Immunity Chapter 38 Part 1

Impacts, Issues Frankie’s Last Wish Infection with a common, sexually transmitted virus (HPV) causes most cervical cancers – including the one that killed Frankie McCullogh

38.1 Integrated Responses to Threats Immunity The capacity to resist and combat infection by pathogens such as viruses, bacteria, and fungi In vertebrates, innate and adaptive immune systems work together to combat infection and injury

Evolution of the Body’s Defenses Proteins in eukaryotic cell membranes have unique patterns that the body recognizes as self Cells of multicelled eukaryotes have receptors that recognize nonself cues (PAMPs) on or in pathogens, and trigger defense responses

Innate Immunity Binding of a receptor with a PAMP triggers immediate, general defense responses that are part of inborn innate immunity Complement Proteins that destroy microorganisms or flag them for phagocytosis An innate immune response

Adaptive Immunity Adaptive immunity is a system of defenses that specifically targets billions of different antigens an individual may encounter during its lifetime Antigen PAMP or other molecule the body recognizes as nonself that triggers an active immune response

Three Lines of Defense 1. Physical, chemical, and mechanical barriers Keep pathogens outside the body 2. Innate immunity General responses destroy invaders inside the body before they become established 3. Adaptive immunity Huge populations of white blood cells form to target and remember a specific antigen

Mucus and Cilia: Physical Barriers

Comparing Innate and Active Immunity

The Defenders White blood cells (leukocytes) specialized for different tasks carry out all immune responses Phagocytes (neutrophils, macrophages, dendritic cells) Secretory cells (eosinophils, basophils, mast cells Lymphocytes (B and T lymphocytes, natural killer cells)

The Defenders All white blood cells secrete chemicals, including cell-to-cell signaling molecules (cytokines) that coordinate all aspects of immunity Interleukins Interferons Tumor necrosis factors

White Blood Cells

Figure 38.3 White blood cells (leukocytes). Staining shows details such as cytoplasmic granules that contain enzymes, toxins, and signaling molecules. Fig. 38-3a, p. 661

Figure 38.3 White blood cells (leukocytes). Staining shows details such as cytoplasmic granules that contain enzymes, toxins, and signaling molecules. Fig. 38-3b, p. 661

Chemical Weapons of Immunity

38.1 Key Concepts Overview of Body Defenses The vertebrate body has three lines of immune defenses Surface barriers prevent invasion by ever-present pathogens General innate responses rid the body of most pathogens Adaptive responses specifically target pathogens and cancer cells

38.2 Surface Barriers Normal flora Billions of microorganisms normally live on human surfaces, including interior tubes and cavities of digestive and respiratory tracts A pathogen can cause infection only if it enters the internal environment by penetrating skin or other protective barriers at the body’s surfaces

Some Normal Flora

Vertebrate Surface Barriers Physical, chemical, and mechanical barriers keep microorganisms outside body tissues Skin Mucus and cilia Lysozyme Gastric fluid and bile salts Normal flora Urination

Vertebrate Surface Barriers

Skin Healthy, intact skin is an effective surface barrier

cells die and become filled with keratin as they are pushed toward skin surface epithelial cells die and become filled with keratin as they are pushed toward skin surface epidermis dividing epithelial cells Figure 38.5 One surface barrier to infection: epidermis of human skin. 0.1 mm Fig. 38-5, p. 663

38.3 Remember to Floss Dental plaque A thick, sticky biofilm of glycoproteins, bacteria, and their products that contribute to tooth decay and gum disease (periodontitis) Nine of every ten cardiovascular disease patients have serious periodontal disease Oral bacteria associated with periodontitis are also found in atherosclerotic plaque

Plaque

38.2-38.3 Key Concepts Surface Barriers Skin, mucous membranes, and secretions at the body’s surfaces function as barriers that exclude most microbes

38.4 Innate Immune Responses Innate immune mechanisms nonspecifically eliminate pathogens that invade internal tissues before they become established Phagocytes Complement Inflammation Fever

Phagocytes Macrophages Large phagocytes that patrol interstitial fluid and engulf and digest pathogens Secrete cytokines when receptors bind to antigen Cytokines attract more macrophages, neutrophils, and dendritic cells to infection site

Complement Complement proteins become activated when they encounter antigen Cascading enzyme reactions concentrate activated complement at infection site Complement attracts phagocytes to infection site and tags pathogens for destruction Forms attack complexes that puncture bacteria Helps mediate active immunity

Complement Attack Complexes

activated complement antibody molecule Figure 38.7 One effect of complement protein activation. Activation causes lysis-inducing pore complexes to form. The micrograph shows holes in a pathogen’s surface that were made by membrane attack complexes. A In some responses, complement proteins become activated when antibodies (the Y-shaped molecules) bind to antigen—in this case, antigen on the surface of a bacterium. Fig. 38-7a, p. 664

