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    Download Curriculum Guidelines Download Curriculum Guidelines Document Transcript

    • Immunology Teachable Unit I. Title: Connecting Microbiology to Human Biology II. Developer: Lisa Lenertz III. Description: This unit introduces non-science majors to human biology through lessons about innate and adaptive immunity, vaccines, autoimmune diseases, allergies, and current events related to immunology. The overarching goal of the unit is to ignite student interest in immunology topics that are directly related to their lives. Although this unit was designed for non-science majors, the context can be modified to accommodate biology majors. This unit spans five days, but ideally a few more classes should be allowed to cover each topic in detail because immunology is often a difficult subject for students to grasp. Lectures, small group discussions, and a large class debate are used in this teachable unit. IV. Learning Goals and Outcomes: Lesson 1 - Introduction to Immunology Learning Goal Learning Outcome The students will understand the major The students will be able to describe the differences between innate and adaptive major differences between innate and immunity in terms of resistance or adaptive immunity. protection against microbial pathogens. Lesson 2 - Innate Immunity Learning Goal Learning Outcomes The students will know the major The students will be able to describe the components of the innate immune major cell players in the innate immune response. response. The students will be able to list major innate immune response processes and describe their purposes. 1
    • Lesson 3 - Adaptive Immunity Learning Goals Learning Outcomes The students will understand the The students will be able to list the major relationship between antigens and immune cells and describe how they work antibodies. with other cells. The students will understand how the The students will be able to describe the various immune cells of the adaptive basic functions of antibodies and how immune response function to combat antibodies are generated following an infections. infection. The students will understand how The students will be able to describe how antibodies work to protect the body against the adaptive immune response has memory. invading pathogenic microbes. Lesson 4 - Autoimmune Diseases and Allergies Learning Goals Learning Outcomes The students will understand how allergen The students will be able to articulate how particles are presented to the immune allergen particles induce allergic reactions. system. The students will research an autoimmune The students will understand how disease of interest and be able to describe hypersensitivities develop. what is and what is not known about its causes, the mechanisms of how the disease The students will understand the basic causes harm, and current treatments. mechanisms by which autoimmune diseases cause harm to the body. Lesson 5 - Vaccines Learning Goals Learning Outcomes The students will understand the basic The students will articulate how mechanism by which vaccines create vaccinations activate the adaptive immune immunological "memory". response and why our bodies are protected against assaults from the pathogen the The students will understand why vaccines vaccine was developed for. do not cause disease. The students will be able to explain why vaccines do not cause disease. The students will defend or refute Texas Governor Rick Perry's attempt to mandate the HPV vaccine. 2
    • V. Scientific Teaching Themes: Scientific Teaching Each lesson addresses a complex and difficult subject for students. The overall goal of this unit is for non-science majors to have a better understanding of how the human body responds to infections and to have a basic understanding of how the immune system can function improperly to cause autoimmune diseases and allergic reactions. Mini lectures, group activities, homework assignments, and a class debate are used in this unit to help address several misconceptions that students have about immunity, allergies, autoimmune diseases and vaccines. Active Learning The active learning activities include question and answer sessions during the beginning of each class and a whole class debate about mandatory vaccinations. In addition, class discussions are incorporated into the lectures. More details about the active learning activities are provided in the instructor materials. Assessment Student learning is assessed through several mechanisms including participation in group discussions, a group debate, a worksheet, short written assignments, and a research paper. I look over the short written assignments after class and address any common problems in the first fifteen minutes of the next class. I also make comments on each assignment and give those to the students during the following class in order for them to assess what they do and do not understand before we move onto new topics. Diversity Once the course begins, we ask students to contact us if they have special needs such as having a learning disability, and we determine how to accommodate those students. To address racial, ethnic, regional, and political diversity, I use examples from different population groups whenever possible. For example, when discussing the smallpox vaccine, I describe how different nations throughout history have dealt with smallpox. As another example, the HPV vaccine debate is about Texas Governor Rick Perry's attempt to mandate the vaccine for girls entering the sixth grade. This addresses regional and political ideology diversity. 3
