Diseases of The Immune System

Diseases of T he Immune S ystem. Violet Aswa-Akeck.

Diseases of the immune system can be divided into: Hypersensitivity reactions Autoimmunity (Autoimmune disorders) Immune deficiency diseases.

Hypersensitivity reactions – there is inappropriate activation of the immune responses, producing tissue damage Autoimmunity – there is immunity to self-antigens Immunodeficiency – the individual is incapable of mounting a normal range of immune responses leading to undue susceptibility to infection.

The purpose of the immune response is to protect against invasion of foreign organisms However in certain situations the introduction or presence of an exogenous antigen elicits an undue severe, tissue damaging, inflammatory hypersensitivity reaction The reaction may be localized to the site of antigen entry or may be generalized (affecting different organs and tissues).

Type I, II, III, and IV This is dependent on the mechanism of immune recognition involved and the inflammatory mediator system recruited Types I, II & III depend upon the interaction of an antibody with the target Type IV reactions depend on recognition of certain antigen receptors on T cells.

The mediator systems involved in the pathogenesis of antibody-dependent hypersensitivity reactions are already present in the plasma, they occur rapidly, often within minutes T ype IV hypersensitivity reactions rely on the recruitment, proliferation and activation of lymphocytes and macrophages..

As a result these take long to evolve and are therefore called delayed-type hypersensitivity reaction. NB: The division of hypersensitivity reactions is made for purposes of classification; however pathogenesis of certain diseases may involve more than one type of hypersensitivity reaction..

These affect up to 35% of the population In majority of cases the symptoms are mild, although some patients may suffer life threatening systemic anaphylaxis.

Predisposing factors to type I hypersensitivity Genetic predisposition – also termed as atopy Individuals with high serum levels of IgE and who produce excessive IgE in response to antigenic stimulation than the normal population It is probable that a genetic factor determines the intensity of IgE responses.

NB: IgE does not have a protective role Individuals coming from countries in which parasitic diseases are endemic have higher IgE levels than those living in developed countries In those individuals IgE antibody production occurs as a defense mechanism against parasitic antigens and therefore type I hypersensitivity reactions may be involved in expulsion of parasites.

For type I hypersensitivity reaction to occur the individual must have previously been exposed to the antigen (allergen) and must have responded by the production of IgE antibody. IgE binds strongly to specific high affinity membrane receptors on tissue mast cells and circulating basophils.

Two types of mast cells exist The connective tissue and Mucosal mast cells NB: Mucosal mast cells may not be involved in type I hypersensitivity reaction Activation of the tissue mast cells or circulating basophils results from the binding of antigen to cell-bound IgE antibody.

For mast cell activation to occur the IgE receptors must be cross-linked and thus, the antigen must be polyvalent – (meaning it has a chemical valence greater than two; and is therefore effective against or sensitive towards more than one toxin, microorganism or antigen). M ast cell activation is associated with degranulation and activation of phospholipases A 2 and C..

Mast cell granules contain preformed mediators i.e. Histamin Heparine Neutrophil chemotactic factor Eosiniphil chemotactic factor and Proteases. The rapid secretion of these preformed mediators accounts for the immediate symptoms following exposure to allergen..

Activation of phospholipase A 2 results in formation of arachidonic acid and the subsequent generation of prostaglondin D 2 , thromboxane and leucotrines These are also collectively known as slow reacting substances of anaphylaxis (SRS-A) Platelet activating factor (PAF) is also released during mast cell activation..

The effects of these mast cell products are those of acute inflammatory reaction. They are responsible for the major features of localized atopic reactions i.e. congestion (vasodilatation); edema due to increased vascular permeability; and infiltration with eosinophil leucocytes..

They also increase secretion of mucosal glands (e.g. in hay fever and asthma) and produce contraction of bronchial smooth muscles ( broncho constriction in asthma) Eosinophils are the predominant cells in the t issue lesions of type I hypersensitivity reactions, and a peripheral eosinophilia is common in these disorders..

Clinical examples of type I hypersensitivity reactions.

The clinical features of type I hypersensitivity reactions occur within minutes of exposure to antigen..

The commonest manifestation of atopy are hay fever and extrinsic asthma These tend to run in families and are sometimes preceded by atopic eczema in infancy and childhood. In hay fever there is acute inflammation of the nasal and conjuctival mucous membranes resulting in sneezing and nasal & conjuctival hypersecretion within minutes of exposure to the causal agent (allergen) – usually grass pollen..

Similarly in the case of asthma, there is difficult breathing and wheezing due to narrowing of the airways by bronchospasm and mucous secretion – which develop rapidly when the asthmatic inhales the allergen to which s/he is hypersensitive e.g. house dust..

Atopic individuals may also may also suffer from food allergies in which absorption of allergic constituents e.g. of milk and eggs, promotes an acute reaction in the gut with colicky pain, vomiting and diarrhoea . Urticaria which consists of acute inflammatory lesions of the skin presenting with wealing due to dermal oedema , is common in atopic subjects and also occurs alone or as an acute or chronic condition..

Atopic patients sometimes develop acute systemic anaphylaxis (anaphylactic shock) – presenting with dyspnoea , urticaria , convulsions and sometimes death Severe anaphylactic shock is rare but sometimes occurs as a hypersensitivity reaction to drugs, notably penicillin and to the venoms of stinging insects, when the allergen is absorbed in large amounts..

Allergens in the blood bind to IgE antibody on the surface of circulating basophils . This activates them followed by degranulation and secretion of arachidonic acid metabolites. These metabolites are similar to those produced by mast cells Circulating antigen also leaves the blood stream and activates tissue mast cells.

The result is wide-spread urticaria and vasodilatation causing severe shock; together with intense contraction of non-vascular smooth muscle, remarkably in the bronchial tree This condition is a medical emergency and prompt intervention is indicated.

This depends upon an accurate clinical history which suggest that acute attacks result from exposure to a particular allergen To confirm the state of hypersensitivity, dilute solutions of the suspected allergen(s) are placed on the skin and pricked in with a needle. – A positive result is indicated by a local weal and flare reaction, developing within minutes and lasting for 1-2 hours..

NB: The results of skin tests may not always be helpful e.g. a large proportion of atopic individuals give reactions to a number of allergens so that the individual allergen which is responsible for a particular set of symptoms may not always be identified. Furthermore, some patients with obvious type I hypersensitivity disease may have negative skin tests.

Provocation tests e.g. bronchial challenge by controlled inhalation of the suspected allergen in asthma, or nasal insufflation in a hay fever patient, may precipitate the symptoms. These tests should only be performed when resuscitation facilities are available..

If the allergen can be identified it should be avoided if at all possible Mast cell stabilization by – Sodium Chromoglycate reduces release of mediators and is useful in prevention of manifestations Agents which increase intracellular cAMP levels reduce mast cell degranulation e.g. Theophyline.

5. Adenylate cyclase activators e.g. Adrenaline or Isoprenaline , which are sympathomimetics 6. Anti histamins which inhibit the binding of histamin to H I receptors 7. Gluco corticoids which have widespread effects on the formation of inflammatory mediators and on the inflammatory response.

8. Desensitization This is performed by giving repeated SC injections of allergen starting with minute doses and increasing gradually to larger doses until desensitization is achieved or a local or systemic allergic reaction occurs.

Desensitization is associated with the production of IgG antibody and this is then thought to bind to the allergen before it reaches IgE antibody on mast cells This procedure should only be done where resuscitation facilities are available.

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