B Complement also becomes activated when it binds directly to antigen. activated complement bacterial cell Figure 38.7 One effect of complement protein activation. Activation causes lysis-inducing pore complexes to form. The micrograph shows holes in a pathogen’s surface that were made by membrane attack complexes. B Complement also becomes activated when it binds directly to antigen. Fig. 38-7b, p. 664

activated complement Figure 38.7 One effect of complement protein activation. Activation causes lysis-inducing pore complexes to form. The micrograph shows holes in a pathogen’s surface that were made by membrane attack complexes. C By cascading reactions, huge numbers of different complement molecules form and assemble into structures called attack complexes. Fig. 38-7c, p. 664

attack complex that causes a pore to form through the lipid bilayer of the bacterium Figure 38.7 One effect of complement protein activation. Activation causes lysis-inducing pore complexes to form. The micrograph shows holes in a pathogen’s surface that were made by membrane attack complexes. D The attack complexes become inserted into the target cell’s lipid envelope or plasma membrane. Each complex makes a large pore form across it. E The pores bring about lysis of the cell, which dies because of the severe structural disruption. Fig. 38-7de, p. 664

Inflammation Inflammation A local response to tissue damage characterized by redness, warmth, swelling and pain, triggered by activated complement and cytokines Mast cells release histamine, increasing capillary permeability Phagocytes and plasma proteins leak out, attack invaders, form clots, and clean up debris

Inflammation Response to Bacterial Infection

A Bacteria invade a tissue and release toxins or metabolic products that damage tissue. D Complement proteins attack bacteria. Clotting factors also wall off inflamed area. E Neutrophils and macrophages engulf invaders and debris. Macrophage secretions kill bacteria, attract more lymphocytes, and initiate fever. B Mast cells in tissue release histamine, which widens arterioles (causing redness and warmth) and increases capillary permeability. C Fluid and plasma proteins leak out of capillaries; localized edema (tissue swelling) and pain result. Figure 38.8 Inflammation in response to bacterial infection. Above, in this example, white blood cells and plasma proteins enter a damaged tissue. Right, the micrograph shows a phagocyte squeezing through a blood vessel wall. Stepped Art Fig. 38-8, p. 665

Fever Fever A temporary rise in body temperature – above the normal 37°C (98.6°F) – that often occurs in response to infection Cytokines stimulate brain cells to release prostaglandins, which act on the hypothalamus Fever enhances the immune response by speeding up metabolism and phagocyte activity Fever over 40.6°C (105°F) can be dangerous

38.4 Key Concepts Innate Immunity Innate immune responses involve a set of general, immediate defenses against invading pathogens Innate immunity includes phagocytic white blood cells, plasma proteins, inflammation, and fever

38.5 Overview of Adaptive Immunity Vertebrate adaptive immunity adapts to different antigens it encounters during its lifetime Lymphocytes and phagocytes interact to effect four defining characteristics: Self/nonself recognition, specificity, diversity, and memory

Self/Nonself Recognition Self versus nonself recognition Each kind of cell or virus has a unique identity MHC markers Plasma membrane self-recognition proteins T cell receptors (TCRs) Antigen receptors that recognize MHC markers as self, antigens as nonself

Specificity and Diversity Defenses are tailored to target specific antigens Diversity There are potentially billions of different antigen receptors on T and B cells

Memory Memory The capacity of the adaptive immune system to remember an antigen If the same antigen appears again, B and T cells make a faster, stronger response

First Step – The Antigen Alert Once a B or T cell recognizes and binds to a specific antigen, it begins to divide by mitosis All descendent cells recognize the same antigen T cells do not recognize an antigen unless it is presented by an antigen-presenting cell Macrophages, B cells, and dendritic cells digest particles and display antigen-MHC complexes

Cell Types Effector cells Memory cells Differentiated lymphocytes (B and T cells) that act at once to fight infection Memory cells Long-lived B and T cells reserved for future encounters with the same antigen

Antigen Processing

Figure 38.9 Antigen processing. (a) A macrophage ingests a foreign cell. (b) From encounter to display, what happens when a B cell, macrophage, or dendritic cell engulfs an antigenic particle—in this case, a bacterium. These cells engulf, process, and then display antigen bound to MHC markers. The displayed antigen is presented to T cells. Fig. 38-9a, p. 666

cell engulfs an antigen-bearing particle antigen–MHC complexes become displayed on cell surface endocytic vesicle forms MHC markers bind fragments of particle particle is digested into bits lysosome fuses with endocytic vesicle Figure 38.9 Antigen processing. (a) A macrophage ingests a foreign cell. (b) From encounter to display, what happens when a B cell, macrophage, or dendritic cell engulfs an antigenic particle—in this case, a bacterium. These cells engulf, process, and then display antigen bound to MHC markers. The displayed antigen is presented to T cells. Stepped Art Fig. 38-9b, p. 666

