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HYPERSENSITIVITY REACTIONS AND AUTOIMMUNITY
BSc in Public Health
11th &12th week
2014
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Innocous materials can cause hypersensitivity in certain individuals
leading to unwanted inflammation damaged cells and tissues
Non-proper reaction of the immune system to foreign substances
Mainly harmless substances – after second or multiple exposure
HYPERSENSITIVITY REACTIONS
Type I. „immediate”
Type II. Type III. Type IV.„late”
Antibody mediated T cell mediated
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TYPES OF ANTIBODY MEDIATED HYPERSENSITIVITY REACTIONS
FcRIα)
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TYPE I HYPERSENSITIVITY
REACTIONALLERGY
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SENSITISATION PROCESS
Once sensitized (immunized), every following exposure to the allergen elicits the allergic reactions.
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Pruritus
TYPES OF ALLERGIC REACTIONS
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chromosome 11q
FcεRβ chain gene
chromosome 11q
IL-3-5 IL-9, IL-13 GMCSF
HLAII DRB1*015
allergy Inproper
immunregulation Th1/Th2 inbalance
regulation of IgE synthesis
high eosinophil counts
Environmental factors
lack of tolerance
Genetic factors
GENETIC/ENVIRONMENTAL PREDISPOSITION TO ALLERGY
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Prick test
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TYPE II HYPERSENSITIVITYIgG type antibodies bound to cell surface or tissue antigens
• cells expressing the antigen become sensitive to complement mediated lysis or to opsonized phagocytosis
• frustrated phagocytosis tissue damage
• the antibody inhibits or stimulates target cell function no tissue damage
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Killing of target cell by effector-macrophage orNK-cell
Killing of targetcell by complement-mediated lysis
complement activation
IgG
IgG
Receptor-specific autoantibodyinterferes withsignal transduction
NKMf
C '
ADCC
MECHANISMS OF TYPE II HYPERSENSITIVITY REACTIONS
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Extensive tissue damage
FcR
C3R
C3b C3b
C3b
C3b C3b C3b
Binding Opsonization Internalization Enzyme release
Opsonized surface Binding Frustrated Enzyme release phagocytosis
FRUSTRATED PHAGOCYTOSIS MEDIATED BY IgG TYPE ANTIBODIES
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DRUG INDUCED ANEMIA
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MYASTHENIA GRAVIS
Autoantibodies against ACh receptors in neuromuscular junction inhibiting transmission
of nerve impulses to muscles
progressive muscle weakness
GRAVES DISEASE
Autoantibodies against TSH receptors on thyroid cells causing stimulation and overproduction of thyroid hormones
hyperthyroidism, goiter, protrusion of eyeballs
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TYPE III HYPERSENSITIVITY
Antibodies binding to soluble antigens forming small circulating immune complexes which are
deposited in various tissuesDepends on:
Size of immune complexes
Antigen-antibody ratio
Affinity of antibody
Isotype of antibody
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• symptoms caused by type III hypersensitivity reactions depend on the site of immune complex deposition
• serum sickness – intravenous immunecomplexes(horse antiserum against snake/spider venom)
• Arthus reaction – localized, skin
• Farmer’s lung – localized, lungs
TYPE III HYPERSENSITIVITY
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T CELL MEDIATED PROCESS
TYPE IV HYPERSENSITIVITY REACTION
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TYPE IV (DELAYED-TYPE) HYPERSENSITIVITY
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TYPE IV (DELAYED-TYPE) HYPERSENSITIVITY
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TYPE IV (DELAYED-TYPE) HYPERSENSITIVITY
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DELAYED-TYPE HYPERSENSITIVITY (DTH) (e.g. tuberculin skin test)
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TUBERCULIN SKIN TEST (MANTOUX TEST)
Introduction of Ag Ag = antigen:
Purified protein derivate (PPD) isolated from mycobacteria
SCREENING PREVIOUS IMMUNIZATION
(MEMORY T CELL RESPONSE)
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CONTACT DERMATITIS
mediated by both helper and cytotoxic T cells recognizing peptide antigens originated from skin
proteins that were modified by the contact sensitizing agents (e.g. cathecol of poison ivy, nickel)
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CELIAC DISEASE
• gluten is recognized as non-self antigen by T cells
• inflammation of the gut wall in the presence of gluten
• tissue damage cause villous atrophy malabsorption
• gluten-free diet can solve the problem
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AUTOIMMUNITY
• Recognition of self-antigens by the cells of the adaptive immunity (B and T cells) normally
induce tolerance
• Tolerance is achieved by different mechanisms in the body: elimination of auto-reactive (self-recognizing) lymphocytes in the bone marrow and thymus (the process
is more strict regarding T cells)
limited access of lymphocytes to some tissues (CNS, eyes, testicles)
suppression by regulator T cells (CD4+ subtype)
induction of anergy (e.g. in the absence of costimulation)
normal tissue cells are not expressing MHC class II and/or costimulatory molecules
If any of these malfunction, activation of auto-reactive lymphocytes
may provoke severe immune response against self tissues
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AUTOIMMUNE DISEASES
• The immune response against self-tissues is the same as against
pathogens
• Continuous presence of self-antigens maintain activation of auto-reactive
cells chronic inflammation
• Tissue destruction surpasses tissue regeneration
Autoimmune responses can be categorized
into type II, III or IV hypersensitivity reactions
(the innocuous agent is the self-antigen in these cases)
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GOODPASTURE SYNDROME (type II)
• auto-antibody production against type IV collagen of the basement membrane
• causing inflammation and tissue damage in the kidneys and lungs
• localized / tissue-specific autoimmune disease
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SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) (type III)
characteristic dermal lesion in SLE patients: the malar rash or butterfly
rash
fluorescent microscopic figure of immunecomplex depositions at the
dermal-epidermal junction
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RENAL FAILURE IN IMMUNECOMPLEX DISEASES
Glomerulus of a healthy individual. Relatively wide spaces between capillary loops.
One of the feared complications of the systemic autoimmune diseases is renal failure. This is most
likely to occur in SLE. Here is a glomerulus in which the capillary loops are markedly pink and thickened such that capillary lumens are hard to
see. This is lupus nephritis.
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REUMATHOID ARTHRITIS (type III and IV)
• cellular immune response against the synovial membranes of joints
• CD4+ and• CD8+ T cells• B cells/plasma cells• neutrophils• macrophages
• Rheumatoid factor: anti-IgG-Fc specific antibodies
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Insulin
b cell d cella cell a cell b cell d cell
Pancreatic islet cells
AUTOREACTIVE CYTOTOXIC T CELLS KILL INSULIN SECRETING β-CELLS
glucagon somatostatin108 insulin secreting cells
MECHANISM OF AUTOIMMUNE INSULIN-DEPENDENT DIABETES (type IV)