hypersensitivity i ii ch 18 19 l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Hypersensitivity I & II Ch. 18-19 PowerPoint Presentation
Download Presentation
Hypersensitivity I & II Ch. 18-19

Loading in 2 Seconds...

play fullscreen
1 / 47

Hypersensitivity I & II Ch. 18-19 - PowerPoint PPT Presentation


  • 249 Views
  • Uploaded on

Hypersensitivity I & II Ch. 18-19 . March 6th, 2006 Ricky Chang. Objectives. Know the mechanism of Type I hypersensitivity Know the mediators of Type I hypersensitivity Know the diseases associated with Type II hypersensitivity. Hypersensitivity.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Hypersensitivity I & II Ch. 18-19' - arleen


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
hypersensitivity i ii ch 18 19

Hypersensitivity I & IICh. 18-19

March 6th, 2006

Ricky Chang

objectives
Objectives
  • Know the mechanism of Type I hypersensitivity
  • Know the mediators of Type I hypersensitivity
  • Know the diseases associated with Type II hypersensitivity
hypersensitivity
Hypersensitivity
  • Adaptive immunity is important against microbial infections, but it is also capable of causing tissue injury and disease (autoimmune diseases)
  • Occurs when immune responses are directed against self-ag and also from uncontrolled or excessive responses to against foreign ag, such as microbes and allergens
hypersensitivity4
Hypersensitivity
  • Common cause is failure of self-tolerance, which ensures that individuals do not respond to their own antigens
  • Leads to tissue injury that occurs in autoimmune diseases due to the same effector mechanisms used to protect against microbes
hypersensitivity5
Hypersensitivity
  • Type I: IgE antibodies bind to Fc receptors on mast cells. IgE induces mast cell degranulation and release inflammatory mediators
  • Type II: Ab mediated immune response against self antigen or foreign antigen (ie ag on transfused RBC)
  • Type III: Immune complexes are deposited in tissue
  • Type IV: T-cell mediated response where Ag sensitized T-cells release lymphokines
roles of mast cells
Roles of Mast Cells
  • Part of connective tissue (contains granules of histamine and heparin)
  • Allergic diseases (asthma,eczema,itch)
  • Anaphylaxis (systemic shock to allergens such as bee sting,nuts,drugs)
  • Autoimmune disorders/Acute or chronic inflammation (MS, Rheumatoid arthritis)
  • Wound healing
  • Innate response for clearing bacteria and viruses
slide9

Mast Cell

Basophil

type i immediate
Ag/allergen stimulate CD4+Th2

Th2 releases IL-4, which promote B-cells specific for that Ag to differentiate into IgE producing cells

Circulating IgE binds to Fc receptors on mast cells and basophils

Elicits a transduction event to release mediators stored in granules (Degranulation)

Immediate hypersensitivity response (5-10 minutes)

Type I (Immediate)
type i mast cells
Type I: Mast Cells
  • Type I reaction is dependent upon the specific triggering of IgE-sensitizedmast-cells by allergen (Ag)
  • Ag enter via mucosal surfaces and are taken up by APC
  • Th2 cells release IL-4 to facilitate the B-cell proliferation and differentiation, producing IgE specific for the allergen
  • REMEMBER: THIS IS A TH2 RESPONSE!
activation of mast cells
Activation of Mast Cells
  • IgE from B-cells binds to FcRI on mast-cells

- is the heavy chain responsible for IgE isotype switching

  • FcRI on mast-cells cross-links with Ag-bounded IgE and induces degranulation of mediators
slide17

Cross-linking of FcRI to

IgE bounded to Ag

Degranulation of Mediators

mast cell mediators
Mast-Cell Mediators
  • Inflammatory Mediators released

-Histamine

-Proteases (tryptase or chymase), acid hydrolases

-Proteoglycans (heparin, chondroitin sulfate)

mast cells lipid mediators
Mast Cells: Lipid Mediators
  • Prostaglandins D2
  • Leukotrienes C4, D4, E4
  • Platelet-activating factor
mast cells cytokines
Mast-Cells: Cytokines
  • IL-3: Promote mast cell proliferation
  • IL-4, IL-5: Promote Th2 differentiation and IgE AB production
  • TNF-, MIP-1 : Enhance inflammatory reaction
allergen induced hypersensitivity
Allergen Induced Hypersensitivity
  • Allergen: are antigens that induce production of specific IgE AB
  • Examples: plant pollens, dust, animal hair, animal anti-serum, insect venom, chemicals, and foods
  • Once the allergen reaches the sensitized mast cells, the allergen crosslinks the surface-bound IgE intracelluar Ca+2 and triggers degranulation of mediators
atopy
Atopy
  • Atopy: Describes individuals that produce IgE AB in response to various environmental Ag and develop immediate hypersensitivity (Type I) responses.(Asthma, eczema, hay fever, and urticaria)
  • These individuals normally have a strong family history (autosomal transmission of atopy)
atopy25
Atopy
  • HLA vs. Allergen Responsiveness

