine ii) serotonine heparine iii) serine proteases iv) cytokines
What cytokines do mast cells produce? TNF-alpha, IL-25, IL-4, IL-5 and IL-6 TNF-alpha is important in the response against bacterial infections. IL-4 and IL-25 are important for TH2 response and IL-5 is important in recruitment and activation of eosinophils
What is the function of the complement system? i) opsonization ii) phagocytosis iii) chemotaxis
What different complement pathways are there? i) classical pathway ii) mannose-binding lectin pathway: binds sugar iii) alternative pathway: spontaneous activation
How is the classical pathway activated? The classical pathway of complement activation is considered part of the adaptive immune system, as it forms an antigen-antibody complex. These complexes may be soluble, these are often referred to as immune complexes. Only immunecomplexes formed by IgM or certain classes of IgG are possible to activate the classical pathway.
Describe the classical pathway i) IgG (certain subclasses) or IgM binds C1. C1 is a macromolecule complex composed of C1q, C1r and C1s held together in a calcium-stabilized complex. The C1 macromolecular complex bind by its C1q globular heads to at least two Fc sites for a stabil interraction to occur. Note: pentameric antigen-bound IgM can bind C1q (have three binding sites for c1q) while circulating non-antigen bound IgM cannot.
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