Ch 51, 52, 53 & 54 immune

Paroxysmal nocturnal hemoglobinuria

acquired clonal stem cell disorder resulting from a somatic mutation in the hematopoietic stem cell. It is characterized by intravascular hemolysis, cytopenia, frequent infections, bone marrow hyperplasia, and a high incidence of life-threatening venous thrombosis

mast cells

connective tissue cells that contain heparin and histamine in their granules

genetics engineering

emerging technology designed to enable replacement of missing or defective genes

reverse transcriptase

enzyme that transforms single-stranded RNA into a double-stranded DNA

Wiskott-Aldrich syndrome (WAS)

immunodeficiency characterized by thrombocytopenia and the absence of T- and B-cells

wasting syndrome

involuntary weight loss of 10% of baseline body weight with chronic diarrhea or chronic weakness and documented fever.

cytotoxic T-cells

lymphocytes that lyse cells infected with virus; also play a role in graft rejection

Kaposi's sarcoma

malignancy that involves the epithelial layer of blood and lymphatic vessels

Mycobacterium avium complex (MAC)

opportunistic infection caused by mycobacterial organisms that commonly causes a respiratory illness but can also infect other body systems

immunocompromised host

person with a secondary immunodeficiency and associated immunosuppression

synovial

pertaining to the joint-lubricating fluid

bradykinin

polypeptide that stimulates nerve fibers and causes pain

apoptosis

programmed cell death that results from the digestion of DNA by endonucleases

antibody

protein substance developed by the body in response to and interacting with a specific antigen

alpha-interferon

protein substance that the body produces in response to infection

atopy

term often used to describe immunoglobulin E-mediated diseases (ie, atopic dermatitis, asthma, and allergic rhinitis) with a genetic component

joint effusions

the escape of fluid from the blood vessels or lymphatics into the joint space

humoral immune response

the immune system's second line of defense; often termed the antibody response

cellular immune response

the immune system's third line of defense, involving the attack of pathogens by T-cells

antigenetic determinant

the specific area of an antigen that binds with an antibody combining site and determines the specificity of the antigen-antibody reaction.

hemarthrosis

bleeding into the joint

p24 antigen

blood test that measures viral core protein; accuracy of test is limited because the p24 antibody binds with the antigen and makes it undetectable

subchondral bone

bony plate that supports the articular cartilage

tophi

accumulation of crystalline deposits in articular surfaces, bones, soft tissue, and cartilage

allergen

allergen---> B-cell---> antibodies---> mast cells---> allergic reaction---> nose/skin cells---> histamine.

viral set point

amount of virus present in the blood after the initial burst of viremia and the immune response that follows

epitope

an immunologically active site on an antigen; a single antigen can have several different epitopes that elicit responses from different antibodies

Complement has three major physiologic functions:

bridging natural and acquired immunity, and disposing of immune complexes and the byproducts associated with inflammation

progressive multifocal leukoencephalopathy (PML)

opportunistic infection that infects brain tissue and causes damage to the brain and spinal cord

IgA (15% of Total Immunoglobulin)

*Appears in body fluids (blood, saliva, tears, breast milk, and pulmonary, gastrointestinal, prostatic, and vaginal secretions) * Protects against respiratory, gastrointestinal, and genitourinary infections *Prevents absorption of antigens from food *Passes to neonate in breast milk for protection

IgE (0.004% of Total Immunoglobulin)

*Appears in serum *Takes part in allergic and some hypersensitivity reactions *Combats parasitic infections

IgG (75% of Total Immunoglobulin)

*Appears in serum and tissues (interstitial fluid) *Assumes a major role in bloodborne and tissue infections *Activates the complement system *Enhances phagocytosis *Crosses the placenta

IgD (0.2% of Total Immunoglobulin)

*Appears in small amounts in serum *Possibly influences B-lymphocyte differentiation, but role is unclear

IgM (10% of Total Immunoglobulin)

*Appears mostly in intravascular serum *Appears as the first immunoglobulin produced in response to bacterial and viral infections *Activates the complement system

Postexposure Prophylaxis for Health Care Providers cont...∝

*Report as quickly as possible to the employee health services, the emergency department, or other designated treatment facility. This visit should be documented in the health care worker's confidential medical record. *Give consent for baseline testing for HIV, hepatitis B, and hepatitis C. Confidential HIV testing can be performed up to 72 hours after the exposure but should be performed as soon as the health care worker can give informed consent for baseline testing.

Postexposure Prophylaxis for Health Care Providers

*Wash the area with soap and water. * Alert your supervisor/nursing faculty and initiate the injury-reporting system used in the setting. * Identify the source patient, who may need to be tested for HIV, hepatitis B, and hepatitis C. State laws will determine whether written informed consent must be obtained from the source patient before his or her testing. OraQuick rapid testing should be used if possible if the HIV status of the source patient is unknown, because results can be available within 20 minutes.

There are 2 types of Acquired Immunity

1.Active immunity developed by your own body-as a result of a prior exposure to an antigen. (through a vaccine or having the disease yourself) •over a number of weeks or months the body produces an immune response that is sufficient to defend against a re-exposure. This form of immunity relies on the recognition of specific foreign antigens.

primary infection

4- to 7-week period of rapid viral replication immediately following infection; also known as acute HIV infection

Age-Related Changes in Immunologic Function--Gastrointestinal Changes

Decreased gastric secretions and motility Decreased phagocytosis by the liver's Kupffer cells Altered nutritional intake with inadequate protein intake

Acquired / Specific Immunity

Acquired / Specific Immunity • Antibodies Immunoglobins: large proteins • Mechanism of action • Bind to foreign substance: Agglutination • Increases •Phagocytosis • Attracts complement: •Opsonization • Increases •Phagocytosis • Promotes release of •vasoactive substances: • Histamine

Acquired / Specific Immunity

Acquired / Specific Immunity • Cell-Mediated Response • Initiated by antigen binding to receptor site on a T cell • Activated T cell delivers antigen to lymph node where other T cells are produced (clones) • Memory T cells will stay in the lymph node • Helper T cells secrete cytokines to activate B cells, cytotoxic T cells, macrophages etc • Cytotoxic T cells attack the antigen directly

Acquired / Specific Immunity

Acquired /Specific Immunity • Cell-Mediated Response (T-Lymphocytes) • Protects against fungi, intracellular bacteria, parasites, • Stimulates antibody production • Defends against malignancies • May cause transplant rejection

Acquired Immunity

Acquired Immunity: pg. 1786 Brunner's. Not present at birth. The response is divided into two mechanisms 1.Cell Medicated (t-cell) and 2.Effector mechanism (B-cell & antibodies).

Acquired / Specific Immunity

Acquired/Specific Immunity • Humoral response: occurs in the blood and tissues in response to bacterial toxins, bacteria, and extracellular viruses • B lymphocytes produce antibodies in response to a specific antibody • B cell 'clones' in the lymph glands produce specific antibodies • B cell memory clones increase rapidity of response

Acquired

Acquired/Specific Immunity • Requires prior exposure to foreign agent • B and T lymphocytes acquire single antigenic specificity

Interferon-γ-- Cytokines

Activates macrophages; increases expression of class I and II MHC antigen processing and presentation

Anaphylaxis

Activation of mast cells and basophils with release of inflammatory mediators that produce smooth muscle contraction and increased vascular permeability-Complement-Mediated Immune Responses

Abnormal menses (Genitalia)

Adverse effect of medication

Altered sense of taste (mouth)

Adverse effect of medication

Cataracts (eye)

Adverse effect of medication

Decreased acuity (ear)

Adverse effect of medication

Decreased peripheral vision (eye)

Adverse effect of medication

Nausea, vomiting, bloating, and pain (abdomen)

Adverse effect of medication

Thinning (Skin)

Adverse effect of medication

Tinnitus (ear)

Adverse effect of medication

Macrophage activation factor-- Cytokines

Allows macrophages to adhere to surfaces more readily

Spondyloarthropathies

Ankylosing Spondylitis Reactive Arthritis (Reiter's Syndrome) Psoriatic Arthritis

Mechanical Stress ∝

Articular cartilage is highly resistant to wear under conditions of repeated movement. However, repetitive impact loading (velocity at which the force is applied) rapidly leads to joint failure at the cartilage level. When a person walks, three to four times the body weight is transmitted through the knee. A deep knee bend transmits up to nine times the body weight through the patellofemoral joint.