Two Arms of Adaptive Immunity Antibody-mediated immune response B cells produce antibodies that bind to specific antigen particles in blood or interstitial fluid Cell-mediated immune response Cytotoxic T cells and NK cells detect and destroy infected or altered body cells

Interactions Between Antibody-Mediated and Cell-Mediated Responses

Intercepting and Clearing Out Antigen After engulfing antigen-bearing particles, dendritic cells or macrophages migrate to lymph nodes, where T cells bind and initiate responses During an infection, lymph nodes swell due to accumulation of T cells Antibody-antigen complexes bound by complement are cleared by the liver and spleen

The Lymphatic System

(thymus gland) lymph node, midsection Figure 38.11 Battlegrounds of adaptive immunity. Lymph nodes along lymph vascular highways hold macrophages, dendritic cells, B cells, and T cells. The spleen filters antigenic particles from blood. spleen Fig. 38-11, p. 667

38.6 Antibodies and Other Antigen Receptors Antigen receptors on B and T cells have the potential to recognize billions of different antigens Antibody Y-shaped antigen receptor (protein), made only by B cells, that binds only to the antigen that prompted its synthesis Activates complement, facilitates phagocytosis, or neutralizes pathogens or toxins

Antibody Structure

binding site for antigen binding site for antigen variable region (dark green) of heavy chain variable region of light chain constant region of light chain constant region (bright green) of heavy chain, including a hinged region Figure 38.12 Antibody structure. (a) An antibody molecule has four polypeptide chains joined in a Y-shaped configuration. In this ribbon model, the two heavy chains are shown in green, and the two light chains are teal. (b) Each chain has a variable and a constant region. Fig. 38-12b, p. 668

Five Classes of Antibodies Constant regions determine 5 classes of antibodies (immunoglobins IgG, IgA, IgE, IgM, and IgD), each with different functions B cell receptors are membrane-bound IgM or IgD antibodies

Five Classes of Antibodies

Making Antigen Receptors Genes that encode antigen receptors occur in several segments on different chromosomes Different versions are randomly spliced together during B or T cell differentiation, producing about 2.5 billion different combinations T cells mature in the thymus, which stimulates production of MHC and T cell receptors

Antigen Receptor Diversity

38.7 The Antibody-Mediated Immune Response Antigen activates naïve B cells and dendritic cells Naïve T cell binds to APC and differentiates into effector and memory helper T cells Helper T cells bind antigen-MHC complexes on activated B cell and secrete cytokines B cell differentiates into effector B cells, which produce antibodies targeting a specific antigen, and memory B cells

Antibody-Mediated Immune Response

antigen- presenting dendritic cell B bacterium antigen- presenting dendritic cell B The dendritic cell engulfs the same kind of bacterium that the B cell encountered. A naive B cell B cell complement A The B cell receptors on a naïve B cell bind to a specific antigen on the surface of a bacterium C The antigen-MHC complexes on the antigen-presenting cell are recognized by antigen receptors on a naïve T cell. naive T cell effector helper T cell memory helper T cell C D cytokines D Antigen receptors of one of the effector helper T cells bind antigen-MHC complexes on the B cell. E memory B cell effector B cell E The cytokines induce the B cell to divide, giving rise to many identical B cells. F F The effector B cells begin making and secreting huge numbers of IgA, IgG, or IgE. Figure 38.14 Example of an antibody-mediated immune response. Stepped Art Fig. 38-14, p. 670

Clonal Selection and Memory Cells Only B cells with receptors that bind antigen divide (clone) and differentiate into effector and memory B cells First exposure (primary response) produces memory B and T cells; secondary response is stronger and faster

Clonal Selection and Memory Cells

to a matching B cell receptor. antigen Antigen binds only to a matching B cell receptor. mitosis clonal population of effector B cells Figure 38.15 B cell maturation. Many effector B cells secrete many antibodies. Fig. 38-15a, p. 671

B cell with bound antigen mitosis primary immune response effector cells memory cells mitosis Figure 38.15 B cell maturation. secondary immune response effector cells memory cells Fig. 38-15b, p. 671

Primary and Secondary Immune Response

38.8 The Cell-Mediated Response Cell-mediated immune response Dendritic cell ingests altered body cell, displays antigen-MHC complexes, migrates to lymph node Naïve helper T and cytotoxic T cells bind to APC Activated helper T divides and differentiates into memory and effector cells; cytokines signal division of activated cytotoxic T cells Cytotoxic T cells circulate and touch-kill altered body cells

