Alergen & Hypersensitivity dlm Kedokteran Gigi

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Alergen

Bahan /material/antigen yang bisa menyebabkan terjadinya alergi Alergi: respon immune patologik , terjadi secara berlebihan sehingga merusak jaringan, diperantarai oleh Ig E . Sensitivitas thd Ag >>>> Terkait dengan reaksi hypersensitivitas type I
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Ag, Alergen

Hidrat arang (polisakarida) umumnya imunogenik Lipid non imunogenik + carrier imunogenik, ex Sfingolipid Asam Nukleat Non imunogenik +carrier imunogenik Protein imunogenik yang multideterminan univalen
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Berdasar epitope

Unideterminan,univalen; hapten Unideterminan, multivalen; polisakarida Multideterminan, univalen; protein Multideterminan, multivalen; kimia kompleks

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Terminology

Ag immunogen allergen

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Exogenous materials (Ag, allergen) and the Skin/mucosa response

1. Allergic contact Dermatitis/Stomatitis/Mucositis 2. Irritan contact Dermatitis/Stomatitis/Mucositis

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Allergic contact dermatitis (ACD)

The term contact dermatitis sometimes is used incorrectly as a synonym for allergic contact dermatitis (ACD). Contact dermatitis is inflammation of the skin induced by chemicals that directly damage the skin as ussualy Irritant Contact Dermatitis

by specific sensitivity in the case of ACD.

ACD

ACD is inflammation of the skin manifested by varying degrees of erythema, edema, and vesiculation. It is a delayed type of induced sensitivity (allergy) resulting from cutaneous contact with a specific allergen to which the patient has developed a specific sensitivity.
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Pathophysiology: ACD

The pathology is a subepidermal blister with collections of neutrophils present within the tips of the dermal papillae associated with edema (papillary microabscesses). Direct immunofluorescence (DIF) reveals a granular deposits of IgA at the dermal papillae of lesional and perilesional skin. It is not found in patients with celiac disease who do not have the skin disease.

Pathophysiology: ACD

Most chemicals able to provoke ACD have small molecules (<500 d). Approximately 3000 chemicals are well documented as specific causes of ACD. The small chemical molecules responsible for ACD must bind to carrier proteins on Langerhans cells, which are situated within the suprabasilar layer of the epidermis. Langerhans cells are the antigen-presenting cells within the skin. Langerhans cells interact with CD4+ T cells (helper T cells).

Diagnosis :ACD

History: A detailed history, both before and after patch testing, is crucial in evaluating individuals with ACD. Potential causes of ACD and the materials to which individuals are exposed should be patch tested. Patients with ACD require a much more detailed history compared to those with most other dermatologic disorders.

Clinical : ACD

Physical: Acute ACD is characterized by pruritic papules and vesicles on an erythematous base. Lichenified pruritic plaques may manifest chronic ACD. Occasionally, ACD may affect the entire integument (ie, erythroderma, exfoliative dermatitis). The initial site of dermatitis often provides the best clue regarding the potential cause of ACD.

Epidemiology: ACD

Frequency:
the prevalence of contact dermatitis to be 13.6 cases per 1000 population using physical examinations by dermatologists of a selected sample of patients.. The National Ambulatory Medical Care Survey conducted in 1995 estimated 8.4 million outpatient visits to American physicians for contact dermatitis. This was the second most frequent dermatologic diagnosis. Of office visits to dermatologists, 9% are for dermatitis. At a student health center dermatology clinic, 3.1% of patients presented for ACD, and 2.3% presented for irritant contact dermatitis.
Internationally: A Swedish study found that prevalence of ACD of the hands was 2.7 cases per 1000 population. A Dutch study found that prevalence of ACD of the hands was 12 cases per 1000 population.

Epidemiology: ACD

Sex: ACD is more common in women than in men. This predominately is a result of allergy to nickel, which is much more common in women than in men in most countries. Age: ACD may occur in neonates. In elderly individuals, the development of ACD may be delayed somewhat, but the dermatitis may be more persistent once developed

Mortality/Morbidity: ACD

Death from ACD is rare in the US. ACD to the weed wild fever few caused deaths

ACD

Picture 1. Onycholysis developing from allergic contact dermatitis to formaldehyde used to harden nails Picture 2. Nickel contact allergy

Allergic Contact stomatitis/Mucositis

Allergic Contact stomatitis/Mucositis

A contact allergy in the mouth or contact stomatitis is a hypersensitivity mechanism of the cellular or delayed type and is, like contact dermatitis on the skin, the result of a sensitization to a substance with which one has previously come in contact, the "contact allergen".

Allergic stomatitis/Mucositis

a contact stomatitis produces primarily subjective symptoms: loss of the sense of taste, numbness, burning sensations, and pain (rarely itching), and sometimes even complaints of generalized itching, dizziness, headache, gastro-intestinal problems, and malaise.

Allergic stomatitis/Mucositis

Immediate hypersensitivity to drugs or contact allergy may often lead to inflammatory oral mucosal red lesions. Antibiotics, sulfonamides, barbiturates and iodine are capable of causing hypersensitive reactions.

Allergic stomatitis/Mucositis

symptoms can be unpleasant and include pain, numbness, a burning sensation and loss of taste Unlike contact allergic dermatitis, which can spread to other parts of the body, the effects of allergic contact stomatitis remain confined to the mouth, strictly where direct physical contact has occurred. Fortunately the condition is rare, as in most people saliva dilutes and washes the allergens away.
Burning of the mucosa or itchiness are consistent features in both hypersensitive and contact allergy patients.

Clinical Feature Allergic stomatitis/Mucositis

1. Diffuse mucosal redness is the hall mark of allergic mucositis. Pseudomembrane and desquamation of epithelium may occur in some cases Contact allergic respone on the other hand is generally discrete. The redness occurs in the area that is in direct contact with the allergen

Allergen of Allergic stomatitis/Mucositis

Some known allergens include; dental materials, topical medications, cosmetics,. toothpaste, including any dyes they contain mouthwash medication applied within the mouth, such as lozenges for sore throats and ulcers fillings, crowns, dentures etc. lipstick nail varnish, if you bite your nails nickel, from sucking jewellery foods
Allergen in the chewing gum can sometimes evoke a generalized erythematous respone of the oral mucosa and the gingiva. This condition is called plasmacytosis gingivae

Treatment of Contact Allergic Stomatitis

History and elimination of the known allergen are of the most importance in the diagnosis and management of these conditions. Try to identify the cause of your contact allergic stomatitis and then avoid it. Antihistaminics help to control systemic reaction and Triamcinalone acetonide in orabase is useful for contact allergy

Irritant stomatitis

Caused by irritant agents ; Self Curing Acrylic Resin, H2O2`,stain removal agent (Ocho), Acids Direct injury from irritan (burning) High concentration chemicals burning mouth syndrome trauma or physical injuries.

Irritant stomatitis

Clinical signs are frequently less pronounced than subjective symptoms, and patients commonly experience severe functional problems despite only mild mucosal alterations.

Clinical Feature; Irritant stomatitis

The clinical manifestations of contact stomatitis are extremely variable and include erythema, erosions, ulcerations, leukoplakialike lesions, and lichenoid reactions.

Treatment of Irritant Stomatitis

A careful history and an accurate examination of the oral cavity, teeth, and dental restorations are essential for a correct diagnosis Patch testing is indicated in all lesions that are not clearly related to trauma or physical injuries. Successful treatment requires the identification and elimination of the causative factor, and Used carefully and optimal concentration of chemicals Topikal medication of lession

Reaksi Hipersenstivitas (Gell & Combs)

Membagi berdasar kecepatan dan mekanisme immun Ada 4 tipe; tipe 1, tipe 2, tipe 3, tipe 4 Reaksi dpt terjadi sendiri-sendiri, atau bersamaan

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Type I Hypersensitivity

Allergy Immediate type Local anaphylaxis Systemic anaphylaxis IgE mediated hypersensitivity Mast cells are involved the antigen is typically called an allergen

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Anaphylaxis: Example of Type I Hypersensitivity

1. Types of Anaphylaxis Generalized anaphylaxis Cutaneous anaphylaxis - localized 2. Cutaneous anaphylaxis- local reaction of antigen with homocytotropic antibody. Contributor to spontaneous disease: hypersensitivity reactions to insect bites, postvaccinal wheal and flare reactions
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Generalized anaphylaxis
a. Pathogenesis and Mediator Release Sensitization to antigen with IgE response IgE binds to mast cells and basophils Re-exposure causes degranulation of mast cells Mediators of immediate hypersensitivity disease

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Mast cell product and function

1) Histamine and serotonin: Increase venular permeability, induce smooth muscle contraction in pulmonary airways, cause arteriolar dilation 2) Leukotrienes: LTC4, LTD4, LTE4 Causes sustained smooth muscle contraction; may be important in prolonged airway constriction in immediate hypersensitivity reaction. LTB4: chemotactic for neutrophils and eosinophils 3) Eotaxin: chemotactic for eosinophils; released from mast cells 4) PAF: released by basophils, neutrophils, macrophages Stimulate:Platelet aggregation, increased vascular permeability, smooth muscle contraction, 5) Prostaglandins: PGE2 stimulates vasodilation
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Phase of Reaction Type I Hypersensitivity