Role of Antibodies

Antibodies are large proteins called immunoglobulins (because they are found in the globulin fraction of the plasma proteins). All immunoglobulins are glycoproteins and contain a certain amount of carbohydrate. The carbohydrate concentration, which ranges from approximately 3% to 13%, is dependent on the class of the antibody. Each antibody molecule consists of two subunits, each of which contains a light and a heavy peptide chain .

Arthrocentesis

Arthrocentesis (needle aspiration of synovial fluid) may be performed not only to obtain a sample of synovial fluid for analysis but also to relieve pain caused by pressure of increased fluid volume, usually in the knee or shoulder, The presence of crystals is indicative of gout, and the presence of bacteria is indicative of infectious arthritis.

Mechanical Stress ß

As a joint undergoes repeated mechanical stress, the elasticity of the joint capsule, articular cartilage, and ligaments is reduced. The articular plate (subchondral bone) thins, and its ability to absorb shock decreases. The joint space narrows, accompanied by a loss of stability. When the articular plate disappears, bony spurs (osteophytes) form at the edges of the joint surfaces, and the capsule and synovial membranes thicken.

Weight change (measure) (abdomen)

Associated with RA (decreased), adverse effect of medication (increased or decreased)

Pleuritic pain (chest)

Associated with RA and SLE

Blanching of fingers on exposure to cold (cardiovascular system)

Associated with Raynaud's phenomenon

Dryness (mouth)

Associated with Sjögren's syndrome

Dryness, itching (Genitalia)

Associated with Sjögren's syndrome

Dryness, grittiness (eye)

Associated with Sjögren's syndrome (commonly occurring with rheumatoid arthritis [RA] and LE)

Decreased chest expansion (chest)

Associated with ankylosing spondylitis

Conjunctivitis, uveitis (eye)

Associated with ankylosing spondylitis and Reiter's syndrome

Urethritis, dysuria (Genitalia)

Associated with ankylosing spondylitis and Reiter's syndrome

Difficulty chewing (mouth)

Associated with decreased range of motion of jaw

Rash, lesions (Skin)

Associated with lupus erythematosus (LE), vasculitis, adverse effect of medication

Dysphagia (mouth)

Associated with myositis

Activity intolerance (dyspnea) (chest)

Associated with pulmonary hypertension in scleroderma

Alopecia or thinning (hair)

Associated with rheumatic diseases or adverse effect of medication

Altered bowel habits (abdomen)

Associated with scleroderma, spondylosis, ulcerative colitis, decreased physical mobility, medication effect

Increased bruising (Skin)

Associated with several rheumatic diseases and adverse effect of medication

Photosensitivity (Skin)

Associated with systemic lupus erythematosus (SLE), dermatomyositis, adverse effect of medication

Headaches (neuro)

Associated with temporal arteritis, adverse effect of medication

Decreased acuity or blindness (eye)

Associated with temporal arteritis, medication complications

Lesions (Genitalia)

Associated with vasculitis

Buccal, sublingual lesions (mouth)

Associated with vasculitis, dermatomyositis, adverse effect of medication

Macrophage chemotactic factor --Cytokines

Attracts macrophages into the area

B-Lymphocytes

B-Lymphocytes • Differentiates into Plasma cells which produce immunoglobulins and antibodies • Responsible for HUMORAL IMMUNITY Pg 1786 ♣♣B cells, a type of lymphocyte (white blood cell), have an important role in the body's immune system. When a B cell encounters an invading bacterium it starts to divide, forming two different types of cell. One type is a clone of itself that begins to produce antibodies to fight the infection; the other is a memory cell that will persist in the bloodstream, ready to produce antibodies should re-infection occur.

Humoral

B-lymphocyte,Produces antibodies or immunoglobulins (IgA, IgD, IgE, IgG, IgM)

Antigen Recognition cont

B-lymphocytes stored in the lymph nodes are subdivided into thousands of clones, each responsive to a single group of antigens having almost identical characteristics. When the antigenic message is carried back to the lymph node, specific clones of the B-lymphocyte are stimulated to enlarge, divide, proliferate, and differentiate into plasma cells capable of producing specific antibodies to the antigen. Other B-lymphocytes differentiate into B-lymphocyte clones with a memory for the antigen. These memory cells are responsible for the more exaggerated & rapid immune response in a person who is repeatedly exposed to the same antigen

Basophils

Basophils ♣Involved in hypersensitivity reactions ♣ Contains histamine ♣ Involved with acute, systemic allergic reactions ♣ Anaphylaxis

Cytophilic antibody --Cytokines

Binds to an Fc receptor on macrophages, thereby permitting macrophages to bind to antigens

Hypersensitivity

Body produces inappropriate or exaggerated responses to specific antigens

CREST syndrome

CREST stands for calcinosis (calcium deposits in the tissues), Raynaud's phenomenon, esophageal hardening and dysfunction, sclerodactyly (scleroderma of the digits), and telangiectasia (capillary dilation that forms a vascular lesion).

Macrophage aggregation factor --Cytokines

Causes clumping of macrophages and lymphocytes

Helper T

Cellular - Attacks foreign invaders (antigens) directly Initiates and augments inflammatory response

Cellular Immune Response cont

Cellular reactions are initiated by the binding of an antigen to an antigen receptor located on the surface of a T-cell. This may occur with or without the assistance of macrophages. The T-cells then carry the antigenic message, or blueprint, to the lymph nodes, where the production of other T-cells is stimulated. Some T-cells remain in the lymph nodes and retain a memory for the antigen. Other T-cells migrate from the lymph nodes into the general circulatory system and ultimately to the tissues, where they remain until they either come in contact with their respective antigens or die.

Helper T2

Cellular- Increases B-cell antibody production

Helper T1

Cellular- Increases activated cytotoxic T-cells

Cytotoxic T (killer T)

Cellular-Lyses cells infected with virus; plays a role in graft rejection

Memory T

Cellular-Remembers contact with an antigen and on subsequent exposures mounts an immune response

Suppressor T

Cellular-Suppresses the immune response

: Differences in Cellular and Humoral Immune Responses

Chart 50-1: Differences in Cellular and Humoral Immune Responses ∴Humoral Responses (B-cells) * ♦ Bacterial phagocytosis and lysis * ♦Anaphylaxis * ♦Allergic hay fever and asthma * ♦Immune complex disease * ♦Bacterial and some viral infections ∴Cellular Responses (T-cells) * ♦Transplant rejection * ♦Delayed hypersensitivity (tuberculin reaction) * ♦Graft-versus-host disease * ♦Tumor surveillance or destruction * ♦Intracellular infections * ♦ Viral, fungal, and parasitic infections

Chemotaxis

Chemical attraction of neutrophils and phagocytic cells to the antigen-Complement-Mediated Immune Responses

Complement System

Circulating plasma proteins are made in the liver and activated when an antibody connects with its antigen.

Complement levels—C3, C4

Complement is a protein substance that binds with antigen-antibody complexes for the purpose of lysis. When the number of complexes increases markedly, complement is used for lysis, thus depleting the amount available in the blood. C3: 55-120 mg/dL (550-1,200 mg/L) C4: 11-40 mg/dL (110-400 mg/L) Decrease may be seen in RA and SLE. Decrease indicates autoimmune and inflammatory activity.

