About
Lymphoma > Biology & Immunity
Last update: 04/22/2008 |
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Antibodies
| Apoptosis
| B-cell maturation | Blood
| CD antigens | Cells
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Growth Factors & Cytokines
| Immune System | Microenvironment
| NK cells | T-cells |
Antibodies
Source: NIH. Click to enlarge
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Wikipedia.org:
"Antibodies are Y-shaped proteins
that are found in blood
or other bodily
fluids .... are used by the immune
system to identify and neutralize foreign objects like bacteria
and viruses."
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Apoptosis
Programmed cell death as signaled by the nuclei in
normally functioning cells when age or state of cell health and
condition dictates.
Apoptosis illustrated
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Apoptosis
and necrosis are two major
processes by which cells die. Apoptosis is the ordered disassembly of
the cell from within.3 is
a natural mechanism by which cells "commit suicide" when
they have outlived their purpose, become defective, or have
aged. Apoptosis prevents cells from accumulating
and forming tumors.
Understanding
of the control of apoptosis in normal and malignant cells will help to
improve the diagnosis and treatment of malignancies.
The goal of many treatments, including chemotherapies is to induce malignant
cells to undergo apoptosis.
Genes control the activity
and life cycles of cells. Pro-apoptosis genes when activated
will induce a cell to die. Anti-apoptosis genes when activated
or over expressed may prevent a cell from dying.
Analogy: Chances are
you've seen a movie with apoptosis as part of the plot ... in almost
any James Bond film. A fortress containing classified
information is rigged for destruction by the owners if the security of
the building is compromised. The process requiring a series of
commands, which are relayed from one authorized person to another.
This to prevent a programmed self-destruction by a careless mistake or
a rouge individual.
The fail safe system is carried out from within by specialists, and
regulated by others. The trigger is not pulled until all the criteria
is met: the security threat is real and it can't be corrected; the
command has been given by authorized individuals and verified by
others, and the actions carried out by specialized personnel.
The security breach starts a chain of events (a cascade); each player
communicating to the other until the big red button is pushed and the
building destroyed; the sensitive information within it evaporating.
Similarly, our cells are rigged for self destruction when they become
old or defective. The main purpose is to protect the body against
replication of defective cells; and to remove old cells.
The program for cellular self-destruction is called apoptosis, which
is a type of quality control. The old or defective cells "take
one for the team." That some cells die and other live on to
replicate helps achieve a balance in the body. If individual cells
just replicated and never died, our organs would never cease growing.
What happens in a cancer cell is that some parts of the cell machinery
that carry out, signal for, or authorize apoptosis no longer function
... because of damage to genes that produce proteins that regulate or
carry out these functions.
Many chemotherapy treatments are designed to exploit apoptosis ... by
causing sufficient damage to the cells that force the issue,
magnifying the urgency to self-destruct. Waking up the components in
the cell that authorize apoptosis, such as the P53 gene.
One way the Rituxan might work is by changing the balance of signals
in the cells it binds to to favor apoptosis. Shifting the balance to
self destruct without causing damage. (Rituxan may also flag bound
cells for destruction by effector cells, which is not dependent on
apoptosis.)
Some investigational targeted agents are designed to wake up or
silence parts of the cell that carry out or block apoptosis. ...
Imagine that a key protein within the cell is overactive and is giving
a STOP order. Then imagine a small molecule drug that fits the shape
of this protein, stopping the STOP order. This class of drugs target
inhibitors of apoptosis. (Note: If normal cells utilize the same or
similar proteins to carry our normal cellular functions, you may
have side effects.) ~ KarlS
Regulation
of Apoptosis in Normal and Malignant Cell bloodjournal
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Details and Overview rndsystems.com
Reference: Thornberry, N.A. and Y. Lazebnik (1998) Science 281:1312.
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Apoptosis kimball.mal
"For every cell, there is a time to live and a time to die.
"
A second way that cells die is called lysis,
a more destructive mechanism in which cell membranes rupture and lose
cytoplasm.
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B-cell
stages of maturation
click image to enlarge
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Wikipedia.org: "B cells are
lymphocytes
that play a large role in the humoral
immune response as opposed to the cell-mediated
immune response that is governed by T
cells. B cells are produced in the bone marrow of most mammals and
are therefore called B cells. The principal function of B cells is to
make antibodies
against soluble antigens.
B cells are an essential component of the adaptive
immune system."
