Chapter 15 - Fall 2024 - Student - Microbiology PDF

Because learning changes everything.® Chapter 15 Adaptive, Specific Immunity, and Immunization Talaro’s Foundations in Microbiology Twelfth Edition Barry Chess © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill...

Because learning changes everything.® Chapter 15 Adaptive, Specific Immunity, and Immunization Talaro’s Foundations in Microbiology Twelfth Edition Barry Chess © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.  Specific Immunities: The Adaptive Line of Defense Third line of defense – adaptive or acquired immunity Product of B and T lymphocytes dual system Immunocompetence: ability of the body to interact with a wide spectrum of foreign substances ________ – molecules that stimulate response by T and B cells © McGraw Hill, LLC 2  Specific Immunities: The Adaptive Line of Defense Two features that characterize specific immunity: __________ – antibodies produced, function only against the antigen that they were produced in response to ________ – lymphocytes are programmed to “recall” their first encounter with an antigen and respond rapidly to subsequent encounters © McGraw Hill, LLC 3  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 © McGraw Hill, LLC 4  Overview of Specific Immune Responses I. Development of the Lymphocyte System. Lymphocytes arise from the same stem cells but differentiate into two distinct cell types early on. T cells mature in the thymus gland and B cells mature in specialized bone marrow sites. Once released, matured cells settle in lymphoid organs and serve as a constant attack force for infectious agents. © McGraw Hill, LLC 5  Overview of Specific Immune Responses II. Contact with Antigens III. Presentation by Antigen-presenting Cells (APCs). Foreign cells bear molecules (antigens) that are recognized and engulfed by APCs such as dendritic cells. For most responses, T helper cells first receive the processed antigen from the APC and go on to activate B and other T cells. © McGraw Hill, LLC 6  Overview of Specific Immune Responses IVA. Activation of T Cells IVB. T-cell Responses. An activated T cell forms memory cells and differentiates into helper cells or cytotoxic cells. T-cell immunity is termed cell mediated because the whole T cell acts directly to destroy microbes, rather than by secreting molecules Into the body fluids. © McGraw Hill, LLC 7  Overview of Specific Immune Responses VA. B-Cell Responses. A B cell activated by T helper cells undergoes a spurt of cell division, producing memory cells that provide a rapid recall of the antigen, and plasma cells that secrete proteins called antibodies. © McGraw Hill, LLC 8  Overview of Specific Immune Responses VB. Humoral Immunity*. Antibodies circulate in fluids (blood, ECF, and lymph) providing humoral immunity. The antibodies react specifically with the antigen and mark it for an enhanced response. *A traditional term for such body fluids is the “humors”. © McGraw Hill, LLC 9  Development of the Immune Response System Cell receptors or markers confer specificity and identity of a cell Major functions of ____________ are: To perceive and attach to nonself or foreign molecules To promote the recognition of self molecules To receive and transmit chemical messages among other cells of the system To aid in cellular development © McGraw Hill, LLC 10  Major Histocompatibility Complex (MHC) Set of cell surface proteins (receptors) essential for the acquired immune system in the recognition of self and in rejection of foreign molecules _________________(receptors) are found on all cells except RBCs The MHC is also known as the human leukocyte antigen (HLA) system The MHC gene family is divided in two main groups: MHC Class I genes MHC Class II genes © McGraw Hill, LLC 11  Functions of MHC Groups ___________MHC – genes code for markers that display unique characteristics of self and allow recognition of self molecules and regulation of immune reactions Required for T lymphocytes to interact with pathogens © McGraw Hill, LLC 12  Functions of MHC Groups 2 ___________ MHC – genes code for immune regulatory receptors found on antigen- presenting cells (APCs): macrophages, dendritic cells, and B cells Involved in presenting antigen to T-cells © McGraw Hill, LLC 13  Lymphocyte Receptors The role lymphocytes play 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 __________ are molecules, so their chemical structures can vary over a very wide range (potentially exhibiting billions of uniquely different structures and shapes) Sources of antigens include microorganisms and chemical compounds in the environment © McGraw Hill, LLC 14  Origin of Diversity and Specificity in the Immune Response Lymphocytes use 500 genes to produce a tremendous variety of specific receptors _______________Theory – Undifferentiated lymphocytes in embryo and fetus undergo a continuous series of divisions and genetic changes that generate hundreds of different cell types, each with a particular/unique receptor specificity © McGraw Hill, LLC 15  Development of Lymphocytes In the bone marrow, lymphocytic stem cells differentiate into either T or B cells B cells stay in the bone marrow while T cells migrate to the thymus Mature T and B cells migrate to secondary lymphoid tissue Secondary lymphoid tissues will constantly be resupplied with B and T cells © McGraw Hill, LLC 16  Proliferative Stage of Lymphocyte Development Lymphocyte specificity exists in the genetic makeup of a lymphocyte even before an antigen has ever entered the system __________ – Each genetically different type of lymphocyte expresses a single specificity Repertoire of lymphocyte clones. each with unique receptor display © McGraw Hill, LLC 17  Proliferative Stage of Lymphocyte Development Antigen-Independent Period 1) During development of early lymphocytes from stem cells, a given stem cell undergoes rapid cell division to form numerous progeny. As cells differentiate, random rearrangement of the genes that code for cell surface protein receptors results in a large array of genetically distinct cells, called clones. Each clone bears a different receptor that reacts with only a single type of foreign molecule or antigen. © McGraw Hill, LLC 18  Proliferative Stage of Lymphocyte Development 2) Lymphocyte clones with receptors that recognize self molecules and could be harmful are eliminated (clonal deletion). T cells undergo further selection in the thymus, where cells that do not recognize self MHC (and are therefore nonfunctional) are also deleted. © McGraw Hill, LLC 19  Proliferative Stage of Lymphocyte Development 3) Each surviving lymphocyte that exits the thymus is specific for a single antigen molecule. The result is an enormous pool of mature but naïve lymphocytes that are ready to further differentiate under the influence of their “home” organs and immune stimuli. © McGraw Hill, LLC 20  Clonal Selection and Expansion First introduction of each type of antigen into the immune system “selects” a genetically distinct lymphocyte (clone) This contact causes the clone to expand, through mitotic divisions, into a larger population of lymphocytes that can react to that antigen (same single specificity) © McGraw Hill, LLC 21  Clonal Selection and Expansion Antigen-Dependent Period 4) Lymphocytes migrate to the lymphatic organs where they are situated to encounter antigens. Entry of a specific antigen selects only the lymphocyte clone or clones that carry surface receptors matching the antigen. This will trigger an immune response, which varies according to the type of lymphocyte involved. © McGraw Hill, LLC 22  B-Cell Receptor: Immunoglobulin ______________ – large glycoproteins that serve as specific receptors of B cells and as antibodies Composed of 4 polypeptide chains in a Y-shaped arrangement: 2 identical heavy chains (H) 2 identical light chains (L) Wide range of variable antigen binding sites at the end of the forks formed by these chains is due to variable (V) regions The constant (C) regions do not vary greatly © McGraw Hill, LLC 23  B-Cell Receptor: Immunoglobulin (c): molekuul_be/Shutterstock © McGraw Hill, LLC 24  Development of Immunoglobulins An undifferentiated lymphocyte has: ~150 genes that code for the variable region of light chains ~250 genes for the variable(V) and diversity (D) regions of the heavy chains Only a small number of genes code for the constant (C) regions and the joining (J) regions that link segments of the final molecule © McGraw Hill, LLC 25  Development of Immunoglobulins After development only the selected V and D gene segments are active in the mature cell, and all the other V and D genes have been deleted This maintains the lymphocytes specificity Once