Chapter 22: The Lymphatic System and Immunity

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1 Bio40C schedule Lecture: Immune system Lecture exam 2 postponed to Tu Feb 23 covers Ch 22, 26, 27 Multiple choice and short answer Study guides posted on website Extra credit total of 15 pts Work sheets for immune system - 2 pts each Due on day of exam (Feb 23) Critical thinking questions at end of chapters 5 pts/chapter Due anytime before Mar 11 Bio40C revised schedule Date Feb 16/18 Feb 23 Feb 25 Mar 2/4 Lecture Ch 22 Immune system Exam 2 Ch18 Endocrine sys Ch18 Endocrine sys Lab Ag-Ab reactions Review Quiz 3 Immunity Ex 27 Endocrine sys Presentations Immune System Presentations Date: Mar 2 or 4 Presentation Briefly describe the pathogen and disease Explain how the immune system responds Nonspecific defenses Cell-mediated immune response Antibody-mediated immune response Summary: Flowchart that shows the nonspecific and specific defense mechanisms involved Turn in Topic and names of team members Flowchart 4 reliable references URLs of Internet sources must end in.edu,.gov or.org Chapter 22: The Lymphatic System and Immunity Introduction Immune system the body s defenses against pathogens that produce disease 2 types of immunity Nonspecific immune mechanisms (Innate immunity) Provide general protection against invasion by a wide range of pathogens Host responds to pathogens in a generic manner Specific immune mechanisms (Adaptive immunity) Cell-mediated immunity (T cells) Antibody-mediated immunity (B cells) Overview of the body s defenses Innate immunity Adaptive immunity Three cooperative lines of defense protect us from pathogens

2 Summary of Nonspecific Defenses When external barriers fail The body s second line of defense First line of defense: external barriers Skin Mucous membranes Secretions - inhibit growth of microbes Lysozyme, gastric acid, sebum Macrophage Phagocytosis of E. coli Macrophages continually search for foreign (nonself) antigenic molecules, viruses, or microbes. When found, the macrophages engulfs and destroys them. Small fragments of the antigen are displayed on the outer surface of the macrophage plasma membrane. Inflammation: a second-line defense When tissue is damaged, the body responds with a coordinated set of nonspecific defenses called the inflammatory response Neutrophils and macrophages surround and kill the pathogens (phagocytosis) Inflammation is usually recognized by its four hallmark symptoms Redness, heat, swelling, pain Mosquito bites how does the immune system respond? Mosquitoes inject saliva which contains an anticoagulant and other substances foreign antigens How does the immune system respond? Mosquito bites how does the immune system respond? Nonspecific defenses 1st line of defense external barriers bypassed Internal defenses? Lymphoctes: macrophages, NK cells Defensive proteins: interferons (attack viruses), complement proteins (lyse invading cells) The inflammatory response

3 The inflammatory response: three stages 1. Vasodilation and increased permeability of blood vessels 2. Movement of phagocytes (neutrophils and macrophages) from the blood into interstitial fluid 3. Tissue repair The inflammatory response: three stages Vasodilation Histamine and other chemical signals cause blood vessels to dilate and leak fluid into the wounded tissue swelling Swelling helps heal tissues by diluting toxins Chemical signals also attract phagocytes (neutrophils and macrophages) into interstitial fluid engulf foreign antigens Tissue repair Specific Defenses The immune system a large collection of cells that work together to respond to infection. Attacks specific kinds of invading microbes and cancer cells Bacteria, toxins, viruses, foreign tissues Outcome: the body is able to defend itself against specific invading agents Specific defenses Two properties distinguish specific from nonspecific defenses Specificity for particular foreign molecules (antigens) Memory for previously encountered antigens So that a 2nd exposure prompts a rapid and strong response Vocabulary Specific defenses: the basics Antigens (Ag) Are foreign substances that elicit an immune response. Antibodies (Ab) Are proteins found in blood plasma that recognize a particular antigen and help counter its effects. Depend on the action of B and T cells T cells Differentiate into helper T cells or cytotoxic T cells Directed against intracellular pathogens, some cancer cells and tissue transplants Cell-mediated immunity B cells Secrete antibodies Directed against extracellular pathogens (bacteria, viruses, toxins) Antibody-mediated immunity

