BIO 381 Exam 2

Fomite

reservoir of pathogen on an inanimate objection

Innate immune response

the body's first line of defense and includes—mechanical & biochemical barriers, phagocytes, chemical mediators, etc.

Iron deficiency anemia

the most common cause of anemia; may be due to low intake, diminished absorption, physiological increase in iron requirements (especially in pregnancy), iron loss (hemorrhage), chronic renal disease, etc. a. Laboratory findings—hypochromic, microcytic RBCs. b. Findings not typical for other anemias can include: i. Pica (craving for nonfood substances such as dirt, clay, ice, laundry starch, cardboard, or hair) ii. Restless legs iii. Glossitis (tongue inflammation) iv. Dysphagia—which is difficult swallowing (here due to esophageal webs—Plummer-Vinson syndrome) v. Erosions at the corners of the mouth (angular chelitis) vi. Atrophic gastritis vii. Splenomegaly, and viii. Changes in the fingernails (koilonychia). 1. Isn't that fingernail term cool?! c. This condition in a male should prompt a search for an underlying GI malignancy—often colon cancer presenting with occult bleeding. (2-4 ml of bleeding/day can cause Fe deficiency anemia.) d. Treatment—usually oral administration of ferrous sulfate (200 mg 3-4 X/day)

Hemophilia

the most common severe inherited coagulation disorders; i. ii. Vitamin K necessary for production of factors II, VII, IX, and X. Cord blood levels of these factors usually 50% of normal adult levels; occasionally will drop enough to cause bleeding. 1. 2. 3. 4. X-linked recessive; Abnormality in intrinsic pathway & subsequent fibrin clot; Hallmark of the disease is Hemarthrosis—knees, elbows, ankles most common, leads to joint deformity. Treatment is avoidance of anti-platelet agents, transfusion of missing coagulation factors (thankfully with recombinant DNA technology the AIDS risk is gone)

Immunity

the state of resistance to infection from a particular pathogen, conferred primarily by high antibody levels.

Epidemiology

the study of health and disease, their distribution, and associated causes in a defined population.

Lymphoid neoplasms

(arise from lymphoid stem cells)—if present in bone marrow, called leukemia; if present in lymph nodes, called lymphoma. Location a consequence of stage of disease, rather than cell type.

Leukocytes (WBCs): Components of the immune system: Myeloid stem cells: Granulocytes

(named because they have granules in their cytoplasm that contain chemicals)—of which there are several varieties: 1. neutrophils or polymorphonucleocytes (PMNs)—which are early responding phagocytic cells to bacterial infections a. Early in acute infections, increased numbers of neutrophils in the bloodstream (neutrophilia) is seen. b. As consumption outpaces demand, immature neutrophils (band cells or banded neutrophils) are released, causing a left shift or leukomyoid reaction. 2. eosinophils—increase in numbers during: a. allergic reactions and b. parasitic helminth (worm) infections. 3. basophils—which are precursors of mast cells found in tissues, and release proinflammatory chemicals (precursor molecules to inflammatory chemicals) in response to IgE antibody binding. This release process is called degranulation, and involves chemicals such as a. histamine, prostaglandins, leukotrienes, platelet-activating factor, heparin, serotonin, & many others (but don't worry about memorizing this list). b. Lymphoid stem cells develop into three major categories of cells, again under the direction of cytokines (including IL7):

Chemical mediators of immune functions

(these are all proteins floating around in the blood stream just waiting for an infection/tissue damage/tumor cell to show up so they have help destroy it.) a. Complement—a series of about 20 plasma proteins synthesized by liver, macrophages, and neutrophils that enhance inflammation, chemotaxis, and lysis of target cells. i. Two different pathways exist to activate the inactivate precursor complement proteins into their active forms: the classical & alternative pathways. 1. These 2 pathways are just different "triggers" that activate the complement system of chemicals. ii. Activation of this cascade results in formation of membrane attack complexes—one of my favorite terms. 1. Complement, kinin, and the clotting system are all cascades: a small stimulus results in a large response. (Positive feedback systems if you want the exact term.) b. Kinins—small polypeptides that are potent vasodilators. Famous ones are bradykinin and kallidin. They also play an important in pain. i. (Use this study guide to give yourself a paper cut in order to remember kinins.) c. Clotting factors—not only are hemostatic, but are involved in inflammation and in triggering the kinin system. d. Cytokines—polypeptide signaling molecules that affect the function of other cells by stimulating surface receptors.

Acute lymphoblastic leukemia/lymphoma (ALL)

80% B cells, remainder T cell precursors. i. Malignant cells resemble immature lymphocytes, called lymphoblasts. ii. Most cases present as leukemias, but lymphoblastic lymphomas are thought to be same condition at later stage. iii. ALL primarily a disease of children—the most common malignancy & the 2nd leading cause of death. iv. Quite curable in children (5 yr. survival 85%); less so in adults (30-50%).

IgM

10% of circulating antibody 1. works best to activate complement (only one molecule of IgM is needed to activate complement, while 2 of IgG is needed) 2. predominant antibody in the primary immune response a. (So this is the predominant antibody made when our immune system is exposed to a particular antigen for the first time.) 3. pentamer. (5 "Y"s)

Immunization

2 goals- 1. confer immunity to host by direct exposure to altered pathogen; 2. decrease number of susceptible hosts in population, thereby limiting disease transmission of disease (called herd immunity).

Specific adaptive immunity—two "arms" exist

. B cells provide "humoral immunity" because they secrete antibody into body fluids or "humors." ii. T cells provide "cell-mediated immunity" because they recognize antigens presented on the surface of cells. b. Major histocompatability complex, or the human leukocyte antigen (HLA) antigen complex is found on chromosome 6, and mark our nucleated cells as "self." c. Mechanisms of cell-mediated immunity i. T cells can recognize foreign antigens displayed on the surface of antigen- presenting cells through specialized receptors called T-cell receptors (TCRs)—each T cell can recognize only a single epitope. ii. T-cells that might react to self-antigens are eliminated in the thymus. iii. Once T cells' own TCRs are stimulated, they react in different ways: 1. T helper (CD4) cells—the CD4 protein binds to a MHC protein, while the TCR binds to its corresponding antigen. a. Next, a huge number of 2nd messengers and cytokines do their thing and activate many other immune functions. b. Does remembering that we have 4 fingers on a "helping hand" help you remember the "CD4" term? 2. Cytotoxic (CD8) cells—Cytotoxic T cells require T helper cells before they can be fully effective—cytokines alone are not adequate. a. Cytotoxic T cells proliferate into 2 cells types: memory cells, and effector cells. b. How about this for a mnemonic?—8-year-olds can be toxic...

Acquired vitamin K deficiency

. Fat malabsorption can also lead to K deficiency (K is fat-soluble) ii. Coumadin (warfarin) type drugs are vitamin K antagonists (used to therapeutically anticoagulate patients) iii. Present with bleeding, prolonged PT iv. Treatment with Vitamin K takes 8-16 hours for liver to synthesize deficient factors. FFP (fresh frozen plasma) transfusion more immediate result in urgent cases.

