Week 13: Blood, Immunity Flashcards
Define neutropenia, causes, consequences
abnormally low number of neutrophils
Causes: may be due to reduced production in the bone marrow or destruction of neutrophils elsewhere in the body
Consequences: inability to respond to bacterial infections
What is the infectious agent of mononucleosis?
Epstein-barr virus - replicates in epithelial cells then within B lymphocytes which stimulates T cytotoxic cells to target the infected B lymphocytes
Transmission, S/S (6) and prognosis of mononucleosis
Transmission: person to person by saliva
S/S: flu-like, fever, sore throat, fatigue; spleen enlargement, lymphadenopathy
Prognosis: self-limiting and does not usually require treatment
Define myelogenous leukemia
involves pluripotent myeloid stem cells in bone marrow, interferes with maturation of all blood cells including granulocytes, erythrocytes and thrombocytes
Define lymphocytic leukemia
immature lymphocytes and their progenitors that originate in bone marrow but infiltrate spleen, lymph nodes, CNS and other tissues
Define acute vs. chronic leukemia
Acute leukemia: rapid increase in # of immature blood cells, most common form in children
Chronic leukemia: buildup of relatively mature but abnormal WBC, generally takes months or years
Characteristics of ALL (3)
- Most common type in young children, but can affect adults usually over age 65
- Precursor B or T lymphoblasts, with most being pre-B
- Structural and numerical changes in chromosomes within leukemic cells such as translocations, deletions, hyperploidy or polyploidy that alter ability to regulate normal hematopoiesis
Characteristics of CLL (3)
- Clonal malignancy of B lymphocytes that most often affects adults over age 55 and does not affect children
- Most common form in adults and 2/3 of all cases are men
- See change in immunoglobulin gene resulting in low levels of CD markers like CD38 and zeta-associated protein (ZAP-70) involved in signaling T cells and natural killer cells do better, while individuals with higher levels of markers tend to do worse
Characteristics of AML (3)
- Occurs more commonly in adults than children and more commonly in men than women
- Diverse set of leukemias affecting myeloid precursors in the bone marrow and are most often associated with acquired genetic changes that inhibit myeloid cell differentiation
- Undifferentiated blast cells replace normal cells within bone marrow causing anemia, neutropenia and thrombocytopenia
Characteristics of CML (6)
- Mainly in adults, may be seen in a small # of children
- Pluripotent hematopoietic progenitor cell
- Characterized by excessive proliferation of marrow granulocytes, erythroid precursors and megakaryocytes
- Philadelphia chromosome
- Begins in a chronic phase that over several years progresses to an accelerated phase that ultimately enters a blast crisis phase = terminal phase where CML acts like AML
- CML treated with tyrosine kinase inhibitor drugs that have improved survival rates to over 95%
2 forms of CLL
- long term survival and eventual death from other causes
2. Rapidly fatal disease despite aggressive therapy
What happens in the formation of the Philadelphia chromosome?
creates a new fusion gene that acts like a tyrosine kinase
Activates the cell cycle - cell division rates increased, inhibition of DNA repair
What cells are affected in non-Hodgkin lymphoma, causes (5)?
Either B-cell or T-cell neoplasms, may originate from any lymphoid tissues but commonly from lymph nodes
Causes largely unknown, may include infection (EBV, HTLV-1, HIV), chemicals, medical treatment, genetic diseases, autoimmune diseases
What is the characteristic cell formation in Hodgkin Lymphoma? Where is it believed these cells originate from?
Reed-Sternberg cells - multinucleated cells
B cells within the germinal centers of the lymph node
Peaks of incidence for Hodgkin Lymphoma, treatment (3)?
Two peaks of incidence - age 15-35 and over 55
Treatment: radiation, chemo, hematopoietic stem cell transplantation
Define multiple myeloma; why it is called a “myeloma”?
