Hapten

• Hapten is a molecule that reacts with specific antibody but is not immunogenic by itself, it can be made immunogenic by conjugation to a suitable
carrier.
• A hapten is essentially an incomplete antigen. These small molecules can elicit an immune response only when attached to a large carrier such as a
protein; the carrier typically does not elicit an immune response by itself.
• Haptens frequently bind to proteins in blood serum, such as albumin. If the hapten-albumin complex is larger than 3,000 MW, it becomes
immunogenic.
• Some haptens can bind to cell membranes,
including red blood cells. In this instance,
the cell-small molecule is then called a
“neoantigen”.
 How do pharmaceutical drugs become haptens ?
• Pharmaceutical drugs are typically small molecules and can be haptens which bind to
proteins in the blood.
• Once the immune response is elicited, this causes an immune reaction to the drug and
this can lead to skin eruptions or anaphylactic shock in severe cases.
• Penicillins antibiotics is broken down by beta-lactamase enzymes and produce
benzylpenicilloyl derivatives which can then bind to other proteins and then elicit an
immune response.
• This is one of the causes of adverse immune-mediated reactions upon subsequent
exposure to penicillins. Adverse reactions are highly dangerous and can range from
urticaria, asthma, angioedema and, in most severe cases, anaphylaxis.
• Cephalosporins, can also elicit and immune response as a hapten.
How do pharmaceutical drugs become haptens ?
Anesthetics
•Halothane became used around 1950s as an anesthetic agent. It is potent, non-
flammable and metabolized to trifluoroacetyl chloride. Trifluoroacetyl chloride
then reacts with proteins in the liver to form a neoantigen, and once the
immune response to this neoantigen is elicited then subsequent exposure to
halothane can lead to inflammation of the liver through the activation of this
immune response.
•Drugs such as ibuprofen can form neoantigens with red blood cells. Once an
immune response is elicited, and this then leads to lysis of the neoantigenic red
blood cells (hemolytic anemia).
 AUTOIMMUNITY
• The immune system normally guards against germs like bacteria and viruses. When it
senses these foreign invaders, it sends out an army of fighter cells to attack them.
• Normally, the immune system can tell the difference between foreign cells and your
own cells.
• An autoimmune disease is a condition in which your immune system mistakenly
attacks your body.
• In an autoimmune disease, the immune system mistakes part of your body, like your
joints or skin, as foreign. It releases proteins called autoantibodies that attack healthy
cells.
• The term autoimmunity refers to a failure of the body’s immune system to recognize
its own cells and tissues as “self”. Instead, immune responses are launched against
these cells and tissues as if they were foreign or invading bodies
• Some autoimmune diseases target only one organ. Type 1 diabetes damages the
pancreas. Other diseases, like systemic lupus erythematosus (SLE), affect the whole
body.
 Autoimmune Disease Mechanism
• Autoimmune disease occurs when an immune response attacks our own tissues.
• In this disorder, tissue injury is caused by an immunologic reaction of the host
to its own tissues.
• The exact mechanisms is still unknown. A number of theory have been
proposed.
Forbidden clone:-
• Mutation cause formation of altered lymphocytes due to which host tissue is
recognized as foreign.
• This is main cause of increased incidence of autoimmune disease in elderly
person.
Altered Antigen
• Surface antigens on host altered by chemical, biological or physical means.
• This new antigenic determinant may be recognized as foreign by the host.
 Autoimmune Disease Mechanism
Sequestered Antigen
•Some antigens in the body are hidden from cells of the immune system.
•If there is damage to these organs causing exposure of these sequestered
antigens an immune reaction to these antigens may occur.
Immunologic Deficiency Theory
•Relates the increased frequency of auto-antibodies and increased immune
system deficiency to age.
•Mutation or loss of immune regulatory powers results in the condition in which
self antigens behave as foreign antigens.
Genetic Influence
•It is well recognized that certain immune disorders predominate in females and
in families.
•Determined by family studies.
•Genetic links have occurred between diseases and HLA antigens
 Classification of Autoimmune Diseases
• It comprising of multiple disorders and symptoms ranging from organ-specific
to systemic.
• Systemic- the auto-immunity is directed against an antigen that is present at
many different sites and can include involvement of several organs.
• Organ specific - Organ specific means
the auto-immunity is directed against a
component of one particular type of organ.
• Both – can get overlap.
 Most common autoimmune diseases
Type 1 diabetes
•The pancreas produces the hormone insulin, which helps regulate blood sugar
levels.
•In type 1 diabetes mellitus, the immune system attacks and destroys insulin-
producing cells in the pancreas.
•High blood sugar results can lead to damage in the blood vessels, as well as
organs like the heart, kidneys, eyes, and nerves.
Rheumatoid arthritis (RA)
•In rheumatoid arthritis (RA), the immune system attacks the joints. This attack
causes redness, warmth, soreness, and stiffness in the joints.
•Unlike osteoarthritis, which commonly affects people as they get older, RA can
start as early as your 30s or sooner.
 Most common autoimmune diseases
Psoriasis/psoriatic arthritis
•Skin cells normally grow and then shed when they’re no longer needed.
•Psoriasis causes skin cells to multiply too quickly. The extra cells build up and
form inflamed red patches, commonly with silver-white scales of plaque on the
skin.
•Up to 30 percent of people with psoriasis also develop swelling, stiffness, and
pain in their joints. This form of the disease is called psoriatic arthritis.
 Most common autoimmune diseases
Multiple sclerosis
•Multiple sclerosis (MS) damages the myelin sheath, the protective coating that
surrounds nerve cells, in your central nervous system.
•Damage to the myelin sheath slows the transmission speed of messages between
your brain and spinal cord to and from the rest of your body.
•This damage can lead to symptoms like numbness, weakness, balance issues, and
trouble walking. The disease comes in several forms that progress at different
rates.
Inflammatory bowel disease (IBD)
•IBD is a term used to describe conditions that cause inflammation in the lining of
the intestinal wall. Each type of IBD affects a different part of the GI tract.
•Crohn’s disease can inflame any part of the GI tract, from the mouth to the anus.
•Ulcerative colitis affects only the lining of the large intestine (colon) and rectum.
 Most common autoimmune diseases
Systemic lupus erythematosus (SLE)
•Systemic lupus erythematosus (lupus). People with lupus develop autoimmune
antibodies that can attach to tissues throughout the body.
•The joints, lungs, blood cells, nerves, and kidneys are commonly affected in
lupus.
Addison’s disease
•Addison’s disease affects the adrenal glands
•Having too little of cortisol can affect the way the body uses and stores
carbohydrates and sugar (glucose).
•Deficiency of aldosterone will lead to sodium loss and excess potassium in the
bloodstream.
•Symptoms include weakness, fatigue, weight loss, and low blood sugar.
 Most common autoimmune diseases
Graves’ disease
•Graves’ disease attacks the thyroid gland in the neck, causing it to produce too much of
its hormones. Thyroid hormones control the body’s energy usage, known as metabolism.
•Having too much of these hormones revs up your body’s activities, causing symptoms
like nervousness, a fast heartbeat, heat intolerance, and weight loss.
•One potential symptom of this disease is bulging eyes, called exophthalmos.
Hashimoto’s thyroiditis
•In Hashimoto’s thyroiditis, thyroid hormone production slows to a deficiency.
Symptoms include weight gain, sensitivity to cold, fatigue, hair loss, and swelling of the
thyroid (goiter)