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CHAPTER I

INTRODUCTION
A. BACKGROUND

The immune system is the body's defense against infectious organisms and other invaders.
Through a series of steps called the immune response, the immune system attacks organisms
and substances that invade body systems and cause disease. The immune system cannot function
if the system reacts with foreign molecules excessively examples include allergies.

Allergy is an abnormal immunological response to an otherwise harmless environmental stimulus.


Allergy is one type from hypersensitivity, that is first type of hypersensitivity. The reaction is the result
of an antigen cross-linking with membrane-bound IgE antibody of a mast cell or basophil. Histamine,
serotonin, bradykinin, and lipid mediators (e.g., platelet activating factor, prostaglandins, and
leukotrienes) are released during the anaphylactic reaction. These released substances have the potential
to cause tissue damage.

To treat allergy can use immunotherapy methods or take antiallergic drug. Antiallergic drug or anoyher
name is antihistamin is drugs that antagonize these effects by blocking or inhibiting histamine receptors
(H receptors).

B. PROBLEMS
1. What is the definition of imunne system?
2. What are types of imunnity?
3. What are types of imunne system disorders?
4. What is hypersensitivity?
5. What are types of hypersensitivity?
6. How is mechanism of allergy?
7. What are causes of allergy?
8. How are prevention of allergy ?
9. What are types of allergy test?
10. What are anthihistamin?
11. Whait is imunnomodulator ?
12. Whait is imunnostimulant?
13. Whait is imunnosupression ?

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C. PURPOSE
1. To know about the imunne system
2. To know about types of imunnity
3. To know about types of imunne system disorders
4. To know about hypersensitivity
5. To know about types of hypersensitivity
6. To know about how mechanism of allergy
7. To know about causes of allergy
8. To know about prevention of allergy
9. To know about types of allergy test
10. To know about anthihistamin
11. To know about imunnomodulator
12. To know about immunostimulantimunnosupression
13. To know about imunnosupression

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SCENARIO
Mr. N came to a pharmacy to buy a drug because he felt itching all over his body after eating
shrimp. all this time Mr. N thought he had recovered from an shirmp allergy so he wanted to eat
it when he was offered shrimp by his friend. Mr. N asked for a drug that did not cause
drowsiness because of his job as a bus driver.

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CHAPTER II
DISCUSSION

A. THE IMMUNE SYSTEM

The immune system is the body's defense against infectious organisms and other invaders. Through a
series of steps called the immune response, the immune system attacks organisms and substances that
invade body systems and cause disease.

The immune system is made up of a network of cells, tissues, and organs that work together to protect
the body. One of the important cells involved are white blood cells, also called leukocytes, which come
in two basic types that combine to seek out and destroy disease-causing organisms or substances.

Leukocytes are produced or stored in many locations in the body, including the thymus, spleen, and
bone marrow. For this reason, they're called the lymphoid organs. There are also clumps of lymphoid
tissue throughout the body, primarily as lymph nodes, that house the leukocytes.

The leukocytes circulate through the body between the organs and nodes via lymphatic vessels and
blood vessels. In this way, the immune system works in a coordinated manner to monitor the body for
germs or substances that might cause problems.

The two basic types of leukocytes are:

1. phagocytes, cells that chew up invading organisms


2. lymphocytes, cells that allow the body to remember and recognize previous invaders and help the
body destroy them
A number of different cells are considered phagocytes. The most common type is the neutrophil,
which primarily fights bacteria. If doctors are worried about a bacterial infection, they might order a
blood test to see if a patient has an increased number of neutrophils triggered by the infection. Other
types of phagocytes have their own jobs to make sure that the body responds appropriately to a specific
type of invader.
The two kinds of lymphocytes are B lymphocytes and T lymphocytes. Lymphocytes start out in the
bone marrow and either stay there and mature into B cells, or they leave for the thymus gland, where
they mature into T cells. B lymphocytes and T lymphocytes have separate functions: B lymphocytes
are like the body's military intelligence system, seeking out their targets and sending defenses to lock
onto them. T cells are like the soldiers, destroying the invaders that the intelligence system has
identified.

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Here's how it works:

When antigens (foreign substances that invade the body) are detected, several types of cells work
together to recognize them and respond. These cells trigger the B lymphocytes to produce antibodies,
which are specialized proteins that lock onto specific antigens.

Once produced, these antibodies stay in a person's body, so that if his or her immune system encounters
that antigen again, the antibodies are already there to do their job. So if someone gets sick with a certain
disease, like chickenpox, that person usually won't get sick from it again.

This is also how immunizations prevent certain diseases. An immunization introduces the body to an
antigen in a way that doesn't make someone sick, but does allow the body to produce antibodies that
will then protect the person from future attack by the germ or substance that produces that particular
disease.

Although antibodies can recognize an antigen and lock onto it, they are not capable of destroying it
without help. That's the job of the T cells, which are part of the system that destroys antigens that have
been tagged by antibodies or cells that have been infected or somehow changed. (Some T cells are
actually called "killer cells.") T cells also are involved in helping signal other cells (like phagocytes) to
do their jobs.

Antibodies also can neutralize toxins (poisonous or damaging substances) produced by different
organisms. Lastly, antibodies can activate a group of proteins called complement that are also part of
the immune system. Complement assists in killing bacteria, viruses, or infected cells.

All of these specialized cells and parts of the immune system offer the body protection against disease.
This protection is called immunity.

