Transcript 04-28-06
IB-202-17-06 The Immune System Chpt 43 (all). • Overview: Reconnaissance, Recognition, and Response • An animal must defend itself from the many dangerous pathogens it may encounter in the environment (pathogenic microbes and parasites) • Two major kinds of defense have evolved that counter these threats ---innate immunity and acquired immunity. • New born that lack an immune system have a short life expectancy (Usually die soon after the maternally derived antibodies fade away). Innate and Acquired Immunity – Innate immunity is present before any exposure to pathogens and is effective from the time of birth. It involves nonspecific responses to pathogens. Here is an example of a white blood cell, a macrophage (big eater) ingesting a pathogenic yeast cell Yeast cell! Figure 43.1 3m • The cellular elements of mammalian blood Cellular elements 45% Cell type Number per L (mm3) of blood Erythrocytes (red blood cells) Separated blood elements White cells can be seen as a buffy layer on the surface of the compacted red blood cells after centrifugation. 60% are neutrophil phagocytes. Figure 42.15 5–6 million Leukocytes (white blood cells) 5,000–10,000 Functions Transport oxygen and help transport carbon dioxide Defense and immunity Lymphocyte Basophil Eosinophil Neutrophil Monocyte Platelets 250,000 400,000 Blood clotting Circulating monocytes turn into large macrophages that are about 50um in diameter. Reside in liver, spleen lymph nodes. Live for days! Acquired immunity • Also called adaptive immunity – Develops only after exposure to inducing agents such as microbes, toxins, or other foreign substances (proteins, cell walls of bacteria etc). – Involves a very specific response to pathogens – (We take advantage of adaptive immunity when we have our children immunized) Over view of body defenses! INNATE IMMUNITY Rapid responses to a broad range of microbes External defenses Invading microbes (pathogens) Figure 43.2 ACQUIRED IMMUNITY Slower responses to specific microbes Internal defenses Skin Phagocytic cells Mucous membranes Antimicrobial proteins Secretions Inflammatory response Natural killer cells With cystic fibrosis the mucous from the bronchi is so thick that it is not easily expelled and hence becomes infected with bacteria. Humoral response (antibodies) Cell-mediated response (cytotoxic lymphocytes) External Defenses • Intact skin and mucous membranes – Form physical barriers that bar the entry of microorganisms and viruses • Certain cells of the mucous membranes produce mucus – A viscous fluid that traps microbes and other particles • In the trachea, ciliated epithelial cells – Sweep mucus and any entrapped microbes upward, preventing the microbes from entering the lungs. We swallow the mucus and it along with the microbes is digested in the stomach. 10m With cystic fibrosis the mucous from the bronchi is so thick that it is not easily expelled and hence becomes infected with bacteria.Figure 43.3 • Secretions of the skin and mucous membranes – Provide an environment that is often hostile to microbes • Secretions from the skin – Give the skin a pH between 3 and 5, which is acidic enough to prevent colonization of many microbes – Also include proteins such as lysozyme, an enzyme that digests the cell walls of many bacteria. Your tears are full of lysozyme, saliva and some mucous secretions. Innate immunity is first line of defense if skin is broken! • Concept 43.1: Innate immunity provides broad defenses against infection • Internal cellular defenses depend mainly on phagocytosis of microbes. • Phagocytes are types of white blood cells that – Ingest invading microorganisms – Initiate the inflammatory response Phagocytic Cells • Phagocytes attach to their prey via surface receptors – And engulf them, forming a vacuole that fuses with a lysosome 1 Pseudopodia surround microbes. Microbes 2 Microbes are engulfed into cell. MACROPHAGE 3 Vacuole containing microbes forms. Vacuole Toxic compounds may be reactive oxygen species such as hydrogen peroxide. Figure 43.4 Lysosome containing enzymes 4 Vacuole and lysosome fuse. 5 Toxic compounds and lysosomal enzymes destroy microbes. 6 Microbial debris is released by exocytosis. • Monocytes circulate in blood for only a few days and then settle in a tissue and develop into a macrophage. Spleen, liver and lymph nodes. • The lymphatic system – Plays an active role in defending the body from pathogens 1 Interstitial fluid bathing the tissues, along with the white blood cells in it, continually enters lymphatic capillaries. Interstitial fluid Adenoid Lymphatic capillary 2 Fluid inside the lymphatic capillaries, called lymph, flows through lymphatic vessels throughout the body. Tonsil 4 Lymphatic vessels return lymph to the blood via two large ducts that drain into veins near the shoulders. Lymph nodes Blood capillary Spleen Peyer’s patches (small intestine) Tissue cells Lymphatic vessel Appendix Lymphatic vessels Figure 43.5 Lymph node Masses of lymphocytes and macrophages 3 Within lymph nodes, microbes and foreign particles present in the circulating lymph encounter macrophages, dendritic cells, and lymphocytes, which carry out various defensive actions. Antimicrobial Proteins in the blood. • Numerous proteins circulate in the blood whose function is to bind directly to microbes and punch holes in their cell membrane. About 30 proteins are involved and they work synergistically to destroy microbes. • Circulating interferons provide innate defense against viruses and help activate macrophages Inflammatory Response • In local inflammation, histamine and other chemicals released from injured mast cells – dilate blood vessels making them leaky causing more fluid, more phagocytes, and antimicrobial proteins to enter the interstitial spaces. This causes the injured area to feel hot and appear red and swollen. Inflammation • Major events in the local inflammatory response Blood clot Pin Pathogen Macrophage Chemical signals Phagocytic cells Capillary Blood clotting elements Phagocytosis Red blood cell 1 Chemical signals released by activated macrophages and mast cells at the injury site cause nearby capillaries to widen and become more permeable. Figure 43.6 2 Fluid, antimicrobial proteins, and clotting elements move from the blood to the site. Clotting begins. 3 Chemokines released by various kinds of cells attract more phagocytic cells from the blood to the injury site. 4 Neutrophils and macrophages phagocytose pathogens and cell debris at the site, and the tissue heals. Natural Killer Cells • Natural killer (NK) cells – Patrol the body and attack virus-infected body cells and cancer cells – Trigger apoptosis in the cells they attack Invertebrate Immune Mechanisms • Many invertebrates defend themselves from infection – By many of the same mechanisms in the vertebrate innate response • Concept 43.2: In acquired immunity, lymphocytes provide specific defenses against infection • Acquired immunity – Is the body’s second major kind of defense – Involves the activity of lymphocytes • An antigen is any foreign molecule – That is specifically recognized by lymphocytes and elicits a response from them • A lymphocyte actually recognizes and binds – To just a small, accessible portion of the antigen called an epitope Antigenbinding sites Antibody A Protein with epitopes being a few amino acids side chains Antigen Antibody B Antibody C Figure 43.7 Epitopes (antigenic determinants)