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Immunology
Text: Biotechnology Demystified
Sharon Walker
Chapter 5 & 6
The immune system
• An army of many types of cells in your
body that defend against disease.
• Designed to destroy and remove foreign
material
• Immune system also detects and
eliminates abnormal cells (cancer) and
cells that are infected (virus, bacteria)
• Progenitors of the immune cells are
produced in the bone marrow.
• White blood cells (leukocytes)
– Monocytes/macrophages eat bacteria and
damaged cells
– Neutrophils secrete toxic chemicals to destroy
nearby cells
– Lymphocytes
Lymphocytes produce antibodies &
mediate immune response
• B-lymphocytes mature in the bone marrow
– Produce antibodies
• T-lymphocytes mature in the thymus
– Mediate immune response
– Include CD-4 cells that get infected by HIV
Antigens
• Molecules that provoke an immune
response
• Antigens may be proteins, lipids, or
carbohydrates on the surface of a virus or
bacterium
• An antigen may have several sites that the
immune system recognizes. Each site is
an epitope.
Cell surface antigens
• Molecules on the cell surface can be antigenic
• Bacteria have many surface molecules that your
immune system recognizes are foreign
• If you receive cells from another person (blood
transfusion, transplant) they can provoke an
immune response (rejection) that may require
immunosuppresive therapy
Antibodies
• Molecules produced by B-lymphocytes
• Recognize and bind to antigens
• Each antibody is specific for one epitope
Antibody binding to an antigen
• Each B-lymphocyte produces one specific
antibody
• Until the B-lymphocyte encounters its antigen, it
is in a resting state (naïve) with its antibodies
sticking out hopefully from its surface
• When an antigen encounters a B-lymphocyte
with a “matching” antibody on its surface, the
antigen is bound to the antibody.
B-lymphocyte encounters its
antigen
• After the antibody/antigen complex has
been formed, the B-lymphocyte is
activated.
• The antibodies it produces are modified so
that, instead of protruding from the cell
surface, they are secreted into the blood.
• In addition, the B-lymphocyte starts to
divide rapidly, making many clones of
itself, all producing the same antibody.
Antibodies have different antigen affinity
Antibodies form complex with target antigen
• After the antigen is eliminated, some of the Blymphocytes remain in circulation
• If the same antigen is encountered later, this
population of circulating cells enables a faster
response
• This amplified response provides immunity
against the antigen.
• Most effective against antigens that have
repetitive structure, such as carbohydrates,
lipids, or nucleic acids. Less effective against
proteins.
• How does the body create antibodies that
are specific for antigens it has never
seen?
• Millions of B-lymphocyte are generated,
each with a different antibody.
• It is just chance that an antigen matches
an antibody.
Cell-mediated immunity
• Viruses and some bacteria enter cells, so
they are hidden from B-lymphocyte and
circulating antibodies.
• In these cases, macrophages, natural
killer cells (NKCs) and killer T-cells attack
and destroy the infected cells.
• Killer T-cells also attack
cancer cells
Immune response to proteins
• Response to proteins involves multiple
types of immune cells
• When a complex antigen such as a protein
is enters the body, it is ingested by an
antigen-presenting cell (APC), typically a
macrophage or dendritic cells.
• The APC breaks the antigen into small
pieces and “presents” these pieces on its
surface.
• T-cells detect the presented antigen
fragments, and initiate a cascade of
responses involving antibodies or cellmediated response.
Monoclonal antibodies
• Monoclonal antibodies (mAbs) are produced by
clones of a single B-lymphocyte.
• B-lymphocyte that produce mAbs against
specific antigens can be identified and grown in
the lab.
Monoclonal antibodies
• Metastatic breast cancers have many copies of
the growth factor protein Her2 on their cell
surface.
• Genentech developed an anti-Her2 mAb called
Herceptin, used to treat metastatic breast
cancer.
Self-recognition
• How does your immune system know what
is you (self) versus what is foreign?
Self-recognition
• During fetal development, and for a few
months after birth, the immune system
“learns” that everything it sees is “self”.
• Later, if a new antigen is presented, the
immune system considers it to be foreign.
Auto-immune disease
• The immune system sometimes makes
mistakes.
• Self tissue may be recognized as foreign, and
attacked by the immune system: auto-immune
disease
• These errors may be caused by antibodies that
have cross-reactivity: they have high affinity for
an antigen that is similar to a self tissue. The self
tissue later becomes the target of the immune
cells, which by feedback develop a stronger and
stronger response.
Auto-immune disease
• Multiple sclerosis: immune system attacks
self-antigens in the nervous system
• Rheumatoid arthritis, lupus, diabetes, have
auto-immune components.
• If we understand the genes that regulate
the immune system, we may be able to
increase or decrease immune responses.