B. THE TYPES OF IMUNNITY


There are two inter-related systems by which the body identifies foreign material: the innate immune
system and the adaptive immune system (Janeway Jr., 1992, 1993; Fearon & Locksley, 1996; Janeway
Jr. & Travers, 1997; Parish & O’Neill, 1997; Carol & Prodeus, 1998; Colaco, 1998; Medzhitov &
Janeway Jr., 1997a,b, 1998).
The innate immune system is so called because the body is born with the ability to recognizecertain
microbes and immediately destroy them. Our innate immune system can destroy manypathogens on
first encounter. An important component of the innate immune response is a class ofblood proteins
known as complement, which has the ability to assist, or complement, the activity. The innate immunity
is based on a set of receptors encoded in thegerminal centers and known as pattern recognition receptors
(PRRs), to recognize molecular patterns associated with microbial pathogens, called pathogen
associated molecular patterns (PAMPs). The PAMPs are only produced by microbes and never by the

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host organism, hence their recognition by the PRRs may result in signals indicating the presence of
pathogenic agents. This way, the structures related to the immune recognition must be absolutely
distinct from our own cells and molecules in order to avoid damage to tissues of the host. The
consequence of this mechanism is that the innate immunity is also capable of distinguishing between
self and nonself, participating in the self/nonself discrimination issue, and plays a leading role in the
boost of adaptive immunity.
The most important aspect of innate immune recognition is the fact that it induces the expression of co-
stimulatory signals in antigen presenting cells (APCs) that will lead to T cell activation, promoting the
start of the adaptive immune response. This way, adaptive immune recognition without innate immune
recognition may result in the negative selection of lymphocytes that express receptors involved in the
adaptive recognition.
The adaptive immune system uses somatically generated antigen receptors which are clonally
distributed on the two types of lymphocytes: B cells and T cells. These antigen receptors are generated
by random processes and, as a consequence, the general design of the adaptive immune response is
based upon the clonal selection of lymphocytes expressing receptors with particular specificities
(Burnet, 1959-1978). The antibody molecules (Ab) play a leading role in the adaptive immune system.
The receptors used in the adaptive immune response are formed by piecing together gene segments.
Each cell uses the available pieces differently to make a unique receptor, enabling the cells to
collectively recognize the infectious organisms confronted during a lifetime (Tonegawa, 1983).
Adaptive immunity enables the body to recognize and respond to any microbe, even if it has never
faced the invader before.

C. THE IMUNNE SYSTEM DISORDERS


The immune system cannot function if the system reacts with foreign molecules excessively. Some
examples include allergies, autoimmunity, and AIDS (Ferdinand and Moekti, 2009).

C.1 ALLERGY (HYPERSENSITIVITY)

Allergies (hypersensitivity) are excessive body immune responses to allergens (foreign bodies
and antigens) that are harmful or not (Anonim, 2013). Some people are allergic to fur, dust,
seafood, insect bites, pollen and so on. . The form of the reaction can vary, from sneezing, itching,
dizziness, vomiting and diarrhea, even to difficulty breathing and death. (Ferdinand and Moekti,
2009).
at first, there are no signs of any resistance to the body when foreign proteins enter the body. at
this stage the body develops immunoglobin (usually from the IgE class). when proteins of the
same type enter the body for the second time, IgE reacts by binding to antigens on the surface of
the membrane mast cell. this reaction is encouraging mast cell secretes histamine. This large
amount of histamine causes various allergic reactions. for example, if an allergic reaction occurs
in the respiratory tract, histamine will be captured by smooth muscle cells in the respiratory
cavity, followed by contracting these muscles so that the airway narrows. histamine also results
in vasodilation, blood capillaries become more permeable, and blood pressure drops. this causes
the tissue to swell. (Ferdinand and Moekti, 2009).

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C.2 AUTOIMMUNITY
Autoimmune disorders are a broad spectrum of disease that can affect any part of the body.
More than 80 have been identified, a considerable number with similar symptoms. Inflammation
is the classic sign of autoimmunity although how this impacts on an individual is determined by
which part of the body is affected. Autoimmune disorders can be placed into two general types:
those that are localised to specific organs or tissues (such as thyroiditis) or those that are systemic
and damage many organs or tissues (such as systemic lupus erythematosus).
Examples of localised autoimmune diseases
• Addison’s disease – this disease results from damage to the outer layer of the adrenal gland
(the adrenal cortex), of which autoimmunity is the most common cause. As a result
of this damage the adrenal gland does not produce enough steroid hormones (primary adrenal
insufficiency), resulting in symptoms which include fatigue, muscle weakness, and a loss
of appetite. This can be fatal if not recognised and treated, but treatment is relatively simple.
• Grave’s disease – affecting the thyroid, Grave’s disease is one of the most common causes
of hyperthyroidism. It results from the production of antibodies that mimic Thyroid
Stimulating Hormone, which produces a false signal causing the thyroid gland to produce
excessive thyroid hormone. Symptoms including insomnia, tremor, and hyperactivity.
• Type 1 diabetes – diabetes mellitus type 1 is a consequence of the autoimmune destruction
of cells in the pancreas which produce insulin. Insulin is essential to control blood sugar
levels and if left uncontrolled the disease can lead to serious complications, such as damage
to the nerves, heart disease, and problems with the retina. Without adequate treatment type
1 diabetes would be fatal.
• Crohn’s disease – a type of inflammatory bowel disease (IBD), Crohn’s is a result of chronic
inflammation of the lining of the gastrointestinal tract that can cause diarrhoea, abdominal
pain, and fatigue.
Examples of systemic autoimmune diseases
• Rheumatoid arthritis – a chronic condition that causes painful stiffness and swelling in the
joints. Rheumatoid arthritis is a result of the immune system attacking tissues in the joint
lining, eventually leading to damage of the joint itself. Rheumatoid arthritis can also effect
inflammation around other organs, such as the heart and lungs. It differs from osteoarthritis,
which is generally caused by mechanical stresses on the joint.
• Multiple sclerosis – a chronic condition that can cause significant disability, multiple
sclerosis is a disease in which the electrically insulating layers of the nerves are destroyed,
thus affecting signalling between the brain and other parts of the body.
• Lupus – systemic lupus erythematosus is a complex condition affecting many parts of the
body, including the skin, joints, heart, lungs and nervous system. It occurs as a result of a
widespread systemic autoimmune reaction and results in symptoms including fatigue, joint
pain, and rashes.

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• Scleroderma – in scleroderma the immune system attacks the connective tissue under the
skin, resulting in a thickening of these tissues. In more severe forms it can affect blood
circulation and internal organs.

