Microbiology Notes Part 2.pdf

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MICR 2420
Emma Allen- Vercoe

Immune System Nonadaptive (Innate Immunity) Adaptive (Acquired Immunity) • Barrier to infection, anatomical, microbiota • Reaction to specific antigens • Nonspecific responses to destroy invading cells • Body reacts to antigens when exposed, they retain memory of • Present at birth those antigens and there will be a faster response if exposed a second time Innate vs. Acquired Immunity   Innate Acquired Bstn with it Involves immune cells, T and B cells and antigen processing cells 1 line of defense Recognizes foreign substances a job for major histocompatibility complex Protective shell Increasing defense molecules Ig(Ab) and cytokines Inflammation, fever Memory (immunity) Phagocytes and killing Vaccines TLR, cationic peptides, interferon, acute phase proteins nd No increase upon 2 exposure to pathogens Microbiota Innate Immunity Acquired Immunity • Skin and mouth 1:10 (aerobe : anaerobe ratio), acquired • Natural / nonspecific host defen ces from birth canal and caregiver • In body fluid – lysozyme, secretory IgA • Cleansing actions – sneezing, coughing, urination, defecation • GI tract 1:100 (aerobe : a naerobe ratio), acquired from surrounding environment • Blood / lymph systems • Intestine 1:1000 (aerobe : anaerobe ratio), acquired • Responsible for blood clots from breast milk   • Interferons, NK cells, TLRs Microbiome • The total community of microbes found within a specified environment. Metagenomics is the use of modern genomic techniques to study microbial communities directly in their natural environment bypassing the need for isolation and laboratory cultivat ion of individual species. This includes DNA sequencing. Risks and Benefits of Microbiota Commensal microbes benefit the human host Opportunistic pathogens cause disease when human system • Make vitamins and digest food barriers are breached • Prevent colonization by pathogens • Host is said to be immunocompromised • Make immunomodulin proteins -> proteins made by • Bacteroides fragilis (anaerobic gas gangrene) and normal microbiota that influences the host immune pseudomonas aeruginosa (burn wounds and cystic response by modifying the secretion of host proteins. fibrosis) • Have potential use as a vaccine delivery vehicle Inflammation and Fever 1. Increase in blood volume 2. Increase in capillary permeability 3. Influx of recruitment of PMN’s • Redness, swelling, heat and pain • Cytokine release complement reactions   • Stops spreading of infection • Involves pyrogens which are and substance that induces fever o Bacterial pyrogens: LPS / endotoxin o Endogenous pyrogen: IL-1, TNFk, IL-6, interferon o A protective mechanism against microbes Extravasation of Leukocytes This is the process by which le ukocytes move from the bloodstream into surrounding tissues. Signal molecules produced by damaged tissue cells induce the production of selectins on the surfaces of endothelial cells and integrins on the surface of the WBC. Selecting capture leukocytes tra velling through blood vessels. Leukocytes begin to roll along the vessel wall and integrins lock onto ICAM -1 and VCAM-1. Leukocytes progressively activated while rolling. Neutrophil ultimately squeezes through the cell wall between endothelial cells.   Endotoxin / LPS LPS is an exogenous (action coming from outside the system) pyrogen, glycolipid, inducer of septic shock and a cell wall component. It has a gram-negative cell wall. The structure of LPS is: lipopolysaccharides, outer -membrane, peptidoglycan and plasma membrane. Inflammation Key Terms Macrophages: mononuclear, phagocytic, APC of the immune system. Cytokines: secreted host protein, binds to receptors on endothelial cells regulating cell response. Endothelim: thin layer of cells that line the interior surface of blood vessels and lymphatic vessels. Selectins: one of a family of cell adhesion molecules. Carbohydrates: an ideal source of energy for the body. It contains O, H and can release energy. Integrin: receptors that mediate the attachment between a cell and the tissues surrounding it. Neutrophils (PMNs): a WBC of the Nonadaptive immune system that phagocytoses and kills microbes. Bradykinin: cell signaling molecule, promotes extravasation, stimulates mast cells and pain. Tight Junctions: two cells whose membranes join together forming an impermeable barrier to fluid. Mast Cells: a WBC that secretes proteins that aid Nonadaptive immunity, does not circulate blood. Prostagladin: modulates inflammation through the control of blood pressure and di lation / constriction of blood