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The Fish Immune System What does the immune system do? War Fish vs. Everything Enemy Pathogens Front Lines Self The good bits that are supposed to be there Foreign The bad stuff: bacteria, fungi, viruses, cancer Planes, Ships Tanks, and Ammunition • (Planes, Ships, Tanks) White blood cells – – – – Lymphocytes Neutrophils Macrophages Eosinophils • (Mines and Booby Traps) Blood Proteins – – – – Complement Lysozyme Antibodies Many more Inside the Liver “Gee Adjwoa, I really like the bling on your cell phone” Complement A defensive protein made by the liver and secreted into the blood. Primary target: Gram negative bacteria. Gram Neg Gram Pos Membrane bi-layer Peptidoglycan layer Complement molecules begin to assemble a complex on the membrane of Gram (-) bacteria Complement forms a channel through the cell wall Complement Recognizes Gram (-) bacteria Lysozyme Lysozyme • Dissolves Gram (+) bacterial cell walls • Found in – Blood – Mucus – Eggs Other Mines…. • • • • Proteases: Damage pathogens Protease inhibitors: Block invasion Histones: Antibacterial Iron-sequestering proteins: Starve bacteria. • Lactoferrin disrupts outer membrane on Gram negs (helps lysozyme) • C-reactive protein: Recognizes bacteria, triggers complement Mines • Blood Proteins • Always there and ready • Work in complexes • Identify foreigners • Destroy or disable Lymphocyte Antibodies Antibodies: Blood proteins that bind to foreigners. Made by lymphocytes Antibody Anatomy Variable Binding Region Antibody Molecule Antibodies bind all over a Rhabdovirus and block it from infecting a cell. Antibodies recognize foreign antigens on an “ich” parasite and mark it for destruction. Antibodies Designate Targets Location of the Thymus in a Grass Carp Life and Death in the Thymus “Lymphocyte Must Die” Thymocyte Self Antigen Antigen More Identical B-Cells Memory Cell B-Cell Plasma cell Memory cells: The Lymphocyte Barracks T-Lymphocyte Viral Proteins (antigens) Cell Killing Chemicals from the T-cell Virus-infected cell Antigen T-Cell More Identical T-Cells Memory Cell Memory cells: The Lymphocyte Barracks B-cells: Secrete antibodies that bind to antigens on foreign things T-cells: Attach to and kill infected cells with foreign antigens Lymphology • Self reacting lymphocytes weeded out by thymus • Lymphocytes proven useful proliferate to make more highly trained fighter pilots (B&T), and… • Copies of useful lymphocytes are put in the barracks in case the same enemy attacks again. Macrophages “Big Eaters" Macrophage Macrophages as Big Eaters Macrophage Diets Bacterial Cell Walls Cell with Compliment Cells with Antibody Flags Vacuoles containing bleach (brown) and peroxide (green) fuse with a vacuole containing a live bacterium More Tricks: Macrophages Searching out Foreigners A roving macrophage detects a parasite trying to hide among a layer of fish cells. Normal cells with MHC “locks” Parasite with fake lock Macrophages Even Run a School for Lymphocytes 2 1 Macrophage 3 Macrophage eating a bacterium 4 Macrophage digesting a bacterium Macrophage using bacterial bits to educate lymphocytes. Macrophage Functions • Eat and kill bad cells • Check cell codes (MHC) • Run a lymphocyte school Eosinophils Eosinophils Eosinophils The worm has been “flagged” by antibody molecules The eosinophil dumps parasitekilling chemicals on a parasitic worm somewhere inside of a fish. Neutrophils Neutrophils Neutrophils •Dump toxins on flagged cells (chemical weapons!) Neutrophils Mediate immune responses Other Tanks and Planes •Neutrophils: Chemical warfare, generals •Eosinophils: Chemical warfare on parasites Natural Killer Cells (NK) Foreign cells Virus infected cells Protozoa Armed Checkpoints The Spleen