Ouch, a shakeout on vlts cost me $3k this week.
Long weekends and Yahoo.com is a bad place to
be when you are long, but nervous. Shame on me
for letting myself get spooked (I am not going
to buy the position back, and my trading money
can sit in cash til I find a real trading vehicle).
This week from scienceweek.com, a little immune system 101.
2. ON INNATE VERSUS ADAPTIVE IMMUNITY
N. Silverman and T. Maniatis (Harvard University, US) discuss
immunity. Innate immunity is the first line of defense against
infectious microorganisms. The innate immune system relies on
germ line-encoded pattern recognition receptors to recognize
pathogen-derived substances. Activation of the innate immune
system through these receptors leads to the expression of a vast
array of antimicrobial effector molecules that attack
microorganisms at many different levels. The innate immune system
appears early in evolution, and the basic mechanisms of pathogen
recognition and activation of the response are conserved
throughout much of the animal kingdom. Insects, for example, have
a very potent innate immune response that effectively combats a
broad spectrum of pathogens. The fruit fly Drosophila can
withstand and clear bacterial burdens that relative to the size
of the host would be lethal to mammals. In contrast to innate
immunity, the adaptive immune system generates antigen-specific
receptors, antibodies, and T-cell receptors by somatic cell DNA
rearrangement. These receptors, found only in higher eukaryotes,
recognize specific pathogen-encoded proteins. Mammals have a
complex immune response, which relies on communication between
the innate and adaptive arms of the immune system. The innate
immune response generates a "costimulatory signal", which is
required in combination with antigen-specific recognition to
activate T-cells and the adaptive immune system. Antigen-specific
recognition in the absence of co-stimulation can lead to absence
of response (anergy) rather than to activation. Thus, the
activation of an antigen-specific response is coupled to
infection through the innate immune system.
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Genes and Development 2001 15:2321
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SCIENCE-WEEK 25 Jan 2002 scienceweek.com
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Related Background:
MEDICAL BIOLOGY: ON THE IMMUNE SYSTEM
Our environment is filled with a variety of infectious agents,
including bacteria, viruses, parasites, and fungi, and the
essential line of defense against these pathogenic invaders is
the "immune system". This system, an evolutionary development in
vertebrates, involves a complex set of dynamic interactions
between various specialized cells, the interactions mediated by
chemistry. An important component is an evolved genomic apparatus
that essentially provides for an "immune memory", which in
general is a capability of the immune system to modify and
enhance its responses based on its previous experience with
particular pathogens. Nowhere is the idea of the human body as a
colony of cells more clear than in consideration of the
cooperative interactions of the various cells of the immune
system functioning to protect the entire organism.
... ... P.J. Delves and I.M. Roitt (University College London,
UK) present an extensive 2-part review of current knowledge
concerning the human immune system, the authors making the
following points:
1) In humans, there are two fundamentally different types of
responses to invading microbes: a) innate (natural) responses
that occur to the same extent however many times the infectious
agent is encountered; b) acquired (adaptive) responses that
improve after repeated exposure to a given infection.
2) The innate immune response involves a) various
specialized "phagocytes" (neutrophils, monocytes, macrophages),
cells that "eat" pathogens; b) various cells (basophils, mast
cells, eosinophils) that release *inflammatory mediator
substances; c) *natural "killer" cells. The molecular components
of innate responses include a variety of identified proteins
(e.g., *complement, *cytokines).
3) The acquired immune response involves the proliferation
of *antigen-specific *B and T cells, which occurs when the
surface receptors of these cells bind to antigen. Specialized
cells, called "antigen-presenting cells", display the antigen to
*lymphocytes and collaborate with them in the response to the
antigen. B cells secrete *immunoglobulins, the antigen-specific
*antibodies responsible for eliminating extracellular
microorganisms. T cells help B cells to make antibody and can
also eradicate intracellular pathogens by activating macrophages
and by killing virally infected host cells. In general, innate
and acquired responses usually work together to eliminate
pathogens.
4) The various cells of the immune system develop from
*pluripotent stem cells in the fetal liver and in bone marrow and
then circulate throughout the extracellular fluid. B cells reach
maturity within the bone marrow, but T cells must travel to the
thymus gland to complete their development.
