Immunity - Body Defenses Non-specific Innate Responsive Specific Humoural (Antibodies) Cell mediated Body Defenses The body is constantly in contact with bacteria, fungi, and viruses The body has a variety of defense systems for foreign materials. They are broadly split into: Innate defenses part of the normal structures Nonspecific defense system Mechanisms to protect against a variety of invaders Responds immediately to protect body from foreign materials Specific defense system Specific defense is developed for each type of invader What is in blood? Types of Leukocytes Slide 10.10a Copyright 2003 Pearson Education, Inc. publishing as Benjamin Cummings Granulocytes Granules in their cytoplasm can be stained Include neutrophils, eosinophils, and basophils Figure 10.4 Types of Leukocytes Slide 10.10b Copyright 2003 Pearson Education, Inc. publishing as Benjamin Cummings Agranulocytes Lack visible cytoplasmic granules Include lymphocytes and monocytes Figure 10.4 Granulocytes Slide 10.11a Copyright 2003 Pearson Education, Inc. publishing as Benjamin Cummings Neutrophils Multilobed nucleus with fine granules Act as phagocytes at active sites of infection Found particularly in response to presence of bacteria Eosinophils Large brick-red cytoplasmic granules Found in repsonse to allergies and parasitic worms Neutrophils the eosinophil's granules contain lytic enzymes, but they're much larger than those of neutrophils, Eosinophils Basophils Slide 10.11b Copyright 2003 Pearson Education, Inc. publishing as Benjamin Cummings Have histamine-containing granules Initiate inflammation Agranulocytes Slide Copyright 2003 Pearson Education, Inc. publishing as Benjamin Cummings Lymphocytes Nucleus fills most of the cell Play an important role in the immune response Monocytes Largest of the white blood cells Function as macrophages Important in fighting chronic infection Lymphocytes Overview of the bodys defenses Non-specific defenses Humoral immunity Cell mediated immunity (Specific) Acquired immunity 1.Skin & mucus membrane barriers 2.Resident (normal) microflora 3. Cellular defenses (granulocytes, NK cells) 4. Inflammation 5. Fever B lymphocytes antibodies T-lymphocytes Pathogenesis Adherence to skin or mucosa Infection & Disease Infection: growth of microbes in the host; not necessarily synonymous with disease. Disease: harmful changes to the host; Infectious diseases are caused by microbes or their products such as toxins. Remember there are many other causes of disease Physical barriers to infection Nonspecific Body Defenses Body surface coverings Intact skin Mucous membranes Special immune cells attack all invaders Chemicals produced by the body Surface Membrane Barriers - First Line of Defense (Innate) The skin Physical barrier to foreign materials pH of the skin is acidic to inhibit bacterial growth Sebum is toxic to bacteria Vaginal secretions are very acidic Stomach mucosa Secretes hydrochloric acid Has protein-digesting enzymes Saliva and lacrimal fluid contain lysozyme Mucous traps microogranisms in digestive and respiratory pathways Skin & mucous membrane barriers Defensive Cells Phagocytes (neutrophils and macrophages) Engulfs foreign material into a vacuole Enzymes from lysosomes digest the material Phagocyte Bacteria Lysosome Phagosome Phagolysosome forms when phagosome & lysosome fuse. This results in lysozymes released round bacteria Bacteria is digested * Phagocytosis Pathogen gone A phagocyte Engulfing foreign particles Non-specific cellular defenses Natural killer cells Type of lymphocyte. Complex system of cell surface receptors; Receptors recognize changes on the surfaces of abnormal cells. Stimulated by cytokines (small powerful proteins produced by immune system) Kill tumour cells Kill virus-infected cells Non-specific cellular defenses Natural killer cells Inflammatory Response - Second Line of Defense Triggered when body tissues are injured Produces four cardinal signs Redness Heat Swelling Pain Results in a chain of events leading to protection and healing Functions of the Inflammatory Response Prevents spread of damaging agents Disposes of cell debris and pathogens Sets the stage for repair Inflammation A splinter or infection enters the skin Tissue is damaged Mast cells (immune cells of epithelium & connective tissue) are waiting Blood is flowing through a nearby capillary 2. Mast cells & damaged tissue release inflammatory chemicals: histamine etc Causes vasodilation of arterioles & increased blood flow. Heat & Redness 3. Capillaries become more permeable Swelling deliver additional inflammatory chemicals Bring leucocytes eg phagocytes such as neutrophils (first to arrive) 4. Phagocytes attach to margins of capillaries and the increased permeability allows them to squeeze through between the cells into the damaged tissue. 