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Immunology Overview
• Definitions
• Cells • Lymphocytes • Antigen-presenting cells • Effector cells
• Responses • The innate immune response • Capturing and displaying antigens • Cell-mediated immunity • Humoral immunity • Immunologic memory
Definitions
• Immunity = protection against infections
• Immune system = collection of cells and molecules that defend us against microbes
• Immune deficiencies → infections
• Immune excesses → autoimmune diseases
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
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)
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
Lymphoid tissues
• Lymphocytes grow up in primary organs, then travel to secondary organs, searching for antigens.
• Primary organs • thymus
• bone marrow
• Secondary organs • lymph nodes
• spleen
• mucosal and cutaneous lymphoid tissues
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…
• …AND bound to an MHC receptor
T-Lymphocytes
• Helper T cells • CD4+ (and CD8-)
• help B cells make antibodies
• help macrophages eat bugs
• Cytotoxic T cells • CD8+ (and CD4-)
• kill virus-infected cells and tumor cells
MHC
• Collection of genes on chromosome 6
• Three regions: class I, class II, class III
• Highly polymorphic!
• Gene products:
• class I molecules
• class II molecules
• class III molecules (and other stuff)
Major histocompatibility (MHC) complex
MHC
• Encoded by three loci: HLA-A, HLA-B, HLA-C
• Display antigens from within the cell (e.g., viral antigens) to CD8+ T cells.
• Present on all nucleated cells! (Good idea.)
Class I MHC molecules
MHC
• Encoded by three loci: HLA-DP, HLA-DQ, HLA-DR
• Display extracellular antigens (e.g., bacterial antigens the cell has eaten) to CD4+ T cells
• Present mainly on antigen presenting cells, like macrophages! (Makes sense.)
Class II MHC molecules
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!)
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 can be free and circulating (don’t have to be bound to MHCs or displayed by other cells to be recognized!)
Antigen-presenting cells
• Main job: catch antigens and display them to lymphocytes
• Dendritic cells • Have fine cytoplasmic projections
• Present all over body: skin, lymph nodes, organs
• Capture bug antigens, display to B and T cells
• 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
Effector cells
• These guys carry out the ultimate immune system task: eliminate infection
• Types of effector cells • NK cells
• Plasma cells
• T cells (both CD4+ and CD8+)
• Macrophages
• Other leukocytes (e.g., neutrophils)
Immunology Overview
• Definitions
• Cells • Lymphocytes • Antigen-presenting cells • Effector cells
• Responses • The innate immune response
The Innate Immune Response
• Main bug barriers: skin, mucosa
• If bugs make it through epithelium, they encounter innate immune system
• What happens in the innate immune system? • Phagocytes eat bugs, kill them
• Cytokines are released
• Complement is activated
• The adaptive immune system is activated
Immunology Overview
• Definitions
• Cells • Lymphocytes • Antigen-presenting cells • Effector cells
• Responses • The innate immune response • Capturing and displaying antigens
Capturing and displaying antigens
• Dendritic cells in epithelium capture bug antigens, transport them to lymph nodes
• APCs in lymph nodes eat antigens, display them (using their MHC receptors) to T cells
• B cells in lymph nodes also recognize antigens
• Antigens and molecules produced during innate immune response trigger proliferation and differentiation of B and T cells
Immunology Overview
• Definitions
• Cells • Lymphocytes • Antigen-presenting cells • Effector cells
• Responses • The innate immune response • Capturing and displaying antigens • Cell-mediated immunity
Cell-mediated immunity
• Naïve T cells are activated by antigen and costimulators in lymph nodes…
• …then they proliferate and differentiate into effector cells that go find the antigen.
• CD4+ T cells help macrophages eat bugs
• CD8+ T cells kill infected cells directly
• All these steps are dependent upon cytokines
How does the process work?
Cell-mediated immunity
• Polypeptides that do lots of different things: • help leukocytes grow and differentiate
• activate T cells, B cells and macrophages
• help leukocytes communicate
• recruit neutrophils
• Made by lymphocytes and macrophages
• Examples: TNF, the interleukins, interferon γ
What are cytokines?
Cell-mediated immunity
• CD4+ T cells differentiate into two kinds of effector cells:
• TH1 cells (activate macrophages, cause B cells to secrete Ab)
• TH2 cells (activate eosinophils, cause B cells to secrete IgE)
• 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.
What kinds of effector T cells are there?
Immunology Overview
• Definitions
• Cells • Lymphocytes • Antigen-presenting cells • Effector cells
• Responses • The innate immune response • Capturing and displaying antigens • Cell-mediated immunity • Humoral immunity
• B cells get activated by exposure to antigens (sometimes with the help of CD4+ T cells)
• B cells differentiate into plasma cells (that make antibodies)
• The antibodies do nasty things to bugs
How does the process work?
Humoral immunity
• Y-shaped glycoprotein • 2 light chains (κ or λ)
• 2 heavy chains (α, γ, δ, ε, or μ)
• Constant regions of heavy chain form the Fc fragment • binds to APCs
• defines isotype (immunoglobulin class: IgA, IgE, etc.)
• Variable regions of both chains form the Fab fragments • binds to antigen
• defines idiotype
What is an antibody again?
Humoral immunity
• Bind to – and “neutralize” – bugs, so they can’t infect cells.
• Coat (“opsonize”) bugs, making them yummy to macrophages and neutrophils (which have receptors for the Fc portion of IgG! How handy!).
• Activate complement.
What do antibodies do?
Humoral immunity
What is complement? Just give me the bottom line.
Humoral immunity
• It’s a bunch of proteins that poke holes in cells.
Okay, give me a little more information.
Humoral immunity
• Consists of about 20 plasma proteins (C1, C2, etc.)
• Can be activated in a few different ways • by antigen-antibody complexes
• by bacterial LPS
• by bugs that have mannan on their surfaces
• Activation proceeds in a cascade fashion
• End results: • cell lysis
• chemotaxis
• opsonization
Immunology Overview
• Definitions
• Cells • Lymphocytes • Antigen-presenting cells • Effector cells
• Responses • The innate immune response • Capturing and displaying antigens • Cell-mediated immunity • Humoral immunity • Immunologic memory
Immunologic memory
• Most effector lymphocytes die after killing the bug.
• 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