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An introduction to Immunology Kate Eaton, DVM, PhD Diplomate ACVP Department of Microbiology and Immunology, 6746 Med Sci II 936-3883 kateaton@umich.edu Mic405 Autumn 2016
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Class details Lecture notes: Intermittent posted reading Please read before lecture so that you can participate ppts on Canvas Approach: Lecture/discussion Contact: Email: kateaton@umich.edu Office hours by appointment Office 6746 MSII
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Immunology resources Texts: Clinical key Abbas and Lichtman, Basic Immunology Male et al, Immunology Delves et al, Roitt’s Essential Immunology Murphy et al, Janeway’s Immunobiology Web: www.microbiologybook.org/book/immunol-sta.htm http://www.niaid.nih.gov/topics/immuneSystem/Pages/default.aspx https://en.wikipedia.org/wiki/Outline_of_immunology#Essence_of_immunology
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Schedule of classes Introduction Innate Immunity Adaptive immunity I Adaptive immunity II Vaccines Immunity gone wrong Problems in immunology I Problems in immunology II
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Schedule for today Introduction to the immune system: Functions and characteristics Innate and adaptive immunity Organs, cells, and mediators Language of immunology
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The language of immunology Historical basis: names describe functions (complement) Different names for the same thing (chemokines, cytokines) Alphabet soup (cytokines) Numerical suffixes (interleukins)
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Infection Inflammation Immune response
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Functions of the immune system ?
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Characteristics of the immune system Broad range: Bacteria Toxins Viruses Parasites Tumor cells Fungi Foreign cells Particulates Highly specific Pathogen species and strains Self vs non-self Memory Widespread Every organ and system Extremely fluid It moves!!!!
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Arms of the immune system Broad range Highly specific Humoral Cellular
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Innate immunity Inborn First line of defense Components: Physical barriers Macrophages, natural killer cells, antigen-presenting cells Soluble mediators Present in all metazoans
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Adaptive (acquired) immunity Develops in response to microbial contact Recognizes features of specific pathogens Immunologic memory Humoral and cellular arms: Humoral immunity: antibodies Cellular immunity: cytotoxicity Characteristic of vertebrates
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Characteristics of innate and adaptive immunity Yes
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Self-recognition Mammals? Vertebrates? Invertebrates? Protozoa? Bacteria? Viruses? What classes of organisms recognize self?
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Sponge allograft rejection Wiens M, Krasko A, Blumbach B, Müller IM, Müller WE. 2000. Cell Death Differ 7:461–469. Müller WEG, Müller IM. 2003.. Integr. Comp. Biol. 43:281–292.
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Self-recognition in vertebrates Molecular patterns Characteristic of broad groups: Bacteria: Lipopolysaccharide, flagella, peptidoglycan Viruses: DS RNA, CpG motifs Innate immune response Antigens Pathogen-specific Adaptive immune response
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Components of the immune system Cells Organs Soluble mediators
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Cells of the immune system Phagocytes: Macrophages Granulocytes Lymphocytes: T cells B cells Antigen-presenting cells: Dendritic cells
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Phagocytes
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Phagocytes First steps of the innate immune response Engulf and digest pathogens and particulates Recognize pathogen-specific patterns: Pathogen-associated molecular patterns (PAMPs) Microbe-associated molecular patterns (MAMPs) Regulate other immune cells Secrete mediators Direct contact Macrophages, granulocytes, dendritic cells
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Peakman Polymorphonuclear leukocyte “Poly”, PMN http://imagebank.hematology.org/AssetDetail.aspx?AssetID=3742&AssetType=Asset Macrophage Male figure 1-2 Macrophage http://imgarcade.com/1/neutrophils-slide/ Granulocyte
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Lymphocytes Adaptive immunity Recognize antigens B cells Recognize antigen directly Produce antibodies T cells Recognize antigen in association with antigen-presenting cells T helper cells (Th): Soluble mediators T cytotoxic cells (Tc): Kill infected cells
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The lymphocyte
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Antigen-presenting cells Link innate and adaptive immunity Process antigen and “present” it to T cells Dendritic cells Phagocytic and motile Resident in epithelial surfaces and lymphoid tissues Mature in response to molecular patterns
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Dendritic cells in culture
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Skin: Langerhans cells http://www.technion.ac.il/~mdcourse/274203/lect12.html Dendritic cells in tissue
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Other cells
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Organs of the immune system Primary immune organs: immune cells develop and mature Bone marrow: Differentiation, B cell maturation? Thymus: T cell maturation Bursa of Fabricius: B cell maturation Secondary immune organs: immune cells become activated Spleen Lymph nodes Mucosa-associated lymphoid tissue
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Gross photo alert!
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Lymphoid follicles http://www.vetmed.vt.edu/education/curriculum/VM8054/ Lymph node
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Mucosa-associated lymphoid tissue http://cal.vet.upenn.edu/projects/histo/Labintestines.htm
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How immune cells communicate Soluble mediators Extracellular Receptor/ligand-specific Paracrine vs endocrine Signal transduction Direct contact: Antigen presentation Cytotoxicity
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Soluble mediators of the immune response Signaling molecules Innate: Cytokines, complement Adaptive: Cytokines, antibodies, chemokines, interleukins Cytotoxic molecules Innate: Enzymes, reactive oxygen mediators Adaptive: Enzymes, reactive oxygen mediators
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Cytokines “Low molecular weight proteins that stimulate or inhibit the differentiation, proliferation, or function of cells” Hundreds exist Multifunctional Overlapping functions Produced by immune and non-immune cells One cell may produce many cytokines One cytokine may be produced by many cells Interleukins: Subset of cytokines that communicate between leukocytes Named consecutively by IL- designation
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Tumor Necrosis Factor Interleukin-1 Endogenous pyrogens
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Important cytokines
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Chemokines A subset of cytokines (chemotaxic cytokines) “A family of structurally related cytokines that selectively induce chemotaxis and activation of leukocytes” Old nomenclature: by function (mostly) New nomenclature: according to N-terminal amino acid sequence: CXC= one amino acid separating two N-terminal cyseine residues CX3C = three amino acids CC= cysteines adjacent C= only one cysteine present L designation = ligand, R designation = receptor: CXCL8 binds CXCR8 (usually)
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A few chemokines
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Communication by direct contact Antigen presentation: The immunological synapse Cytotoxicity
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Chronology of the immune response Bactericidal molecules Phagoyctes, Soluble mediators Antigen presentation, B and T cell maturation
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Innate and Adaptive Immunity
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