    • VI. Teaching Plan: Lesson 1 - Introduction to Immunology Timeline Time Topic Activity Goals 0-8 Introduction of Mini-lecture Familiarize students with the immunology field history of immunology 9-13 Pathogens we are Small group activity Students think about what immunized against they have been vaccinated against. 14-18 Innate vs. adaptive Mini-lecture Students are introduced to the immunity broad, major differences between innate and adaptive immunity. 19-26 Cells of the immune Mini-lecture Students are introduced to the system players in the immune system. 27-33 Overview of innate Mini-lecture Students are familiarized with immunity the basics of innate immunity. 35-42 Overview of adaptive Mini-lecture Students are familiarized with immunity the basics of adaptive immunity. 43-48 How adaptive Mini-lecture Students think about the immunity establishes basics of how vaccines protect memory us from invading pathogens. 49-50 Reflection Short written Students articulate one topic assignment or question that was confusing. Homework assigned: Read chapters in immunology textbook. Our students used Ken Todar's online Bacteriology Textbook. Lesson 2 - Innate Immunity Timeline Time Topic Activity Goals 0-15 Review Discussion of Clarify what students were responses to the short confused about in the previous written assignment class. 16-22 Overview of innate Mini-lecture Students think about our immunity various defenses against components invading pathogens. 23-30 Innate immunity Mini-lecture Students are familiarized with 4
    • components in detail the components of the innate immune system. 31-37 Inflammation Mini-lecture, Students gain an discussion about understanding of the inflammatory fundamentals of inflammation diseases such as and reflect on any asthma inflammatory diseases they may suffer from. 38-44 Phagocytosis Mini-lecture Students are introduced to the process of phagocytosis and its importance. 45-48 Fever Mini-lecture Students acknowledge why getting a fever can be beneficial. 49-50 Reflection Short written Students articulate one topic assignment or question that was confusing. Homework assigned: Read chapters in immunology textbook and do worksheet. Lesson 3 - Adaptive Immunity Timeline Time Topic Activity Goals 0-15 Review Discussion of Clarify what students were responses to the short confused about in the previous written assignment class. 16-22 Introduction to Mini lecture Students are familiarized with adaptive immunity the basics of adaptive immunity. 23-28 Antigens & blood Whole class Students are introduced to the typing discussion about concept of antigens and ABO blood typing immunity. 29-37 Antibodies Mini lecture Students are introduced to the concept of antibodies. 38-44 Primary and Mini lecture Students gain an secondary responses understanding of how vaccines work to protect us from infections. 45-48 Cell-mediated Mini lecture Students are familiarized with immunity the major functions of T cells. 49-50 Reflection Short written Students articulate one topic assignment or question that was confusing. 5
    • Homework assigned: Read chapters in immunology textbook and start research paper. Lesson 4 - Allergies and Autoimmune Diseases Timeline Time Topic Activity Goals 0-15 Review Discussion of Clarify what students were responses to the short confused about in the previous written assignments class. 16-19 Definitions of Mini lecture Students become familiarized allergies and with the concept that the autoimmune diseases immune system can function improperly 20-26 Immediate and Mini lecture Students are introduced to the delayed concept of hypersensitivities hypersensitivities and examples between immediate and delayed. 27-31 Basics of Mini lecture Students are familiarized with autoimmune diseases the basics of a few autoimmune diseases. 32-48 Hypotheses for why Whole class Students realize that there is we seem to have discussion no clear explanation for why more allergies we seem to develop more allergies. 49-50 Reflection Short written Students articulate one topic assignment or question that was confusing. Homework assigned: Short reflection paper about mandatory HPV vaccinations Homework due: worksheet Lesson 5 - Vaccines Timeline Time Topic Activity Goals 0-15 Review Discussion of Clarify what students were responses to the short confused about in the previous written assignments class. 16-20 Vaccines Mini lecture Students review the mechanisms by which vaccines establish "memory" 6
    • 21-50 Mandatory HPV Whole class debate Students defend their personal vaccinations position about mandatory HPV vaccinations. Homework due the following week: research paper, short reflection paper about mandatory HPV vaccinations VII. Instructor Materials: The following is the student handout for the unit with notes that an instructor can use during a chalk talk. Notes that are in addition to what is in the handout are in blue; short active learning activities are in red. This handout can be tailored to different levels of difficulty. I found that is was challenging to cover all of the material in five days, therefore either one or two more days should be allotted for this unit or some material should be cut. For a non-science major course, I think it is important to allow enough time to discuss allergies and autoimmune diseases in detail, which are topics that are important to our daily lives and are interesting to students. Additionally, I routinely discussed my own research throughout the chalk talks in order for the students to gain a better understanding of the relevance of the particular topic and to increase student interest. Immunology: The study of our responses to invading microbes that leads to resistance and protection. Complicated field; origins attributed to Edward Jenner - vaccinated against smallpox using cowpox Immune system protects us from….. Ask students to give examples of the following…. 1) bacteria: E. coli, Staph, Strep, Salmonella, Tetanus, etc 2) viruses: Rhinovirus-common cold, Herpes, influenza, etc 3) fungi: Aspergillis 4) parasites: eukaryotes: tapeworms, flukes, Giardia, etc Have the students pair up and list some bacteria and viruses we are immunized against. Bacteria: tetanus, whooping cough, diphtheria, meningitis Viruses: polio, MMR, hepatitis, HPV, shingles, yellow fever 7
