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Blood: Leukocytes, Granulocytes, etc
Resistance of the Body to Infection I: Leukocytes, Granulocytes, the Monocyte-Macrophage System, and Inflammation
63
Physiology
Graduate
04/01/2012

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Term
What is the first line of defense against foreign invaders?
Definition
skin
Term
What is MALT? Where is it found?
Definition
1. mucosal-associated lymphoid tissue
2. the respiratory, digestive, and urogenital tracts
Term
What is the function of M cells? Where are they located? What is the mechanism of their funnction?
Definition
1. they transport antigens to lymphoid cells
2. in between microvilli-containing epithelia
3. they have a basolateral cleft in which macrophages and other immune cells reside and are introduced to the invading bacteria
Term
What are physiological barriers that help the body resist infection? Explain how they would help.
Definition
a. temperature - the high normal body temperature and fever temperatures that the body can develop are poor environments for most bacteria to grow; temperature is partially regulated by pyrogens (which can be exogenous or endogenous)
b. low pH - many bacterial cannot survive in low pH areas, such as in the stomach or the vagina
c. chemical mediators - lysosomes, interferons (anti-viral), and complement proteins (anti-bacterial)
Term
What physiological barrier appears when tissue is damaged/infected? How can it help prevent infection?
Definition
1. inflammation
2. it will induce leakage of vascular fluid with antibacterial properties and influx phagocytes to the areas
Term
What is the mechanism of inflammation?
Definition
tissue is damaged, releasing histamine and increasing blood flow to the area; histamines cause capillaries to leak, releasing phagocytes and clotting factors to the area; phagocytes engulf the bacteria, dead cells, and debris; platelets move out of the capillaries to seal off the wounded area
Term
What are signs of inflammation? What physiological response occur during inflammation?
Definition
1. rubor (redness), tumor (swelling), calor (heat), dolar (pain, functio laesa (loss of function)
2. vasodilation, increased capillary permeability, and phagocyte influx
Term
What are the types of leukocytes? Which is the most common type? What is the most common leukocyte? Where are they made/matured?
Definition
1. a. granulocytes: neutrophils, basophils, eosinophils
b. non-granulocytes - monocytes and lymphocytes
c. polymorphonuclear - all granulocytes
d. mononuclear - all non-granulocytes
e. phagocytes - neutrophils, monocytes, eosinophils, macrophages
f. non-phagocytes - lymphocytes and basophils
2. granulocytes
3. neutrophils
4. all are made in the bone marrow; lymphocytes mature in the lymph tissue and monocytes turn into macrophages in their respective tissues
Term
What are the qualities of the following cells: neutrophils, monocytes, macrophages, dendritic cells?
Definition
1. non-dividing, short-lived, and most common WBC in the blood
2. long-lived, do not circulate, present in tissues
3. "professional" antigen-presenting cells, activate helper T cells (CD4+)
Term
What are the names for tissue-specific macrophages for the follow tissues: lungs, connective tissue, liver, kidneys, brain, bone, and lymph system?
Definition
1. alveolar macrophages
2. histiocytes
3. kupffer cells
4. mesangial cells
5. microglia
6. osteoclasts
7. dendritic cells
Term
Define: polymorphonuclear, granulocytes, phagocytes
Definition
1. having multiple nuclei/with multiple possible nuclear shapes
2. cells that have granules in them
3. cells that are able to phagocytize/"eat" debris or invading cells
Term
How long does it take neutrophils to live and where do they develop?
Definition
9-10 days: 2-3 days in the bone marrow and 5-7 days in maturation and storage in the bone marrow until need
Term
How can platelets help with immune response?
Definition
they can form clots to wall off an area from the rest of the body or suspend invading debris/bacteria in the clots
Term
What are the major cell lineages from a blood stem cell?
Definition
myeloid, lymphoid, and RBC
Term
How often are the following cells replaced: neutrophils, monocytes, lymphocytes, platelets?
