Hypersensitivity

reactions 2
By Dr. Samia Beshir
Type II HSR

➢ Known as cytolytic or cytotoxic HSR. Also

there are some non-cytotoxic type II
Hypersensitivity reactions
➢ Mediated by immunoglobulins IgG or IgM.
➢ Antigen is found on surface of cells, whether
this antigen is part of the cell membrane or it
is a circulating antigen(hapten) that attaches
to the cell membrane.
➢ Target cell is damaged through a variety of
mechanisms.
.
mechanisms

1- Complement-mediated reactions
 Antibody reacts with a cell membrane
component ( antigen) leading to activation of
complement.
result is: lysis of cell by MAC or
Opsonization - phagocytosis
by C3b
Blood cells are the most commonly
affected by this mechanism.
 2-Phagocytosis enhanced by the antibody
(opsonin) bound to cell antigen leading
to opsonization of the target cell
 3- ADCC (Antibody dependent cell
cytotoxicity) : utilizes the IgG Fc
receptors expressed on many cell types
(NK cells, macrophage,eosinophilss) as a
means of bringing these cells into contact
with IgG-coated target cells.
 4- Ab-mediated cellular dysfunction
Auto-antibodies are formed and bind to
cell surface receptors, thus affecting its
function without causing cell injury or
inflammation. This mechanism cause the
non-cytotoxic HSR
 Examples of non-cytotoxic HSR:
1- Myasthenia gravis
auto-antibody to acetylcholine receptors at
neuromuscular junctions impair neuromuscular
transmission causing muscle weakness.
2- Grave’s disease : Abs against TSH receptors
on thyroid cells bind the receptors and
stimulate the cells to produce excessive
thyroxin, resulting in hyperthyroidism, thus
mimicking the effect of TSH.
Clinical examples of type II
HSR
➢ Blood transfusion reactions due to ABO
incompatibility ( complement-mediated
destruction of transfused cells)
➢ Haemolytic disease of the newborn due to
Rhesus incompatibility ( IgG opsonization
and phagocytosis).
➢ Autoimmune diseases of blood( C-mediated
or opsonization and phagocytosis)
 1- autoimmune haemolytic anaemia (RBC)
 2- idiopathic thrombocytopenia
purpura(platelets)
 3- agranulocytosis (WBC)
➢ Other auto-immune diseases such as Myasthenia
gravis,Goodpasture syndrome syndrome(Auto-Abs
against the basement membrane collagen in lungs
and kidneys) nephrotoxic nephritis and
Hashimoto´s thyroiditis
➢ Drug reactions:
Penicillin,phenacitin and quinidine may attach as
haptens to the surface of red cells and induce
antibodies which are cytotoxic leading to
haemolysis
Quinidine may also attach to platelets and the
antibodies induced cause platelet destruction
leading to thrombocytopenic purpura
Hypersensitivity type II
Type III HSR

➢ Known as immune-complex HSR

➢ Mediated by IgG or IgM
➢ Differs from type II in the type of antigen, location
of antigen and the way in which Ag is brought
together with the Ab.
➢ Stimulated by small soluble Ag-Ab complexes(
type II is stimulated by the binding of Ab directly
to an Ag on surface of a cell).
➢ The Ag-Ab immune complexes get deposited in
tissues on the basement membrane of blood
vessels and cause tissue injury.
➢ Commonest sites include joints,kidneys and skin
Mechanism of tissue injury

 Immune complexes trigger a variety of

inflammatory processes:
 1-Immune complexes activate the complement, with the
release of the anaphylatoxins C3a and C5a which stimulate
degranulation of basophils and mast cells with release of
vasoactive amines (e.g. histamine).These increase vascular
permeability and help deposition of complexes on the
basement membrane.
 2-C5a attract neutrophils to the site of immune complexes.
On trying to phagocytose the complexes neutrophils release
lysosomal enzymes which damage tissues and intensify the
inflammatory process.
 3-Platelets are aggregated with two consequences; they
release vasoactive amines and form microthrombi which
can lead to local ischaemia.
 The antigen is a soluble one, mostly in the
circulation.
 It can be exogenous as in diseases following
infections or endogenous (auto antigen)
 Diseases that are produced by immune complexes
are those in which the antigen persists without being
eliminated as in
 1-repeated exposure to extrinsic antigens
 2-injection of large amounts of antigen
 3-persistent infections.
 4-autoimmunity to self components.

