Download Pathophysiology lecture

Pathophysiology lecture
By
Dr. Raja’a Ali H. Al-Husseini
27-12-2010
College of pharmacy- Kufa University
Disorders of the Immune System
Immunity:-Is the resistance to a disease, that is provided by
the immune system. It can be acquired actively through immunization
or by having a disease, or passively by receiving antibodies or immune
cells from another source.
Immune mechanisms can be classified into two types:1-Specific or acquired immunity which involves: Humoral and Cellular
mechanisms whereby the immune cells differentiate self from nonself and
recognize and respond to a unique antigen.The humoral immune response
involves antibodies produced by activated B lymphocytes. Cell-mediated
immunity depends on T-cell responses to cellular antigens.
2-Non specific immune mechanisms which involve complement system,
cytokines, and the phagocytic activities of neutrophils and
macrophages.It can distinguish between self and non-self but cannot
differentiate among antigens.
THE COMPONENTS OF THE IMMUNE SYSTEM
■ The immune system consists of 1-immune cells, 2-the central immune
structures (the bone marrow and thymus), where immune cells are
produced and mature; and 3-the peripheral immune structures (lymph
nodes, spleen, and other accessory structures), where the immune cells
interact with antigen.
■ The system's principal cells include lymphocytes that recognize
antigens and related accessory cells (such as phagocytic macrophages,
which engulf and destroy foreign material). Lymphocytes arise in the
bone marrow from stem cells, with T lymphocytes ( T cells) migrating to
the thymus to mature and B lymphocytes ( B cells) maturing in the bone
marrow.
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■ Cytokines are molecules that form a communication link between
immune cells and other tissues and organs of the body.
■ Recognition of self from nonself by the immune cells depends on a
system of MHC membrane molecules that differentiate viral-infected and
abnormal cells from normal cells (MHC I) and identify immune cells
from other types of cells (MHC II).
The Immune Response
■ The immune response involves a complex series of interactions
between components of the immune system and the antigens of a foreign
pathogen.
■ Passive immunity represents a temporary type of immunity that is
transferred from another source (in utero transfer of antibodies from
mother to infant).
■ Active immunity depends on a response by the person’s immune
system and is acquired through immunization or actually having a
disease.
■ Humoral immunity consists of protection provided by the B
lymphocyte-derived plasma cells, which produce antibodies that travel in
the blood.
■ Cell-mediated immunity consists of protection provided by cytotoxic T
lymphocytes, which protect against virus-infected or cancer cells.
Disorders in the Immune Response
A- ALLERGIC AND HYPERSENSITIVITY DISORDERS
Hypersensitivity is an immune response that damages the body's own
tissues. They are divided into four classes (Type I – IV) based on the
mechanisms involved and the time course of the hypersensitive reaction [
Table 10-1]. Type I hypersensitivity is an immediate or anaphylactic
reaction, often associated with allergy. Symptoms can range from mild
discomfort to death. Type I hypersensitivity is mediated by IgE, which
triggers degranulation of mast cells and basophils when cross-linked by
antigen. Type II hypersensitivity occurs when antibodies bind to antigens
on the patient's own cells, marking them for destruction. This is also
called antibody-dependent (or cytotoxic) hypersensitivity, and is
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mediated by IgG and IgM antibodies. Immune complexes (aggregations
of antigens, complement proteins, and IgG and IgM antibodies) deposited
in various tissues trigger Type III hypersensitivity reactions. Type IV
hypersensitivity (also known as cell-mediated or delayed type
hypersensitivity) usually takes between two and three days to develop.
Allergies also known as hypersensitivity, is a reaction by your
immune system to something that doesn't bother other people. People
who have allergies usually have sensitivities to more than one thing.
Types of substances that commonly cause allergic reactions are; pollen,
dust and dust mites, mold spores, pet
dander foods, insect stings,
medicines. Allergic reactions include runny nose, itching, rashes and
swelling. Deficiencies in the immune system cause allergies. These
deficiencies have a genetic and and environmental component.
