Normally the immune system plays an important role in protecting the body from microorganisms and other foreign substances. If the activity of the immune system is excessive or overreactive, a hypersensitivity reaction develops. The consequences of a hypersensitivity reaction may be injury to the body or death.

1. HYPERSENSITIVITY
REACTIONS
RESHMA FATHIMA K
Assistant Professor

2. Introduction
• Certain human disorders are attributed to activity of the immune system. These
disorders are commonly known as hypersensitivities, states of increased immune
sensitivity that are mediated by antibody or cellular factors. The disorders may also
involve immunodeficiencies in which failures of antibody‐mediated or cell‐mediated
immunity take place.
• Normally the immune system plays an important role in protecting the body from
microorganisms and other foreign substances. If the activity of the immune system is
excessive or overreactive, a hypersensitivity reaction develops. The consequences of a
hypersensitivity reaction may be injury to the body or death.
• Most injury resulting from hypersensitivities develops after an interaction has taken
place between antigens and antibodies or between antigens and sensitized T-
lymphocytes. The general nature of and symptoms accompanying the reaction
depend upon whether antibodies or sensitized T-lymphocytes are involved.

3. • When antibodies are involved, the reactions fall under the heading of immediate
hypersensitivity. When T-lymphocytes are involved, the reactions are characterized as
delayed hypersensitivity. Immediate hypersensitivity reactions include anaphylaxis,
allergic reactions, cytotoxic reactions, and immune complex reactions. Delayed
hypersensitivity reactions are generally characterized as contact dermatitis or
infection allergies.
TYPES OF HYPERSENSITIVE REACTIONS
TYPE I – IMMEDIATE, ATOPIC, ANAPHYLACTIC
TYPE II – ANTIBODY DEPENDANT (CYTOTOXIC REACTIONS)
TYPE III – IMMUNE COMPLEX
TYPE IV – CELL MEDIATED / DELAYED TYPE OF HYPERSENSITIVITY

4. • Immediate hypersensitivity (TYPE 1) The reactions accompanying immediate
hypersensitivity depend upon the nature of the antigen, the frequency and
route of antigen contact, and the type of antibody reacting with the antigen.
The initial dose of antigen is referred to as the sensitizing dose. This exposure is
followed by a latent period and then a later dose of the same antigen, called
the eliciting dose or shocking dose. The shocking dose sets off the
hypersensitivity reaction, resulting in tissue damage.
• Immediate reactions begin within minutes of contact with the eliciting dose of
antigen. If antigens are introduced directly into the tissues, such as by insect
sting or injection, the result is a systemic reaction such as anaphylactic shock.
When the contact is a superficial one involving the epithelial tissues, the
reaction is more localized, as occurs in asthma or allergic rhinitis (hay fever).
These local reactions are commonly referred to as allergy. Another term used is
atopy.

5. • The antigens eliciting an immediate hypersensitivity are called allergens,
particularly when they are involved in local allergic reactions. Hapten
molecules such as penicillin molecules may be involved when they are
bound to larger protein molecules. Foods, feathers, pollen grains, animal
dander, and dust may be allergens. Animal sera, bee venoms, and wasp
venoms are also allergens.
• The antibodies involved in anaphylaxis reactions are of the type IgE. In
cytotoxic and immune complex reactions, IgG and IgM are involved.
• Anaphylaxis. Anaphylaxis, or type I hypersensitivity, is a whole-body,
immediate hypersensitivity also known as anaphylactic shock. The
allergens are introduced to the body directly to the tissues in a
concentrated form (intramuscular or intravenous injection, for example).

6. After the sensitizing dose has been administered, IgE is
produced by the plasma cells. The antibodies circulate in the
blood and attach at the Fc end to mast cells of the tissues and
basophils in the bloodstream (Figure 1 ). This activity occurs
during the latent period. When the eliciting dose of allergen is
later administered, the antigens combine with antibodies on
the surface of the mast cells and basophils.
Figure 1
The process of anaphylaxis. (a) Allergens stimulate the
production IgE antibodies, which (b) fix themselves to the
surfaces of mast cells. (c) On second exposure to the allergens,
a reaction occurs on the mast cell surface, and (d) the cellular
granules release histamine and other stimulators of smooth
muscle contraction

7. ANTIGEN – ANTIBODY COMBINATION Histamine and serotonin
Induce spasms of the
smooth muscle, such
as bronchioles, small
arteries and GIT lining
A sudden drop in blood pressure occurs, followed by
circulatory collapse and shock. Bronchospasms and edema
cause constriction of the respiratory passageways, and
breathing is very difficult.
Facial edema occurs, and the heart rate increases due to
constriction of the arteries. Swellings called “hives” develop at
the site of injection and other areas of the skin. In severe
cases, anaphylactic shock may result in death within several
minutes to an hour.
To relieve the symptoms, epinephrine is
administered together with a smooth
muscle relaxer, a drug such as cortisone
to reduce swelling, and other drugs as
appropriate
the cells release a number of physiologically active
substances including

8. • Allergic reactions. Allergic reactions (allergy) are a milder, localized form of
anaphylaxis. As noted, such things as foods, pollen grains, and animal dander can
induce these localized reactions. IgE, basophils, and mast cells are involved, but
much less than in anaphylaxis. There appears to be a genetic basis for allergic
reactions, as evidenced by their distribution in families.

