Specific immunity and its applications
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This document provides an overview of chapter 15 from the textbook Foundations in Microbiology. It discusses the development of the dual lymphocyte system involving B cells and T cells. It describes how antigens are processed and presented to lymphocytes, leading to clonal selection and expansion. The roles of antibodies and cell-mediated immunity are explained. The document also covers acquired immunity, both natural and artificial, as well as active and passive types.
Specific immunity and its applications
- 1. PowerPoint to accompany Foundations in Microbiology Fifth Edition Talaro Chapter 15 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
- 2. The Acquisition of Specific Immunity and Its Applications Chapter 15 2
- 3. Chapter Overview 1. Development of the Dual Lymphocyte System 2. Entrance and Processing of Antigens and Clonal Selection 3. Activation of Lymphocytes and Clonal Expansion 4. Products of B Lymphocytes: Antibody Structure and Functions 5. How T cells Respond to Antigen: Cell-Mediated Immunity 3
- 4. Preliminary concepts • Cell receptors or markers confer specificity and identity • Major functions of receptors are 1. to perceive & attach to nonself or foreign molecules 2. to promote the recognition of self molecules 3. to receive & transmit chemical messages among other cells of the system 4. to aid in cellular development. 4
- 5. How are receptors formed? • As a cell matures, certain genes that encode cell receptors are transcribed & translated into protein products with a distinctive shape, specificity and function. • Receptor is modified & packaged by the endoplasmic reticulum & Golgi complex. • It is ultimately inserted into the cell membrane, accessible to antigens, other cells, and chemical mediators. 5
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- 7. Major Histocompatibility Complex (MHC) • Receptors found on all cells except RBCs • Also known as human leukocyte antigen (HLA) • Plays a role in recognition of self by the immune system and in rejection of foreign tissue • Genes for MHC are located on chromosome 6, clustered in a multigene complex of classes I, II, III 7
- 8. MHC receptors 8
- 9. Functions of MHC • Class I – markers that display unique characteristics of self molecules & regulation of immune reactions – Required for T lymphocytes • Class II – receptors that recognize & react with foreign antigens. Located primarily on macrophages & B cells – Involved in presenting antigen to T cells • Class III – secreted complement components, C2 and C4 9
- 10. Clonal selection theory • Lymphocytes use 500 genes to produce a tremendous variety of specific receptors • Undifferentiated lymphocytes undergo genetic mutations & recombinations while they proliferate in the embryo forming a billion different clones with the ability to react with a tremendous variety of antigens. 10
- 11. • Lymphocyte specificity is preprogrammed, existing in the genetic makeup before an antigen has ever entered the system. • Each genetically different type of lymphocyte expresses a single specificity. • First introduction of each type of antigen into the immune system selects a genetically distinct lymphocyte and causes it to expand into a clone of cells that can react to that antigen. 11
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- 13. Specific B cell receptor: Immunoglobulin • Large glycoproteins that serve as specific receptors of B cells • Composed of 4 polypeptide chains – 2 identical heavy chains – 2 identical light chains • Y shaped • Variable regions • Constant regions 13
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- 15. Immunoglobulins • Immunoglobulin genes lie on 3 different chromosomes • Undifferentiated lymphocyte has 150 different genes for the variable region of light chains & 250 for the variable region and diversity region of the heavy chain • During development, recombination causes only the selected V and D genes to be active in the mature cell. 15
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- 17. B cell receptors • Once synthesized, immunoglobulin is transported to cell membrane & inserted there to act as a receptor • First receptor on most B cells is a small form of IgM & mature B cells carry IgD receptors 17
- 18. T cell receptors • Formed by genetic recombination, having variable and constant regions • 2 parallel polypeptide chains • Small, without humoral functions 18
- 19. T cell receptors 19
- 20. Development of the Dual Lymphocyte System • Starting in the embryonic & fetal stages, stem cells in the yolk sac, liver, and bone marrow release immature lymphocytes into the circulation • These undifferentiated cells must mature to be able to react to antigen • Maturation occurs differently for B and T cells 20
