Transcript No Slide Title - Dental Student Pathology

Immunology
Overview
Kristine Krafts, M.D.
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
Follicle
Interfollicular area (brown)
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
Major Histocompatibility Complex (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)
class II MHC genes
Class II MHC molecule
class III MHC genes
class I MHC genes
Class I MHC molecule
Class I MHC Molecules
• 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 II MHC Molecules
• 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.)
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 B 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 (NK) 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)
Monocyte
Macrophage
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
• Capturing and displaying antigens
• Cell-mediated immunity
• Humoral immunity
• Immunologic memory
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
Humoral Immunity
Cell-Mediated Immunity
Humoral Immunity
Cell-Mediated Immunity
Capturing and Displaying Antigens
• 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
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
• Made by lymphocytes and macrophages
• Examples: tumor necrosis factor (TNF),
interleukins, interferons
Types of Effector T Cells
• CD4+ T cells differentiate into:
• 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.
Matt Damon and the “asset”
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
Humoral Immunity
Cell-Mediated Immunity
Humoral Immunity
• B cells are activated by exposure to antigens
(sometimes with the help of CD4+ T cells)
• B cells differentiate into plasma cells
(which make antibodies)
• The antibodies do nasty things to bugs
What is an antibody?
• Y-shaped glycoprotein
• 2 light chains (κ or λ)
• 2 heavy chains (α, γ, δ, ε, or μ)
• Constant regions of heavy chain form Fc fragment
• Binds to APCs
• Defines isotype (Ig class: IgA, IgE, etc.)
• Variable regions of both chains form Fab fragments
• Binds to antigen
• Defines idiotype
What do antibodies do?
• 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 is complement?
Just give me the bottom line.
It’s a bunch of proteins that poke holes in cells.
Okay, give me a little more information.
• Consists of about 20 plasma proteins (C1, C2, etc.)
• Can be activated in a few different ways
• By antigen-antibody complexes
• By bacterial lipopolysaccharides
• 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