Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
79 Cards in this Set
- Front
- Back
what options do haematopoietic stem cells have?
|
1. self-renewal
2. commence down one of the many pathways of maturation to eventually produce mature blood cells. |
|
what are morphological features of neutrophils?
|
-multilobed nucleus
-pale clear to eosinophilic cytoplasm -small (10-12 mu in diameter) |
|
which blood cell will arrive first at sites of injury? and where does it come from?
|
Neutrophils
from blood vessels |
|
What is meant by chemotaxis?
|
the directional locomotion of phagocytes toward an inflammatory stimulus
|
|
What does chemotaxis require to induce motion of phagocytes?
|
energy, Ca2+, and actin-myosin bridging of the cell cytoskeleton
|
|
What can be chematoctic factors for neutrophils?
|
1. complement fragments (C3a and C5a)
2. Bacterial and viral products especially small peptides (FMLP) 3. Immune complexes 4.Kallikein (血漿からキニンを遊離させる酵素) 5.Plasminogen activator 6.Platelet factor 4 7.Fibrin spli products 8.Collagen fragments 9.Oxidized membrane lipids 10.Leukotriene B4 |
|
What kind of tests are available to examine chemataxin?
|
Examine migration under agarose with and without chematoctic factors.
Boyden chambers test |
|
Why are nutrophils good little Kamikaze's in the body defense system?
|
1. highly mobile
2. very active phagocyte 3. powerful microbiocidal machinery |
|
Descirbe steps of neutrophil migration
|
1.margination in capillary beds(はしにくっつく)
2.emigration from vessels 3.chemotaxis 4.phagocytosis 5.intracellular activation 6.degradation of material within phagolysosomes |
|
What makes blood flow slowing during pavementing process?
|
by a combination of vasodilation and fluid loss from leaky vessels as a consequence of the effects of chemical mediators of inflammation
|
|
is pavemeting reversible or not?
|
reversible
|
|
what is the requirment of pavemeting?
|
Ca2+
|
|
what influences the pavementing process?
|
inflammatory mediators
|
|
what molecules plays a major role in the pavementing process for neutrophils?
|
adhesion molecules such as the selectins play
|
|
What does migration of cells during emigration cause?
|
vascular leakage
|
|
What does chemotactic stimuli result in?
|
-binding at cell surface receptors
-production of oriented cell membrane depolarization -activation of cell cytosolic contractile filaments |
|
What is a requirement for phagocytosis?
|
energy
|
|
Can neutrophils phagocyte in hypoxic environment?
|
yes. neutrophils have pathways for anaerobic glycolysis
|
|
Can neutrophils effectively kill bacteria, fungi, protozoa, and virus?
|
yes except viruses
|
|
What process can make phagocytosis more efficeint?
|
opsonization by opsonins (antibody, complement C3b, lysozyme, certain peptides)
|
|
What can phagocytosis by neutrophils lead to?
|
1.metabolism of archidonic acid
→ chemoattractans production, vasolidation, increased vascular permeability, vasocontriction, platelal aggregation etc. 2. Respiratory burst and oxygen radical generation 3. Degranulation |
|
Aranchidonic acid is metabolized to a variety of lipid mediatros.
What are they? and What do they cause? |
1.Prostaglandidn E2(PGE2) & prostacyclin (PGI2) → vasodilation & increase in vasopermeability
2.HETE's and leukotrience B4 → chemoattractants 3. Thronboxanes → vasocontriction & platelel aggregation |
|
Why does steroid is a more effective anti-inflammatory agent than aspirin and indomethacin?
|
Steroid inhibits phospholipase which is the very fist enzyme of arachidonic acid metabolism.
Aspirin & indomethacin inhibit cycloozygenase which catalyzes arachidonic acid → prostaglanding G2 reaction. Thus only formation of prostaglandin is inhibit, not formation of HPTE's. |
|
What does internalization of membrane-bound NADPH-oxidase into the phagosome lead to?
|
-generation of superoxide ion O2-
→ metabolized into more toxic oxygen rerived free radicals (H2O2, hydrozyl radical) if reacted with -myeloperocidase, produce hypohalide acids |
|
What factors are associated with the respiratory burst?
|
1.rapid uptake of oxygen
2.utilization of glucose 3.production of oxygen-derived free radicals 4.chemilumenescence(化学反応において生ずる低温発光現象) |
|
What types of granules do neutrophils contain?
|
1.Primary granules - myeloperoxidase, lysozyme, proteases, and hydrolytic enzymes
2.Secondary granules - aklaline phosphatase, lysozme, vitamin B12 binding protein, lactoferrin |
|
What is the name of disease which is a poorly understood defect prevents lysosomal transport and fusion.
|
Chediak-Higashi syndrome
|
|
What is happening in animals with albino?