9. • TYPE II HYPERSENSITIVITY REACTIONS
Cytotoxic reactions. Cytotoxic reactions are a form of immediate hypersensitivity,
sometimes referred to as type II hypersensitivity. In these reactions, IgE and IgM are
produced in response to stimulation by antigens. The antibodies unite with the
antigens in the bloodstream, but they also unite with analogous antigens on the
surface of the human body's cells. This union sets off the complement system, and
destruction of the local tissue cells ensues.
An example of a cytotoxic reaction is thrombocytopenia. In this disease, antibody
molecules are elicited by certain drug molecules. The antibodies unite with antigens
on the surface of thrombocytes (platelets), and with complement activation, the
thrombocytes are destroyed. The result is an impaired blood-clotting mechanism.
Another example of the cytotoxic reaction is agranulocytosis. In this immune
disorder, antibodies unite with antigens on the surface of neutrophils. As these cells
are destroyed with complement activation, the capacity for phagocytosis is reduced.

10. The cytotoxic reaction in erythroblastosis fetalis.
Cytotoxic reactions are also manifested by the transfusion
reaction occurring when improper blood transfusions are
performed. Another consequence is erythroblastosis
fetalis, also known as hemolytic disease of the newborn,
or Rh disease. In this condition, a pregnant woman
produces Rh antibodies against the developing fetus, and
when the Rh antibodies unite with Rh antigens on the
surface of fetal red blood cells in a succeeding pregnancy,
the red blood cells are destroyed (Figure 2 ).

11. • Immune complex disease. Immune complexes are combinations of antigen and
antibody that have the ability to fix complement. The antibodies involved are IgM
or IgG, and the antigens exist in fluid as soluble antigens. Proteins or nucleic acids
may be involved.
• An example of immune complex hypersensitivity is serum sickness. In this
condition, animal serum is administered to humans, and its proteins elicit
antibody production. When the antibodies and antigens unite, they form immune
complexes, which activate the complement system and cause local tissue
damage. The patient may display edema of the hands, face, and feet, as well as
swelling of the upper respiratory tissues and impairment of normal respiration.
An inflammatory response results.
• Formation of immune complexes is also involved with numerous diseases
includingsystemic lupus erythematosus, rheumatoid arthritis, and
glomerulonephritis.Immune complex hypresensitivity is often called type III
hypersensitivity.

12. In type 3 hypersensitivity reactions, insoluble immune complexes
(aggregations of antigens and IgG and IgM antibodies) form in the
blood and are deposited in various tissues
(typically the skin, kidney and joints)

13. This deposition of the antibodies may trigger an immune
response according to the classical pathway of
complement activation – for eliminating cells presenting
foreign antigens (which are usually, but not in this case,
pathogens). There are two stages relating to the
development of the complexes, firstly the complex forms
when IgG and IgM antibodies are bound to an antigen,
after this, the complexes can form larger ones which can
be cleared by the body. It is at the first stage of this
formation where clearance is not possible and the
antigen-antibody complex will spread and deposit as
stated above. The reaction takes hours to days to
develop

14. Tissue damage results at the site of the
immune complex with the influx of phagocytes
and granuloctyes and the release of
inflammatory mediators
Some examples:
• Immune complex glomerulonephritis
• Rheumatoid arthritis
• Serum sickness
• Subacute bacterial endocarditis
• Symptoms of malaria
• Systemic lupus erythematosus
• Arthus reaction
• Farmer’s Lung (Arthus-type reaction)

15. • Arthus reaction
• In immunology, the Arthus reaction is a type of local type III hypersensitivity
reaction. Type III hypersensitivity reactions are immune complex mediated, and
involve the deposition of an antigen/antibody complex mainly in the vascular
walls, serosa (pleura, pericardium, synovium), and glomeruli.

16. • Delayed hypersensitivity. (TYPE IV) T-lymphocytes rather than antibodies
function in cases ofdelayed hypersensitivity, also called type IV
hypersensitivity. Normally these are the T-lymphocytes involved in cell-
mediated immunity. The T-lymphocytes produce lymphokines, which stimulate
an influx of macrophages to perform phagocytosis. In delayed hypersensitivity,
the result is an exaggeration of the immune response, and the phagocytes
bring about the destruction of the local tissue.
• Delayed hypersensitivity (also called cellular hypersensitivity) is so named
because the reaction requires a day or more to develop. One manifestation of
the reaction isinfection allergy, as in the tuberculin skin test. A purified protein
derivative (PPD) ofMycobacterium tuberculosis is applied to the skin
superficially, and a skin reaction (swelling and redness) occurs 24 to 48 hours
later if the person has had a previous exposure to the antigens of
Mycobacterium tuberculosis, possibly during an episode of tuberculosis.

17. • A second manifestation of delayed hypersensitivity is contact dermatitis.
In many cases, the reaction is accompanied by large, blisterlike lesions in
which vesicles are surrounded by a zone of erythema (redness). Usually,
the vesicles itch intensely.
• Antigens involved in contact dermatitis include metals such as nickel and
mercury, cosmetics, disinfectants, and plant substances such as the
resins of poison ivy, poison oak, and poison sumac. The individual can be
tested to determine which antigen is the cause of allergy by performing a
patch test. In this procedure, a patch containing a specific antigen is
attached to the skin and left in place for 48 hours to determine if a
reaction will take place.