Chapter 14 Altered Immune Responses and Transplantation

passive acquired immunity

implies that the host receives antibodies to an antigen rather than synthesizing them. This may take place naturally through the transfer of immunoglobulins across the placental membrane from mother to fetus. Artificial passive acquired immunity occurs through injection with gamma globulin (serum antibodies). The benefit of this immunity is its immediate effect. Unfortunately, passive immunity is short lived because the person does not synthesize the antibodies and consequently does not retain memory cells for the antigen.

HLA typing

Antigen identification and matching Parents Siblings Genetic Predisposition

Type 1 Hypersensitivity

Assessment History of symptoms, timing and severity Clinical manifestations Diagnostics Allergy testing Blood testing Skin testing **emergency precautions

B lymphocytes

B cells differentiate into plasma cells when activated. Plasma cells produce antibodies (immunoglobulins)

management of anaphylaxis

(1) recognition of signs and symptoms of an anaphylactic reaction, (2) maintenance of a patent airway, (3) prevention of spread of the allergen by using a tourniquet, (4) administration of drugs, and (5) treatment for shock.

Apheresis

is a procedure to separate components of the blood followed by the removal of one or more of these components. Compound words are often used to describe any particular apheresis procedure, depending on the blood components being collected.

Secondary immune defiency

is caused by illness or treatment

Cell Mediated Immunity

Immune responses that are initiated through specific antigen recognition by T cells are termed cell-mediated immunity. Several cell types and factors are involved in cell-mediated immunity. The cell types involved include T lymphocytes, macrophages, and NK cells. Cellmediated immunity is of primary importance in (1) immunity against pathogens that survive inside of cells, including viruses and some bacteria (e.g., mycobacteria); (2) fungal infections; (3) rejection of transplanted tissues; (4) contact hypersensitivity reactions; and (5) tumor immunity.

Graft vs Host Disease

Immunocompromised person gets immunoactive cells Blood transfusions Bone marrow transplants** 7-30 days after introduction of cells Rash on palms and soles Desquamation Liver impairment GI symptoms Supportive Care

Autoimmunity

Inability of the immune system to recognize self from non-self Risk factors: Age Genetics Gender Infection Previous history Categorization Treatment

Tumor Necrosis Factor

Activates macrophages and granulocytes Promotes the immune and inflammatory responses Kills tumor cells Responsible for extensive weight loss Associated with chronic inflammation and cancer Clinical uses for Soluble TNF receptor (Enbrel) Rheumatoid arthritis

Antihistamines

Antihistamines are the best drugs for treatment of allergic rhinitis and urticaria (see Chapter 27, Table 27-2). They are less effective for severe allergic reactions. They act by competing with histamine for H1 -receptor sites and thus blocking the effect of histamine. Best results are achieved if they are taken as soon as allergy symptoms appear. Antihistamines can be used effectively to treat edema and pruritus but are relatively ineffective in preventing bronchoconstriction. With seasonal rhinitis, antihistamines should be taken during peak pollen seasons.

T lymphocytes

Cells that migrate from the bone marrow to the thymus differentiate into T lymphocytes (thymus-dependent cells). The thymus secretes hormones, including thymosin, that stimulate the maturation and differentiation of T lymphocytes. T cells make up 70% to 80% of the circulating lymphocytes and are primarily responsible for immunity to intracellular viruses, tumor cells, and fungi. T cells live from a few months to the life span of an individual and account for long-term immunity. are categorized into T cytotoxic ad T helper cells

atopic reaction

having an inherited tendency to become sensitive to environmental allergens. The atopic diseases that can result are allergic rhinitis, asthma, atopic dermatitis, urticaria, and angioedema.

Transplant Rejection can be

hyperacute, acute, or chronic

Type II: Cytotoxic and Cytolytic Reactions.

hypersensitivity reactions involving the direct binding of IgG or IgM antibodies to an antigen on the cell surface. Antigen-antibody complexes activate the complement system, which mediates the reaction. Cellular tissue is destroyed in one of two ways: (1) activation of the complement system resulting in cytolysis or (2) enhanced phagocytosis. Target cells frequently destroyed in type II reactions are erythrocytes, platelets, and leukocytes.

Primary immune defiecny

if the immune cells are improperly developed or absent

M-CSF

Promotes proliferation, differentiation, and activation of monocytes and macrophages

HLA

The antigens responsible for rejection of genetically unlike tissues are called the major histocompatibility antigens. These antigens are products of histocompatibility genes. In humans they are called the human leukocyte antigen (HLA) system. The genes for the HLA antigens are linked and occur together on the sixth chromosome. HLAs are present on all nucleated cells and platelets. The HLA system is primarily used in matching organs and tissues for transplantation. HLA genes are highly polymorphic. The early interest in HLAs was stimulated by the role of HLAs in matching donors and recipients of organ transplants.

Antipruritic Drugs

Topically applied antipruritic drugs are most effective when the skin is not broken. These drugs protect the skin and provide relief from itching. Common over-thecounter drugs include calamine lotion, coal tar solutions, and camphor. Menthol and phenol may be added to other lotions to produce an antipruritic effect. Some more potent drugs that require a prescription include methdilazine (Tacaryl) and trimeprazine (Temaril). These drugs should be used with great caution because of the associated risk of agranulocytosis.