4 Maturation of T cells and B cells Both develop from stem cells in bone marrow B cells complete their development in bone marrow T cells develop from pre-t cells that migrate to the thymus B cells and T cells are named based on where they mature Recognizing the invader Antigen receptors on the surface of a lymphocyte can bind to only one specific type of antigen Mature B and T cells can recognize a specific antigen and mount an immune response to it One cell may recognize an antigen on the mumps virus, another an antigen on an E. coli bacterium Antibody-mediated immunity Specific defenses Cell-mediated immunity Antibody-mediated immunity The body contains millions of B cells, each able to respond to a specific antigen Steps in antibody-mediated immunity Antigen detection Activation of B cells Antibody production Activated B cells undergo clonal selection forming Plasma cells that secrete antibodies Memory cells Antibodies enter the circulation and neutralize the antigen Antigen detection and activation of B cells Antigen binds to B-cell receptors Some of antigen is processed broken down into peptide fragments in B cell, combined with the MHC-II self-antigen, and moved to surface of B cell Helper T cells secrete interleukin-2 and other cytokines that activate the B cell Activation and clonal selection of B cells Image: Max Planck Institute of Neurobiology B cell #2 recognizes a target antigen This B cell proliferates by clonal selection, differentiates into plasma cells and produces numerous antibodies B cells that don t recognize the target don t produce antibodies. Memory cells ensure a quick response in case the target reappears at a later time. After an infection has passed, plasma cells undergo apoptosis (programmed cell death) leaving the memory cells

5 B cell activation Immune System - B cell Clonal Selection 4:42 Clonal selection in B cells B cells need to be activated by cytokines (chemical messengers produced by helper T cells) A "resting" B cell produces very little antibody When stimulated by cytokines (IL4 and IL6), it multiplies, and matures into a plasma cell. A plasma cell is an activated B cell, secreting lots of antibodies into the blood Activated B cells Plasma cells What are antibodies? Proteins that bind to foreign antigens and cells Combine specifically with the antigen that triggered their production Mark them for destruction by phagocytes Belong to group of glycoproteins called immunoglobulins (Igs) Structure of Antibodies Y-shaped proteins 4 protein chains connected by disulfide bonds 2 heavy chains 2 light chains The trunk of the Y is a constant region that determines the class of the antibody. The end of the arms are the variable regions where antigens bind. a. antigen shape of antigen fits shape of binding site Copyright 2009, John Computer Wiley & model of an antibody Sons, b. Inc. b: Courtesy Dr. Arthur J. Olson, Scripps Institute V V C antigen-binding sites C C V C V heavy chain antigen binds to binding site light chain C = constant V = variable Antibody/antigen interaction The 5 classes of antibodies Ab Ag The antigen binding site is highlighted in purple. The antigen is green. The part of the antigen in direct contact with the antibody is called the epitope, or antigenic determinant. Antibody immune response 0:53 IgG antibodies are the most abundant (~80% of all antibodies) Functions: enhance phagocytosis of viruses and bacteria neutralize toxins trigger the complement system

6 Functions of antibodies Recognize and bind to antigens Inactivate the antigen Activate the complement system when activated, the proteins complement or enhance immune, allergic, and inflammatory reactions Antibodies agglutinate and precipitate antigens Antibodies enhance phagocytosis Antibodies inactivate viruses Mosquito bites how does the immune system respond? Mosquitoes inject saliva which contains an anticoagulant and other substances foreign antigens Is there a role for antibody-mediated immunity? Antibodies neutralize antigens Foreign antigens enter bloodstream