Autoimmune disease symptoms

The early symptoms of many autoimmune diseases are very similar, such as:

 fatigue
 achy muscles
 swelling and redness
 low-grade fever
 trouble concentrating
 numbness and tingling in the hands and feet
 hair loss
 skin rashes

Individual diseases can also have their own unique symptoms. For example, type 1 diabetes
causes extreme thirst, weight loss, and fatigue. IBD causes belly pain, bloating, and diarrhea.

With autoimmune diseases like psoriasis or RA, symptoms come and go. Periods of symptoms
are called flare-ups. Periods when the symptoms go away are called remissions

Tests that diagnose autoimmune diseases

No single test can diagnose most autoimmune diseases. Your doctor will use a combination of
tests and an assessment of your symptoms to diagnose you.

The antinuclear antibody test (ANA) is often the first test that doctors use when symptoms
suggest an autoimmune disease. A positive test means you likely have one of these diseases, but
it won’t confirm exactly which one you have.

Other tests look for specific autoantibodies produced in certain autoimmune diseases. Your
doctor might also do tests to check for the inflammation these diseases produce in the body.

Treatment options for autoimmune diseases

Currently there are no cures for autoimmune diseases, although there is a wide range of
treatment options, which depend on the stage and type of autoimmune disease. The main aims
of treatments for autoimmune diseases are to relieve symptoms, minimise organ and tissue
damage and preserve organ function.

Treatment options include:

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 Replacement of end organ functions (such as insulin in diabetes and thyroxine in
autoimmune thyroid disease)
 Non-steroidal anti-inflammatory medications (NSAIDS)
 Corticosteroid anti-inflammatory medications (such as Prednisolone)
 Immunosuppressive medications
 Therapeutic monoclonals (such as TNF inhibitors) Immunoglobulin replacement
therapy

C.3 AIDS (IMMUNE DEFICIENCY)

Immune deficiency that is not working or disrupting one or all components of the immune system
(Anonymous, 2013).under normal circumstances, the virus can be deactivated by T lymphocyte
cells. However, when the helper T cells are infected with the virus, it does not have the ability to
carry out its function to recognize and deactivate foreign cells that enter the body.Acquired
Immunodeficiency Syndrome (AIDS) is a disease caused by Human Immunodeficiency Virus
(HIV) in T lymphocyte cells.when the virus successfully infects T lymphocyte cells, the virus uses
its cell "device" to replicate inside the cell. a virus that has multiplied then destroys the cell
membrane and leaves old T lymphocytes. these viruses are ready to infect other T lymphocytes that
are still healthy. (Ferdinand and Moekti, 2009).
Immunodeficiency is a condition in which there is a decrease or absence of a normal immune
response. This condition can occur primarily, which is generally caused by genetic disorders
inherited, as well as secondary to other major diseases such as infection, chemotherapy treatment,
cytostatics, radiation, immunosuppressant drugs (suppress the immune system) or in old age and
malnutrition (Malnutrition).

Classification:
Immunodeficiency is divided into two, namely primary immunodeficiency which is almost always
determined by genetic factors. While secondary immunodeficiency can appear as a complication
of diseases such as infection, cancer, or side effects of using drugs and therapy.

a. Primary immunodeficiency
the researchers have identified more than 150 types of primary immunodeficiency.
Immunodeficiency can affect B lymphocytes, T lymphocytes, or phagocytes. Immunodeficiency
disorders, including:
-IgA deficiency (immunoglobulin)

Immunoglobin is found mainly in saliva and other body fluids as the body's first protection.
Genetic causes and Toxoplasma infection, Smallpox virus, and other viruses. People with IgA
deficiency tend to have allergies or have a cold and other respiratory infections. Although not
severe.

-Chronic granulomatos

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Inherited immunodeficiency so that sufferers are susceptible to certain bacterial or fungal
infections. Sufferers cannot fight bacterial infections that are generally mild in normal people.
-Severe immunodeficiency (SCID)
SCID is a serious immune system disorder due to B lymphocytes and T lymphocytes. Those who
are deficient are almost impossible to fight infection. Infants who experience SCID generally
experience oral candidiasis, diaper rash, and failure to develop.

-Sindroma digeorge (thymus dysplasia)


-The syndrome of birth defects with sufferers of children born without the thymus gland. The signs
of this syndrome include decreased T-cell levels, tetanus, and congenital heart defects. ears, face,
mouth and can become abnormal.

-wiskott Aldrich Syndrome


diseases associated with the X chromosome are characterized by thrombocytopenia, eczema, and
are susceptible to infection causing premature death.
a. Immunodeficiency Secondary
disease develops generally after a person experiences an illness. other causes include the results of
injuries, malnutrition or other medical problems. A number of drugs also cause interference with
immune function. Immuno secondary deficiencies, including:

-Infection
HIV (human immunodeficiency Virus) and AIDS (acquired immuno deficiency syndrome) are
common diseases that continue to destroy the body's immune system. The cause is the HIV virus
that kills certain types of lymphocytes called T-helper cells. As a result, the immune system cannot
maintain the body the organism is usually harmless. In adults with AIDS, HIV infection can be life
threatening.
-Cancer
patients with widespread cancer are generally easily infected with microorganisms. Tumor bone
marrow and leukemia that appear in the spinal cord can disrupt the growth of lymphocytes and
leukocytes. tumors also inhibit lymphocyte function as in hodgkin disease.
-drugs
Some drugs suppress the immune system, such as chemotherapy drugs that not only attack cancer
cells but also other healthy cells, including the spinal cord and immune system. In addition,
autoimmune disorders or those who undergo organ transplants can reduce immunity body fight
infection.
- removal of spleen
removal of the spleen as a therapy for trauma or hematologic conditions causes an increase in the
flexibility of infection especially Streptococcus pneumoniae.