Asthma is another type of allergic reaction. The inside of the airway
becomes inflamed and react strongly to allergens to which you're
sensitive. The reaction causes the airway to constrict, reducing airflow to
the lungs. This precipitates wheezing, coughing, and trouble breathing.
An asthma attack is an acute allergic reaction of the airway. Severe
asthma attacks can be serious and can cause death.
B- TRANSPLANTATION IMMUNOPATHOLOGY
Not long ago, transplantation of solid organs (e.g., liver, kidney, heart)
and bone marrow was considered experimental and used only for patients
who have no other options. However organ and bone marrow
transplantation has been enhanced by a greater understanding of
humoral and cellular immune regulation, the development of
immunosuppressive drugs and an appreciation of the role of the MHC
antigens in transplant rejection.
The likelihood of rejection varies with the degree of HLA (Human
Leukocytes Antigens) or MHC (Major Histo-compatibility Complex)
relatedness between donor and recipient.
A rejection can involve:1an attempt by the recipient’s immune system to eliminate the donor
cells, as in HVGD( Host-Versus-Graft Disease which is usually limited
to allogeneic organ transplants),
2an attack by the cellular immunity of the transplanted tissue on the
unrelated recipient tissue, as in GVHD (Graft-Versus-Host Disease
occurs mainly in patients who undergo bone marrow transplant,
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sometimes may also occur after transplantation of solid organs rich in
lymphoid cells (e.g., the liver)).
Three basic requirements are necessary for GVHD to develop:
(1) The donor bone marrow must have a functional cellular immune
component.
(2) The recipient’s tissue must bear antigens foreign to the donor tissue.
(3) The recipient’s immunity must be compromised to the point that it
cannot destroy the transplanted cells.
C –AUTOIMMUNE DISORDERS
Autoimmune diseases represent a group of disorders that are caused
by a breakdown in the ability of the immune system to differentiate
between self- and non self antigens. Normally, there is a high degree of
immunologic tolerance to self-antigens, which prevents the immune
system from destroying the host. Autoimmune diseases can affect almost
any cell or tissue in the body.
Some autoimmune disorders are tissue specific such as Autoimmune
Adrinalitis; others, such as Rheumatoid Arthritis affect multiple organs
and systems,scleroderma, autoimmune haemolytic anemia , autoimmune
adrenalitis, insulin- dependent diabetes mellitus.
■ Immunologic tolerance is the ability of the immunesystem to
differentiate self from nonself.
■ Central tolerance involves the elimination of self-reactive T and B cells
in the central lymphoid organs. Self-reactive T cells are deleted in the
thymus and self-reactive B cells in the bone marrow.
■ Peripheral tolerance derives from the deletion or inactivation of selfreactive T and B cells that escaped deletion in the central lymphoid
organs.
■ Autoimmune disorders result from the breakdown in the integrity of
immune tolerance such that a humoral or cellular immune response can
be mounted against host tissue or antigens, leading to localized or
systemic injury.
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Some people are allergic to a wide range of substances, while others are
affected by only a few or none. Why the difference? The reasons can be
found in the makeup of an individual's immune system, which may
produce several chemical agents that cause allergic reactions. The main
immune system substances responsible for the symptoms of allergy are
the histamines that are produced after exposure to an allergen. When an
allergen first enters the body, the lymphocytes make what are known as E
antibodies. These antibodies attach to mast cells, large cells that are found
in connective tissue and contain histamines. The histamines are chemicals
released by basophils, a type of lymphocyte, during the inflammatory
response.
There are many treatments for allergy, including (obviously) avoidance of
the substance to which the patient is allergic. Among these treatments are
the administration of antihistamines, which either inhibit the production
of histamine or block histamines at receptor sites.
