Hypersensitivity transplant rejection Helath Alterations PDF

Preview

Summary

Anatomy and physiology...

Description

Allergic or hypersensitivity reactions are common. They can be related to something as mild as laundry detergent or as severe as a life-threatening medication allergy. Hypersensitivity reactions happen as a result of the body reacting with a foreign agent. These reactions initiate the inflammatory response. There are four different types of hypersensitivity reactions which are based on the antigen source, the time reaction takes to occur, or the immunological cell responsible for the injury. Types I, II, and III involve humoral immunity. Type IV is a delayed reaction and caused by cellmediated immunity. Transplant-related rejection occurs from the recipient’s immune system recognizing the transplanted organ as foreign, which results in immune system activation. Upon completion of this lesson, you will be able to:  Explain hypersensitivity reactions and the process of organ transplant rejection.

Type I Hypersensitivity Reactions A type I hypersensitivity reaction occurs due to a highly-sensitized response to an allergen as opposed to an autoimmune or allergic disorder. Type 1 hypersensitivities tend to run in families. The hypersensitivity reaction is a series of events that take place in response to an antigen. 1.

When a person is first exposed to the allergen, IgE antibodies are formed, which bind to mast cells and basophils. 2. Located inside the mast cells and basophils are granules that contain powerful chemical mediators (histamine, serotonin, leukotrienes, eosinophil chemotactic factor of anaphylaxis [ECF-A], kinins, and bradykinin). 3. When a person is exposed the next time and each time after that, the allergen binds with the IgE from the mast cells and basophils. This stimulates cell degranulation and the release of chemical mediators from the granules. These mediators attack tissues, which leads to clinical symptoms that could be either localized or systemic symptoms. 4. Chemical mediators affect tissues, which leads to smooth muscle contraction, increased vascular permeability, vasodilation, hypotension, increased mucous secretion, and itching. Though the mediators are short-acting and their effects are reversible, the systemic effects are life-threatening.

Allergic Reactions and Anaphylaxis A type I hypersensitivity reaction can be a small, localized reaction such as a wheal-and-flare reaction, or a systemic response such as anaphylaxis that can affect multiple organs. An anaphylactic reaction is a type 1 hypersensitivity reaction. It results in a rapid release of chemical mediators into circulation. Type of Reaction

Wheal-and-flare reaction

Systemic Anaphylactic reaction

Possible Cause

Manifestations

 Mosquito bite  Urticaria

 Area has a pale wheal that contains serous fluid  The wheal is surrounded by area of redness from hyperemia

 Bee sting  Injection of a medication  Shellfish

        

Pupillary dilation Weak, thready pulse Bronchial edema Airway obstruction Vascular collapse Angioedema Hypotension Dyspnea Cyanosis

Systemic Effects of Anaphylaxis Five types of clinical manifestations of a systemic anaphylactic reaction affect different body systems.(From Lewis SL, Bucher L, Heitkemper MM, Harding MM, Kwong J, Roberts D: Medical-Surgical Nursing: Assessment and Management of Clinical Problems, ed 10, St. Louis, 2017, Elsevier.)

On subsequent exposures, when an allergen enters the body, the IgE antibodies trigger the release of anaphylatoxins (C3a, C4a, C5a from complement activation) from the mast cells. Other chemical mediators are released that lead to systemic effects.      

Platelet activating factor initiates the inflammatory response. Leukotrienes and prostaglandins lead to bronchoconstriction. Prostaglandins also cause vasodilation which leads to hypotension. Histamine increases vascular permeability, causes smooth muscle contraction, and tachycardia. Kinins cause angioedema. Serotonin leads to pupil dilation.

Additional systemic effects from these chemical mediators are shown in the image.

Type 1 Hypersensitivity: Allergens Causing Anaphylaxis There are hundreds of allergens that can induce anaphylactic shock; however, some drugs, foods, insect venoms, and medical treatments in particular can frequently cause reactions. The drugs which cause reactions are the leading cause of deaths related to anaphylaxis. Type of Allergens

Examples

Drugs         

Aspirin Cephalosporins Chemotherapy drugs Insulins Local anesthetics e.g lidocaine Nonsteroidal anti-inflammatory drugs Penicillins Sulfonamides Tetracycline

   

Eggs Milk Nuts and peanuts Shellfish, fish, chocolate, strawberries

Foods

Treatments  Allergenic extracts used in immunotherapy

Type of Allergens

Examples

 Blood products (whole blood and components)  Iodine-contrast media for CT scan or other radiologic procedures Insect Venoms     

Wasps Hornets Yellow jackets Bumblebees Ants

   

Diphtheria antitoxin Rabies antitoxin Snake venom antitoxin Tetanus antitoxin

Animal Sera

Type 1 Hypersensitivity: Atopic Reactions About 20% of the population has atopy, which is an inherited sensitivity to environmental allergens. A person with atopy is hypersensitive to different allergens and usually has one or more of the following: allergic rhinitis, asthma, atopic dermatitis, urticaria, or angioedema.