Primary immunodeficiency disorders:T-cell disorders:

1. DiGeorge syndrome or thymic hypoplasia—total or partial loss of thymus function. Total loss fatal. 2. Chronic mucocutaneous candidiasis—autosomal recessive; selective deficiency of cell-mediated immunity against Candida albicans ("yeast"). The correct cytokine necessary to combat this organism is missing.

Primary immunodeficiency disorders:B-cell disorders:

1. IgA deficiency—affects 1 in 400 people; can be either autosomal recessive or dominant. They tend to have lots of respiratory, GI, and genitourinary tract infections, a higher incidence of vascular & collagen autoimmune diseases. Usually doesn't shorten life, and many cases not diagnosed. 2. Bruton X-linked agammaglobulinemia (congenital hypogammaglobulinemia—lack of normal bursal-equivalent tissue (where B cells mature). a. It was the first immunodeficiency disorder identified— 1952.

Complications of treatment:

1. Nutrition maintenance—difficult due to anorexia, nausea/vomiting, stomaitis. 2. Infection—always troubling, particularly when neutropenic. a. Colony stimulating factors—can be administered to stimulate development of leukocytes and shorten time of neutropenia. 3. Bone marrow suppression—bone marrow transplantation used to treat bone marrow failure caused by treatments. Problems/potential complications include: a. Graft vs. host disease b. Donor sample harvest less difficult due to peripheral stem cell transplantation—for either: i. Autologous—from patient's own cells; or ii. Allogenic—from a different person's cells. c. Graft vs. leukemia—actually may improve prognosis! d. Anemia—erythropoeitin administration helpful. e. Thrombocytopenia—may require platelet transfusions. f. Pain—always a problem g. Loss of epithelial tissues & appendages—mucous membranes, hair, eyebrows/lashes, etc.

Primary immunodeficiency disorders:B-cell & T-cell combined disorders:

1. severe combined immunodeficiency disorders—the most severe form is reticular dysgenesis: failure of ALL leukocytes to form. 2. Wiskott-Aldrich Syndrome—X-linked a. T cells present, but function abnormal. b. Platelets also decreased, so the three manifestations of the disease (a "triad") is: c. Eczema, thrombocytopenic purpura, & infection.

Antibody structure

Antibody structure—shaped like a "Y". 1. An antibody molecule can be connected together to form larger antibody varieties. Monomer=only 1 "Y" molecule; dimer=2 "Y" molecules, etc. There is a slide in my powerpoints that might help you with this concept.

Myeloid neoplasms

Chronic myeloid leukemia (CML)—15% of all leukemia cases in US. Average age of onset 40-50 years old. i. Philadelphia chromosome—unique to this disease. 1. This balanced translocation between chromosome 9 and 22 causes production of a single oncogene which causes the disease. ii. Prognosis not usually good—allogenic bone marrow transplant or some newer chemotherapy drugs can be useful. b. Acute myelogenous leukemia (AML)—cells morphologically & functionally abnormal. i. AML—80% of acute leukemias in adults are AML; 20% in children. 1. Outcome worse if P53 & Rb tumor suppressor gene function lost.

Risk factors for lowered host resistance

Decreased nutrition, chronic illness, extremes of age, immunosuppression, splenectomy (raises risk of Streptococcus pneumoniae sepsis).

Systemic manifestations of inflammation

Fever, neutrophilia (increased neutrophil count), lethargy, muscle catabolism— mostly due to 3 macrophage-derived cytokines: IL-1, IL-6, and TNF-α. These 3 cytokines act on the liver to release a number of protein collectively called acute phase proteins—especially i. C-reactive protein & ii. serum amyloid A 1. both of which seem to help prevent excessive tissue damage from inflammation. c. Acute phase proteins coat RBCs, reducing their electrical charges and allow them to aggregate more readily. This can be measured by a blood test: the erythrocyte sedimentation rate (ESR or sed rate).

Epithelial barriers

INNATE- skin, keratin, sloughing of outer epithelial cell layers, mucous membranes, respiratory mucous, mucociliary system, alveolar macrophages, etc.

Chemical barriers

INNATE-acidic skin, urine & vagina; hydrochloric acid in stomach; lysozyme in saliva, mucous, & tears; lactoferrin keeps iron necessary for bacterial proliferation low in mucous secretions; IgA and IgG in body secretions (more later).

Lipid metabolism

Lipids taken into the gut as food are digested by lipases b. Next, the lipid droplets are surrounded by bile salts to form michelles. c. Next step: the michelles are absorbed across the gut wall, are combined with proteins (to make the lipids soluble in water) to form chylomicrons. d. Then they enter the lymphatic lacteals. e. Triglycerides get deposited into adipose. f. The rest of the lipids need to be transported in blood combined with proteins so they are soluble in water. Lipids combined with proteins are called lipoproteins (of which chylomicrons are one type).

Mechanisms of humoral immunity

Mechanisms of humoral immunity— i. basically, B-cell function, which have B-cell receptors (BCRs), which are specific for a single epitope. ii. BCR binding alone is not adequate to stimulate proliferation of a B-cell clone. B cells must engulf some of the antigen, process it, and present it to T helper cells, which then stimulate clonal proliferation. iii. Some B-cells can respond to nonprotein antigen (like bacterial sugars and lipids). This is important, because T-cells can only respond to protein antigens! These B-cells are T-cell independent. Instead of TH cells, they rely on cytokines, which I haven't memorized, so you shouldn't either. iv. B cells have 2 major subpopulations— 1. memory B cells (which function a lot like memory T cells), and 2. plasma cells—which are antibody production factories. a. They are basically grown-up B cells that have left home and found a full-time job.

Myeloid stem cells give rise to

Megakaryocytes—which give rise to platelets ii. Red blood cells iii. Monocytes—which develop into macrophages (and all the macrophages that carry different names—histiocytes, microglia, Kupffer cells, etc.) iv. Granulocytes 1. Neutrophiles 2. Eosinophils 3. Basophils

Bacterial enzymes

Microorganism characteristics- dissolve host tissues & aid local invasiveness

Microbial adherence

Microorganism characteristics- he ability to latch onto & gain entrance into the host. Facilitated when skin, membranes, etc. are breached, slime layers ("biofilms") are created, adhesives produced, etc.

Encapsulation

Microorganism characteristics- prevents opsonization (making bacteria a target for phagocytes)

Encapsulation- Endospores

Microorganism characteristics-allow some bacteria to survive inert under harsh environmental conditions, awaiting more favorable conditions to reactivate.

Antimicrobial resistance

Microorganism characteristics-conferred by microorganism mutation. Include: i. Not finishing full course of antibiotic therapy; ii. Treating viral infections with antibiotics. iii. Bacterial mobility, such as bacteria with flagella that allow chemotaxis; iv. Bacterial toxin production— 1. exotoxin—polypeptides produced & released by bacteria. They then bind to specific receptors in target cells. Big trouble! Example— a. Clostridium tetani—"tetanus" or "lockjaw" 2. endotoxin—an immunogenic part of a bacterial cell wall. That triggers a massive immune response when the bacteria lyses. Leads to shock, vascular collapse, multi-organ failure, death, and other undesirable problems.

