Chapter 22: The Lymphatic System and Immunity

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1 Bio40C schedule Lecture Immune system Lab Quiz 2 this week; bring a scantron! Study guide on my website (see lab assignments) Extra credit Critical thinking questions at end of chapters 5 pts/chapter Due anytime before Mar 11 Chapter 22: The Lymphatic System and Immunity Introduction Immune system the body s defenses against pathogens that produce disease Vessels and structures of the immune system 2 types of immunity Nonspecific immune mechanisms (Innate immunity) Provide general protection against invasion by a wide range of pathogens Innate present at birth Specific immune mechanisms (Adaptive immunity) Specific lymphocytes combat particular pathogens Overview of the body s defenses Innate immunity Adaptive immunity Three cooperative lines of defense protect us from pathogens When external barriers fail The body s second line of defense Specific Defenses or Adaptive immunity The immune system Consists of 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 1

2 Specific defense mechanisms Two properties distinguish nonspecific and specific defenses Specificity for particular foreign molecules () Memory for previously encountered So that a 2nd exposure prompts a rapid and strong response Vocabulary 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. Specific immune mechanisms: the basics Depend on the action of B and T cells Basics: Maturation of T cells and B cells T cell and B cell receptors Antigen recognition Clonal selection Adaptive immunity specific defenses omit Help protect us against specific pathogens when nonspecific defenses fail Help protect us against cancer Depend on the action of B and T cells Major players in the immune system Maturation of T cells and B cells Lymphocytes White blood cells that produce the immune response Two kinds of lymphocytes B cells Secrete antibodies Directed against extracellular pathogens (bacteria and viruses) T cells Differentiate into helper T cells or cytotoxic T cells Directed against intracellular pathogens, some cancer cells and tissue transplants 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 2

3 Maturation of B cells and T cells During maturation, T cells and B cells become immunocompetent and acquire distinctive surface proteins Some function as antigen receptors, proteins that recognize specific Others are specific cell surface proteins (markers) Helper T cells (CD4 protein) Cytotoxic T cells (CD8 protein) Types of Adaptive Immunity Cell-mediated immunity Destruction of by T cells Particularly effective against intracellular pathogens, some cancer cells and foreign tissue transplants CMI always involves cells attacking cells Antibody-mediated immunity Destruction of by antibodies B cells make antibodies (Abs) Antibodies recognize extracellular pathogens, primarily viruses, bacteria or fungi Helper T cells aid in both types of immunity 2 types of immunity work together Recognizing the invader Antigens foreign substances 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 Many B and T cells with different antigen receptors develop in each person, but only a tiny fraction will ever be used. Antigens have 2 characteristics Immunogenic able to provoke immune response Reactive antigen able to react specifically with antibodies it provoked Antigens are large, complex molecules Entire microbes may act as Typically, small parts of antigen molecules (epitopes or antigenic determinants) trigger immune responses Responding to the invader In most cases, when a pathogen enters the body there is only a small group of B and T cells with the correct antigen receptors to respond But there are many copies of the antigen (or the pathogen) Lymphocytes proliferate and differentiate form a population of identical cells, called a clone, that recognize the same antigen Process is called clonal selection Clonal selection Process by which immune cells proliferate and differentiate in response to a specific antigen Clone population of identical cells that recognize the same antigen Clonal selection thousands of lymphocytes that respond to the antigen 3

4 Clonal selection in B cells Clonal selection Two types of cells result from clonal selection: Effector cells do the work to destroy the antigen Include helper T cells, cytotoxic T cells, plasma cells die after immune response Memory cells respond to 2nd invasion by proliferating and differentiating into effector cells long life spans When an antigen gets past the non-specific defenses Three routes into lymphatic tissue Antigens that enter the blood stream are trapped as they flow through the spleen Antigens that penetrate the skin enter lymphatic vessels and lodge in lymph nodes Antigens that penetrate mucous membranes are trapped by mucosa-associated lymphatic tissue (MALT) Diversity of antigen receptors Human immune system able to recognize and bind to at least a billion different epitopes Due to equally large diversity of antigen receptors Results from genetic recombination shuffling and rearranging a few hundred versions of several small gene segments Specificity of antigen receptors Major Histocompatibility Complex (MHC) Self- located in the plasma membrane of body cells unique to each person Normal function to help T cells recognize foreign or self all body cells except RBCs display MHC Class I Some cells also display MHC Class II 4