OA path

Congenital and developmental disorders of the hip are well known for predisposing a person to OA of the hip. include congenital subluxation-dislocation of the hip, acetabular dysplasia, Legg-Calvé-Perthes disease, & slipped capital femoral epiphysis. Obesity a well-recognized risk factor for the development of OA /Being overweight or obese also increases symptoms associated with the disease. Research has shown that a weight loss of 10% improved function by 28% in people with OA affecting the knee

Joint range of motion

Decreased range of motion may indicate severity or progression of disease.

Primary Immune deficiencies

Deficiency results from improper development of immune cells or tissues; usually congenital or inherited

Secondary Immune deficiencies

Deficiency results from some interference with an already developed immune system; usually acquired later in life

Peripheral pulses (cardiovascular system)

Deficit may indicate vascular involvement or edema associated with medication effect or rheumatic diseases, especially SLE or scleroderma

Deformities

Deformities of the hands and feet are common in RA, The deformity may be caused by misalignment resulting from swelling, progressive joint destruction, or the subluxation (partial dislocation) that occurs when one bone slips over another and eliminates the joint space.

more accurately called "degradation." One theory of degradation is that genetic or hormonal influences, mechanical factors, or prior joint damage causes cartilage failure. Degradation of cartilage ensues, and increased mechanical stress on bone ends causes stiffening of bone tissue. Another theory is that bone stiffening occurs and results in increased mechanical stress on cartilage, which in turn initiates the processes of degradation.

Degeneration

Complement plays an important role in the immune response

Destruction of an invading or attacking organism or toxin is not achieved merely by the binding of the antibody and antigens; it also requires activation of complement, the arrival of killer T-cells, or the attraction of macrophages.

Rheumatoid Factor (RF)

Determines the presence of abnormal antibodies seen in connective tissue disease Negative Positive titer > 1:80 Present in 80% of those with RA Positive RF may also suggest SLE, Sjögren's syndrome, or mixed connective tissue disease. The higher the titer (number at right of colon), the greater the inflammation.

Eosinophils

Eosinophils • Phagocytosis of parasites and foreign protein • Neutralizes histamine • Ingests antigen-antibody complexes

Interferon (type 1α and type β) --Cytokines

Exerts antiviral activity in body cells; induces class I antigen expression; activates NK cells

Muscle atrophy, subcutaneous nodules, popliteal cyst

Extra-articular manifestations

Altered sexual performance (Genitalia)

Fear of pain (or of pain caused by partner) and limitation of motion may affect sexual mobility.

Postexposure Prophylaxis for Health Care Providers cont...ß

Get postexposure prophylaxis for HIV in accordance with CDC guidelines (http://www.hivguidelines.org. Accessed June 2, 2006). Start the prophylaxis medications within 2 hours after exposure. Make sure that you are being monitored for symptoms of toxicity. Practice safer sex until follow-up testing is complete. Continue the HIV medications for 4 weeks. * Follow up with postexposure testing at 1 month, 3 months, and 6 months, and perhaps 1 year. *Document the exposure in detail for your own records as well as for the employer.

Polymyalgia Rheumatica Clinical Man. cont...

Giant cell arteritis, sometimes associated with polymyalgia rheumatica, may cause headaches, changes in vision, and jaw claudication. These symptoms should be evaluated immediately because of the potential for a sudden and permanent loss of vision if the condition is left untreated. Polymyalgia rheumatica and giant cell arteritis typically have a self-limited course, lasting several months to several years

Gout

Gout - heterogeneous group of conditions related to a genetic defect of purine metabolism that results in hyperuricemia. Oversecretion of uric acid or a renal defect resulting in decreased excretion of uric acid, or a combination of both, occurs. - The incidence increases with age and body mass index.occurs more commonly in males than in females

lymphokines

Helper T-cells produce lymphokines, one category of cytokines. These lymphokines activate other T-cells (eg, interleukin-2 [IL-2]), natural and cytotoxic T-cells (eg, interferon-γ), and other inflammatory cells (eg, tumor necrosis factor). Helper T-cells produce IL-4 and IL-5, lymphokines that activate B-cells to grow and differentiate

Humoral Immune Response

Humoral Immune Response B-lymphocytes transform into plasma cells that manufacture antibodies (highly specific proteins) the antibodies are transported in the blood and attempt to disable invaders. The antibodies bind with the antigen rendering it ineffective. Make sure you look on page 1788 in Brunner's. There is a chart, 50-1. There will be 2 questions on the quiz about that chart.

Immobility

Immobilization of a joint is another factor that can produce degenerative changes in articular cartilage.. Cartilage degeneration due to joint immobility may result from loss of the pumping action of lubrication that occurs with joint movement. Approximately three weeks after remobilization of the joint, the cartilage abnormalities are reversed. However, impact exercising (eg, running) prevents reversal of the atrophy. Instead, slow, gradual range of motion is thought to be very important in preventing cartilage injury.

Immune Response: Summary Cont'd

Immune Response: Summary Cont'd • Antibody production results in complement activation • Both cell-mediated and humoral response fight invasion • Suppressor T cells interact with T4 cells to stop reaction • Memory cells wait for another "invasion"

Immune Response: Summary

Immune Response: Summary • Immune Response to pathogens Recognition Stage: initiation of response • Lymphocytes 'patrol' • Proliferation Stage: cell-mediated and humoral systems prepare • Response Stage: Attack! • Effector Stage: destruction of invaders

Immune Response: Summary Cont'd

Immune Response: Summary • Macrophages recognize, process and present antigen to antigen specific T cells • Helper T4 cells are activated by interleukin (IL1) released by the macrophage • T4 cells increase in umber and secrete lymphokines • Lymphokines stimulate the activation and proliferation of B-cells (antibody producing), Cytotoxic T-cells, suppressor T-cells and phagocytic macrophages

Immunity

Immunity • Natural Immunity - you are born with it •Acquired Immunity - you develop it • Actively OR • Passively

Gammopathies

Immunoglobulins are overproduced

Immunological Competence

Immunological Competence • Determined by the immune system's ability to identify and destroy foreign material • Each individual has cellular markers which determine "self" . HLA markers

Age-Related Changes in Immunologic Function--Immune Changes

Impaired function of B- and T-lymphocytes Failure of lymphocytes to recognize mutant or abnormal cells Decreased antibody production Failure of immune system to differentiate "self" from "non-self" Suppressed phagocytic immune response

Altered Lubrication

In addition to the changes in the articular cartilage and subchondral bone, lubrication of the joint is also a factor in joint degeneration. With joint loading (forces carried through the joint), lubrication depends on a film of interstitial fluid that is squeezed out of the cartilage on compression of the opposing surfaces of the joint. The mechanisms that normally operate under high weight loads to produce this lubricating film may be affected.

Assessing for Rheumatic Diseases

In addition to the head-to-toe assessment or systems review, the following are important areas of consideration to be noted when performing the complete physical assessment of a patient with a known or suspected rheumatic disease

Symptoms of RA limitation in function

In the early stages of disease, even before bony changes occur, limitation in function can occur when there is active inflammation in the joints. Joints that are hot, swollen, and painful are not easily moved. The patient tends to guard or protect these joints by immobilizing them. Immobilization for extended periods can lead to contractures, creating soft tissue deformity.

Effector Stage

In the effector stage, either the antibody of the humoral response or the cytotoxic (killer) T-cell of the cellular response reaches and connects with the antigen on the surface of the foreign invader. The connection initiates a series of events that in most instances results in the total destruction of the invading microbes or the complete neutralization of the toxin. The events involve interplay of antibodies (humoral immunity), complement, and action by the cytotoxic T-cells (cellular immunity).

