Allergy And Clinical Immunology

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Allergy is an acquired specific alteration in the capacity of the host to react with an antigen . It is an immunological reaction depending on antigen-antibody complexes.

The allergic reaction may be immediate that occurs after exposure to the antigen or delayed taking few hours or even days or weeks to appear.

Allergic skin diseases constitute the main and bulk of skin dermatoses in children and adults .

Immune function of the skin

The skin is an environmental barrier which initiates an immune response to the penetrating foreign antigens.

This will lead to:

Destruction of infective organisms.

Neutralization and removal of the potential toxins and the damaged tissue.

The skin contains many elements of the immune system, which have been designated, the skin-associated lymphoid tissue (SALT) or the skin immune system (SIS).

Human epidermis contains Langerhans cells, and Keratinocytes which when stimulated will synthesize several types of Cytokines that activate and induce proliferation of lymphocytes and macrophages, which contribute, induce and enhance sensitization.

The immune system functions in the skin as in other body organs are either a non-specific, (innate) or specific type, (adaptive).

A. The non-specific immune system

The non-specific immune mechanism is the first line of the body defense when it is exposed to an antigen which it includes:

  1. Physical defense performed by the skin.

  2. Body Secretions (the mucous, celia in the respiratory tract, sebaceous gland secretions).

  3. Cellular: this is performed by the phagocytes or the natural killer cells (NK).

B. The specific immune system

This type has its role when the non-specific immune system failes to take care of the offending antigen.

The specific immune system includes the cellular and humoral components that characteristically have an immunological mirror memory, where it can enhance an immunological response on repeated exposure to the same antigen.

Functions of the specific immune system

The specific immune system produces the immuno-competent cells, which are the T cells and B-cells .

T- cells modulate both the cellular and humoral immune responses .

B - cells produce the different antibody immunoglobulin groups; IgG, IgE, IgM, IgA and IgD .

Allergic reaction may be related to an endogenous or exogenous factors .

Antigen: is a foreign substance that can stimulate an immunological response.

This will lead to:

Formation of antibodies.

Alters the reactivity of lymphocytes, which is known as cell mediated response.

Chemical characteristics of antigens

Antigens may have high or low molecular weight.

  1. High molecular weight antigens are composed of amino acids and peptides that can stimulate the formation of antibodies.

  1. Low molecular weight antigens cannot stimulate the formation of antibodies unless combined with a protein. These are known as haptens. These can stimulate humoral antibodies or delayed-type (cell-mediated) sensitivity, which is specific for the haptens.

    Antigens that commonly sensitize persons to anaphylactic or to delayed-type hypersensitivity and these are known as allergens.

    Antibody: is a serum immunoglobulin that is formed in response to antigen stimulation. Immunoglobulins are synthesized by plasma cells and are composed of polypeptide chains.

    The basic antibody unit is the immunoglobulin molecule (Ig). There are different immunoglobulins mainly IgG that constitutes around 75 per cent of the immunoglobulins.

    Different Immunoglobulins: IgG, IgE, IgA, IgD are found in varying amounts in the external secretions, e.g. respiratory, intestinal tract.

    Failure of any part of the immune system may predispose to allergy, infection or malignancy.

Different immunological reactions

Antigen-antibody reaction is either an immediat which appears after exposure to a certain antigen or may be delayed type.

Immediate allergic reactions (Type (1, 11, 111) : these reactions represent a humoral response, stimulating B-lymphocytes, plasma cells that produce and activate different immunoglobulins.

Delayed allergic reaction (Type 1V): The allergic reaction may take few hours, days or even weeks to appear from the time of exposure to the antigen. This type is cell mediated by sensitizing T-lymphocytes.

The different hypersensitivity reactions according to Gell and Coombs classification are:

1. The immediate, anaphylactic type (Type I)

The antigens in this type may be foodstuff, pollens, drugs, dust, feathers or others.

The antibodies are immunoglobulins IgE.

The antigen -antibody reaction causes degranulation of mast cells which release different mediators mainly histamine, serotenin, bradykinin and slow reacting substances (SRS-A).

The physiopathological changes are:

  1. Vasodilatation of blood vessels.

  2.  Increase of the vascular permeability.

  3.  Contraction of the smooth muscles.

The clinical manifestations of Type I reactions are: Urticaria, angioedema, anaphylactic shock, bronchial asthma and allergic rhinitis.

2. Cytotoxic antibody (Type II)

The antigen in Type II allergic reaction is haptens, which deposits on the cell wall or cell membrane fragments, which can act as an antigen.

The antibodies are cytotoxic antibodies of the classes IgG, IgA and IgM.

