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characteristics of WBCs (5)
- contain nuclei and organelles
- do NOT contain hemoglobin
- help defend the body against pathogens
- removes toxins, wastes or abnormal or damaged cells
- reside mostly in lymphatic ststem, small amount in circulation
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characteristics of "circulating" WBCs (4)
- 1. can migrate out of the blood stream: can contact and adhere to vessel walls (margination), then squeeze between endothelial cells and enter surrounding tissue (diapedesis)
- 2. capable of amoeboid movement: gliding movement via the flow of cytoplasm into cellular processes; allows WBCs to move through endothelial lining
- 3. all are attracted to specific chemical stimuli: positive chemotaxis guides WBCs to invading pathogens, damaged tissues or other active WBCs
- 4. neutrophils, eosinophils, and monocytes are capable of phagocytosis: cell eating, surrounds and engulfs particles for destruction (never eat monkeys = phagocytes)
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when monocytes leave the blood stream and become actively phagocytic, they are called?
- macrophages
- same cell but different stages of maturity, not actively phagocytic until it leaves the bloodstream!
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see the differences between the WBCs:
focus on how the nucleus looks, size and whether they're grandulated or not
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what are the non-specific WBCs/leukocytes?
- 1. basophils
- 2. eosinophils
- 3. neutrophils
- 4. monocytes
- 5. lymphocytes (NK cells)
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what are the specific WBCs/leukocytes?
lymphocytes (T/B cells)
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which types of WBCs are classified as granulocytes?
- the "-phils"
- 1. basophils
- 2. eosinophils
- 3. neutrophils
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which types of WBCs are classified as phagocytes?
- "never eat monkeys"
- 1. neutrophils
- 2. eosinophils
- 3. monocytes
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neutrophils
-percent of circulating wbcs?
-describe nucleus?
-mobility?
-stain acidic/basic?
-lifespan?
-pus?
- 50-70% of circulating WBCs
- polymorphonuclear: contain a segmented nucleus: with 2-5 lobes
- highly mobile: first to arrive at injury site!
- neutral: doesn't stain with acidic or basic dye
- lifespan: SHORT!!! 10hrs-30mins if actively engulfing pathogens... dies after engulfing ~12-24 bacteria, but its breakdown releases chemicals that attract other neutrophils to that site
- pus: the combination of dead neutrophils, cellular debris and other waste products forms the pus associated with infected wounds
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neutrophils
-how does it attack pathogen?
- attacks and digests bacteria tagged with antibodies or complement proteins: use destructive chemicals such as hydrogen peroxide and superoxide anions to kill bacteria
- the engulfed pathogen fuses with LYSOSOMES in the neutrophil that contain digestive enzymes and defensins (small peptides) that can kill bacteria, fungi and some viruses
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neutrophil
-degranulation?
- the engulfed pathogen fuses with lysosomes in neutrophil that contain digestive enzymes and defensins that can kill bacteria, fungi and some viruses
- defensins: kill pathogens by combining to form large channels in their plasma membrane
- digestive enzymes: breakdown the remains of the pathogen
- called degranulation because it reduces the number of granules in the cytoplasm
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neutrophil
-what it releases when attacking bacteria?
- releases prostaglandins and leukotrienes when attacking bacteria
- prostaglandins: increase capillary permeability... this contributes to local inflammation and inhibits the spread of the injury and infection
- leukotrienes: attract other phagoyctes and help coordinate the immune response
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eosinophil
-% of circulating wbcs?
-stain?
-describe nucleus?
-allergens?
- 2-4% of circulating WBCs
- granules stain with red dye (eosin)
- bi-lobed nucleus
- similar in size to neutrophils
- acidophilic granules!!!
- responds to allergens by increasing in number
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eosinophil
-how does it attack pathogen?
- attacks bacteria, protozoa, or cellular debris that is coated with antibodiesit's first mode of attack is exocytosis of toxic compounds like nitric oxide and cytotoxic enzymes
- this makes these cells very effective against multicellular parasites that are too big for phagocytosis!!!
- responds to allergens by increase in number
- attracted to injury site and release enzymes that decrease inflammation and contain inflammation from spreading to adjacent tissue
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basophil
-% of circulating wbcs?
-stain?
-size?
-mobility?
- <1% of circulating WBCs
- contain numerous granules that stain with BASIC dyes
- smaller in size than neutrophils and eosinophils
- migrates to sites of injury, cross endothelium, accumulate in damaged vessels
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basophil
-doesn't phagocytose... so how does it target pathogen???
