ALLERGY AND HYPERSENSITIVITYIMMUNE RESPONSE IN WHICH THE ANTIGEN IS AN
ENVIRONMENTAL AGENT, FOOD OR DRUG THAT IS NOT
INTRINSICALLY HARMFUL.
MOST WIDESPREAD IMMUNOLOGICAL DISORDER IN
HUMANS; RAPIDLY INCREASING – 27% INCIDENCE;
INDIVIDUAL SUSCEPTABILITY ??
WIDE RANGE OF SERVERITY
MOST EFFECTIVE THERAPY: ALLERGEN AVOIDANCE
ALLERGY AND HYPERSENSITIVITY
IMMUNE RESPONSE IN WHICH THE ANTIGEN IS AN
ENVIRONMENTAL AGENT, FOOD OR DRUG THAT IS NOT
INTRINSICALLY HARMFUL.
MOST WIDESPREAD IMMUNOLOGICAL DISORDER IN
HUMANS; RAPIDLY INCREASING – 27% INCIDENCE;
INDIVIDUAL SUSCEPTABILITY ??
WIDE RANGE OF SERVERITY
MOST EFFECTIVE THERAPY: ALLERGEN AVOIDANCE
HYGIENE HYPOTHESIS OF ALLERGY
RECOGNIZED IN 1989, LACK OF INFECTION FAVORS THE
DEVELOPMENT OF ALLERGIC DISEASE.
MYCOBACTERIA AND HELMINTHS ARE IMPORTANT IN
THIS HYPOTHESIS AS INFECTIONS CAUSED BY THESE
AGENTS GENERATE REGULATORY MECHANISMS
THAT CAN RESTORE IMMUNE BALANCE.
MULTIPLE AND REPETITIVE INFECTIOUS FACTORS
DURING CERTAIN PERIODS OF IMMUNE SYSTEM
DEVELOPMENT INFLUENCE ALLERGY AND ASTHMA
DEVELOPMENT.
TYPE I ALLERGIC RESPONSES –
IMMEDIATE HYPERSENSITIVITY. MEDIATED BY IgE
AND CAUSES THE RELEASE OF HISTAMINE,
LEUKOTRIENES AND PROSTAGLANDINS FROM MAST
CELLS AND BASOPHILS. USUALLY ATOPIC (FAMILIAL
DISPOSITION.
1. IgE BINDS TO MAST CELLS
2. ANTIGEN CROSS BRIDGING
3. HISTAMINE RELEASE (MAST CELL DEGRANULATION)
EFFECTS OF MAST CELL DEGRANULATION
EFFECTS OF MAST CELL DEGRANULATION
HISTAMINE – INCREASES VASCULAR PERMEABILITY
EOSINOPHIL CHEMOTACTIC FACTOR – ATTRACTS EOSINOPHILS
TO THE AREA, EOSINOPHILS RELEASE:
1. MAJOR BASIC PROTEIN –CAUSES BRONCHIAL CONSTRICTION
AND HYPERRESPONSIVENESS, INHIBITS CILIAL FUNCTION,
TOXIC FOR RESPIRATORY EPITHELIAL CELLS AND
PNEUMOCYTES.
2. EOSINOPHIL PEROXIDASE – TOXIC FOR RESPIRATORY
EPITHELIAL CELLS AND PNEUMOCYTES.
LEUKOTRIENES – SLOW REACTING SUBSTANCE OF ANAPHYLAXIS,
CONSTRICTION OF SMOOTH MUSCLE
PLATELET ACTIVATING FACTOR – PLATELET AGGREGATION
AND LYSIS, MACROPHAGE AND NEUTROPHIL ACTIVATION
EXAMPLES: ACUTE ANAPHYLAXIS, HAY FEVER, FOOD ALLERGIES
MEDIATORS OF ALLERGY
A. IgE – ANTIBODY PRODUCED BY B CELLS, SENSITIZES
MAST CELLS FOR MEDIATOR RELEASE, USUALLY IN
VERY LOW AMOUNTS IN SERUM.
B. HISTAMINE - SECRETED BY MAST CELLS, CAUSES
VASODILATION, INC. VASCULAR
PERMEABILITY OF VENULES AND
MUCUS PRODUCTION, CONTRICTS
BRONCHIAL AIRWAYS, STIMULATES
NERVE ENDINGS. H1 RECEPTORS
RESPONSIBLE FOR MOST
ALLERGIC RESPONSES, H4 RECEPTORS
MAY PLAY A ROLE
C. PLATELET ACTIVATING FACTOR - LIPID MEDIATOR,
SECRETED BY BASOPHILS, NEUTROPHILS,
MONOCYTES, MACROPHAGES, ENDOTHELIAL CELLS,
CAUSES RELEASE OF MEDIATORS FROM PLATELETS,
NEUTROPHIL AGGREGATION, NEUTROPHIL
SECRETION AND SUPEROXIDE ANION PRODUCTION,
INCREASES VASCULAR PERMEABILITY, CONSTRICTS
BRONCHIAL AIRWAYS.
D. PROSTAGLANDINS – DERIVED FROM ARACHIDONIC ACID
PGD2 – CONSTRICTS
BRONCHIAL AIRWAYS
PGE2 – CAUSES VASODILATION,
POTENTIATES EFFECTS
OF HISTAMINE AND
LEUKOTRIENES.