|
-melanin transport is affected
-platelets an neutrophils are abnormal |
|
What may operate synergistically (相乗的) to promote tissue destruction and microbiocidal activities?
|
Granule products and oxygen-derived free radicals
|
|
List possible neutrophil-mediated tissue injuries.
|
1.Lysosomal suicide
2.Frustrated phagocytosis 3.Regurgitation during feeding |
|
What is lysosomal suicide?
|
Phagocytized material may be toxic to the neutrophil. Rupture of phagolysozome results in cell death leading release of toxic compounds such as active enzymes and oxygen radicals into tissues
|
|
What is frustrated phagocytosis?
|
Phagocytic stimulus such as immune comples precipitates, fungal organisms, and goreign bodies is too large or too toxic for neutrophils to internalize it after attempting phagocytosis
|
|
What is meant by regurgitation during feeding?
|
Lysosomal fusion with the phagosome occurs prior to cell membrane closure allowing escape of contents into tissues
|
|
List 4 broad categories of cell adhesion olecules
|
1.the selectins
2.the integrins 3.the cadherins 4,immunoglobulin receptor family |
|
Where and when are selectins expressed? to what do they bind?
|
they are expressed on endothelial cells, platelets and leukocytes. They appear to be activated early in inflammatory processes
|
|
What do selectins responsible for?
|
for rolling phenomena and the initial steps of leukocyte margination in the inflammatory response
|
|
What do genetic defects in selectins result in?
|
lead to adhesion defects
|
|
What are the rolls of integrins?
|
-involved in cell/cell and cell/matrix interactions
-promote firm adhesion and escape from blood vessels -imp in the regulation of leukocyte migration into tissues |
|
When do neutrophils express the integrins?
|
after being exposed to chemotaxins
|
|
What does deficiency in leukocyte integrins result in?
|
in an inability to mount effective acute inflammatory responses
|
|
What are the example of integrin deficiency disease?
|
BLAD of Holsterins
|
|
What do cadherins responsible for?
|
for maintaining calcium-dependent cell/cell adhesion and normal embryogenesis and maintenance of surface contacts between cells in nerve, muscle and kidney tissues
|
|
What can cadherin dysfunction result in?
|
cell separation
immune-mediated skin disease spread of malignancies (悪性腫瘍) |
|
What do some immunoglobulin superfamily molecules serve as?
|
intercellular adhesion molecules (ICAM's) allowing homing of lymphocytes to particular tissue sites
|
|
List pahrmacolgic modulation of tissue injury
|
1.Corticosteroid
2.Free radical scavengers(掃除屋) - Aspirin, VitC etc 3.Granule enzyme inhibitors 4.Protease inhibitors 5.Cyclo-oxygenase inhibitors 6.Novel pharmaceuticals and antibodies |
|
How do corticosteroids modulate tissue injury?
|
-suppress membrane phospholipase
-reduction of free archidonic acid & its metabolites at sites of inflammation -inhibition of neutrophil pavementing in capillaries |
|
How does aspirin modulate tissue injury?
|
-As free radical scavengers, reduce toxic unwanted free radicals
-As cyclo-oxygenase inhibitors, suppress its pathway, and lower the local production of prostaglandins and thronboxanes which cause vasoconstriction and plateles aggregation |
|
List chemotactic factors of macrophages
|
1.Lymphokines such as macrophage activation factors → immobilize & activate monocytes
2.Ag-Ab complex 3.Complement 4.Bacterial peptide 5.Products from necrotic tissues 6.Neutrophil products |
|
List macrophage functions
|
1.Antimicrobial phagocytes
2.Removal of effete(活力を失った)/diseased cells 3.Lipid metabolism 4.Immunologic reactions |
|
Macrophages phagocyte poorly deformable and diseased RBC.
What happen to protein, membranes, haemoglobin, and iron fron the ingested RBC? |
Protein & membranes are degrade by proteolysis.
Porphyrin(Hgから得られるピロール無鉄誘導体)is split off the iron-porphyrin portion of haemoglobin iron is split off and bound to apoferritin(鉄と化合してフェリチンをつくる蛋白質)→taken up at sites of erythropoiesis |
|
Sometimes, brown granular pigment is found within macrophage. What is that? and why does it occur?
|
Hemosiderin (細胞内の鉄を含む暗黄色色素)
when the level of apoferritin is inadequate, iron is sequestered withing macrophage without being taken up. |
|
How iron overload is prevented?
|
By a mucosal block in iron uptake
|
|
How can you confirm presence of iron in tissues?
|
Stain the tissue by Perls prussian stain which stains iron in blue colour
|
|
What makes macrophage cytoplasmic foamy appearance?
|
ingested free lipids
|
|
What are macrophages responsible for in immunologic reaction?
|
presenting and processing of antigen to T-cells for the development of cell-mediaed and humoral immunity
|
|
Why are macrophages important in the initiation of repair process?