synthesized, immunoglobulin is transported to cell membrane and inserted there to act as a receptor © McGraw Hill, LLC 26  T-Cell Receptors for Antigen Formed by genetic recombination like B-cell receptors, with variable and constant regions 2 parallel polypeptide chains Unlike B-cell receptors, T-cell receptors are small, not secreted © McGraw Hill, LLC 27  Specific Events in T-Cell Maturation Maturation is directed by the thymus gland and its hormones Different classes of T-cell receptors termed CD receptors or clusters of differentiation CD4 on T helper (TH) cells CD8 on T cytotoxic (Tc) cells Mature T cells migrate to lymphoid organs © McGraw Hill, LLC 28  Specific Events in ______________________ 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 MALT Come into contact with antigens throughout life Have immunoglobulin as surface receptors for antigens © McGraw Hill, LLC 29  B Cells versus T Cells TABLE 15.1 Contrasting Properties of T Cells and B Cells Site of Immune Circulation Receptors for Distribution Require Product General Maturation surface in Blood Antigen in Lymphatic Antigen Antigenic Functions Markers Organs Presented Stimulation with MHC T cells Thymus T- cell High T-cell receptor Paracortical Yes Helper and Regulate gland receptor, numbers (TCR) sites (interior cytotoxic T immune CD to the cells and functions, kill molecules, follicles) memory cells foreign and MHC I infected receptors cells, synthesize cytokines B cells Bone Immunoglo Low numbers Immunoglobulins Cortex (in No Plasma cells Produce marrow bulin MHC I D and M follicles) and memory antibodies to and MHC II cells target, receptors inactivate, and neutralize, antigens © McGraw Hill, LLC 30  Characteristics of Antigens and Immunogens Antigen (Ag) – substance that elicits immune response in specific lymphocytes ________________ – property of behaving as an antigen Foreignness, size, shape, and accessibility Antigens have many antigenic determinants (epitopes) – small molecular group recognized by lymphocytes © McGraw Hill, LLC 31  Effects of Molecular Shape and Size on Antigenicity a) Whole cells of plants, animals, bacteria, fungi and viruses are easily recognized immunogens b) Proteins are good immunogens because they have many epitopes c) The repetitive nature of starches and DNA make them poor immunogens, individual glucose monomers are particularly bad immunogens (simple and small molecules) © McGraw Hill, LLC 32  Effects of Molecular Shape and Size on Antigenicity Complex macromolecules > 100,000 MW are most immunogenic Large size is not sufficient for antigenicity. _______ or antigenic determinant fits with the receptor like a key fits with a lock. © McGraw Hill, LLC 33  Effects of Molecular Shape and Size on Antigenicity ___________ – small foreign molecules that consist only of a determinant group and too small by themselves to elicit an immune response Carrier group contributes to the size of the complex and enhances the orientation of the antigen, while the hapten serves as the epitope © McGraw Hill, LLC 34  Functional Categories of Antigens Alloantigens – cell surface markers and molecules that occur in some members of the same species but not in others Determine blood group and major histocompatibility profile Responsible for incompatibilities in blood transfusion or organ grafting Superantigens – potent T cell stimulators Toxic shock toxin (massive release of cytokines leading to cell death) Allergens – antigens that evoke allergic reactions Autoantigens – molecules on self tissues for which tolerance is inadequate © McGraw Hill, LLC 35  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 antigen- presenting cells and lymphocytes © McGraw Hill, LLC 36  The Role of Antigen Processing and Presentation T-cell dependent antigens must be processed by phagocytes called ______________________ (APC) before their contact with T cells Three cell types can serve as APCs: Macrophages Dendritic cells (most common) B cells APCs modify the antigen; then the antigen is moved to the APC surface and bound to an MHC class II receptor to present to T cells © McGraw Hill, LLC 37  T-Cell Activation © McGraw Hill, LLC 38  T-Cell Responses and Cell-Mediated Immunity ____________________________(CMI) requires the direct involvement of T lymphocytes in the immune response T cells secrete cytokines that act directly on other