Allergic Rhinitis         

Also known as hay fever Most common type I hypersensitivity reaction Airborne substances such as pollens, dust, and molds are primary causes May occur year-round (perennial allergic rhinitis) May be seasonal (seasonal allergic rhinitis) Perennial allergic rhinitis caused by dust, molds, and animal dander Causes of seasonal allergic rhinitis is tree, weed, or grass pollens Target areas are eye conjunctivae and upper respiratory tract mucosa Symptoms include lacrimal watering and itchiness, nasal discharge and stuffiness, sneezing, mucosal swelling with airway obstruction with pruritus around the eyes, nose, throat, and mouth

Asthma

   o o o o     

Usually allergy-related Often have atopic disorders (e.g., infantile eczema, allergic rhinitis, food intolerances) 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 with exacerbations and remissions Caused by several environmental allergens that are hard to identify Present with elevated IgE levels and positive skin tests Do not get typical, localized wheal-and-flare type I reactions Skin lesions more generalized Involve vasodilation of blood vessels Interstitial edema with vesicle formation Localized pruritus

Urticaria       

Also known as hives Cutaneous reaction against systemic allergens in atopic people 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        

Localized cutaneous lesion similar to urticaria Involves deeper layers of the skin and submucosa Mainly involves eyelids, lips, tongue, larynx, hands, feet, GI tract, and genitalia Edema starts in the face then progresses to airways and other areas Capillaries dilate and engorge due to histamine release which causes edema Outer skin normal or with a reddish hue Lesions burn, sting, or itch Lesions can cause acute abdominal pain if in GI tract

Edema may have a fast or slower and insidious onset May last up to 24 hours; with treatment time maybe reduced to half

 

Type II Hypersensitivity Reactions Type II hypersensitivity includes cytotoxic/cytolytic reaction. Type II hypersensitivity reactions are also called cytotoxic reactions because antibodies after binding to the antigens on the surface of the host cell cause cell destruction.      

IgG antibodies found in normal circulation react with antigens present on the cell membrane. Cell is destroyed by phagocytosis (a process by which phagocyte engulfs and causes destruction of foreign substances) or cytolytic enzymes released from complement activation. Targeted cells in cytotoxic reactions are erythrocytes, thrombocytes (platelets), and leukocytes. The reaction leads to anemia, thrombocytopenia, neutropenia, and rapid 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).

This image depicts cell destruction through both phagocytosis and cytolytic enzymes. It begins with anti-A antibodies (found in type B blood) attacking the antigens because it is foreign. This antigen-antibody reaction activates complement which leads to cell wall lysis. Phagocytosis cleans up the area by engulfing all the debris from the dead cells.

Blood Type Compatibility and Hemolytic Reactions Red blood cells are categorized by ABO type and Rh factor. The four blood types include: A, B, AB, and O. The Rh factor can be positive (Rh+) or negative (Rh-). The table below depicts the four different blood types, the type of antigens and antibodies each contains, and which blood type is compatible for blood donation.

ABO Blood Groups and Transfusion Compatibilities Blood Group RBC Antigens Antibodies in Plasma

For Transfusion, Can Receive Donor Blood Group

O A B AB

O O or A O or B O, A, B, or AB

None A B A and B

Anti-A and anti-B Anti-B Anti-A None

An ABO or Rh incompatibility causes hemolytic diseases. This leads to hemolysis of blood cells. There are two disorders that cause type II hypersensitivity reactions: hemolytic transfusion reactions and hemolytic disease of the newborn (erythroblastosis fetalis). Hemolytic transfusion reactions occur due to transfusion of ABO incompatible blood. If the recipient receives an incompatible blood type, antibodies immediately cover foreign erythrocytes which cause agglutination (clumping) of the blood cells. These clumped cells block smaller blood vessels, causing clotting in the extremities. At the same time, these clumped cells are depleting existing clotting factors, so the person bleeds. Within a few hours, neutrophils and macrophages will phagocytize the clumped cells; however, the person is in a life-threatening situation with bleeding and clotting at the same time. Acute kidney injury occurs due to hemoglobin being released into urine (hemoglobinuria). Example:   

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.

Hemolytic Disease of the Newborn Hemolytic disease of the newborn is also called erythroblastosis fetalis. This occurs due to incompatibilities between the mother’s blood and the fetus’ blood. When this occurs, it initiates a series of events that can be life-threatening.

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 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 III Hypersensitivity Reactions There are various stages in the process of a type III hypersensitivity reaction.

