Hypersensitivity Flashcards
What 2 responses can cause a hypersensitivity reaction?
Abnormal response to foreign antigens
Autoimmune response to self antigens
Classify the 4 types of hypersensitivity in terms of timing.
Type I- Immediate
Type II
Type III
Type IV- delayed
What mediates type I hypersensitivity?
IgE as a result from mast cells mediators
What mediates type II hypersensitivity?
What does this cause?
Antibodies that bind to TISSUE antigens
Causes complement dependent tissue injury
What mediates type III hypersensitivity?
What does this cause?
Circulating Ag-Ab complexes which deposit in vessels
Cause complement dependent injury in the vessel wall (vasculitis)
What mediates type IV hypersensitivity?
Cytokines produced from Th1 and Th17 cells, macrophages, or killing of host cells by CD8+ CTLs
What triggers a type I reaction? What does this activate?
What is the timing of this reaction?
Environmental antigens, which activate mast cells in an IgE dependent manner
This reaction is immediate
What is atopy?
When individuals tend to develop allergic diseases due to their genotype.
These individuals are called atopic and develop many Type I hypersensitivities
During Type I hypersensitivity, what is the function of each of the following:
Histamine Protease Prostaglandins Leukotrienes Cytokines
Histamine- causes dilation of small vessels and increases vascular permeability
Protease- causes local tissue damage
Prostaglandins- vascular dilation
Leukotrienes- stimulates prolonged smooth muscle contaction
Cytokines- induce local inflammation
What are the 3 steps that make up type I hypersensitivity starting from when the antigen is first encountered?
- Primary exposure to allergen causes activation of Th2 cells and the production of IgE
- Binding of IgE to Fc epsilon receptors on mast cells where they lie in wait for a specific antigen
- Upon secondary exposure, antigen-dependent cross linking of the membrane bound IgE causes activation of mast cells that result in the release of inflammatory mediators
What are the 2 phases of type I hypersensitivity? Describe each.
Immediate Phase- Vascular and smooth muscle reactions develop within minutes after exposure to the antigen.
-Vasodilation, Congestion, Edema
Late Phase- 2 to 24 hours later. Eosinophils, neutrophils, and T cells are found in the inflammatory infiltrate.
What 2 non-immunologic stimuli cause asthma to occur in the form of bronchospasms?
Cold
Exercise
What causes the systemic reaction, Anaphylaxis?
What are the 3 physiological affects of Anaphylaxis?
Food Allergens cause this
Contraction of smooth muscles in bronchi and bronchioles
Vasodilation of capillary endothelium
BP drops causing vascular shock
What kind of hypersensitivity does Allergen testing utilize?
Type I hypersensitivity
Where on the body are allergen testing performed?
Ventral side of the arm or on the back
What layer of the skin are allergens injected into during allergen testing?
Dermis
During an allergen test, what indicates a positive reaction?
Redness and swelling within 20-30 minutes
If an individual is allergic to something, describe the process of Allergen-Specific Immunotherapy used to treat this.
Administration of increasing doses of allergen
3 goals:
- Induce peripheral T cell tolerance to allergens
- Increase the threshold for mast cell and basophil activation by allergens
- Decrease IgE-mediated histamine release by mast cells
What kind of T cells and what 3 TF/receptors on this T cell is the key mechanism of generating a successful Allergen-Specific Immunotherapy?
Treg cells with FoxP3, CD4+, and CD25+
What kind of cells will increase and decrease during Allergen-Specific Immunotherapy?
*Remember that the goal is to increase tolerance to allergens
Th1 cells increase
Th2 cells decrease
IgG and IgA increases
IgE decreases
Treg cells increase
Decrease Eosinophils, Basophils, and Mast cells
What is the mechanism of how Type II hypersensitivity leads to tissue injury?
IgG and IgM antibodies activate the complement system via the classical pathway
CP leads to the production of C3a and C5a, which recruit leukocytes and induce inflammation
Phagocytosis of the cell causes neutrophils and macrophages to release their inflammatory mediators: ROS and Lysosomal Enzymes which damages tissues
What disease is caused by antibodies against the TSH receptor leading to hyperthyroidism?
Graves Disease
what disease is caused by antibodies that inhibit the binding of acetylcholine to the neurotransmitter ACh receptor by binding to the ACh receptor?
Myasthenia Gravis
What are the 3 types of Drug-Induced Hemolytic Anemias?
Penicillin- Induced
Quinidine- Induced
Methyldopa- Induced
What occurs during Penicillin-Induced Hemolytic Anemia?
Hint: What does the drug bind to and what does this lead to?
The drug binds directly to the erythrocyte surface and induces an anti-drug antibody
These conditions improve when the drug is discontinued
What forms during Quinidine-Induced Hemolytic Anemia? What do these formations bind to?
How do you treat this?
Autoantibodies form immune complexes with the drug
The immune complexes can bind to the erythrocyte surface through CR1
Treatment requires immunosuppression/Plasmaphoresis to remove the immune complexes
What occurs during Methyldopa-Induced Hemolytic Anemia?
How do you treat this?
This drug induces an antidrug antibody that cross-reacts with an Rh antigen.
Tx requires immunosuppresion/plasmaphoresis to remove the autoantibodies.
What are the 7 diseases associated with Type II hypersensitivity?
Autoimmune Hemolytic Anemia
Autoimmune Thrombocytopenic Purpura
Goodpastures Syndrome
Graves Disease
Myasrthenia Gravis
Rheumatic Fever
Pemphigus vulgaris
Describe the mechanism of Type III hypersensitivity.
Ab-Ag complexes form in circulation and deposit in blood vessels and other tissues, including kidney and lungs
Activation of the classical pathway of the complement system to recruit leukocytes
These immune complexes lead to vascular inflammation and ischemia to the tissues. VASCULITIS
What are the 5 diseases of Type III hypersensitivity?
Systemic Lupus Erythematosus
Serum sickness
Polyarteritis Nodosa
Post-streptococcal Glomerulonephritis
Arthus Reaction
What causes Arthus Reaction?
Induced by subcutaneous administratoim of a protein antigen to a previously immunized animal. This results in the formation of immune complexes at the site of antigen injection and causes LOCAL vasculitis (Cutaneous)
What causes Serum Sickness?
Protein antigens are intoduced and form immune complexes that lead to SYSTEMIC vasculitis.
*Compare this to Arthus Reaction
What are the 3 major triggers of Type IV hypersensitivity?
Autoimmunity
Environmental Ags
Microbial Ags (Mycobacterium Tuberculosis)
What does Type IV hypersensitivity reactions lead to?
Tissue injury due to inflammation induced by cytokines produced from:
CD4+ T cells (Th1 and Th17)
Macrophages
CD8+ CTLs
What is Type IV hypersensitivity AKA?
Delayed Type Hypesensitivity
What are the 5 diseases of Type IV hypersensitivity?
Crohn’s Disease
Contact Sensitivity** (Poison Ivy)
Chronic Infections (Ex. TB)
Multiple Sclerosis
Rheumatoid Arthritis
Type 1 Insulin- Dependent Diabetes Mellitus
When does DTH (Type IV) occur?
24-48 hours after antigen exposure
