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28 Cards in this Set

  • Front
  • Back

types of leukocytes

-granulocytes


-agranulocytes

granulocytes

-aka myeloid cells


-contain an irregular-shaped, lobed nucleus and permanent cytoplasmic granules


-classified according to the staining properties of their granules


-inflammatory cells


-aid in direction of adaptive immunity


-types: PMNs; eosinophils; basophils

agranulocytes

-cytoplasmic granulation may often be seen, but is not a permanent feature of this cell class


-types: lymphocytes; monocytes; macrophages

neutrophils

-55-70% of the total circulating WBC pool


-contain 3 types of cytoplasmic granules: primary or azurophilic; secondary/specific/definitive; teritary


-phagocytose bacteria


-chief cell of acute inflammation


-migrate from blood in response to signals; transendotheilial migration involves complex interactions


-short lifespan (6-8hrs in circulation)


-engage in a single phagocytosis --> materials in vacuoles cannot be neutralized and degraded unless these agents are first killed


-neutrophils are cleared by macrophages


-dead PMNs make pus

primary or azurophilic granules

-component of PMNs


-lysosomal granules that contain antimicrobial compounds including myeloperoxidase


-account for 1/3 of the granulae


-following phagocytosis they fuse with endoosome or phagosome to kill and digest

secondary/specific/definitve granules

-component of PMNs


-non-lysosomal granules that do not stain basic or acidically


-contains NADPH-oxidase subunits and MMPs


-some fuse, but most appear to secrete their contents into the extracellular space

tertiary granules

-component of PMNs


-contain gelatinase (MMP-9)

eosinophils

-2-5% of total circulating leukocytes


-conspicuous acidophilic granules


-degrade parasites (this MPO and cationic proteins seem to be effective in lysis of parasites


-modulate inflammatory response (this role is not clear or well-established; they are recruited to sites of allergic reaction, but no direct evidence that they regulate)

basophils

-least numerous circulating leukocytes


-tissue resident counterpart is mast cell


-involved in hypersensitivity reaction


-basophilic granules contain: heparin, histamine


-express receptors for IgE antibodies


-following initial exposure to an antigen and antibody production, reexposure triggers binding the antigen to IgE-IgE receptor complexes and release of granules

lymphocytes

-20-35% of circulating leukocytes


-cooperate to form the basis of adaptive immune response


-two classes: T and B cells

B cells

-responsible for humoral immunity, the cellular basis of which is the maturation of a B cell into a plasma cell in response to a specific antigen


-then produces and secretes an antibody Ig

T cells

-basis of cell-mediated immunity

monocytes

-3-8% of the circulating leukocytes


-two distinct subsets; called in waves


-first wave: inflammatory monocyte CD14+ (clear damage in pro-inflammatory phase)


-second wave: CD16+ heal the wound and resolve inflammation


-once in the tissue the monocytes differentiate into macrophages

macrophages

-longer lifetime than neutrophils


-probably engage in several phagocytotic events


-tissue macrophages include: sinus-lining cells of: lymph sinuses, splenic sinuses, marrow sinuses, levnous sinuses of the liver; histocytes; microglia of CNS; alveolar macrophages; foreign body giant cells; epidermal langerhans cells

functions of macrophages

-phagocytosis


-scavengers: rid the body of worn-out cells and debris; important in development


-antigen presenting cells: crucial in initiation and direction of adaptive immunity


-secretory cells: produce enzymes, complement proteins, and regulatory factors such as interleukin-1 that regulate other cells at the site of injury or infection

consequences of respiratory burst

-increased O2 consumption


-production of superoxide


-production of H2O2 and other ROS

respiratory burst

-membrane bound components = flavocytochrome b


-the other 3 subunits are cytosolic until it's activated


-assembles into NADPH oxidase, which created superoxide

NADPH oxidase

produces superoxide


-mutation in this enzyme inhibits the production of reactive oxidants

superoxide dismutase

produces H2O2

myeloperoxidase

breaks down H2O2 to hypochloric acid

leukocyte migration

-controlled movement of leukocyte through the body


-regulates immune response by promoting proper cell positioning and cell-cell interactions


-also called trafficking, extravasation, diapedesis, recruitment, and homing


-takes place in post capillary venules

control of inflammation

-cell adhesion molecules and chemokines expressed by endothelial cells and leukocytes that regulate migration into and out of tissues


-four families of CAMs: mucin-like CAM and integrins on leukocytes, selectins and Ig-superfamily CAMs on endothelial cells


-selectins <--> mucin-like CAMs


-integrins <--> Ig-superfamily CAMs


-chemokines are small molecule chemoattractants that interact with G-protein coupled receptors

mechanisms of trafficking

-patterns and mechanisms are similar


-best characterized example is neutrophil trafficking in response to injury

multi-step model of leukocyte trafficking

-resident macrophage recognize invader (pattern recognition)


-secrete cytokines that activate endothelial cells


-selectin vesicles in endothelial cells fuse and tether leukocytes causing them to roll (tethering and rolling)


-inflammatory cytokines also initiate transcription of other adhesion molecules (arrest and adhesion)


-transendothelial migration


-steps are overlapping and combinatorial


-specificity and diversity in migration is due to diversity in adhesion molecules and chemokines

tethering and rolling

-selectin-mediated adhesion is very weak interactions so it's catch and release --> allow rolling

activation, arrest, and adhesion

-chemokines are presented by endothelium and interact with their receptor (outside in signaling)


-selectin enables chemokine receptors on the neutrophil to come into contact with chemokines


-integrins on neutrophils are then activated (inside out signaling)


-integrins bond with IgSF-CAM --> even more interactions with endothelium

transendothelial migration

-takes ~90 seconds


-leukocyte extends across endothelial junctions (adhestion molecule zipper)


-some exit through the cells


-vascular integrity is maintained

perivascular regulation of neutrophil egress

-basement membrane: protective meshwork


-perivascular macrophages and mast cells: elicit chemokines to sustain neutrophil attraction


-pericytes: embedded in basement membrane


-once through endothelium, PMNs migrate to gaps between pericytes (integrin dependent)


-preferential sites