B-cells
have many stages of differentiation. The stage of the b-cell in which the cancer developed
will determine the type of lymphoma, and potentially, targets for treatment.
 | B
Cell - British Society for Immunology (link not available)
"Within the bone marrow, B cells are regulated in their
development, and can be deleted when surface Ig receptors are
cross-linked. This leads to cell death, but once B cells reach the
spleen and enter the periarterial lymphoid sheath (PALS) some fine
tuning through the antigen receptor can occur. Under the right
circumstances these B cells will enter germinal centres where they
can proliferate and interact with follicular dendritic cells and
other cells. At each step along the way the B cell can be
triggered via their antigen receptors either to die, or to enter
the follicle and be protected against cell death. Hence, a number
of signaling pathways must exist to regulate these crucial
physiological processes."
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| Interactive
Animation of B Cell Maturation bio.davidson.edu
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B Cell Generation, Activation &
Differentiation users.ipfw.edu/
PDF
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| Lymphocyte Traffic Patterns Dr.
Anderson
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B-cell activation
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| Blood
& Basic Systems
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Basic
information about blood. Lymphoma is a
cancer that affects a type of blood cell, called a lymphocyte.
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CD-antigens
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As
lymphocytes mature, they express different protein receptors on the
cell surface, which can aid in determining the type and maturation
stage of the cells being examined. Some of these receptors, such as
cd20, can be used as treatment targets (Rituxan). These proteins or antigen markers are called
Clusters of Differentiation (CD).
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Cells
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Resources
on normal cell biology
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Growth factors
& cytokines
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Cells
interact and coordinate activities by sending and receiving chemical
signals.
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| Cytokine deregulation in cancer Biomed
Pharmacother.
2001
Nov;55(9-10):543-7. PMID: 11769963 PubMed
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| Hormones, table of U
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| IL-10 and NHL MDACC
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Immune system
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Lymphoma is a cancer that affects immune cells called
lymphocytes. In this section we provide links to articles and
resources on immunity.
| The Immune System: How it Works niaid.nih.gov
pdf
Excellent resource in booklet form. Must read.
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| Understanding
Cancer Series: The Immune System
 cancer.gov
Clear and comprehensive; organized by topics
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| Immune system for kids (and adults) kidshealth.org
Very nice primer for anyone; includes pronunciations of terms
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Introduction to Immunology Tutorial ~ Innate vs.
Adaptive Immunity arizona.edu
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| Auto-immune disease NIH
Also an excellent primer on immunity
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| Autoimmunity and Autoimmune Disease Johns
Hopkins
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| B-Cells and Humoral Immunity Merck Manual
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| Cell-Mediated Immunity: med.sc.edu
Cell interactions in specific immune responses
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| Immune System overview with illustrations
Goldman, Prabhakar
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| Immunology
And Immune System Disorders mfi.ku.dk
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| A Brief
Guide to the Immunology of Peripheral Tolerance molbiol.ox.ac.uk
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| Kimball's
Biology Pages users.rcn.com
Excellent resource for immunity and all manner of
biological processes
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| Normal Immune System - Nice overview and
historical background on immunity edcenter.med.cornell.edu
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| ncbi.nlm.nih.gov
"Infectious agents can cause recurrent or persistent
disease by avoiding normal host defense mechanisms or by
subverting them to promote their own replication. There are many
different ways of evading or subverting the immune response.
Antigenic variation, latency, resistance to immune effector
mechanisms, and suppression of the immune response all contribute
to persistent and medically important infections. In some cases,
the immune response is part of the problem ..."
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Microenvironment
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B-cells (normal
and malignant) do not live alone or behave in a vacuum. They are induced to grow or
become dormant by signals in the host environment (microenvironment). For example,
b-cell tumors may be prompted to grow by external stimuli, such as
antigens or growth factors. There is evidence that surrounding
cells are required to sustain or "nurse" the growth of some
lymphomas.
| Chronic B cell malignancies and bone marrow
microenvironment.
Semin Cancer Biol. 2002 Apr;12(2):149-155. PMID: 12027587 PubMed
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| Tumor cell dissemination in follicular
lymphoma. Blood. 2002 Mar 15;99(6):2192-8.
PMID: 11877297 PubMed
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| Relative distribution of tumour cells and
reactive cells in follicular lymphoma.
J Pathol. 2001 Apr;193(4):498-504. PMID: 11276009 PubMed
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NK-cells
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NK
-cells are already specialized to kill
certain types of target cells, especially cells
that have become infected with virus or have become cancerous.
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T-cells
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T-cells (T - from
thymus) are part of our immune defense. We may be able to recruit this arm of our immune
system to identify and attack malignant b-cells.
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