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Foundations in Microbiology Seventh Edition

Talaro

Chapter 15 To run the animations you must be in Slideshow View. Use the buttons on the animation to play, pause, and turn audio/text on or off. Please Note: Once you have used any of the animation functions (such as Play or Pause), you must first click in the white background before you can advance to the next slide.

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15.1 Specific Immunity – Adaptive Line of Defense Third line of defense – acquired • Dual System of B and T lymphocytes – Immunocompetence

• Antigen – Molecules that stimulate a response by T and B cells • Two features that characterize specific immunity: – Specificity – antibodies produced, function only against the antigen that they were produced in response to – Memory – lymphocytes are programmed to “recall” their first encounter with an antigen and respond rapidly to subsequent encounters 2

Classifying Immunities • Active immunity – results when a person is challenged with antigen that stimulates production of antibodies; creates memory, takes time, and is lasting • Passive immunity – preformed antibodies are donated to an individual; does not create memory, acts immediately, and is short term • Natural immunity – acquired as part of normal life experiences • Artificial immunity – acquired through a medical procedure such as a vaccine 3

• 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 a preparation containing specific antibodies

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Figure 15.1

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Overview of Specific Immune Responses Separate but related activities of the specific immune response: • Development and differentiation of the immune system • Lymphocytes and antigen processing • The cooperation between lymphocytes during antigen presentation • B lymphocytes and the production and actions of antibodies • T lymphocyte responses 6

Figure 15.2 (I)

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Figure 15.2 (II-V)

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15.2 Development of the Immune Response System Cell receptors or markers confer specificity and identity of a cell • Major functions of receptors are: 1. To perceive and attach to nonself or foreign molecules 2. To promote the recognition of self molecules 3. To receive and transmit chemical messages among other cells of the system 4. To aid in cellular development 9

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

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Functions of MHC • Genes for MHC clustered in a multigene complex: – Class I – markers that display unique characteristics of self molecules and regulation of immune reactions • Required for T lymphocytes

– Class II – regulatory receptors found on macrophages, dendritic cells, and B cells • Involved in presenting antigen to T-cells

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Figure 15.3

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Lymphocyte Receptors • Lymphocyte’s role in surveillance and recognition is a function of their receptors • B-cell receptors – bind free antigens • T-cell receptors – bind processed antigens together with the MHC molecules on the cells that present antigens to them

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Clonal Selection Theory • Lymphocytes use 500 genes to produce a tremendous variety of specific receptors • Undifferentiated lymphocytes undergo a continuous series of divisions and genetic changes that generate millions of different cell types • Each cell has a particular/unique receptor specificity

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• In the bone marrow, lymphocytic stem cells differentiate into either T or B cells • B cells stay in the bone marrow • T cells migrate to the thymus • Both T and B cells migrate to secondary lymphoid tissue

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Figure 15.4

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• Lymphocyte specificity is preprogrammed, existing in the genetic makeup before an antigen has ever entered the system • Each genetically different type of lymphocyte (clone) expresses a single specificity • First introduction of each type of antigen into the immune system selects a genetically distinct lymphocyte • Causes it to expand into a clone of cells that can react to that antigen 17

Figure 15.5

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Specific B-Cell Receptor: Immunoglobulin Receptor genes of B cells govern immunoglobulin (Ig) synthesis • Large glycoproteins that serve as specific receptors of B cells • Composed of 4 polypeptide chains: – 2 identical heavy chains (H) – 2 identical light chains (L)

• Y shaped arrangement – ends of the forks formed by light and heavy chains contain a wide range of variable antigen binding sites • Variable regions • Constant regions 19

Figure 15.6 (a)

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Figure 15.6 (b)

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T-Cell Receptors for Antigen • Formed by genetic recombination, with variable and constant regions • 2 parallel polypeptide chains • Small, not secreted

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Figure 15.7 Proposed structure of the T-cell receptor

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15.3 Lymphocyte Responses and Antigens • B-cell maturation – Directed by bone marrow sites that harbor stromal cells, which nurture the lymphocyte stem cells and provide hormonal signals – Millions of distinct B cells develop and “home” to specific sites in the lymph nodes, spleen, and GALT – Come into contact with antigens throughout life – Have immunoglobulin as surface receptors for antigens

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Lymphocyte Responses and Antigens • T-cell maturation – Maturation is directed by the thymus gland and its hormones – Different classes of T-cell receptors termed CD - Cluster of differentiation • CD4 and CD8

– Mature T cells migrate to lymphoid organs

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Entrance and Processing of Antigens and Clonal Selection • Antigen (Ag) is a substance that provokes an immune response in specific lymphocytes • Property of behaving as an antigen is antigenicity – Foreignness, size, shape, and accessibility

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Characteristics of Antigens • Perceived as foreign, not a normal constituent of the body • Foreign cells and large complex molecules over 10,000 MW are most antigenic • Antigenic determinant, epitope – small molecular group that is recognized by lymphocytes • Antigen has many antigenic determinants

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Figure 15.8

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• Haptens – small foreign molecules that consist only of a determinant group – Not antigenic unless attached to a larger carrier • Carrier group contributes to the size of the complex and enhances the orientation of the antigen

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Figure 15.9 The hapten-carrier phenomenon

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Special Categories of Antigens • Alloantigens – cell surface markers and molecules that occur in some members of the same species but not in others • Superantigens – potent T cell stimulators; provoke an overwhelming response • Allergen – antigen that evokes allergic reactions • Autoantigens – molecules on self tissues for which tolerance is inadequate 32

15.4 Cooperation in Immune Reactions to Antigens • The basis for most immune responses is the encounter between antigens and white blood cells • Lymph nodes and spleen concentrate the antigens and circulate them so they will come into contact with lymphocytes

