Hypersensitivity

Nada Mohamed Ahmed ,MD, MT (ASCP)i

Objectives • Definition • Classification • Mediated • Diseases example • Diagnosis

HYPERSENSITIVITY

• Hypersensitivity  refers to undesirable reactions produced by the normal immune system, including  allergies and autoimmunity

• These reactions may be damaging, uncomfortable, or occasionally fatal.

CLASSIFICATION

• TYPE I – immediate, atopic, anaphylactic

• Type II – Antibody Dependant• Type III – Immune Complex Immediate • Type IV – Cell Mediated / delayed

type of hypersensitivity

Coombs and Gell classification

Type I. Immediate or anaphylactic hypersensitivity

• Type I hypersensitivity is also known as immediate or anaphylactic hypersensitivity.

• The reaction may involve skin (urticariaand eczema), eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary tissues (asthma) and gastrointestinal tract (gastroenteritis).

Type I. Immediate or anaphylactic hypersensitivity

• The reaction may cause a range of symptoms from minor inconvenience to death.

• The reaction usually takes 15 - 30 minutes from the time of exposure to the antigen, although sometimes it may have a delayed onset (10 - 12 hours).

• Mediated by IgE antibody to specific antigens

• The primary cellular component in this hypersensitivity is the mast cell or basophil.

• Mast cells stimulated and released histamine

Type I. Immediate or anaphylactic hypersensitivity

causes

• ALLERGEN:Allergens are nonparasite antigens that can stimulate a type I hypersensitivity response.

Atopy

• Atopy is the term for the genetic trait to have a predisposition for localized anaphylaxis.

• Atopic individuals have higher levels of IgE and eosinophils.

Mechanism

• Exposure may be by ingestion, inhalation, injection, or direct contact.

• The reaction is mediated by IgE antibodies and produced by the immediate release of histamine, tryptase, arachidonate and derivatives by basophils and mast cells..

Mechanism• This causes an inflammatory response leading

to an immediate (within seconds to minutes) reaction.

• The reaction may be either local or systemic. Symptoms vary from mild irritation to sudden death from anaphylactic shock.

• Treatment usually involves epinephrine,

antihistamines, and corticosteroids

Mediators of type 1

• Histamine• Cytokines TNF-a, IL-1, IL-6. • Chemoattractants for Neutrophils

and Eosinophils. • Leukotrienes • Prostaglandins

Some examples of type 1:

• Allergic asthma • Allergic conjunctivitis • Allergic rhinitis ("hay fever") • Anaphylaxis • Angioedema • Urticaria (hives)

Diagnosis

• measurement of total IgE and specific IgE antibodies against the suspected allergens.

• Total IgE and specific IgE antibodies are measured by a modification of enzyme immunoassay (ELISA).

• Increased IgE levels are indicative of an atopic condition

Type II Hypersensitivity

• Type II hypersensitivity is also known as cytotoxic hypersensitivity and may affect a variety of organs and tissues.

• The antigens are normally endogenous, although exogenous chemicals (haptens) which can attach to cell membranes can also lead to type II hypersensitivity.

• Drug-induced hemolytic anemia, granulocytopenia and thrombocytopenia are such examples. Pencillin allergy also belong to this class.

Type II Hypersensitivity

• The reaction time is minutes to hours.

• Type II hypersensitivity is primarily mediated by antibodies of the IgM or IgG classes and complement .

• Phagocytes may also play a role.• The lesion contains antibody,

complement and neutrophils.

Hemolytic disease of newborn

Rh factor incompatibility • IgG Abs to Rh RBC antigen – Rh+ baby born to Rh- mother first time

fine. 2nd time can have abs to Rh from 1st pregnancy.

– Ab crosses placenta and baby kills its own RBCs.

– Treat mother with ab to Rh antigen right after birth and mother never makes its own immune response.

Diagnosis

• Antiglobulin test(coomb test)• Treatment involves anti-inflammatory

and immunosuppressive agents

Type III

• Antigen antibody immune complexes. IgG mediated

• Large amount of antigen and antibodies form complexes in blood.

• If not eliminated can deposit in capillaries or joints and trigger inflammation.

• The reaction may be general (e.g., serum sickness) or may involve individual organs including skin (e.g., systemic lupus erythematosus, Arthus reaction), kidneys (e.g., lupus nephritis), lungs (e.g., aspergillosis), joints (e.g., rheumatoid arthritis) or other organs.

Type III

• The reaction may take 3 - 10 hours after exposure to the antigen .

• It is mediated by soluble immune complexes.

• They are mostly of the IgG class, although IgM may also be involved.

• The antigen may be exogenous (chronic bacterial, viral or parasitic infections), or endogenous (non-organ specific autoimmunity: e.g., systemic lupus erythematosus, SLE).

• The antigen is soluble and not attached to the organ involved

Type III

• PMNs and macrophages bind to immune complexes via FcR and phagocytize the complexes.

BUT• If unable to phagocytize the immune

complexes can cause inflammation via C’ activation ---> C3a C4a, C5a and "frustrated phagocytes".

Mechanism of Type III

Diagnosis and Treatment

• Diagnosis involves examination of tissue biopsies for deposits of immunoglobulin and complement by immunofluorescence microscopy.

• The presence of immune complexes in serum and depletion in the level of complement are also diagnostic.

• Treatment includes anti-inflammatory agents.

Type IV delayed type

• Reaction involves sensitized T cells and release of

its lymphokines as mediators and amplifiers

• Mediated by cells rather than antibodies

• Diseases example

• Contact dermatitis, , Transplant rejection, Granuloma

Type IV

Th1 cells release cytokines to activate macrophages causing inflammation and tissue damage.

Continued macrophage activation can cause chronic inflammation resulting in tissue lesions, scarring, and granuloma formation.

• Response starts after 48 -72 hrs

Diagnosis and treatment

• Diagnostic tests in vivo include delayed cutaneous reaction (e.g. Montoux test and patch test (for contact dermatitis).

• In vitro tests for delayed hypersensitivity include mitogenic response, lympho-cytotoxicity and IL-2 production.

• Corticosteroids and other immunosuppressive agents are used in treatment.

Comparison of Different Types of hypersensitivity

characteristics type-Ianaphylactic

type-II(cytotoxic)

type-III(immune complex)

type-IV(delayed type)

antibody IgE IgG, IgM IgG, IgM None

antigen exogenous cell surface soluble tissues & organs

response time 15-30 minutes minutes-hours 3-8 hours 48-72 hours

appearance weal & flare lysis and necrosis erythema and edema, necrosis

erythema and induration

histology basophils and eosinophil

antibody and complement

complement and neutrophils

monocytes and lymphocytes

transferred with antibody antibody antibody T-cells

examplesallergic asthma, hay fever

erythroblastosisfetalis, Goodpasture's nephritis

SLE, farmer's lung disease

tuberculin test, poison ivy, granuloma