Psoriasis…immuno
pathology
-Nilanjita
Chanda
Introduction
Nilanjita
Chanda, final BHMS student, Metropolitan Homoeopathic Medical
College, Kolkata explores the immuno pathology of psoriasis.
Definition:
Psoriasis
is a non-infectious, inflammatory disease of the skin, characterized
by well-defined erythematous plaques with large, adherent,
silvery scales.The precise causes of psoriasis are unknown.
It is generally believed that psoriasis is a disorder in
which factors in the immune system, enzymes, and other biochemical
substances that regulate skin cell division become impaired.
This abnormal immune response causes rapid proliferation
of keratinocytes (immature skin cells) and inflammation.
Such events are likely to be triggered by environmental
factors, such as weather or stress, in people with genetic
factors that make them susceptible.
Histopatholgy
The primary disease activity leading to psoriasis occurs
in the epidermis, the top of the five layers of the skin.
The main abnormality in it is increased epidermal proliferation
due to excessive division of cells in the basal layers.
- The process starts in the basal
layer of the epidermis, where keratinocytes are manufactured.
- Keratinocytes are immature skin
cells that produce keratin, a tough protein that helps
to form hair and nails as well as skin. In normal cell
growth, keratinocytes mature and migrate from the bottom
(basal) layer to the surface and are shed unobtrusively.
This process takes about a month.
- In psoriasis, however, the keratinocytes
proliferate very rapidly and travel from the basal layer
to the surface in about four days. The skin cannot shed
these cells quickly enough so they accumulate as thick,
dry patches, or plaques.
- Silvery, flaky areas of dead skin
build up on the surface of the plaques and are shed.
The underlying skin layer, the dermis , is red and inflamed.
- The dermis contains nerves, blood
and lymphatic vessels, which supply the abnormally multiplying
keratinocytes with their blood supply and also transport
potent immune factors that cause the underlying inflammation
and redness.
Normal Skin
Inflammatory
Response and Autoimmunity
The Normal Immune
System Response:
The inflammatory process is a byproduct of the body’s
immune system, which fights infection and heals wounds and
injuries:
- When an injury or an infection
occurs, white blood cells are mobilized to rid the body
of any foreign invaders, such as bacteria or viruses.
- The masses of blood cells that
gather at the injured or infected site produce factors
to repair wounds, clot the blood, and fight any infective
agents.
- In the process, the surrounding
area becomes inflamed and some healthy tissue is injured.
- Under normal conditions, the immune
system has other factors that control and limit this
inflammatory process.
The
Infection Fighters:
The primary infection-fighting
units are white blood cells: especially lymphocytes and
neutrophils. Lymphocytes include two subtypes known as T-cell
s and B-cells. Both types of cells are designed to recognize
foreign substances (antigens) and to launch a protective
or defensive action against them:
- B-cells produce antibodies, which
are designed to attack the antigens. Antibodies can
either ride along with a B-cell or travel on their own.
- T-cells have special receptors
attached to their surface that recognize the specific
antigen.
- T-cells are further categorized
as killer T-cells or helper T-cells (TH cells).
- Killer T-cells directly attack
antigens found on bacteria or other cells.
- Helper T-cells also recognize antigens,
but their role is two fold. They stimulate B-cells and
other white cells to attack the antigen. They also produce
cytokines, powerful immune factors that have an important
role in the inflammatory process .
Helper T-Cells,
Cytokines, and the Inflammatory Response:
The actions of the
helper T-cells (TH cells) are of special interest. Researchers
have observed high numbers of TH cells in psoriatic plaques:
- The activated TH cells infiltrate
the skin cells in psoriasis and also the joints in the
case of psoriatic arthritis, (There has been some debate
over whether psoriatic arthritis is a unique disorder,
but evidence now suggests that both psoriatic arthritis
and psoriasis are caused by the same faulty immune process.)
- TH cells normally stimulate B-cells
to produce antibodies. In the case of psoriasis, however,
they appear to direct the B-cells to produce autoantibodies
(“self” antibodies), which are directed against the
body’s own cells. In the case of psoriasis, they target
self antigens in skin cells; in psoriatic arthritis,
cells in the joints also come under attack.
- In the resulting autoimmune process,
autoantibodies remain in circulation and continue to
mount an immune attack against these cells.
