Mechanisms of the four types of Hypersensitivity Reactions

1. Hypersensitivity Reactions
Presented by Sarah Elsisi
Undersupervision of Prof.Dr. Nageh
Department of toxicology and pharmacology
year 2020

2. What is hypersensitivity reactions ?
immune responses that are exaggerated or inappropriate against
an benign antigen or allergen.
It's the immune response that's
is harmful not the antigen.
There are four types of hypersensitivity
reactions: Type 1, 2 ,3 (Antibody-
mediated) and Type 4 (T- cell mediated)
In subsequent exposure the
exaggerated immune response occur.
It's antigen specific (after first
exposure*Asymptomatic* immune
system become prime or sensitized
toward antigen)

3. activation of autoreactive Tcells,
or promoting T cell responses to
microbial epitopes that cross
react against self peptides.
Immunological tolerance
Is a complex series of mechanisms that impair the immune system to mount
responses against self antigens.
Break down or Failurein
immunological response
Autoimmunity or autoimmune
disease
Environmental or genetic factor

4. 01Type 1 hypersentivity reaction
(Immediate - allergic reaction)
1.Preformed IgE antibodies.
2.crosslinked by contact with free antigen.
3.genetically predisposed individuals(Patients prone to IgE-mediated allergic
reactions are said to be atopic. Atopy is the genetic predisposition to make IgE
antibodies in response to allergen exposure)
4.early and late phase

5. 01

6. 01

7. Early phase:
Chymase
mucous
secretion
Proteoglycans
heparin
chondroitin sulfate
Tryptase
airway remodeling
through stimulation of
collagen & fibroblast
proliferation
Histamine
vascular
permeability
bronchoconstriction
01
Immediate or acute-phasereactionsoccurwithin secondsto minutes after allergen exposure.
and mediated by preformed mediators.

8. Bradykinin
Prostaglandin • Bronchoconstriction
• Peripheral vasodilation
(edema)
• Coronary Vc
• Platelet aggregationThromboxaneA2
Platelet-
activatingfactor
Leukotrienes
Adenosine
Occurhours after antigenexposureand after the signsor symptoms of the acute-
phasereaction have resolved. Theseeffectscanlastafewhours and usually resolve
within 24-72hours and mediated by newly formed mediators
01Late phase:

9. Examples of type 1 hypersensitivity
1.Atopic eczema
2. Food allergy
3. bronchial asthma
4. Drug allergy : penicillin
5. Anaphylaxis: most severe form of type 1, Life threatening, require
immediate treatment by epinephrine
01

10. 02
Type 2 hypersentivity reaction
(Cytotoxic-Hypersenstivity)
1.IgM or IgG antibodies
2.bind to antigens on the cells of particular tissue types
(Causing tissue damage)
3.Senstization phase occur as Type 1 but with class
switching of B-cell to plasma secreting IGM.

11. 02The Three mechanisms of type
2 hypersenstivity:
1. C o m p le m e nt a cti v a t io n
2 . Ph a g o cy to s is
3 . Ant ib o d y De p e nd e nt C e l lu la r C y to to x ici ty
(AD C C ): b y Nk c e l l w h ich b ind th r o u g h C D16 (FC γRIII)
to th e Fc p o r t io n o f Ig G a nt ib o d ie s t r ig g e r in g th e
ly s is o f c e l ls m e d ia t in g r e le a s e o f g r a nz y m e s a n d p e r fo r in
r e s u l t in g in c e l l d e a th b y a p o p to s is .

12. 02Theresulting Ag-Ab complexesactivatecomplement
(viathe classic pathway)

13. 02

14. 02

15. Examples of type 2 hypersensitivity
1.Pencillin: bind to RBCs causing
anemia
2. Quinine bind to platelet causing
thrombocytopenia
3. Erythroblastosis fetalis
02

16. 03Type 3 hypersentivity reaction
(Immune complex-Hypersenstivity)
1.IgM or IgG antibodies
2.react with soluble antigens forming antigen-antibody
complexes.
3.Same MOA of type 2, But Complement activation cascade is
induced by depostion of immune complexes.

17. 03
Arthus reaction: involves the localize formation of immune
complexes.
Serum sickness: Circulating immune complexes causing systemic
inflammation.
Type 3 hypersentivity reaction
(Immune complex-Hypersenstivity)
Arthus reaction vs Serum sickness

18. 03Arthus reaction

19. 03Serum sickness

20. Examples of type 3 hypersensitivity
1.systemic lupus erythematosus
2. Rheumatoid arthritis
3.post- streptococcal glomerulonephritis
03

21. 04Type 4 hypersentivityreaction
(Delayed - Hypersenstivity)
1.unlike the first three types of hypersensitivity which are antibody mediated,
type IV hypersensitivity is cell mediated and also a delayed reaction.
2.Starting at 2 or 3 days and often last for many days.
3.mediated by specific subsets of CD4+ helper T cells (Th-1 and Th-17 cells)
or by CD8+ cytotoxic T cells.(Direct cell toxicity via perforin and
granzymes)

22. Type 4 hypersentivityreaction
(cell mediated - Hypersenstivity)

23. Examples of type 4 hypersensitivity
Granuloma formation: It is a collection of macrophages
form when the immune system attempts to wall off
substances it perceives as foreign but is unable to
eliminate. (tuberculin test)
Allergic contact dermatitis: Environmental chemicals,
metals or topical medications causing epidermal necrosis,
inflammation, skin rash and blisters.
Type-1 diabetes: The killing of the pancreatic islet cells
by cytotoxic T cellsresulting in insulin deficiency.
04

24. Thank you.