Immunology
• 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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Immunology Overview •
Innate and Adaptive Immunity
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Cells and Tissues of the Immune System • • • •
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Lymphocytes Antigen-presenting cells Effector cells Lymphoid tissues
Normal Immune Responses • • • • •
The innate immune response Capturing and displaying antigens Cell-mediated immunity Humoral immunity Immunologic memory www.indiandentalacademy.com
Immunology Overview •
Innate and Adaptive Immunity
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Innate and Adaptive Immunity 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) • NK cells • Complement
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Innate and Adaptive Immunity Adaptive (Acquired) Immunity • Second line of defense • More specific (adaptive) and powerful than innate • Major components: • Lymphocytes • Lymphocyte products • Two types of adaptive immunity: • Humoral immunity (mediated by antibodies) • Cellular immunity (mediated by T cells) www.indiandentalacademy.com
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Immunology Overview •
Innate and Adaptive Immunity
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Cells and Tissues of the Immune System • • • •
Lymphocytes Antigen-presenting cells Effector cells Lymphoid tissues
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White blood cells
Immunology Overview •
Innate and Adaptive Immunity
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Cells and Tissues of the Immune System •
Lymphocytes
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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 • Recognize millions of different antigens! • Diversity generated by: • rearrangement of antigen receptor genes • different joining of the gene segments • Gene rearrangement studies www.indiandentalacademy.com
lymphocytewww.indiandentalacademy.com (could be B cell or T cell!)
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Lymphocytes T lymphocytes • Live in blood, bone marrow, lymphoid tissues • Two basic functions: • kill stuff • help other cells do their jobs • T-cell receptor (TCR) complex recognizes antigens • binds antigen • sends signals to the T cell • Antigens must be: • displayed by other cells… www.indiandentalacademy.com • …AND bound to an MHC receptor
The T-Cell Receptor
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The T-Cell Receptor Antigen-presenting cell
T cell www.indiandentalacademy.com
Lymphocytes T lymphocytes • Helper T cells • CD4+ (and CD8-) • help B cells make antibodies • help macrophages eat bugs • decreased in patients with AIDS • Cytotoxic T cells • CD8+ (and CD4-) • kill virus-infected cells and tumor cells www.indiandentalacademy.com
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CD8+ T cells surrounding tumor cell
Lymphocytes MHC complex •
Collection of genes on chromosome 6
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Three regions: class I, class II, class III
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Highly polymorphic!
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Gene products: • class I molecules • class II molecules • class III molecules (and other stuff) www.indiandentalacademy.com
class II MHC genes
class III MHC genes
class II MHC molecule
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class I MHC genes
class I MHC molecule
Lymphocytes Class I MHC molecules •
Encoded by three loci: HLA-A, HLA-B, HLA-C
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Display antigens from within the cell (e.g., viral antigens) to CD8+ T cells.
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Present on all nucleated cells! (Good idea.)
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Lymphocytes Class II MHC molecules •
Encoded by three loci: HLA-DP, HLA-DQ, HLA-DR
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Display extracellular antigens (e.g., bacterial antigens the cell has eaten) to CD4+ T cells
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Present mainly on antigen presenting cells, like macrophages! (Makes sense.)
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Lymphocytes B lymphocytes • Live in blood, bone marrow, lymphoid tissues • Basic function: make antibodies (immunoglobulins) • B-cell receptor complex recognizes antigens • binds antigen • sends signals to T cells • Antigens can be free and circulating (don’t have to be bound to MHCs or displayed by other cells to be recognized!) www.indiandentalacademy.com
The B-Cell Receptor
B cell www.indiandentalacademy.com
The B-Cell Receptor
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Lymphocytes Natural Killer Cells • Belong to innate immunity arm • No highly variable receptors like T and B cells • Main job: recognize and kill damaged or infected cells • Antigens don’t have to be bound to MHCs or displayed by other cells!
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www.indiandentalacademy.com Natural killer cell
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Natural killer cell (top) killing infected cell (bottom)
Immunology Overview •
Innate and Adaptive Immunity
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Cells and Tissues of the Immune System • •
Lymphocytes Antigen-presenting cells
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Antigen-presenting cells •
Main job: catch antigens and display them to lymphocytes
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Dendritic cells • Have fine cytoplasmic projections • Present all over body: skin, lymph nodes, organs • Capture bug antigens, display to B and T cells
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Other APCs • Macrophages eat bugs and present antigens to T cells, which tell macrophages to kill bugs • B cells present antigens to helper T cells, which tell B cells to make antibodies www.indiandentalacademy.com
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dendritic cells
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Immunology Overview •
Innate and Adaptive Immunity
•
Cells and Tissues of the Immune System • • •
Lymphocytes Antigen-presenting cells Effector cells
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Effector cells •
These guys carry out the ultimate immune system task: eliminate infection
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Types of effector cells • NK cells • Plasma cells • T cells (both CD4+ and CD8+) • Macrophages • Other leukocytes (e.g., neutrophils)
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Immunology Overview •
Innate and Adaptive Immunity
•
Cells and Tissues of the Immune System • • • •
Lymphocytes Antigen-presenting cells Effector cells Lymphoid tissues
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Lymphoid tissues •
Lymphocytes grow up in primary organs, then travel to secondary organs, searching for antigens.
