HYPERSENSITIVITY
Occasionally, the immune system responds inappropriately to the presence
of antigen. These responses are referred to as hypersensitivities.
Hypersensitivity reactions to usually harmless substances are called allergies
or allergic reactions. Antigens that cause allergic reactions are allergens.
Hypersensitivities are categorized according to which parts of the immune
response are involved and how quickly the response occurs. There are four
different types of hypersensitivities or allergic reactions. These types are
classified as
Type I: Immediate Hypersensitivity (IgE mediated)
Type II:-Cytotoxic Hypersensitivity
Type III: Immune Complex-mediated Hypersensitivity that result
from different alterations of the immune system.
Type IV: Delayed Hypersensitivity(cell mediated) \
The first three types are antibody –dependent while the fourth type is cell
mediated, however some overlapping between the various types does occur.
TYPE IMMUNE MEDIATORS MECHANIS CLINICAL
REACTIONS M OF DISORDERS
CELLS AND TISSUE
MOLECULES INJURY
Type 1 Antibody- IgE, mast cells, Allergic Hay fever,
mediated granules, anaphylactic Asthma
(immediate histamine, reactions. Bronchitis,
hypersensitivity cytokines Rhinitis,
)
Type II Antibody Complement Target cell Good-pastures
dependent effector cells lysis, cell- syndrome
Complement or (Macrophages mediated Haemolytic
cell mediated and cytotoxicity disease of new
hypersensitivity polymorphonucl born (HDN),
ear cells) Blood-mismatch,
pernicious-
anaemia, and
pemphigus
Type Immune Antigen/ Immune Systemic-lupus
III complex- antibody complex erythematosus
mediated complexes deposition, (SLE)
hypersensitivity Complement inflammation Serum sickness
Macrophages, Rheumatoid
cytokines, mast arthritis
cells Glomerulonephri
tis
Farmers lung
Type T –cell Antigen specific Inflammation -Contact
IV mediated T cells,T -cell , hypersensitivity
Hypersensitivit cytokines Cellular -Tuberculin skin
y infiltration test,
(Delayed type) -granuloma
Type I Hypersensitivity
Immediate hypersensitivity reaction (type I) is mediated by an antibody
(IgE) and occurs immediately after a second or subsequent contact with the
same antigen, commonly referred to as allergen. Examples of allergens
include pollen, some drugs (eg penicillin, sulphur), venoms, semen, insect
bites, certain foods, some chemicals etc. the immune response that follows
the contact with a particular allergen is commonly referred to as an allergic
reaction or allergy
The reaction elicited by antigen occurs very rapidly (hence the name
"immediate hypersensitivity").
The hypersensitivity is mediated via serum-derived components (i.e.
antibody). The hypersensitivity is antigen-specific (as one might expect for
an antibody-mediated reaction). The details of this reaction can be
summarized as follows:
Initial introduction of antigen produces an antibody response. More
specifically, the type of antigen and the way in which it is administered
induce the synthesis of IgE antibody in particular. Immunoglobulin IgE
binds very specifically to receptors on the surface of mast cells, which
remain circulating. Reintroduced antigen interacts with IgE on mast cells
causing the cells to degranulate and release large amounts of
Vasoactive intermediates eg, histamine, heparin, bradykininsan
serotonins
lipid mediators and
chemotactic factors that cause smooth muscle contraction,
vasodilation leading to increased vascular permeability,
broncho constriction( bronchospasms) and oedema.
These reactions occur very suddenly, and can lead to death.
Examples of Type I hypersensitivities include allergies to penicillin, insect
bites, molds, etc.
A person's sensitivity to these allergens can be tested by a cutaneous
reaction. If the specific antigen in question is injected intradermally and the
patient is sensitive, a specific reaction known as wheal and flare can be
observed within 15 minutes. Individuals who are hypersensitive to such
allergens must avoid contact with large inocula to prevent anaphylactic
shock.
Type II Hypersensitivity- Cytotoxic
Type II or Cytotoxic Hypersensitivity involves antibody-dependent,
complement mediated cytotoxicity, cytolysis or tissue damage reactions.
However, the immunoglobulin class (isotype) involved is generally IgG. In
addition, this process involves K-cells rather than mast cells. K-cells are
involved in antibody-dependent cell-mediated cytotoxicity (ADCC).
Type II hypersensitivity may also involve complement that binds to cell-
bound antibody. The difference here is that the antibodies are specific for (or
able to cross-react with) "self" antigens. When these circulating antibodies
react with a host cell surface, tissue damage may result.