Leukocytes (WBCs): Components of the immune system: Myeloid stem cells

Myeloid stem cells develop under direction of cytokines into: i. Red blood cells (RBCs) ii. Megakaryocytes, which in turn produce platelets iii. Monocytes—which transform into macrophages iv. Granulocytes v. NK Cells Vi. T Lymphocytes Vii. B lymphocytes

Lymphoid stem cells give rise to

T-cells (T-lymphocytes) ii. B-cells (B-lymphocytes) iii. NK cells

Alterations in lymphatic flow

a. Lymphedema—1. Primary lymphedema due to congenital absence/malformation of lymphatics 2. Secondary lymphedema—usually due to surgical removal of regional lymph nodes for cancer surgery ii. Clinical—chronic congestion produced subcutaneous fibrosis, often called brawny edema. Skin changes (pigmentation, ulceration) seen with venous system usually not seen. Treatment—usually with compressive clothing/dressings. Occasionally with lymphatic bypass surgery

Vitamin K deficiency in infants

Vitamin K necessary for production of factors II, VII, IX, and X. Cord blood levels of these factors usually 50% of normal adult levels; occasionally will drop enough to cause bleeding.

Hemolytic disease of the newborn (HDNB)

You should understand the ABO blood typing system as well as the Rh system. Realize that in the Rh system, Rh- individuals do NOT normally have anti-Rh antibodies in their plasma. b. As many as 25% of pregnancies have some hemolysis, usually due to ABO incompatibility, but serious problems usually arise from Rh incompatibility. c. Laboratory features—anemia, reticulocytosis, nucleated RBCs in peripheral circulation (why?), elevated bilirubin levels, + direct Coombs test (maternal antibodies attached to infant RBCs. d. Clinical features—hemolytic anemia, extramedullary erythropoiesis, hyperbilirubinemia, jaundice, hepatosplenomegaly, kernicterus (if severe) e. Treatment—prophylactic Rhogam (anti-Rh immunoglobulin prophylactic immune globulin, it "takes out" fetal RBCs in maternal circulation so mom doesn't mount an immune response against fetal RBCs. f. 10 % of pregnancies have Rh incompatibility. g. Major fetal antigen presentation occurs during delivery, but can occur earlier in pregnancy as well. h. Mother must be Rh negative, and father Rh+ to have potential for problems. i. Problem infants have: hyperbilirubinemia the end result of which is kernicterus that results in permanent brain damage, often death. j. Coombs testing: i. Indirect looks for maternal Ig ii. Direct looks for Ig bound to surface of fetal RBCs. k. Untreated blood-type incompatibility can result in a stillborn fetus with hydrops fetalis.

Alterations in arterial flow

a. Atherosclerosis—most common; the cause of nearly half of all deaths in US and western Europe! a. 60% of mortality associated with coronary artery disease (CAD), causing myocardial ischemia/infarction. b. In lower extremities, the disease process commonly called either arteriosclerosis or atherosclerosis obliterans. c. 3 primary processes appear to be: i. Response to serum lipid levels—in particular, lipid insudation: 1. High concentrations of cholesterol in the form of low- density lipoproteins (LDLs) are transported into the muscle tissues of the artery where they produce inflammation & smooth muscle proliferation. 2. High-density lipoproteins (HDLs)—seem to be protect against development of atherosclerosis, perhaps by removing cholesterol from arterial wall and transporting it back to liver. 3. Lp(a) seems to act as an additional risk factor for premature CAD. ii. Reaction to injury of vessel wall—causes altered permeability of vessel wall. iii. Cellular transformation d. Risk factors for development of atherosclerosis: some modifiable, some not i. Modifiable risk factors: 1. Smoking—nicotine & carbon monoxide (CO) both bad 2. Elevated blood pressure—diastolic may be more important 3. Glucose intolerance 4. Elevated cholesterol/LDL 5. Decreased physical activity 6. Obesity—body weight 30% greater than ideal 7. Weight fluctuations 8. Ineffective stress management—but difficult to quantify ii. Nonmodifiable risk factors 1. Age 2. Gender—men at increased risk 3. Ethnicity—Blacks, Native Americans, Eskimos, Polynesians, etc. at increased risk 4. Heredity e. Clinical manifestations/diagnosis—depend on the organ system f. Treatment—best done by prevention b. Arterial disorders i. Raynaud syndrome—extreme vasoconstriction of arteries of hands & fingers. Affects women primarily, occurs with stimuli such as stress, cold temperatures. 1. Typical episode is pallor associated with vasoconstriction followed by reactive hyperemia that is extremely painful. 2. Affects up to 4% of females. 3. Treatment is usually to avoid inciting agents, vasodilators. ii. Aneurysms—localized arterial dilations or outpouchings of arterial wall. a. More pressure is directed against aneurismal walls because of Laplace's 2. law: F = P X D i. F (the force exerted against the vessel wall) = blood pressure X diameter of the artery (which is obviously greater in an aneurysm) ii. This is the principle of blowing bubbles with bubble gum. As the bubble gets bigger, eventually the bubble pops. This is what happens with aneurysms. Frequently found in cerebral circulation in the arterial circle (Circle of Willis), called berry aneurysms, and in the thoracic & abdominal aorta. 3. Classification: a. True aneurysms—all 3 tunica (intima, media, & adventitia) involved. b. False aneurysms—at least 1 tunic left untouched; muscle & fascia frequently contain hemorrhage, enhance thrombus formation. 4. Varieties of true aneurysms: a. Saccular—confined to one side of vessel; often due to trauma, infection b. Fusiform—both sides of vessel wall weakened. 5. Dissecting aneurysms—tear in arterial wall creates a false channel for blood flow. iii. Acute arterial occlusion—a surgical emergency. Untreated, gangrene results. 1. Classic signs/symptoms are the six P's: a. Pallor b. Paresthesias c. Paralysis d. Pain e. Polar—cold to the touch f. Pulselessness

Mononuclear phagocyte system: Components of the immune system

a. Composed of monocytes and macrophages that are widely dispersed throughout the body, and are known by various names (like dendritic cells, Kupffer cells, alveolar macrophages, histiocytes, microglia, etc.) depending on which tissue they are found. i. (Monocytes are white blood cells that circulate for 2-3 days, then migrate into tissues and transform into macrophages.)

Epithelial barriers: Components of the immune system

a. Defensins—antimicrobial peptides that kill a wide variety of bacteria & fungi. b. Cryptocidins—prevent many bacteria from colonizing the intestinal wall. c. Immunoglobulin A (IgA)—is secreted onto many mucous membranes, aiding (somewhat) the barrier function of these membranes. i. (Good news for those of us that don't like diarrhea.) ii. (Immunoglobulins are antibodies.) d. When epithelial barriers are disrupted and infectious organisms enter the body through this route, cells of the mononuclear phagocyte system frequently encounter the organism first.