- discharge granules into interstitial fluids that contain HISTAMINE AND HEPARIN which enhances local inflammation
- histamine: dilates blood vessels
- heparin: prevents blood clotting
- releases other chemicals to attract eosinophils and other basophils to the area
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monocytes
-% of circulating wbcs?
-size and nucleus?
- 2-8% of circulating wbcs
- very large spherical shaped WBC, large oval or KIDNEY bean shaped nucleus
- usually double the size of RBC
- enters circulation for 24 hours, then enters peripheral tissue
- at peripheral tissue... matures and becomes phagocytes (macrophages)
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monocytes
-how does it attack pathogen?
- aggresive phagocytes, can engulf large items
- also release chemicals to attract and stimulate neutrophils, monocytes and other phagocytic cells
- can engulf things that the the same size or larger
- secrete substances that attract fibroblast into the region --> these produce scar tissue, wall of the area to help stop inflammation from spreading
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lymphocytes
-% of circulating wbcs?
-size, nucleus?
-location?
- 20-30% of circulating wbcs
- contain a large round nucleus surrounded by a thin halo of cytoplasm
- migrates thorugh the bloodstream, peripheral tissues and back to the bloodstream
- most lymphocytes are located in lymphatic system or connective tissue, not circulation
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what are the 3 types of lymphocytes?
- 1. T cells: cell mediated immunity & coordination of immune response
- 2. B cells: humoral or antibody mediated immunity
- 3. Natural Killer (NK) cells: immunological surveilance
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T cells
-what kind of immunity?
-specific/nonspecific?
-direct/indirect?
-types?
- cell mediated immunity and coordination of immune resoponse
- specific defense against invading foreign cells and tissues
- T cells can enter peripheral tissues & attack foreign cell directly or modulate the activity of other lymphocytes
- types: cytotoxic, helper and suppressor T cells
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B cells
-what kind of immunity?
-specific/nonspecific?
-what happens when activated?
- humoral or antibody mediated immunity
- specific defense
- activated B cells differentiate into plasma cells which produces large amounts of ANTIBODIES
- antibodies can be produces in one location by plasma cells and destroy antigens almost anywhere in the body
- once the antibody gets into the bloodstream, it can go anywhere
- benefit compared to T cell which acts directly on the tissue/cell!!!
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natural killer (nk) cells
-function?
-specific/nonspecific?
- NONspecific defense
- important in detection and destruction of abnormal tissue cells, preventing cancer
- recognizes ANY abnormal tissue cell and destroy it before it can replicate
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WBC summary: neutrophil
-abundance?
-appearance?
-functions?
- abundance: 50-70%
- appearance: round cell, nucleus lobed and may resemble a string of beads, cytoplasm contains large, pale inclusions
- function: phagocytic... engulfs pathogens or debris in tissues, release cytotoxic enzymes and chemicals
- (in class notes... pathogen tagged with antigen or complement)
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WBC summary: eosinophil
-abundance?
-appearance?
-functions?
- abundance: 2-4%
- appearance: round cell, nuleus generally in two lobes, cytoplasm contains large granules that generally stain bright red
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WBC summary: basophil
-abundance?
-appearance?
-functions?
- abundance: <1%
- appearance: round cell, nucleus generally cannot be seen though dense, blue stain granules in cytoplasm
- function: enter damaged tissues and release histamine and other chemicals that PROMOTE inflammation
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WBC summary: monocytes
-abundance?
-appearance?
-functions?
- abundance: 2-8%
- appearance: very large cell, kidney bean shaped nucleus; abundant pale cytoplasm
- function: enter tissues to become macrophages... engulf pathogens or debris
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WBC summary: lymphocytes
-abundance?
-appearance?
-functions?
- abundance: 20-30%
- appearance: generally round cell, slightly larger than RBC, round nucleus, very little cytoplasm
- cells of lymphatic system, providing defense against specific pathogens or toxins
- survives from months to decades, circulate from blood to tissues and back
- produced from bone marrow AND lymphoid
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what stem cells give rise to WBCs?
- myeloid stem cells: give rise to basophils, eosinophils, neutrophils and monocytes
- lymphoid stem cells: give rise to lymphocytes
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regulation by stimulating cofactors (CSFs)
- CSFs stimulate production of specific types of WBCs
- M-CSF: stimulates production of Monocytes
- G-CSF: stimulates production of Granulocytes
- GM-CSF: stimulates production of both Granulocytes and Monocytes
- Multi-CSF: accelerates the production of granulocytes, monocytes, platelets and RBCs
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filgrastin (NEUPOGEN)
- genetically engineered form of G-CSF
- given to chemotherapy patients to stimulate production of neutrophils (=granulocyte)
- NEU-pogen to make NEU-trophils!!! =)
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WBC production pathway:
- hemocytoblasts --> myeloid stem cells --> progenitor cells --> blast cells (myeloblast which makes B-E-N and monoblast which makes monocyte) --> myelocytes --> band cells --> WBCs
- notice where the CSFs are stimulating!!!
