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Chapter 43

Chapter 43. The Immune System Essential Idea: Immunity is based on recognition of self and destruction of foreign material. travismulthaupt.com. The Immune System. Earlier we learned that the body has an innate and an acquired immune system. Innate is built in, we’re born with it.

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Chapter 43

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  1. Chapter 43 The Immune System Essential Idea: Immunity is based on recognition of self and destruction of foreign material. travismulthaupt.com

  2. The Immune System • Earlier we learned that the body has an innate and an acquired immune system. • Innate is built in, we’re born with it. • Acquired is built up over time. • It also has a variety of ways to protect itself from invasion of foreign bodies. • Skin • Mucous membranes • Etc.

  3. Surface Proteins • Every organism has a unique set of proteins on the surface of its cells. • These proteins are what the immune system recognizes when it is determining self vs. non-self.

  4. Surface Proteins • These surface proteins are called antigens. • Antigens are recognized as foreign and stimulate an immune response. • Antigens usually stimulate the production of antibodies by the immune system.

  5. Antigens • Antigens are foreign molecules that are recognized by lymphocytes and elicit a response from them. • Lymphocytes bind to the epitope on an antigen. travismulthaupt.com

  6. Pathogens • Pathogens can be species-specific, while others can cross species barriers and infect multiple types of species.

  7. 1. Innate Immune System • The innate immune system is what we’re born with. • It is what keeps us alive while acquired immunity is built up. • Its components include: • Compliment System • WBCs (Leukocytes) • Inflammation

  8. The Complement System • The complement system comprises part of the innate defense. • Infected cells secrete numerous types of proteins as a part of the Compliment System. • They quickly become active and lyse foreign invaders when detected. • Example: α and β interferon.

  9. Interferon • These are proteins, and there are 2 main types (α and β) which provide innate defense against pathogens. • They act to stimulate neighboring cells to produce substances to prevent further infection. • This is the body’s way of preventing the spread of the infection.

  10. Membrane Attack Complex • The MAC is a part of compliment and is triggered by substances from the body’s innate defenses. • MAC is triggered by the antigen-antibody response. • This complex forms pores in the membrane, and they allow H2O and ions to rush in and lyse an infected cell.

  11. Lysosomes (Compliment) • There are 2 ways lysosomes work: • 1. They poison the invader. • NO and other toxic forms of O2 are made in the lysosome. • 2. Lysozyme and other enzymes degrade invader components. • Some microbes make substances that allow them to go unnoticed against the body’s defenses.

  12. Natural Killer Cells (a type of WBC) • NK cells patrol the body and attack virus infected body cells and cancer cells. • They work with the acquired immune system. • They recognize surface proteins and act to release chemicals into the cell triggering apoptosis. • Not 100% effective. A human natural killer cell is shown conjugated to a tumor cell. The accumulation of actin filaments (blue) and CD2 (red) at the immunologic synapse can be seen preceding the localization of the cytolytic molecule perforin (green).

  13. 2. Acquired Immune System- Lymphocytes • Lymphocytes produce 2 main types of immune responses: • 1. Humoral response • Circulating antibodies produced by B-lymphocytes • 2. Cell mediated response • Antibodies produced by T-lymphocytes

  14. 1. The Humoral Response • Occurs when cells derived from B-lymphocytes become activated and secrete defensive proteins called antibodies. • Secreted antibodies accumulate in the blood and lymph.

  15. 1. The Humoral Response • Antibodies identify and bind to microbes and mark them for elimination. • Clonal selection is also involved. travismulthaupt.com

  16. Clonal Selection • The antibody-driven cloning of T & B lymphocytes is called clonal-selection and is fundamental to acquired immunity. • When antigens bind to specific receptors, a small fraction of the body’s lymphocytes are activated. • This stimulates the production of thousands of clones that work to eliminate an antigen.

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  18. Primary Immune Response • The primary immune response is the first time exposure to an antigen. • Proliferation of lymphocytes occurs. • The individual may become sick. • Eventually antibodies clear the antigen from the system.

  19. Secondary Immune Response • The 2° immune response occurs if an individual is exposed to an antigen again. • It is an example of immunological memory. • It depends on long lived T and B memory cells. • They elicit a quick and specific response to the antigen.

  20. Lymphocytes • Lymphocytes are WBCs that mediate the immune responses. • There are two main types of lymphocytes: • 1. B-cells • 2. T-cells • They are concentrated in the spleen, lymph nodes, and other lymphoid tissues.

  21. Lymphocytes • Lymphocytes act to recognize antigens by a means of antigen specific receptors embedded in their membrane. • They stimulate production of T & B cells. • A single T or B cell has about 100,000 antigen-receptors. • All of them are the same on a particular cell--they recognize the same epitope.

  22. Lymphocytes • Lymphocytes are derived from pluripotent stem cells in the bone marrow. • Each lymphocyte displays specificity for a particular epitope on an antigen • It defends against that antigen and other closely related antigens.

