Hypersensitivity
Hypersensitivity
Hypersensitivity
MEGI KHABAZI
Hypersensitivity:
When immune system works properly, it helps in elimination or removal of
antigens from host body by means of effector molecules.
The effectors molecules generally induce local inflammatory response and
removes antigen without extensively damaging host tissues.
However in certain conditions such as when immune system does not work
properly or over activated, it causes deleterious effects resulting in
significant tissue damage, serious disease and even death. Such unwanted,
inappropriate and damaging immune response is termed
as hypersensitivity.
Hypersensitivity reaction may develops in course of either cell mediated or
humoral immune response
Various autoimmune disorders as well as allergies fall under the umbrella of
hypersensitivity reactions, the difference being that allergies are immune reactions
to exogenous substances (antigens or allergens), whereas autoimmune diseases
arise from an abnormal immune response to endogenous substances
(autoantigens).
Gell and Coomb’s Classification of Hypersensitivity
reaction
2 3
Transmission electron micrograph showing a skin mast cell containing many
prominent electron-dense granules
The reaction of antibody with antigen generates immune complex. In most of the cases, these immune
complexes are removed from blood circulation. Some immune complexes are removed by phagocytic action of
phagocytic cells in blood. Most other immune complexes are first carried by blood to spleen where they are
destroyed by macrophages. Complement system is also needed for removal of immune complexes from blood
to spleen.
In some cases large amount of immune complexes are formed and deposited on various body parts and leads to
tissue damage resulting in Type III hypersensitivity reaction.
If immune complexes are not removed from blood, they accumulate on wall of blood vessels and on tissue .
Type III hypersensitivity reaction is characterized by deposition of immune complexes on various tissues such
as wall of blood vessels, glomerular basement membrane of kidney, synovial membrane of joints and choroid
plexus of brain.
Deposition of immune complexes initiates reaction resulting in damage of surrounding tissue and cause
inflammation.
Type III hypersensitivity reaction is characterized by deposition of immune complexes on various tissues
such as wall of blood vessels, glomerular basement membrane of kidney, synovial membrane of joints
and choroid plexus of brain.
Deposition of immune complexes initiates reaction resulting in damage of surrounding tissue and cause
inflammation.
In some cases large amount of immune complexes are formed and deposited on various body parts and
leads to tissue damage resulting in Type III hypersensitivity reaction.
If immune complexes are not removed from blood, they accumulate on wall of blood vessels and on
tissue .
Factors that causes deposition of immune complex and increase
susceptibility to Type III hypersensitivity reaction:
1. Persistent infection:
In persistent infection such as Malaria, large number of immune complexes are formed and deposited
in tissues.
2. Complement deficiency:
Complement removes immune complexes from blood, but when complement system is deficient,
large amount of immune complexes circulates in blood and deposits in tissues.
3. Autoimmunity:
In autoimmune disease, large amount of immune complexes are formed and deposited in tissues.
4. Genetic defects:
In certain genetic defects, small and soluble immune complexes are formed that can not be
phagocytosed.
Types of Type III hypersensitivity
reaction:
1. Localized Type III hypersensitivity reaction:
2. Generalized Type III hypersensitivity reaction:
1. Localized Type III hypersensitivity
reaction:
Acute Arthus reaction is an example of localized Type
III hypersensitivity reaction.
When antigen is injected or enters intradermally or
subcutaneously, they bind with antibody to form
localized immune complexes which mediate acute
Arthus reaction within 4 to 8 hours.
As the reaction develops, localized tissue damage and
vascular damage results in accumulation of fluids
(edema) and RBCs (erythema) at the site of antigen
entry.
The severity of reaction can vary from mild swelling
and redness to tissue necrosis.
2. Generalized Type III hypersensitivity
reaction:
Serum sickness is an example of generalized Type III hypersensitivity reaction.
When large amount of antigen enter blood stream and bind to antibody, circulating immune
complexes forms.
If antigens are in significantly excess compared to antibody, the immune complexes formed are
smaller and soluble which are not phagocytosed by phagocytic cells leading to Type III
hypersensitivity reaction.
The manifestation of serum sickness depends on the quantity of immune complex as well as
overall site of deposition. The site may vary but accumulation of complexes occurs at site of
blood filtration.
Generalized Type III hypersensitivity reaction at different site results in different diseases such
as Glomerulonephritis (Kideny), vasculitis (arteries), Arthritis (synovial joints).
Serum sickness
The cardinal features of serum
sickness are rash, fever, and
polyarthralgias or polyarthritis,
which begin one to two weeks after
the first exposure to the responsible
agent and resolve within a few
weeks of discontinuation.
Although patients may appear very
ill and uncomfortable during the
acute febrile stage, the disease is
self-limited, and prognosis is
excellent once the responsible drug
is stopped.
Type IV hypersensitivity reaction or
Delayed type hypersensitivity (DTH)
Type IV hypersensitivity reaction is also known as delayed type hypersensitivity (DTH).
When some subpopulation of activated T helper cells encounters certain antigen, they
secrete cytokines that induce a localized inflammatory reaction called delayed type
hypersensitivity (DTH).
The reaction is characterized by influxes of non-specific inflammatory cells particularly
macrophages.
DTH occurs slowly and reaches a peak level within 48-72 hours after 2 nd encounter of
antigen.
In DTH tissue damage is mediated by Th cells and macrophages but not by antibodies.
Although DTH causes some tissue damage, it is very important defense mechanism
against intracellular microorganisms such as Mycobacterium tuberculosis,
Mycobacterium leprae,
DTH occurs in two phases:
Increased phagocytic activity and build up lytic enzyme from macrophages in the
area of infection leads to non-specific destruction of tissues and intracellular
pathogens.
Generally pathogens are killed rapidly with little tissue damage. However in some
case, especially if the antigen is not easily cleared, a pro-long DTH response can
itself become destructive to host as intensive and chronic inflammation develops
into a visible granulomatous reaction.
A granuloma develops when continuous activation of macrophages induces the
epitheloid shape and some time fusion of macrophages to form multinucleated
giant cells. These giant cells displace normal cells forming palpable nodules and
release high concentration of lytic enzymes which destroy surrounding tissues
leading to necrosis.
Some examples of Type IV
hypersensitivity reaction:
Acute and chronic transplant rejection
Contact dermatitis (e.g., nickel, poison ivy, cosmetics, rubber gloves)
Drug reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with
eosinophilia and systemic symptoms (DRESS)
Graft-versus-host disease
Mantoux tuberculin skin test for latent tuberculosis
Candida skin test
Multiple sclerosis
Guillain-Barré syndrome
Hashimoto's thyroiditis
Rheumatoid arthritis
Type 1 diabetes mellitus
Thank you!