Module 9 - Hypersensitivity Reactions and Organ Transplant Rejection Flashcards
Type 1 Hypersensitivity
Occur due to highly-sensitized response to an allergen
Runs in families
Steps in type 1 hypersensitivity
First time exposure to an allergen triggers the immune system.
IgE antibodies are formed from B-lymphocytes.
Antibodies attach to mast cells in precise locations.
Both mast cells and basophils are sensitized.
Release of Mediators
-This occurs with second time allergen exposure.
-Sensitized mast cells and basophils remember previous exposure.
-Chemical mediators release histamine from basophils and mast cells.
Inflammatory response is initiated, which causes:
-Vasodilation
-Increased blood vessel permeability
-Edema
-Redness
-Pruritus
Chemical mediators and their effects during allergies - platelets
activating factor initiates the inflammatory response
Chemical mediators and their effects during allergies - leukotrienes and prostaglandins
lead to bronchoconstriction
Chemical mediators and their effects during allergies - prostaglandins
also cause vasodilation which leads to hypotension
Chemical mediators and their effects during allergies - histamine
increases vascular permeability, causes smooth muscle contraction, and tachycardia.
Chemical mediators and their effects during allergies - Kinins
cause angioedema (swelling that is similar to hives, but the swelling is under the skin instead of on the surface).
Chemical mediators and their effects during allergies - serotonin
leads to pupil dilation.
Type I reaction - wheal-and-flare reactions
(possible cause and manifestations)
Mosquito bite
Urticaria
Area has a pale wheal that contains serous fluid
The wheal is surrounded by area of redness from hyperemia
Type I reaction - systemic anaphylactic
(possible cause and manifestations)
Bee sting
Injection of a medication
Shellfish
Pupillary dilation
Weak, thready pulse
Bronchial edema
Airway obstruction
Vascular collapse
Angioedema
Hypotension
Dyspnea
Cyanosis
Drugs that can cause anaphylaxis
Aspirin
Cephalosporins
Chemotherapy drugs
Insulins
Local anesthetics e.g lidocaine
Nonsteroidal anti-inflammatory drugs
Penicillins
Sulfonamides
Tetracycline
Foods that can cause anaphylaxis
Eggs
Milk
Nuts and peanuts
Shellfish, fish, chocolate, strawberries
Treatments that can cause anaphylaxis
Allergenic extracts used in immunotherapy
Blood products (whole blood and components)
Iodine-contrast media for CT scan or other radiologic procedures
insect venoms that can cause anaphylaxis
Wasps
Hornets
Yellow jackets
Bumblebees
Ants
animal sera that can cause anaphylaxis
Diphtheria antitoxin
Rabies antitoxin
Snake venom antitoxin
Tetanus antitoxin
Atopy
inherited sensitivity to environmental allergens
Allergenic Rhinitis
AKA hay fever
Most common
caused by airborne substances, perennial allergic rhinitis (year round), seasonal allergic rhinitis (seasonal)
targets eye conjunctiva and upper respiratory tract mucosa
Symptoms - lacrimal watering and itchiness, nasal discharge and stuffiness, sneezing, mucosal swelling with airway obstruction with pruritus around the eyes, nose, throat, and mouth
Asthma
Usually allergy-related
Inflammatory mediators produce
-Bronchial smooth muscle constriction
-Excessive viscoid mucous secretion
-Edema of the bronchial mucous membranes
-Decreased lung compliance
–Causes dyspnea
–Wheezing
–Coughing
–Tightness in the chest
–Thick sputum
Atopic Dermatitis
Chronic, inherited skin disorder
Present with elevated IgE levels and positive skin tests
Localized wheal-and-flare type I reaction
Vasodilation of blood vessels occur
Interstitial edema with vesicles form
Localized pruritus occurs
Urticaria
AKA hives
Cutaneous reaction
Characterized by transient wheals (pink, raised, edematous, pruritic areas) vary in size and shape and can occur all everywhere
Develops rapidly after exposure to an allergen which lasts minutes or hours
Histamine causes localized vasodilation (erythema) leaking of fluid (wheal), and flaring
Flaring happens from dilated blood vessels at wheal edge
Histamine causes pruritus with the lesions
Angioedema
a condition that causes swelling in the deeper layers of the skin, which can affect the face, lips, tongue, larynx, abdomen, or arms and legs
Type II hypersensitivity reactions
AKA cytotoxic reactions because antibodies after binding to the antigens on the surface of the host cell cause cell destruction
Steps in type II Hypersensitivity reactions
IgG antibodies found in normal circulation react with antigens present on the cell membrane
Cell is destroyed by phagocytosis or cytolytic enzymes released from complement activation
Target cells in cytotoxic reactions are erythrocytes, thrombocytes (platelets), and leukocytes
The reaction leads to anemia, thrombocytopenia, neutropenia, and rapids tissue damage
Some common antigens involved in a cytotoxic reaction include the ABO blood group as well as the Rh factor.