Inflammatory exudates

a. Exudate—fluid that leaks out of blood vessels, combined with neutrophils & debris from phagocytosis. Their function is to: i. Transport leukocytes & antibodies ii. Dilute toxins & other irritants iii. Transport nutrients necessary for tissue repair. b. Various type of exudates are classified depending on their composition (note that these are arranged in order of increasing severity): i. Serous exudate—watery, low protein content, present in mild inflammatory conditions. (example—fluid found in a blister) ii. Fibrinous exudates—contains fibrinogen, so is more thick and sticky. iii. Purulent exudate or pus—present in more severe inflammation accompanied by bacterial inflammation. Large pockets called abscesses. iv. Hemorrhagic exudates—many RBCs; present in the most severe inflammation.

General mechanisms that cause altered flow

a. Hypoxia—insufficient supply of oxygen b. Ischemia—decreased arterial blood supply; usually results in tissue hypoxia as well. c. Infarction—cell death (necrosis) due to ischemia d. Venous obstruction (venous engorgement)—obstruction to venous flow e. Lymphatic vessel obstruction can cause edema—excessive fluid in interstitial spaces i. Lymphedema—edema due to obstruction in lymphatic flow f. Blood vessel obstructions (we'll talk about causes of obstructions that can occur in all vessels—arteries & veins—then talk about some conditions that occur just in arteries next) i. Thrombosis—a stationary blood clot formed within a vessel or a chamber of the heart. 1. Etiology—think of Virchow's triad: a. Endothelial damage b. Stasis of blood flow c. Hypercoagulability 2. Pathogenesis a. Arterial thrombosis can result in ischemia. Specific examples discussed later include: i. Myocardial ischemia/infarction: heart attacks ii. Brain ischemia/infarction: strokes b. Venous thrombosis results in altered venous return, edema, and accumulation of metabolic wastes. Important terms include: i. Phlebitis—inflammation in a vein ii. Thrombophlebitis—accompanied by thrombosis— usually caused by needles/IVs 3. Clinical manifestations/treatments a. Intermittent claudication—pain in a limb with activity that improves with rest. Limb might also be pale, cool to touch, cyanotic, ulcerated. b. Venous thrombosis—symptoms may be absent or life threatening in case of pulmonary embolism. Usually treated with anticoagulation, thrombolytic therapy. ii. Embolus—material traveling in blood stream that flows to a distant point where it lodges to produce a new site of obstruction. 1. Thromboembolus—broken-off piece of thrombus a. if formed in left side of heart, tends to proceed to cerebral circulation; b. if formed in or passes through the right side of heart, can form a pulmonary embolism: which may also be non- thrombotic (tumor, fat, air, amniotic fluid, bacteria, etc.) c. Risk factors for thromboembolic diseases: i. Obesity ii. Pregnancy iii. Bed rest > 1 week iv. Surgery—especially orthopedic v. Polycythemia vi. Long plane flights etc. d. Treatment—embolectomy if surgically accessible; limited to thromboemboli i. Repeated pulmonary emboli from deep venous thrombosis of lower extremities may be treated by placing a filter in the inferior vena cava. iii. Vasospasm—frequently idiopathic, occasionally severe enough to cause ischemia iv. Inflammation— 1. Vasculitis—inflammation of the intima (lining) of an artery 2. Phlebitis—inflammation of the lining of a vein v. Mechanical compression—causes stasis of flow. Casts, constrictive clothing, compartment syndromes vi. Structural alterations in blood vessels: 1. Valvular incompetence—can lead to varicose veins if present in superficial veins; chronic venous insufficiency if present in deep venous systems. 2. Arteriovenous fistulas (AVF)—abnormal communication between artery & vein. Most common type is an arteriovenous malformation (AVM), most commonly found in brain. 3. Aneurysms—ballooned-out areas of arterial walls fit here, but we'll discuss them in detail below.

Know the structure of arteries:

a. Innermost layer is simple squamous epithelium, in vessels known as endothelium or the tunica intima. b. The middle layer is smooth muscle and elastic tissue: the tunica media. c. The outermost layer is connective tissue, nerves & blood vessels, the tunica adventitia.

Leukocytes (WBCs): Components of the immune system: Myeloid stem cells: T lymphocytes (T cells)

are capable of responding only to peptide antigens. 2 major classes exist: 1. CD4 or T helper cells—activate other T cells and stimulate B cells to start producing antibody. 2. CD8 or cytotoxic T cells—recognize antigen presented along with MHC 1 antigens, which leads to the cell being destroyed.

Lymphoid system: Components of the immune system

a. Primary lymphoid organs i. Bone marrow—has the function of hematopoiesis. Varieties include: red bone marrow (which is active in hematopoiesis); yellow bone marrow (which is inactive) ii. B lymphocytes—are produced & develop here. When they leave bone marrow, they are called naïve B cells because they have not yet encountered antigen. iii. T lymphocytes—develop in the thymus b. Secondary lymphoid organs—are where naïve B cells and young T cells might encounter an antigen, which will be "presented" to them by dendritic cells. i. If lymphocytes encounter an antigen, they migrate towards each other within lymph nodes & begin to proliferate. T cells may travel throughout the blood stream, but B cells tend to stay put in lymph nodes. ii. Tonsils—are interesting for their lack of afferent lymphatics. iii. Spleen—is the largest lymphoid organ, and also lacks afferent lymphatics. It filters blood. iv. Lymph nodes & lymphatics—contain lots of B & T lymphocytes & macrophages. Lymph filters through nodes, allowing these cells to react to foreign material. v. Peyer Patches—basically unencapsuled aggregations of lymphoid tissues that function like lymph nodes. Some alternative names you might see are: 1. mucosa-associated lymphoid tissue (MALT) or 2. gut-associated lymphoid tissue (GALT)

Alterations in venous flow

a. Valvular incompetence i. Varicose veins—superficial venous incompetence. Most common in greater saphenous system. 1. Manifestations—aching, heavy feeling, varicosities appear when upright. 2. Treatment—elastic stockings, elevations of feet when sitting, not crossing leg, sclerotherapy, vein stripping/ligation ii. Chronic venous insufficiency—deep venous system 1. Venous stasis ulcers—develop long-term as superficial veins rupture with increased pressures associated with activity. 2. Brawny (brown) skin pigmentation—from bleeding into tissue. 3. Affects up to 5% of adults in 3rd world countries! iii. Deep vein thrombosis (DVT)—usually in lower extremities. 1. Clinical manifestations/treatment—may be asymptomatic; physical exam unreliable. a. Greatest risk is pulmonary embolism—risk increased if DVT present above knee. b. Treatment—bed rest, anticoagulation, prevention in high- risk patients.

Thalassemia

abnormal red cell produced that are subject to increased destruction or hemolysis. a. Actually a group of diseases with gene mutations that suppress the rate of synthesis of globin chains of hemoglobin—either the α chain or the β chain. Imbalance in globin synthesis causes the normal chain to build up in cytoplasm, damaging the cell membrane, causing premature cell destruction, leading to accumulating of iron in Kupffer cells in liver and macrophages in spleen. b. α-Thalassemia is found primarily in people of Asian descent, while β-thalassemia is found primarily among those of Mediterranean descent. c. Both varieties exist in major (homozygous, thus more severe) and minor (heterozygous, less severe) varieties.

