IMMUNE DISORDER. Reference:-Pathophysiology: A 2-in-1 Reference for Nurses. Philadelphia, PA, USA: LWW (PE), 2004.

Transcription

1 IMMUNE DISORDER Reference:-Pathophysiology: A 2-in-1 Reference for Nurses. Philadelphia, PA, USA: LWW (PE), 2004.

2 Immune system disorders Hypersensitivity is an exaggerated or inappropriate response that occurs on second exposure to an antigen. The result is inflammation and the destruction of healthy tissue. Allergy refers to the harmful effects resulting from a hypersensitivity to antigens, also called allergens. Hypersensitivity reactions may be immediate, occurring within minutes to hours of reexposure, or delayed, occurring several hours after reexposure. A delayed hypersensitivity reaction typically is most severe days after the reexposure. Generally, hypersensitivity reactions are classified as one of four types: type I (mediated by IgE), type II (tissue-specific), type III (immune complex-mediated), type IV (cell-mediated). Type I hypersensitivity: - 1) Exposure to pollen causes IgE antibodies production. 2) IgE becomes attached to mast cells and basophils 3) Activated mast cell and basophil then release histamine and serotonin, in a process called degranulation. 4) Histamine and serotonin cause vasodilation, increase permeability and inflammation (anaphylaxis), rapid drop in blood pressure, shock and death. 5) The antigen and antibody complex deposits in skin joints and eyes and set up inflammatory reaction 6) In the kidney antigen and antibody complex deposits and impair kidney function and (glomerulonephritis). 1

3 Type II hypersensitivity: - 1) Type II hypersensitivity, a tissue-specific reaction, generally involves the destruction of a target cell by an antibody directed against cell-surface antigens. 2) Alternatively, the antibody may be directed against small molecules absorbed to cells or against cell-surface receptors, rather than against the cell constituents themselves. 3) Tissue damage occurs through several mechanisms. Binding of antigen and antibody activates complement, which ultimately disrupts cellular membranes complementmediated lysis. Various phagocytic cells mediate another mechanism with receptors for immunoglobulin (Fc region) and complement fragments. 4) These cells envelop and destroy opsonized targets, such as red blood cells (RBCs), leukocytes, and platelets. Cytotoxic T cells and natural killer cells, although not antigen specific, also contribute to tissue damage by releasing toxic substances that destroy the cells. 5) Antibody binding causes the target cell to malfunction rather than causing its destruction. 2

4 Type III hypersensitivity: - 1) Circulating antigen-antibody complexes (immune complexes) accumulate and are deposited in the tissues. 2) The most common tissues involved are the kidneys, joints, skin, and blood vessels. Normally, they clear excess immune complexes from the circulation. 3) However, immune complexes deposited in the tissues activate the complement cascade, causing local inflammation, and trigger platelet release of vasoactive amines that increase vascular permeability, so that more immune complexes accumulate in the vessel walls. 4) Probably the most harmful effects result from the generation of complement fragments that attract neutrophils. The neutrophils attempt to ingest the immune complexes. They re generally unsuccessful, but in the attempt, the neutrophils release lysosomal enzymes, which exacerbate the tissue damage. The formation of immune complexes is dynamic and always changing. 5) The complexes that form in children may be totally different from those formed in later years. Also, more than one type of immune complex may be present at one time. 3

5 Type IV hypersensitivity:- 1) These cell-mediated reactions involve the processing of the antigen by the macrophages. Once processed, the antigen is presented to the T cells. 2) Cytotoxic T cells, if activated, attack and destroy the target cells directly. When lymphokine T cells are activated, they release lymphokines, which recruit and activate other lymphocytes, monocytes, macrophages, and polymorphonuclear leukocytes. 3) The coagulation, kinin, and complement cascades also contribute to tissue damage in this type of reaction. 4

