Hypersensitivity Reactions

Hypersensitivity Reactions
🞐 When an individual has been
immunologically primed or sensitized,
further contact with antigen can lead not
only to secondary boosting of the immune
response but can also cause tissue-
damaging reactions.We speak of
hypersensitivity reactions.
Videos

🞐 Intro to hypersensitivity reactions

🞐 Type I
🞐 Type 11
🞐 type 111
🞐 Type 1V
Testing for Type I Hypersensitivity
🞐 In-vitro test for IgE antibodies
🞐 In-vivo skin test- direct skin test (prick or puncture test. This is
less expensive, more sensitive and provides immediate results.
- The clinician uses a needle or pricking device to introduce a
small drop of the allergen extracts into the upper layer of the skin
in forearm or the back.
-A neg. control consisting of the diluent used for the allergy extract,
and positive control of histamine are also included.
- after 15-20 min. the clinician examines the testing spots .
- In a positive test, a wheal and flare reaction will appear at the site
where the allergen is applied.
Wheal and flare reaction
Type II Cytotoxic
🞐 IgG or IgM directed
against antigens
found in cell surface
🞐 activates NK and
complement
🞐 cell surface antigens
- target cell
- self ag
- infection
Type II- Cytotoxic
🞐 Generally involve IgG or IgM antibodies
combining with antigen and activates the
complement
🞐 This leads to lysis of the cell, which might
either be a foreign cell or a host cell that carries
a foreign antigenic determinant, like a drug on its
surface.
🞐 When the action of the immune system is in
response to self antigens, causing damage to
one’s organs, this is called autoimmune
disease
Examples of Type II reactions
🞐 Most familiar cytotoxic hypersensitivity
reactions are transfusion reactions, in
which RBC are destroyed as a result of
reaction with circulating antibodies. These
involve the ABO and Rh blood group
system
Rh-HDN- mother Rh(-), father
Rh(+)
Type II reactions- thrombocytopenic
purpura
🞐 Blood platelets are minute cell-like bodies
that are essential to blood clotting.
🞐 They are destroyed by antibodies and
complement in the disease
thrombocytopenic purpura.
Insert thrombocytopenic purpura
Idiopathic thrombcytopenic purpura
Type II Reactions- autoimmune
disorders: Grave’s disease
🞐 Caused by antibodies called long-acting
thyroid stimulators.
🞐 These antibodies attach to receptors in the
thyroid gland that are normal target of the
TSH produced by the pituitary gland.
🞐 The result is that the thyroid gland is
stimulated to produce increased amounts
of thyroid hormones and becomes
enlarged. The most striking signs is goiter
and markedly bulging staring eyes
Goiter
Type II Reactions- autoimmune
disorders: Myasthenia gravis
🞐 A disease in which muscle tone becomes
progressively weaker.
🞐 Caused by antibodies that coat the acetylcholine
receptors at the junctions at which nerve
impulses reach the muscles.
🞐 Eventually, the muscles controlling the
diaphragm and the rib cage fail to receive the
necessary signals, and respiratory arrest and
death result.
🞐 Both diseases involve antibody reactions to cell
surface antigens, although there is no cytotoxic
destruction of the cells.
Type II Reactions- autoimmune
disorders: hemolytic anaemia
🞐 Autoantibodies to the patient’s own red
cells are produced.
🞐 Red cells coated with these antibodies
have a shortened half-life largely through
their adherence to phagocytic cells.
🞐 The serum of patients with Hashimoto’s
thyroiditis contain antibodies which in the
presence of complement are directly
cytotoxic for isolated human thyroid cells
in culture.
Testing for Type II hypersensitivity

