Marieb Human Anatomy & Physiology Twelfth Edition PDF

Marieb Human Anatomy & Physiology Twelfth Edition Chapter 21 The Immune System: Innate and Adaptive Body Defenses PowerPoint® Lecture Slides...

Marieb Human Anatomy & Physiology Twelfth Edition Chapter 21 The Immune System: Innate and Adaptive Body Defenses PowerPoint® Lecture Slides prepared by Justin A. Moore, American River College Copyright © 2025 Pearson Education, Inc. All Rights Reserved Why This Matters (Career Connection) Understanding the signs of a healthy immune response will help you assess your patients Copyright © 2025 Pearson Education, Inc. All Rights Reserved  The Immune System (1 of 2) Immune system provides resistance to disease-causing microorganisms e.g. bacteria, fungi, and viruses Body has three lines of defense that together provide resistance to disease, or immunity; in the order a pathogen would encounter them, the defenses are: 1. Surface barriers ▪ Provide first line of defense ▪ Consists of intact skin and mucosae (structural barriers designed to keep invaders out) 2. Innate internal defenses ▪ Provide second line of defense ▪ Called into action whenever first line penetrated. General response ▪ Relies on inflammation and internal defenses (e.g., antimicrobial proteins and phagocytes) to inhibit spread of invaders 3. The adaptive (specific) defense system ▪ Provides third line of defense ▪ Elite fighting force to attack identified enemies. Specific response ▪ Response takes much longer to mount (than innate response) Copyright © 2025 Pearson Education, Inc. All Rights Reserved The Immune System (2 of 2) Innate and adaptive defenses are integrated, always working together – Specifically: ▪ Innate and adaptive systems release and recognize (bind to) many of the same defensive molecules ▪ Innate responses have specific pathways to target certain foreign substances (not as nonspecific as once thought) ▪ Proteins released during innate responses alert cells of adaptive system to presence of specific foreign molecules in body When immune system operating effectively, it protects body from most infectious microbes and cancer cells. Copyright © 2025 Pearson Education, Inc. All Rights Reserved An Overview of the Immune System Focus Figure 21.1 An overview of the immune system. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Part 1—Innate Defenses Surface barriers and innate internal defenses are in place at birth, ready to resist invading pathogens (harmful or disease-causing microbes) – Adaptive immune system called into action to reinforce and enhance innate defenses when they alone cannot protect us – Innate defenses reduce workload of adaptive system by preventing entry and spread of microbes Copyright © 2025 Pearson Education, Inc. All Rights Reserved 21.1 Surface Barriers Act as the First Line of Defense to Keep Invaders Out of the Body (1 of 2) Surface barriers are skin and mucous membranes, along with their secretions – Heavily keratinized epidermis highly effective for most microbes – Mucosae provide similar mechanical barriers within the body (lining the tracts) These barriers produce protective chemicals that inhibit or destroy microbes – Acid: acidity of skin, vaginal, and stomach secretions inhibits bacterial growth; called acid mantle – Enzymes: lysozyme of saliva, respiratory mucus, and lacrimal fluid kills many microbes; protein-digesting enzymes in stomach kill many microbes – Mucin: sticky mucus (protein mucin dissolved in water) lines digestive and respiratory tract; traps microbes – Defensins: broad-spectrum antimicrobial peptides secreted in response to barrier breach and inflammation; inhibit microbial growth – Other chemicals: some lipids in sebum and dermcidin in eccrine sweat are toxic to bacteria Copyright © 2025 Pearson Education, Inc. All Rights Reserved 21.1 Surface Barriers Act as the First Line of Defense to Keep Invaders Out of the Body (2 of 2) Respiratory tract also has structural modifications to stop pathogens – Mucus-coated hairs in nose trap inhaled particles – Cilia of upper tract sweep dust- and bacteria-laden mucus toward mouth Surface barriers breached by nicks or cuts trigger the internal innate defense to protect deeper tissues Copyright © 2025 Pearson Education, Inc. All Rights Reserved Table 21.1 The First Line of Defense: Surface Membrane Barriers Category/Associated Elements Protective Mechanism Intact skin epidermis Forms a mechanical barrier that prevents entry of pathogens and other harmful substances into the body Acid mantle of skin Skin secretions (sweat and sebum) make the epidermal surface acidic, which inhibits bacterial growth; also contain various bactericidal chemicals Keratin Provides resistance against acids, alkalis, and bacterial enzymes Intact mucous membranes Form a mechanical barrier that prevents the entry of pathogens Mucus Traps microorganisms in the respiratory and digestive tracts Filter and trap microorganisms in the nasal passages Nasal hairs Propel debris-laden mucus away from the nasal cavity and lower respiratory Cilia passages Contains concentrated hydrochloric acid and protein-digesting enzymes that Gastric juice destroy pathogens in the stomach Acid mantle of vagina