This document discusses hypersensitivity reactions, or allergic reactions, caused by an exaggerated immune response. It describes the four main types of hypersensitivity reactions: type 1 involves IgE antibodies and mast cell degranulation, type 2 involves IgG/IgM antibodies attacking self cells, type 3 involves immune complex deposition and complement activation, and type 4 is a delayed T cell mediated response. Tissue injury in hypersensitivity reactions can be caused by the release of inflammatory molecules, phagocytosis, complement activation, and cytokines/enzymes. Each type is then discussed in more detail with examples provided.

1. HYPERSENSITIVITY REACTIONS
Priyansha Singh
NIPER Guwahati

2. What is a Hypersensitivity reaction ?
• Exaggerated immunologic responses in response to an antigen or allergen
• Resulting in tissue injury/cytotoxicity & other pathological changes in blood
vessels or other tissues
• Our immune system identifies between foreign/ non self & self-molecules & the
failure to identify the difference causes hypersensitivity as the immune cells
release inflammatory mediators
• There are 4 types of Hypersensitivity
Type-1: Antibody IgE = Mast cells = release of histamine/PG/LT; quick onset after
exposure
Type-2: Cytotoxic= IgG/IgM mediated= Attack antigen present on self cells
Type-3: Immune complex deposition = complement
Type-4: Delayed/ CD4 T (helper) & rarely CD8 T cell mediated

3. How tissue injury can be caused ?
1. Release of vasoactive substances like leukotrienes, histamine, prostaglandins etc.
2. Phagocytosis
3. Activation of inflammatory & cytolytic components of complement system (mostly seen in SLE)
4. Release of cytokines, proteolytic enzymes & other inflammatory mediators which destroys the overall cellular
structure

4. Hypersensitivity reaction
Type 1
• Completely due to antigen/allergen/immunogen
• Allergens interact with our body cells and the antibodies
fight and bind against that specific antigen
• Mainly IgE mediated.
• IgE recognizes soluble antigens ----> which triggers MAST
CELLS to DEGRANULATE to release HISTAMINE hence causing
allergic symptoms

5. Hypersensitivity reaction Type 2
• By IgG and rarely IgM
• Recognize & bind to the cellular self antigens or tissue specific antigens
(present on host cells)  cytotoxicity/tissue damage.
• Includes the recognition and binding to the self-antigen (autoimmunity)
• This type of hypersensitivity reaction occurs by 3 mechanisms
1. Antibody dependent cell mediated cytotoxicity
2. Antibody & complement mediated destruction (e.g.- Autoimmune
hemolytic anemia, mismatched transfusion of blood cells)
3. Target cell dysfunction (e.g.- Graves disease, Myesthenia gravis,
pernicious anemia)

6. b) Opsonization
Antibody & complement mediated destruction
Here the target cells express antigens with which antibody binds to which
activates the complement system which activates & cleaves several
complement proteins specifically the complement protein C1 causing
activation & cleavage of C3 to C3a & C3b which leads to the formation of
membrane attack complex of C9 proteins which attack the target cell by lysis.
Antibodies & the complement proteins C3b attach to the target cell and
act as Opsonins- they attract macrophages to phagocytose the target cell
C3b
Target cell

7. Antibody dependent cell mediated cytotoxicity
ADCC can occur when certain medications are involved and they
are called HAPTENS which bind to certain tissue and when Ab
binds to these tissue cells that can activate complement
proteins C5a & C3a
They attract WBCs to the site & carry out ADCC
E.g.- Medication induced hemolytic anemia, transplant rejection
Target cells destroyed
by toxic granules
It involves antibodies, that bind to antigen on target cells which
get recognized by immune cells like Macrophages, Natural killer
cells, Eosinophils & Neutrophiles using Fc receptors.
Once bound to antibody these cells release cytotoxic substances
or granules onto the target cells  Cell Death

8. Target cell dysfunction
lets understand it using an example of Graves disease
Hyperthyroidism
In Grave’s disease, Follicular cells of thyroid glands are
involved & they have TSH receptors.
Normal- TSH binds to TSH-R & promotes the production of
Thyroid hormone T3 & T4.
But in Grave’s disease, there is a presence of auto-antibodies-
Thyroid Stimulating Immunoglobulins.
Bind to TSH receptors & over activate them as they are not
subjected to –ve feedback

9. Hypersensitivity Reaction Type 3
When blood soluble antigen
(medication, venom, vaccine)
enters blood circulation
IgM/IgG detect & bind to them
forming antigen antibody/
immune complex
Attach to endothelium of blood vessel
wall (systemic) or other tissues like
synovial of joint/ glomerulus of
kidney/ epithelial lining of alveoli in
lungs (localized)
Activation of complement cascade
C5a
C3b
Activation of complement cascade
starting with C1 which leads to
activation of proteins C5a & C3b
Release of chemotactic factors
recruitment of neutrophils
Neutrophils utilize Fc receptors &
complement receptors to bind to Antibody
and C3b which deposits on tissue
Upon deposition, neutrophils
release cytotoxic granules
containing ROS causing cell/
tissue damage

11. Hypersensitivity reaction Type 4- cell mediated
1. Aka Delayed type HS reaction- cell mediated
2. 2 phases- Sensitization  Effector
3. Requires Incubation time to develop for 1-2 weeks then symptoms are shown but on repeated exposure with the same antigen the response takes lesser
window period.
4. Sensitization- Antigen on engulfment with macrophage/ APC  showcase the fragment of that antigen to the rest of the immune system cells by Major
Histocompatibility Complex-II (MHC II) to alert immune cells. Th cells sense the presence of that antigen by T cell receptor & get differentiated into more
Th cells
5. Effector- Active Th cells activate other macrophages  cytotoxicity/phagocytosis
6. E.g.- TB Test, Poison Ivy

12. Binds at proteins in skin
& alters them
Recognized by immune
system as foreign due to
alterations
Recognized & presented by APC
and presented to naïve Th cells
APCs are antigen presenting cells where antigens/
altered proteins are expressed by MHC-II and it gets
paired up with Th cells and APC then releases Il-12 & Il-6
Differentiation of Th cells
into type 1 Th cell (Th1) &
Th 17 cells
Release of Ifn-g & Il-17
which activates
macrophage
Activated Macrophage
Release of Il-1 & Tnf-a
Expression of receptor on
endothelial cell to recruit more
leukocytes to endothelium
Perform phagocytosis
& release ROS &
lysozymes
VASCULAR
DERMATITIS
Ivy poison (Urushiol)
Lets understand it using an example of Poison Ivy