Immunological Diseases
description
Transcript of Immunological Diseases
Immunological DiseasesImmunological DiseasesSpectrums and MechanismsSpectrums and Mechanisms
Assistant Professor Kiat Ruxrungtham, M.D.Assistant Professor Kiat Ruxrungtham, M.D.
Division of Allergy and Clinical ImmunologyDivision of Allergy and Clinical ImmunologyDepartment of Medicine, Faculty of MedicineDepartment of Medicine, Faculty of Medicine
Chulalongkorn UniversityChulalongkorn University
Principles of Immunology
• Key roles of immune responsesKey roles of immune responses• TerminologyTerminology• Primary and Secondary Immune RespoPrimary and Secondary Immune Respo
nsesnses• Cells and Molecules involvedCells and Molecules involved• Immunological DisordersImmunological Disorders• Mechanisms and Clinical ImplicationsMechanisms and Clinical Implications
Key Roles of Immune System• Prevent and control infection• Prevent and control autoimmune diseas
es• Prevent and control malignancy• Prevent and control allergic diseases• Prevent and control graft-versus-host (
GVH)
Terminology
• Antigen, allergen, immunogen and epitope
• Innate and Acquired Immunity• Allergy• Autoimmunity, autoimmune diseases
Innate and Acquired ImmunityInnate Acquired
Ag specificity no yesMagnitude (10, 20) same higher (20 > 10)Memory no yesKey components PMN, NK T, B lymphocytes
C’, barriers APCs
Primary and Secondary ImmuPrimary and Secondary Immune Responsesne Responses
Primary IR7-10relatively lowMostly IgM
relatively high
Secondary IR2-5 daysrelatively highOther class (IgG,
IgA, etc)relatively low
Lag period
Peak response
Ig class
Antigen [ ]
Cells and Molecules Involved in Immunology
Innate Immunity• Cells: epithelium, phagocytes (neutrophil
s, monocyte-macrophages) NK cells, mast cells
• Molecules: complement, inflammatory mediators, cytokines, chemokines, adhesion molecules
Cells and Molecules Involved in Immunology
Acquired ImmunityAcquired Immunity• CellsCells: APCs (macrophages), T (CD4+, : APCs (macrophages), T (CD4+,
CD8+) and B lymphoctyes (plasma cellsCD8+) and B lymphoctyes (plasma cells), monocytes), monocytes
• MoleculesMolecules: HLA, cytokines, immunoglo: HLA, cytokines, immunoglobulins, adhesion molecules bulins, adhesion molecules
Immunological disorders
• Hypersensitivity mediated disorders
• Immunodeficiency : 10 and 20 ID
Classification of Hypersensitivity
Gell and Coomb’s Classification: 4 Types• Type 1 : IgE-mediated • Type 2 : Cytotoxic antibodies• Type 3 : Ag-Ab Immune complexes• Type 4 : Delayed-type, cell-mediated
hypersensitivity
Type I Hypersensitivity
• Allergen exposure, sensitization and re-exposure
• IgE antibody, mast cells/ basophils and its’ mediators
• Target organ immediate reactions• Clinical allergy: atopic diseases, drug all
ergy, insect allergy and anaphylaxis
Pathogenesis of Allergic DiseasePathogenesis of Allergic Disease
Genetic Susceptibility
Allergic Sensitzation
Upper/lower airway or Skinhyperresponsiveness
Allergic Diseases
Allergen Exposure
Adjuvant factors:• Tobacco smoke• Air pollutantsLack of protective factors:• Infection ?• Immunization ?• Nutrition ?
PollutantsInfectionExcercise
Modified from Ulrich Wahn 1998
Vary in spectrum and severity
Principle Pathogenesis of Allergic Diseases Principle Pathogenesis of Allergic Diseases
Th-2Th-1
IL-12
IFN-gIL-5IL-3GM-CSF
Eosonophil
Mastcell
IL-4 IgE
B-cell
APCAllergenCD4+ T-cell
Late Phase Reaction
_ +
IgG
Durham and Till 1998, Lu 1998, Drazen 1996
CD8+ cell
AllergyChula
IL-5
B-cell
Allergen
Tryptase, LTs
MBPECP, LTs
Other cells
Pathogenesis of Pathogenesis of Allergic DiseasesAllergic Diseases
Cells & MoleculesCells & MoleculesInvolved in Involved in
AllergicAllergicInflammationInflammation
Modified from Modified from Robert DaviesRobert Davies
Mediators of Mast Cells and Basophils
Histamine
Tryptase
Chymotryptase
Heparin/Chondroitin
Kininogenase
Chemotactic Factors
ProstaglandinsLeukotrienes
PAFHistamine RFs
IL-3, 4, 5, 6, 7, 8GM-CSF, TNF
Chemokines -MCP1, MIP1
Oxygen radicals
Primary Mediators Secondary Mediators
Sim TC, Grant JA 1996 AllergyChula
Mediators of Mast Cells and AllergyMediators of Mast Cells and Allergy
Mast CellMast CellBasophilBasophil
Blood VesselsBlood Vessels
Smooth MusclesSmooth Muscles
