Hypersensitivity States

Hypersensitivity Reactions
Serah Wachira MscN

Objectives
Define relevant terms
Differentiate the four types of
hypersensitivity states
Classify the various immune reaction
diseases under the four types
Introduction
When the immune system "goes wrong" .
Immune response should be protective.
In this process damage to host occurs.
Hypersensitivity denotes a state of
increased reactivity of the host to an antigen
and implies that the reaction is damaging to
the host.
The individual must first have become sensitized by
previous exposure to the antigen.
On second and subsequent exposures, symptoms and
signs of a hypersensitivity state occur.
Definition of relevant terms
Immediate hypersensitivity refers to
antibody mediated reactions
symptoms develop within minutes to
hours
Delayed hypersensitivity refers to
cell mediated reaction, symptoms not
observed for 24 to 48 hours.
Four Classifications
Type I (Immediate) Hypersensitivity
Type II (cytotoxic) hypersensitivity
Type III (immune complex mediated)
hypersensitivity
Type IV (delayed) hypersensitivity
Rapid IgE antibody and mast cell mediated vascular
and smooth muscle reaction, often followed by
inflammation that occur in some individuals on
encounter with certain foreign antigens to which they
have been exposed previously
Also called allergy or atopy
Atopy inherited tendency to immunologically
respond to inhaled or ingested allergens with
increased IgE production.
Distinguishing feature short lag time.
Antigens which trigger response are called atopic
antigens or allergens.
Most frequent disorder of the immune system- affect
20% of population
Type I (Immediate)
Hypersensitivity
IgE primarily synthesized in lymphoid tissue
of respiratory and GI tract.
Regulated by T helper cells.
Basophils and mast cells have highest
number of receptors for Fc portion of IgE on
surface.
Type I (Immediate)
Hypersensitivity
Reactions range from mild manifestations
associated with food allergies to life-
threatening anaphylactic shock.
Atopic allergies include hay fever, asthma,
food allergies and eczema.
Exposure to allergens can be through
inhalation, absorption from the digestive
tract or direct skin contact.
Extent of allergic response related to port of
entry, i.e., bee sting introduces allergen
directly into the circulation.
Type I (Immediate)
Hypersensitivity: causes
Type I Hypersensitivity:
Pathophysiology
Production of IgE antibodies in response to an
antigen
Binding of IgE to Fc receptors of mast cells
Cross-linking of the bound IgE by the antigen and
release of mast cell mediators (sensitization)
Mediators cause a rapid increase in vascular
permeability and smooth muscle contraction
Next encounter with the antigen lead to
immediate hypersensitivity reaction
Late phase reaction caused by mast cell
medciator (cytokines) recruitment of neutrophils
and eosinophils to the site of reaction leading to
tissue injury resulting from repeated bouts of this
reaction
Clinical manifestation
This release leads to symptoms of:
sneezing,
runny noses,
red watery eyes and
wheezing.
Symptoms subside when allergen is
gone.
Type I clinical manifestation
Anaphylactic shock is the most serious and
fortunately the rarest form of this Type I
hypersensitivity.
Symptoms are directly related to the massive release
of vasoactive substances leading to fall in blood
pressure, shock, difficulty in breathing and even death.
It can be due to the following:
Horse gamma globulin given to patients who are
sensitized to horse protein.
Injection of a drug that is capable of acting as a
hapten into a patient who is sensitive, ie, penicillin.
Following a wasp or bee sting in highly sensitive
individuals.
Foods peanuts, shellfish, etc.
Type I (Immediate)
Hypersensitivity
Anaphylaxis
Type I (Immediate)
Hypersensitivity
Anaphylaxis
Type I (Immediate)
Hypersensitivity
Treatment
Avoidance of known allergens
Localized reactions use- antihistamines and
decongestants.
Asthma uses combination antihistamines,
bronchodilators and corticosteroids.
Systemic use epinephrine
Hyposensitization inject antigen to cause
production of IgG which binds to antigen
(allergen) before it reaches IgE coated cells.
Monocolonal anti-IgE inject, binds to receptors
on mast cells blocking them from the IgE.
Type I (Immediate)
Hypersensitivity
Testing
In-Vivo Tests - Skin tests
Small amount of allergen injected into skin
Look for wheal formation of 3mm or greater
in diameter
Simple, inexpensive, can screen for
multiple allergens.
Stop anti-histamines 24-72 hours before
test.
Danger of systemic reaction
Not for children under 3
Doctors sometimes use skin tests to diagnose
allergies.
The reactions shown here demonstrate allergic
response.
Type II (Cytotoxic) Hypersensitivity
Triggered by antigens found on cell surfaces
Altered self antigens
Heteroantigens
Manifested by the production of IgG or IgM
antibodies which coat the antigens.
Mechanisms
Antibody coats cell surface promotes phagocytosis
macrophages, neutrophils and eosinophils have Fc
receptors to bind to antibody on target cell.
Natural Kill cells have Fc receptors, bind, results in
cytotoxicity
Complement
Coats cells which enhances phagocytosis
Complement cascade goes to completion results in cell
lysis.
Type II major syndromes
1. Blood transfusion reaction
2. Hemolytic disease of the newborn
3. Drug induced hypersensitivity
Type II (Cytotoxic)
Hypersensitivity
Transfusion reactions
