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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?
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
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?
what is the requirment of pavemeting?
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?
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
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
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
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
-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