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Alergen & Hypersensitivity

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Antigens and immunogens Antigen:

recognized as foreign binds to antigen-specific receptors on

lymphocytes can be small or large can be any kind of biologic molecule

Immunogen: can induce or generate an immune

response proteins and polysaccharides are good

immunogens if they are large not all antigens are immunogens, some are

small

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Hapten: antigenic, i.e., binds antibody not immunogenic, cannot induce immune

response frequently conjugated to carriers; hapten-

carrier complex is immunogenic and antibody against the HAPTEN will be generated

free hapten will bind to antibody

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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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Epitope or antigenic determinant: region of antigen which binds antibody; usually an antigen is much larger than the

antigen -combining region of antibody antibody binds only to a portion of the antigen can be recognized by B or T cell

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Berdasar epitop

Unideterminan, univalen; hapten Unideterminan, multivalen;

polisakarida Multideterminan, univalen;

protein Multideterminan, multivalen;

kimia kompleks

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Terminology

Ag immunogen Allergen epitope

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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, post-

vaccinal 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 FCR 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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Mast cell mediators

Chemokines

NCF-AECF-A

Eotaxin

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IgE mediated reactionsSyndrome Allergens Route Responses

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Antigen presentationCytokineproduction

SensitizationFirstAllergenexposure

Challenge(secondexposure)

Allergenbinds to IgEon mast cellsmediatorrelease

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Clinical manifestation

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

exposure

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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 RBC’s 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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Goodpasture’s syndrome-Type II smooth deposition

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2. Mechanisms:

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Drug induced hemolytic anemia:

RBCDrug (hapten) - penicillin

Hemolytic disease of the newborn

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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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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

Serum Sickness as a model of immune complex injury

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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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SLEantibodies against DNAWomen, primarily affectedcollection of syndromes, fever, joint

paint, CNS damage, kidneytype III hypersensitivity-leading to

glomerulonephritis

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

Mechanisms :1. Helper T-cell Mediated Hypersensitivity

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2. Cytotoxic T-cell Mediated Hypersensitivity                       

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Hypersensitivity reactions

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Tugas

Kel Putra & Kel Putri;

Manifestasi Oral alergi

Presentasi besuk sabtu oleh wakil dari masing2x kelompok kelompok Pa : mas muchtar

Pi : mbak leli


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