Definition
1. varies; may be up to 5 after being released from the bone marrow or as little as a few hours, depending on how quickly and intensely they perform their functions
2. as monocytes, they will only last 10-20 hours before they wander into tissues and differentiate into macrophages; as macrophages they can last months
3. these can last weeks to months as they circulate through the blood, through the tissues, through the lymph, and back through the blood continuously
4. about every 10 days
Term
What is the method by which WBCs move out of blood vessels? The method by which they move through tissues? The process by which they are attracted to inflamed tissue areas?
Definition
1. diapedesis - WBCs squeeze through the capillary pore
2. ameboid motion
3. chemotaxis
Term
What are some chemicals that attract WBCs to an inflamed area?
Definition
bacterial or viral toxins, degenerative products of the inflamed tissues, reaction products of the "complement complex", and reaction products causes by plasma clotting
Term
What are methods of oxygen-dependent microbe killing WBCs can use?
Definition
reactive O2 used in superoxide, hydroxyl radical, hydrogen peroxide, and hypochlorite anion or reaction N used in nitric oxide, nitrogen dioxide, and nitrous acid
Term
What are methods of oxygen-independent microbe killing WBCs can use?
Definition
defensins, TNFα, lysozyme, and hydrolytic enzymes
Term
What is margination?
Definition
the method by which phagocytes move through the blood vessels; it involves rolling while associating to ICAMs and PECAMs
Term
What is the process by which a phagocyte presents an antigen?
Definition
the invading substance binds to the macrophage and is engulfed, undergoes phagocytosis including proteolysis and lysosome fusion, the phagosome membrane is disrupted and part of the material is presented on an MHC II receptor on the cell surface
Term
How is the monocyte-macrophage system involve in: iron metabolism, CSFs, osteoclasts, atherosclerosis?
Definition
1. macrophages can store iron
2. macrophages can produce CSF
3. monocytes are precursors to osteoclasts
4. foam cells are macrophages
Term
What are the local effects of the following cytokines: IL-1, TNF-α?
Definition
1. activates vascular endothelium and lymphocytes; can cause destruction of local tissue; increases access of effector cells
2. activates vascular endothelium and increases vascular permeability, which leads to increased entry of igG, complement, and cells to tissues and increased fluid drainage to lymph nodes
Term
What are the local effects of the following cytokines: IL-6, IL-8, IL-12?
Definition
1. lymphocyte activation and increased antibody production
2. chemotactic factor recruits neutrophils, basophils, and T cells to the site of infection
3. activates NK cells, induces differentiation of CD4 T cells and TH1 cells
Term
What are the systemic effects of the following cytokines: IL-1, TNF-α, IL-6, IL-8, IL-12?
Definition
1. fever and production of IL-6
2. fever, mobilization of metabolites, and shock
3. fever and inducement of acute-phase protein production
4. none
5. none
Term
What substances are involved in the inflammation process?
Definition
bradykinin, histamine, serotonin, complement, coagulation factors, and lymphokines
Term
How can local acute inflammation cause systemic response?
Definition
IL-1, IL-6, and TNF-α can be released, which stimulate the hypothalamus to release prostaglandins to induce fever and ACTH to stimulate the adrenal cortex to release glucocorticoids; inflammation also causes the release of LIF and OSM which, together with IL-1, IL-6, and TNF-α, can stimulate the liver to release C-reactive protein, fibrinogen, and complement proteins; glucocorticoids can also elicit this response from the liver; lastly, IL-6 and TNF-α can cause the bones to increase CSF, which will cause leukocytosis
Term
How can an activated macrophage stimulate bone marrow to produce granulocytes and monocytes?
Definition
the macrophage can release TNF, IL-1, GM-CSF, G-CSF, and M-CSF, which stimulate the bone marrow directly; also, TNF and IL-1 stimulate the endothelial cells, fibroblasts, and lymphocytes to release GM-CSF, G-CSF, and M-CSF, which will stimulate the bone marrow
Term
What immune responses do the following cytokines cause: IL-1, IL-6 with TNF-α, complement proteins?
Definition
1. inflammation and fever
2. innate immunity and elimination of pathogens
3. inflammation and elimination of pathogens
Term
What immune response do the following cytokines cause: INF-α, TNF-α, GM-CSF, G-CSF, and M-CSF?