    • Innate Immunity Adaptive Immunity • 1st line of defense • 2nd line of defense upon initial exposure • nonspecific • specific • responds almost immediately • takes time to react • does not have a "memory" • has a "memory" Multiple cell types comprise the immune system. Some are components of the innate response, some are components of the adaptive response, and may bridge the two responses. 8
    • B cells: bone marrow; antibody-mediated immunity T cells: thymus; cell-mediated immunity; also have memory cells Immune system cells - Overview B cells: ⋅ develop into plasma cells that produce antibodies, proteins that recognize and disable foreign substances called antigens ⋅ establish immunological memory Draw a model of an antibody-antigen complex. Memory cells: longer lived, become plasma cells when activated. Plasma cells have large ER (protein producing machines) & are short lived. T cells: ⋅ recognize and respond to antigens expressed on body cells known as antigen- presenting cells ⋅ establish immunological memory T helper: activate everyone, secrete interferon gamma, complex w/ dendritic cells (they activate each other, T helper cells start dividing, and then they activate B cells, macrophages, neutrophils, etc) Natural killer cells: ⋅ "police" the body ⋅ lyse virus-infected cells ⋅ are relatively non-specific in what cells they kill Scan for cells not expressing MHCI, which is suppressed in viral infected & tumor cells Neutrophils: ⋅ short-lived cells that phagocytose, or engulf, invading microbes ⋅ contain many bactericides Phagocytosis: discussed in detail next lecture; critical component of the innate immune response Eosinophils: ⋅ release cytotoxic proteins that damage parasitic worms ⋅ releases inflammatory mediators, mediating tissue damage in asthmatic individuals Highly granulated cells that have not been extensively studied. "Primed" upon allergen challenge. People with allergies have more eosinophils. 9
    • Basophils: ⋅ have poorly understood functions ⋅ aid in combating parasitic worm infections ⋅ may be involved in inflammation We don't have many of them. Mast cells: ⋅ aid in combating parasitic worm infections ⋅ important in inflammation Found in connective tissue. Many are in the skin, intestinal wall, lungs, mouth, & nose and they interact with the outside environment & are in the vicinity of blood cells. They signal injury & degranulate to release histamine & heparin (blood flows to the area) Dendritic cells: ⋅ present processed antigenic fragments to T cells Antigen presenting cell Macrophages: ⋅ phagocytose foreign microbes & dead cells ⋅ present processed antigenic fragments to T cells ⋅ long-lived cells ⋅ release factors that amplify inflammation Antigen presenting cell Not as activated in newborns & the elderly Innate Immunity - Overview We are exposed or infected by various microbes. Despite this, infectious disease is quite rare because the innate immune system usually takes care of any problems. ⋅ primary defense mechanism upon an initial exposure to a pathogen, is the first to act ⋅ defenses are always present New cells do not need to be made Anatomical defenses (skin, mucous membranes), macrophages, etc ⋅ defenses respond immediately upon infection 10
    • ⋅ reacts similarly to a variety of organisms Undergoes similar processes no matter what the insult is Adaptive Immunity - Overview ⋅ clears most infections that the innate immune response cannot take care of ⋅ reacts to a particular pathogen Specific antibodies react to specific pathogens ⋅ when trigged by first exposure to a pathogen, it takes time to develop Memory B and T cells and antibody-producing plasma cells must fully develop ⋅ can "remember" pathogens that previously invaded the body and can react more quickly the second time the body is invaded by the same pathogen (Active immunity) the cells are already there to react 2 types of adaptive immunity 1) Antibody-mediated immunity Antibodies circulate freely in the blood and lymph. Antibodies are produced by plasma B cells and utilize several mechanisms to help eliminate pathogens. 2) Cell-mediated immunity T cells recognize foreign particles (antigens) and undergo several events to help eliminate the threat. Only active immunity establishes "memory" Active immunity: ⋅ infection ⋅ vaccine 11
    • Killed or inactivated organisms or purified products derived from the organism First known form of vaccinations was variolation of smallpox (used actual smallpox though; current smallpox vaccine is live virus- vaccinia) Edward Jenner Passive immunity: ⋅ certain types of antibodies pass from mother to fetus via the placenta or to infant via milk ⋅ short-lived ⋅ injection of immune serum (antivenom, antitoxin) doesn't establish memory Innate Immunity Components of Innate Immunity: • Natural Resistance: species resistance, individual resistance (age, sex, therapy against other diseases), temp, pH • Normal Flora: resident flora prevent colonization of invaders • Anatomical Defenses: skin, mucous membranes, cilia • Tissue Bactericides: lactoferrin, lysozyme, complement • Inflammation: focuses host defenses, maybe most important component • Phagocytosis: neutrophils and macrophages, cells eat pathogens • Fever: systemic response (whole body response) 12
