Basic Immunology of Allergic

Disease

Tutik Ida Rosanti

Laboratorium Parasitologi
 Hypersensitivity Diseases

• Disorders caused by immune responses:

– failure of self tolerance  autoimmunity
– uncontrolled / excessive immune reactions
against non-self (foreign) antigens

• Classified into 4 type of reactions based

on their effector mechanisms responsible
for cell & tissue injury:
– types I, II, III, and IV
 Table 1 Classification of Immunologic Diseases

Type of Pathologic immune Mechanisms of tissue

hypersensitivity mechanisms injury and disease
Type I: immediate type IgE antibody Mast cells + mediators:
hypersensitivity vasoactive amines, lipid
(Allergy) mediators, cytokines:
TNF-a, Il-4, IL-5, IL-
13, MIP-1a, IL-3
Type II: antibody- IgM, IgG antibodies * Opsonization &
mediated against cell surface or phagocytosis of cells
extracellular antigens * Complement (C) & Fc
receptor-mediated inflam
Type III: immune Imm. complex of C & Fc receptor-mediated
complex-mediated circulating Ags. and IgM recruitment and activation
or IgG Abs. of leukocytes
Type IV: cell-mediated • CD4+ T cells * Macrophage activation,
(delayed type (Tdth) cytokine-mediated inflam
hypersensitivity) • CD8+ CTL * Direct target cell lysis
 The nature of allergens
• Proteins or chemicals bound to proteins
• Low molecular weight, glycosylated-, high
soluble:
– Dietary proteins
• Not often accompanied by natural adjuvant
– Fail to induce IL-12 & IL-18 secreting Th1 cell
responses
• Many potent allergens
– Cysteine protease of house dust mite
– Phospholipase A2 in bee venom
– Others: pollen, mold spores, latex, certain drug, ie.
penicillin
Genetic basis of atopy
 Table 2 Candidate genes assoc. with atopy
Chromosome Candidate genes Role of gene
location products
5q31 IL-4, IL-5, IL-9, IL-13 IL-4 & IL-3 IgE
IL-5  eosinophils
5q32 b2-adrenergic receptor Regulates arterial &
bronchial smooth
muscle contraction
6p Class II MHC Regulates T cell
response  Th2
6p21.3 TNF-a Mast cell inflammatory
mediator
11q13 Fce RI b -chain Mast cell IgE receptor
 Role of T cells

• Allergen specific IL-4 secreting T cells

– Overnumbered in atopic than non-atopic
individuals
• CD4+ Th 2 cells produce cytokines
– IL-4, for isotype switching to IgE, and promotes
eosinophil recruitment
– IL-5, for eosinophil activation
– IL-13, has a similar effect to IL-4, and regulates
inflammation independently to IgE
 Role of IgE antibodies
• Mediate mast cell activation  degranulation
– Through their Fce that interact with a high affinity
to Fce RI  cytophilic (reaginic) antibody
– Antigen-cross linked IgE/FceR

• Normal serum conc: less than 1mg/ml

– Can rise to over 1000 mg/ml in severe atopy and
helminthic infection

• Has totally 5 domains (4 heavy chain constant-

and 1 heavy chain variable domains)
 Role of mast cells

• Effector cell of immediate hypersensitivity /

allergy
• Contain cytoplasmic granules whose contents are
the major mediators of allergic reaction:
– Vasoactive amines, lipid mediators, cytokines
• Two subpopulations are detected:
– Connective tissue (CTMC) and mucosa (MMC)
• Specific locations throughout the body:
– Near blood vessels, nerve, beneath epithelia
Table 2 Mediators produced by mast cells
Mediator category Mediator Function(s)
Preformed structure Histamine Increases vasc. permeability, smooth
muscle contraction

Tryptase, acid hydrolase, Degrade microbial structure, tissue

cathepsin G, carboxypeptidase damage/remodelling

Lipid mediators produced Prostaglandin D2 Vasodilatation, bronchoconstriction,

on activation neutrophil chemotaxis

Leukotrien C4, D4, E4, PAF Prolonged bronchoconstriction,

mucus secretion, increased vasc.
permeability
Cytokines IL-3 Promotes mast cell proliferation

TNF-, MIP-1 Promote inflam./late phase reaction

IL-4, IL-13, and IL-5 Promote Th2 differentiation, and

eosinophil production
 Sequence of events in allergic
reaction
• Initial exposure of antigen/allergen
– Stimulatation of CD4+ T cells  TH2
– IL-4 promotes different. of B cells IgE AFC
– Sensitization of mast cells by IgE Ab. & subsequent
Ag degranulation
• Immediate/early vascular & muscular changes
– Increased vascular permeability& vasodilatation
(eg. ‘wheal and flare reaction’), visceral and
bronchial smooth muscle contraction
• Late phase reaction
– Infiltration of inflammatory cells: eosinophils,
basophils, neutrophils, lymphocytes)
CONCLUSION
Contributing factors to allergic reactions

• Allergens:
– environmental protein antigens genetically
susceptible individuals
• CD4+ Th cells, esp. Th2 subpopulations
- IL-4  IL-4-induced IgE switching factor
• IgE B cells
– IgE antibodies
• Mast cells (tissue) / basophils (blood circul.)
– FceRI
• Others: eosinophils, neutrophils, basophils