Risk Factors for Osteoarthritis

Increased age * Obesity *Previous joint damage *Repetitive use (occupational or recreational) *Anatomic deformity * Genetic susceptibility

Permeability factor --Cytokines

Increases vascular permeability, allowing white cells into area

Skin reactive factor --Cytokines

Induces inflammatory response

Inflammation

Inflammation involves a series of related steps. In response to the triggering event, the antigen stimulus activates monocytes and T lymphocytes (also called T cells). Next, the immunoglobulin antibodies form immune complexes with antigens. Phagocytosis of the immune complexes is initiated, generating an inflammatory reaction

Inflammatory Response

Inflammatory Response The inflammatory response is a major function of the natural immune system that is elicited in response to tissue injury or invading organisms. Chemical mediators assist this response by minimizing blood loss, walling off the invading organism, activating phagocytes, and promoting formation of fibrous scar tissue and regeneration of injured tissue. The inflammatory response (discussed further in Chapter 6) is facilitated by physical and chemical barriers that are part of the human organism.

Inflammatory response

Inflammatory response-chemical mediators assist by minimizing blood loss, walling off invading organisms, activation Phagocytosis and promoting formation of fibrous scar tissue.

Proliferation inhibitor factor-- Cytokines

Inhibits growth of certain antigenic cells

Interleukin-10 ,Cytokines

Inhibits interferon-gamma and mononuclear cell inflammation

Interleukin-13 --Cytokines

Inhibits mononuclear phagocyte inflammation and promotes differentiation of B-cells

Role of Interferons

Interferons have antiviral and antitumor properties. In addition to responding to viral infection, interferons are produced by T-lymphocytes, B-lymphocytes, and macrophages in response to antigens.modify the immune response by suppressing antibody production and cellular immunity. They also facilitate the cytolytic role of macrophages and NK cells.

Interleukin-12 --Cytokines

Introduces helper T-lymphocytes

Cytotoxic factor (lymphotoxin) --Cytokines

Kills certain antigenic cells

Leukocytes

Leukocytes ♦♦White Blood Cells: protect the body from infection and tissue injury • Normal values WBC: 5-10 x 10/ mm3 ♣ Granulocytes: 60-70% • Basophils, eosinophils, neutrophils ♣Agranulocytes: 30-40% • Lymphocytes • Monocytes

Lymphocytes

Lymphocytes • Produce substances that aid in attacking foreign material • T-Lymphocytes: derived from Thymus • B-Lymphocytes: derived from Bone Marrow • Non T-Non B lymphocytes ♣♣Lymphocytes complete their maturation and differentiate in the lymph nodes and the lymphoid tissue of the intestine and spleen after exposure to a specific antigen. Mature lymphocytes are the principal cells of the immune system, producing antibodies and identifying other cells and organisms as "Foreign"

Cytolysis

Lysis and destruction of cell membranes of body's cells or of pathogens-Complement-Mediated Immune Responses

Antinuclear Antibody (ANA)

Measures antibodies that react with a variety of nuclear antigens If antibodies are present, further testing determines the type of ANA circulating in the blood (anti-DNA, anti-RNP). Negative A few healthy adults have a positive ANA. Positive test is associated with SLE, RA, scleroderma, Raynaud's disease, Sjögren's syndrome, necrotizing arteritis. The higher the titer, the greater the inflammation. The pattern of immunofluorescence (speckled, homogeneous, or nucleolar) helps determine the diagnosis.

VDRL (Venereal Disease Research Laboratory)

Measures antibody to syphilis. Nonreactive False-positive results are sometimes found with SLE.

Red Blood Cell Count

Measures circulating erythrocytes Men: Average 4.8 million/µL Women: Average 4.3 million/µL Decrease can be seen in RA, SLE.

White Blood Cell Count

Measures circulating leukocytes 5,000-10,000 cells/mm3 Decrease may be seen in SLE.

Uric Acid

Measures level of uric acid in serum 2.5-8 mg/dL (0.15-0.5 mmol/L) Increase is seen with gout.

HLA-B27 Antigen

Measures presence of HLA antigens, which are used for tissue recognition Negative Found in 80%-90% of those with ankylosing spondylitis and Reiter's syndrome.

Erythrocyte Sedimentation Rate (ESR)

Measures the rate at which red bloodcells settle out of unclotted blood in 1 hour Westergren = Men, 0-15 mm/h, Women, 0-25 mm/h Wintrobe = Men, 0-9 mm/h, Women 0-15 mm/h Increase is usually seen in inflammatory connective tissue diseases. An increase indicates rising inflammation, resulting in clustering of RBCs, which makes them heavier than normal. The higher the ESR, the greater the inflammatory activity.

Hematocrit

Measures the size, capacity, and number of cells present in blood Men: 42-52% Women: 35-47% Decrease can be seen in chronic inflammation (anemia of chronic disease); also, blood loss through bowel due to medication.

Immunoglobulin Electrophoresis

Measures the values of immunoglobulins IgA 50-300mg/dL (0.5-3 g/L) IgG 635-1,400 mg/dL (6.35-14 g/L) IgM 40-280 mg/dL (0.4-238 g/L) Increased levels are found in people who have autoimmune disorders.

Tumor necrosis factor-beta --Cytokines

Mediates inflammation and graft rejection

Creatinine

Metabolic waste excreted through thekidneys 0.6-1.2 mg/dL (50-110 µmol/L) Increase may indicate renal damage in SLE, scleroderma, and polyarteritis.

Metabolic and Endocrine Diseases Associated with Rheumatic Disorders

Metabolic& endocrine diseases may be associated with rheumatic disorders. include biochemical abnormalities (amyloidosis & scurvy), endocrine diseases (diabetes mellitus & acromegaly), immunodeficiency diseases (human immunodeficiency virus [HIV] infection, acquired immunodeficiency syndrome [AIDS]), & some inherited disorders (hypermobility syndromes). However, the most common conditions are the crystal-induced arthropathies, in which crystals such as monosodium urate (gout) or calcium pyrophosphate (calcium pyrophosphate dihydrate disease [CPPD] or pseudogout) are deposited within joints & other tissues

Monocytes

Monocytes • Enters tissue transforms into macrophage especially in the spleen, liver, peritoneum and lungs ♥♥♥♥ Second line of defense♥♥♥♥ • Longer lived (months) • Most effective against bacteria and fungi • Immune surveillance • Splenic monocytes remove old RBC's

RA is a systemic disease with multiple extra-articular features

Most common are fever, weight loss, fatigue, anemia, lymph node enlargement, and Raynaud's phenomenon (cold- and stress-induced vasospasm causing episodes of digital blanching or cyanosis).

Muscle strength (grip)

Muscle strength decreases with increased disease activity.

Natural Immunity

Natural Immunity • With injury comes • Inflammatory response • Cytokines (interleukins) • stimulate macrophage function, destroy antigens and serve as messengers between leu kocytes

Natural Immunity

Natural Immunity •♥♥ First line of defense against illness♥♥ • PREVIOUS EXPOSURE NOT NECESSARY

Natural Immunity

Natural Immunity Pg 1786 • Physical Barriers: • Skin, mucous membranes, tears, cillia • Neutrophils and monocytes • Phagocytosis: ingestion of foreign material and damaged cells

Natural Immunity

Natural Immunity:Pg. 1784 in Brunner's. Immunity provides non specific response to foreign invader. Co-ordinates initial response to pathogens through production of cytokines which either activate cells to eliminate the pathogen or promote the development of the Acquired Immune response.The Inflammatory response is a major function of the Natural Immune System. It is elicited to respond to tissue injury or invading organism.

Neutrophils

Neutrophils ♣The 'workhorse' of the immune system ♥♥♥♥ First line of defense♥♥♥♥ • Phagocytic cell • Triggered by inflammatory response • Neutorphils take 10 days to mature • Segs: mature • Bands: immature • Short lived (2-4 hr) Pg. 1042 Brunner's Neutrophils arrive at a given site within 1 hour after the onset of an inflammatory reaction and initiate phagocytosis, but they are short-lived.

