Type II hypersensitivity is an antibody-mediated immune reaction primarily involving IgG and IgM antibodies that target cellular antigens, leading to cell damage and destruction through mechanisms such as complement activation, antibody-dependent cell-mediated cytotoxicity (ADCC), and opsonization. This hypersensitivity can manifest in various clinical conditions including transfusion reactions, hemolytic disease of the newborn, autoimmune disorders, and drug-induced hemolytic anemia. These reactions are typically immediate, occurring within minutes to hours post-exposure.

1. Type II Hypersensitivity
Anup Muni Bajracharya

2. Type II Hypersensitivity
• refers to an antibody-mediated immune reaction.
• reactions involve IgG and IgM antibodies
• These antibodies are directed against cellular antigens, leading to cell
damage.
• So it involves antibody mediated destruction of cells. It is also known as
cytotoxic reaction.
• The killing of cell can occurs by one of the three mechanisms.
• Activate complement, resulting in an inflammatory response and lysis of
the targeted cells, (Complement mediated lysis of cell)
or
• they can be involved in antibody-dependent cell-mediated cytotoxicity
(ADCC) with cytotoxic T cells.
or
• Opsonisation
• The reaction time is minutes to hours and thus considered as immediate
hypersensitivity.

3. Opsonisation
ADCC
Complement mediated cell lysis
the modification of antigens
by opsonins (antibody) to
make them more accessible
to phagocytic cells

4. Type II Hypersensitivity
• In some cases, the antigen may be a self-antigen, in which case the
reaction would also be described as an autoimmune disease.
• In other cases, antibodies may bind to naturally occurring, but exogenous,
cell-surface molecules such as antigens associated with blood typing
found on red blood cells (RBCs).

5. Mechanism of Type II Hypersensitivity Reactions
• The reaction is completed in two phases – sensitization
phase and effector phase.
• A sensitization phase leads to production of antibodies
that recognize substances or metabolites that accumulate
in cellular membrane structures.
• In the effector phase, target cells become coated with
antibodies which lead to cellular destruction.
• Antibody bound to a surface antigen can induce the death
of the antibody-bound cell by three distinct mechanisms –
• by activation of the complement system,
• cell destruction by antibody dependent cell mediated
cytotoxicity (ADCC) or
• by the process of opsonization.

6. Complement system is a system of
lytic enzyme which are usually
inactive in blood.
Enzymes of complement system are
activated by antigen-antibody
complex.
When antibody binds to antigen
(microorganism or RBC) they form
Ag-ab complex.
Ag-ab complex can activate
complement system by three
different mechanism-classical
pathway, alternate pathway and
lectin pathway.
Activated complement proceeds in
cascade mechanism.
When complement is activated on
the surface of cell (RBC) it causes
lysis of cell.
Complement mediated lysis of cell

7. ➢ Antibody binds with antigen by its Fab portion. However Fc region of antibody has
receptor on cytotoxic cells.
➢ So, antibody cross link target cell (microorganism or RBC) with cytotoxic cells and
promote killing.
➢ Most cytotoxic cells contain storage of hydrolytic and digestive enzymes. These
enzymes are released on the surface of target cell (MOs or RBC or target cell),
killing them.
➢ Here antibody itself does not kill or destroy cell but rather mediate killing by
presenting antigen to cytotoxic cell.
➢ Similarly cytotoxic cell depends upon antibody to bind antigen. So this mechanism
is known as Antibody dependent cell mediated cytotoxicity.
Antibody dependent cell mediated cytotoxicity (ADCC)

8. •When antigen enters into host body, antibodies are produced.
•Antibody binds to antigen through Fab region. Fc region of antibody
remains free.
•Phagocytic cells such as Neutrophils, macrophages and monocytes
have receptors that can bind to Fc region of antibody. The receptor is
known as FcR.
•In this case antibody molecule directly cross links antigen
(Microrganism or RBC or target cell) with phagocytic cells. This cross-
linkage activates phagocytic cells and increases the rate of
phagocytosis.
•This increased rate of phagocytosis by binding of antibody to antigen
is called Opsonization.
Opsonization

9. Some examples of Type II Hypersensitivity
• Transfusion reactions
• Hemolytic disease of the newborn
• Autoimmune hemolytic anemia,
agranulocytosis, and thrombocytopenia
• Specific drug reactions
• Glomerulonephritis
• Myasthenia gravis, Graves disease, and other
autoimmune disorders

10. • Common examples
• Hemolytic transfusion reaction (HTR) --
Transfusion reaction
• Hemolytic disease of the newborn (HDN)--
Rhesus incompatibility

11. ABO Blood Group Incompatibility
The recognition that individuals have different blood types was first described
by Karl Landsteiner (1868–1943) in the early 1900s, based on his observation
that serum from one person could cause a clumping of RBCs from another.
These studies led Landsteiner to the identification of four distinct blood
types.

