BIOL 209 1st Edition Lecture 24 Outline of Last Lecture I. Question/Answer’sII. DefinitionsIII. AntibioticsIV. VaccinesV. Population EffectsA. Herd immunityVI. The Immune System Outline of Current LectureI. Question/Answer’sII. Immune SystemA. DefinitionB. Adaptive ImmunityC. Resistance to InfectionD. AnatomyE. LymphIII. PathogensIV. PathwaysA. Complement Recognition PathwaysV. Immune ProtectionCurrent LectureI. Question/Answer’sA. How do we know we have an immune system? We would otherwise be deadB. The fluid surrounding our cells is: LymphII. Immune SystemA. Natural resistance to pathogen infection1. Innate immune system responds to initial infection and, when activated, alerts adaptive immune responsea. Hard-wiredb. Non-specific, limited recognition of pathogens, or recognition of common pathogen structuresc. Innate immune response to bacterial infection induces inflammation: redness, heat, swelling, and painB. Adaptive immunity recognizes very specific structures – usually protein or carb structures – unique to individual pathogensC. Resistance to pathogen infection starts on the outside1. Mechanical barrier – physically resist pathogensThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.a. Epithelial cell layerb. Mucus2. Clearing mechanisms – clear surfaces of debrisa. Cilia function, coughing, tears, sneezing, etc.3. Secretionsa. Enzymes – lysozyme in tears and salivab. Defensins – anti-bacterial peptidesc. Acidic pH4. Competition (microbiome)D. Anatomy1. Cells of innate immunity (macrophages and dendritic cells) are found throughout the body in organs and tissues (including blood) and directly under skina. Serve as sentries looking out for invading pathogens2. Other innate immune cells (Neutrophils, Natural Killer Cells) are recruited to sites of infection3. Primary sites of immune cell developmenta. Bone marrow and thymus (near the heart)4. Mature cells of adaptive immune system (lymphocytes) found in blood and lymph fluid and in secondary immune organsa. Lymph nodes, spleen, tonsilsb. Some lymphocytes will also go to sites of infectionE. Lymph1. Extracellular fluid that is collected in lymphatic vessels and filtered through lymph nodes to catch invading pathogens2. Muscle movement moves lymph fluid around the bodya. Can’t collect pathogens easilyIII. PathogensA. Invading pathogens can be killed directly using relatively non-specific mechanisms1. Secreted complement proteins can kill pathogens by forming pores in their membranesa. Compliment proteins are present in blood and lymph- Form holes in cell membranes of pathogens to kill themb. Both specific and non-specific mechanisms are used to activate complement to form pores2. Phagocytic proteins – some immune cells can kill pathogens by ingesting themIV. PathwaysA. Complement Recognition Pathways1. ("Alternate" complement pathway) a. Key complement protein C3 can spontaneously bind to cell surfaces where it promotes assembly of a "membrane attack complex" (MAC)b. Recruitment of additional complement proteins leads to pore formation and death of the pathogen2. Can also be directed specifically to pathogensa. "Lectin" pathway: Mannose binding lectin (MBL) binds pathogen-specific carbs- Complement proteins are then able to bind MBL and start pore formationb. "Classical" pathway: Complement can also be directed specifically to the surface of a microbe by binding to antibody molecules already bound to the pathogen surfaceV. Immune ProtectionA. Phagocytic cells such as macrophages and dendritic cells bind and internalize pathogens both non-specifically, and by using carb and antibody binding functions1. Bacteria are engulfed and killed by process of phagocytosisa. Endobytic vesicles containing bacteria are fused with lysosomes to form phagolysosomesb. Phagolysosome environment:- Acidic pH- Anti-bacterial enzymes (ex. proteases)- Damaging reactive oxygen and reactive nitrogen speciesB. Immune cells have receptors that bind common pathogen-specific structures like lipopolysaccharide (LPS)1. Binding to these structures activates phagocytes - they increase phagocytic function and produce inflammatory cytokines like tumor necrosis factor (TNF)C. Macrophages induce inflammatory responses through cytokine release1. Local blood vessels dilate, become permeable, and express adhesion molecules a. Plasma components enter the tissue and migrating immune cells (leukocytes) bind the vessel wall (endothelium), then exit into the site of infectionD. Neutrophils and Natural Killer cells are innate immune cells that are recruited from the blood to the site of infection1. Neurtrophils are highly phagocytic cells recruited to the site of inflammation where their phagocytic function is activateda. Mature neutrophils are short lived (about 2 days)2. NK cells recognize changes in surface of pathogen infected cells and kill them by releasing cytolytic