Non T-Non B Lymphocytes

Non T-Non B Lymphocytes • Null Cells: destroy antigens already coated with antibodies • Natural Killer T: produces cytokines and protects against microorganisms and some tumor cells Helper ♣♣T cells contribute to the differentiation of null and NK cells

Non-T or non-B lymphocyte

Nonspecific

Natural killer (NK) cell (granular lymphocyte)

Nonspecific-Defends against microorganisms and some types of malignant cells; produces cytokines

Null cell

Nonspecific-Destroys antigens already coated with antibody

Autoimmunity

Normal protective immune response paradoxically turns against or attacks the body, leading to tissue damage

synovial fluid

Normally, synovial fluid is clear, viscous, straw-colored, and scanty in volume, with few cells. However, in inflammatory joint disease, the fluid may become cloudy, milky, or dark yellow & may contain numerous inflammatory cells, such as leukocytes (white blood cells), & complement (a plasma protein associated with immunologic reactions). The viscosity is reduced in inflammatory disease, & copious amounts of fluid may be present. Arthrocentesis is diagnostically valuable, but arthrocentesis of small joints (ie, fingers or wrist) may be difficult.

Osteoarthritis

OA affects the articular cartilage, subchondral bone (the bony plate that supports the articular cartilage), and synovium. A combination of cartilage degradation, bone stiffening, and reactive inflammation of the synovium occurs.

Other extra-articular features of RA

Other extra-articular features include arteritis, neuropathy, scleritis, pericarditis, splenomegaly, and Sjögren's syndrome (dry eyes and dry mucous membranes

T-lymphocytes are primarily responsible for cellular immunity.

Pg 1783 Brunner's gives the definition of the cellular immune response. T-lymphocytes are primarily responsible for cellular immunity. Stem cells continually migrate from bone marrow to the thymus gland where they develop into T-cells. There are several types of t-cells and each as a specific designated role in the defense against bacteria, viruses, fungi, parasites and malignant cells.

Natural Killer T

Pg. 1792 Natural Killer T*Subpopulation of lymphocytesDefend against microorganisms & some types of malignant cellsNK cells capable of directly killing invading organismsProduce cytokines

Null Lymphocytes

Pg. 1792 Null Lymphocytes •A subpopulation of lymphocytes •Destroy antigens already coated with antibody •Have special Fc receptor sites on their surface •Connect with the Fc end of antibodies •This is known as antibody-dependent, cell-medicated cytotoxici

Polymyositis path.

Polymyositis is classified as autoimmune because autoantibodies are present. However, these antibodies do not cause damage to muscle cells, indicating only an indirect role in tissue damage. The pathogenesis is multifactorial, and a genetic predisposition is likely. Drug-induced disease is rare. Some evidence suggests a viral link.

Polymyositis

Polymyositis is one of a group of diseases that are termed idiopathic inflammatory myopathies. It is a rare condition, with an incidence estimated at 5 to 10 cases per million adults per year

Hygiene

Poor hygiene may be related to limitations in activities of daily living.

Age-Related Changes in Immunologic Function--Gastrointestinal Changes--Consequences

Proliferation of intestinal organisms resulting in gastroenteritis and diarrhea Increased incidence and severity of hepatitis B; increased incidence of liver abscesses Suppressed immune response

Interleukin-16 --Cytokines

Promotes chemotaxis CD4+ T-lymphocytes and eosinophils

Interleukin-8 ,Cytokines

Promotes chemotaxis and activation of neutrophils

Interleukin-1 (α and β) Cytokines

Promotes differentiation of T- and B-lymphocytes, natural killer (NK) cells, and null cells

Interleukin-11 ---Cytokines

Promotes induction of acute phase proteins

Rheumatoid Arthritis

RA is commonly used as the prototype for inflammatory arthritis. RA affects 0.5% to 1% of the general population worldwide, with a female-to-male ratio between 2:1 and 4:1

Recognition Stage

Recognition of antigens as foreign, or non-self, by immune system/ is the initiating event in any immune response. Body must first recognize invaders as foreign before it can react to them. Body accomplishes recognition using lymph nodes & lymphocytes for surveillance. Lymph nodes are widely distributed internally throughout body & in the circulating blood, as well as externally near body's surfaces. & continuously discharge small lymphocytes into bloodstream. The lymphocytes patrol the tissues & vessels that drain areas served by that node.

Response to Invasion

Response to Invasion • Phagocytic immune response • Humoral immune response • Cellular Immune response

Systemic Lupus Erythematosus

SLE-autoimmune systemic disease that can affect any body system. Involvement of the musculoskeletal system, with arthralgias and arthritis (synovitis), is a common presenting feature of SLE. Joint swelling, tenderness, and pain on movement are also common. Frequently, these are accompanied by morning stiffness.

Scleroderma

Scleroderma ("hard skin") is a relatively rare disease that is poorly understood; the cause is unknown. Its incidence is 18 to 20 people per million per year

Sclerodermal Clinical Man.

Scleroderma starts insidiously with Raynaud's phenomenon & swelling in the hands. The skin & the subcutaneous tissues become increasingly hard & rigid and cannot be pinched up from the underlying structures. Wrinkles & lines are obliterated. The skin is dry because sweat secretion over the involved region is suppressed. The extremities stiffen and lose mobility. The condition spreads slowly; for years, these changes may remain localized in the hands & the feet. The face appears masklike, immobile, & expressionless, and the mouth becomes rigid

C-Reactive Protein Test (CRP)

Shows presence of abnormal glycoprotein due to inflammatory process <1 mg/dL (<10 mg/L) A positive reading indicates active inflammation. Often is positive for RA and SLE

Erythema (Skin)

Sign of inflammation

Warmth (Skin)

Sign of inflammation

Joint redness, warmth, swelling, tenderness, deformity—location of first joint involved, pattern of progression, symmetry, acute vs chronic nature

Signs of inflammation

clinical manifestations of OA cont...

Stiffness which is most commonly experienced in the morning or after awakening, usually lasts less than 30 minutes and decreases with movement. Functional impairment results from pain on movement and limited motion caused by structural changes in the joints.

Interleukin-5 ,Cytokines

Stimulates antibody responses

Interleukin-6 ,Cytokines

Stimulates growth and function of B-lymphocytes and antibodies

Interleukin-9 ,Cytokines

Stimulates growth and proliferation of T-lymphocytes

Interleukin-4 ,Cytokines

Stimulates growth of T- and B-lymphocytes, mast cells, and macrophages

Interleukin-2, Cytokines

Stimulates growth of T-lymphocytes and special activated killer lymphocytes (known as lymphocyte-activated killer cells [LAK cells])

Interleukin-3 ,Cytokines

Stimulates growth of mast cells and other blood cells

Interleukin-7 ,Cytokines

Stimulates growth of pre-B, CD4+ and CD8+ T-lymphocytes and activates mature T-lymphocytes

Tumor necrosis factor-alpha --Cytokines

Stimulates inflammation, wound healing, and tissue remodeling

Lymphocyte blastogenic factor --Cytokines

Stimulates more lymphocytes, recruiting additional lymphocytes into the area

Age-Related Changes in Immunologic Function--Consequences of Immune Changes

Suppressed responses to pathogenic organisms with increased risk for infection Increased incidence of cancers. Anergy (lack of response to antigens applied to the skin [PPD, allergens]). Increased incidence of autoimmune diseases Absence of typical signs and symptoms of infection and inflammation. Dissemination of organisms usually destroyed or suppressed by phagocytes (eg, reactivation or spread of tuberculosis).