Organ Transplantation

Types Living vs cadaver Partial organ Multi organ Legalities organ donor card/driver's license Death notification Matching donor and recipient ABO blood typing HLA typing Recipient specific data

Humoral Response

When a pathogen (especially bacteria) enters the body, it may encounter a B lymphocyte that is specific for antigens located on that bacterial cell wall. In addition, a monocyte or macrophage may phagocytize the bacteria and present its antigens to a B lymphocyte. The B lymphocyte recognizes the antigen because it has receptors on its cell surface specific for that antigen. When the antigen comes in contact with the cell surface receptor, the B cell becomes activated, and most B cells differentiate into plasma cells (see Fig. 14-3). The mature plasma cell secretes immunoglobulins. Some stimulated B lymphocytes remain as memory cells. The primary immune response becomes evident 4 to 8 days after the initial exposure to the antigen (Fig. 14-5). IgM is the first type of antibody formed. Because of the large size of the IgM molecule, this immunoglobulin is confined to the intravascular space. As the immune response progresses, IgG is produced, and it can move from intravascular to extravascular spaces.

examples of primary immune disorders

Chronic granulomatous disease PMNs, monocytes X-linked Job syndrome PMNs, monocytes — Bruton's X-linked agammaglobulinemia B X-linked Common variable hypogammaglobulinemia B— Selective IgA, IgM, or IgG deficiency B Some X-linked DiGeorge syndrome (thymic hypoplasia) T— Severe combined immunodeficiency disease Stem, B, T X-linked or autosomal recessive Ataxia-telangiectasia B, T Autosomal recessive Wiskott-Aldrich syndrome B, T X-linked Graft-versus-host disease B, T—

causes of secondary

Drug-Induced Immunodeficiency • Chemotherapy drugs • Corticosteroids Age • Infants • Older adults Malnutrition • Dietary deficiency • Cachexia Therapies • Radiation • Surgery • Anesthesia Diseases or Disorders • Acquired immunodeficiency syndrome (AIDS) • Cirrhosis • Chronic kidney disease • Diabetes mellitus • Hodgkin's lymphoma • Malignancies • Systemic lupus erythematosus • Burns • Trauma • Severe infection Stress • Chronic stress • Trauma (physical or emotional)

antigen

antigen is a substance that elicits an immune response. Most antigens are composed of protein. However, other substances such as large polysaccharides, lipoproteins, and nucleic acids can act as antigens.

Immunotherapy

Immunotherapy involves administration of small titers of an allergen extract in increasing strengths until hyposensitivity to the specific allergen is achieved. For best results, teach the patient to avoid the offending allergen whenever possible because complete desensitization is impossible. Unfortunately, not all allergy-related conditions respond to immunotherapy. Food allergies cannot be safely treated with this therapy, and eczema may worsen with immunotherapy.

T Cytotoxic Cells (CD8)

are involved in attacking antigens on the cell membrane of foreign pathogens and releasing cytolytic substances that destroy the pathogen. These cells have antigen specificity and are sensitized by exposure to the antigen. Much like B lymphocytes, some sensitized T cells do not attack the antigen but remain as memory T cells. As in the humoral immune response, a second exposure to the antigen results in a more intense and rapid cell-mediated immune response.

T Helper Cells (CD4)

are involved in the regulation of cell-mediated immunity and the humoral antibody response. T helper cells differentiate into subsets of cells that produce distinct types of cytokines (discussed in a later section). These subsets are called T H1 cells and T H2 cells. T H1 cells stimulate phagocyte-mediated ingestion and killing of microbes, the key component of cell-mediated immunity. T H2 cells stimulate eosinophil-mediated immunity, which is effective against parasites and is involved in allergic responses.

the peripheral lymph organs

are the lymph nodes, tonsils, spleen, and gut, genital, bronchial, and skin associated lymphoid tissues

the central lymphoid organs

are the thymus gland and bone marrow

Cytokines types

Interleukins Interferons Tumor necrosis factor Colony-stimulating factors Erythropoietin In general, the interleukins act as immunomodulatory factors, colony-stimulating factors act as growth-regulating factors for hematopoietic cells, and interferons are antiviral and immunomodulatory. Clinical uses for erythropoietin (Epogen, Procrit, Aranesp) Anemia of chronic cancer and chemotherapy

Leukotriene Receptor Antagonists

Leukotriene receptor antagonists (LTRAs) block leukotriene, one of the major mediators of the allergic inflammatory process (see Table 27-2). These medications can be taken orally. They may be used in the treatment of allergic rhinitis and asthma.

thymus and bone marrow

Lymphocytes are produced in the bone marrow and eventually migrate to the peripheral organs. The thymus is involved in the differentiation and maturation of T lymphocytes and is therefore essential for a cell-mediated immune response. During childhood the thymus is large. It shrinks with age, and in the older person the thymus is a collection of reticular fibers, lymphocytes, and connective tissue.