Inhibits growth of most bacteria and fungi in the female reproductive tract Continuously lubricate and cleanse the eyes (tears) and oral cavity (saliva); contain Lacrimal secretion (tears); lysozyme, an enzyme that destroys microorganisms saliva Normally acid pH inhibits bacterial growth; cleanses the lower urinary tract as it Urine flushes from the body Copyright © 2025 Pearson Education, Inc. All Rights Reserved 21.2 Innate Internal Defenses Are Cells and Chemicals That Act as the Second Line of Defense – Includes variety of nonspecific cellular and chemical means to protect body: phagocytes, natural killer cells, antimicrobial proteins, inflammation, and fever – Identifies potential pathogens by recognizing (binding to) specific-shaped molecules (e.g., carbohydrates) found on them, but not normal human cells ▪ The receptors that do this are called pattern recognition receptors – One class, Toll-like receptors (TLRs), play central role in triggering immune responses Humans have 11 TLRs, each recognizes a particular class of attacking microbe – E.g., one responds to glycolipid in cell walls of tuberculosis bacterium – Many cells (including macrophages and epithelial cells lining respiratory and GI tracts) have TLRs, allowing them to recognize invaders and initiate inflammation. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Phagocytes (1 of 3) Phagocytes: white blood cells (WBCs) that ingest and digest (eat) foreign invaders and cellular debris Neutrophils: most abundant phagocytes; phagocytize infectious material in tissues Macrophages: most active phagocytes – Free macrophages wander through tissue spaces; e.g., alveolar macrophages ▪ Derived from WBCs called monocytes – Fixed macrophages are permanent residents of particular organs; e.g., Kupffer macrophages of liver ▪ Formed in embryo (not derived from monocytes) Copyright © 2025 Pearson Education, Inc. All Rights Reserved Phagocytosis (1 of 6) Figure 21.1a Phagocytosis. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Phagocytes (2 of 3) Phagocytosis – Starts when phagocyte receptors bind particle, which is then pulled inside and enclosed within a membrane-lined vesicle – Resulting phagosome fuses with a lysosome to form a phagolysosome – Phagolysosome acidified in macrophages (and neutrophils); then lysosomal enzymes digest contents; but some pathogens are resistant to these enzymes ▪ For those not killed (e.g., tuberculosis bacillus), helper T cells stimulate the macrophage to produce a respiratory burst, killing pathogens by: – Releasing highly destructive free radicals – Producing oxidizing chemicals (e.g., hydrogen peroxide and “bleach”) – Increasing pH and osmolarity of phagolysosome, which activates other protein-digesting enzymes – Defensins (secreted by neutrophils) also help by piercing membrane of pathogen Copyright © 2025 Pearson Education, Inc. All Rights Reserved Phagocytosis (2 of 6) Figure 21.1b Phagocytosis. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Phagocytosis (3 of 6) Figure 21.1b Phagocytosis. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Phagocytosis (4 of 6) Figure 21.1b Phagocytosis. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Phagocytosis (5 of 6) Figure 21.1b Phagocytosis. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Phagocytosis (6 of 6) Figure 21.1b Phagocytosis. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Phagocytes (3 of 3) Phagocytosis (continued.) – Some microbes have external capsules that hide their surface carbohydrate signatures, helping them evade capture ▪ Immune system counters this by coating pathogens with opsonins, which act as “handles” for phagocytes to grab on to, greatly accelerating phagocytosis – Opsonins are complement proteins or antibodies ▪ Any pathogen can be coated with opsonins, a process called opsonization – Phagocytes unable to ingest their targets can release their toxic chemicals into the extracellular fluid ▪ E.g., neutrophils can undergo netosis, releasing a sticky net of their own DNA and proteins to trap and kill extracellular pathogens – Unlike macrophages, neutrophils rapidly destroy themselves in the process of killing their targets Netosis Copyright © 2025 Pearson Education, Inc. All Rights Reserved Natural Killer (NK) Cells Are large granular lymphocytes (nonphagocytic) that police blood and lymph – Rather than react to specific infected or tumor cells, NK cells look for general abnormalities (e.g., lack of “self” cell-surface proteins called MHC) – Can kill cancer and virus-infected cells before adaptive immune system is activated ▪ By inducing apoptosis (same mechanism used by cytotoxic T cells) – Also secrete potent chemicals that enhance inflammatory response Copyright © 2025 Pearson Education, Inc. All Rights Reserved Inflammation: Tissue Response to Injury (1 of 6) Inflammation is a nonspecific response to any tissue injury – Causes include trauma, intense heat, irritating chemicals, or infection – Suffix –itis signifies inflammation (e.g., tonsillitis, appendicitis, and tendonitis) Benefits of inflammation: – Prevents spread of pathogens – Disposes of cell debris and pathogens – Alerts adaptive immune system – Sets stage for repair Four cardinal