12. Transfusion reaction
• A patient may require a blood transfusion because they lack sufficient
RBCs (anemia).
• For instance, if a person with type B blood receives a transfusion of type A
blood, their anti-A antibodies will bind to and agglutinate the transfused
RBCs.
• In addition, activation of the classical complement cascade will lead to a
strong inflammatory response, and the complement membrane attack
complex (MAC) will mediate massive hemolysis of the transfused RBCs.
• The debris from damaged and destroyed RBCs can occlude blood vessels
in the alveoli of the lungs and the glomeruli of the kidneys.
• Within 1 to 24 hours of an incompatible transfusion, the patient
experiences fever, chills, pruritus (itching), urticaria (hives), dyspnea,
hemoglobinuria (hemoglobin in the urine), and hypotension (low blood
pressure).
• In the most serious reactions, dangerously low blood pressure can lead to
shock, multi-organ failure, and death of the patient.

13. Figure- A type II hypersensitivity hemolytic transfusion reaction (HTR) leading to hemolytic
anemia. Blood from a type A donor is administered to a patient with type B blood. The anti-A
isohemagglutinin IgM antibodies in the recipient bind to and agglutinate the incoming donor
type A red blood cells. The bound anti-A antibodies activate the classical complement
cascade, resulting in destruction of the donor red blood cells.

14. Hemolytic disease of the newborn (HDN)
Rhesus incompatibility (Rh hemolytic disease)
• If an Rh− woman carries an Rh+ baby to term, the mother’s immune
system can be exposed to Rh+ fetal red blood cells.
• This exposure will usually occur during the last trimester of pregnancy and
during the delivery process.
• If this exposure occurs, the Rh+ fetal RBCs will activate a primary adaptive
immune response in the mother, and anti-Rh factor IgG antibodies will be
produced.
• IgG antibodies are the only class of antibody that can cross the placenta
from mother to fetus; however, in most cases, the first Rh+ baby is
unaffected by these antibodies because the first exposure typically occurs
late enough in the pregnancy that the mother does not have time to
mount a sufficient primary antibody response before the baby is born.
• If a subsequent pregnancy with an Rh+ fetus occurs, however, the
mother’s second exposure to the Rh factor antigens causes a strong
secondary antibody response that produces larger quantities of anti-Rh
factor IgG. These antibodies can cross the placenta from mother to fetus
and cause HDN, a potentially lethal condition for the baby.

15. When an Rh− mother has an Rh+ fetus, fetal erythrocytes are introduced into the mother’s circulatory system before or
during birth, leading to production of anti-Rh IgG antibodies. These antibodies remain in the mother and, if she becomes
pregnant with a second Rh+ baby, they can cross the placenta and attach to fetal Rh+ erythrocytes. Complement-mediated
hemolysis of fetal erythrocytes results in a lack of sufficient cells for proper oxygenation of the fetus. (b) HDN can be
prevented by administering Rho(D) immune globulin during and after each pregnancy with an Rh+ fetus. The immune
globulin binds fetal Rh+ RBCs that gain access to the mother’s bloodstream, preventing activation of her primary immune
response.

16. Drug induced hemolytic anemia
This drug induced hemolytic
anemia is an example of Type II
hypersensitivity reaction.
Certain drugs such as penicillin,
cephalosporin and streptomycin
can absorb non-specifically to
protein on surface of RBC forming
complex similar to hepten-carrier
complex.
In some patients these complex
induce formation of antibodies,
which binds to drugs on RBC and
induce complement mediated
lysis of RBC and thus produce
progressive anemia

17. Cell Destruction due to Autoantigens
Antibodies to a variety of self antigens such as basement membranes of lung and
kidney (Goodpasture’s Syndrome), the acetylcholine receptor (Myasthenia Gravis)
and erythrocytes (Autoimmune Hemolytic Anemia) can result in tissue damaging
reactions.

18. Autoimmune Hemolytic Anemia

19. Myasthenia gravis

20. An example of a cytotoxic reaction is thrombocytopenia.
In this disease, antibody molecules are elicited by certain drug molecules. The
antibodies unite with antigens on the surface of thrombocytes (platelets), and with
complement activation, the thrombocytes are destroyed. The result is an impaired
blood-clotting mechanism.
Thrombocytopenia

21. Another example of the cytotoxic reaction is agranulocytosis.
In this immune disorder, antibodies unite with antigens on the surface of
neutrophils.
As these cells are destroyed with complement activation, the capacity for
phagocytosis is reduced.
Agranulocytosis