Most organ transplant therapy are intially on triple therapy consisting off

calcineurin inhibitor, a corticosteriod, and mycophenolate mofetil The doses of immunosuppressant drugs are reduced over time after the transplant. Patients taking corticosteroids may be weaned off after a few years. The trend in many transplant centers is to use immunosuppression protocols that do not contain corticosteroids because of their many side effects.

anaphylaxsis

can occur when mediators are released systemically (e.g., after injection of a drug, after an insect sting). The reaction occurs within minutes and can be life threatening because of bronchial constriction and subsequent airway obstruction and vascular collapse. The target organs affected are seen in Fig. 14-7. Initial symptoms include edema and itching at the site of exposure to the allergen. Shock can occur rapidly and is manifested by rapid, weak pulse; hypotension; dilated pupils; dyspnea; and possibly cyanosis. This is compounded by bronchial edema and angioedema. Death will occur if emergency treatment is not initiated. Some of the important allergens that can cause anaphylactic shock in hypersensitive people

Natural Killer Cells

cells are also involved in cell-mediated immunity. These cells are not T or B cells but are large lymphocytes with numerous granules in the cytoplasm. NK cells do not require prior sensitization for their generation. These cells are involved in recognition and killing of virus-infected cells, tumor cells, and transplanted grafts. The mechanism of recognition is not fully understood. NK cells have a significant role in immune surveillance for malignant cell changes.

Calcineurin Inhibitors

cyclosporine (Sandimmune,* Neoral,* Gengraf*) (Neoral and Gengraf are microemulsions with better absorption than Sandimmune.) PO, IV Acts on T helper cells to prevent production and release of IL-2 andγ-interferon. Inhibits production of T cytotoxic lymphocytes and B cells. Nephrotoxicity,↑risk for infection, neurotoxicity (tremors, seizures), hepatotoxicity, lymphoma, hypertension, tremors, hirsutism, leukopenia, gingival hyperplasia. tacrolimus (Prograf, FK506) PO, IV Same as cyclosporine but more effective. Same as cyclosporine.

Immunocompetence

exists when the body's immune system can identify and inactivate or destroy foreign substances. When the immune system is incompetent or underresponsive, severe infections, immunodeficiency diseases, and malignancies may occur. When the immune system overreacts, hypersensitivity disorders such as allergies and autoimmune diseases may develop.

Corticosteriods

Nasal corticosteroid sprays are effective in relieving the symptoms of allergic rhinitis (see Chapter 27 and Table 27-2). Occasionally patients have such severe manifestations of allergies that they are truly incapacitated. In these situations a brief course of oral corticosteroids can be used.

mononuclear phagocytes (system)

includes monocytes in the blood and macrophages found in cytothroughout the body. Mononuclear phagocytes have a critical role in the immune system. They are responsible for capturing, processing, and presenting the antigen to the lymphocytes. This stimulates a humoral or cell-mediated immune response. Capturing is accomplished through phagocytosis. The macrophagebound antigen, which is highly immunogenic, is presented to circulating T or B lymphocytes and thus triggers an immune response

Multiple Chemical Sensitivity

is a chronic condition characterized by symptoms that the affected person attributes to low-level chemical exposure.

Atopic dermatitis

is a chronic, inherited skin disorder characterized by exacerbations and remissions. It is caused by several environmental allergens that are difficult to identify. Although patients with atopic dermatitis have elevated IgE levels and positive skin tests, the histopathologic features do not represent the typical, localized wheal-and-flare type I reactions.

Urticaria (hives)

is a cutaneous reaction against systemic allergens occurring in atopic people. It is characterized by transient wheals (pink, raised, edematous, pruritic areas) that vary in size and shape and may occur all over the body. Urticaria develops rapidly after exposure to an allergen and may last minutes or hours. Histamine causes localized vasodilation (erythema), transudation of fluid (wheal), and flaring. Flaring is due to dilated blood vessels on the edge of the wheal. Histamine is responsible for the pruritus associated with the lesions.

goodpasture syndrome

is a disorder involving the lungs and kidneys. An antibody-mediated autoimmune reaction occurs involving the glomerular and alveolar basement membranes. The circulating antibodies combine with tissue antigen to activate the complement system, which causes deposits of IgG to form along the basement membranes of the lungs or kidneys. This reaction may result in pulmonary hemorrhage and glomerulonephritis.

Hyperacute Rejection

occurs minutes to hours after transplantation because the blood vessels are rapidly destroyed. It occurs because the person had preexisting antibodies against the transplanted tissue or organ. There is no treatment for hyperacute rejection, and the transplanted organ is removed. Fortunately hyperacute rejection is a rare event because the final crossmatch just before transplant usually determines whether the recipient is sensitized to any of the donor HLAs. On occasion, for unclear reasons, the final crossmatch does not detect these preformed antibodies, and hyperacute rejection occurs.

Crossmatch

uses serum from the recipient mixed with donor lymphocytes to test for any preformed antiHLA antibodies to the potential donor organ. The crossmatch can be used as a screening test when multiple possible living donors are being considered or once a cadaver donor is selected. A final crossmatch is done just before transplant.

