The Immune Response • Inside your body there is an amazing protection mechanism called the immune system. It is designed to defend you against millions of bacteria, microbes, viruses, toxins and parasites that would love to invade your body Functions of the immune system • Primary function: defense; resist pathogens, foreign bodies and abnormal cells • Immunity acquired by: – natural infection – vaccination • When it fails: – congenital immunodeficiency diseases – immunocompromise – DEATH Pathogen: a disease causing organism Pathogens 1) 2) 3) 4) 5) Bacteria Viruses Protozoans Fungi Parasitic worms E coli bacteria Bacillus anthracis Bacteria vs. Viruses • First organisms on earth • Most species on earth • Living cells • Prokaryotic (simpler: no nucleus, circular DNA) • A virus is a different breed altogether. • A virus is not really alive. • A virus particle is nothing but a fragment of DNA in a protective coat. • The virus comes in contact with a cell, attaches itself to the cell wall and injects its DNA (and perhaps a few enzymes) into the cell. • The DNA uses the machinery inside the living cell to reproduce new virus particles. Eventually the hijacked cell dies and bursts, freeing the new virus particles; or the viral particles may bud off of the cell so it remains alive. In either case, the cell is a factory for the virus. The Lytic Cycle Bacterial antibiotic resistance How does it happen? 1. Spontaneous mutation Bacterial antibiotic resistance How does it happen? 1. Spontaneous mutation 2 Plasmid transfer Bacterial antibiotic resistance How does it happen? 1. Spontaneous mutation 2. Plasmid transfer 3. Sex Types of WBCs Can be classified based on the appearance of granules when viewed under the light microscope. 1. Granulocytes 1 • – Contain visible granules. Includes: • • • 2. Basophils Eosinophils Neutrophils Agranulocytes – Do not contain visible granules. Includes: • • Lymphocytes Monocytes 2 WBC Circulation and Movement • Use the bloodstream mainly to travel from organ to organ or to quickly go to areas of invasion/injury. • Characteristics of circulating WBCs: – Capable of amoeboid movement • What role might this play in WBC function? – They can migrate out of the bloodstream by squeezing thru endothelial cells (this process is called diapedesis) – They are attracted to specific chemical stimuli. This is known as positive chemotaxis and allows WBCs to converge on pathogens and damaged tissues Agranulocytes Lymphocytes • 20-30% of circulating leukocytes • Slightly larger than RBCs. In blood smears, you typically only see a thin halo of cytoplasm around a relatively large nucleus. • Continuously migrate from the bloodstream thru peripheral tissues and back into the bloodstream. • Circulating lymphocytes are only a minute fraction of the total # in the body. Most are in other connective tissues and in lymphatic organs. • Circulating blood contains 3 classes: – T cells: defend against foreign cells and tissues and coordinate the immune response – B cells: produce and distribute antibodies that attack foreign materials Agranulocytes Monocytes • 2-8% of circulating WBCs • Almost twice as big as an RBC • Nucleus is large and tends to be oval or kidney-shaped • Individual monocytes use the bloodstream as a highway, staying in circulation for only about 24hrs before entering peripheral tissues to become a tissue macrophage, an aggressive phagocyte. Granulocytes Basophils • >1% of circulating leukocytes • Smaller than neutrophils and eosinophils, only about 8-10µm in diameter. • Contain granules that appear deep purple or blue • Basophils migrate to injury sites and discharge the contents of their granules – histamine (a vasodilator and increaser of capillary permeability) and heparin (an anticoagulant). This enhances the local inflammation initiated by mast cells and attracts other WBCs Granulocytes Eosinophils • 2-4% of circulating WBCs • Similar in size to neutrophils but have reddish-orange staining granules (Eos is the Greek goddess of dawn) and a bilobed nucleus. • Move into tissues after several hours and survive from minutes to days. • They will phagocytize antibody-coated bacteria, protozoa, and cellular debris, but their main method of attack is the exocytosis of toxic compounds onto the surface of their target. • Important defenders against large, multicellular parasites such as flukes or parasitic worms. They in # dramatically during a parasitic infection. • Also sensitive to allergens and in # during allergic reactions as well. Granulocytes Neutrophils • 50-70% of circulating WBCs • Cytoplasm is packed with pale (“neutral colored”) granules that contain bactericidal compounds • Mature neutrophils have a segmented nucleus. They are a.k.a polymorphonuclear leukocytes. • About 12µm in diameter. • Highly mobile and generally the first WBCs to arrive at an injury site. • Specialize in attacking and digesting bacteria that have been “marked” for destruction. • Survive in the bloodstream for only about 10hrs Types of acquired immunity • Active immunity • stimulated by immunizations (infection or vaccination) • immune response plays an active role in the generation of response • takes time for it to be generated • memory; next time, response will be faster Types of acquired immunity • Passive immunity • passive transfer of antibodies or cells • no active effort in the part of the immune response • example: antibodies against venoms • works fast • no memory Types of acquired immunity • Humoral immunity • mediated by antibodies produced by plasma cells (B cells) • can be transferred • http://www.msjensen.gen.umn.edu/webanatomy/wa_lymphatic_immunology/wa_lymph_antibody_mov.html • Cellular immunity • mediated by T cells • T cells produce cytokines which activate other cells such as macrophages to effectively deal with antigen • http://www.msjensen.gen.umn.edu/webanatomy/wa_lymphatic_immunology/wa_lymph_cytotox_mov.html Primary and secondary immune response • Primary • after antigen recognition, there is lag phase of 35 days -activation phase • first antibody to be produced is IgM • IgG is produced next • levels of antibody peak between days 20-30 • antibody levels decrease, antigen is cleared Primary and secondary immune response • Secondary • immune response is quicker • antibodies peak 2-5 days (activation phase is short) • higher magnitude response • longer duration • predominantly IgG Features of the specific immune system • Self-regulation • decreases with time because of antigen disappearance • Discrimination of self-non-self • response to FOREIGN antigens • remains unresponsive to self antigens via TOLERANCE; breakdown of tolerance leads to autoimmune diseases Major Histocompatability Complex Protein markers that occur on surface of all body cells Interact with cytotoxic T cells Different for individual--only the same in identical twins Used to distinguish self from nonself This ability to distinguish self happens early in life by T-cell in the Thymus This is the reason organ donors have to closely match recipients MHC Complex How do diseases act as agents that promote natural selection? • Influenza of 1918--can be compared to the plague in terms of its devastation • Changed WWI and killed more than the war Population of NY city with respect to immunity to the 1918 flu 1890’s Natural immunity to the 1918 flu No natural immunity to the 1918 flu Population of NY city with respect to immunity to the 1918 flu 1890’s 1918 Flu Survivors of 1918 flu Their children Population of NY city with respect to immunity to the 1918 flu (assuming no immigration) 1890’s 1990’s