autoimmun desise

1. Hypersensitivity
Assistant lecturer: Zahraa Faris Abdullah

2. "Hypersensitivity"
*Hypersensitivity reaction: Denotes heightened immune
response resulting in exaggerated or inappropriate reactions
harmful to host.
*Both the humoral and cell-mediated arms of the immune
response
may participate in hypersensitivity reactions.
*hypersensitivity has been broadly classified into immediate
type and delayed type
-"Immediate"- Within minutes (Type I)
or hours (Types II and III)
-"Delayed" - Takes one or more days

3. ‫جدا‬ ‫مهم‬Four Types of Hypersensitive (Allergic) Responses

4. Some Definitions and Concepts
-"Allergy“: Generally refers to Type I Immediate Hypersensitivity;
But also hear Types II and III "Allergy“
-An allergen is an antigen that stimulates a hypersensitivity response.
-“Atopic” Allergy (Atopic Individual):
Genetic misregulation of IgE production or response
Atopy is the term for the genetic trait to have a predisposition for localized
anaphylaxis.
• Atopic individuals have higher levels of IgE and eosinophils.
-"Immediate"- Within minutes (Type I)
or hours (Types II and III)
-"Delayed" - Takes one or more days

5. Type I: IgE-Mediated Immediate Hypersensitivity
Localized and Systemic Anaphylaxis
• Type I hypersensitivity reaction is commonly called allergic or
immediate hypersensitivity reaction, type I reactions are also
known as IgE-mediated hypersensitivity reactions.
• Type I reaction is always rapid, occurring within minutes of
exposure to an antigen, and always involves IgE-mediated
degranulation of basophils or mast cells.
• IgE is responsible for sensitizing mast cells and providing
recognition of antigen for immediate hypersensitivity reactions.

6. *Effector cells in anaphylaxis
• Mast cells control the immediate response(mast cells are the prime
mediators of anaphylaxis. .
• Eosinophils and basophils drive late or chronic response.
• All these three cells contain cytoplasmic granules whose
contents are the major mediators of allergic reactions
• Like (Histamine, Serotonin ,Prostaglandins )
• HISTAMINE It is the most important mediators of anaphylaxis. •
It is found in a preformed state in granules of mast cells and
basophils.
• • It causes vasodilatation, increased capillary permeability, and
smooth muscle contraction.

7. Sensitization of Mast Cells:
Isotype-Switching to IgE

8. What Determines Allergic Sensitivity?
-Dose of Allergen
-Route of Exposure or Administration
-Host Genetics
-Time

10. IgE-Mediated Allergic Reactions
(Allergy2)

13. Type II Hypersensitivity
• Antibody Dependent Cytotoxicity
• Antibody Dependent Cell mediated Cytotoxicity
• Target antigens are found on cell or tissues
• Antibody binds to Target Antigen
– complement activated cell destruction
– Ig binds to Fc receptors on NK cells

14. :

15. • Both processes result in lysis of the Ab-coated cell
• 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 recpetors
• Autoimmune hemolytic anemia – Ab’s produced vs RBC membrane Ag’s
– Hemolytic Disease of the Newborn
– Hyperacute graft rejection
• Blood Transfusion rxns

16. Hemolytic Disease of the Newborn

17. Type III Hypersensitivity:
(Immune Complex-mediated cytotoxicity)
• Caused by immune complex deposition in tissues
– Small amts cleared by phagocytic cells
– Activates complement which attracts neutrophils and
stimulate Mast cell degranulation
Depending on location, can be (localized or systemic )
• Most damage from activity of Neutrophils
– Immune complexes can adhere to tissue making it
difficult for Neutrophils to phagocytosis
– Neutrophils continue releasing lytic enzymes, etc.

18. 1. Complement initiates
mast cell
degranulation
2. Neutrophils are
chemotactically
attracted to the site
3. Neutrophils release
lytic enzyme after
failed attempts to
endocytose the
immune complex

19. Type III Hypersensitivity:
Systemic (generalized) reactions
• Produced when large amounts of Ag
enter the bloodstream
– The sites of deposition vary; usually
in tissues where plasma is filtered
– Esp. in kidneys, blood vessels, and
joints
• Can cause tissue damaging:
• Serum sickness
• Autoimmune diseases
• Drug reactions

20. Arthus reaction
 An Arthus reaction is a local vasculitis associated with
deposition of immune complexes and activation of
complement. Immune complexes form in the setting of
high local concentration of vaccine antigens and high
circulating antibody concentration.
 ‫جدا‬ ‫مهم‬Arthus reactions are characterized by severe pain,
swelling, induration, edema, hemorrhage, and occasionally
by necrosis.
 These symptoms and signs usually occur( 4–12) hours
after vaccination.

21. Type IV Hypersensitivity:(Delayed-Type
Hypersensitivity)
• Occurs 48-72 hrs after Ag contact and is mediated
by Ag-specific TH1 cells and activated MØ
• It differs from the other types of hypersensitivity by
being mediated through cell-mediated immunity
• TH1 cells secrete: IFN-γ activates MØ
• This reaction occurs due to the activation of
specifically sensitized T lymphocytes rather than the
antibodies.

22. DTH Response
Cytokines released include: TNF-β, GM-CSF, and IFN – γ

23. DTH Response
Type IV rxns marked by time delay and recruitment of
MØ instead of Neut’s and Eosino’s

24. Contact Dermatitis
Produced by a variety of substances
Mostly small molecules attach to a
protein in the skin
The Ag-protein complex is processed
and presented  sensitize TH1 cells
Subsequent exposure activates TH1
cells  48-72 hrs later MØ infiltrate
Activation of MØ causes the
inflammation that characterizes the
disorder