There are many examples of Type II hypersensitivity related diseases. These
include:
Pemphigus: IgG antibodies that react with the intracellular substance
found between epidermal cells.
Autoimmune haemolytic anaemia (AHA): This disease is generally
inspired by a drug such as penicillin that becomes attached to the
surface of red blood cells (RBC) and acts as hapten for the production
of antibody which then binds the RBC surface leading to lysis of
RBCs.
Good pasture's syndrome: Generally manifested as a
glomerulonephritis, IgG antibodies that react against glomerular
basement membrane surfaces can lead to kidney destruction.
Type III Hypersensitivity –immune complex mediated hypersensivity
Type III or Immune Complex hypersensitivity involves circulating antibody
that reacts with free antigen. These circulating antigen antibody complexes
can then become deposited on tissues. Tissue deposition may lead to
reaction with complement or trigger of the complement cascade, causing
tissue damage. This type of hypersensitivity develops as a result of
systematic exposure to an antigen and is dependent on
i) The type of antigen and antibody involved
Ii) the size of the resulting complex
More specifically, complexes that are too small remain in circulation;
complexes too large are removed by the glomerulus; intermediate
complexes may become lodged in the glomerulus leading to kidney
damage.
Example of Type III hypersensitivity include
a) serum sickness, a condition that may develop when a patient is
injected with a large amount of e.g. antitoxin that was produced
in an animal. After about 10 days, anti-antitoxin antibodies react
with the antitoxin forming immune complexes that deposit in
tissues.
b) Rheumatoid arthritis-this occurs as inflammation of the joints
c) Systemic lupus erythematous
d) Glomerulonephritis affects glomerulus of the kidney nephron
leading to inflammation directed at basement of glomerulus
Type III hypersensitivities can be ascertained by intradermal injection of
the antigen, followed by the observance of an "Arthus" reaction
(swelling and redness at site of injection) after a few hours.
Type IV Hypersensitivity T cell mediated hypersensitivity
DTH occurs when an antigen that remains within a macrophage after
phagocytosis is encountered by previously activated T cells for a second or
subsequent time. The antigen specific T lymphocytes release cytokines following a
secondary contact with the same non self antigen. The released cytokines induce
an inflammatory reaction and activate and attract macrophages, causing cellular
infiltration and resulting to oedema at the tissue site
The reaction elicited by antigen occurs relatively slowly (hence the
name “delayed hypersensitivity").
The hypersensitivity is mediated via T -cells and macrophages.
The hypersensitivity illustrates both antigen-specific (T-cell) and
antigen non-specific (macrophage) characteristics.
.
SUMMARY –HYPERSENSITIVITY
In Type I hypersensitivities, IgE is usually attached to mast cells or
basophils reacts with specific antigen, resulting in the release of powerful
mediators of the allergic reaction.
Localized anaphylactic (type I) reactions include hives, (urticaria), hay fever
(allergic rhinitis), and asthma. Generalized or systemic anaphylaxis is a rare
but serious reaction that can lead to shock and death.
Desensitization or immunotherapy is often effective in decreasing the type I
hypersensitivity state. A new treatment, using an engineered anti-IgE, is
proving effective in treating asthma.
Type II hypersensitivity reactions, or cytotoxic reactions, are caused by
antibodies that can destroy normal cells by complement lysis or by antibody-
dependent cellular cytotoxicity (ADCC). It includes transfusion reactions
and the ABO blood groups have been the major cause of transfusion
reactions. It is also evidenced as the haemolytic disease of the new born. The
rhesus blood groups are usually responsible for this disease
Type III hypersensitivity reactions are mediated by small antigen-antibody
complexes that activate complement and other inflammatory systems, attract
neutrophil, and contribute to inflammation. The small immune complexes
are often deposited in small blood vessels in organs, where they cause
inflammatory disease e.g. glomerulonephritis in the kidney or arthritis in the
joints.
Type IV hypersensitivities also known as delayed hypersensitivity reactions
depend on the actions of sensitized T- lymphocytes. Examples include the
Tuberculin skin test, a positive reaction to protein antigens of the tubercle
bacillus introduced under the skin peaks 2 to 3days after exposure to the
antigen. Contact hypersensitivities involve contact allergy or contact
dermatitis which occurs frequently in response to substances such as poison
ivy, nickel in jewellery and chromium salts in leather products. Delayed
hypersensitivity is important in response to many chronic, long-lasting
infectious diseases.