🞐 Coomb’s discovery of the antiglobulin test in 1945 made possible

the detection of antibody or complement on RBCs.
🞐 Direct antiglobulin test (DAT) is performed to detect
transfusion reactions, HDN, and autoimmune hemolytic anemia.
🞐 Detect antibodies or complement proteins attached to the surface
of RBC.
🞐 Polyspecific antihuman globulin, which is a mixture of antibodies
to IgG, and complement components such as C3b and C3d, is
used for initial testing.
🞐 It the test is positive, it should be repeated using monospecific
anti-IgG, anti-C3b, and anti-C3d to determine which of these is
present.
🞐 If an autoimmune hemolytic anemia is caused by IgM antibody,
only the tests for complement components would be positive.
Direct Coomb’s test
Testing for type II hypersensitivity
🞐 Indirect Coomb’s test is used in the
crossmatching of blood to prevent a
transfusion reaction. Used to detect
antibodies that are floating freely in the
blood.The test detects antibodies against
foreign RBC.
Indirect Coomb’s test
Type III Immune Complex
🞐 IgG or IgM that remain soluble in the
circulation
🞐 soluble immune complex are carried into
the circulation and become lodge in the
basement membrane
🞐 skin, lungs and joints
🞐 This differs from the Type II since antigen
is not a part of the target cell
Type III Immune Complex formation-
when certain ratio of Ag/Ab occur
🞐 A significant excess of antibody leads to
the formation of large complement-fixing
complexes that are rapidly removed from
the body by phagocytosis.
🞐 When there is significant excess of antigen
, soluble complexes form that do not fix
complement and do not cause
inflammation.
🞐 Small, partially crosslinked complexes
form when there is a certain ratio of
Ag/Ab.; there is usually a small excess of
antigen. These complexes fix complement
but are small enough to escape
phagocytosis. They damage tissues when
they are trapped in the basement
membrane of blood vessels.
Formation of immune complexes

a) Large crosslinked complexes form when antibody is in excess. Most of

these are removed from the circulation by phagocytosis. b)small separate
immune complexes form when antigen is in excess. These generally do not
fix complement or cause inflammation. c) Small, partially crosslinked
complexes form when there is a certain ratio of antigen to antibody; there
is usually a small excess of antigen. These complexes fix complement but
are small enough to escape phagocytosis. They damage tissues when they
become trapped in the basement membrane of blood vessels.
Drug Reactions- very complicated
-A Clinical Course of Type III
🞐 after injection of drugs molecule, it may
combine with self proteins to undergo
conversion from hapten to full antigen.
🞐 the host reacts and produce antibodies
🞐 If IgE are produced, anaphylactic
reactions can result
🞐 In some circumstances, particularly with
topically applied ointments, cell-mediated
hypersensitivity can be induced.
🞐 In other cases, type III complex mediated
reactions may arise
Serum sickness- excess in antigen
Type III

Diseases cause by bacterial

toxins are treated by
antiserum from horses
immunized with these toxins.
The antibodies in the horse
serum were intended to
neutralize the toxins, but
repeated injections often led
to fever, itchy rashes, and
swollen, painful joints in the
recipient. These result from
the deposition of soluble
antigen-antibody complexes
formed in excess of antigen
Glumerulonephritis-a clinical course
of type III
🞐 An immune complex condition that causes
inflammatory damage to the kidney
glumeruli, which are sites of blood
filtration.
🞐 Antibodies generated to the M-protein of
streptococci are believed to be one cause
of this disease
Autoimmune disorders (Type III reactions)-
Systemic Lupus Erythematosus (SLE)
🞐 Mainly affects women. Etiology is not
completely understood , but affected
persons produce antibodies directed at
components of their own cells, like
antibodies against DNA, which is probably
released during breakdown of tissues, esp.
the skin.
🞐 The most damaging effects of the disease
result from deposits of immune complexes
in the kidney glumeruli.
Testing for Type III Hypersensitivity
🞐 In autoimmune diseases such as SLE and
RA, antinuclear antibodies can be
detected by a variety of methods including
indirect immunofluorescence, ELISA, and
fluorescent microsphere multiplex
immunoassays.
Type IV- Cell-mediated (delayed
type)
🞐 This form is encountered in many allergic
reactions to:
🞐 bacteria, viruses and fungi,
🞐 in the contact dermatitis resulting from
sensitization to certain simple chemicals
🞐 In the rejection of transplanted tissues
Type IV (CMI)
🞐 part of normal cell immune
response
🞐 no antibodies are involved
🞐 24-72 hours
🞐 Best known example is the
Mantoux reaction
obtained by injection of
tuberculin into the skin of
an individual in whom
previous infection with
mycobacterium had
induced a state of CMI
1st Exposure
🞐 poison ivy produces contact dermatitis
🞐 urishiol binds to proteins in EC and
becomes sensitizing antigen
🞐 TDH that bear matching antigen receptors
come in contact with the antigen and
proliferate clones, which sensitize the
individuals