    • Natural Resistance: Some pathogens cannot colonize and survive in certain host environments. Dogs, not humans get distemper. Some species can evolve and infect hosts they didn't infect before (avian flu). Sex: orchitis- inflammation in testicles; mastitis- infection that occurs after breast feeding. Normal Flora: Normal flora prevent the colonization of foreign microorganisms. Competition for binding sites. Proteins called bacteriocins and a variety of metabolites produced by indigenous species kill or inhibit other bacteria. 13
    • Anatomical Defenses: Protective surfaces that keep pathogens out. • Skin Is compromised by cuts, burns and bites • Mucous membranes/epithelium ⋅ Respiratory tract Mucus flow and epithelial cilia keeps pathogens from attaching to epithelia ⋅ Digestive tract Peristalsis keeps pathogens from attaching ⋅ Genitourinary tract ⋅ Eyes Epithelial Tissues show point power slides Ask the students what it is about epithelia that keep pathogens out. Ciliated epithelium 14
    • cilia Tissue Bactericides: Molecules that have anti-microbial properties. ⋅ Lysozyme - lyses bacteria ⋅ Lactoferrin - inhibits bacterial growth by withholding needed iron ⋅ Interleukin-1 & tumor necrosis factor alpha - cause fever ⋅ Complement - promotes lysis of bacteria, participates in inflammation & opsonization (coating of foreign particles to make them "tasty" to phagocytic cells) Inflammation: A tissue reaction to injury or infection. Symptoms are redness, swelling, heat, & pain. Essential to combating infections 15
    • ⋅ redness: due to increased blood flow to injured area ⋅ swelling: due to increased extravascular fluid & phagocyte infiltration to affected area ⋅ heat: due to increased blood flow & action of pyrogens (fever-inducing agents) ⋅ pain: caused by local tissue destruction & irritation of sensory nerves Antimicrobial effects of inflammation: 1) increases the blood supply & temperature in affected area, which promotes maximal metabolic activity of immune response cells 2) delivers inflammatory exudate to affected area, which contains phagocytes, lymphocytes, lysozyme, antibodies & other factors Inflammation is normally a good thing, but excessive inflammation can cause harm to the body. ⋅ asthma Ask the students if they have asthma and start a brief discussion. Common chronic disease Increasing problem in the developed world Excessive inflammation in the airway Episodes can be triggered by common cold, exercise, allergens ⋅ arthritis Inflammation in the joints ⋅ Crohn's disease Classified as an inflammatory bowel disease; not pleasant Genetic link Abdominal pain, diarrhea, increased risk of cancer in inflamed areas ⋅Chostochondritis Inflammation of cartilage that connects a rib to the breastbone Pain may mimic the pain of having a heart attack Induced by excessive exercise, injury, etc Painful when breathing 16
    • Phagocytosis: Engulfment & destruction of pathogens Phagocytic cells: 1) neutrophils - contain granules; are short-lived cells 2) macrophages - local & blood-borne cells; longer-lived cells Show power point slide Steps of phagocytosis: shower power point slide 1) phagocytic cells wrap their cell membranes around pathogen to form a phagosome 2) phagosome becomes acidified 3) phagosome fuses with lysosomes (contain digestive enzymes) to form a phagolysosome 4) targets killed within phagolysosome 17
    • Fever: Increase in body temperature Ask the students what can be detrimental about high fevers. ⋅ systemic response ⋅ sequesters iron & zinc which are needed for bacteria to multiply ⋅ increases the metabolic rate of cells to speed up repair Adaptive Immunity: Stalks and eliminates nearly every infection that cannot be cleared by the innate response. Unlike the innate immune response it must be primed by an initial exposure to the foreign substance (antigen). Vaccination, chickenpox, etc 4 important aspects: 18
    • 1) It is specific - recognizes specific pathogens Recognizes specific antigens on the pathogens - proteins exposed on the surface of pathogens 2) It is systemic - not restricted to initial infection site Whole body response 3) It has "memory" - after an initial exposure, it recognizes & mounts an even stronger attack antibodies are produced upon initial exposure - able to react the 2nd time 4) It is tolerant - it generally does not react to "self" proteins Doesn't attack proteins on the surface of body cells 2 types: 1) antibody-mediated immunity 2) cell-mediated immunity Complete Antigens: ⋅ substances that mobilize the immune response; what antibodies recognize ⋅ molecules found on pathogens ⋅ not normally present in the body ⋅ are nonself Self Antigens: ⋅ not foreign to us ⋅ foreign to others (transplant rejection, receiving the wrong blood type) ABO blood activity: List each blood type with what antigens are presented and what antibodies are produced. Ask the students what blood type they have. Ask the students what blood type is the universal donor and what is the universal acceptor. 19