Drug Alert: Tacrolimus and cyclosporine

• A substance in grapefruit and grapefruit juice prevents metabolism of these drugs. • Consuming grapefruit or grapefruit juice while using these drugs could increase their toxicity.

Effects of Aging on the Immune System

• Thymic involution • ↓Cell-mediated immunity • ↓Delayed hypersensitivity reaction • ↓IL-1 and IL-2 synthesis • ↓Expression of IL-2 receptors • ↓Proliferative response of T and B cells • ↓Primary and secondary antibody responses • ↑Autoantibodies

Immunosuppressive: Corticosteriods

prednisone, methylprednisolone (Solu-Medrol) PO, IV Suppress inflammatory response. Inhibit cytokine production (IL-1, IL-6, TNF) and T cell activation and proliferation. Peptic ulcers, hypertension, osteoporosis, Na + and H2 O retention, muscle weakness, easy bruising, delayed healing, hyperglycemia,↑risk for infection.

Innate Immunity

present at birth, and its primary role is first line defense against pathogens

Angioedema

is a localized cutaneous lesion similar to urticaria but involving deeper layers of the skin and the submucosa. The principal areas of involvement include the eyelids, lips, tongue, larynx, hands, feet, GI tract, and genitalia. Swelling usually begins in the face and then progresses to the airways and other parts of the body. Dilation and engorgement of the capillaries secondary to the release of histamine cause the diffuse swelling. Welts are not apparent as in urticaria. The outer skin appears normal or has a reddish hue. The lesions may burn, sting, or itch, and can cause acute abdominal pain if in the GI tract. The swelling may occur suddenly or over several hours and usually lasts for 24 hours.

lymphoid system

is composed of central (or primary) and peripheral lymphoid organs

Plasmapheresis

is the removal of plasma containing components causing or thought to cause disease. It can also be used to obtain plasma from healthy donors to administer to patients as replacement therapy. The most common complications are hypotension and citrate toxicity. Hypotension is usually the result of a vasovagal reaction or transient volume changes. Citrate is used as an anticoagulant and may cause hypocalcemia, which may manifest as headache, paresthesias, and dizziness.

allergy skin test types

(1) a scratch or prick test, (2) an intradermal test, or (3) a patch test.

Major immunosuppressant agents

(1) calcineurin inhibitors, including cyclosporine (Sandimmune, Neoral, Gengraf) and tacrolimus (Prograf, FK506); (2) corticosteroids (prednisone, methylprednisolone [Solu-Medrol] IV); (3) mycophenolate mofetil (CellCept); and (4) sirolimus (Rapamune). Azathioprine (Imuran) and cyclophosphamide (Cytoxan) can also be used. Antilymphocyte globulin (ALG) and muromonabCD3 (Orthoclone OKT3) are IV medications used for short periods to prevent early rejection or reverse acute rejection.

Allergy blood testing

(1) is using a drug that interferes with skin test results (e.g., antihistamines, corticosteroids) and cannot stop taking it for a few days, (2) cannot tolerate the many needle scratches required for skin testing, or (3) has a skin disorder (e.g., severe eczema, dermatitis, psoriasis).

Primary immunodeficiency disorder categories

(1) phagocytic defects, (2) B cell deficiency, (3) T cell deficiency, and (4) a combined B cell and T cell deficiency

immunodeficiency disorders involve impairement of one or more immune mechanisms

(1) phagocytosis, (2) humoral response, (3) cellmediated response, (4) complement, and (5) a combined humoral and cell-mediated deficiency.

IgD

1% Plasma Is present on lymphocyte surface Assists in the differentiation of B lymphocytes

Immune response functions

1. Defense: The body protects against invasions by microorganisms and prevents the development of infection by attacking foreign antigens and pathogens. 2. Homeostasis: Damaged cellular substances are digested and removed. Through this mechanism, the body's different cell types remain uniform and unchanged. 3. Surveillance: Mutations continually arise in the body but are normally recognized as foreign cells and destroyed.

IgA

15% Body secretions, including tears, saliva, breast milk, colostrum Lines mucous membranes and protects body surfaces.

IgG

76% Plasma, interstitial fluid Is only immunoglobulin that crosses placenta Is responsible for secondary immune response Largest component of total immune globulins; found in plasma and interstitial fluid; only Ig to cross placenta and provide newborn with passive acquired immunity

IgM

8% Plasma Is responsible for primary immune response Forms antibodies to ABO blood antigens

hemoyltic transfusion reaction

A classic type II reaction occurs when a recipient receives ABO-incompatible blood from a donor.