TD TD

TD TD TD TD
2nd Exposure
🞐 2nd exposure activates TD cells which
proliferates and release lymphokines
🞐 it will stimulate macrophage to attack
targeted epithelial cells

TD
 2nd Exposure
🞐 the itchy, painful dermatitis of poison ivy
appears 48 hours after
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Immunopathology
1. host responses to transplantation
1.1 types of graft
1.2 rejection of transplanted organ
1.3 graft -vs.- host disease
Types of transplants
🞐 Some transplants or grafts do not stimulate an
immune response.
🞐 A transplanted cornea, for example, is rarely
rejected, mainly because antibodies do not
circulate into the anterior chamber of the eye,
which is considered an immunologically
privileged site.
🞐 The brain is also another privilege site probably
because it does not have lymphatic vessels and
because the blood vessels in the brain differ from
blood v. elsewhere.
1.1 Types of graft
🞐 Autograft- a graft transplanted from one
site to another site on the same person
🞐 Isograft – a graft between genetically
identical persons- identical twins
🞐 Allograft- a graft between genetically
different members of the same species
🞐 Xenograft – a graft between different
species- for ex. A transplant of a baboon
heart to a human
1.2 Rejection of transplanted organ
🞐 In an attempt to prevent rejection , the recipient
of an allograft usually received treatment the
normal immune response against the graft.
However the treatments used in the past
suppressed the immune response to all antigen,
by both humoral and CMI. The person so treated
become very susceptible to infectious disease and
cancer
🞐 Cyclosporine, a drug isolated from a fungus has
revolutionized transplant medicine. It selectively
inhibits of certain lymphokines without interfering
with the synthesis of other proteins. The drug
prevents the formation of Tc cells that are
responsible for transplant rejection, inhibits the
release by macrophages of lymphokines that
cause inflammation, and prevents the differentia-
tion of B cells into antibody-secreting plasma
cells. It does this without suppressing the ability
of the bone marrow to produce RBC and platelets
The greatest drawback is inc. risk of CA. A new
drug FK506 has a mode of action similar to
cyclosporine
Transplant rejection / Graft vs. Host
Disease
🞐 Transplant rejection occurs when the host
rejects the graft
🞐 Graft vs.Host Disease occurs when the
graft rejects the host.
1.3 graft vs. host disease
🞐 When bone marrow is transplanted into persons
with a defective immune system, the
transplanted tissue may attack the host.
🞐 The purpose of the transplant is to provide such
persons with the B-cell and T-cell with
manufacturing capability they lack.
🞐 However, the result can be graft-vs.-host
(GVH) disease
🞐 The transplanted bone marrow contains
immunocompetent cells that mount a CMI
response ag. the tissue into which they have
been transplanted.
Graft vs. Host
🞐 There are two possible situations leading
to g.v.h. reactions
🞐 When competent lymphoid cells are
inoculated into a host incapable of
reacting against them, the grafted cells
are free to react against the antigens on
the host’s cells which they recognize as
foreign.
Graft vs. host reaction
Three criteria must be met in order
for Graft vs. Host to occur
🞐 An immunocompetent graft is
administered with viable and functional
cells.
🞐 The recipient is immunologically different
from the donor- (histo-incompatible)
🞐 The recipient is immunocompromised and
therefore cannot destroy or inactivate the
transplanted cells.
GVHD does not occur when people
receive their own cells. This type of
transplant is called autologous.

Before a transplant, tissue and cells

from possible donors are checked to
see how closely they match the
recipient. GVHD is less likely to
occur, or symptoms will be milder,
when the match is close. The chance
of GVHD is:

Around 30% to 40% when the donor

and recipient are related
Around 60% to 80% when the donor
and recipient are not related