The allergic reaction occurs as a result of reaction of the circulating antibodies or the cellular antibodies with the circulating antigens, which lead to attachment of complements with the antigen-antibody complex leading to lyses of the target cells.

The effect of such reaction is cytolysis.

The clinical manifestations of the cytotoxic reactions are: Thrombocytopenia, hemolytic anemia, agranulocytosis and autoimmune diseases.

3. Antigen - antibody immune complex (Type III), Arthus reaction.

The antigens in this type may be drugs, foreign serum and other different antigens such as from streptococci and tumors.

The antibodies of Type III reaction are immunoglobulins IgG and complements.

The allergic reaction occurs as a result of complex mechanism.

Physico-chemical changes:

  1. Deposition of antigen-antibody complexes in the capillary walls.

  2.  Activation of the complement system.

  3.  Leucotaxis and phagocytosis of the immune complex by leukocytes.

  4.  Lyses of the phagocytosing cells.

  5.  Destruction of the cell walls by the lysosomal enzymes.

The effects of these complex reactions are inflammation and necrosis of tissues.

The clinical manifestations of type III allergic reactions are:

  1.  Arthus reactions, arthus phenomenon, serum sickness.

  2.  Drug rash.

  3.  Toxic epidermal necrolysis

  4.  Erythema multiforme and erythema nodosum.

4. Delayed type cell mediated (Type IV). The antigens are different types of chemicals and other substances.

The antibody is the T-lymphocytes.

The allergic reaction is due to lymphocyte-antigen reaction due to humoral factors released (lymphokines).The effects of these reactions are: vasodilatation, edema, and monolymphocytic infiltration.

The clinical manifestations are: allergic contact dermatitis, allergic photodermatitis, allergic exanthemas, id eruptions, and transplacental rejection.

The manifestation of the allergic reaction may be localized only to the skin , internal organs or both.

The immediate and delayed type of hypersensitivity reactions are the most important in dermatitis -eczema mechanism.

The immediate reaction

Occurs as a result of degranulation of mast cells due to an antigen stimulation leading to release of mediators as histamine, leukotrienes, platelet activating factor, proteases and others. This reaction may elicit skin disorders such as in early stages of atopic eczema, urticaria and angioedema.

Investigation of this type includes: skin prick test, serum IgE and (RAST) test.

The delayed reaction

Repeated contact of a specific antigen with a previously sensitized T-cells leads to stimulation and the release of lymphokines. Lymphokines induce inflammatory reactions and activate macrophages to release mediators.

This type of reaction corresponds to the delayed type of contact dermatitis, photo-allergic dermatitis and late stages of atopic dermatitis.

Cell mediated immune reactions are common in the defense against fungal, viral, granulomatous infections of the skin and mediating reactions to insect bite.

Patch tests and lymphocyte transformation may help to detect the sensitizing allergen.

Skin tests may be of value in detecting the sensitizing antigen.



Eczema is an inflammatory skin reaction in response to an antigen stimulation. Eczema is Greek word , which means "to boil out" or "to effervesce".

Baer describes eczema as a pruritic papulovesicular reaction, which is associated in its acute phase with erythema and edema, and in its chronic phase by thickening, lichenifecation, scaling, and retaining some of its papulovesicular features.

Dermatitis constitutes more than thirty per cent of clinical dermatology.

Classification of Eczema

There are different classifications of eczema, which are sometimes confusing and therefore most authors prefer the word ‘dermatitis‘.

In spite that all cases of eczema is dermatitis, not all cases of dermatitis is considered as eczema since dermatitis means skin inflammation.

Classification of eczema is sometimes arbitrary depending on the causative triggering factors.

Eczema may be classified into: endogenous, which is due to processes originating within the body or exogenous eczema that is, mediated by exogenous factors.

  1. Endogenous Eczema

    The term endogenous eczema implies that the eczematous condition is not due to exogenous or external environmental factors, but is mediated by processes originating within the body.

    In some conditions, however, there are both external and internal precipitating factors.

    Endogenous eczema includes:

    Atopic dermatitis

    Seborrheic dermatitis

    Nummular (Discoid)

    Pompholyx (dyshidrotic)

    Metabolic eczema or eczema associated with systemic diseases.

    Juvenile planter dermatoses

    Eczematous drug eruption

    Stasis dermatitis

  2. Exogenous eczema

    This type of eczema is due to different exogenous factors that include the following:

    Primary irritant dermatitis

    Allergic contact dermatitis

    Photo allergic dermatitis

    Polymorphous light eruption.

    Infective dermatitis

  3. Unclassified types of eczema

    Neurodermatitis (Lichen simplex chronicus)

    Nodular prurigo

    Eczema can be also classified according to the course and clinical picture in to:

    Acute eczema

    Sub acute eczema

    Chronic eczema



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