Sensitization Phase Production Ig E Bind to FCe-R of Mast cell/basophil Activation Phase Re-exposure released granule of mast cell; Metilation Phospholipid membraneCa influx>> phospholipase GlikolisisEnergigranule movement cAMP<<cGMP>> degranulation Effector Phase Complex response from mediator of granule; histamin,bradikinin
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Alergen

Sel B

Sel Th2

Sel Plasma Ig E

Sel Mast

Sel Mast+IgE Degranulasi Sel Mast

Alergen

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Sel MasAmin Vasoaktif, sitokin

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Sel mast+IgE+Alergen

Degranulasi sel mast

Sekresi mediator inflamasi

Sekresi sitokin

Amin vasoaktif, protease

PG Leukotrin
Delatasi vas, Kontraksi otot polos

TNF alfa

Delatasi vas, Kerusakan jar

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Reaksi inflamasi
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Clinical manifestation

Erythem ( red) vena delatation Edema release serum into tissue bronchoconstriction Peak 10-15 min after reexposure

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Type II Hypersensitivity

Cytotoxic antibody -- IgG or IgM reacts with antigen on cells and then complement activation destroys cells. (Also may have NK cell via ADCC cells involved) Hemolytic disease of the newborn (erythroblastosis fetalis) Transfusion reactions Anti-streptococcal M-protein crossreacts with heart muscle in rheumatic fever malaria infected RBCs coated with malaria antigens
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Type II Hypersensitivity - Cytotoxic Reactions

1. Examples Autoimmune hemolytic anemia Isoimmune hemolytic anemia and transfusion reactions Drug-induced hemolytic anemia (e.g.-penicillin) Autoimmune thrombocytopenia
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Penyakit Hipersensitivitas Tipe 2

Anemia hemolitik autoimun; fagositosis eritrosithemolisis,anemia Trombositopenia purpura autoimun;fagositosisTrombositperdarahan Vaskulitis;degranulasi netrofil & inflamasi Goodpasture;inflamasi oleh komplemen &R-Fc nefritis Demam reumaaktifasi makrofage,inflamasimiokarditis Miastenia gravis: ikatan asetilkolin dihambatparalisis Diabetes insulin resisten; Ab mencegah ikatan insulinhiperglikemia Anemia pernisiosa; netralisasi faktor intrinsikenemia
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Goodpastures syndrome-Type II smooth deposition

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2. Mechanisms:

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Mekanisme Kerusakan jaringan pada Hypersensitivitas Type III

Komplek imune ( antigen+antibodi) Aktifasi komplemen

Release C3a dan C5a Aktifasi makrofage Stimulasi sel mast Mediator inflamasi
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Kerusakan jaringan
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Type III Hypersensitivity - Immune (Toxic) Complex Disease

1. Examples of Immune Complex Disease Serum Sickness Immune Complex Glomerulonephritis Arthus reaction Extrinsic Allergic Alveolitis SLE
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Serum Sickness as a model of immune complex injury

Antigen-Antibody complexes form in antigen excess and are deposited in vessel walls, joints and glomeruli. Fixation of complement and neutrophil infiltration induces tissue damage and vasculitis, arthritis and glomerulonephritis. Antigen, Antibody and complement can be demonstrated in lesions
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Serum Sickness as a model of immune complex injury

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Immune complex glomerulonephritis

1. Examples of immune complex glomerulonephritis Viral Diseases

Lymphocytic choriomeningitis Equine infectious anemia Chronic hog cholera Aleutian mink disease Feline leukemia virus infection

Parasitic Diseases: Dirofilariasis Autoimmune diseases: Systemic lupus erythematosus Idiopathic (largest group of cases)
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Mechanisms of formation of toxic immune complexes in glomeruli

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Morphologic changes: glomerulonephritis

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SLE Butterfly Rash

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SLE
antibodies

against DNA Women, primarily affected collection of syndromes, fever, joint paint, CNS damage, kidney type III hypersensitivity-leading to glomerulonephritis

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Type IV Hypersensitivity - Cell Mediated (T-cell Hypersensitivity )

Mechanisms :
1. Helper T-cell Mediated Hypersensitivity CD4

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2. Cytotoxic T-cell Mediated Hypersensitivity CD 8

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Type IV

Type I DM Arthritis reumathoid Neuritis perifer Dermatitis kontak karena kimia Sklerosis multiple

Tugas

Kel Putra & Kel Putri; Manifestasi Oral alergi Presentasi besuk pagi oleh wakil dari masing2x kelompok

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