signs of acute inflammation: redness, heat, swelling, and pain Copyright © 2025 Pearson Education, Inc. All Rights Reserved Inflammation: Tissue Response to Injury (2 of 6) Inflammatory chemical release – Inflammation begins with flood of inflammatory chemicals released into ECF by injured or stressed tissue cells, and immune cells ▪ Histamine released by mast cells is a potent inflammatory chemical; others include kinins, prostaglandins, and cytokines – If inflammation prompted by pathogens, a group of plasma proteins known as complement is activated to form potent inflammatory chemicals – All Inflammatory chemicals dilate local arterioles and make their capillaries leakier ▪ Many also attract phagocytes to area ▪ Some mobilize lymphocytes and other elements of adaptive immunity Copyright © 2025 Pearson Education, Inc. All Rights Reserved Table 21.2 Inflammatory Chemicals Chemical Source Physiological Effects Histamine Granules of mast cells and basophils.(◄ p. 653). Promotes vasodilation of local Released in response to mechanical injury, arterioles, increasing blood flow to presence of certain microorganisms, and injured area. Increases permeability of chemicals released by neutrophils. local capillaries, promoting formation of exudate. Kinins (bradykinin and A plasma protein, kininogen, is split by the Same as for histamine. Also induce others) enzyme kallikrein found in plasma, urine, saliva, chemotaxis of leukocytes and prompt and in lysosomes of neutrophils and other types neutrophils to release lysosomal of cells. Splitting releases active kinin peptides. enzymes, thereby enhancing generation of more kinins. Induce pain. Prostaglandins (◄ p. 48) Fatty acid molecules produced from arachidonic Same as for histamine. Also induce acid found in all cell membranes; generated by neutrophil chemotaxis. Induce pain. enzymes of neutrophils, basophils, mast cells, (Some prostaglandins are anti- and others. inflammatory.) Blank Complement See Table 21.3.(p. 791). Blank Cytokines See Table 21.8.(p. 809). Copyright © 2025 Pearson Education, Inc. All Rights Reserved Inflammation: Tissue Response to Injury (3 of 6) Vasodilation and increased vascular permeability – Local vasodilation causes local hyperemia (increased blood flow), which brings more immune cells and chemicals to affected area ▪ Accounts for two cardinal signs—redness and heat – Increased capillary permeability allows exudate—fluid containing clotting factors and antibodies—to seep from blood into tissue ▪ Flushes foreign material into lymphatics for processing in lymph nodes ▪ Delivers important proteins like complement and clotting factors to ISF ▪ Fibrin mesh (clot) acts as scaffold for repair and isolates injured area to prevent spread of pathogens – Results in local swelling (edema); pressure on nerve endings contributes to pain (as do bacterial toxins and sensitizing effects of prostaglandins and kinins) Copyright © 2025 Pearson Education, Inc. All Rights Reserved Inflammation: Tissue Response to Injury (4 of 6) Phagocyte mobilization – Neutrophils (followed by monocytes) flood damaged tissue; four steps: 1. Leukocytosis: increase in number of WBCs; characteristic of inflammation 2. Margination: phagocytes cling to wall of capillaries and postcapillary venules 3. Diapedesis: soon the neutrophils flatten and squeeze between endothelial cells—a process called diapedesis 4. Chemotaxis: inflammatory chemicals act as chemotactic agents (like homing devices); promote positive chemotaxis of WBCs toward injured area Copyright © 2025 Pearson Education, Inc. All Rights Reserved Inflammation: Tissue Response to Injury (6 of 6) 12 hours after entering tissue, monocytes transformed into macrophages – Replace dying neutrophils – Responsible for the final disposal of cell debris as acute inflammation ends ▪ Also predominate at sites of chronic inflammation Goal of inflammation is to clear injured area of pathogens, dead tissue cells, and any other debris so that tissue can be repaired Copyright © 2025 Pearson Education, Inc. All Rights Reserved Phagocyte Mobilization (1 of 4) Figure 21.2 Phagocyte mobilization. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Phagocyte Mobilization (2 of 4) Figure 21.2 Phagocyte mobilization. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Phagocyte Mobilization (3 of 4) Figure 21.2 Phagocyte mobilization. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Phagocyte Mobilization (4 of 4) Figure 21.2 Phagocyte mobilization. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Antimicrobial Proteins (1 of 5) Antimicrobial proteins enhance innate defenses by: – Attacking microbes directly, or – Hindering their ability to reproduce Most important antimicrobial proteins are: – Interferons – Complement proteins Copyright © 2025 Pearson Education, Inc. All Rights Reserved Antimicrobial Proteins (2 of 5) Interferons – Interferons (IFNs): family of immune modulating proteins produced by various cells. – Virus-infected cells can secrete IFNs that “interfere” with viral replication in healthy neighboring cells ▪ IFNs enter neighboring cells and stimulate production of proteins that block further protein synthesis and degrade viral RNA – IFN alpha ( ) and beta () also activate NK cells – IFN gamma (  ), or immune interferon, is secreted by lymphocytes and has widespread defense mobilizing effects (e.g., activates macrophages) – IFNs used to treat disorders like hepatitis C, genital warts, and multiple sclerosis Copyright © 2025 Pearson Education, Inc. All Rights Reserved The Interferon Mechanism Against Viruses (1 of 5) Figure 21.4 The interferon mechanism against viruses. Copyright © 2025 Pearson Education, Inc. All Rights Reserved The Interferon Mechanism Against Viruses (2 of 5) Figure 21.4 The interferon mechanism against viruses. Copyright © 2025 Pearson Education, Inc. All Rights Reserved The Interferon Mechanism Against Viruses (3 of 5) Figure 21.4 The interferon mechanism against viruses. Copyright © 2025 Pearson Education, Inc. All Rights Reserved The Interferon Mechanism Against Viruses (4 of 5) Figure 21.4 The interferon mechanism against viruses. Copyright © 2025 Pearson Education, Inc. All Rights Reserved The Interferon Mechanism Against Viruses (5 of 5) Figure 21.4 The interferon mechanism against viruses. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Antimicrobial Proteins (4 of 5) Complement system consists of at least 20 plasma proteins that circulate in inactive state. - Include those numbered C1–C9, plus several others regulatory proteins – Activated via three different pathways: ▪ Classical pathway involves antibodies – First step of pathway is for antibodies to bind to the pathogen, and then bind to complement components ▪ Lectin pathway involves lectins – Proteins produced by innate system to recognize foreign invaders – Once they bind to specific sugars on the surfaces of microbes, they can bind to and activate complement ▪ Alternative pathway involves spontaneous activation of complement cascade – As activated C3 and other factors interact on surface of microbes that lack the inhibitors of complement activation that body cells have Copyright © 2025 Pearson Education, Inc. All Rights Reserved The Complement System 39 Fever Fever, an abnormally high body temperature, is a systemic response to invading microbes Leukocytes and macrophages exposed to foreign substances secrete pyrogens – Chemicals that act on group of neurons in hypothalamus (body’s thermostat), raising temperature above normal – Fever increases ability of T lymphocytes and monocytes to migrate into lymph nodes, enhancing immune response – Increases metabolic rate, which increases rate of repair and T lymphocyte production – Suppresses bacterial growth by making it more difficult for bacteria to obtain certain metal ions such as iron Copyright © 2025 Pearson Education, Inc. All Rights Reserved Table 21.3 The Second Line of Defense: Innate Cellular and Chemical Defenses Category/Associated Protective Mechanism Elements Phagocytes Engulf and destroy pathogens that breach the surface membrane barriers; macrophages also contribute to the adaptive immune responses Natural killer (NK) Promote apoptosis (programmed cell death) by directly attacking virus- cells infected or cancerous body cells; recognize general abnormalities rather than specific antigens Inflammatory Prevents injurious agents from spreading to adjacent tissues, disposes of response pathogens and dead tissue cells, and promotes tissue repair; released inflammatory chemicals attract phagocytes (and other immune cells) to the area Antimicrobial proteins Proteins released by virus-infected cells and certain lymphocytes; act as Interferons (  ) chemical messengers to protect uninfected tissue cells from viral takeover; mobilize the immune system Complement A group of bloodborne proteins that, when activated, lyse microorganisms, enhance phagocytosis by opsonization, and intensify inflammatory and other immune responses Fever Systemic response initiated by pyrogens; high body temperature inhibits microbes from multiplying and enhances the body repair processes Copyright © 2025 Pearson Education, Inc. All Rights Reserved Part 2—Adaptive Defenses Adaptive immune system is a specific defensive system (third line of defense) that targets and eliminates almost any pathogen that invades the body Unlike innate defense, adaptive must first “meet” (be primed by initial exposure to) the specific substance (antigen) it will soon fight; priming takes time Consists of two separate but overlapping arms, each using various attack mechanisms: – Humoral immunity (antibody-mediated immunity) is provided by antibodies – Bind primarily to extracellular targets (bacteria, bacterial toxins, viruses) to inactivate and mark them for destruction by phagocytes or complement – Cellular immunity (cell-mediated immunity) is provided by lymphocytes themselves and has cellular targets (infected body cells, cancer cells, foreign cells) ▪ Can act directly, killing target cell, or indirectly, releasing inflammatory chemicals, activating macrophages Copyright © 2025 Pearson Education, Inc. All Rights Reserved Table 21.4 Key Differences Between Adaptive and Innate Defenses Adaptive Defenses Innate Defenses Involve B and T lymphocytes Involve diverse cells, processes, and structures (e.g., NK cells, phagocytes, antimicrobial proteins, inflammatory