cells Before T cells get activated, the antigen must be presented in association with an MHC complex on a APC, to ensure recognition of self Once activated, the T cell transforms in preparation for mitotic divisions to become a subset of effector and memory cells Differentiation will be determined by APC interleukin secretion © McGraw Hill, LLC 39  Types of T Cells TABLE 15.2 Characteristics of Subsets of T Cells Primary Receptors Types Functions/Important Features on T Cell Activates other CD4 and CD8 cells; secretes IL-2, tumor T helper cell 1 (TH1) CD4 necrosis factor, and interferon gamma; responsible for delayed hypersensitivity; interacts with MHC-II receptors Drives B-cell proliferation; secretes IL-4, IL-5, IL-6, IL-9, IL- T helper cell 2 (TH2) CD4 10, IL-13; can dampen TH1activity T helper 17 CD4 Promotes inflammation; secretes IL-17 Involved in development of immune tolerance; suppression T regulatory cell (Treg) CD4, CD25 of harmful immune responses, inflammation, autoimmunity Destroys a target foreign cell by lysis; important in destruction of cancer cells, virus-infected cells; graft T cytotoxic cell (TC) CD8 rejection; requires MHC I for function; may have some regulatory functions. © McGraw Hill, LLC 40  Types of T Cells T Helper (TH) cells (also called CD4 cells) They express CD4 receptors and are activated by antigen/MHC II Most prevalent type of T cell in blood and lymphoid organs Regulate immune reaction to antigens, including other T and B cells Also involved in activating macrophages and increasing phagocytosis Differentiation (TH1 or TH2 cells) depends on what set of cytokines is released from APCs © McGraw Hill, LLC 41  Types of T Cells Cytotoxic T (Tc) cells (also called CD8 cells) They express CD8 receptors and are activated by antigen/MHC I Destroy foreign or abnormal cells by secreting perforins and granzymes Natural killer (NK) cells Lack specificity; circulate through the spleen, blood, and lungs © McGraw Hill, LLC 42  T-Cell Activation and Differentiation © McGraw Hill, LLC 43  Cytotoxic T Cells Cancer cell being attacked by two small cytotoxic T cells. The Tc cell release perforins and granzymes, which will perforate the membrane of the cancer cell. The cancer cell will soon collapse, which the T cells will remain alive and active. (left, right): Source: Susan Arnold, Dr. Raowf Guirguis/ National Cancer Institute © McGraw Hill, LLC 44  __________________(NK) Cells 1) NK cell releases perforins, which polymerize and form a hole in the foreign cell membrane. 2) Granzymes from NK cell enter perforin hole and degrade foreign cell proteins. 3) Foreign cell dies by apoptosis. 4) Macrophage engulfs and digests dying cell. (b): Science History Images/Alamy Stock Photo © McGraw Hill, LLC 45  T Cells and Superantigens Reaction has drastic consequences _______________ are found primarily in bacteria and viruses, and are a form of virulence factor Enterotoxin from pathogenic staphylococci, certain toxins of group A streptococci, and proteins of Epstein-Barr virus Provoke overwhelming immune responses by large numbers of T cells regardless of specificity Release of massive amount of cytokines Blood vessel damage Toxic shock Multiorgan failure © McGraw Hill, LLC 46  Events in 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 © McGraw Hill, LLC 47  Events in B-Cell Responses The main events involved in B-cell responses are: 1. Clonal selection and binding of antigen 2. Induction by chemical mediators 3. B-cell/TH cell cooperation and recognition 4. B cell activation 5. Clonal expansion 6. Antibody production and secretion © McGraw Hill, LLC 48  B-Cell Activation and Differentiation © McGraw Hill, LLC 49  Antibody Structure and Functions ________________ (Ig): molecule with 4 polypeptide chains connected by disulfide bonds All antibodies have two functionally distinct segments (fragments): Antigen binding fragments (Fabs) “arms” with their amino-terminal end (variable regions of the heavy and light chains) as antigen-binding sites Crystallizable fragment (Fc) binds to various cells and molecules of the immune system © McGraw Hill, LLC 50  Antibody Structure and Functions Diagrammatic view of IgG depicts the principal regions (Fabs and Fc) of the molecule. Note that the fabs can swivel at the hinge region and provide flexibility in position. (b): Source: Dr. Timothy Vickers © McGraw Hill, LLC 51  Working Models of Antibody Structure (b): Source: Dr. Timothy Vickers Three-dimensional model of immunoglobulin shows the tertiary and quaternary structure achieved by intrachain and interchain bonds and the positioning of the light- and heavy-chain components. © McGraw Hill, LLC 52  Antigen-Antibody Binding The Fab antigen-binding site is composed of hypervariable regions with an extremely variable amino acid content The groove of this antigen binding site has a specific three- dimensional fit for the antigen The specificity of the two Fab sites is identical for each antigen An Ig molecule can bind two epitopes on the same cell or on two separate cells, linking the cells together © McGraw Hill, LLC 53  Antigen-Antibody Binding a) Good fit © McGraw Hill, LLC 54  Antigen-Antibody Binding b) No fit c) Poor fit © McGraw Hill, LLC 55  Antibody-Antigen Interactions The goal of antibodies secreted antibodies is to bind to the antigen that initiated the antibodies’ formation ______________ – process of coating microorganisms or other particles with specific antibodies so they are more readily recognized by phagocytes. Carried out by antibodies called “opsonins” ____________ – Antibodies fill the surface receptors on a virus or the active site on a microbial enzyme to prevent it from attaching © McGraw Hill, LLC 56  Antibody-Antigen Interactions Agglutination – Ab aggregation; cross-linking cells or particles into large clumps Complement fixation – Activation of the classical complement pathway can result in the specific rupturing of cells and some viruses Precipitation - Aggregation of particulate antigen © McGraw Hill, LLC 57  Antibody-Antigen Interactions © McGraw Hill, LLC 58  Functions of the Fc Fragment Fc fragment binds to cell membranes macrophages, neutrophils, eosinophils, mast cells, basophils, lymphocytes Regions on the Fc portion in certain antibodies fix complements Binding of Fc may cause release of cytokines © McGraw Hill, LLC 59  Classes of Immunoglobulins 5 functional classes (isotopes) of immunoglobulins (Ig): IgG – monomer, produced by plasma cells (primary response) and memory cells (secondary), most prevalent IgA – monomer circulates in blood, dimer in mucous and serous secretions IgM – pentamer, first class synthesized following Ag encounter IgD – monomer, serves as a receptor for antigen on B cells IgE – monomer, involved in allergic responses and parasitic worm infections The differences in these classes are primarily due to variations in the Fc © McGraw Hill, LLC 60  Antibodies in Serum Regardless of the site where antibodies are first secreted, a large quantity eventually ends up in the blood ________________: serum containing specific antibodies If separated by electrophoresis, globulins in antiserum separate into 4 bands: Alpha-1 (α1), alpha-2 (α2), beta (β), and gamma (γ) Most globulins are antibodies Gamma globulin (γ) is composed primarily of IgG β and α2 globulins are a mixture of IgG, IgA, and IgM © McGraw Hill, LLC 61  Monitoring Antibody Production over Time: Primary and Secondary Responses to Antigens © McGraw Hill, LLC 62  Monitoring Antibody Production over Time: Primary and Secondary Responses to Antigens Primary response. A latent period with no measurable antibody occurs early on. The first antibody to appear is IgM, followed later by IgG arising from activation of the first memory cells. Within weeks, the titer tapers back to low levels. Secondary response. A latent period is lacking because other memory lymphocytes from the earlier response are immediately ready to react. A rapid rise in antibody titer, mainly of IgG, is sustained for several weeks. A smaller amount of IgM Is also produced by naive B cells. © McGraw Hill, LLC 63  _________________ 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 © McGraw Hill, LLC 64  Use of Monoclonal Antibodies for Treatment Drug Names Used in Therapy for (Chemical and Trade) Cancer Drugs Trastuzumab Herceptin Breast cancer Rituximab Rituxan B-cell disorders (lymphomas, leukemias) Alemtuzumab Campath Chronic T-cell leukemia and lymphoma Pembrolizumab Keytruda Metastatic melanoma and lung cancer Other Applications Omalizumab Xolair Asthma Belimumab Benlysta Systemic lupus erythematosus Daclizumab Biogen Multiple sclerosis Ibalizumab Trogarza HIV Erenumab Aimovig Migraine Adalimumab Humira Rheumatoid