5) Adaptive immune responses are generated in the *lymph
nodes, spleen, and *mucosa-associated lymphoid tissue, all of
which are called "secondary lymphoid tissues": a) In the spleen
and lymph nodes, the activation of lymphocytes by circulating
antigen occurs in distinctive B cell and T cell compartments of
lymphoid tissue. b) The mucosa-associated lymphoid tissues,
including the tonsils, adenoids, and *Peyer's patches, defend
mucosal surfaces. c) Diffuse collections of lymphoid cells are
present throughout the lung and *lamina propria of the intestinal
wall.
6) To establish an infection, a pathogen must first overcome
numerous surface barriers, such as enzymes and mucus, that are
either directly antimicrobial or that inhibit attachment of the
microbe. Because neither the *keratinized surface of the skin nor
the mucus-lined body cavities are ideal habitats for most
organisms, microbes must breach the *ectoderm. Any organism that
breaks through this first barrier encounters the two further
levels of defense, the innate and acquired immune responses.
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New Engl. J. Med. 2000 343:37,108
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Notes:
... ... *inflammatory mediator substances: In general, an
"inflammatory change" is a response of tissues to irritation or
injury. The response involves a dynamic complex of cellular and
chemical reactions that occur in the affected blood vessels and
adjacent tissues.
... ... *natural "killer" cells: Cells of the innate immune
response that recognize and then kill abnormal cells such as
certain infected cells and tumor cells.
... ... *complement: A group of 9 interacting serum proteins,
mostly enzymes, which are activated during the immune response,
and which participate in bacterial lysis (destruction of bacteria
by disruption of cell membrane) and macrophage chemotaxis
(chemical attraction of macrophages, immune system amoeba-like
cells active in phagocytosis of bacteria and other particulates.)
... ... *cytokines: A cytokine is any substance that promotes
cell growth and cell division. Cytokines mediate many functions
of the immune system.
... ... *antigen: In general, an antigen is any entity that
provokes an immune response, and this includes, in certain
disease states, entities that are not "foreign" to the body.
... ... *B and T cells: (B and T lymphocytes) Lymphocytes (lymph
cells, lympho-leukocytes) are a type of leukocyte (white blood
cell) responsible for the immune response. In general, there are
two classes of lymphocytes: 1) the B-cells, when presented with a
foreign chemical entity (antigen), change into antibody producing
plasma cells; 2) the T-cells, which interact directly with
foreign invaders such as bacteria and viruses, and some types of
which assist B-cells in the B-cell response. The general
terminological differentiation between B-cells and T-cells is
based on where the cells mature: B-cells mature in (b)one marrow,
and T-cells mature in the (t)hymus gland.
... ... *lymphocytes: See above note.
... ... *immunoglobulins: (antibody): The immunoglobulins are a
large glycoprotein category that includes antibodies as a subset.
In general, an "antibody" is a protein molecule produced by the
immune system of vertebrate organisms, the molecule designed to
specifically interact with a particular antigen.
... ... *antibodies: See above note.
... ... *pluripotent stem cells: In general, the term "stem"
cells refers to undifferentiated cells that upon differentiation
can give rise to various specialized cell lines such as blood
cells, skin cells, nerve cells, etc. Adult bone marrow, for
example, contains stem cells that are the precursors of the
various specialized types of blood cells. "Pluripotent stem
cells" are stem cells that have the capacity to differentiate
into various cell types.
... ... *lymph nodes: The lymphatic system is a complex network
for the distribution of lymph fluid (which is similar to blood
plasma -- blood without red cells). Lymph is collected by
drainage from the tissues throughout the body, flows in the
lymphatic vessels through the lymph nodes, and is eventually
added to the venous blood circulation. Lymph consists of a clear
liquid portion, varying numbers of white blood cells (chiefly
lymphocytes), and a few red blood cells. The lymph nodes are
small bodies located throughout the lymph system and varying in
diameter from 0.1 to 2.5 centimeters.
... ... *mucosa: In general, a multilayer tissue lining various
tubular structures in the body.
... ... *Peyer's patches: Aggregated lymphoid nodules of the
small intestine.
... ... *lamina propria: The layer of connective tissue
underlying the *epithelial layer of a mucosa.
... ... *epithelial layer: In animals and humans, epithelial
cells compose the cell layers that form the interface between a
tissue and the external environment, for example, the cells of
the skin, the lining of the intestinal tract, and the lung airway
passages.
