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Background Topics:
Glossary
| Diagnostic terms | Genes
| Lymphatic System | Lymphoma
Simplified | Remission & Response
| Treatment background
Also see General Abbreviations & Acronyms-
remission.org
Clinical Research and Good Clinical Practice Dictionary (Glossary of
Terms and Acronyms) - med.umich.edu
This page is a work in progress
We update this list in response to visitor
questions.
active immunity
is an acquired immunity in which the immune system recognizes an
antigen as foreign and generates an attack on the invading pathogen or
abnormal cell that expresses the antigen (a unique protein
signature). The goal of cancer vaccines is to induce active
immunity against unique proteins specific to the tumor
cells. Here the immune system "learns" about the identity
of part of the tumor and "remembers" this information in order to
produce a sustained attack and long-term surveillance against the
cancer cells.
agammaglobulinemia - a deficiency or lack of
immunoglobulins, or antibody.
allergen - a substance that causes an
inappropriate reaction by the immune system to normally harmless
substances.
anaphylactic shock - a life threatening
allergic reaction causing swelling, difficulty breathing, and a drop
in blood pressure.
anergy - describes an unresponsive state of
immune cells to antigen stimulation.
adaptive Immunity (specific immunity) is a
response to a specific immune stimulus (antigen) that involves cells
of the immune system and frequently leads to a state of immune memory.
The adaptive immune system marshals antibodies and T cells that are highly specific for a particular
pathogen (or antigen). Once created, the antibodies and T cells can
eliminate the pathogen if it appears even years later - so-called
immune surveillance.
antibody (Ab) - a protein molecule (also called an immunoglobulin)
secreted by B cells in response to an
antigen (Ag). When an antibody attaches to an antigen, it destroys the antigen.
Picture-it
Antibody-dependent Cell-mediated Cytotoxicity (ADCC) - An
immune response triggered by the presence of antibody (Abs)
coating the target cell (such
as Rituxan).
Upon binding its antigen, the Antibody's Fc region is exposed and
will bind its receptor on the NK cell (or other effector cells) to form a bridge. Once the
bridge is formed, a poorly understood lytic (killing) signal is
delivered to the target cell by the effector cell, resulting in its demise. - (adapted from
the Merck Manual) Picture-it
antigen - the portion of a foreign substance or germ that can cause the immune system to become active against it.
Picture-it
Also from Merck Manual: "Substances that stimulate an immune
response in the body are called antigens. Antigens may be contained
within or on bacteria, viruses, other microorganisms, or cancer cells.
Antigens may also exist on their own—for example, as pollen or food
molecules. A normal immune response consists of recognizing a foreign
antigen, mobilizing forces to defend against it, and attacking
it."
antigen presenting cell (APC) - immune cells - such as b-cells,
macrophages, and dendritic cells - that recognize foreign
antigens, and present it to T-cells to initiate an immune
response.
antigen receptors - molecules on the surface
of b- and t-cells that allow the cells to engage a specific antigen in
the body in order to mount an immune response that is specific to the
foreign molecule it binds to. Picture-it
antibiotics - Medicines used to treat some bacterial diseases.
apoptosis 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. Picture
it
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
attenuated - no longer capable of causing
infection, as in an attenuated virus to make a vaccine. Also
means weakened.
autoantibody - an antibody that reacts against the body's own tissue.
autoimmune disease - a disease that results when the immune system mistakenly attacks the body's own tissues.
Examples: Rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes.
Picture-it
b-cells (also called B lymphocytes) - a type of white blood cells that come from bone marrow and develop into plasma cells, mature B cells capable of producing
antibody.
Picture-it
Each b-cell is capable of making an antibody specific to the
triggering antigen. The antigen trigger causing it to produce
numerous plasma cells capable of manufacturing the antibody.
