Download Camp 1 - Evangel University

Mary K. Campbell
Shawn O. Farrell
http://academic.cengage.com/chemistry/campbell
Chapter 14
Viruses, Cancer, and Immunology
Paul D. Adams • University of Arkansas
Viruses
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Viruses are pathogens of bacteria, plants, and animals
Can be deadly (e.g., Ebola, HIV)
Can be merely annoying (e.g., Rhinovirus)
Viruses are small particles composed of nucleic acid and
protein
Entire particle is known as a virion
Capsid- surround the center of the virion
Nucleocapsid- combination of the nucleic acid and the
capsid
Membrane envelope- surrounds the nucleocapsid
Protein spikes- help viruses attach themselves to the host
cell
Architecture of a Virus
Families of Viruses
The Virus Life Cycle
How Does a Virus Infect a Cell
• A Virus must attach to the
host cell before it can
penetrate
• A common method of
attachment involves the
binding of one of the spike
proteins on envelope of the
virus to a specific receptor
on the host cell
• An example is HIV
attachment
Retroviruses
• A retrovirus implies that replication is backward
compared to the central dogma of molecular biology
• The genome of a retrovirus is single-stranded RNA
• Once it infects the cell, the RNA strand is used as
template to make double-stranded DNA
• Retroviruses have been linked to cancer and AIDS
Life cycle of a Retrovirus
Retroviruses (Cont’d)
• Retroviruses have certain genes in common
• Coat proteins- genes for proteins of the
nucleoplasmid
• All retroviruses have genes for reverse
transcriptase (RT), and for envelope proteins (EP)
Typical Retrovirus Genes
Summary of Retroviruses
• Retroviruses have a genome based on DNA. When
they infect cells, their RNA is turned into DNA by RT.
The DNA is then incorporated into the host’s DNA
genome as a part of the replication cycle for the virus
• Retroviruses all have certain genes in common
• Some retroviruses also have identifiably unique
genes, e.g., the Sarcoma oncogene and the Rous
sarcoma virus
- Viruses are also used in Gene Therapy (see
Biochemical Connections, pg. 412)
The Immune System
• The immune system allows for the distinction
between self from nonself
• This allows cells and molecules responsible for
immunity to recognize and destroy pathogens
• The immune system can also go awry in
distinguishing self from nonself. This results in an
autoimmune disease, in which the immune system
attacks the body’s own tissues
• Allergies are also another type of improper
functioning of the immune system
Innate Immunity (Cont’d)
• There are several parts to innate immunity: physical
barriers, cells of the immune system (dendritic
cells, macrophage, and natural killer (NK) cells)
• Dendritic cells are members of a class of cells called
antigen-presenting cells (APCs)
• T cells release chemicals called cytokines that
stimulate other members of the immune system, e.g.
killer T cells and B cells
• Another important cell type in the innate immunity
system is the natural killer (NK) cells, which is a type
of leukocyte
Innate Immunity (Cont’d)
• T cells differentiate, and become specialized for one
of several possible functions
• Killer T cells involve T-cell receptors (TCRs) on
their surfaces that recognize and bind to antigens
• Proliferation of killer T cells is triggered when
macrophages bound to T cells produce small
proteins called interleukins
Growth and Differentiation of T cells
Interaction Between Cytotoxic T cells and
Antigen-Presenting Cells
Clonal Selection
• The process by
which only the
cells that respond
to a given antigen
grow in
preference to
other T cells is
called clonal
selection
Interaction Between Helper T Cells and
Antigen-Presenting Cells
How Helper T Cells Aid in the Development
of B Cells
Antibodies
• Antibodies are Y-shaped
molecules consisting of
two identical heavy
chains and two identical
light chains held together
by disulfide bonds
• Antibodies are
glycoproteins
Antibodies (Cont’d)
• The variable region is
found at the prongs of
the Y and is the part of
the antibody that binds to
the antigen
• The binding sites for the
antibody on the antigen
are called epitopes
Antibody Heavy and Light Chains
Antibodies (Cont’d)
• If a cell’s receptors encountered self-antigens that
are recognized with high affinity, it undergoes a
process called negative selection and is
programmed for apoptosis, or cell death
• There are several safeguards that leads to the
delicate balance that must be maintained by the
immune system
Differentiation of T Cells
Summary
• Vertebrates have an immune system
• Innate immunity consists of physical barriers and
cellular warriors
• Acquired immunity is based on two types of T cells
and on B cells. These cells are generated randomly
with receptors that can be specific for an
unimaginable number of antigens
• When cells encounter their specific antigens, they
are stimulated to multiply
Summary (cont’d)
• When cells encounter their specific antigens, they
are stimulated to multiply
• Acquired immune cells also leave behind memory
cells so that if the same pathogen is seen again, the
body is faster to eliminate it
• Immune cells must be able to recognize self from
nonself. T cells and B cells are conditioned not to
recognize proteins from that individual
• In some cases, the immune system breaks down,
and a person may be attacked by his or her own
immune system leading to an autoimmune disease
Cancer
• Cancer is the leading cause of death in human
beings
• It is characterized by cells that grow and divide out of
control, often spreading to other tissues and causing
them to become cancerous
Cancer (Cont’d)
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All life-threatening cancers have at least six characteristics in
common
1) Cancer cells continue to grow and divide in situations in which
normal cells do not
2) Cancer cells continue to grow even when the neighboring cells
send out “stop-growth” signals
3) Cancer cell manage to deep going and avoid a “self-destruct”
signal that usually occurs when DNA damage has occurred
4) The can co-opt the body’s vascular system, causing the growth
of new blood vessels to supply the cancerous cells with
nutrients
5) They are essentially immortal
6) Cancer cells have the ability to break loose, travel to other
parts of the body and create new which tumors make them
lethal, this is called metastasis
What Causes Cancer?
• Changes in DNA cause changes to specific proteins
that are responsible for controlling the cell cycle
• Most mutations of DNA affect two types of genes:
1) Tumor suppressor, a gene that makes a protein
that restricts the cell’s ability to divide
2) An oncogene is one whose protein product
stimulates growth and cell division. Mutations of
an oncogene cause it to be permanently active
Proto-oncongenes
MAP Kinase Signal Transduction
Tumor Suppression
• Tumor suppressors inhibit transcription of genes that
would cause increased replication
• When a mutation occurs in any suppressor,
replication and division become uncontrolled and
tumors result
Action of p53
• Mutations in the p53
gene are found in
more than 50% of all
human cancers
How do We Fight Cancer?
• Cancer has been treated in a variety of ways
• Traditional approaches include:
1) Surgeries to remove tumors
2) Radiation and chemotherapy
3) Treatment with monoclonal antibodies to target
specific tumors
• More current foci include attempts to reactivate p53
in cancerous tissues when they have lost their
function
Drug Targets in the p53 Pathway
Transductional Targeting in Virotherapy
Transcriptional Targeting in Virotherapy
(Cont’d)
Summary
• All potentially fatal cancers have several things in
common, such as having cells that are immortal, that
divide despite “stop growth” signals from nearby
cells, that stimulate blood-vessel formation near to
themselves, and that spread to other parts of the
body
• The development of cancer requires multiple
breakdowns in normal metabolism
Summary (Cont’d)
• Most cancers have been linked to specific genes
called oncogenes or to tumor-suppressor genes.
When these genes mutated, the cell loses the ability
to control its replication
• There are many classical ways to fight cancer, such
as radiation therapy and chemotherapy
• Novel techniques using viruses are now being tried
to target cancer cells more directly, and some of
these are showing tremendous promise