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PowerPoint® Lecture Slides prepared by Vince Austin, University of Kentucky The Immune System: Adaptive Body Defenses Part B Human Anatomy & Physiology, Sixth Edition Elaine N. Marieb Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Adaptive (Specific) Defenses - know The adaptive immune system: Recognizes specific foreign (nonself) substances Acts to immobilize, neutralize, or destroy foreign substances Amplifies inflammatory response and activates complement Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Adaptive Immune Defenses - know The adaptive immune system is antigen-specific, systemic (entire body), and has memory It has two separate but overlapping arms Humoral, or antibody-mediated immunity (B lymphocytes) Cellular, or cell-mediated immunity (T lymphocytes) Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Antigens - know Substances that can mobilize the immune system and provoke an immune response The ultimate targets of all immune responses are mostly large, complex molecules not normally found in the body (non-self) Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Complete Antigens have important functional properties – know definitions, examples Immunogenicity – the ability to stimulate proliferation of specific lymphocytes and antibody production Reactivity – the ability to react with the products of the activated lymphocytes and the antibodies released in response to them Complete antigens include foreign protein, nucleic acid, some lipids, and large polysaccharides Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Haptens (Incomplete Antigens) – know differences from complete antigens, examples Small molecules, such as peptides, nucleotides, and many hormones, that are not immunogenic alone but are reactive when attached to protein carriers If they link up with the body’s proteins, the adaptive immune system may recognize them as foreign and mount a harmful attack (allergy, autoimmunity) Haptens are found in penicillin, poison ivy, dander, some detergents, and cosmetics Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Antigenic Determinants - know Only certain parts of an entire antigen are immunogenic Antibodies and activated lymphocytes bind to these antigenic determinants Most naturally occurring antigens have many antigenic determinants that: Mobilize several different lymphocyte populations Form different kinds of antibodies against it Large, chemically simple molecules (e.g., plastics) have little or no immunogenicity Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Antigenic Determinants - illustration Figure 21.6 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Self-Antigens: MHC Proteins - know Our cells are dotted with protein molecules (self-antigens) that are not antigenic to us but are strongly antigenic to others One type of these, MHC proteins (Major Histocompatability complex), mark a cell as “self” The two classes of MHC proteins are: Class I MHC proteins – found on virtually all body cells bind to T cells Class II MHC proteins – found on certain cells in the immune response (B cells, macrophages, monocytes and dendritic cells) or “antigen presenting cells” Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings MHC Proteins – know Are coded for by genes of the major histocompatibility complex (MHC) and are unique to an individual Each MHC molecule has a deep groove that binds and “displays” a peptide, which is a normal cellular product of protein recycling In infected cells, MHC proteins bind to fragments of foreign antigens, which play a crucial role in mobilizing the immune system Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Peptide antigen in MHC groove - understand Top view MHC molecule Peptide Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Side view, MHC groove - illustration Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings MHC Restriction - know Antigens (Ag) are recognized as a complex of antigenic peptide and a specific MHC molecule molecule This co-recognition of peptide and MHC molecule is known as MHC restriction because the MHC molecule is said to “restrict” the ability of the T cell to recognize antigen Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings MHC Restriction – know concept T cell recognition and activation requires correct combination of antigen + MHC molecule Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Cells of the Adaptive Immune System - know 1. Two types of lymphocytes that respond to Ag B lymphocytes – oversee humoral immunity T lymphocytes – non-antibody-producing cells that constitute the cell-mediated arm of immunity 2. Antigen-presenting cells (APCs): Do not respond to specific antigens Degrade proteins, bind antigen fragments to MHC molecules, “display” them to T and B cells Needed to produce a response from a B and T cell Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings B and T Lymphocytes - know Immature lymphocytes released from bone marrow are essentially identical Whether a lymphocyte matures into a B cell or a T cell depends on where in the body it becomes “immunocompetent” or “educated” to recognize self vs nonself B cells mature in the bone marrow T cells mature in the thymus Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Antigen-Presenting