    • Antibody-mediated immunity: ⋅ Upon antigenic stimulus, B lymphocytes become transformed into antibody- secreting plasma cells or long-lived memory cells. ⋅ Each antibody (also known as immunoglobulin) recognizes a specific antigen. Antibody-antigen complexes Explain constant & variable regions. Discuss how we produce antibodies in the lab. ⋅ Antibodies have multiple functions. Opsonization: coat foreign particles & make them susceptible to phagocytosis Makes them "tasty" for phagocytic cells Steric hindrance: block microbe attachment to host cells Microbes can't adhere to epithelium & invade Toxin neutralization: block the interaction of bacterial toxins with their targets Agglutination or precipitation: combine with the surfaces of microbes, causing them to agglutinate or precipitate and making them susceptible to phagocytosis 20
    • Activation of complement: the complement cascade has 4 major effects Complex system 1) induction of inflammation 2) attract phagocytes to infection site 3) opsonization of microbes 4) lysis of bacteria or viral-infected cells There are different classes of antibodies: IgG, IgM, IgA, IgE, IgD IgD: bound to B cells IgE: anaphylaxis, troublemaker IgG: ⋅ predominant immunoglobulin in the body (Body glad) ⋅ can diffuse into extravascular spaces ⋅ crosses the placental barrier, providing passive immunity to fetus for 6 months of life ⋅ basis of passive immunity provided by most natural antiserums IgM: ⋅ first immunoglobulin to be synthesized by infants (body mad) made weeks to months after birth ⋅ first immunoglobulin to appear in the blood stream during an infection ⋅ secreted onto mucosal surfaces IgA: ⋅ participates in local defense of mucosal surfaces (ears, eyes, nose, throat) ⋅ antibodies secreted onto mucosal surfaces Highest Ig found in breast milk: shielded by secretory components with protects it from degradation in digestive tract When the body is infected with a particular pathogen the second time (secondary response), memory B cells are able to quickly recognize the pathogen and stimulate a faster immunological response than after the first encounter with that pathogen (primary response). 21
    • Primary and secondary immunological responses Cell-mediated immunity: More complicated than antibody-mediated immunity 2 main cell types involved: 1) CD4 cells: are primarily helper T cells What HIV attacks, along with macrophages & dendritic cells 2) CD8 cells: cytotoxic T cells MHC class I: most cells, normally display self antigens; recognized by CD8+ MHC class II: mature B cells, some T cells, APCs; recognized by CD4+ T helper cells stimulate B cells & T cytotoxic cells (link between cell-mediated & antibody-mediated immunity) Helper T cells: ⋅ bind to antigens present on an antigen presenting cells ⋅ stimulate cytotoxic T cells and B cells to help fight the invader 22
    • Cytotoxic T cells: ⋅ also called killer T cells Kill HIV-infected helper T cells ⋅ lyse infected cells by releasing the contents of its granules ⋅ activated by antigens present on any cell, not just antigen presenting cells ⋅ activity is enhanced by helper T cells ⋅ involved in rejection of foreign tissue grafts Regulatory T cells: suppress immune responses at sites of inflammation 1) direct killing of cytotoxic cells 2) inhibition of cytokine production 3) secrete anti-inflammatory factors Vaccines 4 main types of vaccines: 1) killed microbes 2) live, attenuated virus 3) toxoids - inactivated toxic compounds from the microbes 4) proteins - Hepatitis B, HPV - In the case of smallpox, vaccination using the live, related viruses, cowpox and vaccinia virus, provided protection against smallpox. - DNA-based viruses are under investigation: easier to transport and store Ask the students how the body responds to vaccines. Discuss B cells and primary vs. secondary responses. List of vaccine-preventable diseases (CDC) Anthrax Cervical cancer Diphtheria Hepatitis A Hepatitis B Haemophilus influenzae type b 23
    • Influenza Japanese Encephalitis Lyme disease Measles Meningococcal Monkeypox Mumps Whooping cough Pneumococcal Polio Rabies Rotavirus Rubella (German measles) Shingles (Herpes Zoster) Smallpox Tetanus (Lockjaw) Tuberculosis Typhoid Fever Chickenpox (Varicella) Yellow Fever Allergies and Autoimmune Diseases Allergies and autoimmune diseases develop when the immune system has gone haywire. Allergies: The immune system attacks something that is not normally harmful to the body. ⋅ exaggerated response to presented antigens Autoimmune disease: The body perceives itself as "nonself" and mounts an attack. ⋅ body is no longer tolerant to "self" Immediate hypersensitivity (Type I hypersensitivity) ⋅ can happen quickly (usually more severe) 24
    • ⋅ can also be a delayed response ⋅ Anaphylactic shock is a life threatening, severe whole body response to an allergen ⋅ Treatment options: 1) Benadryl 2) corticosteroids to decrease inflammation Anaphylaxis: most common type I First encounter: - APCs present allergen to T cells - IL-4 secretion by T helper cells - B cells secrete IgE that attach to mast cells & basophils Second encounter: - allergen binds to IgE & causes degranulation Atopy: - don't need to be sensitized to allergen - react immediately Delayed hypersensitivity (Type IV hypersensitivity): ⋅ appear within 1-3 days ⋅ mediated by cells ⋅ allergic contact dermatitis: poison ivy, heavy metals, cosmetics; can be passed through transfusions of T cells; TB skin test Discuss hygiene hypothesis: Th1 vs Th2 (decreased number of childhood diseases, less Th1, more Th2) 25
    • VIII. Student Materials: Immunology Handout Immunology: The study of our responses to invading microbes that leads to resistance and protection. Immune system protects us from….. 1) bacteria 2) viruses 3) fungi 4) parasites Innate Immunity Adaptive Immunity • 1st line of defense • 2nd line of defense upon initial exposure • nonspecific • specific • responds almost immediately • takes time to react • does not have a "memory" • has a "memory" 26
