Immunology Type 2 hypersensitivity reaction

1. TYPE II HYPERSENSITIVITY
REACTION
HARISH R
DOS&R IN MICROBIOLOGY
TUMKUR UNIVERSITY

2. TYPE II HYPERSENSITIVITY REACTION
 Unlike Type I hypersensitivity, Type II hypersensitivity
reaction is an immediate reaction, showing a “hyper” or
exaggerated response to harmless antigens within 24
hours. Also Called As Antibody Dependent Cytotoxic
Hypersensitivity
 Due to the interaction of antibodies and cell associated
antigens,
 when antibodies attach to the antigens located on the
surface of cells the cells becomes cytotoxic.
 A hypersensitivity reaction type II requires a target cell
with bound antigen and antibody, which activates
mechanisms to damage the target cell.
 It is mediated by IgG or IgM antibodies against antigens
on cells or extracellular space.

3. TYPES OF CYTOTOXIC HYPERSENSITIVITY
1) Isoimmune reaction
The reaction brought about by the Ag and Ab of two
individuals belonging to the same species are called
isoimmune reactions.
a) Transfusion reaction
The agglutination or lysis of recipient blood due to
mismatched blood group is called transfusion reaction.
It occurs in ABO blood group as well as Rh blood group.

4. TYPES OF CYTOTOXIC HYPERSENSITIVITY
b) Erythroblastosisfoetails
Haemolytic disease caused by the reaction of Rh-
mother
It occurs in the Rh+ baby developing in an Rh- mother
The Rh antibody involved in this reaction belongs of IgG
type.
c) Transplant rejection reaction
A transplant can produce antibodies to transplantation
antigens these antibodies are cytotoxic to graft tissue.

5.  2. AUTOIMMUNE REACTIONS
 The reaction brought about by the interaction of an
antigen and antibody of the same individual is called
autoimmune reaction.
 Ex Autoimmune heamolyticanaemia
 Abs produced against its own RBC antigens.
 Autoimmune thyroiditis
 Autoimmune glomerulonephritis
TYPES OF CYTOTOXIC HYPERSENSITIVITY

6. DRUG INDUCED HEMOLYTIC ANEMIA

7. COMPONENTS OF HYPERSENSITIVITY TYPE II
1) Antigen
Antigens involved in type II hypersensitivity reactions
are intrinsic and exogenous antigens.
a) Intrinsic antigen
 Protein on the cell membrane, e.g., Rh ag on RBCs
 An antigen on a space/matrix between cells, like on a
basement membrane
 Self-antigen (causing autoimmune diseases)
 Receptors antigens on cells, like hormone receptors
b) Exogenous antigens
 Microbes, parasites, drugs
 Antigens of blood transfusion reaction

8. COMPONENTS OF HYPERSENSITIVITY TYPE II
2) Antibody
Hypersensitivity type II takes place by the
involvement of mainly IgG and
occasionally IgM antibodies. Rarely IgA can give such
reactions.
3) The effector cells
The effector cells of hypersensitivity type II reaction
are macrophages, neutrophils, eosinophils, and
natural killer (NK) cells .

9. MECHANISM HYPERSENSITIVITY TYPE II
 Hypersensitivity type II reactions affect the cells
where the target antigens are present. Hence such
reactions are not often systemic.
 But sometimes, target antigens may be present on
the surface of mobile cells like erythrocytes and
leukocytes, affecting the whole body.
Type II hypersensitivity has three mechanisms:
1) Antibody And Complement-mediated Lysis
2) Antibody-dependent Cell-mediated Cytotoxicity
(ADCC)
3) Dysfunction Of The Target Cell.

10. 1) ANTIBODY AND COMPLEMENT-MEDIATED LYSIS
 Here, the destruction is mediated either by a
complement system or antibodies via
opsonization.
 The antibody attaches to the antigen on the
surface of cells and activates the complement
system via the classical pathway.
 This leads to the formation of membrane attack
complex (MAC), which creates pores in foreign
cell membranes leading to cell lysis. In
opsonization, antibodies coat an antigen and
make it a target for phagocytosis.
 Examples of this mechanism are erythroblastosis
fetalis and mismatched blood transfusion

11. 1) ANTIBODY AND COMPLEMENT-MEDIATED LYSIS
 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
(Microorganism 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

12. 2) ADCC (ANTIBODY-DEPENDENT CELL-
MEDIATED CYTOTOXICITY)
 If antigen-antibody complexes are too large to
be phagocytosis, these are recognized by
different immune/cytotoxic cells, like
macrophages, NK cells, eosinophils, and
neutrophils.
 These cells have Fc-receptor and, therefore,
bind to the Fc region of the antibody and
release cytotoxic granules on the target cell,
and this causes cell death.
 An example of such a mechanism can be a
medication acting as a hapten and binding to
cells of a specific tissue.

13. 3) TARGET CELL DYSFUNCTION
 It is a non-cytotoxic mechanism.
 Autoantibodies binding typical cellular receptors
or other proteins may interfere with the functions
of these receptors or proteins and cause
disease without inflammation or tissue damage.
 However, the cell function is impaired, causing
an abnormal activation/blockade of the signaling
process.
 Examples are Myasthenia Gravis, Graves
disease, and pernicious anemia.

14. MECHANISM HYPERSENSITIVITY TYPE II

15. DIAGNOSIS AND CONTROL
 Diagnostic tests include detection of circulating
antibody against the tissues involved and the
presence of antibody and complement in the
lesion (biopsy) by immunofluorescence.
 Antithyroid drugs, Thyroidectomy, or
immunotherapy are used for Grave’s disease.
 Antibiotics against Streptococcus are used to
control rheumatic fever.
 Treatment involves anti-inflammatory and
immunosuppressive agents