© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION © Science photo/Shutterstock© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION CHAPTER 2 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORFundamentals SALE OR DISTRIBUTION of theNOT FOR SALE OR DISTRIBUTION © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE ORImmune System DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Barsha Dash, PhD; Brittney Dinkel, PhD; and Ian Clift, PhD, MLS(ASCP)CM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC KEY NOTTERMS FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Alternative pathway Immune organs Neutrophils Basophils Lectin pathway Pattern recognition receptors Chemokines Lymphoid tissue inducer (PRR) © JonesClassical & Bartlett pathway Learning, LLC cells (LTi) © JonesPlasma & cells Bartlett Learning, LLC NOT FORClonal SALE expansion OR DISTRIBUTIONMacrophages NOT FORPrimary SALElymphoid OR tissues DISTRIBUTION Cytokines Major histocompatibility Secondary lymphoid tissues Dendritic cells (DCs) complex (MHC) Terminal pathway Hematopoietic stem cells (HSCs) Mast cells Histology Monocytes © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION LEARNING OBJECTIVES Upon completion of this chapter, the reader should be able to: 1. Review© Jones the hist &ory Bartlett of immunology Learning, up to present LLC laboratory practices. © Jones & Bartlett Learning, LLC 2. UnderstandNOT FOR and differentiateSALE OR the DISTRIBUTION three lines of defense that make up the immuneNOT system. FOR SALE OR DISTRIBUTION 3. Specify the function of the major immune organs. 4. Outline the pathway of development for B and T cells via lineage and location. 5. Compare and contrast the pathophysiological role of the various complement pathways. 6. Identify and specify pattern recognition particles involved in innate immune response based on pathology. © Jones & 7.Bartlett Demonstrate Learning, understanding LLC of the cell types, function and form© Jones of MHC molecules. & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION © Jones & Bartlett Learning,© Jones LLC & Bartlett Learning LLC, an Ascend Learning© Jones Company. & NOT Bartlett FOR SALE Learning, OR DISTRIBUTION. LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 9781284173017_CH02_Clift.indd 15 30/12/19 8:24 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 16 Chapter 2 Fundamentals of the Immune System ▸ in cattle, and Koch experimentally demonstrated Introduction© Jones & Bartlett Learning,the LLC virulence of the bacteria by© firstJones isolating & Bartlett Learning, LLC The immune systemNOT hasFOR the SALE remarkable OR abilityDISTRIBUTION it, and then injecting healthy animalsNOT FOR with it.SALE OR DISTRIBUTION to discriminate between host and pathogens to Injected animals developed disease, definitively eliminate infections and preserve organismal demonstrating the bacteria to be the causative homeostasis. To this end, it relies on two key agent of the disease. Koch developed numer- elements—the innate and adaptive systems— ous techniques to isolate, grow, and inoculate © tJoneshat work & hand Bartlett in hand Learning, to eradicate LLC bacte- bacteria that are© Jonesstill in use & Bartletttoday. The Learning, works LLC NOTria, FORviruses, SALE and parasites.OR DISTRIBUTION Innate responses of Pasteur and NOTKoch elucidatedFOR SALE the importance OR DISTRIBUTION are driven by encoded pattern recognition of hypothesizing and developing experimental receptors (PRR) that detect a limited and con- tools to demonstrate the cause of an infectious served set of molecular patterns present on disease, enabling departure from early ideas of microbes and usually absent on mammalian spontaneous generation of disease. Koch went © Jones & Bartlettcells. Learning,However, adaptive LLC mechanisms depend © onJones to demonstrate & Bartlett that Learning,tuberculosis wasLLC caused NOT FOR SALEon OR many DISTRIBUTION genetic rearrangements, engender- NOTby aFOR bacterium SALE ( Mycoba OR DISTRIBUTIONcterium tuberculosis). ing spectacular diversity in molecules that aid Pasteur also discovered that long-term culturing in recognition of pathogen-derived substances of bacteria attenuated the bacteria or made them called antigens. In addition, a salient feature of less virulent, generating the roots for attenuated the adaptive immune system is clonal expan- © Jones & Bartlett Learning,vaccine LLC applications, which involves© Jones adminis & -Bartlett Learning, LLC sion whereby adaptive cells that find their cog- tration of a weakened pathogen as