    • Multiple cell types comprise the immune system. Some are components of the innate response, some are components of the adaptive response, and may bridge the two responses. 27
    • Immune system cells - Overview B cells: ⋅ develop into plasma cells that produce antibodies, proteins that recognize and disable foreign substances called antigens ⋅ establish immunological memory T cells: ⋅ recognize and respond to antigens expressed on body cells known as antigen- presenting cells ⋅ establish immunological memory Natural killer cells: ⋅ "police" the body ⋅ lyse virus-infected cells ⋅ are relatively non-specific in what cells they kill Neutrophils: ⋅ short-lived cells that phagocytose, or engulf, invading microbes ⋅ contain many bactericides 28
    • Eosinophils: ⋅ release cytotoxic proteins that damage parasitic worms ⋅ releases inflammatory mediators, mediating tissue damage in asthmatic individuals Basophils: ⋅ have poorly understood functions ⋅ aid in combating parasitic worm infections ⋅ may be involved in inflammation Mast cells: ⋅ aid in combating parasitic worm infections ⋅ important in inflammation Dendritic cells: ⋅ present processed antigenic fragments to T cells Macrophages: ⋅ phagocytose foreign microbes ⋅ present processed antigenic fragments to T cells ⋅ long-lived cells ⋅ release factors that amplify inflammation 29
    • Innate Immunity - Overview We are exposed or infected by various microbes. Despite this, infectious disease is quite rare because the innate immune system usually takes care of any problems. ⋅ primary defense mechanism ⋅ defenses are always present ⋅ defenses respond immediately upon infection ⋅ reacts similarly to a variety of organisms Adaptive Immunity - Overview ⋅ clears most infections that the innate immune response cannot take care of ⋅ reacts to a particular pathogen ⋅ when trigged by first exposure to a pathogen, it takes time to develop ⋅ can "remember" pathogens that previously invaded the body and can react more quickly 30
    • the second time the body is invaded by the same pathogen (Active immunity) 2 types of adaptive immunity 1) Antibody-mediated immunity Antibodies circulate freely in the blood and lymph. Antibodies are produced by plasma B cells and utilize several mechanisms to help eliminate pathogens. 2) Cell-mediated immunity T cells recognize foreign particles (antigens) and undergo several events to help eliminate the threat. Only active immunity establishes "memory" Active immunity: ⋅ infection ⋅ vaccine Passive immunity: ⋅ certain types of antibodies pass from mother to fetus via the placenta or to infant via milk ⋅ short-lived ⋅ injection of immune serum (antivenom, antitoxin) 31
    • Innate Immunity Components of Innate Immunity: • Natural Resistance • Normal Flora • Anatomical Defenses • Tissue Bactericides • Inflammation • Phagocytosis • Fever 32
    • Natural Resistance: Some pathogens cannot colonize and survive in certain host environments. Normal Flora: Normal flora prevent the colonization of foreign microorganisms. Anatomical Defenses: Protective surfaces that keep pathogens out. 33
    • • Skin • Mucous membranes/epithelium ⋅ Respiratory tract ⋅ Digestive tract ⋅ Genitourinary tract ⋅ Eyes Epithelial Tissues 34
    • Ciliated epithelium cilia Tissue Bactericides: Molecules that have anti-microbial properties. ⋅ Lysozyme - lyses bacteria ⋅ Lactoferrin - inhibits bacterial growth by withholding needed iron ⋅ Interleukin-1 & tumor necrosis factor alpha - cause fever ⋅ Complement - promotes lysis of bacteria, participates in inflammation & opsonization (coating of foreign particles to make them "tasty" to phagocytic cells) 35
    • Inflammation: A tissue reaction to injury or infection. Symptoms are redness, swelling, heat, & pain. ⋅ redness: due to increased blood flow to injured area ⋅ swelling: due to increased extravascular fluid & phagocyte infiltration to affected area ⋅ heat: due to increased blood flow & action of pyrogens (fever-inducing agents) ⋅ pain: caused by local tissue destruction & irritation of sensory nerves Antimicrobial effects of inflammation: 1) increases the blood supply & temperature in affected area, which promotes maximal metabolic activity of immune response cells 2) delivers inflammatory exudate to affected area, which contains phagocytes, lymphocytes, lysozyme, antibodies & other factors Inflammation is normally a good thing, but excessive inflammation can cause harm to the body. ⋅ asthma 36
    • ⋅ arthritis ⋅ Crohn's disease ⋅Chostochondritis Phagocytosis: Engulfment & destruction of pathogens Phagocytic cells: 1) neutrophils - contain granules; are short-lived cells 2) macrophages - local & blood-borne cells; longer-lived cells 37
    • Steps of phagocytosis: 1) phagocytic cells wrap their cell membranes around pathogen to form a phagosome 2) phagosome becomes acidified 3) phagosome fuses with lysosomes (contain digestive enzymes) to form a phagolysosome 4) targets killed within phagolysosome 38
    • Fever: Increase in body temperature ⋅ systemic response ⋅ sequesters iron & zinc which are needed to bacteria to multiply ⋅ increases the metabolic rate of cells to speed up repair 39
    • Adaptive Immunity: Stalks and eliminates nearly every infection that cannot be cleared by the innate response. Unlike the innate immune response it must be primed by an initial exposure to the foreign substance (antigen). 4 important aspects: 1) It is specific - recognizes specific pathogens 2) It is systemic - not restricted to initial infection site 3) It has "memory" - after an initial exposure, it recognizes & mounts an even stronger attack 4) It is tolerant - it generally does not react to "self" proteins 2 types: 1) antibody-mediated immunity 2) cell-mediated immunity 40