-Some allergens response have a relationship to HLA

-HLA-DR2 and HLA-A2: high responder to low dos of ragweed

-HLA-B8: high responder to ragweed and also associated to other forms of hyperimmunity (autoimmunity)

slide26
IgE
  • IgE blood concentrations are often increased in allergic disease and are grossly elevated in parasitic infections
  • IL-4: promote B-cells to differentiate into IgE-producing specific cells
eosinophil
Eosinophil
  • Th2 produce IL-5: Promotes the synthesis and secretion of IgA from B-cells and also important in stimulating eosinophil development and activation
  • IL-4 and IL-5 production by Th2 cells may account for the eosinophilia seen in type I hypersensitivity and parasitemia
two types of mast cells
Two Types of Mast Cells
  • Connective tissue mast cells (CTMCs)
  • Mucosal mast cells (MMC)
connective tissue mass cells
Connective Tissue Mass Cells
  • CTMCs are found most in blood vessels but vary in size and number of granules at different regions of the body
  • Diseases such as Crohn’s disease, ulcerative colitis, and RA all present with increase in CTMCs
types of fc receptors for ige
Types of Fc Receptors for IgE
  • There are two types of receptors for IgE

1) FcRI (high affinity): Expressed on mast cells and basophils

2) FcRII (low affinity): Expressed by lymphocytes

mast cells activation
Mast Cells Activation
  • Cross-linking can be artificially induced with lectins such as PHA (Polyhydroxyaldehyde) and ConA
  • These carbohydrates cross-link with IgE and cause degranulation
  • This explains urticaria in individuals allergic to fruits (ie strawberries-contain large amt of lectin
degranulation
Degranulation
  • C’ products of C3a and C5a are very active in degranulating mast cells
  • Compounds that affect Ca+2 influx into mast cells can induce degranulation
  • Drugs such as morphine, codeine, synthetic ACTH can create clinical manifestations related to mast cells
therapy for allergy
Therapy for Allergy

1) Agents that increase intracellular cAMP (-agonist)-inhibits contraction

-Theophyllines: Prevents cAMP degradation

2) Blocking mediator release, such as sodium cromolyn: mechanism not clear, but seem to antagonize IgE-induced mediator release.

therapeutics
Therapeutics
  • Direct Inhibitors

-Theophyllines, Xanthines

-Sodium cromolyn

-Epinephrine

-PGE1, PGE2

  • Indirect Inhibitor

-Glucocorticoids

histamine receptors
H1

Bronchial constriction

Musous secretion

Intestinal smooth muscle contraction

Itching and pain at sensory nerve endings

H1 and H2

Reduces BP

Increase permeability in skin

H2

- Gastric secretion in stomach

Histamine Receptors
antihistamines
Nausea,vertigo,motion sickness

-Cyclizine

-Dimenhydrinate

-Diphenhydramine (Benadryl, Tylenol PM)

-Meclizine

H1 Antagonists

-Promethazine (Phenergan)

-Cetirizine (Zyrtec)

-Desloratadine (Clarinex)

-Fexofenadine (Allegra)

-Loratadine (Claritin)

Antihistamines
type ii
Type II
  • Antibodies are directed against ag on particular cells/tissue or extracellular matrix, causing damage (ie RBC transfusion)
  • These cell- or tissue-specific Ab cause diseases

-Myasthenia Gravis: Ab blocks Ach-binding and cause muscle weakness and paralysis

-Graves’ Disease: Ab stimulate TSH and casue hyperthyroidism)

type ii41
Type II
  • Type II causes disease by 3 mechanism

1) Opsonization and phagocytosis of cells

2) Complement and Fc receptor-mediated inflammation and tissue injury

3) Interference of normal cellular function by binding to important molecules or receptors

reaction against rbcs and platelets
Reaction Against RBCs and Platelets
  • Transfusion Reactions: There are 200 genetic variant of the RBC, but the ABO is the main designation
  • The Rh system is also important because its cause of hemolytic disease in the newborn
reaction against rbcs and platelets44
Reaction Against RBCs and Platelets
  • Hemolytic disease of the newborn (2nd born)

-RhoGam: It’s an Anti-Rh+ Antibody given to mother after the first born to prevent future complications in later newborns

  • Autoimmune Hemolytic Anemia

-When provoked by allergic reactions to certain drugs, including Penicillin, quinine, and sulphonamides

idiopathic thrombocytpenic purpura itp
Idiopathic Thrombocytpenic Purpura (ITP)
  • Autoantibody to platelets from the rapid removal of platelets from circulation
  • Most often develop in women after bacterial or viral infections
  • Associated with autoimmune disease Systemic Lupus Erythematosus (SLE)
type ii mediated autoimmune diseases
Type II Mediated Autoimmune Diseases
  • Myasthenia Gravis
  • Graves’ Disease
  • Insulin-resistance Diabetes
  • Hemolytic Anemia
  • Rheumatoid Arthritis
slide47

Advise of the Day

TYPE III & Type IV..To Be Continued…