Process of a type III hypersensitivity reaction. Type III hypersensitivity reactions happen when an antigen combines with IgG and IgM and form a complex. These complexes are too small to be eliminated by phagocytes. As a result, this leads to an Arthus reaction where these complexes deposit in the smaller blood vessels and in tissues that activate the complement system. This activation 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 are kidneys, skin, joints, blood vessels, and lungs: o Related to autoimmune disorders o Systemic lupus erythematosus o Acute glomerulonephritis o Rheumatoid arthritis

Type IV: Cell Mediated or Delayed Hypersensitivity Reactions

A type IV hypersensitivity reaction is a delayed cell-mediated immune response that happens when sensitized T-lymphocytes attack antigens. It is different from the other hypersensitivity reactions as it is cell-mediated rather than antibody mediated. As a result of this response, lymphokines or other chemical mediators are released. This causes an inflammatory response and antigen destruction. This hypersensitivity reaction can take 24-48 hours to develop. The process of a type IV hypersensitivity reaction includes these stages.

Example Type IV Reaction: Contact Dermatitis Contact dermatitis caused due to exposure to rubber. Contact dermatitis is an example of a delayed hypersensitivity reaction involving the skin. Stages of the reaction, potential allergens, and symptoms are discussed here.

Stages of Reaction 1.

Skin is exposed to substances that enter the skin. These substances combine with epidermal proteins. 2. The substance develops antigens. 3. Memory cells form in 7 to 14 days as a response to the antigen. 4. When the person is re-exposed to the substance, eczematous skin lesions develop within 48 hours.

Allergens The most common potentially antigenic substances that cause allergic skin rashes are:      

Metal compounds (nickel or mercury-containing substances) Rubber compounds Poison ivy/poison oak/poison sumac Cosmetics Laundry detergents Some dyes

Symptoms

   

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 A positive Mantoux tuberculin skin test showing type IV allergy developed at the injection site. (From The Centers for Disease Control and Prevention, Courtesy of Gabrielle Benenson.) A positive tuberculin skin test is a good example of a microbial cell-mediated immune reaction. It demonstrates a type IV hypersensitivity reaction. 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. Application: When a person who has had tuberculosis in the past receives a purified protein derivative (PPD) tuberculosis skin test it will cause a reaction. The purpose of this test is to determine prior exposure to the tuberculosis organism. When a small amount of antigen is injected into the skin [purified protein derivative (PPD)] of a previously sensitized person, an area of induration (inflammation, swelling and hardened mass) develops at the injection site, indicating a positive test. The injection area is assessed 48-72 hours later. This positive reaction does not mean the person has a current infection, however, it does indicate exposure to the tuberculosis bacterium in the past. An x-ray and sputum culture will determine the absence or presence of active tuberculosis.

Tissue and Organ Transplants A transplant is the surgical removal of tissue or an organ from one person (donor) and surgically inserting it into another person (recipient). Transplants have become more successful over time. Surgical techniques have improved as well as histocompatibility testing and immunosuppressant medications. In order for a transplant to be successful, the recipient must take immunosuppressant medications for the rest of their life to prevent rejection. There are different types of tissues and organs that may be transplanted.

Different types of tissues and organs may be transplanted. (From Lewis SL, Bucher L, Heitkemper MM, Harding MM, Kwong J, Roberts D: Medical-Surgical Nursing: Assessment and Management of Clinical Problems, ed 10, St. Louis, 2017, Elsevier.) Four different types of transplants can be performed based on where the transplant tissue originates.

Allograft (homograft) Isograft Autograft Xenograft (Heterograft)

Tissue transplanted from one human to another human. This carries the highest risk of rejection. Tissue transplanted between two genetically identical bodies; e.g., identical twins Tissue transplanted from one part of the body to another part on the same individual; e.g., skin or bone Tissue transplanted from a member of one species to a different species; e.g., pig to human

The majority of transplants involve tissue or organs from one human donor to another human recipient (allograft). Because the genetic makeup of cells is the same only in identical twins, the obstacle to complete success of transplantation has been how the recipient’s immune system responds to the HLAs (human leukocyte antigens). The goal of immunosuppressant medications is to lower the immune system to prevent rejection of the graft tissue.

Transplant Rejection Process Rejection occurs when the recipient’s immune system attacks the transplanted organ or tissue. It is a complex process involving a type IV cell-mediated hypersensitivity reaction. It also involves a humoral response. Both systems lead to inflammation and tissue necrosis.

Impact of Rejection on Transplantation Procedures     

Rejection can destroy the transplanted organ necessitating another transplant; however, many recipients live a long, successful life. Survival time is increased when there is a 6/6 Human leukocyte antigen (HLA) match. HLA is used to match the donor and recipient. HLA matching identifies best donor and works very well if a transplant is from a living donor and the recipient is compliant with immunosuppressive therapy. Corneas and cartilage lack blood supply, so rejection is not a problem with these transplants. With improved surgical techniques and antirejection medicat...