    • Complete Antigens: ⋅ substances that mobilize the immune response; what antibodies recognize ⋅ molecules found on pathogens ⋅ not normally present in the body ⋅ are nonself Self Antigens: ⋅ not foreign to us ⋅ foreign to others (transplant rejection, receiving the wrong blood type) Antibody-mediated immunity: ⋅ Upon antigenic stimulus, B lymphocytes become transformed into antibody- secreting plasma cells or long-lived memory cells. ⋅ Each antibody (also known as immunoglobulin) recognizes a specific antigen. 41
    • Antibody-antigen complexes ⋅ Antibodies have multiple functions. Opsonization: coat foreign particles & make them susceptible to phagocytosis Steric hindrance: block microbe attachment to host cells Toxin neutralization: block the interaction of bacterial toxins with their targets Agglutination or precipitation: combine with the surfaces of microbes, causing them to agglutinate or precipitate and making them susceptible to phagocytosis 42
    • Activation of complement: the complement cascade has 4 major effects 1) induction of inflammation 2) attract phagocytes to infection site 3) opsonization of microbes 4) lysis of bacteria or viral-infected cells There are different classes of antibodies: IgG, IgM, IgA, IgE, IgD IgG: ⋅ predominant immunoglobulin in the body ⋅ can diffuse into extravascular spaces ⋅ crosses the placental barrier, providing passive immunity to fetus for 6 months of life ⋅ basis of passive immunity provided by most natural antiserums IgM: ⋅ first immunoglobulin to be synthesized by infants ⋅ first immunoglobulin to appear in the blood stream during an infection ⋅ secreted onto mucosal surfaces IgA: ⋅ participates in local defense of mucosal surfaces ⋅ antibodies secreted onto mucosal surfaces 43
    • When the body is infected with a particular pathogen the second time (secondary response), memory B cells are able to quickly recognize the pathogen and stimulate a faster immunological response than after the first encounter with that pathogen (primary response). Primary and secondary immunological responses Cell-mediated immunity: More complicated than antibody-mediated immunity 2 main cell types involved: 1) CD4 cells: are primarily helper T cells 2) CD8 cells: cytotoxic T cells 44
    • Helper T cells: ⋅ bind to antigens present on an antigen presenting cells ⋅ stimulate cytotoxic T cells and B cells to help fight the invader Cytotoxic T cells: ⋅ also called killer T cells ⋅ lyse infected cells by releasing the contents of its granules ⋅ activated by antigens present on any cell, not just antigen presenting cells ⋅ activity is enhanced by helper T cells ⋅ involved in rejection of foreign tissue grafts Vaccines 4 main types of vaccines: 1) killed microbes 2) live, attenuated virus 3) toxoids - inactivated toxic compounds from the microbes 4) proteins - Hepatitis B, HPV 45
    • - In the case of smallpox, vaccination using the live, related viruses, cowpox and vaccinia virus, provided protection against smallpox. - DNA-based viruses are under investigation: easier to transport and store List of vaccine-preventable diseases (CDC) Anthrax Cervical cancer Diphtheria Hepatitis A Hepatitis B Haemophilus influenzae type b Influenza Japanese Encephalitis Lyme disease Measles Meningococcal Monkeypox Mumps Whooping cough Pneumococcal Polio Rabies Rotavirus Rubella (German measles) Shingles (Herpes Zoster) Smallpox Tetanus (Lockjaw) Tuberculosis Typhoid Fever Chickenpox (Varicella) Yellow Fever 46
    • Allergies and Autoimmune Diseases Allergies and autoimmune diseases develop when the immune system has gone haywire. Allergies: The immune system attacks something that is not normally harmful to the body. ⋅ exaggerated response to presented antigens Autoimmune disease: The body perceives itself as "nonself" and mounts an attack. ⋅ body is no longer tolerant to "self" Immediate hypersensitivity (Type I hypersensitivity)" ⋅ can happen quickly (usually more severe) ⋅ can also be a delayed response ⋅ Anaphylactic shock is a life threatening, severe whole body response to an allergen ⋅ Treatment options: 1) Benadryl 2) corticosteroids to decrease inflammation 47
    • Delayed hypersensitivity (Type IV hypersensitivity): ⋅ appear within 1-3 days ⋅ mediated by cells ⋅ allergic contact dermatitis: 48
    • Immunology Worksheet 1. Name two antigen presenting cells. 2. How do antigen presenting cells help combat infection? 3. Name three cells that are involved in combating parasitic worm infections. 4. Name two cells that respond immediately to an initial infection and describe their roles in fighting invading pathogens. 5. Define inflammation and list one cell that amplifies the process. 6. Name one cell that kills virus-infected cells. 7. What cells establish immunological memory? 49
    • 8. Which of the following statements about inflammation is correct? a) Inflammation is a component of the adaptive immune response. b) Excessive inflammation can harm the body. c) Pain, swelling, and redness are hallmarks of inflammation. d) b and c are correct e) none of the above 9. Which of the following statements about epithelium is correct? a) Epithelial tissues are only found on the outside of our bodies and in the digestive tract. b) The tight junctions between epithelial cells help keep pathogens from invading nearby tissues. c) Some epithelial cells contain cilia. d) b and c are correct e) all of the above 10. Which of the following events establish immunological "memory"? a) infections and vaccination b) vaccination and breast feeding c) breast feeding and administering antivenom d) 2 or more of the above e) none of the above 11. Which is the predominant immunoglobulin in the body? a) IgA b) IgD c) IgE d) IgG e) IgM 12. Which blood type are you? (If you don't know, assume you're A for the sake of this quiz). People with what blood type(s) may receive a transfusion from you? What blood type(s) may you receive? 50