Mucus GlandsMucus Glands
Sensory NervesSensory Nerves
LeukocytesLeukocytes
H, PGDH, PGD22, , LTs, PAFLTs, PAF
KininKinin
HH
H, PGDH, PGD22, , LTs, PAFLTs, PAF
LTB4LTB4PAFPAFIL3, IL5IL3, IL5ChemokinesChemokines
Urticaria, AngioedemaUrticaria, AngioedemaLaryngeal edema, ShockLaryngeal edema, Shock
BronchospasmBronchospasmAbd. pain, VomitingAbd. pain, Vomiting
Diarrhea, RhinorheaDiarrhea, RhinorheaBronchial secretionBronchial secretion
ItchingItching
Inflammation - LPAR Inflammation - LPAR
AllergyChula
โรคภมแพทพบบอยโรคภมแพทพบบอย โรคภมแพทางจมก โรคภมแพทางจมก Allergic Allergic
RhinitisRhinitis โรคหดจากภมแพ โรคหดจากภมแพ Allergic Asthma Allergic Asthma โรคภมแพทางผวหนง โรคภมแพทางผวหนง Atopic Atopic
DermatitisDermatitis โรคลมพษโรคลมพษ UrticariaUrticaria โรคโรค แพอาหาร แพอาหาร Food AllergyFood Allergy การการแพยาแพยา Drug AllergyDrug Allergy
Allergy Chula 1999
Epidemiology of Allergic Diseasesin Thai Children
13
17.9
404.2
13
0 10 20 30 40
Prevalence (%)
AtopicDermatitis
AllergicRhinitis
Asthma1990 1995
พยนต บญญฤทธพงษ และมนตร ตจนดา 2533; ปกต วชยานนท และคณะ 2541
Skin Prick TestSkin Prick Test
สงแวดลอม กบ โรคภมแพ สงแวดลอม กบ โรคภมแพ
ตวไรฝน ทกกฝนเกสร
ฝนบาน เชอราฝนบนอน สตวเลยง
อาหาร
สงเหลานมอยรอบตวเรา มทงในบานและนอกบาน แตมหลายอยางทเราหลกเลยงได หากเรารวธทถกตอง
ควนบหรควนบหรควนธปควนธป
Factors Affecting Clinical OutcomesFactors Affecting Clinical Outcomes of Allergic Diseases of Allergic Diseases
AllergyChula
Enivronmental• Allergens• Irritants• Westernization
Infection• Viral• Bacterial
Treatment• Anti-inflammatory• Anti-allergic• Relievers
Compliance• Avoidance• Medication uses
Allergic DiseasesAllergic Diseases
RemissionRemission ModerateMild SevereSevere
Allergen Immunotherapy
Genetic Degree of atopy
Future Therapy ?
Clinical Uses of H1 AntagonistsGeneration of Antihistamines
Clinical First Second and Third
Allergic Rhinitis ++ ++ (better compliance)
Urticaria ++ ++ (better compliance)
Atopic dermatitis ++/+++ ++ (better compliance)
Asthma - -/++ (Meta-analysis= NS)URI/NAR ++ -Itching dermatosis ++/+++ ++Anti-motion sickness ++ -Antiemetic ++ -Appetite stimulation++ - (+ for astemizole)
Insomnia ++ -
AllergyChula
Treatment of Allergic Rhinitis in AdultsTreatment of Allergic Rhinitis in Adults
Allergy 1994; suppl. 19
Drug Itch/sneezing
Rhinorrhea Blockage Anosmia
Antihistamines +++ ++ + -Topical CS +++ +++ ++ +
Oral CS +++ +++ +++ ++
Topicaldecongestants
- - +++ -
Ipratropiumbromide
- +++ - -
Sodiumcromoclycate
+ + + -
Treatment of Allergic Asthma
Allergy 1994; suppl. 19
Treatment Mildintermittant
Mildpersistant
Moderatepersistant
Sverepersistant
Avoidnace + + + +Beta-2Agonist, prn
+ + + +
Inhaled steroid - +/- + +
Long-actingbeta-2 agonist
- no +/- +
Slow releasetheopphylline
- - +/- +
Anti-leukotrienes - + +/- +/-
Type II Hypersensitivity• Cytotoxic antibodies: IgG, IgMCytotoxic antibodies: IgG, IgM• Mechanisms of cytolysis: Fix complement and/or Mechanisms of cytolysis: Fix complement and/or
ADCCADCC• Clinical spectrums:Clinical spectrums:
– Autoimmune Hemolytic anemia (AIHA)Autoimmune Hemolytic anemia (AIHA)– ABO Miss-matchedABO Miss-matched– ITPITP
• Stimulatory antibody: Stimulatory antibody: Grave’s diseaseGrave’s disease
• Inhibitory antibody: Inhibitory antibody: Myasthenia gravis (anti-Ach Rc)Myasthenia gravis (anti-Ach Rc)
Principle treatments in Type II
• ABO matching• For AIHA, ITP: Steroid, immunosuppres
sive agents, +/- splenectomy
Type III Hypersensitivity• Mechanisms: Ag (protein, drugs) + Ab (IgG, I
gM) --> Immune complex --> deposit at subendothelial basement membrane --> fix complement --> chemotaxis ---> PMNs --> vasculitis
• Immune complex diseases:– Serum sickness– Autoimmune diseases: prototype-SLE– Vasculitis
Principle treatments in Type III
• Serum sickness: Avoidance of heterogeneous protein injection: ERIG antirabies
• Autoimmune diseases: SLE– Avoidance sun exposure– Steroid– Immunosupressive agents
Type IV Hypersensitivity
• Delayed-type cell-mediated reaction• Mechanism: Antigen (contactants) --> s
ensitized T-lymphoctyes --> re-exposure --> T cells activation --> cytokines ---> mononuclear cell recruitment --> DTH
• Clinical disorder: Atopic contact dermatitis
Principle treatments in Type IV • Avoidance• Topical steroid• Systemic steroid, if severe