Primary Cell-Mediated Response

A A dendritic cell engulfs a virus-infected cell. antigen- presenting dendritic cell A A dendritic cell engulfs a virus-infected cell. B effector helper T cell memory helper T cell B Receptors on a naïve helper T cell bind to antigen-MHC complexes on the dendritic cell. naive helper T cell naive cytotoxic T cell C activated cytotoxic T cell C Receptors on a naïve cytotoxic T cell bind to the antigen-MHC complexes on the surface of the dendritic cell. D cytokines memory cytotoxic T cell effector cytotoxic T cell D The activated cytotoxic T cell recognizes cytokines secreted by the effector helper T cells as signals to divide. Figure 38.17 Example of a primary cell-mediated immune response. Figure It Out: What do the large red spots represent? Answer: Viruses E E The new cytotoxic T cells circulate through the body. Stepped Art Fig. 38-17, p. 672

Cytotoxic T Cells Cytotoxic T cells touch-kill cells displaying antigen-MHC markers; perforin and proteases puncture cells and kill them by apoptosis

cytotoxic T cell cancer cell Figure 38.18 T cell receptor function. (a) A TCR (green) on a T cell binds to an MHC marker (tan) on an antigen-presenting cell. An antigen (red) is bound to the MHC marker. (b) A cytotoxic T cell caught in the act of touch-killing a cancer cell. Fig. 38-18b, p. 673

Natural Killer Cells Cytokines secreted by helper T cells also stimulate natural killer (NK) cell division Unlike cytotoxic T cells, NK cells can kill infected cells that are missing all or part of their MHC markers

38.5-38.8 Key Concepts Adaptive Immunity In an adaptive immune response, white blood cells destroy specific pathogens or altered cells Some make antibodies in an antibody-mediated immune response; others destroy ailing body cells in a cell-mediated response

38.9 Allergies Allergy An immune response to a typically harmless substance (allergen) First exposure stimulates production of IgE, which becomes anchored to mast cells and basophils Later exposure stimulates secretion of histamine and cytokines that initiate inflammation Anaphylactic shock is a severe and potentially fatal allergic reaction

Allergies: Annoying or Life-Threatening

38.10 Vaccines Immunization Vaccine (active immunization) The administration of an antigen-bearing vaccine designed to elicit immunity to a specific disease Vaccine (active immunization) A preparation containing an antigen that elicits a primary immune response Passive immunization Administration of antibodies; no immune response

Smallpox Vaccine Edward Jenner created the first vaccine against smallpox, which has now been eradicated

Recommended Immunizations

38.11 Immunity Gone Wrong Misdirected or compromised immunity is sometimes the result of mutation or environmental factors The outcome is often severe or lethal

Autoimmune Disorders Sometimes lymphocytes and antibodies fail to discriminate between self and nonself Autoimmune response An immune response that is misdirected against the person’s own tissues Rheumatoid arthritis, Graves’ disease, multiple sclerosis

Immunodeficiency In immunodeficiency, the immune response is insufficient to protect a person from disease Primary immune deficiencies are present at birth SCIDs, ADA Secondary immune deficiency results from exposure to an outside agent, such as a virus AIDS

Gene Therapy Primary immunodeficiency is the result of mutation; Cindy Cutshwall was successfully treated for ADA, a type of severe combined immunodeficiency (SCID), using gene therapy

38.12 AIDS Revisited—Immunity Lost Acquired immune deficiency syndrome (AIDS) A group of disorders resulting from a failure of the immune system due to HIV infection Includes rare cancers and infections caused by normally harmless microorganisms Human immunodeficiency virus (HIV) A retrovirus that attacks specific cells of the immune system, including helper T cells

T Cells and AIDS

Global HIV and AIDS Cases

Transmission and Treatment Common modes of HIV transmission Unprotected sex, mother to child, shared syringes HIV testing Antibodies are found in blood, saliva or urine Drugs There is no cure; protease inhibitors and reverse transcriptase inhibitors can slow its progress

Prevention Vaccines Education Experimental vaccines are mostly ineffective or risky; the virus’ high mutation rate is an obstacle Education The best option for preventing the spread of HIV is teaching people how to avoid being infected

The Global AIDS Program The global battle continues; researchers are using several strategies to develop an HIV vaccine

38.9-38.12 Key Concepts Immunity In Our Lives Vaccines are an important part of any health program Failed or faulty immune mechanisms can result in allergies, immune deficiencies, or autoimmune disorders The immune system itself is a target of human immunodeficiency virus (HIV)

Animation: Inflammatory response

Animation: Complement proteins

Animation: Antibody-mediated response

Animation: Clonal selection of a B cell

Animation: Immune memory

Animation: Cell-mediated response

Animation: Antibody structure

Animation: Cell mediated response

Animation: Gene rearrangements

Animation: Human lymphatic system

Animation: Immune responses

Animation: Innate defenses

ABC video: Food Allergy Increase

Video: HPV vaccine

Video: Gene therapy