    • 13. Define the terms antibody and antigen. 14. Explain why our immune system can respond faster the second time we encounter a particular pathogen. 15. What are the functions of helper T cells, cytotoxic T cells and regulatory T cells? 51
    • Autoimmune Disease/Allergy Paper The immune system is essential in protecting us from pathogens, but when immune responses are not properly regulated, autoimmune diseases and allergies may develop. Write a 3 to 4 page double-spaced paper about one of the following and include references (maximum of six references). Wikipedia is not an acceptable reference but can be used as a starting point to find primary articles. The Mayo Clinic and WebMD have useful information. When citing internet sources, list the web address and the date you went to that website. Lupus: Lupus is a complicated autoimmune disease where the body makes antibodies against DNA and nuclear proteins. This disease can affect multiple organs including the skin, kidneys and heart. Rheumatoid arthritis: Rheumatoid arthritis is a chronic painful inflammatory disease where cartilage at the joints is attacked by immune cells. Multiple sclerosis: Multiple sclerosis is an autoimmune disease where the central nervous system is attacked, specifically the protein myelin. Asthma: Asthma is a chronic disorder and it is thought is has an increased prevalence in the United States. Inflammation in the lungs leads to airflow obstruction. Celiac disease: Celiac disease in an autoimmune disorder of the small intestine. The immune system reacts with the protein gluten which is found in wheat products. Poison oak: Contact with poison oak can result in an annoying allergic reaction that affects the skin. Drug allergy (including penicillin): Commonly prescribed drugs can cause allergic reactions, particularly antibiotics. If you would like to write about a different disease/allergy talk to me and I will determine whether I may accommodate you. This assignment is open-ended, but you may want to consider the following when writing your paper. 1) What is the definition of the disease/allergy? 2) What is known and not known about the autoimmune disease/allergy? 3) Are there any known or suspected genetic or environmental connections? 4) What are the causes and triggers? 5) What are effective treatments including lifestyle and home remedies? 6) What is its incidence rate? 52
    • HPV Vaccine Assignment In early 2007 Texas Governor Rick Perry mandated that girls in the public school system entering the sixth grade receive the HPV vaccine, a vaccine that protects women from developing cervical cancer caused by the sexually transmitted virus HPV. Under the mandate, parents could have their children opt out of the vaccine for religious or conscience reasons. Governor Perry, a pro-life, anti-stem cell research Republican received immense criticism from the religious right who argued the mandate violated parental rights and promoted promiscuity. In contrast, he also received enormous praise from women's rights groups who argued his mandate would protect millions of women from developing cervical cancer. The Texas state legislature opposed Perry's executive mandate and passed a law that postponed the implementation of mandatory HPV vaccinations for at least four years. There was enough support in the state legislature for the bill that Governor Perry did not veto it. As your assignment for the next class, be prepared to debate/discuss whether you agree with Governor Perry's attempt to require the HPV vaccine for public school system girls. Issues to consider include cost of the vaccine, parental rights, vaccine safety, the significance of being able to prevent cancer with a vaccine, etc. After our class discussion, write a half page, single-spaced opinion about your personal views concerning mandatory HPV vaccinations. 53
    • IX. Evaluation of Assessment: At the end of each class every student wrote one or two questions related to a concept he or she was confused about. I reviewed each question and addressed common misconceptions the following class. Based on the responses I received, it was clear I did not adequately explain how memory B and T cells are formed. I did not focus on clonal selection, but I now think it is important to explain how memory cells and plasma B cells develop. These concepts are critical in understanding adaptive immunity. In addition, it was also clear after reading the student responses that they were interested in learning more about how common drugs such as Tylenol influence the immune response and how various allergies may be controlled with home remedies. I think that being able to incorporate real world examples into the classes is essential for integrating the material together and maintaining student interest. At the end of the entire course, the students were asked to complete a survey. In the survey several students wrote they enjoyed writing the autoimmune disease/allergy research paper because they were able to learn about a health issue that either affects them or someone they know. 54