Diseases of Diseases of ImmunityImmunity (1)

Hypersensitivity ReactionsHypersensitivity Reactions

Normally, a balanced system optimizes the eradication of infecting organisms without serious injury to host tissues.

However, immune responses may be inadequately controlled or inappropriately targeted to host tissues, and in these situations, the normally beneficial response will cause of disease.

Hypersensitivity ReactionsHypersensitivity Reactions

The term hypersensitivity is used to describe immune responses which are damaging rather than helpful to the host.

WHY? WHY? This term originated from the idea that individuals who

mount immune responses against an antigen are said to be "sensitizedsensitized" to that antigen, and therefore, pathologic or excessive reactions are manifestations of "hypersensitivityhypersensitivity."

CAUSES OF HYPERSENSITIVITY CAUSES OF HYPERSENSITIVITY REACTIONSREACTIONS

Autoimmunity. Reactions against microbes. Reactions against environmental antigens.

Hypersensitivity ReactionsHypersensitivity Reactions Classification:

Type I “Allergy & anaphylaxis”

Type II “Antibody dependant”

Type III “Immune complex - mediated”

Type IV “Cell-mediated (delayed type)”

N.B:N.B: First 3 types are antibody-mediated injury & the last type is cell-mediated injury

Type I Type I HypersensitivityHypersensitivity

ReactionReaction ALLERGIC REACTIONALLERGIC REACTION

ANAPHYLACTIC REACTIONANAPHYLACTIC REACTION

Type I Hypersensitivity

DefinitionDefinition : It is rapidly developing immunologic reaction

occurring within minutes after the interaction of an antigen (allergen) with IgE antibodies bound to surface of mast cells or basophils in individuals previously sensitized to the antigen

Antigen is usually exogenous , environmental and is called allergenallergen

Allergens may be introduced by inhalation, ingestion, touch, or by intravenous injection.

The reaction is mediated by IgE produced by previously sensitized B lymphocytes..

IgE binds to the main effector cells ; the mast cell (in tissues) or basophils (in blood).

The initiated reaction passes through 2 phases an early one and a late one.

Type I Hypersensitivity

Type I Hypersensitivity:Phases

As Seen in the localized reactions Initial response:Initial response:

Characterized by; Vasodilatation, Vascular leakage, and Smooth muscle spasm Increased glandular secretions These changes become evident within 5 to 30 minutes

after exposure to an allergen and subside in 60 minute. It is mainly mediated by histaminehistamine released by MAST

CELLS.

Type I Hypersensitivity:Phases

Late-phase reaction:Late-phase reaction: Develop in 2 to 8 hours later without additional

exposure to antigen and lasts for several days. Characterized by intense infiltration of tissues with

eosinophils, neutrophils, basophils, monocytes, and CD4+ T cells, and tissue destruction.

Occurs under effect of esinophils and neutrophils chemotactic factors released by mast cells.

Type I Hypersensitivity:Clinical Manifestations

The resultant reaction can occur as a systemic disorder or as a local reaction depending on the route of entry of allergen

Type I Hypersensitivityclinical presentationclinical presentation

Local reactions:Local reactions: Antigen is confined to a particular site Skin contact Localized cutaneous swellings (urticaria,

hives) and eczema, Ingestion Allergic gastroenteritis (food allergy)

diarrhoea Inhalation bronchospasm allergic rhinitis, and

bronchial asthma .

Type I Hypersensitivity:

Clinical ManifestationsClinical Manifestations

Systemic Anaphylaxis:Systemic Anaphylaxis: This usually follows an intravenous injection of an antigen to which the host

has already became sensitized for. systemic vasodilatation “anaphylactic shock” is produced and even death

within minutes Example: IV administration of Penicillin, Bee venom.

NOTE: The immune response in the late-phase inflammatory reaction, plays an important protective role in parasitic infectionsparasitic infections.

Type II Type II HypersensitivitHypersensitivit

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reactionreaction

Type II Hypersensitivity

Antibody-mediated diseases;Antibody-mediated diseases; Target antigens are present on the surface of cells or other

tissue components

The antigens may be intrinsicintrinsic to the cell membrane, or they may take the form of an exogenousexogenous antigen, such as a drug metabolite, adsorbed on the cell surface

The antibodies unite with the antigens MAINLY in the bloodstream,

This union sets off the complement system, and destruction of the local tissue cells ensues.