Biological marker (biomarker): A characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.
www.fda.gov/cder/guidance/6400fnl.pdf
bronchi - airways in the lungs
CD (clusters of differentiation)- As b-cells
mature, they express different protein receptors on their surface. Some of these receptors
can be used as treatment targets. These proteins or antigen markers are called
Clusters of Differentiation (CD).
cell - building block that makes up tissues, organs, systems, and
blood of the body.
chemokines are molecules released by pathogens and infected tissues
that attract lymphocytes
chromosome - physical structure in a cell that contains genes. Almost every human cell has 23 pairs of chromosomes.
complement - a series of blood proteins whose action "complements" the work of antibodies. Complement destroys bacteria, produces inflammation, and regulates immune reactions.
complement-dependent cytotoxicity (CDC): A mechanism of killing
cells in which antibody bound to the target cell surface fixes
complement, which results in assembly of the membrane attack complex
that punches holes in the target cell membrane resulting in subsequent
cell lysis. Picture-it
| Picture-it
cytokines are molecules released by cells to alter lymphocyte function.
DNA - Deoxyribonucleic acid - the basic instruction set for the development and activities of cells.
is like a library which contains thousands of books, called genes. DNA exists in all cells except mature erythrocytes. DNA is made up of bases (nucleotides) that are arranged in a specific sequence. The specificity of the sequence accounts for the production of a specific protein.
effector cells perform a specific function
in response to a stimulus; usually used to describe cells in the
immune system (such as NK- and Cytotoxic T-cells) that are
activated to kill a pathogen or a cancer cell. Also see
Antibody-dependent Cell-mediated Cytotoxicity above.
etiologies are the causes of disease.
epigenetic refers to the regulation of gene expression - how, when, where, how much, etc.. Two key areas of epigenetic control are and Chromatin
Remodeling and DNA Methylation.
epitope refers to the minimal
structural unit of an antigen, recognizable for antibodies and
lymphocyte antigenic receptors.
familial describes a trait or disease that is observed with higher frequency
within the same family, whether the etiology [cause] is genetic or environmental, or a combination of the two. Where a hereditary disease is
one that is caused by a genetic trait.
gene - a unit of genetic material that is inherited from a parent. A gene carries the directions a cell uses to perform a specific function, like making proteins. Genes are made of DNA, the basic chemical unit of life.
Genes contain the instructions or recipes for the creation (expression) of unique proteins that carry out
cellular functions, such as divide, migrate, or die.
germline mutation - a mutation (genetic
defect) that is inherited from your parents. Compare with a
somatic mutation, which is acquired by chance or by exposure to
toxins. The majority of cancers result from somatic mutations.
Graft vs Disease (GvD) - the action of donor cells against the
cancer cells following a stem cell translant.
Graft vs Host Disease (GvHD) - a sometimes
serious complication of stem cell transplants in which cells
from a donor attack organs of the body. Also see GvHD
granulocyte - a cell filled with potent chemicals that destroy germs and reduce inflammation.
hepatitis - a liver disease.
HLA stands for Human Leukocyte Antigens. These proteins
are unique markers found on the surface of nearly every cell in the
body, and are in especially high concentrations in white blood cells.
histiocytic -connective tissue containing large
white blood cells
humoral immunity - mainly involves b-cells,
with the cooperation of helper t-cells. Like macrophages,
b-cells take in and process antigens recognized as not belonging in
the body. Unlike macrophages, a b-cell can bind only to an
antigen that matches it's antibody receptor (idiotype). When
helper t-cell signals are present the antigen exposed b-cell will
multiply, and soon differentiate into plasma cells that create vast
quantities of identical antigen-specific antibodies. Released
into the blood, the antibodies lock onto matching antigens, which may
trigger complement-dependent cytotoxicity (CDC) and/or antibody-dependent
cell-mediated cytotoxicity (ADCC).
hypermethylation - [a term describing the activity
of genes] can cause oncogenes to produce proteins that cause malignant behavior.
Chromatin Remodeling - Protein fibers called histones that interact with DNA. Drugs that inhibit histone deacetylases, for example, may enable expression of tumor suppressor genes.
hyperplasia (hye-per-PLAY-zha) - An abnormal increase in the number of cells in an organ or tissue.
(source NCI)
hypomethylation - [ [a term describing the activity
of genes] can quiet genes that normally suppress cancer (tumor suppressor genes).
IgA, immunoglobulin A - a type of antibody concentrated in mucous membranes and body fluids like tears, saliva, and secretions of the respiratory and gastrointestinal tract.
IgG, immunoglobulin G - the major antibody found in the blood that can enter tissues. It coats germs, helping other cells to seek and destroy them.