B-cell cancer of the plasma cells that normally produce antibodies
Name comes from impact on all different kinds of cells - generates losses of myeloid function due to infiltration of bone marrow
What are Bence Jones proteins and which disease process do they accompany?
cells release protein part of the immunoglobulins
Multiple myeloma
Risk factors (4) and manifestations of multiple myeloma (6)
Risk factors: chronic immune stimulation, autoimmune disorders, exposure to ionizing radiation, occupational exposure to pesticides
Manifestations: anemia, neutropenia, thrombocytopenia, infection, renal failure, neurologic symptoms
Explain why liver dysfunction; vessel defects; and platelet defects can give rise to coagulation pathology
Liver dysfunction: clotting factor synthesis, bile synthesis and clearing of clotting factors disrupted
Vessel defects: exposure to subendothelial lining triggers the clotting pathway
Platelet defects: clotting factor reactions normally take place on the surface of platelets
What are examples of vessel defects (4) and platelet defects (3)
Vessel defects: marfan’s syndrome, vitamin C deficiency, inflammatory responses, atherosclerosis
Platelet defects: thrombocytopenia, splenomegaly, platelet destruction
What are examples of clotting disorders (5)
- Hemophilia
- DIC
- Vit K deficiency
- Fibrinolytic defects: increased circulating clotting factors, plasmin inhibitor deficiencies
- Inherited prothrombic disorders: AT III deficiency, protein C defects
What are the clotting dysfunction tests (3)?
- Platelet count
- aPTT (activated partial thromboplastin time): measures effectiveness of intrinsic pathway
- PT (prothrombin time): measures extrinsic pathway
How do aspirin, warfarin and heparin impact blood clotting?
Aspirin: inhibits cyclooxygenase
Warfarin: competes with vitamin K
Heparin: interacts with AT III to bind coagulation factors including thrombin and prevent hemostasis
Define DIC
complication of diseases that accelerate clotting, causing small blood vessel occlusion, organ necrosis, depletion of circulating clotting factors and platelets, activation of fibrinolytic system and consequent severe hemorrhage
Causes of DIC (4)
- disorders that produce necrosis - burns, trauma, hepatic necrosis, transplant rejection
- Infection - septicemia, fungal, protozoal, viral infection
- Neoplastic disease
- Other conditions - cardiac arrest, cirrhosis, shock
Patho of DIC
excessive clotting and consumption of clotting components, excessive circulating thrombin activates fibrinolytic system which dissolves clots
Define thrombocytopenia
Most common cause of what?
relative decrease in thrombocytes or platelets
Hemorrhagic disorders
Causes of thrombocytopenia (4)
- Blood loss
- Decreased platelet production - leukemia, aplastic anemia, drug toxicity
- Increased platelet destruction - liver cirrhosis, DIC, severe infection
- Sequestration - increased blood in limited vascular area like spleen
Define idiopathic thrombocytopenia
deficiency of platelets as a result of immune system destroying own platelets
What populations does idiopathic thrombocytopenia affect?
Acute: children ages 2-4
Chronic: adults under age 50, particular women between 20-40
Define Von Willebrand disease
Inheritance pattern
hereditary bleeding disorder characterized by prolonged bleeding time
Autosomal dominant
Consequences of Von Willebrand disease on clotting
Deficiency of Von Willebrand’s factor which stabilizes clotting factor VIII
Define anemia
How is it diagnosed?
reduction in total RBC mass leads to decreased O2 carrying capacity
Assess Hct, Hgb, total RBC
Causes of anemia
Reduced RBC production: reduced Hgb or DNA synthesis, bone marrow suppression
Enhanced RBC destruction: hemolysis, chronic disease
Symptoms of anemia (7)
Headache, fatigue, dyspnea, poor exercise tolerance, pallor, syncope, tachycardia
3 most common types of anemia
- Microcytic hypochromic: reduced hemoglobin synthesis d/t iron deficiency, thalassemia, sideroblastic anemia
- Macrocytic normochromic: altered DNA synthesis, megaloblastic anemia, vitamin B12 deficiency
- Normocytic normochromic: compromise to hematopoiesis (bone marrow suppression) or enhanced RBC destruction
Define the following terms related to anemia: aplastic; folic acid or iron deficiency; pernicious; and sideroblastic.
aplastic: loss of stem cells or bone marrow matrix causing pancytopenia
folic acid deficiency: common, slowly progressive megaloblastic anemia; folate required for DNA synthesis
iron deficiency: iron required for Hgb and O2 binding
pernicious: malabsorption of B12 - most common megaloblastic anemia
sideroblastic: heterogenous disorders with common defect preventing use of iron in Hgb synthesis even though there are sufficient iron stores
General cause of: sickle cell disease, thalassemia, glucose-6-phosphate deficiency
sickle cell disease: genetic disorder where genetic change in beta-globin causes sickling, especially in low levels of O2
Thalassemia: genetic disorders causing defect in globin chains that comprise hemoglobin
Glucose-6-phosphate deficiency: genetic disorder that limits the amount of oxidative stress that can be protected against in erythrocytes, resulting in hemolysis
What does thalassemia give rise to?