E. LEUKOTRIENES – DERIVED FROM ARACHIDONIC ACID VIA 5-LIPOXYGENASE PATHWAY, MOST CONTRIBUTE TO INC. VASCULAR PERMEABILITY, CAN INDUCE BRONCHOCONSTRICTION, “SLOW REACTING SUBSTANCE OF ANAPHYLAXIS”.
LTB4 – CHEMOTACTIC FOR NEUTROPHILS, INC. VASCULAR PERMEABILITY IN THE PRESENCE OF PGE2.
LTC4 – INC. VASCULAR PERMEABILITY, INDUCES BRONCHOCONSTRICTION.
LTD4 & LTE4 – INC. VASCULAR PERMEABILITY
LTC4, LTD4 & LTE4 – TOGETHER WERE CONSIDERED SRSA
F. CYTOKINES –
1. INTERLEUKIN 3 – STIMULATES EOSINOPHILS, MAST
CELL GROWTH FACTOR.
2. INTERLEUKIN 4 – STIMULATES PRODUCTION OF IgE
BY B CELLS, INDUCES B & T CELL PROLIFERATION, INDUCES T HELPER CELLS, HAS INHIBITORY EFFECT ON MACROPHAGES, ACTIVATES MAST CELLS, INC. MUCUS PRODUCTION, BASEMENT MEMBRANE THICKNESS AND SMOOTH MUSCLE HYPERTROPHY IN BRONCHIAL TISSUE.
3. INTERLEUKIN 5 – EOSINOPHIL GROWTH FACTOR,
INC. IL-4 INDUCED IgE PRODUCTION
4. INTERLEUKIN 13 – STIMULATES IgE SYNTHESIS BY B CELLS, HAS INHIBITORY EFFECT ON MACROPHAGES, SIGNIFICANTLY INC. MUCUS PRODUCTION, BASEMENT MEMBRANE THICKNESS AND SMOOTH MUSCLE HYPERTROPHY IN BRONCHIAL TISSUE.
4. GRANULOCYTE-MONOCYTE COLONY STIMULATING FACTOR – INC. GRANULOCYTE
(INCLUDING EOSINOPHIL) AND MONOCYTE
COLONY FORMATION, ACTIVATES
MACROPHAGES
5. TUMOR NECROSIS FACTOR-a – INCREASES
NEUTROPHIL PHAGOCYTOSIS & DEGRANULATION,
PRODUCTION OF REACTIVE OXYGEN SPECIES,
CHEMOTACTIC FOR BOTH MACROPHAGES AND
NEUTROPHILS, INC. PGE2 PRODUCTION BY
MACROPHAGES.
ALLERGY TREATMENTS
IMMUNOLOGIC APPROACHES
ALLERGIC DESENSITIZATION
- INDIVIDUAL VARIATION
- MULTIPLE ALLERGEN ISOFORMS
(ANTIGEN SPECIFIC PEPTIDE THERAPY)
ANTI-IgE THERAPY: OMALIZUMAB (XOLAIR), GOOD FOR AEROALLERGINS AND ASTHMA TREATMENT, EFFICACY NOT SHOWN IN OTHER ALLERGIC CONDITIONS. HUMAN IgG1 BINDS TO IgE TO REMOVE IT FROM CIRCULATION, INHIBITS BINDING OF IgE TO HIGH AFFINITY RECEPTORS ON MAST CELLS AND BASOPHILS.
ALLERGY TREATMENTS
IMMUNOLOGIC APPROACHES (CONT.)
SOLUBLE IL-4Ra: DEC. DEVELOPMENT OF T CELLS,
REMOVES CIRCULATING IL-4 BY TRAPPING
IL-4 MUTEIN: IL-4 VARIENT, CAN BIND TO CELL
SURFACE RECEPTOR BUT NOT TRIGGER RESPONSE
SOLUBLE IL-13Ra2: DEC. AIRWAY RESPONSIVENESS
IN MOUSE STUDIES, REMOVES CIRCULATING IL-13
CHEMICAL APPROACHES - ANTIHISTAMINES
ASTHMA
DISEASE CHARACTERIZED BY REVERSIBLE
OBSTRUCTION OF THE BRONCHI. ACCOMPANIED BY
NONSPECIFIC BRONCHIAL HYPERRESPONSIVENESS OR
“IRRITABILITY”, ASSOCIATED WITH ATOPY,
SPONTANEOUS RELEASE OF MEDIATORS FROM MAST
CELLS IS INCREASED
PATHOPHYSIOLOGY OF ASTHMA
PATHOGENESIS OF ASTHMA
PATHOLOGY
EARLY RESPONSES - RAPID RELEASE OF PREFORMED
INFLAMMATORY MEDIATORS BY MAST CELLS,
SYNTHESIS OF EICOSANOIDS, BRONCHOCONSTRICTION
LATE RESPONSE - SECOND ROUND OF
BRONCHOCONSTRICTION
ACUTE ATTACK CAN BE FATAL, ACUTE ASPHYXIATION,
MARKED CONSTRICTION AND OCCLUSION OF THE
BRONCHI.
Comments