Migration inhibitory factor --Cytokines

Suppresses movement of macrophages, keeping macrophages in area of foreign cells

Symptoms of RA

Symptoms are usually bilateral and symmetric. In addition to joint pain and swelling, another classic sign of RA is joint stiffness, especially in the morning, lasting at least 30 to 45 minutes

T cells, a type of lymphocyte (white blood cell

T cells, a type of lymphocyte (white blood cell), have an important role in the body's immune system. When a T cell encounters an invading virus it begins to divide, forming different types of T cell, each with a different function. Killer T cells destroy cells that have become infected with the virus by lysis. Helper T cells activate more killer T cells and also stimulate B cells to begin antibody production

T-Lymphocytes

T-Lymphocytes • Kills invaders/cells directly or thru the release of lymphokines (chemicals) that enhance the activity of other phagocytic cells • Responsible for delayed allergic reactions, foreign tissue rejection, and the destruction of tumor cells • Responsible for: CELLULAR IMMUNITY

thymic hypoplasia

T-cell deficiency that occurs when the thymus gland fails to develop normally during embryogenesis; also known as DiGeorge syndrome

T-cells attack foreign bodies

T-cells attack foreign bodies directly rather than by producing antibodies like the B-cell. Cellular reactions are initiated when an antigen binds to the antigen receptor site on the surface of the T-cell. The T-cell with the "blueprint" of the antigen goes to the lymph nodes ...where some of the T-cells remain as a memory T-cell of that antigen. Other T-cells move into the circulation and ultimately in to the tissue where they remain until they die or come in contact with respective antigens. It's the immune system's third line of defense it involves the attack of pathogens by T-cells

Role of T-Lymphocytes

T-cells include effector T-cells, suppressor T-cells, & memory T-cells. Two major categories of effector T-cells exist: helper T-cells and cytotoxic T-cells. These effector T-cells participate in the destruction of foreign organisms. T-cells interact closely with B-cells, indicating that humoral and cellular immune responses are not separate, unrelated processes, but rather, branches of the immune response that interact.

T-cells interact with B-cells

T-cells interact with B-cells showing that the Humoral and Cell mediated responses do not act alone but rather in unison. ♣♣When Helper-T cells are activated by familiar antigens the T-cells send out Cytokines. These cytokines are "programmed" if you will to tell the immune system to start the cell medicated or antibody immune responses. Pg. 1791 Brunner's

Cellular

T-lymphocyte

Opsonization

Targeting of the antigen so that it can be easily engulfed and digested by macrophages and other phagocytic cells-Complement-Mediated Immune Responses

Antigen Recognition

The B-lymphocytes appear to respond to some antigens by directly triggering antibody formation; however, in response to other antigens, they need the assistance of T-cells to trigger antibody formation. The T-lymphocytes are part of a surveillance system that is dispersed throughout the body and recycles through the general circulation, tissues, & lymphatic system. With the assistance of macrophages, the T-lymphocytes are believed to recognize the antigen of a foreign invader. The T-lymphocyte picks up the antigenic message, or "blueprint," of the antigen & returns to the nearest lymph node with that message.

Cellular Immune Response

The B-lymphocytes are responsible for humoral immunity, and the T-lymphocytes are primarily responsible for cellular immunity. Stem cells continuously migrate from the bone marrow to the thymus gland, where they develop into T-cells. T-cells continue to develop in the thymus gland, despite the partial degeneration of the gland that occurs at puberty. By spending time in the thymus, these cells are programmed to become T-cells rather than antibody-producing B-lymphocytes. Several types of T-cells exist, each with designated roles in the defense against bacteria, viruses, fungi, parasites, & malignant cells. T-cells attack foreign invaders directly rather than by producing antibodies.

The Immune Response

The Immune Response • Cellular Immune Response • T-cells • Differentiate into different kinds of T- cells •T4,T2,T1 • Suppressor T • KillerT • Memory T

The Immune Response

The Immune Response • Humoral Immune Response • Sometimes called antibody response • Begins with B-cells • Transform into plasma • Plasma cells manufacture antibodies

The Immune Response

The Immune Response • Phagocytic Immune Response • WBCs • Ingest foreign particles • At point of attack • Engulf and destroy invading agents

The Immune System

The Immune System • Spleen • Lymph nodes • Thymus • Bone marrow • Appendix • Tonsils • Adenoids • Peyer's Patches • WBC's

Proliferation Stage

The circulating lymphocyte containing the antigenic message returns to the nearest lymph node. Once in the node, the sensitized lymphocyte stimulates some of the resident dormant T- and B-lymphocytes to enlarge, divide, and proliferate. T-lymphocytes differentiate into cytotoxic (or killer) T-cells, whereas B-lymphocytes produce and release antibodies. Enlargement of the lymph nodes in the neck in conjunction with a sore throat is one example of the immune response.

Classic Pathway of Complement Activation

The classic pathway (the first method discovered) is activated by antigen-antibody complexes; it begins when antibody binds to a cell surface and ends with lysis of the cell. This involves the reaction of the first of the circulating complement proteins (C1) with the receptor site of the Fc portion of an antibody molecule after formation of an antigen-antibody complex. The activation of the first complement component then activates all the other components, in the following sequence: C4, C2, C3, C5, C6, C7, C8, and C9. (The components are named in the sequence in which they were discovered.)

Humoral Immune Response

The humoral response is characterized by the production of antibodies by B-lymphocytes in response to a specific antigen. Although the B-lymphocyte is ultimately responsible for the production of antibodies, both the macrophages of natural immunity and the special T-cell lymphocytes of cellular immunity are involved in recognizing the foreign substance and in producing antibodies.

The inflammatory reaction

The inflammatory reaction is normally characterized by 5 distinct signs, each of which is due to a physiological response to tissue injury. ♣Pain (due to chemicals released by damaged cells) ♦Swelling or Edema (due to an influx of fluid into the damaged region) ♥Redness (due to vasodilatation-the widening of blood vessels) ♠Heat (due to an increase in blood flow to the area) °°Loss of function (due to increased swelling and pain) ???What are the stages of the Inflammatory reaction??? The inflammatory reaction is the combination of a number of overlapping reactions within the body. Although alot of these occur simultaneously a certain order of events may be seen:

Mechanical Stress γ

The joint cartilage degenerates and atrophies (shrinks), the bones harden and hypertrophy (thicken) at their articular surfaces, and the ligaments calcify. As a result, sterile joint effusions (fluid escaping from the blood vessels or lymphatics into the joint cavity) and secondary synovitis may be present

Sclerodermal Clinical Man. cont...

The left ventricle of the heart is involved, resulting in heart failure. The esophagus hardens, interfering with swallowing. The lungs become scarred, impeding respiration. Digestive disturbances occur because of hardening (sclerosing) of the intestinal mucosa. Progressive renal failure may occur.

Polymyositis Clinical Man.

The onset ranges from sudden with rapid progression to very slow and insidious. Proximal muscle weakness is typically a first symptom. Muscle weakness is usually symmetric and diffuse. Dermatomyositis, a related condition, is most commonly identified by an erythematous smooth or scaly lesion found over the joint surface.

Response to Invasion (3)

The phagocytic immune response The humoral or antibody immune response The cellular immune response

"falling domino" effect

The proteins that comprise complement interact sequentially with one another in a cascading or "falling domino" effect. The complement cascade is important to modifying the effector arm of the immune system. Activation of complement allows important events, such as removal of infectious agents & initiation of the inflammatory response, to take place. These events involve active parts of the pathway that enhance chemotaxis of macrophages and granulocytes, alter blood vessel permeability, change blood vessel diameters, cause cells to lyse, alter blood clotting, & cause other points of modification. These macrophages & granulocytes continue the body's defense by devouring the antibody-coated microbes & by releasing bacterial products.