6 Autoimmune disease:- 1) In autoimmune reactions, the body s normal defenses become selfdestructive, recognizing self-antigens as foreign. 2) What causes this misdirected response isn t clearly understood. For example, drugs or viruses have been implicated as causing some autoimmune reactions, but in diseases such as rheumatoid arthritis and systemic lupus erythematosus, the mechanism for misdirection is unclear. 3) Autoimmune reactions are believed to result from a combination of factors, including genetic, hormonal, and environmental influences. Many are characterized by B-cell hyperactivity and by hypergammaglobulinemia. Example: - RHEUMATOID ARTHRITIS Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that primarily attacks peripheral joints and the surrounding muscles, tendons, ligaments, and blood vessels. Partial remissions and unpredictable exacerbations mark the course of this potentially crippling disease. Rheumatoid arthritis is three times more common in women than in men. CAUSES:- 1. The cause of the chronic inflammation characteristic of Rheumatoid arthritis isn t known. 2. Possible theories include an abnormal immune activation occurring in a genetically susceptible individual leading to inflammation, complement activation, and cell proliferation within joints and tendon sheaths. 3. Possible infection (viral or bacterial), hormone action, or lifestyle factors may influence disease onset. Some patients develop an immunoglobulin (Ig) M antibody against the body s own IgG (also called rheumatoid factor). 5

7 4. Rheumatoid factor aggregates into complexes, generates inflammation, causing eventual cartilage damage and triggering other immune responses. PATHOPHYSIOLOGY 1. If not arrested, the inflammatory process in the joints occurs in four stages. 2. First, synovitis develops from congestion and edema of the synovial membrane and joint capsule. Infiltration by lymphocytes, macrophages, and neutrophils continues the local inflammatory response. These cells, as well as fibroblast-like synovial cells, produce enzymes that help to degrade bone and cartilage. 3. Formation of pannus thickened layers of granulation tissue marks the onset of the second stage. Pannus covers and invades cartilage and eventually destroys the joint capsule and bone. 4. Progression to the third stage is characterized by fibrous ankylosis fibrous invasion of the pannus and scar formation that occludes the joint space. 5. Bone atrophy and misalignment cause visible deformities and disrupt the articulation of opposing bones, which cause muscle atrophy and imbalance and, possibly, partial dislocations (subluxations). In the fourth stage, fibrous tissue calcifies, resulting in bony ankylosis and total immobility. SIGNS AND SYMPTOMS: Rheumatoid arthritis usually develops insidiously and initially causes nonspecific signs and symptoms, most likely related to the initial inflammatory reactions before the inflammation of the synovium, including fatigue, malaise, anorexia and weight loss, persistent low-grade fever, lymphadenopathy, and vague articular symptoms. 1. As the disease progresses, signs and symptoms include specific localized, bilateral, and symmetric articular symptoms. These commonly occur in the 6

8 fingers at the proximal interphalangeal, metacarpophalangeal, and metatarsophalangeal joints, possibly extending to the wrists, knees, elbows, and ankles from inflammation of the synovium. 2. The affected joints stiffen after inactivity, especially on arising in the morning, due to progressive synovial inflammation and destruction. 3. Spindle-shaped fingers develop from marked edema and congestion in the joints. Joint pain and tenderness occur at first only with movement but eventually even at rest, due to prostaglandin release, edema, and synovial inflammation and destruction. 4. The patient experiences a feeling of warmth at the joint from inflammation. Ultimately, diminished joint function and deformities occur as synovial destruction continues. 7

9 Immunodeficiency: - 1) Immunodeficiency disorders are a group of disorders in which part of the immune system is missing or defective. 2) Therefore, the body's ability to fight infections is impaired. As a result, the people have frequent infections 3) The defects can be inherited and/or present at birth (congenital) or acquired later in life due to protein deficiency, acute infection and bone marrow depression. 4) Immunodeficiency may be primary, reflecting a defect involving T cells, B cells, or lymphoid tissues, or secondary, resulting from an underlying disease or factor that depresses or blocks the immune response. 5) The most common forms of immunodeficiency are caused by viral infection or are iatrogenic reactions to therapeutic drugs. AIDS - ACQUIRED IMMUNE DEFICIENCY SYNDROME 1) Human immunodeficiency virus (HIV) infection may cause acquired immunodeficiency syndrome (AIDS). 2) Although it s characterized by gradual destruction of cell mediated (T cell) immunity, it also affects humoral immunity and even autoimmunity because of the central role of the CD4 ϩ (helper) T-lymphocyte in immune reactions. 3) The resulting immunodeficiency makes the patient susceptible to opportunistic infections, cancers, and other abnormalities that define AIDS. CAUSES:-The HIV-I retrovirus is the primary etiologic agent. 8