Type IV Delayed Hypersensitivity Reaction

A delayed hypersensitivity reaction—a type IV reaction—is also called a cell-mediated immune response. Although cell-mediated responses are usually protective mechanisms, tissue damage occurs in delayed hypersensitivity reactions. The tissue damage in a type IV reaction does not occur in the presence of antibodies or complement. Rather, sensitized T lymphocytes attack antigens or release cytokines. Some of these cytokines attract macrophages into the area. The macrophages and enzymes released by them are responsible for most of the tissue destruction. In the delayed hypersensitivity reaction, it takes 24 to 48 hours for a response to occur.

immune response sequence

A, A virus invades the body through a break in the skin or another portal of entry. The virus must make its way inside a cell to replicate itself. B, A macrophage recognizes the antigens on the surface of the virus. The macrophage digests the virus and displays pieces of the virus (antigens) on its surface. C, A T helper cell recognizes the antigen displayed and binds to the macrophage. This binding stimulates the production of cytokines (interleukin-1 [IL-1] and tumor necrosis factor [TNF]) by the macrophage and interleukin-2 (IL-2) and γ-interferon (γ -IFN) by the T cell. These cytokines are intracellular messengers that provide communication among the cells. D, IL-2 instructs other T helper cells and T cytotoxic cells to proliferate (multiply). T helper cells release cytokines, causing B cells to multiply and produce antibodies. E, T cytotoxic cells and natural killer cells destroy infected body cells. F, The antibodies bind to the virus and mark it for macrophage destruction. G, Memory B and T cells remain behind to respond quickly if the same virus attacks again.

Type 1 Hypersensitivity (anaphylaxsis)

AIRWAY Breathing Circulation Meds Epinephrine Albuterol Diphenhydramine Corticosteroids Ongoing Monitoring

Colony stimulating factors

Granulocyte colony-stimulating factor (G-CSF) Granulocyte-macrophage colony-stimulating factor (GM-CSF) Macrophage colony-stimulating factor (M-CSF)

HLA Typing

HLA typing is done on potential donors and recipients. Currently only the A, B, and DR antigens are thought to be clinically significant for transplantation. Because each locus has two alleles that encode for antigens, a total of six antigens are identified. In transplantation an attempt is made to match as many antigens as possible between the HLA-A, HLA-B, and HLA-DR locations. typing depends on the type of organ

Transplant Rejection

Prevention Pre transplant matching Immunosuppresive therapy Hyperacute Minutes to hours, hemolysis Acute Within the first 6 months Cell mediated (lymphocytes) Antibody development Treatment—usually reversible Chronic Months to years Irreversible Resembles organ failure

Cytokines 2

Soluble factors secreted by WBCs and a variety of other cells in the body Act as messengers among cell types Instruct cells to alter their proliferation, differentiation, secretion, or activity Currently at least 100 different cytokines Have a beneficial role in hematopoiesis and immune function Can have detrimental effects Chronic inflammation

hypersensitivity reactions

Sometimes the immune response is overreactive against foreign antigens or reacts against its own tissue, resulting in tissue damage.

GM-CSF

Stimulates proliferation and differentiation of PMNs and monocytes Clinical uses for GM-CSF (Leukine) Neutropenia, myeloid recovery after bone marrow transplantation

G-CSF

Stimulates proliferation and differentiation of neutrophils Enhances functional activity of mature PMN Clinical uses for G-CSF (Neupogen, Neulasta) Chemotherapy-induced neutropenia

Microbial Hypersensitivity Reaction

The classic example of a microbial cell-mediated immune reaction is the body's defense against the tubercle bacillus. Tuberculosis results from invasion of lung tissue by the highly resistant tubercle bacillus. The organism itself does not directly damage the lung tissue. However, antigenic material released from the tubercle bacilli reacts with T lymphocytes, initiating a cell-mediated immune response. The resulting response causes extensive caseous necrosis of the lung. After the initial cell-mediated reaction, memory cells persist, so subsequent contact with the tubercle bacillus or an extract of purified protein from the organism causes a delayed hypersensitivity reaction. This is the basis for the purified protein derivative (PPD) tuberculosis skin test, which is read 48 to 72 hours after the PPD is injected intradermally.

Primary and secondary immune response

The introduction of antigen induces a response dominated by two classes of immune globulins—IgM and IgG. IgM predominates in the primary response, with some IgG appearing later. After the host's immune system is primed, another challenge with the same antigen induces the secondary response, in which some IgM and large amounts of IgG are produced.

Type III Immune Complex Reactions

Tissue damage in immune-complex reactions, which are type III reactions, occurs secondary to antigen-antibody complexes. Soluble antigens combine with immunoglobulins of the IgG and IgM classes to form complexes that are too small to be effectively removed by the mononuclear phagocyte system. Therefore the complexes deposit in tissue or small blood vessels. They cause activation of the complement system and release of chemotactic factors that lead to inflammation and destruction of the involved tissue. Type III reactions may be local or systemic and immediate or delayed. The clinical manifestations depend on the number of complexes and the location in the body. Common sites for deposit are the kidneys, skin, joints, blood vessels, and lungs. Severe type III reactions are associated with autoimmune disorders such as systemic lupus erythematosus, acute glomerulonephritis, and rheumatoid arthritis.

antigens and normal response

When antigens are introduced into the body, they may be carried by the bloodstream or lymph channels to regional lymph nodes. The antigens interact with B and T lymphocytes and macrophages in the lymph nodes. The two important functions of lymph nodes are (1) filtration of foreign material brought to the site and (2) circulation of lymphocytes.