arthritis, psoriasis Casirivimab and Regeneron COVID-19 Imdevimab © McGraw Hill, LLC 65  Immunity Categories by Mode of Acquisition Active immunity – results when a person is challenged with antigen that stimulates production of antibodies; creates memory, takes time to develop, 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 © McGraw Hill, LLC 66  Examples of Origins of Immunity 1. _____________________________: Getting an infection After recovering from infectious disease, a person may be actively resistant to reinfection (period varies according to the disease) 2. ________________________________: Mother to Child IgG antibodies bodies from the maternal bloodstream can pass or be actively transported across the placenta to the fetus IgA antibodies from breast milk react against microbes entering the intestine © McGraw Hill, LLC 67  Examples of Origins of Immunity 3. ________________________________: Immunotherapy A patient at risk for acquiring a particular infection is administered a preparation that contains specific antibodies against that infectious agent 4. ___________________________________: Vaccination Microbial (antigenic) stimulus, which triggers the immune system to produce antibodies and memory cells © McGraw Hill, LLC 68  Categories of Acquired Immunities Acquired Immunity Natural Immunity acquired through the normal life experiences not induced through medical means. © McGraw Hill, LLC 69  Categories of Acquired Immunities Active Immunity results when a person develops his own immune response to a microbe through infection. (left): Rido/Shutterstock © McGraw Hill, LLC 70  Categories of Acquired Immunities Passive Immunity results when a person receives preformed immunity through the placenta or nursing. (left-center): EyeWire Collection/Getty Images; © McGraw Hill, LLC 71  Categories of Acquired Immunities 4 Acquired Immunity Artificial Immunity produced purposefully through medical procedures (also called immunization). © McGraw Hill, LLC 72  Categories of Acquired Immunities Active Immunity (vaccination) results when a person develops his own immune response to a prepared microbial antigen. (center-right): Source: Amanda Mills/CDC © McGraw Hill, LLC 73  Categories of Acquired Immunities Passive Immunity results when a person is given selected immune substances made by another individual. (right): Arthur Tilley/Getty Images © McGraw Hill, LLC 74  Immunization: Providing Immune Protection Through Therapy 1. ________________________________immunization Useful for immunocompromised patients who cannot be vaccinated. Acts immediately; protection lasts 2 to 3 months Human antisera Intravenous immune globulin (IVIG), gamma globulin; Igs extracted from pooled blood of a large group of donors; treatment of choice in preventing measles and hepatitis A and in replacing antibodies in immunodeficient patients Specific immune globulin (SIG) from donors in a hyperimmune state after being vaccinated or infected by pertussis, tetanus, chickenpox, and hepatitis B © McGraw Hill, LLC 75  Immunization: Providing Immune Protection Through Therapy Antisera and antitoxins of animal origin Sera produced in horses are available for diphtheria, botulism, and spider and snake bites © McGraw Hill, LLC 76  Immunization: Providing Immune Protection Through Therapy 2. Artificial active immunity Can be conferred artificially by vaccination– 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 © McGraw Hill, LLC 77  Principles of Vaccine Preparation Most vaccines are prepared from: Killed whole cells or inactivated viruses Live, attenuated cells or viruses Antigenic molecules derived from bacterial cells or viruses Genetically engineered microbes or microbial agents © McGraw Hill, LLC 78  Principles of Vaccine Preparation TABLE 15.5 Checklist of Requirements for an Effective Vaccine It should have a low level of adverse side effects or toxicity and not cause serious harm. It should protect against exposure to natural, wild forms of pathogen. It should stimulate both antibody (B-cell) response and cell- mediated (T-cell) response. It should have long-term, lasting effects (produce memory cells). It should work with minimal doses or boosters. It should be inexpensive, have a relatively long shelf life, and be easy to administer. © McGraw Hill, LLC 79  ______________ versus ______________ Vaccines