the presentation is about the notes for hypersensitivity reaction

1. HYPERSENSITIVITY
REACTION(TYPE I and TYPE II)
BY: JEGANATHAN C
DEPARTMENT OF BIOMEDICAL SCIENCE
E.Mail : jeganathanbms@gmail.com
Cell.no: 9626307988

2. INTRODUCTION
• Hypersensitivity (also called hypersensitivity
reaction or intolerance) is a set of undesirable
reactions produced by the normal immune
system, including allergies and autoimmunity.
• Inflammatory response can have deleterious
effects ,resulting in significant tissue damage
or even death. this appropriate immune
response is termed hypersensitivity or allergy.

3. • Hypersensitivity reaction may develop in the
course of either humoral or cell mediated
responses

4. TYPES
• IgE mediated (type I) hypersensitivity
• Antibody-mediated cytoxic (type II)
hypersensitivity
• Immune complex –mediated (type III)
hypersensitivity
• Delayed- type hypersensitivity (DTH)

5. IgE mediated hypersensitivity
• Type 1 reaction also called as immediate
hypersensitivity reaction
• It is induced by certain types of antigen ,referred
to as allergens
• The allergen induces a humoral antibody
response
• IgE binds with high affinity to Fc receptors on the
surface of tissue mast and basophils
• Such IgE- coated mast cells and basophils are
sensitized

6. Continuous………
• A later exposure to the same allergen cross-
links the membrane- bound IgE on sensitized
mast cells and basophils, causing
degranulation of these cells
• The pharmacologically active mediators
released from the granules act on the
surrounding tissues

8. COMMON ALLERGEN ASSOCIATED
WITH TYPE 1 REACTION
• Proteins-foreign serum , vaccines
• Plant pollens-rye grass ,ragweed, timothy
grass,birch trees
• Drugs- penicillin, sulfonamides, local
anesthetics,salicylates
• Foods-nuts, seafood,eggs,peas,beans,milk
• Insect products-bee venom, wasp venom,ant
venom,cockroach calyx,dust mites
• Mold spores , animal hair and dander

9. MECHANISM OF ACTION
• Receptor cross linkage
• Intracellular events leading to mast-cell
degranulation

10. RECEPTOR CROSSLINKAGE

11. RECEPTOR CROSS LINKAGE

12. Mechanism of type I allergy: Calcium
influx to mast cell

14. NON IgE ANTIBODY-RELATED INITIATORS
OF TYPE I HYPERSENSITIVITY
Complement Activation Products:
C3a, C4a, C5a
"Anaphylotoxins"
Various Drugs: ACTH, Codeine,
Morphine, Penicillin

15. MEDIATORS

16. Mediators of Type I Hypersensitivity:
Stored in Mast Cell Granules
Histamine, Heparin and Serotonin
Increased vascular
permeability;
Smooth Muscle Contraction
Chemotactic Factors for
Eosinophils and Neutrophils Attract Eosinophils & Neutrophils
Proteases Degrade Basement membranes of blood vessels;
Activate bronchial mucous secretions;
Activate Complement

17. Secondary Mediators of Type I Hypersensitivity:
Synthesized and Released After Mast Cell Activation
Platelet Activating Factor Platelet Aggregation&
Degranulation;
Smooth muscle contraction
Prostaglandins Vasodilation; Smooth muscle contraction
Leukotrienes (SRS-A)* Increased vascular permeability;
Pulmonary smooth muscle contraction
(*SRS-A : Slow Reacting Substance of Anaphylaxis)
Bradykinin Increased vascular permeability;
Smooth muscle contraction
Cytokines: Systemic Anaphylaxis;
(IL1 & TNF-a; Others*) Altered Cell adhesion
* See Slide 42

18. Detection of type I hypersensitivity
• Radioimmunosorbent test (RIST)- Quantify
Nano gram amounts of total serum IgE
• Radioallergosorbent test (RAST)-Quantify
Nano gram amounts of serum IgE specific for a
particular allergen

19. To Treat Type I Immediate Hypersensitivity Based on
the Underlying Mechanisms
• Block Effects of Primary Mediators on Target
Cells (e.g. respiratory smooth muscles or vascular
endothelium) : Antihistamines; Cortisone
• Block Calcium Ion Influx: Cromolyn
• Block the Effects of Calcium Ion Influx
a. Keep cyclic AMP (cAMP) from Falling
Theophylline
• Increase production of cAMP:
Adrenaline(epinephrine)

21. ANTIBODY – MEDIATED CYTOTOXIC
HYPERSENSITIVITY
• Type II hypersensitivity reaction involve
antibody- mediated destruction of cells
• This type is best exemplified by blood –
transfusion reactions, in which host antibodies
react with foreign antigens on the
incompatible transfused blood cells and
mediate destruction of these cells

22. Type II Hypersensitivity
• Results when Ig or IgM bind to cell surface
Ag’s
– Activating Complement
– Binding Fc receptors on Tc cells promoting ADCC
• Both processes result in lysis of the Ab-coated
cell

23. • Clinical examples of Type II responses include:
– Certain autoimmune diseases where Ab’s produced
vs membrane Ag’s
• Grave’s Disease – Ab’s produced vs thyroid hormone
receptor
• Myasthenia Gravis – Ab’s produced vs acetylcholine
receptors
• Autoimmune hemolytic anemia – Ab’s produced vs RBC
membrane Ag’s
– Hemolytic Disease of the Newborn
– Hyperacute graft rejection
• Blood Transfusion
• Graft rejection

24. Type II Hypersensitivity:
Produced by mismatched blood
types
Destroys foreign RBC by
complement-mediated lysis
triggered by IgG
Produces fever, intravascular
clots, lower back pain, Hgb in
urine
Free Hgb produced has 2 fates:
passes to the kidneys –
hemoglobinuria
Breaks down to bilirubin. Can
be toxic

25. Type II Hypersensitivity:
Hemolytic Disease of the
Newborn
• Occurs via maternal IgG Ab’s crossing the placenta
• In severe cases causes erythroblastosis fetalis
– Most commonly develops in Rh- mother with Rh+ fetus
– Exposure to Rh+ fetal RBC’s stimulates prod of
memory/plasma
– Activation of memory cells in subsequent pregnancy IgG
Ab’s which can cross the placenta
– mild-severe hemolytic anemia ensues along with bilirubin
which affects the brain/CNS

26. • Treatment centers on anti-Rh antibodies (Rhogam)
• Mothers can be tested for anti-Rh antibodies to
check for a rise in titer
• Isolated fetal RBC’s can be checked for anti-Rh IgG w/
Coombs test

27. Hemolytic Disease of the Newborn

28. Drug-induced hemolytic anemia
• Drugs such as aspirin and antibiotics can bind
to the surfaces of RBC’s
• These interactions act similar to hapten-
carrier conj.
• Such complexes can trigger Ab-mediated cell
lysis by complement activation

29. REFERRENCE
• Kuby immunology- chapter 16th fourth edition
,pp 397- 415