Role of Antibodies cont

The subunits are held together by a chemical link composed of disulfide bonds. Each subunit has a portion, referred to as the Fab fragment, that serves as a binding site for a specific antigen. The Fab fragment (antibody-binding site) binds to the antigenic determinant similar to a lock-and-key mechanism . The Fab fragment provides the "lock" portion that is highly specific for an antigen. An additional portion, known as the Fc fragment, allows the antibody molecule to take part in the complement system

Rheumatoid Arthritis

The symptom of a rheumatic disease that most commonly causes a person to seek medical attention is pain. Other common symptoms include joint swelling, limited movement, stiffness, weakness, and fatigue.

Acquired Immunity

The two types of acquired immunity are known as active and passive

There are two types of Effector T-cells

There are two types of Effector T-cells -they participate in the destruction of foreign organisms. 1.The Helper T-cells 2.Cytotoxic T-cells

Anti-DNA, DNA binding

Titer measurement of antibody to double-stranded DNA Negative High titer is seen in SLE; increases in titer may indicate increase in disease activity.

Two categories: Granulocytes and Lymphocytes

Two categories: Granulocytes and Lymphocytes These types of leucocytes primarily protect the body against infection and tissue damage. Pg 1041 ♣WBCs in Brunner's Basophils, eosinophils, Neutrophils. ♣The major function of the neutrophils is phagocytosis. Basophils and eosinophils function in hypersensitivity reactions. Lymphocytes produced mainly in the cortex of the thymus are known as T-lymphocytes (or T-Cells) and t-cells can also be produced in the marrow. But B-cells are typically made in the marrow. B is for bone (good way to remember where the b cells are formed.)

EIA (enzyme immunoassay)

a blood test that can determine the presence of antibodies to HIV in the blood or saliva; also referred to as enzyme-linked immunosorbent assay (ELISA). Positive results must be validated, usually with Western blot test.

Western blot assay

a blood test that identifies antibodies to HIV and is used to confirm the results of an EIA (ELISA) test

osteophyte

a bony outgrowth or protuberance; spur

immunoglobulins

a family of closely related proteins capable of acting as antibodies

leukotrienes

a group of chemical mediators that initiate the inflammatory response

diarthrodial

a joint with two freely moveable parts

Inflammatory Response

a major function of the natural immune system that is elicited in response to tissue injury or invading organisms. Chemical mediators assist this response by minimizing blood loss, walling off the invading organism, activating phagocytes, and promoting formation of fibrous scar tissue and regeneration of injured tissue.

complement

a plasma protein associated with immunologic reactions

antibody

a protein substance developed by the body in response to and interacting with a specific antigen

polymerase chain reaction (PCR)

a sensitive laboratory technique that can detect and quantify HIV in a person's blood or lymph nodes

cytomegalovirus (CMV)

a species-specific herpes virus that may cause retinitis in people with AIDS

antigen

a substance that induces production of antibodies

retrovirus

a virus that carries genetic material in RNA instead of DNA and contains reverse transcriptase

hypersensitivity

abnormal heightened reaction to a stimulus of any kind

Paresthesias of extremities (neuro)

abnormal reflex pattern Nerve compressions associated with carpal tunnel syndrome, spinal stenosis, etc.

epitope

any component of an antigen molecule that functions as an antigenetic determinant by permitting the attachment of certain antibodies

Helper T-cells

are activated on recognition of antigens and stimulate the rest of the immune system. When activated, helper T-cells secrete cytokines, which attract and activate B-cells, cytotoxic T-cells, NK cells, macrophages, and other cells of the immune system. Separate subpopulations of helper T-cells produce different types of cytokines & determine whether the immune response will be the production of antibodies or a cell-mediated immune response

Memory cells

are responsible for recognizing antigens from previous exposure and mounting an immune response

Cytotoxic T-cells (killer T-cells)

attack the antigen directly by altering the cell membrane and causing cell lysis (disintegration) and by releasing cytolytic enzymes and cytokines. Lymphokines can recruit, activate, and regulate other lymphocytes and WBCs. These cells then assist in destroying the invading organism. Delayed-type hypersensitivity is an example of an immune reaction that protects the body from antigens through the production and release of lymphokines

ataxia-telangiectasia

autosomal recessive disorder affecting T- and B-cell immunity primarily seen in children and resulting in a degenerative brain disease

CCR5

cell surface molecule that is needed along with the CD4 molecule to fuse with the membranes of the host's immune system cells

T-cells

cells that are important for producing a cellular immune response

B-cells

cells that are important for producing a humoral immune response

B lymphocyte

cells that are important in producing circulating antibodies

memory cells

cells that are responsible for recognizing antigens from previous exposure and mounting an immune response

T lymphocytes

cells that can cause graft rejection, kill foreign cells, or suppress production of antibodies

phagocytic cells

cells that engulf, ingest, and destroy foreign bodies or toxins

Polymyalgia Rheumatica Clinical Man.

characterized by severe proximal muscle discomfort /mild joint swelling. Severe aching in the neck, shoulder, and pelvic muscles. Stiffness most often in the morning and after periods of inactivity. Systemic features include low-grade fever, weight loss, malaise, anorexia, and depression. Because polymyalgia rheumatica usually occurs in people 50 years of age and older, it may be confused with, or disregarded as, an inevitable consequence of aging.

serotonin

chemical mediator that acts as a potent vasoconstrictor and bronchoconstrictor

leukotrienes

chemical mediators formed from constituents (ie, arachidonic acid) of cell membranes; they initiate and mediate the inflammatory response

clinical manifestations of OA

clinical manifestations of OA are pain, stiffness, and functional impairment----pain is caused by an inflamed synovium, stretching of the joint capsule or ligaments, irritation of nerve endings in the periosteum over osteophytes, trabecular microfracture, intraosseous hypertension, bursitis, tendinitis, and muscle spasm. Stiffness,

anaphylaxis

clinical response to an immediate immunologic reaction between a specific antigen and antibody

agglutination

clumping effect occurring when an antibody acts as a cross-link between two antigens

B-cell lymphoma

common malignancy in patients with HIV/AIDS

Pneumocystis jiroveci pneumonia (PCP)

common opportunistic lung infection caused by an organism, initially thought to be a protozoan but now believed to be a fungus based on its structure

Fibromyalgia

common syndrome/ involves chronic fatigue, generalized muscle aching,& stiffness. Two percent of the United States population is affected by this syndrome, with a prevalence rate of 3.4% in women and 0.5% in men / Although criteria for the classification of fibromyalgia were identified in 1990 /controversy exists as to whether this diagnosis represents a unique syndrome. The cause is unknown, and no specific pathologic characteristics have been identified

immunoregulation

complex system of checks and balances that regulates or controls immune responses

angioneurotic edema

condition characterized by urticaria and diffuse swelling of the deeper layers of the skin

angioneurotic edema

condition marked by development of urticaria and an edematous area of skin, mucous membranes, or viscera

HIV encephalopathy

degenerative neurologic condition characterized by a group of clinical presentations including loss of coordination, mood swings, loss of inhibitions, and widespread cognitive dysfunctions; formerly referred to as AIDS dementia complex (ADC)

erythema

diffuse redness of the skin

peripheral neuropathy

disorder characterized by sensory loss, pain, muscle weakness, and wasting of muscles in the hands or legs and feet

severe combined immunodeficiency disease (SCID)

disorder involving a complete absence of humoral and cellular immunity resulting from an X-linked or autosomal genetic abnormality

agammaglobulinemia

disorder marked by an almost complete lack of immunoglobulins or antibodies

ankylosis

fixation or immobility of a joint

panhypoglobulinemia

general lack of immunoglobulins in the blood

cytokines

generic term for non-antibody proteins that act as intercellular mediators, as in the generation of immune response

cytokines

generic term for nonantibody proteins that act as intercellular mediators, as in the generation of immune response

eosinophil

granular leukocyte

suppressor T-cell

has the ability to decrease B-cell production, thereby keeping the immune response at a level that is compatible with health (eg, sufficient to fight infection adequately without attacking the body's healthy tissues).