  23. 1. B-Cell Lymphocytes • Originate and mature in the bone marrow. • B-cell chains are anchored into a membrane of the B-cell. • They are sometimes called membrane antibodies or membrane immunoglobulins. • B-cells recognize intact antigens.

  24. 1. B-Cell Lymphocytes • B-cells help with presenting antigens to helper T-cells in the course of the humoral response. 26 http://en.wikipedia.org/wiki/File:B_cell_activation.png

  25. MHC • Major histocompatibility complex genes code for MHC molecules. • When MHC molecules are synthesized, they get transported to the plasma membrane. • On the way, they bind with fragments of antigen protein within a cell and bring it to the surface.

  26. MHC • MHC is what is called antigen presentation. • Due to antigen presentation, nearby T-cells can recognize the fragment on the cell surface and act accordingly. • MHC proteins are very polymorphic.

  27. Foreign Antigens • There are 2 ways foreign antigens end up inside cells of the body. Their source determines which MHC molecule gets used and which T-cell assists in its removal. • 1. Foreign antigens synthesized within the cell (viruses, cancer). • 2. Foreign materials can become internalized by phagocytosis or endocytosis

  28. Class I MHC Molecules • These are found on most nucleated cells in body. • They bind antigens synthesized within the cell. • Infected cells and cancerous cells display such antigens. • Cytotoxic T-cells destroy cells displaying Class I MHC molecules.

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  30. Class II MHC Molecules • Class II MHC molecules are made by only a few types of cells-dendritic cells, macrophages, and B-cells. • These bind peptides derived from foreign materials that have been fragmented and internalized.

  31. Class II MHC Molecules • Class II MHC molecules display these antigens to helper T-cells. • Helper T cells alert nearby B-cells and cytotoxic T cells by secreting cytokines. travismulthaupt.com

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  34. Immunoglobulin Gene Rearrangement • There are many different types of B-cell and T-cell antibodies. • This is due to the random nature of the recombinase enzyme. • It can create a number of different gene products which are the B-cell (or T-cell) antigen receptors.

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  36. B-Cell & T-Cell Activation • When B-cells and T-cells become activated by antigens, they are stimulated to divide many times. • 2 clones of daughter cells are created. • 1 is short lived, antibody secreting cell. • The other is a memory cell that is long lived and bears receptors for the same antigen.

  37. B-Cell Activation • Many antigens recognized by B-cells contain multiple epitopes. • Exposure to a single antigen can stimulate a variety of different B-cells. • This gives rise to a clone of thousands of plasma cells (effector and memory). • These clones secrete antibodies specific to the epitope that provoked their production.

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  39. B-Cell Activation • Activated B-cells secrete antibodies that have a Y-shaped antigen-binding structure, but no transmembrane region. • These binding sites are responsible for identifying specific antigens. • Identification of antigens facilitates their removal.

  40. 2. The Cell Mediated Response • When the cell mediated response and clonal selection occurs: • Cytotoxic lymphocytes directly destroy infected body cells, cancer cells, or foreign tissue. • There are 2 main types of T-cells • 1. Helper T-cells • 2. Cytotoxic T-cells

  41. 2. T-Cell Lymphocytes • T-cell lymphocytes originate in the bone marrow and mature in the thymus. • They consist of 2 polypeptide chains, α & β. • They, too, are linked into a cell’s plasma membrane. • They also have V and C regions. • T-cells recognize fragments of antigens that are bound to normal cell-surface proteins called MHC molecules.

  42. Helper T-Cells • Helper T-cells are central to the network of cellular interactions. • They respond to peptide antigens displayed on antigen presenting cells. • They stimulate activation of B-cells and cytotoxic T-cells.

  43. Helper T-Cells • When helper T-cells encounter a class II MHC molecule-antigen complex, they stimulate the production of clones of helper T-cells and memory helper T-cells. • This promotes the removal of infected cells.

  44. Helper T-Cells • Helper T-cells secrete many different cytokines (signals) to stimulate other lymphocytes. • This promotes humoral and cell mediated responses. travismulthaupt.com

  45. Cytotoxic T-Cells • When activated, cytotoxic T-cells secrete proteins which destroy the infected cell. • Circulating antibodies then mark the exposed pathogens for disposal. • Cytotoxic T-cells are the effectors. travismulthaupt.com

  46. Ways to Prevent Infection • Immunity depends upon the persistence of memory cells. • There are 2 types of immunization: • 1. Active immunity • 2. Passive immunity

  47. 1. Active Immunity • This is immunity conferred by a natural exposure to an infectious agent. • It also can develop following immunization.

  48. 2. Passive Immunity • Passive immunity results from the transfer of antibodies from an immune individual to someone who isn’t. • Transferred antibodies are immediately available to attack antigens to which they are specific.

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