Type II Hypersensitivity MechanismMechanism

A, OpsonizationOpsonization

B, InflammationInflammation

C, Antireceptor antibodiesAntireceptor antibodies

Type II HypersensitivityMechanism

Clinical examples;Clinical examples; Incompatible transfusion reactions (mismatched blood

transfusion reaction) Erythroblastosis fetalis “Rhesus antigen

incompatibility” Autoimmune haemolytic anemia, or thrombocytopenia Certain drug reactions “penicillin hemolysis”

Type III Type III HypersensitivitHypersensitivit

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reactionreaction

Type III Hypersensitivity

Immune Complex - MediatedImmune Complex - Mediated Type III hypersensitivity is mediated by the deposition of

antigen-antibody complexesantigen-antibody complexes formed in blood vessels.formed in blood vessels. The antigens may be

Exogenous antigensExogenous antigens, such as bacteria, or viruses Endogenous antigensEndogenous antigens, such as DNA.

Immune complexes deposit in blood vessels in various tissue beds ,they have the ability to fix complement and trigger the subsequent injurious inflammatory reaction (either systemic or systemic or Localized )Localized )

Systemic Immune Complex DiseaseSystemic Immune Complex DiseaseMechanismMechanism

Favoured sitesFavoured sites of immune complex deposition are;

Renal glomeruli, Joints, Skin, Heart, Serosal surfaces, Small blood vessels

Type III Hypersensitivity Examples

Autoimmune diseases as:Autoimmune diseases as: Systemic lupus erythematosis Scleroderma Sjogren syndrome

Type IV Type IV HypersensitivitHypersensitivit

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reactionreaction

Type IV Hypersensitivity (Cell Mediated)(Cell Mediated)

Two types of T-cell reactions are capable of causing tissue injury and disease:

(1) delayed-type hypersensitivity (DTH), initiated by TH1-type CD4+ T cells

(2) direct cell cytotoxicity, mediated by cytotoxic CD8+ T cells that are responsible for tissue damage.

1-Delayed-Type Hypersensitivity

It is responsible for mediating immune reaction in case of; Defence against variety of intracellular persistent or persistent or

non-degradable antigensnon-degradable antigens, such as tubercle bacilli. pathogens, including mycobacteria, fungi, and certain

parasites, It may also be involved in transplant rejection. Tumour immunity

NOTE: In AIDS loss of CD4+ T lymphocytes increased

susceptibility for developing TB & fungal infection.

Delayed-Type HypersensitivitySequence of Cellular Events

On subsequent exposure of an individual previously sensitised, the memory TH1 cells interact with the antigen on the surface of APC .

APC become activated, they produce IL-12 that activate CD+4 cells. In turn CD+4 cells will secrete:

IFN-γ that activates macrophages to produce substances that cause tissue damage and promote fibrosis,

TNF promotes inflammation. When macrophages become activated they transform into epithelioid cells epithelioid cells

And they occasionally fuse multinucleated giant cells.giant cells.

Delayed-Type HypersensitivityMorphology

DTH is characterized histologically by the

formation of GranulomaGranuloma ( (a specific form

of chronic inflammation)

It refers to microscopic aggregate of

epithelioid cells, usually surrounded by a

collar of lymphocytes with or without the

formation of multinucleated giant cells.

Example for DTHExample for DTHTuberculin reactionTuberculin reaction

A classic example of DTH elicited by antigen challenge in an individual

already sensitized to the tubercle bacillus by a previous infection.

Between 8 and 12 hours after intracutaneous injection of tuberculin

(a protein extract of the tubercle bacillus), a local area of erythema and

induration appears, reaching a peak (typically 1-2 cm in diameter) in 24 to 72

hours (hence the adjective, delayed) and thereafter slowly subsiding.

2- Direct cell cytotoxicity In this variant of type IV hypersensitivity, sensitized CD8+

T cells kill antigen-bearing target cells

These effector cells are called cytotoxic T lymphocytes (CTLs)

They mediate their action through class I MHC molecule, where they directly lyse infected cells or stimulates their apoptosis.

It plays an important role in graft rejection, resistance to virus infections, and possibly tumor immunity