5. Phagocytes attracted to the site. Phagocytes ingest & digest antigens (phagocytosis) Pain arises from damaged nerve endings, and chemicals released form cells & damaged tissue or bacterial toxins. Slide Steps in the InflammatoryResponse Copyright 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.7 Antimicrobial Chemicals Interferon Secreted proteins of virus-infected cells Bind to healthy cell surfaces to inhibit viruses binding Fever Abnormally high body temperature Hypothalmus heat regulation can be reset by pyrogens (secreted by white blood cells) High temperatures inhibit the release of iron and zinc from liver and spleen needed by bacteria Fever also increases the speed of tissue repair Specific Defense: The Immune System Third Line of Defense Antigen specific recognizes and acts against particular foreign substances Systemic not restricted to the initial infection site Has memory recognizes and mounts a stronger attack on previously encountered pathogens Antigens (the flags that identify the invaders) These are substances that are part of the pathogen and: are recognised as foreign by the host cell trigger an immune response Antigens are recognised by: - immune cells - antibodies So long as they are presented properly Macrophages do this. Immune Cells overview Phagocytes eg macrophages process the antigen on the invader & activate lymphocytes. Lymphocytes primary cells of the specific immune response. types: B Cells - produce antibodies T Cells cellular response Natural Killer Cells non specific Antigen presenters Macrophages engulf & digest foreign particles that have entered the tissues They also activate fever & both the inflammatory response and specific immune responses: act as antigen presenting cells secrete signalling chemicals (cytokines) Antigens (Nonself) Any substance capable of exciting the immune system and provoking an immune response Examples of common antigens Foreign proteins Nucleic acids Large carbohydrates Some lipids Pollen grains Microorganisms Kinds of Specific Lymphocytes T cells Mature in the Thymus Helper T cells (T H ) Initiate & control the response Cytotoxic (killer) T cells (Tc) Kill infected cells & pathogens CELL MEDIATED B cells Mature in the Bone marrow etc Plasma cells Produce antibodies Antibodies Circulate in blood & kill pathogens in blood and outside cells HUMOURAL Types of Immunity Humoral immunity Antibody-mediated immunity Cells produce chemicals for defense Cellular immunity Cell-mediated immunity Immune cells target virus infected cells Self-Proteins (MHC) Animal cells have many surface proteins Immune cells do not attack cells with self proteins Cells from one animals body can trigger an immune response in another animal because they have slightly different markers (proteins) and are identified as foreign Restricts donors for transplants Cells of the Immune system Macrophages Arise from monocytes Become widely distributed in lymphoid organs Lymphocytes Originate in the red bone marrow B lymphocytes mature in the bone marrow T lymphocytes mature in the thymus Immune Cells overview Phagocytes eg macrophages process the antigen on the invader & activate lymphocytes. Lymphocytes primary cells of the specific immune response. types: B Cells - produce antibodies T Cells cellular response Natural Killer Cells non specific Development of B & T cells (lymphocytes) Howstuffworks "How Your Immune System Works" Howstuffworks "How Your Immune System Works" The lymphatic system includes the thymus, spleen, lymph nodes and lymph vessels. The lymphatic system is part of the immune system that helps the body fight off disease. The lymphatic system also works with the cardiovascular system to return fluids that escape from the blood vessels back into the blood stream. Lymph Nodes Located along lymph ducts