Definition
1. antiviral proteins
2. antitumor effects
3. promotes hematopoiesis
4. promotes hematopoiesis
5. promotes hematopoiesis
Term
What are the cellular responses to inflammation?
Definition
tissue macrophage activity, neutrophil invasion, macrophage proliferation, and stimulation of granulocyte and monocyte production (by TNF, IL-1, and CSF)
Term
How can apoptosis contribute to chemotaxis?
Definition
in apoptosis, the cell membrane can be turned inside out and phosphotidyl serine, which is normally an integral protein exposed to the ICF, is exposed to the ECF and acts as a chemoattractant
Term
What factors can increase the probability of phagocytosis?
Definition
rough surfaces, the lack of protein coating (which exists on body cells), or antibodies on the surface
Term
What cells release pyrogens?
Definition
macrophags
Term
Which is the more powerful phagocyte: a neutrophil or a macrophage? What makes it more capable?
Definition
1. a macrophage
2. macrophages can phagocytize 5-30 times more bacteria and can phagocytize large particles compare to neutrophils; also, macrophages possess lipases to digest thick lipid membranes of certain bacteria
Term
Why do phagocytes contain bactericidal agents if they can phagocytize bacteria?
Definition
1. some bacteria have protective coats or other factors that resist digestive enzymes
Term
What bacteria is responsible for tuberculosis? Why is it so resistant to destruction?
Definition
1. tuberculosis bacillus
2. it has a coating that is resistant to lysosomal digestion and also secretes substances that partially resist the bactericidal agents
Term
What is the reticuloendothelial system?
Definition
the combination of the monocytes, the mobile macrophages, the fixed macrophages, and a few specialized cells in the bone marrow, spleen, and lymph nodes; it is sometimes used synonymously with the monocyte-macrophage system because almost all these cells originate from monocytes
Term
Define: neutrophilia, leukopenia, neutropenia
Definition
1. the acute increase in neutrophil count in the blood (released from the bone marrow)
2. a decreased in the number of leukocytes
3. decreased number of neutrophils
Term
What are the lines of defense in inflammaion?
Definition
1st: tissue macrophages
2nd: invading neutrophils
3rd: invading monocytes, which will eventually mature into macrophages
4th: production of granulocytes and monocytes by the bone marrow
Term
What is the function of eosinophils? Basophils?
Definition
1. attack parasites, skin diseases, and chronic infections; they are phagocytic and immunomodulatory and they decrease infection
2. similar to mast cells (which contain granules of histamine, sometimes bradykinin, and some other chemicals); they release histamine (and other chemicals) in response to binding to IgE
Term
What are mast cells? What is their function?
Definition
1. resident granule-containing cells found in connective tissue in organs andmucosal epithelia of the respiratory, genital, and digestive tracts
2. release histamine in response to allergens and work with basophils in the development of allergies
Term
What are possible causes of leukopenia? What can occur with leukopenia?
Definition
1. irradiation, exposure to benzene or antracene-containing chemicals, chloramphenicol, thiouracil
2. aside from increased risk of infection, normal bacterial flora increases and can cause mouth and colon ulcers within 2 days and; respiratory and urogenital infections may occur
Term
What are possible causes of neutropenia?
Definition
decreased production (possibly from chemical toxicity or stem cell disorders), ineffective granulopoiesis, increased margination to peripheral pools, increased neutrophil destruction (possibly from chronic infections or immune mechanisms)
Term
What are possible congenital causes of neutropenia?
Definition
Kostmann syndrome (severe congenital neutropenia), cyclic neutropenia, familial benign neutropenia, Diamond-Blackfan syndrome, Schwachman-Diamond syndrome, Chediak-Higashi syndrome, glycogen storage disease type 1b, fanconi anemia; neutropenia may also be common in certain races; African-Americans are more likely to have neutropenia; however, some races, including Jews, have naturally low neutrophil levels, so that must be considered
Term
What are possible acquired causes of neutropenia?