Psoriasis
Helper-T-Cells
and Cytokines:
TH cells also secrete
or stimulate the production of powerful immune factors called
cytokines. In small amounts, cytokines are indispensable
for healing. If overproduced, however, they can cause serious
damage, including inflammation and injury during the psoriasis
disease process. In psoriasis, researchers are particularly
interested in cytokines known as GRO-alpha, tumor necrosis
factor, and interleukins 8 (IL-8), 11 (IL-11), and 12 (IL-12),
which appear to play strong roles in the destructive psoriatic
process, and in IL-10, which may be protective and block
cell growth leading to psoriasis.
Neutrophils:
Cytokines attract to the scene large numbers of large white
blood cells known as neutrophils. Neutrophils stimulate
the production of arachidonic acid, which triggers about
30 different chemicals, including two key players in the
inflammatory process:
l Leukotrienes, which
attract even more white blood cells to the area, and
l Prostaglandins, which
open blood vessels and increase blood flow.
Genetic
Factors
A combination of
genes is involved with increasing a person’s susceptibility
to the conditions leading to psoriasis.
HLA Molecules:
The processes leading to all autoimmune disease involve
the human leukocyte antigen (HLA) system, which is genetically
regulated. HLA molecules are designed to pick off parts
of antigens and present them on the surface of a cell so
that the various infection-fighting factors in the immune
system can recognize and destroy them. Malfunction of this
system is at the root of most immune disorders, including
psoriatic arthritis. For example, psoriasis patients with
a specific HLA genetic factor called HLA-CW6 tend to develop
psoriasis at an earlier than average age. It should be noted,
however, that only 10% of people who harbor these genes
develop psoriasis. Other genetic and environmental factors,
then, are required to actually trigger the disease.
PSORs:
Researchers have now identified four key genes (named PSORs
1-4) that are involved with psoriasis. Of particular interest
are the genes located in regions on specific chromosomes
that are linked to HLA and tumor necrosis factor, an immune
component strongly associated with psoriasis.
Environmental
and others trigger
Outside factors,
including weather, stress, injury, and infection, while
not direct causes, are often important in triggering the
disease process leading to onset and worsening of psoriasis.
Weather. Weather is a strong factor in psoriasis:
- Cold, dry weather is a common
precipitant of psoriasis flare-ups.
- Hot, damp, sunny weather helps
relieve the problem in most patients.
- To confuse matters, some people
have photosensitive psoriasis, which actually improves
in winter and worsens in summer when skin is exposed
to sunlight.
Stress and Strong
Emotions:
Stress, unexpressed
anger, and emotional disorders, including depression and
anxiety, are strongly associated with psoriasis flare-ups.
In one study, nearly 40% of patients remembered a specific
stressful event that occurred within a month of a psoriasis
flare. A 2001 study suggested that stress can trigger specific
immune factors associated with psoriasis flares. Some evidence
indicated that people with psoriasis may respond to stress
differently from those without the skin disease. In one
study, psoriasis patients had fewer aggressive verbal responses
than others did when confronted with hostile situations.
Infection:
Infections caused
by viruses or bacteria can trigger some cases of psoriasis.
Some examples include the following:
- Streptococcal infections in the
upper respiratory tract, such as tonsillitis, sinusitis,
and so-called “strep” throat, are known to trigger guttate
psoriasis in children and young adults. The infections
may also worsen ordinary plaque psoriasis.
- The human immunodeficiency virus
(HIV) is also associated with psoriasis.
- An uncommon form of human papillomaviruses
(HPV) called EV-HPV has been associated with psoriasis.
Although EV-HPV is probably not a direct cause, it may
play an indirect role in the perpetuation of psoriasis.
(This HPV form is not the virus associated with cervical
cancer and genital warts.)
- Helicobacter pylori (H. pylori
) infection, a major cause of peptic ulcers, has been
proposed as a possible cause of psoriasis. Research
in 2001 indicated that this is highly unlikely, at least
in children.
It seems reasonable
to assume that pustular psoriasis, which resembles an infection,
is caused by some organism, but none to date have been identified.
Skin injuries and the Köbner Response :
The Köbner response is a delayed response to skin injuries,
in which psoriasis develops later on at the site. In some
cases, even mild abrasions can cause an eruption, which
may be a factor in the frequency of psoriasis on the elbows
or knees. (It should be noted that psoriasis can develop
in areas with no history of skin disruption.)
Drugs:
A number of drugs can worsen or induce pre-existing latent
psoriasis.
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Nilanjita Chanda
Metro Politan Homoeopathic Medical
College & Hospital
Ramchandrapur
Sodepur
Kolkata - 700110
Phone : 98302 66311
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