Autoimmune diseases

a type of hypersensitivity response, occur when the body fails to recognize self-proteins and reacts against self-antigens.

anergy

an immunodeficient condition characterized by lack of or diminished reaction to antigen or a group of antigens

Lymphocytes

are produced in the bone marrow and they differentiate in B and T lymphocytes

Principal factors in the development of autoimmunity disease

(1) the inheritance of susceptibility genes, which may contribute to the failure of self-tolerance; and (2) initiation of autoreactivity by triggers, such as infections, which may activate self-reactive lymphocytes.

Graft vs Host Disease cont

(GVHD) occurs when an immunoincompetent (immunodeficient) patient receives immunocompetent cells. 16 A GVHD response may result from the infusion of any blood product containing viable lymphocytes, as in therapeutic blood transfusions, and from the transplantation of fetal thymus, fetal liver, or bone marrow. In most transplantation situations the biggest concern is the patient's (host's) rejection of the organ or transplant. However, in GVHD disease, the graft rejects the host. response usually begins 7 to 30 days after transplantation .

Panel of Reactive Antibodies

(PRA) indicates the recipient's sensitivity to various HLAs before receiving a transplant. To detect preformed antibodies to HLA, the recipient's serum is mixed with a randomly selected panel of donor lymphocytes to determine reactivity. The potential recipient may have been exposed to HLA antigens by means of previous blood transfusions, pregnancy, or a previous organ transplant. For the PRA, the results are calculated in percentages. A high PRA indicates that the person has a large number of cytotoxic antibodies and is highly sensitized, which means there is a poor chance of finding a crossmatch-negative donor. In patients awaiting transplantation, a PRA panel is usually done on a regular basis. Plasmapheresis and IV immune globulin have been used to lower the number of preformed HLA antibodies in highly sensitized patients.

IgE

0.002% Plasma, interstitial fluids Causes symptoms of allergic reactions Fixes to mast cells and basophils Assists in defense against parasitic infections

Contact Dermatitis

Allergic contact dermatitis is an example of a delayed hypersensitivity reaction involving the skin.. reaction occurs when the skin is exposed to substances that easily penetrate the skin to combine with epidermal proteins. The substance then becomes antigenic. Over a period of 7 to 14 days, memory cells form to the antigen. On subsequent exposure to the substance, a sensitized person develops eczematous skin lesions within 48 hours. The most common potentially antigenic substances encountered are metal compounds (e.g., those containing nickel or mercury); rubber compounds; catechols present in poison ivy, poison oak, and poison sumac; cosmetics; and some dyes.

Mast Cell - stabilizing drug

Cromolyn (Intal, NasalCrom) is a mast cell-stabilizing agent that inhibits the release of histamines, leukotrienes, and other agents from the mast cell after antigen-IgE interaction. It is available as an inhalant nebulizer solution or a nasal spray. Cromolyn is used in the management of allergic rhinitis

Cytokines etc

Cytokines such as erythropoietin (see Chapter 47), colony-stimulating factors (see Table 16-14), interferons (see Table 16-13), and interleukin-2 (see Table 16-13) are used clinically to (1) stimulate hematopoiesis, (2) stimulate the bone marrow to make WBCs, and (3) treat various malignancies. In addition, inhibitors of cytokines such as soluble tumor necrosis factor receptor antagonist and interleukin-1 are used as antiinflammatory agents. (Clinical uses of cytokines are listed in Table 14-4.) Interferon helps the body's natural defenses attack tumors and viruses. Three types of interferon have now been identified (see Table 14-3). In addition to their direct antiviral properties, interferons have immunoregulatory functions. These include enhancement of NK cell production and activation, and inhibition of tumor cell growth. Interferon is not directly antiviral but produces an antiviral effect in cells by reacting with them and inducing the formation of a second protein termed antiviral protein (Fig. 14-4). This protein mediates the antiviral action of interferon by altering the cell's protein synthesis and preventing new viruses from becoming assembled.

Dendritic Cells

Dendritic cells make up a system of cells that are important to the immune system, especially the cellmediated immune response. They have an atypical shape with extensive dendritic processes that form and retract. They are found in many places in the body, including the skin (where they are called Langerhans cells) and the lining of the nose, the lungs, the stomach, and the intestine. Especially in the immature state, they are found in the blood. 2 They primarily function to capture antigens at sites of contact with the external environment (e.g., skin, mucous membranes) and then transport an antigen until it encounters a T cell with specificity for the antigen. In this role, dendritic cells can have an important function in activating the immune response.