chemicals, and physical barriers) Are specific—recognize and target Are nonspecific—like “guards,” check identification to see antigens (identified pathogens or foreign whether friend or foe substances) Slow to mobilize Fast; always ready Have memory—react even more Usually no memory strongly to successive encounters of the same antigen Are systemic (bodywide)—not Largely restricted to site of initial infection (except fever) restricted to initial infection site Copyright © 2025 Pearson Education, Inc. All Rights Reserved 21.3 Antigens Are Substances That Trigger the Body’s Adaptive Defenses Antigens are substances that can mobilize the adaptive defenses, provoking an immune response – They are the targets of all adaptive immune responses – Most are large, complex molecules (natural or synthetic) that are foreign ▪ Not normally found in body, so viewed as nonself by our immune system Copyright © 2025 Pearson Education, Inc. All Rights Reserved Most Antigens Have Several Different Antigenic Determinants (Epitopes) Figure 21.6 Most antigens have several different antigenic determinants (epitopes) Copyright © 2025 Pearson Education, Inc. All Rights Reserved Self-Antigens: MHC Proteins Self-antigens: all body cell surfaces covered with variety of proteins that are not (normally) antigenic to self, but strongly antigenic to others – Basis of transfusion reactions and graft rejection – Includes a group of glycoproteins called MHC proteins ▪ Coded by genes of major histocompatibility complex (MHC) and unique to each individual ▪ T lymphocytes can only bind antigens that are presented on MHC proteins Copyright © 2025 Pearson Education, Inc. All Rights Reserved 21.4 B and T Lymphocytes and Antigen-Presenting Cells Are Cells of the Adaptive Immune Response Adaptive immune system involves three crucial types of cells: – Two populations of lymphocytes ▪ B lymphocytes (B cells), which provide humoral immunity ▪ T lymphocytes (T cells), which provide cellular immunity – Antigen-presenting cells (APCs) ▪ Play essential auxiliary roles in immunity; present antigens to T cells Copyright © 2025 Pearson Education, Inc. All Rights Reserved Lymphocyte Development, Maturation, and Activation (1 of 5) Figure 21.7 Lymphocyte development, maturation, and activation. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Lymphocyte Development, Maturation, and Activation (2 of 5) Figure 21.7 Lymphocyte development, maturation, and activation. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Lymphocyte Development, Maturation, and Activation (3 of 5) Figure 21.7 Lymphocyte development, maturation, and activation. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Lymphocyte Development, Maturation, and Activation (4 of 5) Figure 21.7 Lymphocyte development, maturation, and activation. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Lymphocyte Development, Maturation, and Activation (5 of 5) Figure 21.7 Lymphocyte development, maturation, and activation. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Lymphocytes (1 of 2) How does antigen receptor diversity in lymphocytes come about? – Our genes, not antigens we encounter, determine which specific foreign substances our immune system will be able to recognize and resist – Antigen just determines which existing T or B cells will be activated and attack it Lymphocytes make up to a billion different types of antigen receptors (but don’t require a billion different genes) – Stem cells contain 100’s of genetic bits (like a “Lego® set” for antigen receptor genes) – To form each cell’s antigen receptor, the gene pieces are shuffled and combined in different ways, a process called somatic recombination Copyright © 2025 Pearson Education, Inc. All Rights Reserved Lymphocytes (4 of 4) How are lymphocytes educated during maturation? – T cell selection process (education) consists of positive and negative selection in thymus 1. Positive selection (first test) – Ensures only T cells with receptors that can recognize self-MHC proteins survive ▪ Those that cannot are destroyed via apoptosis 2. Negative selection (second test) – Ensures T cells are not stimulated by (and attack) self-antigens displayed on self MHC proteins ▪ Those that do are destroyed via apoptosis—process called clonal deletion ▪ Only  2% survive to become immunocompetent, self-tolerant T cells Copyright © 2025 Pearson Education, Inc. All Rights Reserved T Cell Education in the Thymus Figure 21.8 T cell education in the thymus. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Antigen-Presenting Cells (APCs) Antigen-presenting cells (APCs) engulf antigens and display fragments for T cells to recognize (i.e., they present antigens to the cells that will deal with them) – Major types of APCs: dendritic cells, macrophages, and B lymphocytes Dendritic cells – Specialized to capture (phagocytize) antigens, then enter lymphatics to present them to T cells in lymph nodes ▪ Most effective antigen presenter known (its their only job) ▪ Migration of dendritic cells to secondary lymphoid organs now recognized as most important way of ensuring that lymphocytes encounter invading antigens Copyright © 2025 Pearson Education, Inc. All Rights Reserved Antigen-Presenting Cells (APCs) (2 of 2) Macrophages – Widely distributed throughout lymphoid organs and in connective tissues – Present antigens to naive T cells to activate them (like dendritic cells do), but also: ▪ To maintain T cell activation, or ▪ Become activated macrophages themselves, insatiable phagocytes that also: – Trigger powerful inflammatory responses – Recruit additional defenses B lymphocytes – Present antigens to helper T cell to assist their own activation (they do not activate naive T cells) Copyright © 2025 Pearson Education, Inc. All Rights Reserved Table 21.5 Overview of B and T Lymphocytes Bl a nk B Lymphocytes T Lymphocytes Type of immune Humoral Cellular response Antibody secretion Yes No Primary targets Extracellular pathogens (e.g., Intracellular pathogens (e.g., virus- bacteria, fungi, parasites, viruses infected cells) and cancer cells* in extracellular fluid) Site of origin Red bone marrow Red bone marrow Site of maturation Red bone marrow Thymus Effector cells Plasma cells Cytotoxic T (TC ) cells ( Tsubc) Helper T (TH ) cells ( TsubH) (TReg ) cells Regulatory T (T su bReg) Memory cell formation Yes Yes * In addition, helper T cells coordinate both B and T lymphocyte responses. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Activation and Differentiation of B Cells Naive B cell activated when its surface receptors bind to its antigen (clonal selection) – Quickly followed by receptor-mediated endocytosis of antigen-receptor complexes, leading to proliferation and differentiation of B cell into effector cells Most clone cells become plasma cells, antibody-secreting effector cells – Secrete at rate  2000 antibodies per second for 4 to 5 days, then die of ▪ All identical, with same antigen-binding properties as the antigen receptors on the parent B cell surface – Antibodies circulate in blood or lymph, binding to free antigens, marking them for destruction by innate or adaptive mechanisms Remaining clone cells become memory cells – Provide immunological memory – Mount an almost immediate humoral response to future exposures to same antigen Copyright © 2025 Pearson Education, Inc. All Rights Reserved Clonal Selection of a B cell Figure 21.10 Clonal selection of a B cell. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Immunological Memory Primary immune response: cell proliferation and differentiation upon initial exposure to antigen – Lag period of 3–6 days after encounter; the time required for: ▪ The few B cells specific for that antigen to proliferate (  12 generations) ▪ Their offspring to differentiate into plasma cells – Peak levels of plasma antibody reached in  10 days (then decline) Secondary immune response – Faster, more prolonged and effective response when re-exposed to same antigen ▪ Sensitized (“on alert”) memory cells provide immunological memory – Can form new army of plasma cells within hours ▪ In 2–3 days, plasma antibody concentration (antibody titer) peaks at much higher levels, and these antibodies bind with greater affinity ▪ Also, antibody titer remains high for weeks to months Copyright © 2025 Pearson Education, Inc. All Rights Reserved Primary and Secondary Humoral Responses Figure 21.11 Primary and secondary humoral responses. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Active and Passive Humoral Immunity Active humoral immunity: B cells encounter and produce antibodies against antigens; two types: 1. Naturally acquired: via infection with a particular bacterium or virus; often develop symptoms of disease 2. Artificially acquired: via receiving vaccine; usually consisting of dead or attenuated pathogens, or their components ▪ Vaccines provide two benefits: – Provide antigenic determinants that are immunogenic and reactive – Spare us most of the symptoms and discomfort of a primary response (via infection with disease) ▪ Vaccine booster shots (providing later encounters with same antigen) used in some cases to intensify immune response Copyright © 2025 Pearson Education, Inc. All Rights Reserved Active and Passive Humoral Immunity Figure 21.12 Active and passive humoral immunity. Copyright © 2025 Pearson Education, Inc. All Rights Reserved  Antibodies Antibodies, also called immunoglobulins (Igs), are proteins secreted by plasma cells – Bind specifically with antigens detected by B cells – Grouped into one of five Ig classes Basic antibody structure – Four looping polypeptide chains linked by disulfide bonds combine to form Y shaped antibody monomer ▪ Molecule has two identical halves, each made of a: – Heavy (H) chain (with flexible hinge region near middle) – Light (L) chain (about half as long as H chain) ▪ Each chain has variable (V) region at one end, constant (C) region at other end – Variable regions of H and L chains in each arm combine to form an antigen- binding site Copyright © 2025 Pearson Education, Inc. All Rights Reserved Antibody Structure Figure 21.13 Antibody structure. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Antibodies Antibody classes – IgG, IgA, IgM, IgE, and IgD ▪ Remember the word GAMED to recall the five major Ig classes ▪ Each has different characteristics, biological roles, and locations found in body – IgG: monomer; 75–85% of circulating antibodies; main Ig of both secondary and late primary responses ▪ Crosses placental barrier to confer passive immunity from mother to fetus – IgA exists in two forms: dimer and monomer (limited amounts in plasma) ▪ Dimer called secretory IgA; in secretions to help prevent entry of pathogens – IgM: potent agglutinating agent in plasma where it exists as huge pentamer (made of five linked Y-shaped monomers); first antibody released during primary response – IgE: monomer; stem binds to mast cells or basophils (for histamine release) ▪ Secreted in skin, mucosae of the GI and respiratory tracts, and tonsils; levels rise during severe allergic attacks – IgD: monomer; functions as B cell surface receptor Copyright © 2025 Pearson Education, Inc. All Rights Reserved Table 21.6-1 Immunoglobulin Classes Table 21.6 Immunoglobulin Classes* The first immunoglobulin class secreted by plasma cells during the primary response. (This fact is diagnostically useful because presence of IgM in plasma usually indicates current infection by the pathogen eliciting IgM’s formation.) Str uc t ureof I gManti b ody,apentamer. Keycharacteri s t ic: Th ef ir s t i mmuno gl o buli nclassec re t edbyp la smacellsduri ngthepri maryr e spon se.( Thisfact isdiagn o stica l lyuse f ulbec ausep r es enc eof I gMi nplas m au suallyi n di c atescurr e nt inf e cti onbythepat hogeneli c i tingI gM' sfor ma t ion. Re adil ya cti v at e scomplemen t. E xist sinmonomerandpen t ame r ( fi v eunit e d mon omer s )fo r ms.Themonomerservesa sanantigenr ece pt oront heBce l lsurf ac e. T hepentamer cir c ulat e si nblood. Numerousan t igen-bindingsit e sm a keit apotent a gglut ina t ingagent. Readily activates complement. Exists in monomer and pentamer (five united monomers) forms. The monomer serves as an antigen receptor on the B cell surface. The pentamer circulates in blood. Numerous antigen-binding sites make it a potent agglutinating agent. IgM (pentamer) The dimer, referred to as “secretory IgA,” is found in body secretions such as saliva, sweat, intestinal juice, and milk. Secretory IgA helps stop pathogens from attaching to epithelial cell surfaces (including mucous membranes and the epidermis). Str uc t ureof I gAantibody,adim er. Keyc haracteri s t ic: Th edi me r , refer edtoasse cr e t oryI gA, isfoundin b odyse cr e t ionss uchass ali v a, s weat, int e sti na l juice , andmil k. Se cr e t oryI gAhelpsstoppathoge nsf romat tac hi n g toepit h eli a l ce l lsurf ac es(i nc lu di n g muc ousmembrane sandt heepide r mis).Themonome r existsin limi tedamoun t sinpl a sma. The monomer exists in limited amounts in plasma. IgA (dimer) Copyright © 2025 Pearson Education, Inc. All Rights Reserved Table 21.6-2 Immunoglobulin Classes Table 21.6 (cont.) inue d Keyc haracteri s undont St t ic: Fo r uc he Btce ur l elsur off Ia cg e.Dantibody, Funct ionsaas monom l er aBce. i ge lant nr ec eptor (asdoe sI gM). Found on the B cell surface. Functions as a B cell antigen receptor (as does IgM). IgD (monomer) The most abundant antibody in plasma, accounting for 75–85% of circulating antibodies. The main antibody of both secondary and late primary responses. Keyc haracteri s ac t ivatesc t ic: Th ompl e em ost abundan ment. Prot e t anti b ct sa odyin pla gainstbacteri a sma, acco , viruses , an d toxinsc Str uct ureof I gGantibody,amonomer. unt ingfor 75to85perce i rculati n nt of c i rculati n ga g inbloodandlymph.Cr os nt ibod ie s. Th em a sestheplac i nant ibod yof bothsec entaandconfer sp assiv ondaryandlatepr imaryr e ei mmunit yfr o m themot he spons es.Read r t othef e t us. i ly Readily activates complement. Protects against bacteria, viruses, and toxins circulating in blood and lymph. IgG (monomer) Crosses the placenta and confers passive immunity from the mother to the fetus. Str uc t ureof I gEan t ibody , amonomer. Stem end binds to mast cells or basophils. Antigen binding to its receptor end triggers Key allec h r ar ia gcct reerit s ac tioic n.:Secr Stem eend bin tedby plds mtom as ea acs l tsc e inlsk s i or n,baso phi ales mucos.ofAnt thiegenbi gas att a t ron d init n g st to e inia l tsre cep andretsp cksorchronicparasit icinf e or i rae n todr tyritr g cti on cer ats sof t h , tan s he dse toce li ls ns egastr o lst.Oo i ntes reletr nly ase hiso ces a t inalt ract. ftaIm ginEear and othderchem ef oun ica inplasmla.sLev that elsm re disiea tdu erininflga m mea sevtreioal nland r gican e these cells to release histamine and other chemicals that mediate inflammation and an allergic reaction. Secreted by plasma cells in skin, mucosae of the gastrointestinal and respiratory tracts, and tonsils. Only traces of IgE are found in plasma. IgE (monomer) Levels rise during severe allergic attacks or chronic parasitic infections of the gastrointestinal tract. *Key characteristics are listed in boldface. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Antibodies Plasma B cells can switch from making one class of antibodies to another – Retain specificity for same antigen – IgM first Ig released during primary response; later plasma cells begin to secrete IgG (also primary Ig for all secondary responses) – Switching from IgM to IgA or IgE also occurs Antibody targets and functions – Antibodies cannot destroy antigens; they inactivate and tag them for destruction ▪ Form antigen-antibody (immune) complexes – Defensive mechanisms used by antibodies include: ▪ Neutralization ▪ Agglutination ▪ Precipitation ▪ Complement activation Copyright © 2025 Pearson Education, Inc. All Rights Reserved Mechanisms of Antibody Action Figure 21.14 Mechanisms of antibody action. Copyright © 2025 Pearson Education, Inc. All Rights Reserved Clinical—Homeostatic Imbalance 21.2 The “PLAN” attack from antibodies may be insufficient for infections by large parasitic worms like Ascaris and Schistosoma IgE antibodies still play a critical role in worm’s destruction by binding to its surface, marking it for destruction by eosinophils – Eosinophils bind to exposed stems of IgE, which triggers eosinophils to release toxic chemical onto prey, lysing it from the outside Copyright © 2025 Pearson Education, Inc. All Rights Reserved 21.6 Cellular Immunity Consists of T Lymphocytes That Direct Adaptive Immunity or Attack Cellular Targets (1 of 2) T cells provoke a cellular immune response when presented with antigens – Some directly kill cells that are ▪ Infected by viruses or bacteria ▪ Cancerous or abnormal ▪ Foreign (e.g., transplanted cells) – Others release chemicals that regulate immune response Two major T cell populations (CD4, CD8) based on their cell differentiation glycoproteins – Activated CD4 and CD8 cells differentiate into the three major kinds of effector cells Copyright © 2025 Pearson Education, Inc. All Rights Reserved 21.6 Cellular Immunity Consists of T Lymphocytes That Direct Adaptive Immunity or Attack Cellular Targets (2 of 2) ▪ Most CD4 cells become helper T (TH ) cells that help activate B cells, other T cells, and macrophages, and direct adaptive immune response – Some become regulatory T (TReg ) cells that moderate immune response ▪ Most CD8 cells become cytotoxic T cells (TC ), capable of destroying infected and abnormal or foreign cells – Activated CD4 and CD8 cells can also become memory T cells Copyright © 2025 Pearson Education, Inc. All Rights Reserved Major Types of T Cells Figure 21.15 Major types of T cells. Copyright © 2025 Pearson Education, Inc. All Rights Reserved MHC Proteins and Antigen Presentation (1 of 3) T cells respond only to processed fragments of antigens displayed on surfaces of cells by major histocompatibility complex (MHC) proteins— class I or class II – Antigen presentation required to activate naive T cells and for normal functioning of effector T cells Class I MHC proteins – On surface of virtually all body cells except RBCs – Display endogenous antigens made inside cell – Healthy cell displays pieces of normal body proteins (self-antigen) ▪ Infected cell also displays parts of proteins that “belong” to pathogen (antigen) ▪ Cancer cell displays pieces of abnormal proteins (antigen) – Roles: activating naive CD8 cells and “informing” cytotoxic T cells that pathogens are hiding in body cells Copyright © 2025 Pearson Education, Inc. All Rights Reserved MHC Proteins and Antigen Presentation (2 of 3) Class II MHC proteins – Only on the surfaces of cells that present antigens to CD4 cells: dendritic cells, macrophages, and B cells – Display exogenous antigens—antigens from outside the cell that have been engulfed by the cell displaying them ▪ Engulfed antigen broken down by proteases inside phagolysosome (into larger, 14–17 amino acid fragments) ▪ Vesicles from ER containing class II proteins fuse with phagolysosome ▪ Fragments bind to groove of MHC protein before it is inserted onto cell surface – Role: activating naive CD4 cells, letting them know that “help” is required ▪ As if showing the CD4 (soon to become TH ) cells what the invader “looks like” Copyright © 2025 Pearson Education, Inc. All Rights Reserved Table 21.7 Role of MHC Proteins in Cellular Immunity Bl a nk Class I MHC Proteins clasone Class II MHC Proteins clast wo Displayed by All nucleated cells APCs (dendritic cells, macrophages, B cells) Threen uclea te dcellswi thClassRo mannume r al1M HCpr o te in sontheir sur facedisplayin gantigen s. Aden dri ticcell withCl a ssRomann umeral 2MHC p r oteinonitssurfaced i splayinga nantigen. Thed end r it ccel ha scellularexte nsion sall over it sb ody. Recognized by Naive CD8 cells and cytotoxic T cells Naive CD4 cells and helper T cells AC D8ce l lwi thaTce l lr eceptorandaCD8pr o te i no ni tssu r face. AC D4ce l lwi thaTce l lr eceptorandaCD4pr o te i no ni tssu r face. Foreign antigens Endogenous (intracellular pathogens or Exogenous (phagocytized on MHC are proteins made by cancerous cells)* Anicosahe dral virus. extracellular pathogens) Ar o d-sh ape dbacte r ia. Cells displaying If the cell is an APC: “I belong to self, but have captured “I belong to self, but have captured a foreign antigens a foreign invader. This is what it looks like. Kill any cell foreign invader. This is what it looks on MHC send that displays it.” like. Help me mount a defense this message If the cell is not an APC: “I belong to self, but have been against it.” invaded or become cancerous. Kill me!” *Dendritic cells are an exception because they can present anot