Qualitative platelet disorders

abnormalities of platelet function—most commonly associated with drugs such as aspirin and other non-steroid anti- inflammatory drugs (NSAIDs) i. Von Willebrand disease—disease of abnormal platelet adhesion. See 4.b below.

Disseminated intravascular coagulation (DIC)

acquired syndrome in which both clotting & bleeding occur simultaneously. i. Widespread clotting in small vessels leads to consumption of clotting factors & platelets, which leads to bleeding. ii. DIC can be severe (a real nightmare, even) due to things such as malignancy, sepsis, snakebite, abruption placenta, trauma, crush injuries, burns, shock, severe liver disease. iii. Mortality rates 50-80%! iv. Laboratory—elevated D-dimer with low fibrinogen & platelet count, elevated antithrombin complex.

Hypertension

adult BP persistently elevated 140 systolic, 90 diastolic or both. (120/80 or less is better) a. Risk factors: i. Increasing age, race (esp. African-Americans), obesity, high-sodium diet, genetics, smoking, sedentary life style, b. Classification of Hypertension: i. Primary (essential or idiopathic) hypertension—95% of cases 1. Physiology a. Renin-angiotensin-aldosterone system—you should understand how this system works. b. Vascular endothelium is a hormone-producing endocrine gland in its own right—endothelin-1 in particular is vasoconstrictive. c. Hyperinsulinemia & insulin resistance—account for about 1⁄2 of all cases of essential hypertension. Still lots to learn about that situation. Will probably end up classified as part of the metabolic syndrome. ii. Secondary hypertension—can be explained by a specific disease. For example: 1. Renal disorders—most common cause; for instance, renal artery stenosis causes reduced renal perfusion & activation of the renin- angiotensin-aldosterone system. 2. Endocrine disorders (these are examples—not an exhaustive list)— a. Adrenocortical hormone excess (both mineralcorticoids & glucocorticoids) b. Pheochromocytoma (rare, but obvious) c. Acromegaly d. Hypo- or hyper-thyroidism 3. Vascular disorders— a. Arteriosclerosis—increases systemic vascular resistance, therefore blood pressure; also narrows renal arteries as in #1 above b. Coarctation of the aorta—markedly elevated BP in arms, low BP in legs c. Neurologic disorders—elevated intracranial pressure, spinal cord injuries can cause autonomic hyperreflexia 4. Drugs—amphetamines, steroids, oral contraceptives, caffeine, nicotine, cocaine, etc. etc. etc. iii. Isolated systolic hypertension in the elderly—affects about 1⁄2 of people > age 65; 1. Defined as systolic BP > 140 with diastolic < 90 2. More common in women 3. Associated with decreased arterial distensibility iv. Hypertension during pregnancy—BP normally decreases in 1st & 2nd trimesters, returns to normal in 3rd. 1. Complicates 12-22% of pregnancies; defined as BP > 140/90 after 20 weeks of pregnancy 2. Predisposing factors— a. Young (teenage) & older (late 30's & 40's) mothers b. Multiple fetuses c. Preexisting diabetes, HTN, renal, or cardiovascular disease 3. Preeclampsia—elevated BP, proteinuria, & edema a. a serious threat to mother & fetus 4. Eclampsia—further progression to seizures & possibly coma 5. Chronic hypertension may also pre-date pregnancy & continue into & through it. 6. Complicates 0.5-10% of pregnancies in US; elevated BP accompanied by proteinuria. v. Accelerated (malignant) hypertension—rapidly progressive, potentially fatal; diastolic BP > 120; present < 1% of hypertensives; 1-year mortality if untreated = 90%! 1. Most likely in males, African-Americans, middle-aged, bilateral renal artery stenosis 2. Target organ damage present, usually kidneys 2. Effects of hypertension— a. b. 3. Signs a. b. c. d. e. Cardiac— i. Left ventricle (LV) must work harder to overcome resistance to ejection of blood (afterload). ii. This causes LV hypertrophy, iii. Increases myocardial O2 consumption, iv. Raises risk of ischemia, heart failure. Vascular effects i. Atherosclerosis & arteriosclerosis—lesions in brain, retinas, kidneys. HTN is one of the leading preventable causes of renal failure & symptoms of hypertension—very few!! "Silent killer" Signs/symptoms usually only appear when target organ damage occurs. Strokes and all forms of cerebrovascular disease Coronary artery disease in all its forms; Development & rupture of aortic aneurysms; Renal problems— i. Proteinuria—loss of protein in urine, ii. Nocturia—urination during sleeping hours iii. Azotemia—accumulation of nitrogenous wastes in the blood stream) 4. Diagnosis of hypertension—made after a minimum of 2 BP measures on separate occasions. a. Avoid the white coat phenomenon b. Ambulatory blood pressure monitoring may play an increasing role. 5. Management—goal should be AT LEAST 130/80 a. Lifestyle modifications—weight reduction, decrease alcohol consumption, sodium restriction, high K+ & Ca2+ intake, exercise, cholesterol reduction b. Medications— i. Typically begin with diuretics or β-blockers ii. ACE (angiotensin converting enzyme) inhibitors & angiotensin receptor blockers useful in hypertension, congestive heart failure & diabetes. iii. Good enough for us, but lots of other info out there! 6. Low blood pressure a. Shock—inadequate blood pressure to perfuse vital organs. More later. b. Orthostatic hypotension—excessive drop in blood pressure when upright posture assumed. If present in elderly, care must be taken to minimize risk of falling, fractures, etc.

Leukocytes (WBCs): Components of the immune system: Myeloid stem cells:B lymphocytes (B cells)

are able to make antibody (immunoglobulin), and possess antibody-like receptors (B-cell receptors or BCRs) on their cell surfaces. Each B cell is capable of recognizing only one antigen epitope (basically a region). 1. Exposure to the appropriate antigen causes B cells to develop into either: a. Plasma cells—which actually make antibody; or b. Memory B cells—that are responsible for the "secondary" or "anamnestic" immune response. i. This memory function is the main thing that differentiates the innate from the adaptive immune systems. ii. There are memory T cells as well.

