L:22 Hypersensitivity disorders Flashcards
What is hypersensitivity
Exaggerated immune response harmful to organism itself
Classifications of the 4 types of hypersensitivity reactions
Antibody-mediated
Cell-mediated
Antibody mediated effector mechanisms
Type I, II, and III
Correspond to defenses against extracellular pathogens
Cell-mediated effector mechanisms
Type IV- corresponds to defense against intracellular pathogens
Clinical manifestation of Type I hypersensitivity caused by?
Mediators secreted by Mast cells
What type of hypersensitivity takes place when antibodies specific for the cell and tissue Ags cause injury or disease to the tissue?
Type II
What is it called when Abs bind to circulating Ags to form immune complexes, which deposit in vessels, leading to inflammation in the vessel walls (vasculitis)
Immune Complex diseases (type III hypersensitivity)
What is the cause of type IV hypersensitivity?
T cell mediated disease caused by inflammation caused by cytokines produced by CD4 Th1 and Th17, or killing of host by CD8 CTLs
Individuals with a strong propensity to develop allergic reaction is said to be what?
Atopic
Type I hypersensitivity rxn is controlled by the binding of what?
IgE Abs to FcĘR1 located on the membrane of MAST CELLS, BASOPHILS and EOSINOPHILS
Most IgE produced following initial contact with Ag becomes?
Fixed on the surface of mast cell and basophils..
Second contact with Ag, the Ag-Ab rxn occurs predominantly on mast cell and basophil membrane
Hallmarks of Immediate hypersensitivity
Acute vascular, smooth muscle reactions, and inflammation
What causes vascular dilation
Prostaglandins
Histamines
What causes prolonged smooth muscle contractions?
Leukotrienes
What induces local inflammation (the late phase rxn)
Cytokines
Time frame of immediate and late phase rxn
Immediate vascular and smooth muscle develops within minutes.
The late-phase rxn develops 2-4 hrs. later characterized by inflammation
reversible airway obstruction often caused by inflammatory mediators from mast cells
Asthma
*spasmatic contraction of smooth muscle surrounding bronchi decreasing lumen size and causing SOB
Anaphylaxis
Rapid release of vaso active amines from mast cells and basophils as well as cytokines. Results in smooth muscle contraction in vasculature and vasodilation of capillary epithelium. **BP decreases leading to vascular shock* contraction of smooth muscles in bronchi cause difficulty breathing
In type II hypersensitivity IgG and IgM activate what pathways?
Complement system by classical pathway. results in byproducts that recruit leukocytes to induce inflammation
Type II
What activates leukocytes resulting in pro-inflammatory response?
IgG antibodies binding to neutrophil and macrophage Fc receptors.
Reactive oxygen and lysosomal enzymes are released and damage adjacent tissue because Ab-Ag complexes are formed on target cell
Type III
Ab-Ag complexes deposit where?
blood vessels and other sites resulting in vascular inflammation, and subsequent ischemic damage to tissue
Type III
Major mechanism triggering tissue damage
Classical activation of complement
Type III
Tissue damage is mediated by?
- Complement activation
- Mast cell degranulation
- Neutrophil chemotaxis
- Inflammation caused by immune cells
Type IV (delayed type hypersensitivity DTH) is caused by?
Activation of Th1 cells
Unlike Type I, II, III passive transfer of type IV requires the transfer of ?
Antigen- specific TH1 clones
What type of hypersensitivity is T cell mediated?
Type IV
Tissue injury is caused by what in type IV
Inflammation induced by cytokines that are produced by CD4 Th1 cells and Th17
Inflammation associated with T-cell mediated disease is typically chronic
The classical T cell mediated inflammatory reaction is called?
**Delayed-type hypersensitivity
TB test is type of delayed reaction
Types Of type IV disease
MS, rheumatoid, type 1 diabetes, Crohns, contact dermatitis (poison ivy) Chronic Infections (tb)
Types of type I syndromes
Food alergy, asthma, allergic rhinitis
SLE systemic lupus erythematosus is what type of hypersensitivity?