IgM, immunoglobulin M - an antibody that remains in the bloodstream where it can kill bacteria that enter the blood stream.
immunoglobulins - a large family of proteins, also known as antibodies. There are five classes of immunoglobulins: IgA, IgM,
IgG, IgD, and IgE.
Picture-it
immune response - reactions of the immune system to foreign substances.
immune system - complex network of specialized cells and organs that has evolved to defend the body against attacks by foreign invaders.
immunity - protection from disease-causing microbes or pathogens.
immunization - the process of inducing protection (immunity) against the destructive forces of a disease-causing microbe.
immunoblastic - large lymphocyte that has been
stimulated by an antigen
Immunophenotyping:
tests that reveal the kinds of surface molecules that are present on
cells (typically immune cells), such as CD20, CD22. CDs stand
for clusters of differentiation, which show the developmental
stage of the cell and the cell type. CD20, for example, is
expressed only on mature b-cells, but not t-cells.
Innate immunity (non-specific immunity) -
consists of the pre-existing and fast-acting defenses of the body,
such as skin, mucous, cilia, cytokines, and other secretions. It
may be that innate immunity also emits signals that activate adaptive
immunity.
Induction therapy typically consists of
conventional doses of chemotherapy administered in an attempt to
reduce the amount of cancer in a patient’s body prior to high-dose
therapy to be followed by a stem cell transplant.
infection - a state in which microorganisms have
taken residence and multiplied in body tissues.
inflammation - an immune system reaction to stop the progression of disease-causing microbes, sometimes seen at the site of an injury. Signs
of inflamation include redness, swelling, and heat.
Leukemogenic* therapies. - * "The risk of leukemia was greatest four or five years after chemotherapy began, and the risk was elevated for at least eight years after the cessation of chemotherapy. The drugs cyclophosphamide, chlorambucil, melphalan, thiotepa, and treosulfan were independently associated with significantly increased risks of leukemia, as was the combination of doxorubicin hydrochloride and cisplatin. Chlorambucil and melphalan were the most leukemogenic drugs, followed by thiotepa; cyclophosphamide and treosulfan were the weakest leukemogens, and the effect per gram was substantially lower at high doses than at lower doses. The extent to which the relative risks of leukemia are offset by differences in chemotherapeutic effectiveness is not known."
http://content.nejm.org/cgi/content/abstract/322/1/1
lymph nodes - small bean-shaped organs of the immune system, distributed widely throughout the body.
They provide an
environment where lymphocytes can receive initial exposure to foreign
antigens (viruses, bacteria, fungi, etc.). This activates the
lymphocytes to perform immune functions. Most lymph nodes form
in clusters throughout the system, such as in the neck, armpit, and
groin.
lymphocytosis is an abnormal increase in the number of
lymphocytes — a type of white blood cell — in your blood. The most
common cause is viral infection, such as EBV, CMV, rubella, whooping
cough, toxoplasmosis, brucellosis, chronic lymphatic leukaemiam, and
leukemic phase lymphoma.
lymphoblastic - immature lymphocyte - white blood cell in
early stage of development.
lymphocytes - small white blood cells (B and T cells) that
provide immune defense.
neoplasia (NEE-o-PLAY-zha) Abnormal and uncontrolled cell growth.
(source NCI)
neutrophils - an important white blood cell that is both a phagocyte and a granulocyte abundant in the blood.
nodular - well-defined knot of tissue
macrophage - a large immune cell that
gobbles microbes and presents antigens from the ingested pathogen to
other immune cells. To further orchestrate an immune attack,
macrophages send protein signals none as monokines.
MHC molecules - At the heart of immunity is the ability of immune cells to distinquish self from none self. So a fundamental question is how do immune cells do this? Is it by shape? Color? Scent?
As it turns out cell-to-cell communication is a touchy/feely thing, and that when immune cells bump into other cells in the night they grope for a specific molecule called the MHC. Your immune cells can tell by
feeling for the distinctive structure of this molecule (it's protein signature) if it's one of your own ... so the correct MHC is a password for safe passage in your body.
The diversity of the MHC molecule from one individual to another is sometimes referred to as polymorphism, and this diversity that's encoded onto each cell of your body is the reason transplanted tissue is typically rejected.