urticaria

hives

opportunistic infection

illness caused by various organisms, some of which usually do not cause disease in persons with normal immune systems

Acquired (adaptive) immunity

immunologic responses acquired during life but not present at birth—usually develops as a result of prior exposure to an antigen through immunization (vaccination) or by contracting a disease, both of which generate a protective immune response. Weeks or months after exposure to the disease or vaccine

allergy

inappropriate and often harmful immune system response to substances that are normally harmless

hapten

incomplete antigen

rhinitis

inflammation of the nasal mucosa

phagocytic immune response

involves the WBCs (granulocytes and macrophages), which have the ability to ingest foreign particles. These cells move to the point of attack, where they engulf and destroy the invading agents

hypogammaglobulinemia

lack of one or more of the five immunoglobulins; caused by B-cell deficiency

macrophage

large immune cell that devours invading pathogens and other intruders. Can harbor large quantities of HIV without being killed, acting as a reservoir of the virus.

monocyte

large white blood cell that ingests microbes or other cells and foreign particles. When a monocyte enters tissues, it develops into a macrophage.

prostaglandins

lipid-soluble molecules synthesized from constituents (ie, arachidonic acid) from cell membranes; they mediate the inflammatory process

ataxia

loss of muscle coordination

anergy

loss or weakening of the body's immunity to an irritating agent or antigen

helper T-cells

lymphocytes that attack foreign invaders (antigens) directly

suppressor T-cells

lymphocytes that decrease B-cell activity to a level at which the immune system is compatible with life

natural killer cells (NK cells)

lymphocytes that defend against microorganisms and malignant cells

null lymphocytes

lymphocytes that destroy antigens already coated with the antibody

viral load test

measures the quantity of HIV RNA in the blood

protease inhibitor

medication that inhibits the function of protease, an enzyme needed for HIV replication

antihistamine

medication that opposes the action of histamine

Degeneration

more accurately called "degradation." One theory of degradation is that genetic or hormonal influences, mechanical factors, or prior joint damage causes cartilage failure. Degradation of cartilage ensues, and increased mechanical stress on bone ends causes stiffening of bone tissue. Another theory is that bone stiffening occurs and results in increased mechanical stress on cartilage, which in turn initiates the processes of degradation.

pannus

newly formed synovial tissue infiltrated with inflammatory cells

matrix

noncellular component of tissue

Rheumatoid nodules

noted in patients with more advanced RA, & they develop at some time in the course of the disease in about 25% of patients . These nodules are usually nontender & movable in the subcutaneous tissue. They usually appear over bony prominences such as the elbow, are varied in size, & can disappear spontaneously. Nodules occur only in people who have rheumatoid factor. often associated with rapidly progressive & destructive disease.

Polymyalgia Rheumatica path

occurs predominately in Caucasians and often in first-degree relatives. An association with the genetic marker HLA-DR4 suggests a familial predisposition. Immunoglobulin deposits in the walls of inflamed temporal arteries also suggest an autoimmune process.

stem cells

precursors of all blood cells; reside primarily in bone marrow

In RA, the autoimmune reaction

primarily occurs in the synovial tissue. Phagocytosis produces enzymes within the joint. The enzymes break down collagen, causing edema, proliferation of the synovial membrane, and ultimately pannus formation. Pannus destroys cartilage and erodes the bone. The consequence is loss of articular surfaces and joint motion. Muscle fibers undergo degenerative changes. Tendon and ligament elasticity and contractile power are lost.

interferons

proteins formed when cells are exposed to viral or foreign agents; capable of activating other components of the immune system

arthroplasty

replacement of a joint

HIV-1

retrovirus isolated and recognized as the etiologic agent of AIDS

Scleroderma pathology

scleroderma (also known as systemic sclerosis) course with remissions and exacerbations.- prognosis is not as optimistic as that of SLE. ♠ disease commonly begins with skin involvement. Mononuclear cells cluster on the skin & stimulate lymphokines to stimulate procollagen. Insoluble collagen is formed & accumulates excessively in the tissues. Initially, inflammatory response causes edema formation, with a resulting taut, smooth, & shiny skin appearance. ♠ skin then undergoes fibrotic changes, leading to loss of elasticity & movement. Eventually, the tissue degenerates and becomes nonfunctional. ♠ chain of events, from inflammation to degeneration, also occurs in blood vessels, major organs, & body systems

complement

series of enzymatic proteins in the serum that, when activated, destroy bacteria and other cells

immunopathology

study of diseases resulting in dysfunctions within the immune system

histamine

substance in the body that causes increased gastric secretion, dilation of capillaries, and constriction of the bronchial smooth muscle

allergen

substance that causes manifestations of allergy

antigen

substance that induces the production of antibodies

lymphokines

substances released by sensitized lymphocytes when they come in contact with specific antigens

lymphokines

substances released by sensitized lymphocytes when they contact specific antigens

Passive acquired immunity

temporary immunity transmitted from a source outside the body that has developed immunity through previous disease or immunization.

immunity

the body's specific protective response to an invading foreign agent or organism

opsonization

the coating of antigen-antibody molecules with a sticky substance to facilitate phagocytosis

Response Stage

the differentiated lymphocytes function in either a humoral or a cellular capacity. The production of antibodies by the B-lymphocytes in response to a specific antigen begins the humoral response. Humoral refers to the fact that the antibodies are released into the bloodstream and therefore reside in the plasma (fluid fraction of the blood).

joint effusion

the escape of fluid from the blood vessels or lymphatics into the joint space

phagocytic immune response

the immune system's first line of defense, involving white blood cells that have the ability to ingest foreign particles

active acquired immunity

the immunologic defenses are developed by the person's own body. This immunity typically lasts many years or even a lifetime

window period

time from infection with HIV until seroconversion detected on HIV antibody test

atopic dermatitis

type I hypersensitivity involving inflammation of the skin evidenced by itching, redness, and a variety of skin lesions

prostaglandins

unsaturated fatty acids that have a wide assortment of biologic activity

Clinical manifestations of RA

vary, usually reflecting the stage and severity of the disease. Joint pain, swelling, warmth, erythema, and lack of function are classic symptoms. Palpation of the joints reveals spongy or boggy tissue. Often fluid can be aspirated from the inflamed joint. Characteristically, the pattern of joint involvement begins in the small joints of the hands, wrists, and feet. As the disease progresses, the knees, shoulders, hips, elbows, ankles, cervical spine, and temporomandibular joints are affected. The onset of symptoms is usually acute.

telangiectasia

vascular lesions caused by dilated blood vessels

provirus

viral genetic material in the form of DNA that has been integrated into the host genome. When it is dormant in human cells, HIV is in a proviral form.

HIV-2

virus closely related to HIV-1 that has also been found to cause AIDS

human papillomavirus (HPV)

virus that causes venereal warts

The immunologic inflammatory process

when antigens are presented to T lymphocytes, leading to a proliferation of T and B cells. B cells are a source of antibody-forming cells, or plasma cells. In response to specific antigens, plasma cells produce and release antibodies. Antibodies combine with corresponding antigens to form pairs, or immune complexes. The immune complexes build up and are deposited in synovial tissue or other organs in the body, triggering the inflammatory reaction that can ultimately damage the involved tissue.

candidiasis

yeast infection of skin or mucous membrane

T-Lymphocytes

• Helper T4: attacks antigens and begins and supports inflammatory response • Helper Ti: increases killer T cells • Helper T2: increases B cell antibody production

T-Lymphocytes (con't)

• Suppressor T: suppresses the immune response • MemoryT: "remembers" antigens and triggers immune response on next contact • Killer T (cytotoxic): destroys cells infected with viruses; involved in graft rejection