overview

IMMUNOLOGY
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); doesnt 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 (dont 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 (dont 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
Nave 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
What are cytokines?
Cell-mediated immunity
CD4+ T cells differentiate into two kinds of effector cells:
T
H
1 cells (activate macrophages, cause B cells to secrete Ab)
T
H
2 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?
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
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 ( or )
2 heavy chains (, , , , or )
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 cant
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
Its 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 nave 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