ALLERGOLOGY

BAILON, MARIA CECILIA

PEDIA RESIDENT
 ALLERGY AND ATOPY
• Allergic diseases are complex genetic conditions susceptible to environmental triggers.
• The clinical expression of IgE-mediated allergic diseases that have a familiar predisposition
and that manifest as hyperresponsiveness in target organs (lungs, skin, GIT, nose)
• Atopic persons respond to allergen exposure with rapid expansion of T helper type 2 (Th2)
cells that secrete cytokines (IL-4, IL-5, IL-13) → favors IgE synthesis and eosinophilia
• IL-5 & IL-9: development of eosinophils
• IL-3, IL-4 & IL-9: mast cell activation
• A fraction of immune response to allergen results in proliferation of Th1 cells (involved in the
eradication of IC organisms like microbacteria) → contributes to chronicity and the effector
phase in allergic disease
• Chronic allergic reactions are characterized by infiltration of Th1 and Th17 cells.
 • 3 REACTION PATTERNS OF IGE-MEDIATED IMMUNE
RESPONSES:
o Early-phase response
 Immediate response after allergen is introduced into target organs
 Mast cell degranulation & release of preformed mediators
 Occurs within 10 minutes after allergen exposure and resolves within 1-3 hours
 Increased local vascular permeability → leakage of plasma proteins, tissue swelling,
increase blood flow (Itching, sneezing, wheezing, abnormal cramps)
o Late-phase response
 Occur within hours after allergen exposure (max 6-12 hours) and resolves in 24 hours
 Edema, redness, or induration of the skin; sustained nasal blockage; persistent wheezing
 Early infiltration of neutrophils and eosinophils
o Chronic allergic disease
 Tissue inflammatation can persist for days to years
 Repeated stimulation of allergic effector cells contributes to unresolved inflammatory
conditions
 Th-2 type cytokines (IL-3, IL-5, GM-CSF) secreted during allergic reactions can prolong
survival of allergic effector by delaying apoptosis
 Tissue remodeling leads to irreversible changes in target organs
 • GENETIC BASIS OF ATOPY & COMMON
MANIFESTATION
o Atopic diseases have a strong familiar predisposition with about 60% heritability
o The 5q23-35 region comprises several genes implicated in allergic disease pathogenesis
o The risk of allergy disease in a child approaches 50% when one parent is allergic and 60%
when both parents are allergic
o Allergic salute, nasal crease, allergic cluck, allergic shiners with Dennie-Morgan foldS
 • DIAGNOSTIC:
o In vitro test:
 CBC and nasal and bronchial secretions are checked for eosinophilia
 Serum IgE (1 IU is equal to 2.4 ng fo IgE)
 Allergen-specific IgE assay
o In vivo tests:
 Allergy skin tests by prick/puncture technique
 Selective skin test by intradermal technique
 Oral food challenge
 • MANAGEMENT

o Control of allergens
 House dust mites (Dermatophagoides pteronyssinus, D. farinae, Euroglyphus maynei) feed
on animal and human skin scales and do not survive with relative humidity <50%.
 Hair, dander, and saliva from dogs and cats
 Fel d 1, a major cat allergen, is highly charged protein that readily sticks to surfaces
 Air cleaners with high-efficiency particulate air (HEPA) filters help in reducing the amount
of airborne cat allergen
 Aspergillus and Penicillum – most prevalent fungi in damp houses
o Allergen immunotherapy
 For seasonal or perennial AR, asthma triggered by allergen exposures, and insect
venom sensitivity
 Consider the patient’s duration and severity of symptoms in spite of a trial of allergen
avoidance and appropriate medications, the quality of life, and cost
 For seasonal allergies: document >2 consecutive seasons of symptoms
 Not for <5 years old because of the increases risk of systemic reactions
 Contraindicated in patients under beta-blocker medications
 ALLERGIC RHINITIS
• Diagnosis generally established by 6 years old
• 20% are seasonal, 40% perennial, 40% mixed
• Pathogenesis:
o Exposure of an atopic host to an allergen leads to specific IgE production
o Early-phase reaction: degranulation of mast cells & release of inflammatory mediators
o Late-phase reaction: arises 4-8 hours following allergen exposure
• Clinical Manifestations
o Sneezing, rhinorrhea, nasal obstruction, itching of the nose, palate, pharynx & ears,
itching, redness & tearing of the eyes
o Pale mucosa, clear mucoid nasal discharge, allergic salute, rabbit nose
• Management
o Avoidance of exposure to suspected allergens and irritants
o Immunotherapy for those who cannot avoid inhalant allergens and drug therapy
o Oral antihistamines; inhaled budesonide, fluticasone, mometasone
 ADVERSE REACTION TO FOOD
• Any untoward reaction following ingestion of food and devided into:
o Food intolerance – adverse physiologic responses based on functional properties of
food
o Food hypersensitivity – adverse immunologic response and allergies due to IgE-
mediated and/or cell-mediated mechanisms
• Most children “outgrow” milk and egg allergies with about 50% doing so within 3-5 years
• About 80-90% of children with peanut or seafood allergy retain their allergy for life
• Etiology: egg, milk, peanuts, fish soy, wheat account for 90% of food allergies during
childhood
• Class 1 food allergens: penetrates the GI barrier
• Class 2 food allergens: penetrates the respiratory tract
• All milk allergies develop by 12 months of age and all egg allergies by 18 months of age
• Clinical Manifestations: GIT, skin, respiratory tract
• Management: Elimination diet for 14 days followed by food challenge.
 ADVERSE REACTIONS TO DRUGS

