What is type I hypersensitivity and antigen form?
IgE and soluble antigen
What is type II hypersensitivity?
IgG OR IgM and cell-bound
... [Show More] antigen
What is type III hypersensitivity?
IgG AND IgM and soluble antigen
What is type IV hypersensitvity?
T Cells and soluble or cell-bound antigen
What is type I hypersensitivity mechanism of activation?
-Allergen-specific IgE antibodies bind to mast cells via their Fc receptor.
-When the specific allergen binds to the IgE, cross-linking of IgE induces degranulation of mast cells.
What is type II hypersensitivity mechanism of activation?
-IgG or IgM antibody binds to cellular antigen, leading to complement activation and cell lysis.
-IgG can also mediate ADCC with cytotoxic T cells, natural killer cells, macrophages and neutrophils.
What is type III hypersensitivity mechanism of activation?
- Antigen-antibody complexes are deposited on tissues.
- Complement activation provides inflammatory mediators and recruits neutrophils.
-Enzymes released neutrophils damage tissue.
What is type IV hypersensitivity mechanism of activation?
- TH1 cells secrete cytokines, which activate macrophages and cytotoxic T cells.
What is a type I hypersensitivity reaction?
- Local and systemic anaphylaxis
-Seasonal hay fever
- Food allergies
- Drug allergies
What is a type II hypersensitivity reaction?
- RBC destruction after transfusion with mismatched blood types during hemolytic disease of the newborn
What is a type III hypersensitivity reaction?
- Post-streptococcal glomerulonephritis
-Rheumatoid arthritis
-Systemic lupus erythematosus
What is a type IV hypersensitivity reaction?
- Contact dermatitis
-Type I diabetes mellitus
-Multiple sclerosis
(slowest)
What is excessive immune response?
A type of alteration in immune function: over or hyper-function of immune system
What is deficient immune response?
A type of alteration in immune function: ineffective immune response
What is autoimmunity?
Immune system attacks own tissues
What is the cause of autoimmunity?
Abnormal excessive immune responses toward own
tissues.
What is the MHC gene? (HLA)
Appear to increase risk of autoimmune disorders
females at higher risk
What is hypersensitivity?
-Describes the mechanism of injury
-May or may not involve autoimmunity
What is the treatment of autoimmunity?
Individualized immunosuppressive therapy -
1. Corticosteroids and cytotoxins (MTX)
2. Tumor necrosis factor inhibitors and
immunomodulators - (Monoclobal Antibodies (MAB))
3. Therapeutic plasmapheresis
What is the mechanism of treatment for type I hypersensitivity of IgE blocker therapy?
Inhibits binding of IgE to mast cells (Only for Type I)
What is the mechanism of treatment for hypersensitivity of antihistamines?
Block the effects of histamine
What is the mechanism of treatment for hypersensitivity of epinephrine?
(counter effects of Histamine)
-Adrenergic agent given subQ or IV during acute allergic reactions
-Highly allergic people can carry an EpiPen
What is the mechanism of treatment for hypersensitivity of Beta-adrenergic?
Decrease broncho-constriction
What is the mechanism of treatment for hypersensitivity of corticosteroids?
Decrease inflammatory response
What is the mechanism of treatment for hypersensitivity of anticholinergics?
Block parasympathetic system
What is leukemia?
Circulating tumors that primarily involve blood and bone marrow
What is lymphoma?
tends to localize in lymph tissues; is often disseminated to other sites at diagnosis
What is plasma cell myeloma?
malignant transformation
of B-cell plasma cells; likes to form localized tumors in bony structures
What are the most common clinical manifestations of hematologic neoplasms?
-Anemia
-Thrombocytopenia
-Leukopenia
--Neutropenia
What is Acute Lymphoblastic Leukemia/Lymphoma/(ALL) most common of?
Primarily a children's disorder: most common
malignancy in children
What is Acute Lymphoblastic Leukemia/Lymphoma/(ALL) peak incidence?
Between 3 and 7 years; 2nd peak: middle age
What is Acute Lymphoblastic Leukemia/Lymphoma/(ALL) symptom onset?