hemolytic anemia
What triggers oxidative stress in glucose-6- phosphate deficiency (4)
Triggered by infections, severe stress, certain foods (fava beans) or certain medicines (antimalarial drugs)
Define ABO and Rh incompatibility
ABO incompatibility: exposure to blood group antigens that are foreign initiates formation of antibodies
Rh incompatibility: exposure to Rh factor
How does ABO and Rh incompatibility occur?
woman who is Rh negative develops antibodies against an Rh-positive fetus (not an issue until 2nd pregnancy)
What are the risks for ABO/Rh incompatibility to fetal development (2)
Erythroblastosis fetalis: refers to a hemolytic disease of the fetus and neonate based upon incompatibilities between fetal and maternal blood
Hydrops fetalis: severe form of erythroblastosis fetalis associated with profound anemia or edema
How does RhoGAM work?
medicine containing IgG antibodies that attack Rh-D found on fetal RBCs to prevent isoimmunization
Define polycythemia
increase in RBC mass
Define primary polycythemia
What age does this occur?
Causes?
chronic disorder characterized by increased RBC mass, erythrocytosis, leukocytosis, thrombocytosis, increased hemoglobin levels
Occurs between ages 40-60
Cause unknown likely related to stem cell defect
Define secondary polycythemia
Causes?
What is another name?
excessive RBC production due to hypoxia, tumor or disease
Causes: prolonged tissue hypoxia or increased production of erythropoietin
Reactive polycythemia
Define spurious polycythemia
causes?
increased hematocrit with a normal or low RBC mass
Causes: dehydration, hypertension, elevated serum cholesterol, uric acid levels
What happens during the cellular injury, vascular phase, cellular phase of wound healing and what are consequences of acute inflammation?
Cellular injury: initiates inflammatory response
Vascular phase: includes vasodilation and increased vascular permeability
Cellular phase: leukocytes enter the injured tissue to destroy infective organisms, remove damaged cells and release inflammatory mediators
Consequences: an exaggerated response may be harmful and process is nonspecific so it may be difficult to control.
What is the general patho behind the cardinal signs of inflammation: heat, redness, swelling
mediators increase vasodilation and vascular permeability
What are mast cells and mast cell degranulation?
Mast cells: activation results in release of preformed contents of granules, synthesis of lipid mediators derived from cell membrane precursors and stimulation of cytokine and chemokine synthesis by other inflammatory cells
Mast cell degranulation: allergy antibody IgE present, results in release of inflammatory mediators
What is histamine?
one of the first mediators to be released from mast cell granules during an acute inflammatory reaction; causes vasodilation and increases permeability
Define: chemotactic factor, leukotriene, prostaglandin
Chemotactic factor: substances that stimulate cellular movement - eg. Chemokines, complement system
Leukotriene: induces smooth muscle contraction, constricts pulmonary airways, increases microvascular permeability
Prostaglandin: induces vasodilation and bronchoconstriction, inhibits inflammatory cell function
Define complement
effector mechanism of innate and adaptive immunity that allows body to localize infection and destroy invading microorganisms; 3 different pathways: classical, alternative and lectin
Classical vs. alternative pathways of complement system
Classical: initiated by an antigen-antibody complex, reactive site on the antibody uncovered and binds to the C1 molecule in the complement system
Alternative: inactive circulating complement proteins activated when exposed to microbial surface molecules, complex polysaccharides
Define membrane attack complex, opsonization, chemotaxis
Membrane attack complex: assembled during the complement pathway, penetrates microbial cell membrane allowing the passage of ions, small molecules and water into the cell causing cell lysis
Opsonization: coating of an antigen with antibody or complement to enhance binding
Chemotaxis: directed cell migration - inflammatory mediators directed to the site of injury by chemoattractants
Define the clotting & kinin system, bradykinin
Clotting and kinin system: blood proteins that play a role in inflammation, BP control, coagulation and pain
Bradykinin: increases vascular permeability and causes contraction of smooth muscle, dilation of blood vessels and pain
Define interleukin, lymphokine, interferon
Interleukin: produced by macrophages and lymphocytes in the presence of an invading microorganism or when inflammatory process initiated; enhance the acquired immune response or regulate through suppression or enhancement the inflammatory process
Lymphokine : substance produced by lymphocytes that acts upon other cells of the immune system
Interferon: cytokines that protect the host against viral infections and play a role in the modulation of the inflammatory response
Define fever, leukocytosis and acute-phase reactants in relation to inflammation
Fever: cytokines affect the thermoregulatory center in the hypothalamus and produces fever
Leukocytosis: increased white blood cells - sign of inflammatory response, usually caused by bacterial infection
Acute-phase reactants: liver dramatically increase the synthesis of acute-phase proteins
What are the acute-phase reactants (3)
fibrinogen, C-reactive protein, serum amyloid A protein
How do granulomas form in chronic inflammation?