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Etiology
Several causes of immunodeficiency are obtained:
1. Hereditary diseases and metabolic disorders. Eample : Diabetes, Down syndrome, kidney failure,
malnutrition, sickle cell disease
2. Chemicals and treatments that suppress the immune system: Cancer chemotherapy,
corticosteroids, immunosuppressant drugs, radiation therapy
3. Infection: HIV (AIDS) infection, infectious mononucleosis, severe bacterial infection, severe
fungal infection, severe tuberculosis
4. Blood disease and cancer

D. HYPERSENSITIVITY
Hypersensitivity reactions are a group of conditions in which the immune system, which normally serves
a protective role, has a harmful effect. Allergy: an abnormal immunological response to an otherwise
harmless environmental stimulus (e.g., food, pollen, animal dander). Both allergiesand many
autoimmune disorders fall under the umbrella of hypersensitivity reactions, the difference being
that allergies involve an immune reaction to common substances in the environment, whereas
autoimmune diseases involve a direct immune reaction to tissues within the body.

D.1 TYPES OF HYPERSENSITIVITY


The response of the host to the presence of foreign substances can trigger four types of
hypersensitivity reactions:

Type I: Immediate Hypersensitivity (Anaphylactic Reaction)


These allergic reactions are systemic or localized, as in
allergic dermatitis (e.g., hives, wheal and erythema
reactions). The reaction is the result of an antigen cross-
linking with membrane-bound IgE antibody of a mast cell
or basophil. Histamine, serotonin, bradykinin, and lipid
mediators (e.g., platelet activating factor, prostaglandins,
and leukotrienes) are released during the anaphylactic
reaction. These released substances have the potential to
cause tissue damage.

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Type II: Cytotoxic Reaction (Antibody-dependent)
In a cytotoxic reaction, the antibody reacts directly with the
antigen that is bound to the cell membrane to induce cell
lysis through complement activation. These antigens may be
intrinsic or “self” as in autoimmune reactions or extrinsic or
“non-self.” Cytotoxic reactions are mediated by IgG and
IgM. Examples of cytotoxic reaction are the Rh
incompatibility of a newborn, blood transfusion reactions,
and autoimmune diseases like Pemphigus Vulgaris, Bullous
Pemphigoid, autoimmune hemolytic anemia and
Goodpasture's syndrome to name a few.

Type III: Immune Complex Reaction


IgG and IgM bind antigen, forming antigen-antibody
(immune) complexes. These activate complement, which
results in PMN chemotaxis and activation. PMNs then
release tissue damaging enzymes. Tissue damage present in
autoimmune diseases (e.g., systemic lupus erythematosus),
and chronic infectious diseases (e.g., leprosy) can be
attributed, in part, to immune complex reactions.

Type IV: Cell-Mediated (Delayed Hypersensitivity)


Cell-mediated reactions are initiated by T-lymphocytes
and mediated by effector T-cells and macrophages. This
response involves the interaction of antigens with the
surface of lymphocytes. Sensitized lymphocytes can
produce cytokines, which are biologically active
substances that affect the functions of other cells. This
type of reaction takes 48-72 hours, or longer, after contact
with the antigen to fully develop. Many chronic infectious
diseases, including tuberculosis and fungal infections,
exhibit delayed hypersensitivity.
Evidence suggests that hypersensitivity reactions,
particularly Type III and IV, may be involved in the
pathogenesis of periodontal disease.

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D.2 MECHANISM OF ALLERGY
Mechanism for the occurrence of allergies
In the body there are 5 types of antibodies or immunology, including G, A, M, E, and D. Which
plays a role in allergic reactions are antibodies or immunoglobulins E. Antibodies or high
immunoglobulin E are found in the body of patients who suffer from allergic diseases that are
specific to certain substances that can cause allergic reactions (allergen substances), such as dust,
milk, sea fish, and so on. In body tissues, antibodies or immunoglobulin E that react to these
allergens attach to mast cells, which are cells that play a role in allergic reactions and
inflammation. If these antibodies contact again with related substances, such as cow's milk
protein, egg protein, house dust mites and others, then these mast cells will degranulate (break)
and release substances such as histamine, kinin, and bradykinin which contained in the granules
which play a role in allergic reactions. These substances cause allergic symptoms such as hives
(biduran), respiratory system (allergic asthma, allergic rhinitis), gastrointestinal tract (diarrhea,
vomiting), kuliy (eczema, biduran), eyes (allergic conjunctivities) , and nervous system
(headaches and others).
Allergic reactions after exposure to allergens
require time or what is called the sensitization
process, which is the time from contact with
allergens to an allergic reaction. Allergic
reactions can occur if the level of
immunoglobulin E is sufficient. At the beginning
of contact with allergens, resistance starts from
the body that has atopic talent, namely the
formation of specific antibodies or
immunoglobulins. If contact with these allergens
occurs continuously, the level of immunoglobulin
E that is specific to allergens is increasing until
one day it can cause an allergic reaction when exposed to the allergen again.
The emergence of an allergic reaction to allergens when first contacted or referred to as
sensitization process can occur in a short time or several months or up to several years later. If
allergens are not avoided, then the level of immunoglobulin E that is specific to these allergens
will increase. Mast cells that have granulated or ruptured can secrete substances called interleukin
4 which can stimulate B lymphocyte cells to produce even more immunoglobulin E. Continuing
allergen reactions can produce a new, more potent mediator than histamine, namely leukoterin.
This condition mainly occurs in allergic diseases that have entered the stage of chronic allergies.
If something like this happens, generally a person will be immune to the usual antihistamine
allergy medication. Better inflammatory drugs are needed, such as corticosteroid drugs to treat
allergic reactions that occur.
Avoiding allergens or substances that can trigger allergies is one of the right preventative steps
to take. By avoiding allergy prevention, patients can prevent allergic reactions that have occurred

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so as not to get worse. Do a check with your doctor to find out the next development of an allergic
reaction.

D.3 CAUSES OF ALLERGY


Everything can trigger allergies, depending on the person concerned is allergic to what. Starting
from air temperatures, certain substances in the air such as dust or pollen, certain foods, soaps or
substances contained in personal care products, medicines, animal hair, and so forth. Different
people, different types of allergies. Most allergies are heredity or are passed from parents to
children. Allergic reactions in the body When a person is exposed to an allergen, his body will
react to produce IgE antibodies, to bind to the allergen. Antibodies attach to blood cells called
mast cells. Mast cells can be found in the respiratory tract, digestive tract and other places. Mast
cells will release various chemicals into the blood. The main chemical compounds produced by
mast cells are histamine, which causes most symptoms of allergic reactions.