vessels. Exudation: and fluid that filters from the circulatory system into lesions or areas of inflammation. Inflammation Response i. Bacteria infect tissue ii. Macrophages engulf bacteria and release chemical mediators iii. Cytokines induce selectins capillary endothelial that bind to neutrophils iv. Vasoactive factors induce integrins on neutrophils which bind ICAM -1 and VCAM-1 v. Bradykinin loosens junctions to allow extravasation and triggers prostaglandin synthesis Phagocytosis Key Terms Phagocytosis: is an effective nonspecific immune response. Monocytes: a WBC with a single nucleus that can differentiate into macrophages or dendritic cells. Pseudopods: a locomotory extension of cytoplasm bounded by the cell membrane. Phagosomes: a large intracellular vesicle that forms as a result of phagocytosis. Lysosomes: an acidic eukaryotic organelle that aids digestion of molecules (not in plants). Phagolysosomes: a cytoplasmic body formed by the fusion of a phagosome / ingested particle. APC: a cytoplasmic body formed by the fusion of a phagosome / ingested particle. MHC: transmembrane cell proteins important fore recognizing self and for presenting foreign antigens to the adaptive immune system . Autophagy: intracellular bacteria that can be sequestered from the cytoplasm and killed fusion with lysosome. PMN (polymorphonuclear leukocyte): neutrophils (professional microbial killers). Opsonization Opsonization is the coating of foreign cells to make them more attractive to be recognized and engulfed by phagocytes. Fc receptors bind the Fc region of antibodies binding to bacteria. Step 1: Extracellular bacteria approach macrophage. Step 2: Antibodies bind to bacteria and the Fc portion of the antibodies binds to receptors on the macrophage surface. Step 3: Ingestion by macrophage, antibodies link bacteria and macrophage, aiding phagocytosis. Phagocytes and Phagocytosis Monocyte and macrophage (dendritic cells) long -lived, killing an antigen processing monocytes circulate in the blood stream macrophages are residents in tissues and organs. Phagocytes include PMN, monocyte, dendritic cell, kupffer cell but not mast cells. *These bacteria resist phagocytosis or phagocytic killing: Bacteria Disease Mycobacterium tuberculosis TB or consumption Listeria monocytogenes Food poisoning Legionella pneumophila Pneumonia Rickettsia rickettsii Rocky Mountain Spotted Fever Staphylococcus aureus MRSA, caMRSA Burkholderia cepacia complex Fulminant necrotizing pneumonia Innate Host Defenses Defensins are small antimicrobial, cationic peptides that destroy invader’s cell membrane. Many human cells produce them. There are two types of vertebrate defensins: alpha-defensins (stored in cytoplasmic granules) and beta-defensins (not stored in granules). Autophagy Cell function not restricted to phagocytes. Host cells adapt to eradicate intracel lular parasites. Autophagosomes are double membranes forming around a pathogen. Fusion: lysosome autophagosomes. Caveat: intracellular pathogens developing to suppress autophagy. Toll-Like Receptors (TLRs) / SURFACE Pattern Recognition Receptors (PRRs) TLRs are evolutionarily conserved cell surface glycoproteins present on the cells of many eukaryotic genera. It is an alarm signaling system produced by many immune cells and tissues. It recognizes pathogen associated molecular patterns (PAMPs) which are molecules associated with groups of pathogens that are recognized by cells of the innate immune system. • LPS gene renamed TLR4 • TLR4 was first identified among TLRs based on sequence homology to toll of drosophila • Contains 3 domains: LRR (leucine rich repeat), TM (transmembrane region) and TIR (toll-IL-1 receptor) • Each TLR recognizes distant ligands • LBP and CD14 (secreted) mop up LPS, transport trapped LPS to interact with TLR4-MD2-CD14 (membrane bound form) triggering signal transduction via adapter protein called myeloid differential factor 88 (myD88) containing TIR Toll-like receptors in humans (p. 887-888) domain, leading to activation of NF kB   Nod-Like Receptors (NLRs) / INTRACELLULAR Pattern Recognition Receptors (PRRs ) • Family of nucleotide binding do main, LRR, containing proteins (Ref.: Akira S., Toll-like receptor signaling. • CaspasJ. Biol. Chem. 278:38105-38108, 2003)e in apoptosis • >20 NLR genes in humans • Nod 1 recognizes mesodiaminopimelic acid, found in G+ peptidoglycan (PG) • Nod 2 recognizes muramye dipeptide found in PG of both G+ and G- • Important for signaling the presence of intracellular pathogens and activation of NFkB *** NLR can cause apoptosis while TLR cannot cause apoptosi
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