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- 22. B cell maturation • Directed by bone marrow sites that harbor stromal cells, which nurture the lymphocyte stem cells & provide hormonal signals • Millions of distinct B cells develop & home to specific sites in the lymph nodes, spleen, and GALT where they come into contact with antigens throughout life 22
- 23. T cell maturation • Maturation is directed by the thymus gland and its hormones • 7 classes of T-cell receptors termed CD cluster • Mature T cells migrate to lymphoid organs and occupy specific sites 23
- 24. Entrance and Processing of Antigens and Clonal Selection
- 25. Antigen (Ag) • substance that provokes an immune response in specific lymphocytes • perceived as foreign, not a normal constituent of the body • Foreign cells & large complex molecules over 10,000 MW are most antigenic • Foreign molecules less than 1,000 MW (haptens) are not antigenic unless attached to a larger carrier • Antigenic determinant, epitope – small molecular group that is recognized by lymphocytes. An antigen has many antigenic determinants. 25
- 26. Antigens 26
- 27. Antigens 27
- 28. Special categories of antigens • Autoantigens – molecules on self tissues for which tolerance is inadequate • Alloantigens – cell surface markers of one individual that are antigens to another of that same species • Heterophilic antigens – molecules from unrelated species that bear similar antigenic determinants • Superantigens – potent T cell stimulators, provoke an overwhelming response • Allergen – antigen that provokes allergy 28
- 29. • T-cell dependent antigens must be processed by phagocytes called antigen presenting cells (APC). • An APC alters the antigen and attaches it to its MHC receptor. • Antigen presentation involves a direct collaboration among an APC, a T helper cell and an antigen-specific B or T cell. • Interleukin -1 is secreted by APC to activate TH cells • Interleukin-2 is produced by TH to activate B & other T cells 29
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- 31. Activation of Lymphocytes and Clonal Expansion
- 32. B cell activation & antibody production • Once B cells process the Ag, interact with TH cells and are stimulated by growth and differentiation factors, they enter the cell cycle in preparation for mitosis and clonal expansion. • Divisions give rise to plasma cells that secrete antibodies and memory cells that can react to the same antigen later. 32
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- 34. Nature of antibodies • Immunoglobulins • A large Y-shaped protein • Consists of 4 polypeptide chains • Contains 2 identical fragments (Fab) with ends that bind to specific antigen • Fc binds to self 34
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- 37. Ag-Ab reactions • Opsonization • Neutralization • Agglutination • Complement fixation 37
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- 40. • Primary response – after first exposure to an Ag immune system produces IgM and a gradual increase in Ab titer • Secondary response –after second contact with the same Ag, immune system produces a more rapid, stronger response due to memory cells 40
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- 42. Monoclonal antibodies • single specificity antibodies formed by fusing a mouse B cell with a cancer cell. • used in diagnosis of disease, identification of microbes and therapy 42
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- 44. T cells & Cell Mediated Immunity • T cells act directly against Ag and foreign cells. • T cells secrete cytokines that act on other cells. • Sensitized T cells proliferate into long- lasting memory T cells. 44
- 45. 4 types of T cells • T helper cells (CD4 or TH) assist other T and B cells; conductor of immune response • Cytotoxic T cells (CD8 or TC) destroy foreign or abnormal cells by secreting perforins that lyse cells • Delayed hypersensitivity cells (TD) responsible for allergies occurring several hours or days after contact • T suppressor cells (TS) limit the actions of other T cells and B cells 45
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- 49. Acquired immunity • Natural immunity – acquired as part of normal life experiences • Artificial immunity - acquired through a medical procedure such as a vaccine • Active immunity – results when a person is challenged with Ag that stimulates production of Ab. It creates memory, takes time and is lasting • Passive immunity – preformed Ab are donated to an individual. It does not create memory, acts immediately, and is short term. 49
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- 51. Types of acquired immunity • Natural active immunity – acquired upon infection and recovery • Natural passive immunity – acquired by a child through placenta and breast milk • Artificial active immunity – acquired through inoculation with a selected Ag • Artificial passive immunity – administration of immune serum or globulin 51