01 Immunology overview...Adaptive (Acquired) Immunity • Second line of defense • More specific...
Transcript of 01 Immunology overview...Adaptive (Acquired) Immunity • Second line of defense • More specific...
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Immunology
Kristine Krafts, M.D.Overview
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Immunology Overview
Definitions
Cells• Lymphocytes • Antigen-presenting cells
Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity• Immunologic memory
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Immunology Overview
Definitions
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Definitions
• Immunity = protection against infections
• Immune system = collection of cells and molecules that defend us against microbes
• Immune deficiencies → infections
• Immune excesses → autoimmune diseases
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Innate (Natural) Immunity
• Always present (innate); doesn’t change over time
• First line of defense when bugs come
• Major components:• Epithelial barriers (skin, GI, respiratory)• Phagocytes • NK cells• Complement
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Adaptive (Acquired) Immunity
• Second line of defense
• More specific (adaptive) and powerful than innate
• Major components:• Lymphocytes• Lymphocyte products (like antibodies)
• Two types of adaptive immunity:• Humoral immunity (mediated by antibodies)• Cellular immunity (mediated by T cells)
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Immunology Overview
Definitions
Cells• Lymphocytes
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White Blood Cell Development
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White blood cells
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Lymphocytes
• Present in lymphoid organs and in blood
• Groups• T-lymphocytes (grow up in thymus)• B-lymphocytes (grow up in bone marrow)
• Each one has receptors for a specific antigen!
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Lymphocyte (could be B cell or T cell!)
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• Lymphocytes grow up in primary organs, then travel to secondary organs, where they get exposed to antigens.
• Primary organs• Thymus• Bone marrow
• Secondary organs• Lymph nodes• Spleen• Mucosal and cutaneous lymphoid tissues
Lymphoid Tissues
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B cells are in follicles; T cells are in interfollicular areas
Lymph Node
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T Lymphocytes
• Two basic functions:• Kill stuff (cytotoxic T cells)• Help other cells do their jobs (helper T cells)
• T-cell receptor (TCR) complex recognizes antigens• Binds antigen• Sends signals to the T cell
• Antigens must be:• Displayed by other cells…• …AND bound to an MHC molecule (receptor)
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Cytotoxic T cells surrounding tumor cell
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The T-Cell Receptor Bound to AntigenAntigen-presenting cell
T cell
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Class I MHC moleculeClass II MHC molecule
class II MHC genes class I MHC genesclass III MHC genes
Major Histocompatibility Complex (MHC)
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Class I and II MHC Molecules
Class I molecules
• Display antigens from within the cell (e.g., viral antigens) to cytotoxic (CD8+) T cells.
• Present on all nucleated cells! (Good idea.)
Class II molecules
• Display extracellular antigens (e.g., bacterial antigens the cell has eaten) to helper (CD4+) T cells.
• Present only on antigen-presenting cells, like macrophages! (Makes sense.)
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B Lymphocytes
• Basic function: make antibodies
• B-cell receptor complex recognizes antigens• Binds antigen• Sends signals to B cells
• Antigens can be free and circulating (don’t have to be bound to MHC molecules or displayed by other cells to be recognized!)
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Natural Killer (NK) Cells
• Belong to innate immunity arm
• Receptors are not highly variable (like T and B cell receptors are)
• Main job: recognize and kill damaged or infected cells
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Natural killer cell
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Natural killer cell (top) killing infected cell (bottom)
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Immunology Overview
Definitions
Cells• Lymphocytes • Antigen-presenting cells
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Antigen-Presenting Cells
Dendritic cells• Present mostly in two places: under epithelia and in
germinal centers of lymph nodes• Capture bug, present antigens to B and T cells• Super important in activating the adaptive system
Macrophages
• Present all over the body• Eat bugs and present antigens to T cells• Their role in activating the adaptive system is not as
pivotal though!
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Dendritic cell surrounded by lymphocytes
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Dendritic cell (right) talking to lymphocyte (left)
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MacrophageMonocyte
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Macrophage reaching for bacterium
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Macrophage gorging on bacteria
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Immunology Overview
Definitions
Cells• Lymphocytes • Antigen-presenting cells
Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity• Immunologic memory
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Immunology Overview
Definitions
Cells• Lymphocytes • Antigen-presenting cells
Responses• The innate immune response
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The Innate Immune Response
• If bugs make it through epithelium, they encounter cells of the innate immune system
• What happens in the innate immune system?• Phagocytes eat bugs• Complement is activated • NK cells find and kill infected cells • Dendritic cells migrate to lymph nodes to
activate the adaptive immune system
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What is complement?Just give me the bottom line.
It’s a bunch of proteins that poke holes in cells.
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Okay, give me a little more information.
• Consists of about 20 plasma proteins (C1, C2, etc.)
• Can be activated by bacterial components
• Activation proceeds in a cascade fashion
• End results:• Cell lysis• Chemotaxis (attraction of neutrophils)• Opsonization (coating of cells to make them
“yummy” to macrophages)
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Complement, ridiculously oversimplified
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Immunology OverviewDefinitions
Cells• Lymphocytes • Antigen-presenting cells• Effector cells
Responses• The innate immune response• Capturing and displaying antigens
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Capturing and Displaying Antigens
• Dendritic cells in epithelium capture bug antigens, transport them to lymph nodes
• Dendritic cells display antigens to B and T cells
• Antigens and cytokines trigger proliferation and differentiation of B and T cells
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Immunology Overview
Definitions
Cells• Lymphocytes • Antigen-presenting cells
Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity
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The Main Players in Cell-Mediated Immunity
Helper (CD4+) T cells• These guys help macrophages eat bugs.• They also call in neutrophils.
Cytotoxic (CD8+) T cells• These guys kill infected cells.• They are like highly-trained assassins.
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Matt Damon and the “asset”
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Cell-Mediated Immunity
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Immunology Overview
Definitions
Cells• Lymphocytes • Antigen-presenting cells
Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity
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Humoral Immunity
Bacteria enter body
B cells make antibodies against
bacteria
Antibodies bind to bacteria
Phagocytes ingest bacteria
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What is an antibody?
• Y-shaped glycoprotein • 2 light chains (κ or λ)• 2 heavy chains (α, γ, δ, ε, or μ)
• Fab fragments• Upper part of Y (the arms)• Binds to antigen
• Fc fragment• Lower part of Y (the stem)• Binds to cells like macrophages, neutrophils.
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What happens when antibodies bind to bugs?
• Bugs are neutralized (they can’t infect cells).
• Antibody-coated bugs are “opsonized,” making them yummy to macrophages and neutrophils (which have receptors for the Fc portion of IgG! How handy!).
• Complement is activated (bad news for bugs).
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Immunology Overview
Definitions
Cells• Lymphocytes • Antigen-presenting cells
Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity• Immunologic memory
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Immunologic Memory
• After an infection is over, most immune cells die.
• A few memory cells remain and live on for years.• Expanded pool of antigen-specific lymphocytes• Respond faster, better than naïve lymphocytes• Vaccines depend on these guys
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Summary of the Adaptive Immune Response
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Immunology Overview
Definitions
Cells• Lymphocytes • Antigen-presenting cells
Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity• Immunologic memory
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Summary of the Adaptive Immune Response
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Immunology Overview
Definitions
Cells• Lymphocytes • Antigen-presenting cells
Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity• Immunologic memory