D.4 PREVENTION OF ALLERGY


Basically allergic diseases can be prevented and divided into 3 stages, namely:
1. Primary prevention, namely the process of early recognition of allergens to prevent
sensitization. The first action is to identify babies who have atopic risk. Pregnant women are
given a retriction diet (without milk, eggs, sea fish and peanuts) starting in the third trimester
and during breastfeeding, babies get exclusive breastfeeding for 5-6 months. In addition,
environmental controls are carried out to prevent exposure to allergens and pollutants.
2. Secondary prevention, to prevent clinical manifestations of allergies in children in the form
of asthma and colds. Sensitized allergies with allergic symptoms in the early stages are food
allergies and skin. Actions taken with avoidance of exposure to inhalant allergens and food
that can be known by skin testing.
3. Tertiary prevention, to reduce clinical symptoms and the severity of allergic diseases with
allergen avoidance and treatment. Avoidance of allergens by maintaining cleanliness such as
cleaning the house from dust, using masks, avoiding pets, and others.

D.5 THE TYPES OF ALLERGY TEST


An allergic diagnosis is made based on the history of the symptoms experienced and the possible
causes of allergens, a physical examination to see the symptoms of allergies that appear, and if
there is still doubtful investigation should be done. Investigation can be carried out in vivo or in
vitro

IN VITRO ALERGY TEST

Calculate eosinophils in secret An increase in the number of eosinophils in smear nasal secretions
is a more sensitive indicator than peripheral blood eosinophilia, and can distinguish allergic
rhinitis from rhinitis due to other causes. However, it cannot determine specific causes of
allergens. Nasal esophilia in children when eosinophils are found is more than 4% in smear nasal

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secretions, whereas in adolescents and adults more than 10%. Eosinophilia nasal secretions can
also predict therapeutic responses with topical nasal corticosteroids. Eosinophil counts can also
be performed on bronchial and conjunctival secretions.

TOTAL IgE TEST


Serum total IgE levels Increased serum IgE levels are often found in allergic diseases so it is
often done to support the diagnosis of allergic diseases. Patients with atopic dermatitis have the
highest IgE levels and asthma patients have higher IgE levels than allergic rhinitis. Although the
average IgE level of total allergic patients in the population is higher than that of non-allergic
patients, the overlapping IgE levels in allergic and non-allergic populations causes the total IgE
diagnostic value to be low. Total IgE levels are found normally in 50% of allergic patients, and
vice versa increases in non-allergic diseases (viral / fungal infections, immunodeficiency,
malignancy)

SPECIFIC IgE TEST


Specific IgE levels Examination of specific IgE levels for a particular allergen can be done in
vivo by skin testing or in vitro with the RAST method (Radio Allergosorbent Test), ELISA
(Enzyme-linked Immunosorbent Assay), or RAST enzymes. The advantages of the RAST
method compared to skin testing are safety and the results are not affected by drugs or skin
disorders. RAST results correlate quite well with skin test and provocation test, but RAST
sensitivity is lower.

ALERGY IN VIVO TEST

SKIN TEST
There are 3 ways to do a skin test, namely intradermal method, prick test (skin prick test / SPT),
and scratch test.

1. Intradermal skin test: 0.01-0.02 ml of allergen extract is injected into the dermis layer so that
bubbles appear 3 mm in diameter. It starts with the lowest concentration that gives rise to a
reaction, then increases gradually with a concentration of 10 times to an accuracy of 5-15 mm.
The intradermal skin test technique is more sensitive than the skin prick test (SPT), but it is
not recommended for food allergens because it can trigger an anaphylactic reaction.
2. Scratch test (scratch test): it has been abandoned because it is less accurate.
3. Skin prick test (SPT): Prick tests can be performed on inhaled allergens, allergens in the
workplace, and food allergens. The best location is the forearm volar area with a minimum
distance of 2 cm from the fold of the elbow and wrist. A drop of allergen extract in glycerin
is placed on the surface of the skin. The superficial layer of the skin is pierced and raised
upward with a special needle for the puncture test. Positive results if the wheal is formed> 2
mm. Antihistamine preparations, ephedrine / epinephrine, corticosteroids and β-agonists can
reduce skin reactivity, so it must be stopped before skin testing. Skin testing is best done after
the patient is three years old. The SPT sensitivity to food allergens is lower than inhaled
allergens. Compared to the intradermal test, SPT has a lower sensitivity but higher specificity
and has a better correlation with the symptoms that occur.

PROVOCATION TEST
Provocation tests were conducted to see the relationship between allergen exposure and
symptoms in various organs (skin, conjunctiva, gastrointestinal tract, lung), provocation testing
can be carried out.