5 Pathways of antigen processing In immune responses, B and T cells must recognize that a foreign antigen is present B cells bind to in extracellular fluid T cells must be presented with processed T cells only recognize fragments of antigenic proteins that first have been processed and presented in association with MHC self- Pathway of antigen processing depends on whether antigen is outside or inside body cells Processing of found outside the cell Exogenous found in extracellular fluid Bacteria, toxins, parasitic worms, inhaled pollen Antigen-presenting cells (APCs) Process and present exogenous APCs include macrophages, B cells, dendritic cells Immune responses occur primarily in the lymph nodes and spleen, which contain large numbers of APCs Exogenous antigen Processing and presenting exogenous Phagosome or endosome Antigenpresenting cell (APC) 1 Phagocytosis or endocytosis of antigen 2 Digestion of antigen into peptide fragments APC Vesicles containing antigen peptide fragments and MHC-II molecules fuse 6 Packaging of MHC-II molecules into a vesicle Synthesis of MHC-II molecules Antigen peptide fragments bind to MHC-II molecules Endoplasmic reticulum Key: Vesicle undergoes exocytosis and antigen MHC-II complexes are inserted into plasma membrane APCs present exogenous in association with MHC-II molecules 7 Antigen peptide fragments MHC-II self-antigen Presenting exogenous After processing the antigen, the APC migrates to lymphatic tissue to present the antigen to T cells. Triggers an immune response Processing of Antigens found inside the cell Processing and presenting endogenous Endogenous that are present inside body cells e.g. viral proteins from virus-infected cells, abnormal proteins synthesized by cancer cells, toxins made by intracellular bacteria Most cells of the body can process and present endogenous Infected cells present the endogenous antigen in association with MHC-I molecules 5

6 Presenting endogenous The display of an endogenous antigen bound to MHC-I signals that a cell has been infected Antigen presentation APCs encounter the foreign invader and present the invader's to a group helper T cells (T H cells). APCs first engulf an invader, break it apart into its and move these to the cell surface. Each T H cell has a different receptor, allowing it to recognize a different antigen. The APC "shows" the antigen to the T H cells until there is a match between a T H cell receptor and the antigen. T cell activation The contact between the APC and T H cells stimulates the T H cell to divide rapidly. This process is called clonal selection because only the T H cells that recognize the antigen are selected to reproduce. Stimulated T H cells also produce chemical messengers called cytokines. Cytokines control the immune response. Cytokines Small protein hormones needed for many normal cell functions Control immune responses Examples (see Table 22.2) Interleukins (IL-1, IL-2, IL-4, IL-5) Tumor necrosis factor (TNF) Interferons Immunologic memory Immunologic memory T C Tumor cell The 1st exposure to an antigen, the primary immune response, takes several days to produce immune cells by clonal selection and peak levels occur at 1-2 weeks Clonal selection also produces memory cells that can last decades in the lymph nodes, ready to be activated by a 2nd exposure to the antigen. If the antigen appears again, the memory cells initiate a faster, stronger response called a secondary immune response. Due to the presence of longlived Abs and thousands of memory B and T cells Next time antigen appears, memory cells proliferate and differentiate within hours Antibody titer a measure of immunological memory Amount of Ab in serum Primary immune response Secondary response faster and stronger 6

7 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. T cells Respond to pathogens that have already entered body cells Cell-mediated immune response Two main types of T cells Helper T cells Cytotoxic T cells Helper T cells 1. Antigen processing 2. Antigen display 3. Binding of T H cell receptor to antigen-mhc II complex activates the T H cell 4. The activated T H cell promotes the immune response: Clonal selection more activated T H cells and memory cells Stimulates the activity of cytotoxic T cells and Copyright B cells 2009, John Wiley & Roles of activated helper T cells Cytotoxic T cells the only T cells that actually kill other cells 7

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