Cells (APCs) - know Major rolls in immunity are: To engulf and degrade particles To present fragments of antigens on their own surfaces, to be recognized by T cells Major APCs are dendritic cells (DCs), macrophages, and activated B cells The major initiators of adaptive immunity are DCs, which actively migrate to the lymph nodes and secondary lymphoid organs and present antigens to T and B cells Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Macrophages and Dendritic Cells - understand Secrete soluble proteins that activate T cells Activated T cells in turn release chemicals that: “Rev up” the maturation and mobilization of DCs Cause “resting” macrophages to become “activated” macrophages, which are insatiable phagocytes that secrete bactericidal chemicals Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Adaptive Immunity: Summary - understand Defensive system that uses lymphocytes, APCs, and specific molecules to identify and destroy nonself particles Its response depends upon the ability of its cells to: Recognize foreign substances (antigens) by binding to them Communicate with one another so that the whole system mounts a response specific to those antigens Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings PowerPoint® Lecture Slides prepared by Vince Austin, University of Kentucky Components Of The Immune System Human Anatomy & Physiology, Sixth Edition Elaine N. Marieb Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Cellular components of the immune system illustration All develop from the pluripotent hematopoietic stem cell. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Cellular components - know The cellular components of the immune system are: 1. Lymphocytes 2. Monocytes/Macrophages 3. Dendritic cells 4. Granulocytes 5. Mast cells Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Cellular components - know 1. Lymphocytes - Constitute 20-40% of the white blood cells and 99% of the lymph. - Lymphocytes are divided into 3 subsets: a. T lymphocytes ( 60-80% ) b. B Lymphocytes (10-20%) c. Natural Killer (NK) cells (10%) Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings a. T Lymphocytes - understand Generated from immature precursors in the thymus (located in chest, over heart). - Mature in the thymus, hence they are named T lymphocytes (T = thymus derived). - Also found in T-cell zones of the peripheral lymphoid organs such as the spleen, tonsils and lymph nodes. - Lymphocytes can be distinguished by their expression of surface CD (“cluster of differentiation”) molecules. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Lymphocyte lymphocyte Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Major Histocompatibility Complex (MHC) understand Collection of genes located on chromosome 6 in humans. Genes codes for 2 major classes of molecules: i. Class I MHC ii. Class II MHC Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Subsets of T cells – know definitions Based on the expression of surface molecules, T-cells are divided into 2 subsets: CD4 Cells (helper T cells, TH ) CD8 Cells (cytotoxic T cells, TC ) - CD4 molecules bind to MHC II during antigen presentation. - CD8 molecules bind to MHC I during antigen presentation. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings T-Cell Receptor Complex - illustration CD4 T cells bind CD8 T cells bind Class II molecules Class I molecules Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings How antigens appear on cell surfaces - know Cells digest proteins into short 5-10 amino acid long peptide antigens Antigens appear on cell surfaces as combinations of the cell’s own MHC molecules + the peptide MHC = major histocompatibilty complex molecules There are two classes of MHC molecules: class I and class II Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Processing and Presentation of Endogenous and Viral antigens - illustration MHC Class I Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Structure of Class I MHC - understand Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Processing and Presentation of Exogenous Antigen - illustration MHC Class II Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Structure of Class II MHC - understand Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings b. B Lymphocytes - understand - Develop from immature precursors in the bone marrow, hence the name B lymphocyte. - Also present in the peripheral lymphoid organs, such as the spleen, lymph nodes, tonsils and extra-lymphatic organs such as gastrointestinal tract. - Membrane bound Ig immunoglobulins serve as B-cell receptors. - Products of B cells are also secreted Ig Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Structure of an Immunoglobulin (Ig) molecule, also called an antibody molecule - know Varies, antigenspecific Same for class of Ig Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings c. Natural Killer (NK) cells - understand - Cytoplasm contains a large number of granules. - Also referred to as Large Granular Lymphocyte. - Do not have receptors for antigen binding on their cell surface. - Can kill tumor cells, virus infected cells without prior sensitization (exposure to them). - Destroy cells based on what they lack instead of what they express Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings