Transcript Immunological Diseases Spectrums and Mechanisms Assistant Professor Kiat Ruxrungtham, M.D. Division of Allergy and Clinical Immunology Department of Medicine, Faculty of Medicine Chulalongkorn University.

Immunological Diseases
Spectrums and Mechanisms
Assistant Professor Kiat Ruxrungtham, M.D.
Division of Allergy and Clinical Immunology
Department of Medicine, Faculty of Medicine
Chulalongkorn University
Principles of Immunology
• Key roles of immune responses
• Terminology
• Primary and Secondary Immune
Responses
• Cells and Molecules involved
• Immunological Disorders
• Mechanisms and Clinical Implications
Key Roles of Immune System
• Prevent and control infection
• Prevent and control autoimmune
diseases
• 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 Immunity
Innate
Acquired
Ag specificity
no
yes
Magnitude (10, 20)
same
higher (20 > 10)
Memory
no
yes
Key components
PMN, NK T, B lymphocytes
C’, barriers APCs
Primary and Secondary
Immune Responses
Lag period
Primary IR
Secondary IR
7-10
2-5 days
Peak response relatively low
relatively high
Ig class
Mostly IgM
Other class (IgG,
IgA, etc)
Antigen [ ]
relatively high
relatively low
Cells and Molecules Involved
in Immunology
Innate Immunity
• Cells: epithelium, phagocytes
(neutrophils, monocyte-macrophages)
NK cells, mast cells
• Molecules: complement, inflammatory
mediators, cytokines, chemokines,
adhesion molecules
Cells and Molecules Involved
in Immunology
Acquired Immunity
• Cells: APCs (macrophages), T (CD4+,
CD8+) and B lymphoctyes (plasma
cells), monocytes
• Molecules: HLA, cytokines,
immunoglobulins, 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 reexposure
• IgE antibody, mast cells/ basophils and
its’ mediators
• Target organ immediate reactions
• Clinical allergy: atopic diseases, drug
allergy, insect allergy and anaphylaxis
Pathogenesis of Allergic Disease
Adjuvant factors:
Genetic Susceptibility
Lack of protective
factors:
Allergic Sensitzation
• Tobacco smoke
• Air pollutants
• Infection ?
• Immunization ?
• Nutrition ?
Allergen
Exposure
Upper/lower airway or Skin
hyperresponsiveness
Pollutants
Infection
Excercise
Allergic Diseases
Modified from Ulrich Wahn 1998
Vary in spectrum
and severity
Principle Pathogenesis of Allergic Diseases
Durham and Till 1998, Lu 1998, Drazen 1996
APC
Allergen
CD4+ T-cell
IL-12
Th-1
IL-4
IFN-g
B-cell
CD8+ cell
IgG
_
Other cells
IL-5
IL-3
GM-CSF
+
Late Phase Reaction
AllergyChula
Allergen
Th-2
IgE
B-cell
Mast
IL-5 cell
MBP
ECP, LTs
Eosonophil
Tryptase, LTs
Pathogenesis of
Allergic Diseases
Cells & Molecules
Involved in
Allergic
Inflammation
Modified from
Robert Davies
Mediators of Mast Cells and Basophils
Primary Mediators
Secondary Mediators
Histamine
Prostaglandins
Leukotrienes
PAF
Histamine RFs
IL-3, 4, 5, 6, 7, 8
GM-CSF, TNFa
Chemokines MCP1, MIP1
Oxygen radicals
Tryptase
Chymotryptase
Heparin/Chondroitin
Kininogenase
Chemotactic Factors
Sim TC, Grant JA 1996
AllergyChula
Mediators of Mast Cells and Allergy
H, PGD2,
LTs, PAF