In cases of extreme allergic reaction leading to anaphylactic shock, the
patient may require an injection of epinephrine (also sometimes called
adrenaline), a hormone that the body produces for responding to
situations of fear and danger. In the case of anaphylactic shock, which
involves such severe constriction of the breathing passages that the
patient runs a risk of suffocation, epinephrine causes the passages to
open, making it possible to breathe again.
Rheumatoid arthritis, as its name suggests, is a type of both rheumatism
and arthritis, which are general names for diseases associated with
inflammation of connective tissue. Rheumatoid arthritis occurs when the
immune system attacks and destroys the tissues that line bone joints and
cartilage. The disease can affect any part of the body, although some
joints may be more susceptible than others are. As it progresses, joint
function diminishes sharply, and deformities arise.
Pernicious anemia was so named at a time when it, too, was almost
always fatal (pernicious means "deadly"), though treatments developed in
the twentieth century have changed that situation. A disorder in which the
immune system attacks the lining of the stomach in such a way that the
body cannot metabolize vitamin B12 (see Vitamins), pernicious anemia
manifests symptoms that include weakness, sore tongue, bleeding gums,
and tingling in the extremities.
Autoimmune disorders are diagnosed and monitored through auto-antibody
blood tests, blood tests that measure inflammation and organ function,
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family history, physical examination, and diagnostic tools such as x rays,
etc.
There is no cure for autoimmune disorders. Sometimes these
disorders may disappear on their own, get worse or lessen in intensity
over time. Treatment for these diseases must be tailored by the physician
to relieve pain, minimize risk to the patient, and preserve organ function.
D-IMMUNODEFICIENCY DISORDERS
IMMUNO-DEFICIENCY (ID)can be defined as an abnormality in
one or more branches of the immune system that renders a person
susceptible to diseases normally prevented by an intact immune system,
resulting from absolute or partial loss of the normal immune response.
Abnormalities of the immune system can be classified :
1- Primary Immune deficiency (congenital or inherited)P.I.D.
■ In Primary ID Most primary immunodeficiency states are inherited and
are either present at birth or become apparent shortly after birth.
2- secondary I.D. (when the immunodeficiency is acquired later in
life). These are more common than primary disorders of genetic
origin.
AIDS (Acquired Immun-Deficiency Syndrome) is the most common
type of secondary immunodeficiency. It is an infectious disease of the
immune system caused by the retrovirus HIV (human
immunodeficiency virus HIV .
HIV is transmitted from one person to another through: 123-
sexual contact.
through blood exchange.
perinatally.
Acquired immune deficiency disorders often are the result of side
effects from drugs used to treat serious disorders. Corticosteroids, for
example, are immunosuppressants used to suppress inflammation
resulting
from
disorders
such
as
rheumatoid
arthritis.
Immunosuppressants, however, also suppress the body's ability to fight
disease and infections. Some cancer treatments and chemotherapy drugs
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are
also
powerful
immunosuppressants.
Immune deficiency disorders can also result from any prolonged illness.
Diabetes for example can cause immune deficiency disorder, because
white blood cells don't work well when blood sugar levels are high. Acquired Immune deficiency disorder (AIDS) can result from the
infection by the human immunodeficiency virus (HIV).
Malnutrition can cause immune deficiency disorders. Being more than
20% underweight is a risk factor for acquiring a severe impairment of the
immune system.
There is no cure for AIDS. Treatment largely involves the use of drugs
that interrupt the replication of the HIV virus and prevention or treatment
of complications such as opportunistic infections.

Infected women may transmit the virus to their offspring in utero,
during labor and delivery, or through breast milk.
Currently available antiretroviral drugs for the treatment of HIV fall into
three categories: nucleoside reverse transcriptase inhibitors ,nonnucleoside reverse transcriptase inhibitors
And protease inhibitors.
Examples: zidovudine (AZT), didanosine
Non-nucleoside reverse transcriptase inhibitors
Examples: nevirapine, efavirenz
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