Advantages of live preparations are: Organisms can multiply and produce infection (but not disease) like the natural organism They confer long-lasting protection Usually require fewer doses and boosters Disadvantages include: Require special storage, can be transmitted to other people, can conceivably mutate back to virulent strain © McGraw Hill, LLC 80  Whole Pathogen Vaccines © McGraw Hill, LLC 81  Vaccines from Microbe Parts Acellular and subunit vaccines rely on just a portion of the cell of virus as an antigen. Cell structures including capsules, cell wall , or flagellar proteins generally make excellent antigens. Toxoid vaccines use a denatured exotoxin as the antigen, providing immunological protection against the toxin but not the bacterial cell. Tetanus and diphtheria vaccines use this approach because the toxin is far more dangerous than the bacteria that produce it. © McGraw Hill, LLC 82  Vaccines from Microbe Parts Exact antigenic determinants can be used when known: Capsules – pneumococcus, meningococcus Surface protein – anthrax, hepatitis B Exotoxins – diphtheria, tetanus Antigen can be taken from cultures, produced by genetic engineering, or synthesized © McGraw Hill, LLC 83  Genetically Engineered Vaccines Purified Antigen Vaccine Vaccines reliant on surface antigens can be produced by engineering a plasmid that contains the gene for the antigen and then inserting the plasmid into a yeast cell. The yeast cell will synthesize the antigen, which can be purified for use as a vaccine. © McGraw Hill, LLC 84  Genetically Engineered Vaccines _____________________vaccine – A cloning host can be stimulated to synthesize and secrete a protein product (antigen), which is then harvested and purified for use as a vaccine. Hepatitis and human papillomavirus currently being prepared this way Antigens from syphilis, Schistosoma, and influenza are currently being considered as potential vaccine material © McGraw Hill, LLC 85  Genetically Engineered Vaccines Viral vector vaccines – use modified virus to deliver the genetic code of the antigen to human cells, mimicking what happens during a viral infection. Johnson & Johnson COVID vaccine Vaccine for Ebola in 2019 Trials for adenovirus-based vaccines against HIV and Zika are ongoing © McGraw Hill, LLC 86  Viral Vector Vaccines Barry Chess/McGraw Hill © McGraw Hill, LLC 87  Genetically Engineered Vaccines RNA vaccines – viral RNA is inoculated into the recipient Primary means of protecting against COVID-19 Vaccine against influenza currently in clinical trials Inoculation causes B and T to be sensitized, forming memory cells The mRNA from the vaccine is eventually destroyed by enzymes in the cell, leaving no permanent trace. © McGraw Hill, LLC 88 © McGraw Hill 89  mRNA Vaccines Barry Chess/McGraw Hill © McGraw Hill, LLC 90  Development of New Vaccines No reliable vaccines are available for HIV, various diarrheal diseases (E. coli, Shigella), a number of respiratory diseases, and worm infections Distribution of vaccines poses a difficulty Companies are using plants to mass produce vaccine antigens to economically harvest vaccine antigens. Tests are underway to grow tomatoes, potatoes, and bananas that synthesize proteins from cholera, hepatitis, papillomavirus, and E. coli pathogens. © McGraw Hill, LLC 91  Routes of Administration and Side Effects of Vaccines Most administered by injection; few oral, nasal Some vaccines require an ________, compound 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 When known or suspected adverse effects have been detected, vaccines are altered or withdraw © McGraw Hill, LLC 92  Herd Immunity Immune individuals will not harbor it, reducing the occurrence of pathogens – ____________________ Less likely that a nonimmunized person will encounter the pathogen © McGraw Hill, LLC 93  Vaccine Protection: Magical but Not Magic TABLE 15.6 Protective Effects of Vaccines Annual 20th century morbidity and 2021 morbidity of selected diseases in the U.S. 20th Century Reported Percentage Decrease Annual Morbidity Cases in 2021 Measles 530,217 5 >99% Pertussis 200,752 1251 92% Mumps 162,344 126 99% Rubella 47,745 4 >99% Smallpox 29,005 0 100% Polio (paralytic) 16,316 0 100% © McGraw Hill, LLC 94  Because learning changes everything. ® www.mheducation.com © McGraw Hill LLC. 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