Microbio 2500B PDF

Innate Immunity Anatomy of The Immune Response The Human Lymphatic System Structure of a Lymph Node Structure of the Spleen...

Innate Immunity Anatomy of The Immune Response The Human Lymphatic System Structure of a Lymph Node Structure of the Spleen parallel to circulatory system highly organized fxn : recycle RBC · has a passive pumping system (w movement) T cell, B cell areas organized into red pulp, white pulp, follicle constantly recycled by macrophages lymphocytes located here follicles present (B cells) Thin veins arteries travel Thick through here red : primary organs cells develop here blue : secondary organs cells reside here Pathogen Recognition Detection Intracellular Signalling Pathways innate - same mag speed all signal transduction pathways have large diversity of signal transduction pathways bc PRR is encoded into genome receptors that recognize signal mlcs most involve many protein cascades how do cells sense the presence of the pathogens? receptors : usually tmbn prots usually, prots assoc tg, phosphorylate e o, (a) cell surface receptors interacts w signal mlc, transmits signal to transferring a signal (b) phagocytosis signal transduction pathway pathways can overlap and talk to e o reprogramming of cell to secretion to carry info to cell can get a signal that activates multiple pathways of cytokines transmits signal usually involves changing gene expression in cell by acting in nucleus Pattern Recognition Receptors (PRRs) 4 Families of PRRs : TLRs can : PRRs are expressed at the surface and within many cell toll like receptors (TLR) recognize things outside cell and induce a signal types (WBC, some lymphocytes, and some epithelial cells) can be at mbn or endosome recognize things after phagocytosis recognize evolutionarily conserved, invariant regions of pathogens C-type lectin receptors (CLR) can also recognize damage or infection signals in nucleus Toll-Deficient Fruit Flies cannot prevent infection specificity is germline-encoded nucleotide oligomerizAtion receptors (NLR) if (toll) gene deficient critical for initiating immune responses (signals danger) in cytoplasm they cant fight fungi infection. RIG-I like receptors (RLR) PRRs and PAMPs TLRs PAMPs PRRs Phagocytosis PAMPs : pathogen associated molecular patterns TLRs recognize a wide variety of PAMPs - PRRs induce phagocytosis in dendritic cells and PRRs recognize PAMPs they signal pathogen to immune system · macrophages to initiate immune responses early warning signals > to activate cells direct them to pathogen a PRR innately recognize flagellum TLR4 recognizes gram - bacteria (lipopolysaccharide) if present, danger signal turns on at plasma mbn lysosome alerts that pathogens present DAMPs Extracellular Signaling : Cytokines Cytokines Modes of Action · DAMPs : damage associated molecular patterns cytokine = cell movement Pleiotropy: same cytokine act on different cells DAMPs are self-mlcs released after cellular damage cytokines are chemical "messages" (proteins that allow to evoke different responses : recognized by receptors activates immunity cell injured cell breaks releases chemicals > TLRs can recognize sense these DAMPs 3 > communication between cells of the immune system) target cells can only respond to cytokines if they have the receptor for it Redundancy: different cytokines evoke same response in cells Cascade induction: action of a cytokine on a cell recipient cells can turn off receptors to the cytokines they dont want induces production of one or more additional cytokines The 6 Major Cytokine Families Receptors Interleukin-2 Signaling Pathway receptors can be monomeric, dimetric, IL2 is present in many cells including B-Cells and T-cells or multimeric IL2 tells cells to divide (important for immune responses) JAK : janice kinase STAT : signal transduction activation of transcription all signal tduct paths : always a receptor at cell mbn - smaller Kd : higher affinity receptor start signal tduct cascade (ex JAK) then response (ex by STAT) receptor recruits JAK Activation of Cellular Responses phosphorylates themselves STAT changes in gene expression (transcription) " then dimerise changes in prot expression (translation) , translocation into nuc cell division (ex IL2 tells cell to divide) - then interact w DNA to turn genes cell movement (IL2 tells cell to move) - on off in nuclei cell differentiation (cells can mature) - cell survival; (life death) · ex tumour necrosis factor can tell cell to die survive