Type III
Type III
Forms of type III reaction

 2 forms of reaction :
 1- localized type III reaction
 2- systemic type III reaction
 End result in both is the same i.e. rupture of blood
vessel wall and haemorrhage accompanied by necrosis
of the tissue.
Clinical examples of type III
HSR
 1-Arthus reaction: is the prototype of localized type III
HSR
 Follow repeated intradermal injection of foreign protein
and manifested as erythema(redness) and
oedema(accumulation of fluid) within 24 hours of
injection. It finally ends in haemorrhage and necrosis
following subsequent injections of the antigen.
 2- Post-streptococcal glomerulonephritis
: infection -associated immune complex
disease
 3- Goodpasture’s syndrome, following
viral respiratory infection.
 4- Farmer’s lung or allergic alveolitis,
following inhalation of mould antigen or
spores of actinomycetes on spoiled hay
(occupational disease)
 5- other occupational diseases include
Pigeon’s disease, Cheese washer’s disease
 6- Serum sickness : this is the prototype
of systemic immune complex diseases .
 follows passive immunization with
horse serum in tetanus and diphtheria,
after treatment with penicillin or
sulphonamides.
 7- Autoimmune diseases: such as
 Rheumatoid arthritis
 SLE(systemic lupus erythematosus)
SLE
Type IV HSR

➢ Also known as delayed-type hypersensitivity (DTH)

because the response is delayed (starts hours or days
after contact with the antigen and often lasts for days)
➢ T-cell mediated
➢ Can be transferred only with T cells whereas antibody-
mediated HSR can be transferred by serum from an
immunized or sensitized individual to a nonimmune
individual.
 Antigens may be:
 foreign tissue (graft tissue antigen)
 intracellular microorganism
(parasites,fungi,bacteria)
 chemicals,metals
 Auto antigen
 The clinical features depend on the
sensitizing antigen and the route of
antigen exposure.
Mechanism

 As with Ab-mediated HSR, previous

exposure to the antigen is required to
generate DTH.
 Involves two stages :
 1- sensitization stage : previous
exposure to the antigen. This activates
and expands the number of antigen-
specific memory TH1 cells.
 This stage occurs over a 1 to 2 week
period, during which normal
mechanism of T cell activation occur
 2- elicitation stage : requires 24-72 hours from time of
 antigen challenge or second exposure
 the Ag-challenged TH1 cells produce several cytokines
 mostly chemokines and IFNɣ, which cause chemotaxis
 and activation of antigen-nonspecific macrophages.

 IL12 suppresses the TH2 subpopulation and promotes

 the expansion of TH1 subpopulation, thereby driving the
response
 to produce more TH1-synthesized cytokines that activate
 macrophages and other inflammatory cells

 Inflammatory cells infiltrate and cause accumulation of plasma

and
 local tissue damage


 The tissue injury results from the products of activated
macrophages such as hydrolytic enzymes,reactive
oxygen intermediates,nitric oxide and proinflammatory
cytokines(TNF,IL-1,IL-6).
Examples of DTH

 1-Contact dermatitis:
 target organ is the skin
 inflammatory response is produced
as the result of contact with
sensitizing substances on the surface
of the skin
 it is primarily epidermal reaction
characterized by eczema at the site of
contact with the allergen and typically
peaks 48-72 hours after contact.
 antigens include: poison ivy (oil secreted by leaves of
poison-ivy vine)
 nickel and chromium present in jewelry, oil present
in some paints,cosmetics,soap.
 Clinically : induration(raised thickining) and erythema
(redness)
 Can be tested for by skin patch test
Contact dermatitis
 2- Granulomatous hypersensitivity:
 characterized by a granuloma that is
maximal 21-28 days after antigen is
introduced. Typical in chronic diseases
such as Tuberculosis, Leprosy and
Schistosomiasis
 3- Tuberculin-test hypersensitivity
characterized by an area of firm red
erythema and induration within 48-72
hours after Ag challenge.
 4- Allograft rejection
 5-Autoimmune Diseases :
 Rheumatoid arthritis, type 1 diabetes
mellitus and multiple sclerosis.
Tuberculin skin test
(mantoux)
Rheumatoid arthritis