Transcript HYPERSENSITIVITY REACTIONS

HYPERSENSITIVITY REACTIONS
Immune responses that are inadequately controlled,
inappropriately targeted to host tissues, or triggered by
commensal microorganisms or usually harmless
environmental antigens.
AN OVERVIEW OF HYPERSENSITIVITY
REACTIONS
Type I.
Type II.
„immediate”
Type III.
Type IV.
„late”
Antibody mediated
T cell mediated
Types of antibody mediated hypersensitivity reactions
FcRIα)
TYPE I HYPERSENSITIVITY REACTION
ALLERGY
Immune responses to nonmicrobial environmental
antigens that involve TH2 cells, immunoglobulin E,
mast cells, and eosinophils
Common allergic symptoms
Sequence of events in immediate hypersensitivity
reactions
TFH
Cellular and Molecular Immunology, 7th ed., 2012 Elsevier
Sensitization to an inhaled allergen
Comparison of the diversity of allergen-specific
antigen receptors on a B cell and a mast cell
Biochemical events of mast cell activation
The physical effects of IgE-mediated mast-cell degranulation vary
with the tissue exposed to allergen
Allergic reactions consist of an immediate reaction
followed after some hours by a late-phase reaction
The acute response in allergic asthma leads to
TH2-mediated chronic inflammation of the airways
Defense against many helminthic infections is mediated
by IgE antibodies and activation of eosinophils
Activated eosinophils release toxins, cytokines and
other inflammatory mediators
Systemic anaphylaxis
Normal larynx
Laryngeal oedema
Systemic anaphylaxis is caused by allergens that reach the
blood stream
Genetic/environmental predisposition to allergy
Genetic factors
chromosome 11q
FcεRβ chain gene
chromosome 11q
IL-3-5 IL-9, IL-13 GMCSF
HLAII DRB1*015
Inproper
immunregulation
Th1/Th2 inbalance
regulation of IgE synthesis
high eosinophil counts
allergy
Environmental
factors
lack of tolerance
Hygiene Hypothesis
early childhood infections inhibit the tendency to develop allgergic disease
Hygiene Hypothesis - Infection history makes a
difference
The wheal and flare reaction in the skin
Cellular and Molecular Immunology, 7th ed., 2012 Elsevier
ImmunoCAP
Specific IgE Blood Test
Anti-IgE
Serum IgE
Allergen
Solid phase
Possible approaches to decrease allergic reactions
Enhancement of T reg activity
Inhibition of IgE production
Hyposensitization – IgE vs. IgG
Inhibition of IgE binding
Inhibition of allergen binding
Inhibition of signal transduction
Inhibition of degranulation
Blocking of mediators’ effects
TYPE II HYPERSENSITIVITY
IgG or IgM antibodies bound to antigens
of particular cells or the extracellular matrix
Mechanisms of type II
hypersensitivity
reactions
Cellular and Molecular Immunology, 7th ed., 2012 Elsevier
Frustrated phagocytosis mediated by IgG antibodies
Binding
Opsonization Internalization
C3b
C3b
C3b
C3b
Enzyme
release
C3b
C3R
FcR
The target, which
cannot be
phagocytosed, is
damaged
C3b
Absorbed antigen
Opsonized surface Binding Frustrated
(drug)
Enzyme release
phagocytosis
Examples of type II hypersensitivity
Development of drug sensitivity I.
Development of drug sensitivity II.
TYPE III HYPERSENSITIVITY
Antibodies form immune complexes in the circulation,
and the complexes are subsequently deposited in
tissues, particularly in blood vessels, and cause injury
Immune complex–mediated tissue injury
Cellular and Molecular Immunology, 7th ed., 2012 Elsevier
Tissue damage caused by deposited immune complexes
Frustrated
phagocytosis
Immune complexes activate the complement system, neutrophils, basophils and
thrombocytes
Examples of human immune complex–mediated diseases
Symptoms caused by type III hypersensitivity reactions
depend on the site of immunecomplex deposition
Arthus-reaction
• Localized Type III hypersensitivity
• Local vasculitis develops as a result of immune complex deposition
• Inhaled antigens (fungi, animal feces) may induce similar reaction in the
lung (Farmer’s lung and piegeon-breeder’s lung)
Localized deposition of immune complexes within a
tissue causes a type III hypersensitivity reaction
TYPE IV HYPERSENSITIVITY REACTION
T lymphocytes injure tissues either by triggering
inflammation or by directly killing target cells
Type IV hypersensitivity reactions
Mechanisms of T cell–mediated hypersensitivity reactions
Cellular and Molecular Immunology, 7th ed., 2012 Elsevier
Delayed-type hypersensitivity (DTH)
(e.g. tuberculin skin test)
TH1 from a previous
immunization (memory)
Tuberculin skin test
Introduction of Ag
Ag = antigen
Purified protein derivate (PPD)
DTH as a result of a contact-sensitizing agent*
CONTACT DERMATITIS
*a contact-sensitizing agent is usually a small molecule that penetrates the skin
then binds to self-proteins, making them “look” foreign
CONTACT DERMATITIS
Physical contact with
poison ivy transfers
pentadecacatechol,
which causes dermatitis
CELIAC DISEASE
Delayed-type hypersensitivity