10 PATHOPHYSIOLOGY 1) AIDS begins with infection by the HIV retrovirus, which is detectable only by laboratory tests, and ends with death. 2) Twenty years of data suggests that casual household or social contact doesn t transmit HIV. The HIV virus may enter the body by any of several routes involving the transmission of blood or body fluids, for sexual contact, sharing contaminated needles, and transplacental or postpartum transmission from infected mother to fetus (by cervical or blood contact at delivery and in breast milk). 3) HIV strikes helper T cells bearing the CD4 ϩ antigen. Normally a receptor for major histocompatibility complex molecules, the antigen serves as a receptor for the retrovirus and allows it to enter the cell. Viral binding also requires a coreceptor (believed to be the chemokine receptor CCR5) on the cell surface. 4) The virus may also infect CD4 ϩ antigen-bearing cells of the GI tract, cervix, and neuroglia. Like other retroviruses, HIV copies its genetic material in a reverse manner compared with other viruses and cells. Through the action of reverse transcriptase, HIV produces deoxyribonucleic acid (DNA) from its viral ribonucleic acid (RNA). 9

11 5) Transcription is typically poor, leading to mutations, some of which make HIV resistant to antiviral drugs. The viral DNA enters the nucleus of the cell and is incorporated into the host cell s DNA, where it s transcribed into more viral RNA. If the host cell reproduces, it duplicates the HIV DNA along with its own and passes it on to the daughter cells. 6) Thus, if activated, the host cell carries this information and, if activated, replicates the virus. Viral enzymes, proteases, arrange the structural components and RNA into viral particles that move out to the periphery of the host cell, where the virus buds and emerges from the host cell. The virus is now free to travel and infect other cells. 7) HIV replication may lead to cell death or it may become latent. HIV infection leads to profound structural and functional changes, either directly through destruction of CD4 ϩ cells, other immune cells, and neuroglial cells, or indirectly through the secondary effects of CD4 ϩ T-cell dysfunction and resulting immunosuppression. 8) The HIV infectious process takes three forms: immunodeficiency (opportunistic infections and unusual cancers), autoimmunity (lymphoid interstitial pneumonitis, arthritis, hypergammaglobulinemia, and production of autoimmune antibodies), and neurologic dysfunction (AIDS dementia complex, HIV encephalopathy, and peripheral neuropathies). 10

12 SIGNS AND SYMPTOMS:- 1. HIV infection manifests in many ways. After a high-risk exposure and inoculation, the infected person usually experiences a mononucleosis-like syndrome, which may be attributed to flu or another virus and then may not produce symtoms for years. 2. In this latent stage, the only sign of HIV infection is laboratory evidence of seroconversion. When symptoms appear, they may take many forms, including persistent generalized lymphadenopathy secondary to impaired function of CD4 ϩ cells; nonspecific symptoms, including weight loss, fatigue, night sweats, fevers related to altered function of CD4 ϩ cells, immunodeficiency, and infection of other CD4 ϩ antigen bearing cells; neurologic symptoms resulting from HIV encephalopathy and infection of neuroglial cells; and opportunistic infection or cancer related to immunodeficiency. COMPLICATIONS:- Complications of AIDS are repeated opportunistic infections. TREATMENT: - 1) No cure has yet been found for AIDS. Primary therapy includes the use of various combinations of three different types of antiretroviral agents to try to 11

13 gain the maximum benefit of inhibiting HIV viral replication with the fewest adverse reactions. 2) The drugs include protease inhibitors to block replication of virus particles 3) Additional treatment may include immunomodulatory agents to boost the immune system weakened by AIDS and retroviral therapy, human granulocyte colony-stimulating growth factor to stimulate neutrophil production (retroviral therapy causes anemia, so patients may receive epoetin alfa), and anti-infective and antineoplastic agents to combat opportunistic infections and associated cancers (some prophylactically to help resist opportunistic infections). 9) Supportive therapy, including nutritional support, fluid and electrolyte replacement therapy, pain relief, and psychological support is essential. 12