Transcript
Immunology overview
Dendritic cell
A hairy person (or someone who doesn’t mind being hairy)
Dendritic cell
• Hairy projections
• Eats bugs
• Presents antigens
Natural killer cell
An indiscriminate bully
Natural killer cell (top) killing infected cell (bottom)
Natural killer cell
• A brute
• Indiscriminate killer
• Part of innate immune system
Helper T cell
A person who is always helpful
Helper T cell
• Helps other cells do their jobs
• Recognizes MHC II
• Part of adaptive immunity
Cytotoxic T cell
A highly trained, expert killer
Cytotoxic T cell
• Deadly, accurate killer
• Recognizes MHC I
• Part of adaptive immune
system
B cell
An extremely productive person
B cell
• Turns into plasma cell
• Makes antibodies
• Part of adaptive immune
system
Macrophage
Someone who likes to eat
Macrophage
• Eats bugs
• Presents antigen
• Part of adaptive immune
system
Neutrophil
Someone filled with toxic chemicals
Neutrophil
• Eats stuff
• Releases toxic stuff
• Part of adaptive immune
system
Infected cell
A sick person
Infected cell
• Virus laden
• Expresses MHC I
• Gets killed by cytotoxic T
cell
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
Immunology Overview
• Definitions
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)
Immunology Overview
• Definitions
• Cells • Lymphocytes • Antigen-presenting cells • Effector cells
White Blood Cell Development
White blood cells
Immunology Overview
• Definitions
• Cells • Lymphocytes
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
Lymphocyte (could be B cell or T cell!)
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
Lymph node
Interfollicular area (brown)
Follicle
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
The T-Cell Receptor
The T-Cell Receptor Bound to Antigen Antigen-presenting cell
T cell
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
Helper T cell Cytotoxic T cell
Cytotoxic T cells surrounding tumor cell
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
class I MHC molecule class II MHC molecule
class II MHC genes class I MHC genes class III MHC genes
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!)
The B-Cell Receptor
The B-Cell Receptor Bound to Antigen
B cell
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!)
Natural killer cell
Natural killer cell (top) killing infected cell (bottom)
Immunology Overview
• Definitions
• Cells • Lymphocytes
• Antigen-presenting cells
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
Dendritic cell surrounded by lymphocytes
Dendritic cell (right) talking to lymphocyte (left)
Dendritic cell (orange) talking to T lymphocytes (green)
Macrophage Monocyte
Macrophage reaching for bacterium
Macrophage gorging on bacteria
Immunology Overview
• Definitions
• Cells • Lymphocytes
• Antigen-presenting cells
• Effector cells
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)
Plasma cell
Neutrophil
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 Humoral Immunity
Cell-Mediated Immunity Humoral 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?
Cell-Mediated Immunity
Immunology Overview
• Definitions
• Cells • Lymphocytes • Antigen-presenting cells • Effector cells
• Responses • The innate immune response • Capturing and displaying antigens • Cell-mediated immunity • Humoral immunity
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
Complement, ridiculously oversimplified
Humoral Immunity
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
Summary of the Adaptive Immune Response
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
Innate immunity
1. Dendritic cell eats bugs
Innate immunity
1. Dendritic cell eats bugs
• Displays antigen to naïve T cells (which MHC?)
Innate immunity
1. Dendritic cell eats bugs
• Displays antigen to naïve T cells (which MHC?)
• T cells mature (put on costumes, and get ready to do their jobs)
Innate immunity
1. Dendritic cell eats bugs
• Displays antigen to naïve T cells (which MHC?)
• T cells mature (put on costumes, and get ready to do their jobs)
2. Neutrophil eats bugs; kills with toxic chemicals
Innate immunity
1. Dendritic cell eats bugs
• Displays antigen to naïve T cells (which MHC?)
• T cells mature (put on costumes, and get ready to do their jobs)
2. Neutrophil eats bugs; kills with toxic chemicals
3. NK cell kills bugs
Adaptive immunity: Cell-mediated
1. Helper T cell does stuff
Adaptive immunity: Cell-mediated
1. Helper T cell does stuff
• Tells macrophage to eat bugs
Adaptive immunity: Cell-mediated
1. Helper T cell does stuff
• Tells macrophage to eat bugs
• Tells B cell to make antibodies
Adaptive immunity: Cell-mediated
1. Helper T cell does stuff
• Tells macrophage to eat bugs
• Tells B cell to make antibodies
2. Cytotoxic T cell does stuff
Adaptive immunity: Cell-mediated
1. Helper T cell does stuff
• Tells macrophage to eat bugs
• Tells B cell to make antibodies
2. Cytotoxic T cell does stuff
• Finds and kills infected cell (how?)
Adaptive immunity: Humoral
1. B cell makes antibodies, which coat bugs
• “Neutralizes” bugs
• Opsonizes bugs (yummy for who?)
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