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Alergen & Hypersensitivity

Thursday, January 23, 2014

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 Thursday, January
23, 2014

Hapten:
antigenic,

i.e., binds antibody not immunogenic, cannot induce immune response frequently conjugated to carriers; haptencarrier 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, 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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Mast cell mediators


NCF-A ECF-A

Chemokines

Eotaxin

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IgE mediated reactions


Syndrome Allergens Route Responses

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First Allergen exposure

Antigen presentation Cytokine production

Sensitization Challenge Allergen (second binds to IgE exposure) on mast cells mediator release

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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

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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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Drug induced hemolytic anemia:


RBC Drug (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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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


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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

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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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