Common reactions include ABO and Rh incompatibility transfusion reactions, and erythroblastosis fetalis (hemolytic disease of the newborn).
Hemolytic transfusions can cause a reaction
When the blood type does not match antibodies attack it and cause agglutination (clumping) of blood cells, causes blocking of blood vessels and depleted existing clotting factors causing the person to bleed and have high blood pressure
Within a few hours, neutrophils and macrophages will phagocytize the clumped cells; however the situation is still life threatening
Acute kidney injury may occurs due to hemoglobin begin released into urine
example of hemolytic transfusions reaction
Person with type “A” blood has naturally occurring anti-B antibodies on the erythrocytes.
Person with type “B” blood has naturally occurring anti-A antibodies on the erythrocytes.
If the person with type “A” blood receives type “B” blood, the anti-B antibodies attack the transfused blood which causes clumping of RBCs, clotting, and bleeding.
Erythroblastosis fetalis
This occurs due to an Rh-positive (Rh+) father and an Rh-negative (Rh-) mother conceiving an Rh+ fetus.
Rh- mother carries Rh+ fetus.
In the first pregnancy, naturally occurring antibodies are formed against Rh+ blood from the fetus as it crosses the placenta into the mother’s circulation.
Mother is sensitized against Rh+ blood.
With subsequent pregnancies, these antibodies will attack the fetal red blood cells (RBCs); this can lead to a stillbirth.
This condition can be prevented.
-When Rh incompatibility is detected, administer anti-Rh immune globulin (Rhogham) during the first pregnancy. This prevents the disease in subsequent pregnancies.
Type II hypersensitivity reactions
This occurs when IgG and IgM and an antigen form a complex.
An Arthus reaction then occurs - the complexes are deposited in the smaller blood vessels and in tissues that activate the complement system
This then leads to the release of chemical factors and lysosomal enzymes that initiate the inflammatory response and cause tissue destruction
Serum sickness can also happen - It is a complex-mediated hypersensitivity reaction where the person presents with systemic symptoms including fever, rash, arthritis, and arthralgia.
Reaction can be local or systemic.
Reaction can be immediate or delayed.
Symptoms seen are based on number of complexes and location.
common sites and related disorders for Type III hypersensitivity
Common sites are kidneys, skin, joints, blood vessels, and lungs:
Related to autoimmune disorders
Systemic lupus erythematosus
Acute glomerulonephritis
Rheumatoid arthritis
Type IV hypersensitivity
mediated or delayed hypersensitivity reactions
steps in Type IV hypersensitivity
Macrophages with antigens on the cell membrane circulate in the vascular compartment.
Sensitized T-lymphocyte attacks the antigens located on the macrophage.
Lymphokines and other cytokines are released when the macrophages are attacked.
These chemical mediators initiate the inflammatory process. This also results in cell lysis.
Cell lysis leads to tissue destruction.
Examples of Type IV hypersensitivity - contact dermatitis
Stages of the reaction
Skin is exposed to substances that enter the skin. These substances combine with epidermal proteins.
