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HYPERSENSITIVITY
REACTIONS AND
AUTOIMMUNITY
BSc in Physiotherapy
12th week
2015
HYPERSENSITIVITY REACTIONS
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
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
SENSITISATION PROCESS
Once sensitized (immunized), every following
exposure to the allergen elicits the allergic reactions.
TYPES OF ALLERGIC REACTIONS
Pruritus
GENETIC/ENVIRONMENTAL PREDISPOSITION TO ALLERGY
Genetic factors
Improper
immunoregulation
allergy
Environmental
factors
Prick test
TYPE II HYPERSENSITIVITY
IgG 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
FRUSTRATED PHAGOCYTOSIS MEDIATED BY
IgG TYPE ANTIBODIES
Binding
Opsonization Internalization
C3b
Enzyme
release
C3b
C3b
C3R
FcR
Extensive tissue
damage
C3b
C3b
C3b
Opsonized surface Binding Frustrated Enzyme release
phagocytosis
DRUG-INDUCED ANEMIA
MYASTHENIA GRAVIS
GRAVES DISEASE
Autoantibodies against ACh receptors in
neuromuscular junction inhibiting transmission
of nerve impulses to muscles
Autoantibodies against TSH receptors on
thyroid cells causing stimulation and
overproduction of thyroid hormones
progressive muscle weakness
hyperthyroidism, goiter, protrusion of eyeballs
TYPE III HYPERSENSITIVITY
Antibodies binding to soluble antigens forming
small circulating immune complexes which are
deposited in various tissues
Depends on:
Size of immune complexes
Antigen-antibody ratio
Affinity of antibody
Isotype of antibody
TYPE III HYPERSENSITIVITY
• 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 IV HYPERSENSITIVITY
REACTION
T CELL MEDIATED PROCESS
TYPE IV (DELAYED-TYPE) HYPERSENSITIVITY
DELAYED-TYPE HYPERSENSITIVITY (DTH)
(e.g. tuberculin skin test)
TUBERCULIN SKIN TEST (MANTOUX TEST)
SCREENING PREVIOUS
IMMUNIZATION
(MEMORY T CELL
RESPONSE)
Introduction of Ag
Ag = antigen:
Purified protein
derivate (PPD)
isolated from
mycobacteria
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)
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
AUTOIMMUNITY
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
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)
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
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
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.
REUMATHOID ARTHRITIS (type III and IV)
• cellular immune response
against the synovial
membranes of joints
• involves many cell types:
•
•
•
•
•
CD4+ and
CD8+ T cells
B cells/plasma cells
neutrophils
macrophages
• Rheumatoid factor: anti-IgG-Fc
specific antibodies
MECHANISM OF AUTOIMMUNE INSULINDEPENDENT DIABETES (type IV)
AUTOREACTIVE CYTOTOXIC T CELLS KILL INSULIN
SECRETING β-CELLS
Insulin
a cell a cell
glucagon
b cell
b cell
d cell
108 insulin secreting
cells
Pancreatic islet cells
d cell
somatostatin