WIKIPEDIA
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Hypersensitivity
Hypersensitivity (also called hypersensitivity reaction or
intolerance) is an abnormal physiological condition in which
there is an undesirable and adverse immune response to
antigen.“l2] Jt is an abnormality in the immune system that
i i including allergies and autoimmunity. It
is caused by many types of particles and substances from the
external environment or from within the body that are recognized
by the immune cells as antigens.{3) The immune reactions are
usually referred to as an over-reaction of the immune system and
they are often damaging and uncomfortable.!41
Hypersensitivity
‘Types of hypersensitivity reactions
In 1963, Philip George Houthem Gell and Robin Coombs
introduced a systematic classification of the different types of
hypersensitivity based on the types of antigens and immune responses involved. According to this
system, known as the Gell and Coombs classification!) or Gell-Coombs's classification, |®! there are
four types of hypersensitivity, namely, type I, which is an IgE mediated immediate reaction; type II,
an antibody-mediated reaction mainly involving IgG or IgM; type III, an immune complex-mediated
reaction involving IgG, complement system and phagocytes; type IV, a cytotoxic, cell-mediated,
delayed hypersensitivity reaction involving T cells.'7!
Specialty Immunology
The first three types are considered immediate hypersensitivity reactions because they oceur within
24 hours. The fourth type is considered a delayed hypersensitivity reaction because it usually occurs
more than 12 hours after exposure to the allergen, with a maximal reaction time between 48 and 72
hours.81 Hypersensitivity is a common occurrence, it is estimated that about 15% of humans have at
least one type during their lives, and has increased since the latter half of the 20th century.!9!
Gell and Coombs classification
The Gell and Coombs classification of hypersensiti
is the most widely used, and distinguishes four
types of immune response which result in bystander tissue damage.1Type Alternative names
= Allergy
= Immediate
= Anaphylactic
& Antibody-dependent
Ms Immune complex
= Delayed,!*tlt2]
+ cell-mediated immune
memory response,
= Antibody-independent
= Cytotoxic
Immunologic aspects of hypersensitivity reactions
Immunologie
React
Fast response which
occurs in minutes, rather
than maltiple hours or
days, Free antigens
cross link the IgE on
mast cells and basophils
which causes a release
of vasoactive
biomolecules, Testing
can be done via skin test
for specific IgE")
= Antibody Ig
Antibody (IgM or 1g)
tinds to antigen on a
target cell which is
actualy ahost coll thats
perceived by the immune
System as foreign,
teading o celular
destruction via the MAC.
Testing includes both the
direct and indrect
Coombs test!"
= Antibody IgM
= Antibody lg
= Complement
= MAC
Antibody (IgG) binds to
soluble antigen, forming
a circulating immune
complex. This is offen
deposited in the vessel
walls of the joints and
kidney, initiating a local
inflammatory reaction (13)
= Antibody 1g
= Complement
= Neutrophils
Cells CTL's and T helper cells
(specifically Tt and
Ty17 celts)"4l are
activated by an antigen
presenting cell. When the
antigen is presented
again in the future, the
memory Tht cells will
activate macrophages
and cause an
inflammatory response.
This ultimately can lead
to tissue damage [1
= Tells
Examples
‘Atopy
Anaphylaxis
Asthma
Churg-Strauss
‘Syndrome
‘Autoimmune
hemolytic anemia
Rheumatic heart
disease
Thrombocytopenia
Erythroblastosis
felalis
Goodpasture's
syndrome
Graves’ disease
Myasthenia gravis
Pemphigus vulgaris
Serum sickness
Rheumatoid arthritis
Arthus reaction
Post streptococcal
glomerulonephritis
Membranous
nephropathy
Reactive arthritis
Lupus nephritis
Systemic lupus
erythematosus
Extrinsic allergic
alveolits
(hypersensitivity
pneumonitis)
Contact dermatitis,
including Urushiol:
induced contact
dermatitis (poison
ivy rash).
Mantoux test
Chronic transplant
rejection
Multiple sclerosis!
Cooliac diseaseAntibodies or Cell Immunologic
Type Alternative names bodies or ununolog Examples
+ Hashimoto's
thyroiditis
+ Granuloma annulare
Type I hypersensitivity
logy
Type I hypersensitivity occurs as a result of exposure to an aa
antigen, The antigens are proteins with a molecular weight
ranging from 10 to 40 kDa.!9! The response to the antigen occurs
in two stages: the sensitization and the effect stage. In the
"sensitization" stage, the host experiences an asymptomatic
contact with the antigen. Subsequently, in the "effect" period, the
pre-sensitized host is re-introduced to the antigen, which then “jype hypersensitivity
leads to a type I anaphylactic or atopic immune response.17]
Types of antigens involved
= Food: nuts, eggs, soy, wheat, shellfish, etc,
= Animal source: bees, wasp, cats, insects, rats, etc.
= Environmental factors: dust mites, latex, pollen, mold, flowers smell, etc.
= Atopic diseases: allergic asthma, allergic rhinitis, conjunctivitis, dermatitis, ete.
= Medication-induced reactions: antibiotics!"7)
Type II hypersensitivity
‘Type II hypersensitivity reaction refers to an antibody-mediated immune reaction in which antibodies
(IgG or IgM) are directed against cellular or extracellular matrix antigens with the resultant cellular
destruction, functional loss, or damage to tissues.(9! The antigens may be for example glycoproteins
on the cell membrane of erythrocytes that are key molecules that determine blood types. Depending
on the chemical nature of the antigens, blood types have different levels of hypersensitivity; for
instance, A and B are more antigenic than other antigens. 9!