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1. Bronchial provocation test, an allergen extract with higher concentration is inhaled through
the nebulizer to see airway obstruction. Atkins in the study showed that bronchial provocation
testing correlated both with skin testing and in vitro allergy testing.
2. Food provocation tests, carried out based on suspected food history and skin test results or
RAST on these foods. Implementation can be done in an open, single-blind, double-blind, or
double-blind placebo-controlled manner. If the skin test is negative and a history of reaction
to food is doubtful then an open food provocation test can be done after an elimination diet
for three weeks. The provocation test for cow's milk is done by giving cow's milk starting
from 1 drop / 15 minutes to 30 ml / 15 minutes, and if it has reached 200 ml there is no allergic
reaction, then the patient can consume cow's milk.
3. Colonoscopic allergen provocation, done through a colonoscopy by injecting an allergen
extract into the mucosal mucosa. Positive results are in the form of wheal and mucosal redness.
The degree of allergy is determined semiquantitatively, that is 0 = no reaction, 1 = doubt, 2 =
moderate reaction (2 cm diameter) .10 COLAP results are in accordance with the history of
allergies, but not in accordance with the results of the SPT and RAST. The possibility is
because the specific IgE of the intestinal mucosa is not circulating systemically, or the
hypersensitivity reaction in the intestine is not (not just) an IgE-dependent mechanism.
4. Patch test, generally used in cases of contact dermatitis. Allergens suspected of being placed
on the skin and positive results in the form of eksatema reactions in 48-72 hours. In addition
to contact dermatitis, patch testing is also done to diagnose food allergies in children with
atopic dermatitis and eosinophilic esophagitis. Found 67% of children with a positive cow
milk provocation test showed positive SPT (fast type allergic reaction) results, while patch
tests showed negative results. Conversely, patch testing was positive in 89% of children with
slow type allergic reactions (25-44 hours). It is said that the combination of puncture test and
patch test has the highest positive predictive value and can replace the food provocation test.
5. Immuno CAP Phadiatop Infant (PI), useful for detecting IgE in infants up to the age of 2 years.
When compared with skin prick test (SPT) and RAST in infants with SPT and RAST results
all positive or negative, then PI has a sensitivity of 96%, specificity 98%, positive predictive
value 89%, and negative predictive value 99% but in infants with positive SPT or RAST
results, PI showed sensitivity of 82%, specificity of 98%, positive predictive value of 94%,
and negative predictive value of 95%. There is a statistically significant correlation between
eczema and positive PI results, but the correlation with asthma and rhinoconjunctivitis
symptoms is inconclusive because above the age of two years there has been a role for viral
infection. Thus PI can be used as an allergy test in infants because it can replace SPT and does
not require specific antigen selection both in SPT and RAST.

E. ANTIHISTAMIN

Histamine is a biologically active substance that potentiates the inflammatory and immune responses of
the body, regulates physiological function in the gut, and acts as a neurotransmitter. Drugs that
antagonize these effects by blocking or inhibiting histamine receptors (H receptors) are called
antihistamines. Antihistamines are divided into two classes (H1 antihistamines and H2 antihistamines),
based on the type of H receptor targeted. H1 antihistamines are mostly used to treat allergic reactions
and mast cell-mediated disorders. This subtype is further divided into two generations. While the first-
generation H1 antihistamines have a central effect and, thus, are also used as sedatives, second-
generation H1 antihistamines have less central effects and are used primarily as antiallergenic drugs. H2
antihistamines are indicated primarily for gastric reflux disease because they reduce the production of
stomach acid by reversibly blocking the H2 histamine receptors in the parietal cells of the gastric

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mucosa. Use of most H1 and H2 antihistamines is contraindicated during pregnancy and childhood.
First-generation H1 antihistamines are specifically contraindicated in angle-closure glaucoma and
pyloric stenosis

Mechanisme of antihistmanine
The working relationship of antihistamine drugs in overcoming problems that occur through competition
by inhibiting histamine binding to H1 or H2 receptors in the target organ. High levels of histamine will
produce more H1 receptors. The new receptor will be filled by antihistamines. This molecular event will
prevent a temporary reaction.

H1 receptors are found in the brain, retina, adrenal medulla, liver, endothelial cells, cerebral blood
vessels, lymphocytes, respiratory muscles, gastrointestinal tract, genitourinary tract and vascular tissue.
H2 receptors in the digestive tract and in the liver. While the H3 receptor is in the cerebral cortex and
bronchial smooth muscle. On the skin there is also an H3 receptor which is an autoreseptor, given
histamine release and synthesis. Still unclear.

1. First Generation Antihistamine

This first generation antihistamine is easily available, either as a single drug or in combination with
decongestant drugs, for example for the treatment of influenza. This class includes
chlorpheniramine, difenhidramine, promethazine, hydroxycin and others. In general, the first
generation antihistamine drugs have similar effectiveness when used according to the
recommended dosage and can be distinguished from each other according to the side effects.
However, the undesirable effect of this drug is to cause drowsiness which disrupts work activities,
must be careful when driving a vehicle, drive an airplane and

operate heavy machinery. This sedative effect is caused by generation antihistamines this first has
lipophilic properties that can penetrate the blood brain barrier so that it can attach to H1 receptors
in brain cells. With the absence of histamine attached to brain cell H1 receptors, alertness decreases
and drowsiness arises. (1.6) In addition, the sedative effect is aggravated by alcohol use and
antidepressant drugs such as minor tranquillizers. Therefore, users of this drug must be careful. In
addition, some antihistamines have anticholinergic side effects such as dry mouth, pupillary
dilatation, foggy vision, urinary retention, constipation and impotence.

2. Second Generation Antihistamine

After 1972, a new group of antihistamines were found that could inhibit gastric acid secretion due
to histamine, namely burinamide, methylamide and cimetidine. It turns out that this second
generation antihistamine gives hope for the treatment of peptic ulcer, gastritis or duodenitis. Second
generation antihistamines have anti-allergic effectiveness like the first generation, having lower
lipophilic properties is difficult to penetrate the blood brain barrier. The brain cell H1 receptors
remain filled with histamine, so the side effects caused are somewhat lacking without the effects
of drowsiness. This drug is very well tolerated, can be given in high doses to relieve allergy
symptoms throughout the day, especially for allergy sufferers who depend on the season. This drug
can also be used for long-term treatment of chronic diseases such as urticaria and bronchial asthma.
The role of histamine in asthma is still not fully known. At doses that can prevent
bronchoconstriction due to histamine, antihistamines can relieve mild symptoms of chronic asthma
and symptoms of inhalation of allergens in patients with bronchial hyperreactivity. However, in

17
general it has limited effects and especially for fast reactions compared to slow reactions, so that
second generation antihistamines are doubtful for the treatment of chronic asthma. Which is
classified in the second generation antihistamines namely terfenadin, astemizol, loratadine and
cetirizin.

3. Third Generation Antihistamine

Which includes third generation antihistamines, namely fexofenadine, norastemizole and


deskarboetoksi loratadin (DCL), all three are second generation antihistamine metabolites. The aim
of developing third generation antihistamines is to simplify their pharmacokinetics and metabolism,
and avoid side effects associated with previous drugs.

