abbas chapter 2 Flashcards
phagocytes
neutrophils are most abundant - production of them increases with infection
monocytes also
blood cells recruited to site of infection - ingest tiniest microbes for intracellular killing
healthy neutrophil count
4000-10000/mm^3
with infection can get up to 20000
production stimulated by cytokines
neutrophils
ingest macrophages etc in blood and enter tissue and ingest more microbes
die within a few hours
migrate by binding endothelial adhesion molecules and in response to chemoattractants that are produced on encounter with microbes
healthy monocyte count
500-1000 mm^3
monocytes
migrate by binding endothelial adhesion molecules and in response to chemoattractants that are produced on encounter with microbes - macrophages in tissue release cytokines
also ingest microbes in blood and tissues but differentiate into macrophages in tissue
TNF and IL1
act on endothelium of small vessels at site of infection
released by macrophages
E and P selectin and phagocytes binding to endo cells
adhesion molecules expressed by endo cells
neutrophils and macrophages have surface carbs that loosely bind to these
blood causes them to roll => repeated bindings
chemokines expressed on endo cells cause phagocytes to increase integrin expression => eventually in firm binding
chemokines
released by endo cells to increase phagocyte binding and by macrophages
stimulate motility - encourage phagocytes to migrate into extravascular space
inflammation
caused by accumulation of leukocytes, vascular dilation, and increased vascular permeability
toll-like receptors
specific for different composition of microbes
when engaged => activation of transcription factor NF-kappaB
actions of macrophages and neutrophils
phagocytose microbes
recruit more macrophages and lymphocytes => granulomas
granulomas
collections of cells around microbes
macrophages
can also release cytokines, GF and enzymes that remodel injured tissue and replace it with connective tissue
stimulate T-lymphocytes
natural killer cells
lymphocytes that repond to intracellular microbes by killing infected cella dn by producing the macrophage-activating cytokine IFN-8
recognize host cells that have been altered by microbial infection
when activated, release proteins from granules toward infected cells = molecules create holes in plasma membrane and other proteins that enter cells and induce apoptosis
also synthesize and secrete cytokines IFN-gamma
NK cell receptors
Killer cell Ig-like receptors (KIRs)
CD94 protein/lectin subunit NKG2
both have cytoplasmic domains with immunoreceptor tyrosine based inhibitory motifs (ITIMs)
phos on tyrosine residues when bind class I MHC
binding promotes activation of cytoplasmic protein tyrosine phosphatases - remove phos from secondary molecules => inhibits NK activity => keeps NK cells shut off when encounter self NK cells
IFN-gamma
cytokine released by NK cells
activates macrophages
IL-12
released by macrophages when stimulated by IFN-gamma
activates NK cells to secrete more IFN-gamma
alternative pathway
when complement proteins activated on microbial surfaces and cannot be controlled because complement regulatory proteins not present on microbes (innate)
classical pathway
triggered after antibodies bind to microbes or other antigens (humoral)
lectin pathway
when the plasma protein mannose-binding lectin binds to terminal mannose residues on surface glycoprotein of microbes => activation of proteins of classical pathway
complement activation
when activated, C3 cleaved to C3b and C3a
breakdown products of complement proteins attract neutrophils, monocytes, promote inflammation
activation also results in formation of protein complex that makes pores in microbial cell membrane
C3b
covalently attaches to microbes - activates downstream complement proteins on microbial surface
coats microbes and promotes phagocyte binding
cytokines
soluble proteins that mediate immune and inflammatory responses
communication between lymphocytes and each other and other cells
most in innate immunity produced by macrophages
in cell-mediated immunity can be produced by T lymphocytes
can be paracrine or autocrine
circulating levels increase after infection
TNF
cytokine
causes septic shock when overproduced by macrophages responding to bacterial LPS => decreased BP
plasma-mannose-binding lectin (MBL)
recognizes microbial carbs and coats microbes for phagocytosis or activates compliment via lectin pathway
c-reactive protein (CRP)
binds on microbes and coats them for phagocytosis by macrophages (macrophages have CRP receptor)
signals produced by dendritic cells and macrophages
both types activate T lymphocytes
costimulators - surface molecules that bind to naive T cells - activate
secrete IL-12 - stimulates diff. of naive T cells into effector cells
C3d
B cells recognize it on microbes - this and antigen differentiation => b cell differentiation