Damage can be accomplished via three different mechanisms:!91
= Antibody binding to cell surface receptors and altering its
activity
= Activation of the complement pathway.
= Antibody-dependent cellular cytotoxicity.
The pathophysiology of type II hypersensitivity reactions can be
@ I hypersensitivity
broadly classified into three types:!9] ype Il hype y
= Cell depletion or destruction without inflammation= Inflammation mediated by complement or Fe receptor
= Cellular dysfunction by antibodies
The process involves a series of immune-mediated events that might take different forms.(!8]
Type III hypersensitivity
In type III hypersensitivity reaction, an abnormal immune EEE
response is mediated by the formation of antigen-antibody Saaah aioe
aggregates called "immune complexes". They can precipitate in =e
various tissues such as skin, joints, vessels, or glomeruli, and
trigger the classical complement pathway. Complement activation
leads to the recruitment of inflammatory cells (monocytes and
neutrophils) that release lysosomal enzymes and free radicals at
the site of immune complexes, causing tissue damage.!71
Type Ill hypersensitivity
The most common diseases involving a type III hypersensitivity reaction are serum sickness, post-
streptococcal glomerulonephritis, systemic lupus erythematosus, farmers’ lung (hypersensitivity
pneumonitis), and rheumatoid arthritis.
The principal feature that separates type III reactions from other hypersensitivity reactions is that in
type III reaction, the antigen-antibody complexes are pre-formed in the circulation before their
deposition in tissues.!7)
Type IV hypersensitivity
‘Type IV hypersensitivity reactions are, to some extent, normal
physiological events that help fight infections, and dysfunction in eae
this system can predispose to multiple opportunistic infections. we :
Adverse events can also occur due to these reactions when an
undesirable interaction between the immune system and an
allergen happens.'8!
Type IV hypersensitvly
Pathophysiology
A type IV hypersensitivity reaction is mediated by T cells that provoke an inflammatory reaction
against exogenous or endogenous antigens. In certain situations, other cells, such as monocytes,
eosinophils, and neutrophils, can be involved. After antigen exposure, an initial local immune and
inflammatory response occurs that attracts leukocytes. The antigen engulfed by the macrophages and
monocytes is presented to T cells, which then becomes sensitized and activated. These cells then
release cytokines and chemokines, which can cause tissue damage and may result in illnesses.)
Examples of illnesses resulting from type IV hypersensitivity reactions include contact dermatitis and
drug hypersensitivity. Type IV reactions are further subdivided into type IVa, IVb, IVe, and IVd based
on the type of T cell (Th1, Th17, and CTLs) involved and the cytokines/chemokines produced.|8)Delayed hypersensitivity plays a crucial role in our body's ability to fight various intracellular
pathogens such as mycobacteria and fungi. They also play a principal role in tumor immunity and
transplant rejection. Since patients with acquired immunodeficiency syndrome (AIDS) have a
progressive decline in the number of CD4 cells, they also have a defective type four hypersensitivity
reaction,/81
Treatment
Immediate hypersensitivity reactions
The treatment of immediate hypersensitivity reactions includes the management of anaphylaxis with
intramuscular adrenaline (epinephrine), oxygen, intravenous (IV) antihistamine, support blood
pressure with IV fluids, avoid latex gloves and equipment in patients who are allergic, and surgical
procedures such as tracheotomy if there is severe laryngeal edema.!9!
1. Allergic bronchial asthma can be treated with any of the following: inhaled short- and long-acting
bronchodilators (anticholinergics) along with inhaled corticosteroids, leukotriene antagonists, use
of disodium cromoglycate, and environmental control. Experimentally, a low dose of methotrexate
or cyclosporin and omalizumab (a monoclonal anti-IgE antibody) has been used
2. Treatment of autoimmune disorders (e.g., SLE) include one or a combination of NSAIDs and
hydroxychloroquine, azathioprine, methotrexate, mycophenolate, cyclophosphamide, low dose IL-
2, intravenous immunoglobulins, and belimumab.
3. Omalizumab is a monoclonal antibody that interacts with the binding site of the high-affinity IgE
receptor on mast cells. It is an engineered, humanized recombinant immunoglobulin. Moderate to
severe allergic bronchial asthma can improve with omalizumab.!°l
Delayed hypersensitivity reactions
Treatment of type 4 HR involves the treatment of the eliciting cause.
1. The most common drugs to treat tuberculosis include isoniazid, rifampin, ethambutol, and
pyrazinamide. For drug-resistant TB, a combination of antibiotics such as amikacin, kanamycin, or
capreomycin should be used.
2. The most common drugs to treat leprosy include rifampicin and clofazimine in combination with
dapsone for multibacillary leprosy. A single dose of antimicrobial combination to cure single lesion
paucibacillary leprosy comprises ofloxacin, rifampicin, and minocycline,
3. Praziquantel can be useful for treating infections caused by all Schistosoma species
4, Hydroxychloroquine and chloroquine can use in the therapy of sarcoidosis involving the skin,
lungs, and the nervous system.
5. The use of anti-TNF monoclonal antibodies such as adalimumab and certolizumab have been
approved for Crohn disease.!'9]
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