Unpredictable drug reactions (idiosynctatic

reactions, allergic reactions, pseudoallergic
reactions)

 Dose dependent  Dose independent

 Related to known pharmacologic actions  Often NOT related to known
of the drug pharmacologic actions of the drug
 Occur in patients without any unique  Occur in patients who are genetically
susceptibility predisposed
 Allergic reactions require prior sensitization,
manifest with allergic and occur in
genetically susceptible individual
 ORGANS OF THE IMMUNE SYSTEM
I. The Reticuloendothelial System
II. The Lymphoid Organs
1. Bone marrow
2. Thymus
3. Lymph Nodes
4. Spleen
III. Other Peripheral Lymphoid Tissues

THE RETICULOENDOTHELIAL SYSTEM

• Mesenchymal cells and tissues distributed throughout the body
• Either fixed or wandering and able to engulf particulate materials
• Exhibit cytokine-secreting function
• Fibrocytes, reticulum cells, macrophages, monocytes
 LYMPHOID ORGANS
• Bone Marrow
o Growth-promoting cytokines push precursor cells to differentiate (also called colony-
stimulating factors like IL-3)
• Thymus
o 2 major functions: maturation of precursor T-lymphocytes & induction of
immunocompetence
o T-cells first detected in the thymus on the 7th-8th week of gestation & undergoes physiologic
involution at puberty; maturation & selection of T lymphocytes continue into adult life
• Lymph Nodes
o Small encapsulated nodular aggregates of lymphoid tissues with anatomical groupings in
the neck, axilla, femoral and popliteal areas
o Antigens are delivered via the lymphatics to lymph nodes where specific immune
responses are generated
o Both T-cells and B-cells are found here
o Anatomy & size vary with the state of lymphocyte activation
• Spleen
o Vital for immune responses to blood-borne antigens
o Acts as a waste disposal system
o Lymphocytes occupy the periarteriolar sheath where 2/3 are CD4+T-cells and 1/3 are
CD8+T-cells
o B-cells occupy the follicular and germinal centers
o Asplenic patients susceptible to infection by encapsulated bacteria

OTHER PERIPHERAL LYMPHOID TISSUES

• Mucosal immune system
o A function of the aggregates of lymphocytes, macrophages & other accessory cells
located beneath the mucosal
o Mucosa associated lymphoid tissue (MALT):
 Peyer’s patches in the lamina propria of the SI
 Lymphoid follicles in the appendix
 Tonsils in the pharynx
 Submucosal lymphoid tissue throughout the upper airways & bronchi
 CELLULAR ELEMENTS OF THE IMMUNE SYSTEM
1. Lymphocytes
• Serve as memory & effector cells performing as killer & immunoregulatory cells & Ig-
producing cells
• Synthesize and secrete cytokines which mediate cell growth and differentiation
• 2 major classes: T-cells (70%) & B-cells (30%)
2. T-cells
• Stem cells mature in thymus → develop cell membrane proteins called cluster
differentiation (CD) proteins  used to different subsets of T-cells
• CD4+ cells are helper/inducer cells
• CD8+ are suppressor/cytotoxic cells (kill microorganisms by direct action on their
surfaces)
• Normal ratio CD4+:CD8+ is 2:1
3. Natural killer cells:
• Subpopulation of lymphocytes identified as larger granular lymphocytes that
comprise 5% of peripheral blood lymphocytes
• Nonphagocytic and perform antibody dependent cell cytotoxicity
• Bind and trigger release of cytolysin (a protein that creates pores on cell
membranes of target cells resulting in lysis)
• Principally involved in lysis of tumor & virus infected target cells
• First line of defense against neonatal herpes virus infection
4. Phagocytes:
• Two important cell types: polymorphonuclears & mononuclear phagocytes that arise
from the BM
• It takes 14 days for a PMN to mature from a myeloblast; t1/2 in bloodstream 6 hours;
t1/2 in tissues is 1-2 days
• MNPs (monocytes and tissue macrophages) circulate 1-4 days
 CLINICAL DISORDER OF NEUTROPHIL FUNCTION
o Degranulation abnormality
 Chediak-Higashi syndrome – disorder coalescence of lysosomal granules (failure of
phagolysosomal fusion)  decreased neurtophil chemotaxis ; neutropenia; recurrent
pyogonic infections; hepatosplenomegaly. treatment: antibiotics
o Adhesion abnormality
 Leukocyte adhesion deficiency – neutrophilia; mutations in integrins or defective adhesion
proteins (LFA-1) proteins on the phagocyte surface  recurrent bacterial infection
associated with a lack of pus formation; delayed separation of umbilical cord. Treatment:
Antibiotic, BMT
o Depressed motile response
 Hyper-IgE syndrome
- autosomal dominant and the responsible gene is Stat3
- impaired chemotaxis and regulation of cytokine production
- recurrent skin and sinupolmonary infections, eczema, mucocutaneous candidiasis,
eosinaphilia,
retained primary teeth, scoliosis, characteristic facies
o Lack of NADPH oxidase activity
 Chronic Granulomatous Disease
- Failure of oxidative burst
- Normal B- and T-cell activity
- Recurrent infections with catalase-positive bacteria and fungi;
widespread granulomas of unknown etiology
- Treatment: antibiotic chemoprophylaxis