Table 14 -1

Etiology • Injection of, inhalation of, ingestion of, or topical exposure to substance that produces profound allergic response (See Table 14-9 for more complete listing.) Assessment Findings See Fig. 14-7. Interventions Initial • Ensure patent airway. • Administer high-flow O2 via non-rebreather mask. • Remove insect stinger if present. • Establish IV access. • epinephrine 1:1000, 0.01 mL/kg (0.3-0.5 mL) IM into midanterior lateral thigh; repeat every 5-15 min.* • Nebulized albuterol (Proventil). • Diphenhydramine (Benadryl) IM or IV. • Corticosteroids: methylprednisolone (Solu-Medrol) IV. Hypotension • Place recumbent and elevate legs. • epinephrine 1:10,000, 0.1 mL/kg IV every 2-5 min. • Maintain blood pressure with fluids, volume expanders, vasopressors (e.g., dopamine [Intropin]). Ongoing Monitoring • Monitor vital signs, respiratory effort, O2 saturation, level of consciousness, and cardiac rhythm. • Anticipate intubation with severe respiratory distress. • Anticipate cricothyrotomy or tracheostomy with severe laryngeal edema.

Allergies Assessment

Subjective Data Important Health Information Past health history: Recurrent respiratory problems, seasonal exacerbations; unusual reactions to insect bites or stings; past and present allergies Medications: Unusual reactions to any medications; use of over-thecounter drugs, use of medications for allergies Functional Health Patterns Health perception-health management: Family history of allergies; malaise Nutritional-metabolic: Food intolerances; vomiting Elimination: Abdominal cramps, diarrhea Activity-exercise: Fatigue; hoarseness, cough, dyspnea Cognitive-perceptual: Itching, burning, stinging of eyes, nose, throat, or skin; chest tightness Role-relationship: Altered home and work environment, presence of pets Objective Data Integumentary Rashes, including urticaria, wheal and flare, papules, vesicles, bullae; dryness, scaliness, scratches, irritation Eyes, Ears, Nose, and Throat Eyes: Conjunctivitis; lacrimation; rubbing or excessive blinking; dark circles under the eyes ("allergic shiner") Ears: Diminished hearing; immobile or scarred tympanic membranes; recurrent ear infections Nose: Nasal polyps; nasal voice; nose twitching; itchy nose; rhinitis; pale, boggy mucous membranes; sniffling; repeated sneezing; swollen nasal passages; recurrent, unexplained nosebleeds; crease across the bridge of nose ("allergic salute") Throat: Continual throat clearing; swollen lips or tongue; red throat; palpable neck lymph nodes Respiratory Wheezing, stridor; thick sputum Possible Diagnostic Findings Eosinophilia of serum, sputum, or nasal and bronchial secretions; ↑serum IgE levels; positive skin tests; abnormal chest and sinus x-rays

Examples of autoimmune diseases

Systemic Diseases • Mixed connective tissue disease • Progressive systemic sclerosis (scleroderma) • Rheumatoid arthritis • Systemic lupus erythematosus Organ-Specific Diseases Blood • Autoimmune hemolytic anemia • Immune thrombocytopenic purpura • Hemochromatosis Central Nervous System • Guillain-Barré syndrome • Multiple sclerosis Muscle • Myasthenia gravis Heart • Rheumatic fever Endocrine System • Addison's disease • Graves'disease • Hypothyroidism • Thyroiditis • Type 1 diabetes mellitus Gastrointestinal System • Celiac disease • Pernicious anemia • Ulcerative colitis Kidney • Glomerulonephritis • Goodpasture syndrome Liver • Autoimmune hepatitis • Primary biliary cirrhosis Eye • Uveitis

Cytokines

The immune response involves complex interactions of T cells, B cells, monocytes, and neutrophils. These interactions depend on cytokines (soluble factors secreted by WBCs and a variety of other cells in the body) that act as messengers between the cell types. Cytokines instruct cells to alter their proliferation, differentiation, secretion, or activity. The net effect of an inflammatory response is determined by a balance between proinflammatory and antiinflammatory mediators. Sometimes cytokines are classified as proinflammatory or antiinflammatory (see Table 14-3). However, it is not that clear-cut, since many other factors (e.g., target cells, environment) influence the inflammatory response to a given injury or insult.

Sympathomimetic/Decongestant Drugs

The major sympathomimetic drug is epinephrine (Adrenalin), which is the drug of choice to treat an anaphylactic reaction. Epinephrine is produced by the adrenal medulla and stimulates α- and β-adrenergic receptors. Stimulation of the α-adrenergic receptors causes vasoconstriction of peripheral blood vessels. β-Receptor stimulation relaxes bronchial smooth muscles. Epinephrine also acts directly on mast cells to stabilize them against further degranulation. The action of epinephrine lasts only a few minutes. For the treatment of anaphylaxis, the drug must be given parenterally (intramuscular [IM], IV). Several specific, minor sympathomimetic drugs differ from epinephrine because they can be taken orally or nasally and last for several hours. Included in this category are phenylephrine (Neo-Synephrine) and pseudoephedrine (Sudafed). The minor sympathomimetic drugs are used primarily to treat allergic rhinitis.

