PowerPoint PresentationSlide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Evolution by Natural Selection is a Evolution by Natural Selection is a SelfSelfish Processish ProcessThings (units) that survive & reproduce relatively more of self become relatively more common over time. An important way to increase survival & reproduction is to form cooperative coalitionsform cooperative coalitions.In evolutionary theory, the main mechanisms that underpin cooperation (by stabilizing against cheating) are reciprocityreciprocity and kin selectionkin selection.By helping kin, a ‘unit’ helps reproduce copies of shared genes (replicators).By helping kin, a ‘unit’ helps reproduce copies of shared genes (replicators).In diploid sexual species, full siblings share 1/2 of their genes by common descent.All the cells within a bodycells within a body (vehicle) that descend from a fertilized egg are a clonea clone and share all genes (except for mutations, ex cancers) & kinship = 1; this makes for a very cooperative coalition - a bodya very cooperative coalition - a body.Most cells in a clonal body don’t reproduce across generations; they increase copies of shared genes in their ‘close kin’ - the gametes. It is the job of the immune system It is the job of the immune system to stabilize this big cooperative coalition of cellsto stabilize this big cooperative coalition of cells by making sure everyone is on the same team - the ‘self team.’ by making sure everyone is on the same team - the ‘self team.’Other Myeloid Myeloid stem cells develop into phagocytes … neutrophils neutrophils – fast & briefMonocytesMonocytes become big persistent macrophagesmacrophagesMyeloid Myeloid stem cells develop into granule-containing inflammatory cells:Basophils Basophils – release histamines, prostaglandinsChemokines, pyrogens, etc. Eosinophils & Eosinophils & Natural Killer cellsNatural Killer cells– ‘bombs’Cells of the Immune SystemCells of the Immune SystemFig 43.1: An overview of defensesLymphoidLymphoid stem cells develop into lymphocytes. … two major classes are B cellsB cells and T cellsT cells.(antigen-independent)Beyond their role as a physical barrier, the skin & mucous membranesskin & mucous membranes counter pathogens with chemical defenses. MucusMucus is also rich in phagocytes and IgA antibodies Mucus traps microbes and other particles that contact it. In the trachea, ciliated epithelial cells sweep out mucus with its trapped microbes, preventing them from entering the lungs. Most microbes in food or water or swallowed mucus are destroyed by the highly acidic environment of the stomach. However, Hepatitis A virus is one of many pathogens that survives gastric acidity and enters to the body via the digestive tract.In humans, for example, secretions from sebaceous and sweat glands give the skin a pHpH ranging from 3 to 5; acidic enough to prevent colonization by many microbes. (Normal skin bacteria are adapted to acidic, relatively dry env.) Microbial colonization is also inhibited by the washing action of saliva, tears, and mucous secretions. These secretions contain antimicrobial proteins, like the enzyme lysozymelysozyme, which digests peptidoglycan (fig 27.5) in the cell walls of many bacteria.(antigen-independent)(antigen-independent)Microbes that penetrate the first line of defense, face the internal nonspecific defense: phagocytosisphagocytosis, ingestion by certain types of white cells.Phagocytic neutrophilsneutrophils constitute 60-70% of all leukocytes. Damaged cells release chemical signals that attract neutrophils {proinflammatory cytokines like interleukin-8 (Il-8) – aka chemokines}. The neutrophils enter the infected tissue, engulfing and destroying microbes.http://www.cat.cc.md.us/courses/bio141/lecguide/unit1/bacpath/cytogn.html#neutLipopolysaccharide LPS (aka endotoxin) from the gram-negative bacterial cell wall binds to LPS receptors on monocytes, macrophages and neutrophils. The binding of LPS to the LPS (CD14) receptor and Il-8 to Il-8 receptors on neutrophils stimulates them to release proteases and toxic oxygen radicals for extracellular killing. All components of the non-specific immune system are modulated by products of the specific immune system, such as interleukins, interferon-gamma, antibody, etc(antigen-independent)Phagocytic Monocytes Monocytes (5% of leukocytes) circulate in the blood for only a few hours, then migrate into tissues, developing into large macrophages ("big eaters") = MacrophagesMacrophages, the largest phagocytic cells. Fig 43.3 Phagocytosis: This micrograph shows fibril-like pseudopodia of a macrophage attaching to rod-shaped bacteria, which will be ingested and destroyed. A macrophagemacrophage engulfs a microbe in a vacuole that fuses with a lysosome (Fig 7.14). The lysosome has two ways of killing the trapped microbe: 1) w/ toxic forms of oxygen like superoxide anion and nitric oxide, 2) w/ lysosomal enzymes, including lysozyme.Some microbes have evolved mechanisms for evading phagocytic destruction. Some bacteria have outer capsules to which a macrophage cannot attach. Others, like Mycobacterium tuberculosistuberculosis, are readily engulfed {it binds to macrophage surface receptors for the sugar mannose} but are resistant to lysosomal destruction {it can inhibit phagosome-lysosome fusion; the exact mechanism is not known} and can even reproduce inside a macrophage.(antigen-independent)Phagocyte function is intimately associated with an effective inflammatory response and also with certain antimicrobial proteins. About 1.5% of all leukocytes are eosinophilseosinophils. Their main contribution is against larger parasitic invaders, such as the blood fluke Schistosoma mansoni.Eosinophils position themselves against the external wall of a parasite Eosinophils position themselves against the external wall of a parasite and discharge destructive enzymes from cytoplasmic granules. and discharge destructive enzymes from cytoplasmic granules. These cells have only limited phagocytic activity.Nonspecific defense also includes natural killer (NK) cellsnatural killer (NK) cells. NK cells do not attack microorganisms directly; instead, they destroy virus-infected