CELLULAR MORPHOLOGY Coccus, Bacillus, Spirillum Coccobacillus (football shaped) Fusiform CELLULAR ARRANGEMENT AND NUMBER Strepto (Chain of 7+) Staphylo (cluster) Mono (singular) Diplo (pair, e.g. Streptococcus pneumonia or Nisseria gonorrhea) Trio (triplet) Tetrado (quartet) COLONIAL MORPHOLOGY Mucoid, punctifoid, irregular, color (pigments in cytochromes) 1 IMMUNOLOGY: Host defense for pathogenic bacteria INNATE Constitutive (always on) ACQUIRED (Adaptive) Inducible (arises in response to organisms) Non-specific (blind to particular organism) Specific (responds specifically to the organism) Anamnesic (has memory) Delayed response time Less effective discrim. Required when innate fails Amnesic (no memory) Swift response time Effectively discriminates between self/non-self First line of defense Innate Inflammatory response: Recruits more cells from local blood vessels Induces clotting downstream to prevent spread 2 ROUTES OF INFECTION Mucosal Surfaces: Airway, GI, urogenital tracts (easier to infect) External Epithelia: External surface, wounds & abrasions, insect bites COMPONENTS OF IMMUNITY 1) Complement (made of proteins, circulates in plasma): Innate immunity 2) Humoral Immunity (made of antibodies; immunoglobin) Adaptive. Made up of B Lympohocytes 3) Cell Mediated Immunity (directed by cells, mostly T lymphocytes) Both innate and adaptive 4) Phagocytes (Made up of both innate and acquired phagocytes) CONTROL OF IMMUNE RESPONSE is important. If it goes overboard, your own immune system can kill you in a few hours! * Know what the effectors are of immunity (What is it that effects the mechanism that is directly doing the work?) 3 THE IMMUNE SYSTEM CELLS: (Originate in the bone marrow) 1. Myeloid: tissue based and filled with granules = granulocytes A. GRANULOCYTES 1) Basophils 2) Eosinophils 3) Neutrophils (PMN’s) Short-lived, abundant in blood but not in healthy tissues The major component of pus B. DENDRITIC CELLS C. MONOCYTES: innate functions, but guided by acquired functions (like hardware waiting for software instructions) 1) Macrophages (in submucosa of lung, GI; liver, spleen) They are long-lived, first on site, followed by PMN’s. Derived from monocytes, they engulf and initiate inflammatory response by releasing cytokines and chemokines to bring PMN’s to the site. Also initiate adaptive immune response a) Super-killer macrophages 4 MACROPHAGES AND PMN’S Macrophages and PMN’s have cell-surface receptors that distinguish self from non-self. They bind to the pathogen, surround it, pull it internally into its phagosome (internal vacuole) where its lysosome granules release enzymes, proteins/peptides, and the cell itself also creates acids, NO, O2-, and H2O2 to kill the pathogen. NOTE: Polysaccharide capsules of bacteria are not recognized by phagocyte receptors, so the bacteria cannot be bound by them. Some bacteria inhibit the effect of the phagocytes’ lysosomes, so they can grow inside a macrophage. THREE ROLES OF INFECTION: Delivers additional effector cells to site Microvascular coagulation physically prevents spread to bloodstream Promotes repair of injured tissue 5 2. Erythroid A. RBC’s B. Megakaryocytes Platelets 3. Lymphoid A. Lymphoblasts 1) Bone Marrow a) B Lymphocytes (lymphoblast receives signals and matures in bone marrow) 2) Thymus a) T Lymphocytes (lymphoblast receives signals and matures in thymus) i) CD4 ii) CD8 6 INNATE IMMUNE MECHANISMS 1. Structural (First line of defense) A. Integument (epithelium lines internal and external surfaces) 1) Keratin (dermis and epidermis) 2) NaCl (creates a high osmotic gradient) 3) Sebum (antimicrobial fatty acids) 4) pH (acid / base) 2. Mechanical A. Gravity: Pushes fluids of head, bladder, etc downward toward orifices; prevents entry of organisms. B. Eyelids/ Conjunctiva: sebum, lysosyme, mechanical blinking C. Mucocilliary Elevator: mucus/ cilia move debris out of lungs NOTE: 109 organisms inhaled per deep breath, caught in nares, lung, eyelids Mucus contains glycoproteins (mucins), prevents adherence. 7 3. Biochemical A. Lysosyme and Phospholipase A: (Lysosyme is an enzyme that cleaves the crosslink in peptidoglycan) (Phospholipase A digests phospholipids) - present in tears, saliva, airway secretions, and mucus - harms bacteria, but not humans - pain and tears go together B. Fatty Acids (on skin) C. Acids and bile salts GI tract) D. Enzymes (pepsin in stomach) E. Antibacterial peptides 1) Cryptins made by Panth cells in sm. intestine 2) Surfactant Proteins A & D in lungs Opsonization = To coat bacteria, aiding in phagocytosis 8 4. Genetic: Many infections are species-specific - receptor specificity (if no receptor, no infection) 5. Cellular A. Non-pathogenic bacteria (normal flora) compete for nutrients with pathogens, and secrete antimicrobial substances B. Phagocytes (The effector cells of innate immunity) 1) Dendritic Cells (the “guardians”) 2) Neutrophils (PMN’S) 3) Monocytes a) Macrophages i) Superkiller macrophages All phagocytes except Dendritic cells are controlled by cytokines. Oxidative Killing (NO, O2-, H2O2, and OH-) Non-Oxidative killing (antimicrobial peptides, Phospholipase A, lysosymes) 9 Phagocytes grab bacteria and pull them in. Dendritic cells don’t kill the bacteria; they just take them to the T lymphocytes to report what they’ve found. DENDRITIC CELLS Have Toll-like receptors: TLR 1-10 in humans They are pattern recognition receptors, can recognize signals in pathogen. TLR 2 = peptidoglycan (PG) (in bacteria only) TLR 3 = Viral double-stranded RNA TLR 4 = Lipopolysaccharide (LPS) (in bacteria only) Requires a co-molecule to trigger its signaling: LPS-binding protein in plasma = LBP. CD14 is a coreceptor that functions with LBP to recognize LPS. TLR 6 = Endotoxin TLR 9 = CpG immunostimulatory sequences of DNA (in bacteria only) 10 SIGNAL TRANSDUCTION IN DENDRITES Purpose: to allow DNA to express genes to respond to pathogen 1) The pathogen component binds to the receptor on the Dendritic cell membrane. 2) MyD88 (which underlies the receptor and is within the Dendritic cell) allows an inactive kinase (IRAK)i to become active (IRAK)a. 3) TRAF-6 becomes active and controls two transcription factors: NfKB (promotes transcription of genes) and IKB (inhibits NfKB) 4) NfKB (Transcription factors) enters nucleus of cell 5) NfKB causes mRNA to activate by promoting appropriate cytokine gene transcription (yielding corresponding mRNA) 6) mRNA leaves the nucleus as cytokine mRNA 7) Cytokine mRNA encounters ribosomes and Golgi apparatus, is translated and processed, and cytokines are then packaged, and secreted outside of the cell. * Cytokines are proteins that cause other cells to take action and modulate systems. 11 FUNCTIONS OF DENDRITIC CELLS 1) Sense pathogen components 2) Produce cytokines 3) Phagocytize without killing, takes it to the lymph system to show T cells 12