Hypersensitivity

an excessive or inappropriately triggered immune response. Four varieties exist: I-III involve antibody; IV only T cells. c. Mnemonic for these 4 types: ACID 1. Type I—Anaphylaxis 2. Type II—Cytotoxic-mediated 3. Type III—Immune complex 4. Type IV—Delayed hypersensitivity ii. Type I—IgE mediated; 1. strongly genetic; 2. also known as immediate hypersensitivity reaction because signs/symptoms of allergic reaction occurs immediately after contact with an allergen. 3. Mast cells are the principal effector cells, with cross-linking of IgE receptors on mast cell membranes the stimulus for degranulation and release of chemical mediators, including histamine which causes reactions like: a. Increased vascular permeability b. Vasodilatation (with flushing) c. Urticaria--hives d. Smooth muscle constriction e. Pruritis f. Increased gut permeability 4. Treatment ranges from: nothing (mild cases), antihistamines, epinephrine, steroids, allergic desensitization, allergen avoidance, mast cell stabilization, etc. iii. Type II—tissue-specific, cytotoxic, or cytolytic hypersensitivity 1. Mechanism involves antibody binding to tissue-specific antigens, which then causes complement activation, as well as stimulates activity of other effector cells. 2. Examples of Type II reaction mechanisms include: a. Transfusion reactions—you should understand ABO blood typing system and the basics of this reaction, which is complement mediated. b. Hemolytic disease of the newborn—direct phagocytosis by effector cell (like macrophages) of antibody-coated fetal erythrocytes. c. Myasthenia gravis—antibodies against acetylcholine receptors at the motor end-plate causes complement to attack the receptor. iv. Type III—immune complex or Arthus reaction. 1. Not tissue specific: the damage is done when complexes of antigen/antibody are deposited in tissues, then complement is activated & neutrophils & mast cells go into action. 2. The different between II & III is that in type III reactions, the antigen/antibody complexes precipitate out of the bloodstream into whatever tissue is nearby, or oppositely electrically charged, or being inhabited by aliens, etc. 3. Examples: a. Immune complex glomerulonephritis—usually occurs after streptococcal bacterial infections, with immune complexes deposited in the glomerular basement membrane. b. Systemic lupus erythematosus (SLE)—characterized by autoantibodies against nuclear antigens. ANY organ system can be involved. v. Type IV—delayed hypersensitivity 1. Tissue damage caused by delayed reaction to an antigen. 2. Antibody not involved; 3. principal mediators are lymphokines—produced by lymphocytes; 4. principal effector cells are mast cells (only early in the reaction), lymphocytes & macrophages (not neutrophils). 5. Examples: a. Contact hypersensitivity—an epidermal reaction to a hapten, which is processed by Langerhans cells. Antigens include such things as nickel, clothing, plant oils (poison ivy/oak), ointments, etc. b. Tuberculin-type reaction—a dermal reaction to injected tuberculosis antigen. Used to diagnose previous TB exposure. c. Granulomatous hypersensitivity—indigestible antigen engulfed by macrophages, which then form epitheliod cells +/or multinucleated giant cells.

Hepatic disease—

an lead to hemorrhage due to decreased synthesis of clotting factors, and fat (and fat soluble vitamin) malabsorption. More common in chronic liver disease. i. Decreased bile production can cause malabsorption of vitamin K, with decreased production of factors II, VII, IX, and X as above. ii. Fibrinogen also decreased. iii. Liver also removes activated coagulation proteins & fibrinolytic proteins from circulation. If this function fails, DIC picture can develop. iv. Thrombocytopenia also common in liver disease—may be due to portal hypertension and increase blood flow to spleen with hypersplenism. v. Treat with transfusion of missing components, removal of underlying problem (if possible), avoidance of anti-platelet and anticoagulant agents, etc.

Sickle cell anemia

another genetic defect of hemoglobin synthesis found almost entirely in Blacks: in hemoglobin S, valine is substituted for glutamic acid in the sixth position of the β chain. i. Under decreased oxygen tension, hemoglobin S polymerizes, causing the red cells to assumed a sickled shape, which is usually not permanent, but are very adhesive, causing vascular occlusion. ii. Sickle cell disease—homozygous; produce ONLY hemoglobin S iii. Sickle cell trait—heterozygous; both normal & S chains are formed, with hemoglobin A usually exceeding amount of S. 1. This seems to bestow some genetic resistance to malaria, allowing these children to reach reproductive age. 2. Present in 7-13% of African-Americans; 50% of East Africans! Most dangerous feature is sickle cell "crisis" (of which there are several varieties, but we'll cover just one): i. Vasoocclusive crisis (infarctive crisis)—blood flow in small vessels is obstructed by sickled cells. 1. This causes vasospasm, which amplifies the thrombosis. It terribly painful and may last for days.

Virulent organisms- host parasite relationship

are capable of causing disease in all hosts.

Leukocytes (WBCs): Components of the immune system: Myeloid stem cells:Natural killer (NK) cells

are considered part of the innate immune response because they can effectively kill tumor cells, virally infected cells, etc. without previously having been exposed to those cells/viruses etc. 1. They can also recognize antibody-coated target cells in a process known as: a. antibody-dependent cellular cytotoxicity (ADCC). 2. They kill virally infected cells & tumor cells, because these defective cells fail to display a group of cell surface markers known as MHC I proteins (major histocompatibility complex I).

Leukocytes (WBCs): Components of the immune system

arise from stem cells in bone marrow. These stem cells develop into either a myeloid stem cell or a lymphoid stem cell.

Hereditary spherocytosis—

autosomal dominant; defective membrane skeletons, membrane properties, and altered metabolism causing decreased survival time in patients with intact spleen. a. The most common hereditary hemolytic anemia. b. Responds universally to splenectomy. 4. Glucose-6-phosphate Dehydrogenase (G6PD) deficiency—patients do not have anemia unless challenged by drugs or chemicals— classically by the anti-malaria drug primaquine. a. Present in 11% of African-American males and in Sephardic Jews. b. X-linked recessive c. Treatment—avoid inciting agents

Anemia related to vitamin B12 (cobalamin) or folate deficiency

both cause disruption in DNA synthesis of blast cells in bone marrow, which leads to: a. Abnormal cells called megaloblasts in the marrow and b. large (macrocytic) RBCs in circulation. c. Hypersegmented granulocytes (> 6 lobes in nuclei) are famous, and their presence sufficient for diagnosis. i. B12 deficiency is known as pernicious anemia, and is associated with lack of intrinsic factor (required for B12 absorption) secretion by parietal cells in the stomach. 1. Etiology often autoimmune ii. Intrinsic factor binds to B12 in the stomach, and the B12-IF complex is absorbed in the distal small bowel (terminal ileum). iii. Classic neurological defects include: peripheral nerve degeneration, posterior column spinal cord degeneration or both. iv. Megaloblastic madness—one of my favorite terms d. Folate deficiency is also associated with neural tube defects (and other birth defects), so all sexually active females of childbearing years should be taking 1 mg/day of folic acid!!!!!

Malignant disorders of White Blood Cells:Bone marrow suppression

common because normal blood cell precursors "crowded out" by malignant cells) causes 1. Anemia—(low hematocrit or hemoglobin levels), manifests with pallor, fatigue, malaise, shortness of breath, and decreased activity tolerance. 2. Thrombocytopenia—causes bleeding difficulties: petechiae, easy bruising, bleeding gums, occult hematuria, and bleeding in body organs such as retinas, brain, etc. 3. Neutropenia—infections, frequently opportunistic in nature. ii. Infiltrative manifestations (malignant cells invading solid organs) cause enlargement and dysfunction of whatever organ is involved— hepatomegaly, splenomegaly, CNS dysfunction, lymphadenopathy, joint swelling/pain, weight loss, anorexia, etc

Colonization- host parasite relationship

consists of normal microbial flora or resident flora. These normal floral organisms can become pathogenic if they invade into a different environment, or if the host immune system is compromised: so- called opportunistic infections (a big problem in AIDS patients).

Chemotherapy

drugs work by disrupting some phase of cell life cycle, particularly rapidly dividing cells, and inducing apoptosis. 1. Treatment phases of chemotherapy: a. Remission induction phase—goal to induce a CR b. Postremission or consolidation phase—starts after CR, with goal to eliminate malignant cells that escaped induction chemo c. Remission maintenance phase—goal to prolong remission.