The substance develops antigens.
Memory cells form in 7 to 14 days as a response to the antigen.
When the person is re-exposed to the substance, eczematous skin lesions develop within 48 hours.
possible causes of dermatitis
Metal compounds (nickel or mercury-containing substances)
Rubber compounds
Poison ivy/poison oak/poison sumac
Cosmetics
Laundry detergents
Some dyes
symptoms of dermatitis
In acute contact dermatitis, the skin lesions appear erythematous and edematous and are covered with papules, vesicles, and bullae. The involved area is pruritic but may also burn or sting.
When contact dermatitis becomes chronic, the lesions resemble atopic dermatitis because they are thickened, scaly, and lichenified.
The main difference between contact dermatitis and atopic dermatitis is that contact dermatitis is localized and restricted to the area exposed to the allergens, whereas atopic dermatitis is usually widespread.
These reactions take 24 hours to show.
Microbial hypersensitivity reactions example and explanation
A positive tuberculin skin test
When a person has had tuberculosis, antigens are released from the bacteria, which react with T-cells. This begins the cell-mediated immune response, which results in extensive caseous lung necrosis. Memory cells are created when a person is exposed to the tubercle bacillus.
Transplant
the surgical removal of tissue or an organ from one person (donor) and surgically inserting it into another person (recipient)
what is needed to make a transplant successful
the recipient must take immunosuppressant medications for the rest of their life to prevent rejection
-success of transplantation has been how the recipient’s immune system responds to the HLAs (human leukocyte antigens) - that is why patients have to take immunosuppressants
Allograft (homograft)
Tissue transplanted from one human to another human. This carries the highest risk of rejection.
Isograft
Tissue transplanted between two genetically identical bodies; e.g., identical twins
Autograft
Tissue transplanted from one part of the body to another part on the same individual; e.g., skin or bone
xenograft (heterograft)
Tissue transplanted from a member of one species to a different species; e.g., pig to human
Transplant Rejection Process
Involves type IV cell-mediated hypersensitivity reaction, as well as a hormonal response, which lead to inflammation and tissue necrosis
Impact of rejection on transplantation procedures
Rejection can destroy the transplanted organ necessitating another transplant
what factors can increase the success of a transplant?
Survival time is increased when there is a 6/6 Human leukocyte antigen (HLA) match.
a living donor increases the likelihood of the transplant doing well
What organs do not need experience rejection and why?
Corneas and cartilage lack blood supply, so rejection is not a problem with these transplants
Hyperacute rejection
happens immediately after transplantation when circulation to the transplanted organ is re-established. It happens more often in patients with pre-existing antibodies from prior blood transfusions. The blood vessels are affected, resulting in lack of blood flow to the transplanted tissue.
Acute rejection
develops after several weeks when unmatched antigens cause a reaction.
Chronic or late rejection
occurs after months or years, with gradual degeneration of the blood vessels
Host vs. graft disease (HVGD)
s a form of rejection occurs when the host (recipient’s) immune system rejects the graft (transplanted organ) and can occur with kidney transplants.
ex: Bone marrow transplants can lead to the other type of rejection that happens when the graft tissue contains T-cells that attack the host cells (graft-versus-host disease [GVHD]).
Neonates and young infants can receive heart transplants from donors without a good tissue match due to
an underdeveloped immune system in infants. It does not respond to the foreign tissue.
Common medications
Cyclosporine (Neoral)
Azathioprine (Imuran)
Prednisone (Deltasone) a glucocorticoid
Side effects include of immunosuppressant drugs
Increased risk of opportunistic infections, which can be life threatening
Why can a person with diabetes not take prednisone?
Diabetic patients develop hyperglycemia due to high doses of prednisone used as an immunosuppressant.
why should dental professionals be notified when a patient starts taking cyclosporine?
Dental professionals should be notified when people take cyclosporine due to the side effect of gingival hyperplasia.