F. THE IMUNNOMODULATOR
Immunomodulators are certain compounds that can enhance the body's defense mechanisms both
specifically and non-specifically, and non-specific inductions occur both cellular and humoral defense
mechanisms. This non-specific defense against antigens is called paramunitas, and substances related to
inducers are called paraimunitas. Such inductors usually do not or have very little antigen work, but
most work as mitogens, which increases cell proliferation which plays a role in immunity. The target
cells are macrophages, granulocytes, T and B lymphocytes, because this paramunitas inductor works to
stimulate cellular defense mechanisms. This mitogen can work directly or indirectly (for example
through the complement or lymphocyte system, through the production of interferon or lysosomal
enzymes) to increase micro and macro phagocytosis (Figure 1). Specific and non-specific defense
mechanisms generally influence each other. In this case the influence on some defense systems may
occur, making it difficult to use immunomodulators in practice.

Characteristics of immunomodulators and testing methods


The activity of a compound that can stimulate the immune system does not depend on the size of a
particular molecule. This effect can be given either by compounds with small molecular weights or by
polymer compounds. Therefore efforts to search for such compounds can only be done by
immunbiological test methods. Test methods that can be done are in vitro and in vivo methods, which
will measure the effect of chemical compounds on the functions and abilities of mononuclear systems,
as well as the stimulated ability of B and T lymphocytes.

Immunomoduator activity test methods that can be used, namely:


1. Carbon cleaning method ("Carbon-Clearance")
Spectropluorometric measurement of the elimination rate of carbon particles from animal regions. This is a
measure of phagocytic activity.
2. Granulocyte test
In vitro experiments by measuring the number of yeast cells or bacteria that were difagositir by
granulocyte fraction obtained from human serum. This experiment was carried out under a
microscope.
3. Radical Biolumination

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The amount of radical 02 released due to mitogen contact with granulocytes or macrophages, is a
measure of the amount of stimulation achieved.
4. T lymphocyte transformation test
A population of T lymphocytes is incubated with a mitogen. Marked thymidine (3 H) will enter the
lymphocyte nucleic acid 1. By measuring the formation rate can be determined the amount of
stimulation compared to phytohemagglutinin A (PHA) or konkanavalin A (Con A).

Immunomodulatory requirements

According to WHO, immunomodulators must meet the following requirements:


1. Chemically pure or chemically defined.
2. Biologically can be described quickly.
3. It is not cancerous or co-cancerous.
4. Both acute and chronic are not toxic and have no adverse pharmacological side effects.
5. Does not cause stimulation that is too small or too large.

Paramunitas functional basis (according to A. Mayr)


1. The increase in the work of microfags and macrophages and the release of mediators.
2. Stimulates lymphocytes (which play a role in immunity but have not been specific to certain antigens),
especially potentiating lymphocyte proliferation and activity.
3. Activate spontaneous cytotoxicity.
4. Induction of the body's own interferon formation.
5. Activate non-specific humoral defense factors (eg the properdin-opsonin complement system).
6. Liberation or increased reactivity of lymphokines and mediators or other activators.
7. Strengthens the work of regulation of prostaglandins.

G. IMMUNOSTIMULANT
Immunostimulants also known as immunostimulators, are substances (drugs and nutrients) that
stimulate the immune system by inducing activation or increasing activity of any of its components.
One notable example is the granulocyte macrophage colony-stimulating factor.There are two main
categories of immunostimulants
Specific immunostimulants provide antigenic specificity in immune response, such as vaccines or
any antigen.

19
Non-specific immunostimulants act irrespective of antigenic specificity to augment immune response
of other antigen or stimulate components of the immune system without antigenic specificity, such
as adjuvants and non-specific immunostimulators.
Non-specific
Many endogenous substances are non-specific immunostimulators. For example, female sex
hormones are known to stimulate both adaptive and innate immune responses.Some autoimmune
diseases such as lupus erythematosus strike women preferentially, and their onset often coincides
with puberty. Other hormones appear to regulate the immune system as well, most
notably prolactin, growth hormone and vitamin D.
Some publications point towards the effect of deoxycholic acid (DCA) as an immunostimulant of the
non-specific immune system, activating its main actors, the macrophages. According to these
publications, a sufficient amount of DCA in the human body corresponds to a good immune reaction
of the non-specific immune system.
Immunostimulants enhance the humoral and cellular response in both specific and non-specific ways.
These agents are widely used for impaired immune function and to stabilize the improved immune
status. The use of immunostimulants in fish culture or in aquaculture of other species for prevention of
diseases is a promising new development. In general, immunostimulants comprise a group of biological
and synthetic compounds that enhance the non-specific defense mechanisms in animals, thereby
imparting generalized protection. This protection may be particularly important for fish that are raised
in or released into environments where the nature of pathogen is unknown and immunization by specific
vaccine may be futile. Several immunostimulants have been evaluated in fin fishes.
Many occasions arise in the course of fish culture that calls for enhancement of immune response.
These include strengthening of the normal immune response in order to enhance protection and reduce
immunosuppressive conditions. Immunostimulants can be classified into several categories by their
origin and mode of action bacteria and bacterial products,complex carbohydrates,vaccines,immunity
enhancing drugs,nutritional factors,animal extracts,cytokines, and Lectins, plant extracts.
Two main procedures for evaluating the efficiency of an immunostimulants are:
In vivo, eg., protection tests against fish pathogens: and
In vitro, eg, measurement of the efficiency of cellular and humoral immune mechanism.
Attention is focused on the lymphocyte proliferation test as an adequate method for providing a correct
evaluation of the cellular immune condition which can be adopted together with the more commonly
used parameters, such as phagocytosis and respiratory burst. It may be mentioned here that the use of
immunostimulants in the diets of marine fish and the evaluation of their effect on the immune system
of fish has been investigated.
As immunostimulants, as such, which can be useful in preventing diseases in land based aquaculture,
in pens and hatcheries rarely occurs alone in the natural environment, the subject deserves a discussion
here.
Specific and non-specific immunostimulants:
Specific immunostimulation is related to the potentiation of the host's immune system towards a unique
specific antigen. Vaccination is perhaps the best example of producing specific immunity.