7 Role of the complement system in immunity Complement enhances phagocytosis Complement system made up of over 30 proteins found circulating in blood plasma These proteins complement immune responses and help clear antigens from the body Complement proteins destroy microbes Cause phagocytosis, cytolysis and inflammation PHAGOCYTOSIS Enhances phagocytosis by coating with C3b COMPLEMENT PROTEINS C3 1 2 C3b C3a C5 3 C5b C5a 4 C6 C7 C8 C9 Complement proteins act in a cascade one reaction triggers another reaction. Amplifies the response C3b protein enhances phagocytosis by coating the microbe Complement lyses microbial cells PHAGOCYTOSIS Enhances phagocytosis by coating with C3b Channel Microbial plasma membrane COMPLEMENT PROTEINS C3 Complement proteins join together 1 and form a cylinder-shaped 2 C3b C3a membrane attack complex 4 C7 C5 3 C5b C5a C6 C8 C9 C5b C6 C7 C8 C9 Complement proteins form membrane channel CELL LYSIS microbial cell Copyright 2009, John bursts Wiley open& Inserts into the plasma membrane Lyses the cell Complement enhances inflammation PHAGOCYTOSIS Enhances phagocytosis by coating with C3b Channel Microbial plasma membrane COMPLEMENT PROTEINS 2 4 C7 1 C3b C3 C5 3 C5b C5a C6 C3a C8 C9 C5b C6 C7 C8 C9 Histamine Mast cell C5a attracts phagocytes CELL LYSIS (chemotaxis) microbial cell bursts Copyright open 2009, John Wiley & INFLAMMATION Increased blood vessel permeability Chemotactic attraction of phagocytes C3a and C5a bind to mast cells and cause them to release histamine Increased blood vessel permeability How does the body respond to a bacterial infection? Immunologic memory The first responders Phagocytes NK cells Inflammation Complement Specific responses B cells produce antibodies to epitopes on bacteria Helper T cells Cytotoxic T cells attack invading pathogens Memory for specific antigens that have triggered immune responses in the past How does this happen? Long-lived memory B and memory T cells remain after a primary response to an antigen

8 Immunologic memory Primary immune response: the 1st exposure to an antigen takes several days to produce immune cells by clonal selection peak levels occur at 1-2 weeks Clonal selection also produces memory cells that can last in the lymph nodes for decades Secondary response a faster, stronger response Due to the presence of long-lived Abs and thousands of memory B and T cells Immunologic memory the basis for vaccinations The secondary response provides protection should the same microbe enter the body again. There is rapid proliferation of memory cells, resulting in a far greater antibody titer than during a primary response Immunizations trigger active immunity, stimulating the body to defend itself. Test your understanding Self-recognition and self-tolerance What makes a secondary immune response faster than a primary immune response? It takes a week or two for a clone of effector cells to be formed during the primary response. In a secondary response, preexisting memory cells can respond more quickly. To function properly, your T cells must have 2 traits: They must be able to recognize self-mhc antigens Self-recognition But do not react to other self-proteins Self-tolerance Self-recognition develops by positive selection Pre-T cells that can t recognize your own MHC undergo apoptosis Self-tolerance occurs through negative selection T and B cells that recognize self-proteins are eliminated Autoimmune diseases Loss of self-tolerance leads to development of autoimmune diseases The immune system attacks the person s own tissues e.g. in type 1 diabetes, T cells attack the insulin-producing pancreatic beta cells Multiple sclerosis (MS) - T cells attack myelin sheaths around axons of neurons Graph or organ rejection Graph or organ rejection Immune system recognizes the proteins in the transplanted organ as foreign and mounts an immune response Depends on MHC antigens Tissue typing (histocompatibility testing) Match MHC proteins of donor and recipient Why do organ transplant recipients receive immunosuppressive drugs?

9 Allergies Allergies Immune Disorders If the interplay of immune cells malfunctions, problems in the immune response can result. Are abnormal sensitivities to antigens in the environment. Allergens Are antigens that cause allergies. The symptoms of an allergy result from a two-stage reaction sequence The symptoms of an allergy result from a two-stage reaction sequence Stage 1 Stage 1 Stage 1 Stage 2 Allergen binds to B cells with complementary receptors B cells proliferate by clonal selection and secrete large amounts of antibodies to that allergen Some of the antibodies attach to receptor proteins on mast cells (cells that produce histamine and other chemicals that trigger the inflammatory response) Anaphylactic shock Homework A life-threatening allergic reaction Some people are extremely sensitive to allergens peanuts, shellfish, bee sting toxin Contact with these allergens causes a sudden release of histamine and other inflammatory chemicals Blood vessels dilate abruptly circulatory collapse bronchial and tracheal swelling suffocation Causes 1,500 deaths per year in the U.S. Can be counteracted with injections of epinephrine. How are cell-mediated and antibodymediated immune responses similar and different?

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