-Abrupt
-Bone pain, bruising, fever, infection
-Children may refuse to walk---why? (Hematothrosis: low platelets)
-Loss of appetite, fatigue, abdominal pain
-Enlarged spleen, liver, lymph nodes
-3% may present with CNS signs
What is Acute Lymphoblastic Leukemia/Lymphoma/(ALL) prognosis and treatment?
- 85% 5-year survival rate in children; 30%
to 50% in adults (Better prognosis in children than adults)
-Certain forms of ALL more responsive to
therapy
-Chemotherapy for remission induction
What is Chronic Myeloid Leukemia (CML) average onset?
40-50 years/Adult
What is Chronic Myeloid Leukemia (CML) characterized by?
malignant granulocytes that carry the Philadelphia chromosome (Ph+): Translocation of
chromosomes 9 and 22 to creates a new fusion gene: bcr/abl (increases cell proliferation and reduces apoptotic cell death)
What is Chronic Myeloid Leukemia (CML) usual clinical presentation?
-High granulocyte count on the CBC
-Splenomegaly
What is Chronic Myeloid Leukemia (CML) anti-bcr/abl therapy (imatinibi)?
reduce number of
leukemic cells with bcr/abl type to undetectable levels
What does Chronic Myeloid Leukemia (CML) not respond well to?
chemotherapy: poor
overall survival time, untreated patients have median survival 2 years
What does Chronic Lymphoid Leukemia (CLL) accounted for?
30% of all cases of
leukemia in the United States — most common
What is pathogenesis of Chronic Lymphoid Leukemia (CLL)?
95% are malignant B-cell precursors
--Follows an indolent course; asymptomatic
--Usually found by accident in routine blood
examinations
What is another pathogenesis of Chronic Lymphoid Leukemia (CLL)?
5% associated with more aggressive T-cell transformation
What are the symptomatic of Chronic Lymphoid Leukemia (CLL)?
-Fatigue, weight loss, anorexia
-Increased susceptibility to infections
-B & T cells divide uncontrollably and rapidly
What happens when malignant lymphocytes invade lymphoid tissues and bone marrow in Chronic Lymphoid Leukemia (CLL)?
disrupts function
-Lymphadenopathy: Enlarged, painless lymph nodes
-Splenomegaly: Enlarged spleen
-Hepatomegaly: enlarged liver
What happens in bone marrow infiltration in Chronic Lymphoid Leukemia (CLL)?
-Reduces production of red blood cells/platelets---s/s??
-Preponderance of lymphoid cells
What is the pathogenesis of Plasma Cell Myeloma (Multiple Myeloma)?
- Malignant plasma cells produce excessive identical monoclonal antibodies
-Accumulate in the bloodstream
-Detected by serum protein electrophoresis
-Large amount of one type of antibody; forms a characteristic spike
**Think CRAB
What does CRAB stand for in multiple myeloma?
-hyperCalcemia,
-Renal insuff,
-Anemia,
-Bone lytic lesions/Back pain
What is Bence Jones protein?
-Malignant plasma cells produce light-chain antibody fragments that accumulate in
blood and urine
--Helps confirm diagnosis
--Can accumulate in kidneys and damage them
What are the pathologic fractures common in Plasma Cell Myeloma (Multiple Myeloma)?
-Bone destruction releases calcium into bloodstream
-hypercalcemia
What is the most clinical manifestation caused by in Plasma Cell Myeloma (Multiple Myeloma)?
Most clinical manifestation caused by bone/renal damage
What is the diagnosis based on for Plasma Cell Myeloma (Multiple Myeloma)?
-Monoclonal antibody peak
-Presence of Bence Jones protein
-Hypercalcemia
-Evidence of bone lesions
What are the cells in Hodgkin Disease?
B cells
What are the cells for non-hodgkin?
B, T & NK cells
What are the risk factors in Hodgkin Disease?
Epstein-Barr Virus (EB virus)
What are the risk factors in non-hodgkin?