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Non specific immunostimulation generally is an attempt to upgrade immunologic capabilities at a time
when an animal may be exposed to one or several pathogens and/or be immuno-compromised.
Characteristics of an ideal immunostimulants:
1. It should be non-toxic, even at a high dose rate.
2. It should be non-carcinogenic or have long term side effects.
3. At therapeutic levels, it should have a short withdrawal period with low tissue residues
4. It should stimulate a wide range of non-specific immune responses against bacteria, fungi, virus,
protozoa and helminthes.
5. It should be capable of amplifying primary and secondary immune responses to infectious agents.
6. Breakdown products of compound concerned should be either inactive or readily biodegradable
in the environment.
7. It should be having defined chemical composition or biological activity.
8. It should be active by oral route and should be stable both in its native state and after incorporation
into food and water.
9. It should be compatible with arrange of drugs including antibiotics and anthelmintics, and
10. It should be inexpensive and either tasteless or palatable.

Objectives of immunostimulation
Promoting a greater and more effective sustained immune response to those infectious agents producing
subclinical disease without risks of toxicity, carcinogenicity or tissue residues.
Hastening the maturation of non-specific and specific immunity in young susceptible animals.
Enhancing the level of duration of specific immune response, both cell mediated and humoral,
following vaccination.
Overcoming of immunosuppressive effects of stress and of those infectious agents that damage or
interface with the functioning of cells of immune system.
Selectively stimulating the relevant components of the immune system or non-specific immune
mechanism that preferentially confer protection against micro-organisms. For example via interferon
release, especially for those infectious agents for which no vaccines currently exists; and
Maintaining immune surveillance at hightened level to ensure early recognition and elimination of
neoplastic changes in tissues.
Some common immunostimulants:
1. Muramyl dipeptide: Muramyl dipeptide is a simple glycoprotein, also a purified form of mycobacteria. Its
activity includes:
2. Enhancement of antibody activity.
3. Stimulation of polyclonal activation of lymphocytes, and
4. Activation of macrophages.
5. Endogenous immunostimulants
6. Deoxycholic acid, a stimulator of macrophages
7. Synthetic immunostimulants
8. Imiquimod and resiquimod, activate immune cells through the toll-like receptor 7

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H. IMMUNOSUPRESSION
Immunosuppressants are a group of drugs that are used to suppress immune responses such as
preventing rejection of transpalansi, overcoming autoimmune diseases and preventing rhesus and
neonatal hemolysis. Some of these groups are cytotoxic and are used as anticancer.

Immune response
In high-level creatures such as vertebrates and humans, there are two systems of defense (immunity),
namely non-specific immunity (adaptive immunity).
1.Non-specific immunity

Is a leading defense mechanism that includes physical components such as the integrity of the skin
and mucosa; biochemical components such as stomach acid, lysozyme, komploment; and
nonspecific cellular components such as neutrophils and macrophages. Neutrophils and
macrophages phagocytosis of foreign bodies and produce various mediators to attract other
inflammatory cells in the area of infection. Furthermore, foreign objects will be destroyed by an
inflammatory mechanism.
2. Specific immunity
Having a special characterization includes the ability to react specifically with certain antigens; the
ability to distinguish foreign antigens from their own antigen (nonself to self); and the ability to react
faster and more efficiently to previously known antigens. This specific immune response consists of
two immune systems, namely cellular immunity and humoral immunity. Seluer immunity involves
T lymphocyte cells, while humoral immunity involves B lymphocytes and plasma cells that function
to produce antibodies.Activity of specific immune responses.Specific immune system activity
requires the participation of cell groups called antigen presenting cells

Immunosuppressant indications
Immunosuppressants are used for three main indications namely, organ transplantation, autoimmune
disease, and prevention of Rhesus hemolysis in neonates.
1. organ transplant
2. autoimmune disease
3. prevention of Rhesus hemolysis in neonates
General principle of immunosuppressant therapy
The general principle of using immunosuppressants to achieve optimal therapeutic results is as
follows:
1. Primary immune responses are easier to control and suppress compared to secondary immune
responses. The initial stage of the primary response includes: antigen treatment by APC,
lymphokine synthesis, proliferation and differentiation of immune cells. This stage is the most

22
sensitive to immunosuppressant drugs. Conversely, once formed memory cells, the effectiveness
of immunosuppressant drugs will be much reduced.
2. Immunosuppressant drugs have different effects on different antigens. The dose needed to
suppress the immune response to an antigen is different from the dose for other antigens.
3. Inhibition of the immune response is more successful if immunosuppressant drugs are given
before exposure to antigens. Unfortunately, almost all autoimmune diseases can only be known
after autoimmunity develops, so it is relatively difficult to overcome.

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CONCLUDING

1. The immune system attacks organisms and substances that invade body systems and cause disease.
2. The imunnity has 2 types, that are nature and adaptive
3. There are 3 types of imunne system disorders. That are hypersensitivity,autoimunne, and
imunnodeficiency
4. .hypersensitivity has 4 types that are type 1,2,3 and 4.
5. Allergy is an abnormal immunological response to an otherwise harmless environmental stimulus.
Allergy is one type from hypersensitivity, that is first type of hypersensitivity. The reaction is the
result of an antigen cross-linking with membrane-bound IgE antibody of a mast cell or basophil.
6. Suplement cannot treat alergy because the character imunne system of alergy is specific
7. Allergy treatment can use imunnotherapy or antihistamin drug. Antihistamin drug that don’t causes
drowsiness are second type of anthihistamin.
8. Immunomodulators are certain compounds that can enhance the body's defense mechanisms both
specifically and non-specifically, and non-specific inductions occur both cellular and humoral
defense mechanisms. It has 3 types, that are imunnomodulator, imunnostimulant, and
imunnodeficiency.

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