Kinin
Urticaria, Angioedema
Laryngeal edema, Shock
Blood Vessels
Smooth Muscles
H, PGD2,
LTs, PAF
H
Mast Cell
Basophil
Diarrhea, Rhinorhea
Bronchial secretion
Mucus Glands
Sensory Nerves
LTB4
PAF
IL3, IL5
Chemokines Leukocytes
Bronchospasm
Abd. pain, Vomiting
Itching
Inflammation - LPAR
AllergyChula
โรคภูมแิ พ้ ทพี่ บบ่ อย






โรคภูมิแพ้ทางจมูก Allergic Rhinitis
โรคหืดจากภูมิแพ้ Allergic Asthma
โรคภูมิแพ้ทางผิวหนัง Atopic Dermatitis
โรคลมพิษ
Urticaria
โรคแพ้อาหาร Food Allergy
การแพ้ยา
Drug Allergy
Allergy Chula 1999
Epidemiology of Allergic Diseases
in Thai Children
1990
13
Asthma
1995
4.2
40
Allergic
Rhinitis
17.9
Atopic
Dermatitis
13
0
10
20
30
Prevalence (%)
พยนต์ บุญญฤทธิพงษ์ และมนตรี ตูจ้ ินดา 2533; ปกิต วิชยานนท์ และคณะ 2541
40
Skin Prick Test
สิ่ งแวดล้ อม กับ โรคภูมแิ พ้
ฝุ่ นบ้าน
ฝุ่ นบี่นอน
เกสร
ตัวไร่ ฝนุ่
เชื้อรา
ที่กกั ฝุ่ น
สัตว์เลี้ยง
อาหาร
สิ่ งเหล่านี้มีอยูร่ อบตัวเรา มีท้ งั ในบ้านและนอกบ้าน
แต่มีหลายอย่างที่เราหลีกเลี่ยงได้ หากเรารู ้วิธีที่ถูกต้อง
ควันบุหรี่
ควันธูป
Factors Affecting Clinical Outcomes
of Allergic Diseases
Treatment
Enivronmental
• Allergens
• Irritants
• Westernization
Genetic
Degree of atopy
• Anti-inflammatory
• Anti-allergic
• Relievers
Compliance
• Avoidance
Infection
• Medication uses
• Viral
• Bacterial
Allergen
Immunotherapy
Allergic Diseases
Remission
Mild
Future Therapy ?
Moderate
Severe
AllergyChula
Clinical Uses of H1 Antagonists
Clinical
Generation of Antihistamines
First
Second and Third
Allergic Rhinitis
++
++ (better compliance)
Urticaria
++
Atopic dermatitis ++/+++
Asthma
NS)URI/NAR
++
Itching dermatosis ++/+++
Anti-motion sickness
++
Antiemetic
++
Appetite stimulation
++
Insomnia
++
++ (better compliance)
++ (better compliance)
-/++ (Meta-analysis=
++
- (+ for astemizole)
AllergyChula
Treatment of Allergic Rhinitis in Adults
Drug
Itch/
sneezing
Rhinorrhea Blockage
Anosmia
Antihistamines
Topical CS
+++
+++
++
+++
+
++
+
Oral CS
+++
+++
+++
++
Topical
decongestants
-
-
+++
-
Ipratropium
bromide
-
+++
-
-
Sodium
cromoclycate
+
+
+
Allergy 1994; suppl. 19
Treatment of Allergic Asthma
Mild
intermittant
Mild
persistant
Moderate
persistant
Svere
persistant
+
+
+
+
+
+
+
+
-
+/-
+
+
Long-acting
beta-2 agonist
-
no
+/-
+
Slow release
theopphylline
-
-
+/-
+
Anti-leukotrienes
-
+
+/-
+/-
Treatment
Avoidnace
Beta-2
Agonist, prn
Inhaled steroid
Allergy 1994; suppl. 19
Type II Hypersensitivity
• Cytotoxic antibodies: IgG, IgM
• Mechanisms of cytolysis: Fix complement
and/or ADCC
• Clinical spectrums:
– Autoimmune Hemolytic anemia (AIHA)
– ABO Miss-matched
– ITP
• Stimulatory antibody: Grave’s disease
• Inhibitory antibody: Myasthenia gravis (anti-Ach
Rc)
Principle treatments in Type II
• ABO matching
• For AIHA, ITP: Steroid,
immunosuppressive agents, +/splenectomy
Type III Hypersensitivity
• Mechanisms: Ag (protein, drugs) + Ab
(IgG, IgM) --> 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) -->
sensitized T-lymphoctyes --> reexposure --> 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