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Primary organs • thymus • bone marrow
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Secondary organs • lymph nodes • spleen • mucosal and cutaneous lymphoid tissues www.indiandentalacademy.com
Immunology Overview •
Innate and Adaptive Immunity
•
Cells and Tissues of the Immune System • • • •
•
Lymphocytes Antigen-presenting cells Effector cells Lymphoid tissues
Normal Immune Responses •
The innate immune response
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The Innate Immune Response •
Main bug barriers: skin, mucosa
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If bugs make it through epithelium, they encounter innate immune system
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What happens in the innate immune system? • Phagocytes eat bugs, kill them • Cytokines are released • Complement is activated • The adaptive immune system is activated
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Immunology Overview •
Innate and Adaptive Immunity
•
Cells and Tissues of the Immune System • • • •
•
Lymphocytes Antigen-presenting cells Effector cells Lymphoid tissues
Normal Immune 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
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APCs in lymph nodes eat antigens, display them (using their MHC receptors) to T cells
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B cells in lymph nodes also recognize antigens
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Antigens and molecules produced during innate immune response trigger proliferation and differentiation of B and T cells
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Immunology Overview •
Innate and Adaptive Immunity
•
Cells and Tissues of the Immune System • • • •
•
Lymphocytes Antigen-presenting cells Effector cells Lymphoid tissues
Normal Immune Responses • • •
The innate immune response Capturing and displaying antigens Cell-mediated immunity www.indiandentalacademy.com
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Cell-mediated immunity How does the process work? •
Naïve T cells are activated by antigen and costimulators in lymph nodes…
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…then they proliferate and differentiate into effector cells that go find the antigen.
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CD4+ T cells help macrophages eat bugs
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CD8+ T cells kill infected cells directly
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All these steps are dependent upon cytokines www.indiandentalacademy.com
Cell-Mediated Immunity
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Cell-mediated immunity What are cytokines? •
Polypeptides that do lots of different things: • • • •
help leukocytes grow and differentiate activate T cells, B cells and macrophages help leukocytes communicate recruit neutrophils
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Made by lymphocytes and macrophages
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Examples: TNF, the interleukins, interferon γ www.indiandentalacademy.com
Cell-mediated immunity What kinds of effector T cells are there? •
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CD4+ T cells differentiate into two kinds of effector cells: •
TH1 cells (activate macrophages, cause B cells to secrete Ab)
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TH2 cells (activate eosinophils, cause B cells to secrete IgE)
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These guys go to the site of infection, and with the help of macrophages and cytokines, do their thing.
CD8+ T cells differentiate into cytotoxic T cells • •
These guys kill cells that have microbes in their cytoplasm. They are like little assassins.
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www.indiandentalacademy.com Matt Damon and the “asset�
Cell-Mediated Immunity
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Immunology Overview •
Innate and Adaptive Immunity
•
Cells and Tissues of the Immune System • • • •
•
Lymphocytes Antigen-presenting cells Effector cells Lymphoid tissues
Normal Immune Responses • • • •
The innate immune response Capturing and displaying antigens Cell-mediated immunity Humoral immunity www.indiandentalacademy.com
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Humoral immunity How does the process work? •
B cells get activated by exposure to antigens (sometimes with the help of CD4+ T cells)
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B cells differentiate into plasma cells (that make antibodies)
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The antibodies do nasty things to bugs
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plasma cell
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Humoral immunity What is an antibody again? •
Y-shaped glycoprotein • •
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Constant regions of heavy chain form the Fc fragment • •
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2 light chains (κ or λ) 2 heavy chains (α, γ, δ, ε, or μ)
binds to APCs defines isotype (immunoglobulin class: IgA, IgE, etc.)
Variable regions of both chains form the Fab fragments • •
binds to antigen defines idiotype www.indiandentalacademy.com
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Humoral immunity What do antibodies do? •
Bind to – and “neutralize” – bugs, so they can’t infect cells.
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Coat (“opsonize”) bugs, making them yummy to macrophages and neutrophils (which have receptors for the Fc portion of IgG! How handy!).
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Activate complement.
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Humoral immunity What is complement? Just give me the bottom line.
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It’s a bunch of proteins that poke holes in cells.
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Humoral immunity Okay, give me a little more information. •
Consists of about 20 plasma proteins (C1, C2, etc.)
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Can be activated in a few different ways • • •
by antigen-antibody complexes by bacterial LPS by bugs that have mannan on their surfaces
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Activation proceeds in a cascade fashion
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End results: • • •
cell lysis chemotaxis opsonization www.indiandentalacademy.com
Complement, ridiculously oversimplified
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Humoral Immunity
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Immunology Overview •
Innate and Adaptive Immunity
•
Cells and Tissues of the Immune System • • • •
•
Lymphocytes Antigen-presenting cells Effector cells Lymphoid tissues
Normal Immune Responses • • • • •
The innate immune response Capturing and displaying antigens Cell-mediated immunity Humoral immunity Immunologic memory www.indiandentalacademy.com
Immunologic memory
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Most effector lymphocytes die after killing the bug.
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A few memory cells live on for years. • expanded pool of antigen-specific lymphocytes • respond faster, better than naïve cells • vaccines depend on these guys
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Summary of the Adaptive Immune Response
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Immunology Overview •
Innate and Adaptive Immunity
•
Cells and Tissues of the Immune System • • • •
•
Lymphocytes Antigen-presenting cells Effector cells Lymphoid tissues
Normal Immune Responses • • • • •
The innate immune response Capturing and displaying antigens Cell-mediated immunity Humoral immunity Immunologic memory www.indiandentalacademy.com
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