... ... *keratinized: Keratin is a protein which helps waterproof
and protect the skin and underlying tissues.
... ... *ectoderm: In the embryos of higher animals, there
occurs the transformation of a single-layer "blastula" into a
3-layered "gastrula" consisting of ectoderm (outermost layer),
mesoderm (middle layer), and endoderm (innermost layer)
surrounding a cavity with one opening. The 3 layers are called
the "germ layer", and these layers, via further cell
differentiation and proliferation, determine the development of
all the major body systems and organs.
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SCIENCE-WEEK 2000 21 Jul
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Related Background:
ON MODELS OF IMMUNE MEMORY
Higher vertebrates, including humans, have through evolution
developed an immune system that can selectively destroy or
inactivate foreign molecules and foreign cells (*antigens)
without harming the molecules or normal cells of the host. The
vertebrate immune system apparently retains a "memory" of each
antigen attack, allowing the immune system to respond more
efficiently the next time it encounters the same invader. One
group of immune system cells involved in this immune system
memory is a small fraction of the proliferating *B-lymphocyte
cell population, the fraction effectively set aside as a reserve
population of cells to be directed against a specific stimulating
antigen. Such cells, called "memory B cells", are
indistinguishable in appearance from other unstimulated
lymphocytes and like them do not secrete antibody. But if the
organism is exposed to the same antigen a second time, the
reserve population of antigen-specific memory cells quickly
proliferates and differentiates into antibody-secreting plasma
cells, thereby allowing what is called the "secondary response"
to a given antigen to occur more rapidly and produce more
antibody than the initial or "primary response". The
effectiveness of the secondary response is the apparent reason
why humans, for example, rarely contract such diseases as chicken
pox or mumps more than once. One of the central problems in
immunology is to provide a molecular explanation for immune
system memory (also called "immune memory). There has been much
debate concerning the relative contributions to immune memory of
processes such as the persistence of antigens, *cross-reactive
stimulation, *homeostasis, competition between different lineages
of lymphocytes, and the rate of cell turnover
... ... R. Antia et al (3 authors at 2 installations, US) present
several mathematical models designed to investigate the
contributions of the various processes to the longevity of immune
memory. The authors define immune memory as the maintenance of an
elevated population of antigen-specific cells, and they define
the longevity of immune memory as the rate of decline of the
population of antigen-specific memory cells. The models presented
by the authors incorporate a repertoire of immune cells, each
lineage with distinct antigenic specificities, the basic
equations describing the dynamics of individual lineages and the
total population of cells. The authors suggest their results
indicate that if homeostatic control regulates the total
population of memory cells, then immune memory will be long-lived
(half-life > 1 year). The authors also suggest that the longevity
of immune memory in this situation will be insensitive to the
relative rates of cross-reactive stimulation, the rate of
turnover of immune cells, and the functional form of the
mathematical term for the maintenance of homeostasis. Further,
the authors suggest their models predict that when the frequency
of antigenic stimulation from other infectious agents is very
high, the duration of immune memory is likely to be relatively
low: i.e., sufficiently frequent exposure to new pathogens will
result in a relatively high rate of decline of immune memory with
respect to a given pathogen.
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Proc. Natl. Acad. Sci. 1998 95:14926
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Notes:
... ... *antigens: See main report.
... ... *B-lymphocyte cell: See main report.
... ... *cross-reactive stimulation: In general, in this context,
a "cross-reaction" is an immunological phenomenon in which an
antigen reacts with an antibody that has been raised (produced)
against a different antigen. The term "cross-reactive
stimulation" refers to the production of cross-reacting antibody
(or immune cell), i.e., an antibody (or immune cell) able to
react with an antigen that did not specifically stimulate its
original production.
... ... *homeostasis: The term "homeostasis" refers to a
physiological equilibrium necessary in general for the viability
of an organism, and in particular for the operation of many
cellular functions. Homeostatic mechanisms in biological systems
usually involve an element of negative feedback signaling. In
vertebrates, for example, when blood temperature is too high,
temperature receptors provoke a sequence of events involving many
pathways that ultimately results in a lowering of body
temperature. Similar homeostatic mechanisms operate at cellular
levels.
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SCIENCE-WEEK 1999 12 Feb
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SCIENCE-WEEK 25 Jan 2002 scienceweek.com |