-Burkitt lymphoma
-Epstein-barr virus
-HIV
What is the histology of Hodgkin Disease?
Reed-sternberg cells
What is the growth/metastasis in Hodgkin Disease?
contiguous lymphatic pathways (grow/spread in predictable way)
What is the growth/metastasis in non-hodgkin?
Non-predictable
What is the initial place/common place for Hodgkin Disease?
cervical nodes
What is most common for Hodgkin Disease?
Single node or localized node chain
What is most common for non-hodgkin?
spread
What is the treatment for Hodgkin and non-hodgkin disease?
radiation and chemo
What is the survival rate of Hodgkin Disease?
>85%
What is the survival rate of non-hodgkin?
about 50%
What does Hodgkin disease represent?
Represents about 30% of malignant lymphoma
What is the life span of Hodgkin disease?
Occurs across life span; half of cases between
ages 20 and 40 years
What is higher incident in males for Hodgkin disease?
males; also have worse
prognosis
What is malignant disorder of lymph nodes of Hodgkin disease characterized by?
-Reed-Sternberg cells
-Originate from B cells in germinal centers of
lymph nodes
--Malignant but grow/spread in predictable way; sets
HD apart from other lymphomas
How does Hodgkin disease metastasizes along?
contiguous lymphatic pathways (Predictable metastasis route)
What is frequently found in Hodgkin disease?
Epstein-Barr virus in
genome of transformed Reed-Sternberg
cells; may be important in pathogenesis of HD
Where is Hodgkin disease present in?
single node or localized
node chain
What is the most common treatment for Hodgkin disease?
Radiation therapy but if disease is disseminated = chemotherapy
What are B-Cell, T-Cell, and NK-Cell
Lymphoma (Non-Hodgkin) pathogenesis and clinical manifestations?
-Similar to other malignancies
-Tumor cells derived from single mutant
precursor cell and are clonal
-Viruses suspected in development of some
lymphomas (e.g., Burkitt lymphoma and Epstein-Barr virus)
-5-year survival rate: 50%
What are two serious oncologic emergencies in B-Cell, T-Cell, and NK-Cell Lymphoma (Non-Hodgkin)?
-Superior vena cava obstruction
-Spinal cord compression
What are other complications in B-Cell, T-Cell, and NK-Cell Lymphoma (Non-Hodgkin)?
-infection
-bone metastasis
-joint effusions
What is aplastic anemia?
Stem cell disorder characterized by
reduction of hematopoietic tissue, fatty marrow replacement, and pancytopenia
(low RBC, WBC, and platelets) **
What is aplastic anemia caused by?
toxic, radiant, or immunologic
injury to the bone marrow stem cells
What is aplastic anemia diagnosed with?
bone marrow biopsy
What is the age group for aplastic anemia?
young (15-25) or old (>60)
What is the treatment for aplastic anemia?
- Determine efficacy of bone marrow
transplantation **
- Administer immunosuppressive therapy or stimulate hematopoiesis and bone marrow regeneration
What is the prognosis for aplastic anemia?
Fatal unless bone marrow transplant successful
What is iron deficiency anemia?
- Most common nutritional deficiency in the world
-Insufficient iron for hemoglobin synthesis
What are the sign and symptoms of iron deficiency anemia?
- Pica (craving for nonfood substances such
as dirt, clay, ice, laundry starch, cardboard,
or hair)
-Koilonychias (spoon-shaped nails)
-Blue sclerae
What is MCV?
mean corpuscular volume - average volume and size of individual red blood cells
What is MCHC?
mean corpuscular hemoglobin concentration - checks the average amount of hemoglobin in a group of red blood cells
What is ferritin?
1. Iron-protein complex
2. Cellular storage protein for iron
3. Acute phase reactant
What is transferrin?
A plasma protein that transports iron through the blood to the liver, spleen and bone marrow.
What is iron deficiency anemia insufficient in?
Hypochromic, microcytic RBCs; low MCV, MCH, and MCHC
What serum decreases in iron deficiency anemia?