Chronic inflammation

prolonged inflammation often impairs healing and results in an accumulation of macrophages, fibroblasts, and collagen: called a granuloma. i. Hopefully the acute inflammatory process and the immune systems will together resolve the tissue damage, but if these systems are overwhelmed, then chronic inflammation can result. Generally a bad thing. 1. Example—tuberculosis causes granulomas because our immune system can't handle the infection on its own.

Polycythemia

excess of red cells, which can cause increased viscosity of blood i. Polycythemia vera—a type of chronic panmyelosis, and one of the myeloproliferative disorders. 1. All cells are overproduced—white cells, red cells, & platelets. Cause unknown. 2. No cure. Treatment is repeated phlebotomy, some chemotherapy agents as well. Leukemic transformation possible. ii. Secondary polycythemia—increased RBC production in response to external stimulus: high altitude, lung disease, smoking, etc. iii. Relative polycythemia—increased hematocrit with NORMAL RBC mass. A spurious finding. Seen in situations such as dehydration.

Hemophilia B

factor IX deficiency; also known as Christmas disease;

IgA

found in secretions onto mucus membranes. 1. Dimer. (There are 2 legs on an "A")

IgE

found on basophils & mast cells; important in allergies; 1. monomer

Leukocytes (WBCs): Components of the immune system: Myeloid stem cells: Monocytes

functions: 1. Phagocytosis—macrophages can live for months to years and are very efficient phagocytes. a. Opsonization—the coating of antigen by antibodies or complement, enhances phagocytosis. 2. secretion— a. of cytokines that promote inflammation, as well as the activity of other WBCs; and b. proteins important in wound healing, some of which break down tissue, & others stimulate the growth of new tissue. 3. antigen presentation—for T cells to be able to recognize antigen, they must be first processed & presented on the surface of antigen- presenting cells (such as macrophages, B-cells, or dendritic cells.

Hemostasis

he arrest of bleeding. The physiology of the process involves: i. Primary hemostasis— 1. Vascular spasm—lasts minutes to hours 2. Platelet plug formation—complete within 3-7 minutes ii. Secondary hemostasis— 1. Coagulation—formation of a fibrin clot at the site of injury to maintain the primary hemostasis. a. To achieve this, clotting factors activated via 2 possible pathways: intrinsic pathway & extrinsic pathway. Both catalyze the conversion of fibrinogen to fibrin. Process takes 3-10 minutes 2. Clot retraction—final stage; all of the above compressed to form a firm clot. Takes approx. 1 hour. b. Platelets (thrombocytes)—adhere to subendothelial collage exposed by trauma, become activated, and degranulate, releasing the contents of alpha granules and dense bodies. c. Blood coagulation factors—mostly circulate in inactive form in plasma. I won't have you memorize them. d. Fibrin clot i. Know what a cascade is, and the concept of the intrinsic, extrinsic, and common final pathways. e. Fibrinolysis—clot dissolution is accomplished when plasminogen is activated into plasmin.

Autoimmunity

he immune system recognizing ones own antigens as foreign and mounting an immune response against them: the loss of self-tolerance

Thrombocytosis

high platelet count; can be: 1. Transitory—following stress/exercise 2. Secondary (reactive)—response to hemorrhage, inflammatory disease, malignancy, infection, hemolysis, splenectomy. ii. Primary thrombocytosis (thrombocythemia)—seen in polycythemia vera or chronic granulocytic leukemia. iii. Bleeding time may be either normal or even prolonged!

Acute blood loss—

i. 10% loss usually doesn't cause symptoms, ii. 20% doesn't cause symptoms at rest iii. 30%--flat neck veins when supine, postural hypotension, exercise tachycardia iv. 40%--central venous pressure, cardiac output, and BP to fall while patient supine & at rest; also air hunger, tachycardia, cold/clammy skin. v. 50%--death unless treated quickly b. Treatment—stop the bleeding (duh...) transfusion, IV fluid support to maintain blood pressure, tissue perfusion.

B-cell, T-cell, and NK-cell (Non-Hodgin) Lymphomas

i. 95% in older adults, common in AIDS patients. ii. Lifetime risk of developing one of these lymphomas: 1 in 50! iii. Overall 5-year survival about 50% iv. Subtypes to know: 1. Burkitt lymphoma—the African variety is caused by Epstein-Barr virus, doubles in size daily!, and actually responds well to treatment. 2. T-cell lymphomas in adults are associated with infection by human T-cell leukemia virus, type I (HTLV-1)

Anemia

i. General effects of anemia: 1. Reduced oxygen-carrying capacity 2. Tissue hypoxia 3. Compensatory mechanisms to restore tissue oxygenation a. Increased heart rate, cardiac output, circulatory rate, and shunting of blood flow to vital organs. b. Increased erythropoietic activity 4. Manifestations—(you shouldn't have to memorize this list—just think of all the efforts the body might make to compensate for the lack of oxygen carrying capacity) a. Vasoconstriction (in non-essential organs like skin), pallor, tachypnea, dyspnea, tachycardia, transient murmurs, angina pectoris, heart failure, intermittent claudication, night cramps in muscles, headache, light-headedness, tinnitus, roaring in the ears, faintness. ii. Anemia related to decreased red cell production: 1. Aplastic anemia—decreased functional bone marrow, resulting in pancytopenia—reduction in all blood cells: white cells, red cells, & platelets. a. Causes—acquired (drugs, radiation, infectious, etc.) or familial b. The neutropenia is particularly critical when it occurs because of the infectious complications. c. Thrombocytopenia (of course) presents with bleeding complications. d. Treatment—transfusions, allogenic bone marrow transplantation if compatible donor can be found. Usually eventually fatal without transplant

Findings on physical examination of hemostats

i. Petechiae—flat, pinpoint capillary hemorrhages in skin or mucous membranes usually caused by vascular & platelet disorders. ii. Purpura—petechiae in groups or patches. Often pruritic (itchy) iii. Ecchymosis—blood escaped into tissues: a bruise. 1. If raised, called a hematoma. 2. Hemarthrosis—bleeding into a joint. iv. Telangectasia—lesion created by dilatation of capillaries & small arteries. Bleed easily! v. Hematochezia—bright red stools vi. Melena—black, tarry stools (caused by partial digestion of blood) vii. Hematuria—bleeding into urine viii. Hemoptysis—bleeding into sputum ix. Menorrhagia—excessive menstrual bleeding

Deficient immune responses—come in two type

i. Primary immune deficiencies—not attributable to another cause; ii. Secondary immune deficiencies—consequence of other disease processes or treatments.

Components of the immune system:

i. Skin & mucus membrane barriers- Epithelial ii. Mononuclear phagocyte system iii. Lymphoid system (spleen, thymus gland, lymph nodes) iv. Bone marrow Each above is inhabited by different WBC's

Secondary immunodeficiency disorders

i. Stress—burns, trauma, pregnancy, infancy, ii. surgery, iii. nutritional deficiencies (both malnutrition and overnutrition!), iv. cancer chemotherapy drugs, v. viruses, vi. post-splenectomy patients reduces serum IgM and the antibody response to encapsulated bacteria. vii. Advanced age viii. Taking this course, ix. And lots of others...