Definition
acute leukemia, myelodysplastic syndrome, chronic lymphocytic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, aplastic anemia, chronic idiopathic neutropenia, drug toxicity, certain types of infections, SLE (systemic lupus erythematosus, RA, and a deficiency of copper, B12, or folate
Term
Where are complement proteins produced?
Definition
the liver
Term
What are UCPs?
Definition
thermogenic proteins that maintain body heat in cold temperatures
Term
What are possible causes of leukocytosis?
Definition
bone marrow response to infection, inflammation (necrosis, infarction, burns, arthritis), stress (overexertion, seizures, anxiety, anesthesia), drugs (corticosteroids, lithium, beta-agonists), trauma (splenectomy, hemolytic anemia, leukemoid malignancy), or abnormal bone marrow (acute and chronic leukemias, myeloproliferation disorders)
Term
What are possible types of leukocytosis?
Definition
neutrophilia, eosinophilia, basophilia, monocytosis
Term
What are possible causes of primary neutrophilia? Secondary neutrophilia?
Definition
1. myeloproliferative disorders, leukocyte adhesion deficiency, CML (chronic myelogenous leukemia), Down syndrome
2. infection, smoking, sickle cell disease, stress, metastasis to bone marrow
Term
What are possible causes of primary eosinophilia? Secondary eosinophilia?
Definition
1. leukemias or hypereosinophilic syndrome
2. allergies, parasites, infections (scarlet fever, leprosy, genitourinary tract), autoimmune (RA, lupus), lymphomas, CML, polycythemia vera, adrenal insufficiency
Term
What are possible causes of basophilia? Monocytosis?
Definition
1. chronic inflammation from TB or ulcerative colitis, or CML
2. infections: TB or other bacteria, or CML
Term
What are defining characteristics of lymphocytic leukemia? Myelogenous leukemia? What is the consequence of leukemia?
Definition
1. it includes cancerous lymphocytes and begins in lymphoid tissues and spreads to others
2. it includes cancerous myeloblasts and begins in the bone marrow and spreads from there; if cells are partly differentiated, one can distinguish what kind of cell it originates from, which can be more helpful for treatment (this occurs mostly with chronic leukemias)
3. leukemic cells are non-functional immune cells; this can cause persistent infections, anemia, thrombocytopenia, and cachexia
Term
What are normal neutrophil numbers? Lymphocyte numbers?
Definition
1. 1.8-7.7 X 10^9 cells/L
2. 1.2-3.3 X 10^9 cells/L; 80% should be T cells and 20% B cells; 60% of the T cells should be helper T cells
Term
What are the qualities of type 1 macrophages? Type 2?
Definition
1. inflammatory; have ROS, MMP, and cytokines to attract B and T cells; they can also lyse tumor cells
2. anti-inflammatory; produce angiogenic factors, secrete mitogens, immunosuppressant factors, and ROS
Term
Where does the massive number of neutrophils that invade tissues during infection come from?
Definition
about 3X as many neutrophils in the blood are stored in the marrow for use
Term
What is the most cause of neutropenia: acquired or congenital?
Definition
acquired
Term
What is ANC? How is it calculated?
Definition
1. absolute neutrophil count
2. ANC = % neutrophils X total WBC
Term
How is lymphopenia acquired?
Definition
immunosuppressants, certain types of infections, chronic diseases (hepatitis, renal insuficiency), autoimmune disease (HIV), and a few congenital forms (severe combined immunodeficiency disorder, congenital thymic aplasia, and X-linked agammagobulinemia
Term
How do Hodgkin's and non-Hodgkin's lymphomas vary in causes and variety?
Definition
Hodgkin's arises in B cells and has about 5 subtypes
Non-Hodgkin's arises in either B cells or T cells and has about 30 subtypes
Term
What is the difference between acute and chronic leukemia with regard to origin of the leukemia? How about the difference between who they affect?
Definition
1. acute leukemia originate in WBCs that are not yet differentiated; chronic usually occurs in WBCs that have differentiated enough for us to tell what kind of cell it will become
2. acute leukemia is more common in children
Term
What is the most common type of blood cancer?
Definition
lymphomas
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