Type III
Type 1:
Pathologic immune mechanism
TH2 cells, IgE antibodies, mast cells, eosinophils
Type 1:
Mechanism of tissue injury and disease
Mass cell derived mediators (vasoactive amines, lipid mediators, cytokines)
Cytokine-mediated inflammation (eosinophils, neutrophils)
Immediate type 1 hypersensitivity is a type of pathologic reaction that is caused by what?
Release of mediators from mast cells
Type 1 hypersensitivity is most often triggered by what?
Production of IgE Ab against environmental Ags and the binding of IgE to Mast cells
IgE-Fc∑R1 binding has high affinity for ?
IgE
What are the sequence of events in the development of immediate hypersensitivity?
- production of IgE after activation of Th2 cells by 1˚ exposure to allergen
- Binding of IgE to Fc receptors of mast cells
- Release of mediators by mast cells after 2˚ exposure to Ag and cross-linking of the membrane-bound IgE by Ags
The activation of TH2 cells causes what to happen to start production of IgE
Stimulation of IgE class switching in B cells
What mediators case Imediate HS reaction within minutes
Mast cells releasing Vasoactive amines, lipid mediators
What mediator cause late-phase reaction within 6-24 hrs.after repeat exposure?
Mast cells releasing Cytokines
Examples of type 1 hypersensitivity
Anaphylaxis Acute urticaria Allergic rhinitis Asthma Food allergy
Type 2 hypersensitivity:
Pathological immune mechanism
IgM, IgG, antibodies against cell surface of extracellular matrix antigens
Type 2 hypersensitivity
mechanism of tissue injury and disease
Complement and Fc receptor mediated recruitment and activation of leukocytes (Neutrophils, macrophages)
Opsonization and phagocytosis of cells
Abnormalities in cellular function, e.g. hormone receptor signaling
Examples of type 2 hypersensitivity
Hemolytic anemia Thrombocytopenic purpura Goodpasture syndrome Graves disease Myasthenia gravis Pemphigus vulgaris Blood Transfusion rxn Rheumatic fever
Type 3 hypersensitivity:
Pathological mechanism:
Immune complexes of circulating antigens and IgM or IgG antibodies deposited in vascular basement membrane of blood vessel
Type 3 hypersensitivity mechanism of tissue injury or disease
Complement and Fc receptor mediated recruitment and activation of leukocytes
Type 3 is mediated by the deposition of what in BV
Soluble Ab-Ag complexes formed in circulation
The complexes initiate the complement to release what anaphylatoxin products
C3a and C5a
Examples of type 3 hypersensitivity
Systemic lupus polyarteritis nodosa post-strep glomerulonephritis serum sickness arthus reaction
Type 4 hypersensitivity
pathological mechanism
CD4 Tcells (cytokine-mediated inflammation) CD8 CTLs (T-cell mediated cytolysis)
Type 4 hypersensitivity
mechanism of tissue injury or disease
- Macrophage activation, cytokine-mediated inflammation
2. Direct target cell lysis, cytokine-mediated inflammation
The major causes of T-cell mediated (type 4) hypersensitivity is?
Autoimmunity and exaggerated or persistent response to environmental Ag
**Type 4 tissue injury may also accompany a T-cell response to microbes such as
M. tuberculosis
Type 4 killing of host cells is caused by?
CD8 CTLs
Type 4 cytokine mediated inflammation and tissue injury is primarily caused by
Cytokines produced by CD4 Th1 and Th17 cells
What are Th1 cells
Th1 cells protect against intracellular organisms and secrete IFN¥ and TFNå. They help activate B-cells stimulation to secrete IgG, macrophages, and assist in activation of CD8. **ˆIFN-¥ inhibits IgE production reducing allergic responses
What are Th2 cells
Protect against Extracellular organisms and secrete IL-4,5,10, and 13. release mediators that cause sneezing, coughing, and diarrhea to expel extracellular microbes
HS type systemic lupus erythematous
Type 3
HS type rheumatoid arthritis
Type 2 and 4
diagnostic test for rheumatoid factor
HS type MS
Type 4
HS type Diabetes mellitus type 1
TYPE 4
HS type Inflammatory bowel
Type 4