Macrophages unable to protect against host tissue damage, the body tries to wall off the site by forming a granuloma
Basic characteristics of Type I hypersensitivity disorders
I: IgE mediated response leads to inflammatory mediators from sensitized mast cells
Describe how sensitization, primary response and secondary response occur in allergic reactions
Sensitization of mast cell/basophil results in priming the reaction
Primary response: results from degranulation and release of mediators
Secondary response: membrane phospholipids and recruitment of inflammatory cells that release cytokines
Clinical consequences of local vs. systemic allergic reaction
local: allergic rhinitis characterized by sneezing, itching, water discharge from eyes and nose
systemic: affects the areas in the body where mast cells are located - skin, GI tract and respiratory system
Define anaphylaxis
systemic life-threatening hypersensitivity reaction with widespread edema, difficulty breathing, vascular shock s/t vasodilation
What are the 3 types of grafts?
Autologous - donor and recipient are the same
Syngeneic - donor and recipient are identical twins
Allogenic - share similar HLA types
Define rejection, what are the phases?
immune responses that occur as the recipient’s immune system sees the graft as foreign and begins attacking it immunologically
Hyper acute reaction: occurs immediately after transplant and involves existing recipient antibodies to grant antigens
Acute rejection: within months of transplantation, involves cytotoxic T cells and activation of inflammatory responses that attack the graft
Chronic rejection: prolonged period of time - caused by fibrotic processes mediated by cytotoxic T cells
Define graft-versus-host disease
Immune competent cells attack tissues in recipient and may manifest as skin lesions, involvement of the GI tract that can become life-threatening
Define SCID (severe combined immunodeficiency)
primary immunodeficiency characterized by lack of all T and B cell function, sometimes missing NK cells
Define primary vs. secondary immunodeficiency
Primary: congenital or inherited
Secondary: acquired
What are the three forms of wound healing?
Resolution: minimal tissue damage, tissue returns to normal in short period of time
Regeneration: healing process occurs in damaged tissue in which cells are capable of mitosis, damaged tissue replaced by identical tissue from proliferation of nearby cells
Replacement: replaced by connective tissue when extensive damage or when cells are incapable of mitosis, chronic inflammation or complications results in fibrosis
What are the phases of wound healing?
Inflammatory phase: phagocytes eliminate debris
Proliferative phase: building new tissue, including fibroblasts that secrete collagen and growth factors for angiogenesis and stimulation of endothelial cells
Contraction and remodeling phase: development of fibrous scar that is remodeled to become stronger and smaller
Define cicatrization, debridement
Cicatrization: contraction of fibrous tissue formed at a wound site by fibroblasts
Debridement: cleaning the site of infection
Define first-intention vs. second-intention wound healing
First-intention: scar tissue laid down across a clean wound with edges in close approximation
Second-intention: parallels first-intention but occurs in wounds in which large sections of tissue have been lost or in wounds complicated by infection
Explain how the following relate to compromised wound healing: use of anti-inflammatory drugs; scurvy; infection; and, dehiscence
Anti-inflammatory drugs: inhibits wound healing
Scurvy (impaired collagen synthesis): compromises wound healing
Infection: may result in compromised wound healing/prevents epithelialization
Dehiscence: results in bursting open or a previously closed wound
Basic characteristics of Type II hypersensitivity disorders
II: antibody mediated responses against cell surface or extracellular matrix antigens that result in complement-mediated phagocytosis, inflammation and cell injury or abnormal physiological responses without cell injury
Basic characteristics of Type IIi hypersensitivity disorders
III: generated by immune complexes that activate complement resulting in activation of inflammatory cells that release tissue-damaging products
Basic characteristics of Type IV hypersensitivity disorders
IV: tissue damage in which cell-mediated immune response with sensitized T lymphocytes cause cell and tissue injury