Cholesterol

i. Very low-density lipoprotein (VLDL)—contains most of the lipids leaving the liver going out to body tissues ii. Low-density lipoprotein (LDL)—is VLDL minus the triglycerides deposited in adipose. So, LDLs are very high in cholesterol. iii. High-density lipoprotein (HDL)—contain excess lipids the cells don't need, which are transported back to liver.

Pathogen

infectious organisms

Plasma cell myeloma (multiple myeloma)

malignancy of antibody-secreting matured, monoclonal B-cells (plasma cells), which invade bone and form multiple tumor sites. Exclusively adult. i. Monoclonal antibodies detectable in blood on serum protein electrophoresis. ii. Bence Jones protein—are antibody light chains found in urine; can cause kidney damage. (Renal insufficiency develops in 50% of patients.) iii. Pathologic fractures and the bone pain associated with the bone infiltration are very miserable! iv. Onset of disease usually slow, with some patients having only excess monoclonal antibodies, but no Bence Jones protein or bone lesions—a condition called monoclonal gammopathy of undetermined significance (MGUS).

Hodgkin disease

malignancy of lymph nodes characterized by Reed-Sternberg cells (which originate from B-cells). i. Epstein-Barr virus—frequently found in genome of these cells. ii. Disease usually progresses in a predictable step-by-step pattern along lymph node chains. iii. Staging (I-IV) includes the letters "A" and "B" 1. A—no clinical symptoms 2. B—symptoms include: loss of >10% body weight, unexplained fevers, night sweats, pruritus (itching) iv. Treatment with chemo/radiation; prognosis as good as 90% at 10-years, depending on stage.

Thrombocytopenia

many different causes, but one common cause is: i. Idiopathic thrombocytopenic purpura (ITP)—immune mediated, 1. Acute form usually follows a viral illness, resolution usually spontaneous 2. Chronic form usually in adults 3. Treatment depends on severity & duration; ranges from watchful waiting, steroids, or splenectomy.

Hairy cell leukemia

rare, chronic leukemia, very curable.

Colonization

microorganism existing in/on a body without causing harm or infection.

IgG

most common (75-80% of circulating antibody), 1. predominates in the secondary (anamnestic) immune response. a. (Memory B cells remember antigens that they have previously been exposed to—and when they are re-exposed to the same antigen a subsequent time, our B-cells produce mainly IgG.) 2. Monomer

Hemophilia A

most common, due to factor VIII deficiency 1. 85% of cases

Antibody functions

most of what they do is to aid other immune functions) 1. precipitation—pulling antigens out of solution (blood stream) 2. agglutination—sticking groups of antigens together. 3. neutralization—just by binding, can make some bacterial toxins ineffective. 4. opsonization—enhance the function of phagocytic cells. 5. complement activation—particularly IgM & IgG are good at this

Principles of treatment: Complete response (CR)

no detectable malignant cells, normal hematopoiesis, for leukemias less than 5% blast cells in bone marrow maintained for 4 weeks. 1. NOT necessarily a cure—there may be lots of malignant cells escaping detection. 2. (A partial response to chemotherapy in any malignancy is a reduction of at least 50% in cancer cell burden.)

Active immunity

occurs by antigen exposure and immune response of the person's own immune system. Can be either: 1. immunization—deliberate administration of vaccines or 2. active infection—actually get infected by an organism.

Anemia of chronic renal failure

occurs due to things like: i. Erythropoietin deficiency, uremia-induced hemolysis, bone marrow depression, blood loss, etc. b. Clinical manifestations— i. Anemia usually limited to erythrocytes (not thrombocytes, leukocytes too); ii. Pericardial effusions may occur 1. (Fluid in pericardial sac which may impair heart function) iii. Hematocrit falls in proportion to degree of renal insufficiency. c. Treatment—erythropoietin, iron supplementation.

Inflammation

occurs whenever cells are injured, whatever the cause. The suffix -itis is used to denote inflammatory conditions. Purposes include: i. Neutralize & destroy invading and harmful agents ii. Limit spread of harmful agents to other tissues iii. Prepare damaged tissues for repair. localized signs of inflammation are really important: Redness (rubor) Swelling (tumor) Heat (calor) Pain (dolor) b. Five cardinal 1. 2. 3. 4. 5. Loss of function (function laesa) ii. By localized, I mean these are signs of inflammation that occur just at the site of the inflammation. iii. Systemic signs also can occur (like listed in #9 below) c. Important distinctions: infection is always accompanied by inflammation, but not all inflammation is of infectious origin. d. Sequence of events in the inflammatory process: i. Increased vascular permeability—mast cells release chemicals such as histamine, prostaglandins, & leukotrienes, which cause vasodilatation, and increased vascular permeability. ii. Emigration (diapedesis) of leukocytes from the bloodstream into tissues— neutrophils (and other WBCs) roll and stick to the sides of blood vessels, a process called margination or pavementing. 1. selectins—are receptors that aid neutrophil pavementing 2. integrins—aid neutrophil movement through the capillary walls (diapedesis). 3. chemotaxis—is the process by which leukocytes are attracted to inflamed tissue. iii. Phagocytosis—if a microbe is small enough to be internalized, the phagosome is fused by a lysosome and digested. Larger particles are attacked by extracellular secretion of digestive enzymes.

IgD

ound on B-cell membranes. Functions not well understood. 1. Monomer.

Diagnosis of WBC malignancies is accomplished by

peripheral blood smear, bone marrow biopsy, lymph node biopsy.

Passive immunity

transfer of pre-formed antibody against a particular antigen from an immune person to a non-immune person. i. Indications for passive immunity medical treatment are: 1. B-cell immunodeficiencies 2. Following exposure of a person with high susceptibility to a disease without adequate time for active immunity 3. when antibody injections may alleviate or suppress the effects of an antigenic toxin. ii. Passive immunity can occur in situations such as: 1. in the fetus 2. in breast milk (breast feeding is a good idea) 3. serotherapy—injection of specific "immune globulins. Examples: rabies immune globulin, hepatitis B immune globulin, West Nile Virus immune globulin, etc.

Von Willebrand disease

usually autosomal dominant disorders of factor VIII carrier protein & platelet function. i. Factor VIII and Von Willebrand factor (VWF) usually circulate in plasma as a complex, with VWF necessary for stabilization of factor VIII in circulation & normal platelet adherence. ii. Can be a really major pain in the neck cause of post-surgical bleeding if not diagnosed preoperatively. iii. Mild form treated with drug called desmopressin—causes release of VIII- VWF complex from vascular endothelial cells. iv. More severe forms with factor transfusions.

Chronic lymphoid leukemia (CLL)

—30% of all leukemias in US. i. 95% have malignant B-cell precursor. ii. Indolent course, frequently found accidently in CBC blood tests, with no symptoms usually apparent. iii. Average age of diagnosis 65-70 years; so frequently treatment not necessary (patients more likely to die of another condition than CLL).