vaccine to nate antigen undergo rapid expansion. These NOT FOR SALE OR DISTRIBUTIONcreate memory. Edward Jenner, anNOT 18th FOR century SALE OR DISTRIBUTION cells then partake in pathogen elimination and physician from England, had already shown that memory formation, which is essential for rapid inoculation with cowpox conferred protection elimination of pathogens upon reencounter. To against smallpox by immunizing a young boy summarize, collective specificities of the innate with bacteria from cowpox of a dairy farmer. © andJones adaptive & Bartlett responses Learning, allow for detection LLC and © Jones & Bartlett Learning, LLC NOTmounting FOR ofSALE potent OR defenses DISTRIBUTION against invading These observationsNOT FORand heroic SALE experimental OR DISTRIBUTION pathogens, while minimizing harm to the host. endeavors emphasized the importance of under- The specificity of the adaptive cell repertoire to standing biology, establishing methodologies minimize host damage is called immune toler- to find disease etiology and methods to exploit ance. Breakdown of tolerance can result in auto- immunological memory, although immunity © Jones & Bartlettimmune Learning, diseases that LLC entail immune-mediated © hadJones not yet & beenBartlett understood. Learning, LLC NOT FOR SALEdestruction OR DISTRIBUTION of organs. This chapter aims to pro- NOT FORIn the SALE 1800s, OR Paul DISTRIBUTION Erlich, a German vide an overview of immune cell development, physician-scientist, developed histologic meth- function, and immune organs at the anatomical ods to examine innate cells such as neutrophils, and molecular levels. basophils, and eosinophils. Histology involves staining of cells with different compounds to © Jones & Bartlett Learning,enable LLC visualization of cell morphology.© Jones Erlich’s & Bartlett Learning, LLC History NOT FOR SALE OR DISTRIBUTIONbackground in chemistry allowedNOT him FOR to put SALE OR DISTRIBUTION Nineteenth century paradigms created a fer- forth early theories of immune recognition of tile foundation for modern immunology. Louis microbes and microbe-derived substances. He Pasteur, a French scientist, and Robert Koch, a proposed that “antitoxins,” produced by certain German scientist, put forth the “germ theory”, cells of the host, bind via chemically specific © i.e.,Jones the postulation & Bartlett that Learning, microorganisms LLC cause interactions with© Jonestoxins, neutralizing & Bartlett their Learning, vir- LLC NOTdiseases. FOR Pasteur SALE hypothesized OR DISTRIBUTION that the bacte- ulence. He demonstratedNOT FOR this SALE by isolating OR serumDISTRIBUTION rium Bacillus anthracis caused Anthrax disease containing “antitoxin” and inoculating animals © Jones & Bartlett Learning,© Jones LLC & Bartlett Learning LLC, an Ascend Learning© Jones Company. & NOT Bartlett FOR SALE Learning, OR DISTRIBUTION. LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 9781284173017_CH02_Clift.indd 16 30/12/19 8:24 PM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Antimicrobial Small Molecules as the First Barrier of Protection 17 exposed to diphtheria toxin. Animals that were must cooperate to mount immune responses, given the© “antitoxin” Jones &survived. Bartlett Learning, LLCi.e., phagocytes express MHC© Jones molecules & that Bartlett dis- Learning, LLC Now,NOT it is wellFOR known SALE that OR B cells, DISTRIBUTION cells of play peptides derived fromNOT antigens FOR for SALE activa- OR DISTRIBUTION adaptive immunity, produce antibodies that tion of T cells. Currently, with the help of gene bind to toxins and neutralize their virulence, sequencing and protein structure determination, protecting the host. This was the first step it is well appreciated that MHC molecules are toward understanding humoral or B-cell medi- highly diverse (polymorphic) within the human © Jonesated & immunity. Bartlett AsLearning, new methodological LLC tools, population© andJones govern & susceptibility Bartlett Learning, to infectious LLC NOT FORenabling SALE protein OR separation DISTRIBUTION based on charge and diseases,NOT autoimmunity, FOR SALE and cancer. OR DISTRIBUTION size, enzymatic digestive methods for proteins, Elegant experiments of the past have built and protein structural analysis techniques were the foundations of modern immunology. Our developed, appreciation of the structure and understanding of immunology has led to devel- chemical nature of antibodies grew. In the 20th opment of diagnostic tools, which, in turn, have © Jones & Bartlett Learning,century, focus LLC shifted to an examination