Hundreds of different antigens expressed on RBCs
Antibodies can be produced naturally or through
exposure, transfusion or pregnancy most common
Most well known example due to ABO
incompatibility.
Individuals form potent antibodies against ABO
antigens not present on their red blood cells.
Group O individuals have anti-A and if transfused
with group A blood will have an immediate, and
possibly fatal, reaction
Other blood groups may cause delayed reaction
or acute reactions.
Type II (Cytotoxic)
Hypersensitivity
Hemolytic disease of the fetus and newborn
Mother exposed to blood group antigens due to
previous pregnancy with antigen positive child
or transfusion.
Antibody must be IgG
Crosses placenta and coats fetal RBCs,
destruction of RBCs causes increased bilirubin
and anemia.
If first pregnancy is first exposure infant usually
not affected.
Subsequent pregnancies have increased risk
and the disease ranges from mild to fatal.
Type II (Cytotoxic)
Hypersensitivity
Autoimmune hemolytic anemia
Patients form antibodies to antigens on their
own RBCs.
Drug induced hemolysis
Some drugs may act as haptens, attach to
the RBC membrane causing antibodies to be
formed.
Antibody reacts with drug on RBC causing
hemolysis.
Type II (Cytotoxic)
Hypersensitivity
Some individuals make antibody which cross
reacts with self antigens found in both the
lung and kidney.
Goodpasture syndrome most well known example
Antibody produced against basement membrane
protein.
This protein present in lungs and kidneys.
Antibody binding results in inflammation
Symptoms are hemoptysis and hematuria.
Others conditions:
Hashimotos disease
Myasthenia Gravis
Diabetes mellitus
Management
ABO compatibility check on all mothers
Anti D therapy
GXM of blood
Steroids in the autoimmune conditions
Hypersensitivity
Similar to Type II, IgG or IgM involved and
destruction is complement mediated.
Difference is that antigen is SOLUBLE.
Soluble antigen and antibody combine to form
complexes.
Usually complexes cause no symptoms, quickly
disappear from the circulation.
Size of complexes produced seems important in
determining whether they will be eliminated
quickly from the body or retained long enough
to cause damage.
In some individuals the immune complexes
persist in circulation causing clinical symptoms,
some of them serious.
Hypersensitivity
Mechanism
Soluble immune complexes which contain a
greater proportion of antigen than antibody
penetrate blood vessels and lodge on the basement
membrane
At the basement membrane site, these complexes
activate the complement cascade.
During complement activation, certain products of
the cascade are produced,`attract neutrophils to the
area. Such substances are known as chemotactic
substances.
Once the polymorphs reach the basement membrane
they release their granules, which contain lysosomal
enzymes which are damaging to the blood vessel.
This total process leads to the condition recognized
histologically as vasculitis.
Hypersensitivity
Type III (immune complex
mediated) Hypersensitivity
Tissues most frequently affected are:
Glomerular basement
Vascular endothelium
Joint linings
Pulmonary alveolar membranes
Classical clinical symptoms of immune complex
disease are due to blood vessel involvement,
i.e., vasculitis.
Blood vessels of joints and the kidney are most
frequently affected, giving rise to symptoms of
arthritis and glomerulonephritis.
Type III (immune complex
mediated) Hypersensitivity
Serum Sickness
Due to passive immunization with animal serum,
bovine or horse.
Vaccines and bee stings may also trigger.
Symptoms appear 7 21 days after exposure to
animal serum.
Headache, fever, nausea, vomiting, joint pain,
rashes and lymphadenopathy.
Symptoms due to antibody being formed at same
time antigen is present = immune complexes
form.
Benign, self limiting, 7-30 days for recovery.
Hypersensitivity
Chronic immune complex diseases are
naturally occurring diseases caused by
deposits of immune complex and
complement in the tissues. Produce
hypersensitivity like reaction:
Systemic Lupus Erythematosus (SLE)
Acute glomerulonephritis
Rheumatic fever
Rheumatoid arthritis
management
Read
Type IV (delayed)
Hypersensitivity
Used to describe the signs and symptoms
associated with a cell mediated immune
response.
Results from reactions involving T
lymphocytes.
Characteristics of this phenomenon are:
Delayed, taking 12 hours to develop.
Causes accumulation of lymphs and
macrophages.
Reaction is not mediated by histamine.
Antibodies are not involved in the
reaction.
Type IV (delayed)
Hypersensitivity
Most well known is the Koch
Phenomenon
Inject tuberculoprotein (PPD test)
intradermally
Reaction results in an area of induration of 5
mm or more in diameter and surrounded by
erythema
Reaction which occurs within 48 hours is a
positive.
Type IV (delayed)
Hypersensitivity
Positive TB Test
Type IV (delayed)
Hypersensitivity
Contact dermatitis due to contact with chemicals
Poison ivy
Nickel, rubber, formaldehyde, hair dyes,
cosmetics
Latex allergies
Function as haptens
Causes erythema, swelling and formation of
papules
Hypersensitivity Pneumonitis
Response of sensitized T cells to inhaled
allergens.
Caused by chronic inhalation of microorganisms.
Occupationally related pigeons, farmers
Type IV (delayed)
Hypersensitivity
Type IV (delayed) Hypersensitivity
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Hypersensitivity Reactions

Serah Wachira MscN

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