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Antigen Processing and Presentation to Lymphocytes • T-cell dependent antigens must be processed by phagocytes called antigen presenting cells (APC) • APCs modify the antigen; then the Ag is moved to the APC surface and bound to MHC receptor • Antigen presentation involves a direct collaboration among an APC, and a T helper cell – Interleukin-1 is secreted by APC to activate TH cells – Interleukin-2 is produced by TH to activate B and other T cells 34

Figure 15.10

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15.5 B Cell Responses • B-cell activation and 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

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Figure 15.11

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Antibody Structure and Functions • • • •

Immunoglobulins Large Y-shaped protein Consist of 4 polypeptide chains Contains 2 identical fragments (Fab) with ends that bind to specific antigen • Fc binds to various cells and molecules of the immune system

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Figure 15.12

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Figure 15.13

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Antibody-Antigen Interactions Principle antibody activity is to unite with the Ag, to call attention to, or neutralize the Ag for which it was formed • Opsonization – process of coating microorganisms or other particles with specific antibodies so they are more readily recognized by phagocytes • Agglutination – Ab aggregation; cross-linking cells or particles into large clumps • Neutralization – Abs fill the surface receptors on a virus or the active site on a microbial enzyme to prevent it from attaching – Antitoxins are a special type of Ab that neutralize bacterial exotoxins 41

Figure 15.14

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Functions of the Fc Fragment • Fc fragment binds to cells – macrophages, neutrophils, eosinophils, mast cells, basophils, and lymphocytes • Certain antibodies have regions on the Fc portion for fixing complement – Binding of Fc may cause release of cytokines

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Classes of Immunoglobulins 5 classes of immunoglobulins (Ig): 1. IgG – monomer, produced by plasma cells (primary response) and memory cells (secondary), most prevalent 2. IgA – monomer circulates in blood, dimer in mucous and serous secretions 3. IgM – five monomers, first class synthesized following Ag encounter 4. IgD – monomer, serves as a receptor for antigen on B cells 5. IgE – Involved in allergic responses and parasitic worm infections 44

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Primary and Secondary Responses to Antigens • Primary response – after first exposure to an Ag immune system produces IgM and a gradual increase in Ab titer (concentration of antibodies) with the production of IgG • Secondary response – after second contact with the same Ag, immune system produces a more rapid, stronger response due to memory cells – Anamnestic response 46

Figure 15.16

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Monoclonal Antibodies • Originate from a single clone and have a single specificity for antigen • Pure preparation of antibody • Single specificity antibodies formed by fusing a mouse B cell with a cancer cell • Used in diagnosis of disease, identification of microbes and therapy

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Insight 15.2

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Insight 15.2

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15.6 T Cells & Cell-Mediated Immunity • Cell-mediated immunity requires the direct involvement of T lymphocytes • T cells act directly against Ag and foreign cells when presented in association with an MHC carrier • T cells secrete cytokines that act on other cells • Sensitized T cells proliferate into long-lasting memory T cells

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Types of T Cells 1. T helper cells (CD4 or TH) most prevalent type of T cell; regulate immune reaction to antigens, including other T and B cells; also involved in activating macrophages and increasing phagocytosis; differentiate into T helper 1 (TH1) cells or T helper 2 (TH2) cells 2. Cytotoxic T cells (CD8 or TC) destroy foreign or abnormal cells by secreting perforins that lyse cells 3. Natural killer cells – lack specificity; circulate through the spleen, blood, and lungs

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Figure 15.17

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T Cells and Superantigens • Reaction has drastic consequences • Superantigens are a form of a virulence factor • Provoke overwhelming immune responses by large numbers of T cells – – – –

Release of cytokines Blood vessel damage Toxic shock Multiorgan damage 55

15.7 Immunization: Manipulating Immunity • Passive immunity – immune serum globulin (ISG), gamma globulin, contains immunoglobulin extracted from pooled blood; immunotherapy • Treatment of choice in preventing measles and hepatitis A and in replacing antibodies in immunodeficient patients • Sera produced in horses are available for diphtheria, botulism, and spider and snake bites • Acts immediately; protection lasts 2-3 months 56

Vaccination • Artificial active immunity – deliberately exposing a person to material that is antigenic but not pathogenic • Principle is to stimulate a primary and secondary anamnestic response to prepare the immune system for future exposure to a virulent pathogen • Response to a future exposure will be immediate, powerful, and sustained 57

Vaccine Preparation Most vaccines are prepared from: 1. Killed whole cells or inactivated viruses –

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Live, attenuated cells or viruses –

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Eliminate virulence

Antigenic molecules derived from bacterial cells or viruses – –

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Grown in substance that kills virus

Capsules, exotoxins, surface proteins Can be genetically engineered, synthesized or produced from culture

Genetically engineered microbes or microbial agents – Either insert genes for pathogen’s antigen into plasmid vector, and clone them in an appropriate host, purify protein • DNA Vaccines (Expreimental- hep C, Lyme disease)

– Or use “Trojan horse” vaccine – genetic material from a pathogen is inserted into a live carrier nonpathogen; the recombinant expresses the foreign genes • Experimental vaccines for AIDS, herpes simplex 2, leprosy, tuberculosis

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Figure 15.19

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Figure 15.20

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Route of Administration and Side Effects • Most administered by injection; few oral, nasal • Some vaccines require adjuvant to enhance immunogenicity and prolong retention of antigen • Stringent requirements for development of vaccines • More benefit than risk • Possible side effects include local reaction at injection site, fever, allergies; rarely back-mutation to a virulent strain, neurological effects 62

Herd Immunity • Immune individuals will not harbor it, reducing the occurrence of pathogens – herd immunity • Less likely that a nonimmunized person will encounter the pathogen

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