Serum ferritin level decreased; serum iron
level decreased; total iron binding capacity
(TIBC) increased
What is the treatment for iron deficiency anemia?
- Oral administration of ferrous sulfate or
intravenous ferric gluconate (only in severe cases); continue for 4-6 months **
-Treat underlying cause
What is iron deficiency anemia prognosis?
Excellent
What is Anemia Related to Vitamin B12 (Cobalamin) or Folate Deficiency?
Disruption in DNA synthesis of blast cells
produces megaloblasts (macrocytic *)
What is pernicious anemia in Anemia Related to Vitamin B12 (Cobalamin) or Folate Deficiency?
Pernicious anemia due to lack of intrinsic
factor leading to vitamin B12 deficiency
What are folate deficiencies from?
-Folate deficiencies from dietary deficiencies,
alcoholism, cirrhosis, pregnancy, or infancy
--Low folate levels associated with neural tube deficits
What are the clinical manifestations of Anemia Related to Vitamin B12
(Cobalamin) or Folate Deficiency —Macrocytic?
Pernicious anemia
-Low RBC, WBC, and platelet counts with increased
-MCV; megaloblastic dysplasia
-Peripheral nerve degeneration
-Shillings test indicates low B12
-Gastric analysis reveals achlordydria (absence of hydrochloric acid in the gastric secretions)
-Megoblastic madness
What is the treatment for Anemia Related to Vitamin B12
(Cobalamin) or Folate Deficiency?
-B12: administer B12 parenterally or orally
and potassium supplements
-For folate: administer folic acid
What is sickle cell anemia?
Genetically determined defect of hemoglobin
synthesis resulting in hemoglobin instability and insolubility
What is the pathogenesis of sickle cell anemia?
- Sickled cells cause vascular occlusion
- Severe anemia, RBCs of different shapes and
sizes, recurrent painful episodes
Sickle cell anemia is common in who?
African American
What is the treatment of sickle cell anemia?
of choice is stem cell transplant (cures)
What is the prognosis of sickle cell anemia?
death if no/unsuccessful
transplant
What is hemolytic disease of the newborn?
Fetal RBCs cross placenta, stimulate
production of maternal antibodies against
Rh+ antigen on fetal RBC not inherited
from mother
(mother: Rh- blood type)
What happens when maternal antibodies cross in hemolytic disease of the newborn?
the fetal circulation causing destruction of fetal cells
-ABO incompatibility most common
-Rh incompatibility more clinically relevant
What is the treatment of hemolytic disease of the newborn?
- Standard dose of anti-Rh immune globulin
(RhoGAM) is given to the mother before or after delivery
-Severe cases, in utero blood transfusion and early
delivery
What is the prognosis of hemolytic disease of the newborn?
Death, possible retardation, or barely perceptible hemolytic process
What is hematopoiesis?
blood cell formation- stem cells---reticulocytes (erythroblasts)
--mature red blood cells (erythrocytes)
What is erythropoietin (EPO)?
hormone that stimulates RBC production
Where is erythropoietin (EPO) made?
adults - kidney
fetus/newborn - liver and kidney
-renal disease causes anemia
What are the functions and results of erythropoietin (EPO)?
Functions - bone marrow
Results - erythrocyte production
What are the nutritional requirements for Erythropoiesis?
adequate amounts of iron, protein,
vitamins, and minerals
How is the absorption of B12 in Erythropoiesis?
In small intestine requires intrinsic factor,
which is produced by the parietal cells of the stomach. (pernicious anemia—IF deficiency)
What does iron need in Erythropoiesis?
Hemoglobin
What does folate and b12 deficiencies lead to in Erythropoiesis?
impaired DNA
synthesis in erythroid cells because the vitamins are coenzymes of key reactions in cellular metabolism
Where is B12 stored?
liver
What happens in red cell destruction?
Intestinal bacteria convert conjugated bilirubin into
urobilinogen; excreted primarily in the stool but also in urine
What is vitamin k deficiency normal bleeding time?
...
What is pernicious anemia caused by?
deficiency of intrinsic factor (deficiency of vit B-12) [Show Less]