"One group of proteins encoded by the genes of the MHC are the markers of self that appear in almost all body cells. Known as class I MHC antigens, these molecules alert killer t cells to the presence of body cells that have been changed for the worse - infected with a virus or transformed by cancer - and that need to be eliminated. "
"A second group of MHC proteins, class II antigens, are found on b cells, macrophages and other cells responsible for presenting foreign antigen to helper t cells. Class II products combine with particles of foreign antigen in a way that showcases the antigen and captures the attention of the helper t cells. "
Source: Understanding the Immune System ~ NIH: Picture
it
microbes - bacteria, fungi, or virus that invades
the body. Also called a pathogen.
molecule - The smallest physical unit made up of a chemical substance such as a protein or a fat. Molecules are the building blocks of a cell, and a gene determines how each molecule is produced.
mucous membrane - The moist lining of certain body cavities such as the mouth.
mutation - a change in a cell's DNA that may cause the cell to produce an abnormal protein.
methylation - is a hallmark of cancer. Specifically, it is the addition of a methyl group to specific cytosines (the components of DNA) that regulates gene activity.
oncogenes - mutated and/or over-expressed versions of normal genes that can cause a cell to lose growth restraints, fail to differentiate (mature to a next stage), or prevent the cell from initiating the programmed cell death process called apoptosis. Some oncogenes turn on other genes that promote cancer.
opsonization - a process that identifies cells or bacteria to
the phagocytic system (immune cells that engulf pathogens) that then
and attack and engulf cells or bacteria that have been identified to
them by the complement or antibody system. animation
opportunistic infections - infections caused by microbes that usually do not cause disease in healthy individuals, but which can result in overwhelming and widespread infection in people with immune deficiency.
palliative care - the goal is to
achieve the best possible quality of life for patients and their
families when the patients disease is not responsive to curative
treatment.
pathogen is a disease causing microorganism
phagocytes - large white blood cells that contribute to immune defense by engulfing microbes, such as bacteria and fungi, or other cells and foreign particles.
refractory is resistance to standard
treatment.
RNA - In order for DNA to produce a protein, an intermediate step is required. In this step, DNA is transcribed into RNA (messenger RNA, or mRNA). The sequence of mRNA that encodes a protein is oriented in only one direction, which is known as the "sense" orientation.
Salvage therapy -- a term often applied to combinations of chemotherapy drugs
used to treat lymphomas after relapse in which the patient is either not
responsive to standard protocols, or the patient has general health
consideration (allergies, lung, or heart problems) that require the use of
unusual combinations of treatment agents, dosing or dosing schedules. Be
aware that despite the negative connotation of "salvage," these
novel treatments regimens can sometime achieve remissions.
somatic mutation - a mutation (genetic defect) which is
acquired by chance or by exposure to toxins. The majority of cancers
result from somatic mutations. Compare with germline mutations
that are inherited from your parents.
stem cell transplant (bone marrow transplant) - the goal of
this treatment is to cure the patient with aggressive therapies that
partially or completely kills off (ablates) the normal stem cells in
the marrow - the spongy tissue found in the cavities of the body's bones, where all the body's blood cells are produced.
These cells are then replaced with the patient's own stem cells
(harvested prior to treatment), or matched donor cells.
T cells (T lymphocytes) - white blood cells that either orchestrate the immune response (regulatory T cells) or directly attack infected or malignant cells (cytotoxic T cells).
tissue - a group of similar cells joined to perform the same function.
tissue type - the type of histocompatibility antigens on a person's cells or tissues. If the histocompatibility antigens do not match well, there is a much greater chance that the recipient will reject the donated tissue.
Titers is a measurement of the concentration of a substance in
a solution. It usually refers to the amount of medicine or antibodies
found in a patient's blood.
Tolerance is a non-reactivity of the immune system to self.
tumor suppressor genes - genes that protect cells from cancer. They may put the brakes on accelerated growth, or initiate cell death when DNA damage is detected. DNA damage. The under expression of tumor suppression genes can lead to malignant behavior.
Vaccinal effect - when a therapy leads to recognition of tumor
antigens (abnormal proteins) as foreign leading to attack of remaining
tumors by t-cells.
vaccine - substance that contains parts of antigens from an infectious microbe. By stimulating an immune response (but not disease), it protects the body against subsequent infection by that organism.