Immunity Chapter 38
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
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
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
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
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 Specificity 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 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
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
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
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 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
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
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
Cytotoxic T Cells Cytotoxic T cells touch-kill cells displaying antigen-mhc markers; perforin and proteases puncture cells and kill them by apoptosis
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 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 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)