Remove foreign matter from lymph before it enters the bloodstream Centres for proliferation of immune cells contain macrophages, & maturing T & B cells B cells mature into Plasma cells These cells remain in the nodes and pump out large quantities of antibodies into the circulation Memory B cells stay in the nodes Thymus The Thymus produces mature T lymphocytes (T cells) Contains both immature T cells & phagocytes immature lymphocytes multiply and mature. Mature T cells leave in 2-3 days Production of Antibodies Antigens stimulate B cells to develop into plasma cells & memory cells The plasma cells can only secrete one kind of antibody that is the one against the antigen that it responded to it in the first place Antibodies enter the circulation and interact with these antigens to inactivate them. Memory cells respond quickly to subsequent infections B Lymphocytes Differentiation of Plasma cells and production of antibodies Antigen fragment on surface of B cell 2. Stimulates Helper T cell B cell Helper T cell 3. Releases Cytokines 4. B cells proliferate 1. Antigen attaches to receptor 5. B cells Differentiate Y Y Y Y Y Memory B cell Antibodies Memory B cell Plasma cell B B B B B Humoral Immune Response Copyright 2003 Pearson Education, Inc. publishing as Benjamin Cummings Secondary Response Memory cells are long- lived A second exposure causes a rapid response The secondary response is stronger and longer lasting Antibodies (Immunoglobulins) (Igs) Soluble proteins secreted by B cells (plasma cells) Carried in blood plasma Capable of binding specifically to an antigen Antibody Structure Four amino acid chains linked by bonds Two identical amino acid chains are linked to form the heavy chains The other two identical chains are light chains Specific antigen-binding sites are present Antibody specificity Antibody Classes Antibodies of each class have slightly different roles Five major immunoglobulin classes IgM can fix complement IgA found mainly in mucous IgD important in activation of B cell IgG can cross the placental barrier IgE involved in allergies Antibody classes IgG Cross placenta High conc IgD Low conc IgE Hypersensitivity Anti-parasitic IgA colostrum IgM First antibody Low conc Antibody Function Antibodies inactivate antigens in a number of ways Complement fixation Neutralization Agglutination Precipitation Slide Antibody Function Copyright 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.14 Cellular (Cell-Mediated) Immune Response Macrophages engulf antigens and activate Helper Tcells Helper T cells will respond only to those antigens that label the specific pathogen After antigen binding, the Helper T cells multiply and: Recruit other cells to fight the invaders Interact directly with B cells Activate Cytotoxic T cells which: Specialize in killing infected cells Insert a toxic chemical (perforin) A few of each become memory cells. Cellular (Cell-Mediated) Immune Response Copyright 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.15 Summary of the Immune Response Copyright 2003 Pearson Education, Inc. publishing as Benjamin Cummings Allergies (Hypersensitivity) Abnormal, vigorous immune responses Types of allergies Immediate hypersensitivity Triggered by release of histamine from IgE binding to mast cells Reactions begin within seconds of contact with allergen Anaphylactic shock dangerous, systemic response Delayed hypersensitivity Triggered by the release of chemicals from activated helper T cells Symptoms usually appear 13 days after contact with antigen Passively acquired immunity Natural Transfer of active immunity: In contrast to active immunity, passive immunity is the transfer of immunity from one individual to another. Dam to offspring: The most important natural occurrence of passive immunity is that from dam to offspring. This occurs either via transplacental transfer or via milk, especially colostrum. Powerful but temporary: Passively acquired immunity can be very powerful in fighting disease. The effects of passive immunity, however, are both temporary and cannot be restored without additional passive infusion. Artificially acquired immunity The administration of antiserum is an example of artificially acquired passive immunity. Vaccination, on the other hand, is an example of artificially acquired active immunity.