Acute Rejection

most commonly manifests in the first 6 months after transplantation. This type of rejection is usually mediated by the recipient's lymphocytes, which have been activated against the donated (foreign) tissue or organ (Fig. 14-12). In addition to cell-mediated rejection, another type of acute rejection occurs when the recipient develops antibodies to the transplanted organ. It is not uncommon to have at least one rejection episode, especially with organs from deceased donors. These episodes are usually reversible with additional immunosuppressive therapy, which may include increased corticosteroid doses or polyclonal or monoclonal antibodies. Unfortunately, immunosuppressants increase the risk for infection. To combat acute rejection, all patients with transplants require long-term use of immunosuppressants, putting them at a high risk for infection, especially in the first few months after transplant when the immunosuppressive doses are highest.

Cytotoxic (antiproliferative drugs)

mycophenolate mofetil (CellCept) mycophenolate acid (Myfortic) PO, IV Inhibits purine synthesis. Suppresses proliferation of T and B cells. Diarrhea, nausea and vomiting, severe neutropenia, thrombocytopenia,↑risk for infection,↑incidence of malignancies. cyclophosphamide (Cytoxan, Neosar) PO, IV Cross-links DNA, leading to cell injury and death. Results in decrease in number and activity of T and B cells. Neutropenia, hemorrhagic cystitis. azathioprine (Imuran) PO, IV Blocks purine synthesis. Suppresses cellmediated and humoral immune responses by inhibiting proliferation of T and B cells. Bone marrow suppression: neutropenia, anemia, thrombocytopenia. sirolimus (Rapamune) PO Binds to mammalian target of rapamycin (mTOR), thereby suppressing T cell activation and proliferation. ↑Risk for infection, leukopenia, anemia, thrombocytopenia, hyperlipidemia, hypercholesterolemia, arthralgias, diarrhea. ↑incidence of malignancies. Not used in liver and lung transplants. everolimus (Zortress) PO Same as above Peripheral edema, constipation, hypertension, nausea, anemia, urinary tract infection, hyperlipidemia.

Immunotherapy considerations

new-strength dose, after a previous reaction, or after a missed dose. Early manifestations of a systemic reaction include pruritus, urticaria, sneezing, laryngeal edema, and hypotension. Emergency measures for anaphylactic shock should be initiated immediately. Describe a local reaction according to the degree of redness and swelling at the injection site. If the area is greater than the size of a quarter in an adult, report the reaction to the health care provider so that the allergen dosage may be decreased. Record keeping must be accurate and can be invaluable in preventing an adverse reaction to the allergen extract. Before giving an injection, check the patient's name against the name on the vial. Next, determine the vial strength, amount of last dose, date of last dose, and any reaction information. Always administer the allergen extract in an extremity away from a joint so that a tourniquet can be applied for a severe reaction. Rotate the site for each injection. Aspirate for blood before giving an injection to ensure that the allergen extract is not injected into a blood vessel.

Chronic Rejection

rejection is a process that occurs over months or years and is irreversible. Chronic rejection can occur for unknown reasons or from repeated episodes of acute rejection. The transplanted organ is infiltrated with large numbers of T and B cells characteristic of an ongoing, lowgrade, immune-mediated injury. Chronic rejection results in fibrosis and scarring. In heart transplants it manifests as accelerated coronary artery disease. In lung transplants it manifests as bronchiolitis obliterans. In liver transplants it is characterized by loss of bile ducts. In kidney transplants it manifests as fibrosis and glomerulopathy. There is no definitive therapy for this type of rejection. Treatment is primarily supportive. This type of rejection is difficult to manage and is not associated with the optimistic prognosis of acute rejection.

Active Acquired Immunity

results from the invasion of the body by foreign substances such as microorganisms and subsequent development of antibodies and sensitized lymphocytes. naturally from a disease or artifically through immunization

allergic rhinittis

rhinitis, or hay fever, is the most common type I hypersensitivity reaction. It may occur year-round (perennial allergic rhinitis), or it may be seasonal (seasonal allergic rhinitis). Airborne substances such as pollens, dust, and molds are the primary causes of allergic rhinitis. Perennial allergic rhinitis may be caused by dust, molds, and animal dander. Seasonal allergic rhinitis is commonly caused by pollens from trees, weeds, or grasses. The target areas affected are the conjunctiva of the eyes and the mucosa of the upper respiratory tract. Symptoms include nasal discharge; sneezing; lacrimation; mucosal swelling with airway obstruction; and pruritus around the eyes, nose, throat, and mouth.

Guidelines for preventing allergic latex reactions

• Use nonlatex gloves for activities that are not likely to involve contact with infectious materials (e.g., food preparation, housekeeping). • Use powder-free gloves with reduced protein content. • Do not use oil-based hand creams or lotions when wearing gloves. • After removing gloves, wash hands with mild soap and dry thoroughly. • Frequently clean work areas that are contaminated with latexcontaining dust. • Know the symptoms of latex allergy, including skin rash; hives; flushing; itching; nasal, eye, or sinus symptoms; asthma; and shock. • If symptoms of latex allergy develop, avoid direct contact with latex gloves and products. • Wear a Medic Alert bracelet and carry an epinephrine pen (e.g., EpiPen).

Mycophneolate Mofetil

• When given IV, it must be reconstituted in D5 W and no other solution. • Do not give as IV bolus. Give over 2 or more hours.