5. Eosinophils:
• Contains granules with major basic protein that are toxic for helminths
• IL-5 activates and influences its production
• Major cationic proteins mediate late-phase allergic reaction
6. Mast cells & Basophils
• Effectors of immediate hypersensitivity since they carry Fc receptors for IgE
• In allergic individuals, there is an increased number of allergen specific IgE molecules
bound to these receptors
 HUMORAL ELEMENTS
• Ig or antibodies are produced by B-cells (surface Igs) & plasma cells (secretory Igs)
• Found in germinal centers of lymph nodes, splenic follicles, Peyer patches, tonsils,
adenoids, appendix, colostrum, saliva, GI and urinary tracts
• Comprise 20% of the total plasma proteins

1. Immunoglobulins
• IgM: Largest; 10% normal serum Igs; earliest Ab in response to an Ag
• IgG: Most abundant; only Ig that can traverse the placental barriers
• IgA: Synthesized in the submucosa of the respiratory & GIT & excretory glands; does not
fix
complement or cross the placenta
• IgD: Predominantly found on the human B lymphocytes like IgM; differentiation of B-
cells
• IgE: Less than 10% in the serum; role in parasitic infection & allergic reaction
2. Complement
• Main function: mediates inflammatory processes, facilitates ingestion by opsonizing
pathogens for phagocytosis, mediates cell lysis & stimulates B- & T-cell responses
• 2 pathways of activation: classical & alternative
• Classical components: C1q, C1r, C1s, C2, C3, C4
• Alternative components: properdin, C3, factor B, factor D
• Common to both pathways: C5, C6, C7, C8, C9 (precursor of the membrane attack
complex)

3. Cytokines
• Growth regulating factors for hematopoietic cells; immunomodulators
• 5 distinct families: interleukins, colony stimulating factors, interferons, chemokines,
growth factor
o Interferon – antiviral
o Chemokines – chemoattracctant & growth regulating
o Growth factors control tissue function
4. Accessory molecules
• Also called phenotypic markers as they identify and differentiate between cell
populations
• Adhesion molecules
o Potential use: monitors graft rejection, SLE. and RA
• Cluster differentiation (CD) antigen
o Cell surface proteins that identify a particular cell lineage that have a defined structure
• Human leukocyte antigens (HLA) or major histocompatibility complex (MHC)
o HLA-A, B, C, DR, DQ, DP
o Basis of tissue compatibility in recipient-donor screening
o HLA matching predicts short- and long-term graft survival
o Associated with susceptibility to certain diseases
 IMMUNOPATHOLOGIC REACTIONS

• Type I – Immediate hypersensitivity

• Type II – Cytotoxic reaction
• Type III – Immune complex-mediated reaction
• Type IV – Delayed type hypersensitivity

Type I:
• Due to the release of mediators like histamine, leukotriene, serotonin, after activation by
allergens of specific cells (mast cells, basophils) which are passively sensitized by IgE
• Effects on target organs: bronchoconstriction, edema, increased mucosal secretion
• Examples: asthma urticaria, allergic rhinitis, anaphylaxis
Type II:
• Ab bind to Ag and the immune complex formed activates complement  membrane
attack complex (MAC) is formed  cell lysis
• Examples:
1. Hemolytic disease
2. Erythroblastosis fetalis
3. Graft rejection
4. Goodpasture’s syndrome
5. Blood transfusion reaction
6. ITP

Type III:
• Ab reaction with Ag  immune complex is formed  release lysosomal enzymes  tissue
destruction
• Examples:
1. Post-infectious glomerulonephritis
2. Serum sickness
3. Rheumatoid arthritis
4. Systemic lupus erythematosus
5. Stevens-Johnson syndrome
6. Polyarteritis nodosa
Type IV:
• Cell infiltration with accumulation of CD4+ & CD8+ cells & macrophage activation 
release of cytokines  stimulate fibroblast proliferation & collagen production  fibrosis
• Examples:
1. PPD test
2. Contact allergic dermatitis
3. Syphilis
4. Leprosy