|
Since they are important source of metalloprotease, a group of zinc-dependent protease enzymes responsible for the remodelling of matrix and connective tissues following inflammatory events
|
|
What are giant cells?
|
Macrophage modifications (変化)
|
|
List types of giant cells
|
1.epithelioid cells
2.foreign body giant cells (multinucleate giant cells) 3.langhans giant cells (multinucleate) 4.touton giant cells (multinucleate) |
|
What are characteristic features of epithelioid cells?
|
-have an epithelial appearance
-enlarged oval nuclei -abundant pale eosinophilic cytoplasm(pinky) -↓phagocytosis ↑microbiocidal capacity -in systemic fungal and mycobacterial disease |
|
What are characteristic features of foreign body giant cells?
|
-capable of ingesting large particles
-Randomly scattered nuclei throughout the cytoplasm -engulf endogenous material such as bone, keratin, hair or exogenous material such as sutures(縫い糸) |
|
What are characteristic features of langhans giant cells?
|
-usually seen with epithelioid cells
-common in fungal and mycobacterial infections -distinctive appearance of up to 20nuclei placed peripherally in the cytoplasm -abundant cytoplasm, tends to be pale eosinophilic unless many mycobacteria present when it becomes greyish |
|
What does greyish cytoplasm of langhans giant cells indicate?
|
the presence of mycobacteria
|
|
What are characteristic features of Touton giant cells?
|
-often associated with fat break down
-have a ring of peripherally placed nuclei with foamy pale eosinophilic cytoplasm |
|
Why does cytoplasm of Touton giant cells have foamy appearance?
|
due to fat breakdown
|
|
List giant cells which are not macrophage derived
|
1.Osteoclasts → remodel bone
2.Epithelial giant cells → induced by certain viral infection & may have viral inclusion 3.Tumor giant cells - common in alignant connective tissue tumours 4.Megakaryocytes - multinucleate bone marrow cells that produce paltelets |
|
What are eosinophils responsible for?
|
-killing of parasites
-control of mast cell related events -motile, phagocytic cells |
|
What are morphological features of eosinophils?
|
-bilobed nucleus
-strongly eosinophilic (redish pink) cytoplasm due to the presence of eosinopil granules |
|
List eosinophil products
|
1.Sevrete PGE's - anti-inflammatory
2.Eosinophil granule products: -major basic protein -Antiheparin activity -Aryl surfatase B -Histaminase -Phospholipase D plus substances in neutrophils |
|
What is a distinctive structure of eosinophil lysosomes?
|
inner core of major basic protein and an outer matric of other enxymes
|
|
List eosinophil chemotaxis
|
1.ECF-A from mast cells
2.Ag-Ab complexes 3.other mast cell products such as histamine 4.neutrophil chemotactic factors |
|
When can eosinophilia (increase in eosinophilic) be seen?
|
in helminth(ぜん虫) parasitism & allergic condition
|
|
When can eosinopaenia (decrease in eosinophilic) be seen?
|
as a consequence of stress, corticosteroid administration
|
|
What do mast cells have important role in?
|
producing inflammatory mediateors which alter local blood flow and permeability to allow fluid leakage into tissues
|
|
What is the characteristic of mast cell granules?
|
-metachromatic using toluidine blue → with toluidine blue, true blue is altered to purple, magenta or red
-contain heparin, histamine, and serotonin -pale grey on H&E stain → looks poorly granular cytoplasm |
|
What is description of basophil?
|
small cell packed with dense basophilic granules of ten obscures(はっきりしない)nucleus
|
|
What are mast cell products?
|
1.preformed products stored in granules
-ECF-A: chemotactic for eosinophil -Histamin & serotonin: causes ↑vascular permeability & dilation & hypersecretion 2.Synthesized from stimulated cells -PAF:lipid mediator,platelet activation and wide spread proinflammatory effects -Arachidonic acid metabolites: diverse groups of lipids such as prostanoid, thromboxianes |
|
How can mast cell reactions be regulated?
|
by adrenergic and cholinergic influences
-adrenergic agonists:in the treatment of asthma and other allergies -Corticosteroids:reduce archidnate availability -Cromalin and nedocromil: stabilize mast cell membranes and used in preventative strategies |
|
What is the condition where there is cardiovascular collapse and systemic sings called? and why does it happen?
|
Anaphylaxis (過敏症、急激なショック症状)
the degranulation of mast cells is so intense that mast cell proucts begin to circulate |
|
Explain about atopy
|
-inherited disorder
-individual produce excessive IgE in response to antigens to which most individuals are tolerant -cause wheals(蕁麻疹), blisters(水ぶくれ), skin inflammation as primary changes -lead to chronic skin thickening and alopecia(脱毛) as secondary changes |