- G-CSF - stilumates myeloblast (blast cell)
- M-CSF - stimulates monoblast (blast cell)
- GM-CSF - stimulates progenitor cells (becomes myeloblast or monoblast)
- Mutli-CSF - stimulates myeloid stem cells (because it makes everything besides lymphocytes so NOT lymphoid stem cells)
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difference between leukopenia, leukocytosis and leukemia?
- leukopenia: decrease in # of WBCs
- leukocytosis: increase in # of WBCs, normal during an infection
- leukemia: EXTREME leukocytosis, abnormal non functioning WBCs
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difference between myeloid leukemia and lympoid leukemia?
- myeloid: cancer of the cells of the bone marrow
- lymphod: cancer of the lymphocytes
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difference between acute leukemia and chronic leukemia?
- acute: short & severe; formation of non-functional cells and blast cells; multiplying of these cells crowd out other bone marrow cells and results in anemia and thrombocytopenia (low platelets)... linked to radiation exposure, hereditary susceptibility, viral infections, or unknown causes
- chronic: prolonged; few to no blast cells; increase in number of WBCs can cause a decrease in blood flow and anemia; excess lymphocytes can crowd out regular lymphoicytes and weaken the immune system... related to acquired chromosomal abnormalities in cancerous cells or immune system malfunctions
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what are the 4 main types of leukemia?
- ALL, CLL, AML and CML
- first letter = acute or chronic
- 2nd letter = myeloid or lymphoid
- last = leukemia
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acute lymphoid leukemia (ALL) vs acute myeloid leukemia (AML)
- ALL:
- most common in children (under 15)
- when detected early 85-90% of patients held in remission for 5 years or longer
- AML:
- only 10-15% survive 5 yrs or longer
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hormones of the immune system: cytokines
- allow communication
- act as autocrine and paracrine factors and as hormones
- can stimulate cells to proliferate, differentiate (turn into another cell type), activate (become pro inflammatory), deactivate (anti-inflammatory), die (apoptosis)
- just a reminder:
- autocrine: a cell secretes something that affects itself
- paracrine: a cell secretes something that affects adjacent cells
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hormones of the immune system: interleukins (a type of cytokine)
- produced primarily by lymphocytes and macrophages (IL-1 is also produced by endothelial cells, fibroblasts and astrocytes)
- increase T cell sensitivity to antigens exposed on macrophage surfaces (leads to increase production of T cells)
- enhances non specific defenses: stimulation of inflammation, formation of scar tissue by fibroblast, increase body temp, increase mast cell formation (mast cell involved in immune response, tissue repair and angiogenesis), promotion of ACTH secretion, moderating the immune response
- stimulates B cell activity, plasma cell formation and antibody production
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which interluekin plays a role in prostaglandin synthesis... and using a drug to block this can be used in treatment for rheumatoid arthritis?
interleukin-1
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which interleukin stimulates growth and activation of T cells & NK cells.. can be used as cancer drug to boost the immune system?
IL-2: aldesleukin
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which interleukin can be used to treat chemotherapy-induced thrombocytopenia?
IL-11: oprelvekin (Neumega)
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hormones of the immune system: interferons
-function?
-how are they used to treat cancers?
- function: involved in slowing the spread of a virus... another cytokine
- cancer: bec they stimulate NK cell activity... can be used to treat cancer
- ex. alpha-interferons used to treat malignant malinoma, bladder cancer, ovarian cancer, two types of leukemia... beta-interferons used to treat multiple sclerosis... etc
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what are the 3 types of interferons?
- alpha: attract and stimulate NK cells
- beta: slow the progression of inflammation associated with viral infections
- gamma: attract and stimulate NK cells, stimulate macrophages (makes them more efficient at killing bacterial or fungal pathogens)
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hormones of the immune system: tumor necrosis factors (TNFs)
- slow growth of tumor and kill sensitive tumor cells
- produced by activated macrophages and cytotoxic t cells
- also stimulates granular leukocyte production, increase eosinophil activity, causes fever, increase T cell sensitivity to interleukins
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hormones of the immune system: colony stimulating factors (CSFs)
- remember... G-CSF, M-CSF, GM-CSF and multi-CSF
- produced by active T cells, monocyte/macrophages, endothelial cells and fibroblasts
- stimulates production of blood cells in bone marrow
- stimulates production of lymphocytes in lyphoid tissues and organs
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