Transcript Immunopathology - Tehran University of Medical Sciences

Immunopathology
Dr JG Lawrenson
Immunopathology
• Hypersensitivity
• Autoimmunity
• Immunodeficiency
© Dr JG Lawrenson 2001
Hypersensitivity
• Hypersensitivity reactions are exaggerated or
inappropriate immune responses that lead to
tissue damage
• Four types of hypersensitivity reaction are
recognised: Type I, II, III and IV
© Dr JG Lawrenson 2001
Type I Hypersensitivity
• Type I (immediate type)
reactions include: asthma,
hay fever, food allergy
• Also referred to as atopy
• Triggered within minutes of
exposure to a variety of
environmental antigens e.g.
pollen, house dust mite
• Strong genetic link
• Caused by an overproduction
of IgE
© Dr JG Lawrenson 2001
Type I Mechanism
• Mast cells display a high
affinity receptor for IgE
• IgE is synthesised in response
to certain antigens (allergens)
• Allergens are deposited on
mucous membranes and
taken up and processed by
antigen presenting cells (e.g.
Dendritic cells or B cells)
© Dr JG Lawrenson 2001
Type I Mechanism
• Allergen presented to TH2
cells which provide cytokine
signals to B cells to produce
IgE Ig E binds to mast cells
• Cross linking of IgE by
subsequent exposure to
allergen causes mast cell
degranulation
© Dr JG Lawrenson 2001
Type I Mechanism
• Mast cell degranulation is the
major initiation of the acute
allergic reaction
• Mast cell mediators include
histamine, heparin and other
factors
• These cause, mucus
secretion, vasodilation and
oedema
© Dr JG Lawrenson 2001
© Dr JG Lawrenson 2001
Mast cell mediators
• Mast cell mediators
include pre-formed and
newly formed mediators
• Pre-formed mediators
include : histamine,
heparin and neutral
protease
• Newly formed mediators
include leukotrienes,
prostaglandin D2 and
platelet activating factor
© Dr JG Lawrenson 2001
Type II Hypersensitivity
© Dr JG Lawrenson 2001
• Antibody mediated
hypersensitivity
• Antibody directed against
membrane and cell surface
antigens (autoantibodies)
• Antigen-antibody reactions
activate complement
producing membrane
damage
• Examples include:
transfusion reactions and
haemolytic disease of the
newborn
Type II Mechanism
• Antibodies bind to cell
surface
• Phagocytes bind to the
antibody via their Fc receptor
• Phagocytosis of target cell
• Antibody binding also
activates complement via the
classical pathway
• Complement mediated cell
lysis
© Dr JG Lawrenson 2001
Haemolytic disease of the newborn
© Dr JG Lawrenson 2001
Type III Hypersensitivity
• Immune complex mediated
• Excessive formation of
immune complexes e.g.
pesistent low-grade infection,
repeated inhalation of
antigens
• Examples of Type III
hypersensitivity include:
Farmers lung, immune
complex glomerulonephritis
© Dr JG Lawrenson 2001
Type III Mechanism
• Normally immune complexes
are degraded by
phagocytosis, particularly in
the liver and spleen
• Excessive immune complex
formation results in
deposition in the tissues,
particularly arterioles, kidney
and joints
© Dr JG Lawrenson 2001
Type III Mechanism
• Complexes induce platelet
aggregation and complement
activation
• Attempted phagocytosis
causes enzyme release and
results in tissue damage
© Dr JG Lawrenson 2001
Type IV Hypersensitivity
• Delayed type hypersensitivity
• Takes more than 12 hrs to develop after
antigenic challenge
• Examples include: contact dermatitis and
tuberculin reaction
• Antigens include large molecules or small
molecules (haptens) linked to carrier
molecules
© Dr JG Lawrenson 2001
© Dr JG Lawrenson 2001
© Dr JG Lawrenson 2001
Type IV Mechanism
• APC resident in the skin
process antigen and migrate
to regional lymph nodes
where they activate T cells
• Sensitised T cells migrate
back to the the skin where
they produce cytokines which
attract macrophages which
cause tissue damage
© Dr JG Lawrenson 2001
© Dr JG Lawrenson 2001
© Dr JG Lawrenson 2001
Autoimmunity
• Autoimmunity is a reaction of the immune
system to the bodies own tissues
• Self molecules are recognised as antigens due
to a breakdown of self-tolerance
• Antibodies (autoantibodies) react against these
components
• Includes organ-specific and non-organ specific
diseases
© Dr JG Lawrenson 2001