Macrophages Flashcards
How does Mo extravasion differ from N extravasion?
involves Mo-specific chemokines and adhesion molecules
How are Mo more efficient than N?
sustained pathogenic activity and longer life span
What does Mo extravasion occur?
Immediately following N influx
What is Mo extravasion facilitated by?
release of Mo-specific chemokines and chemotactic agents
What are Mo-specific chemokines secreted by?
endothelial cells (CCL2-CCR4)
N (CCL4-CCR1)
M0 (CCL7-CCR2)
What are the chemotactic agents involved in Mo extravasion?
beta-defensins, chimerin, TNFalpha
What do E-cells and Mo express respectively during the tethering stage?
E-cells = P-selectin Mo = P-selectin glycoprotein ligand (PSGL-1)
What do E-cells and Mo express respectively during the rolling stage?
E-cells = E-selectin Mo = CD62L (L-selectin)
What do E-cells and Mo express respectively for adhesion molecules?
E-cell = ICAM 1&2 and VCAM 1 Mo = LFA-1 & MAC-1
What complement receptors do M0 express?
CD35 (CR1) and CD11b/CD18 (CR3)
What do complement receptors on M0 do?
enables the M0 to phagocytize microbes opsinised by C3 components
M0 express Fc receptors enabling them to?
carry out antigen-specific phagocytosis
What do mammalian M0 express?
high affinity CD64 and low affinity CD32 and CD16
What does expression of CD64 allow M0 to do?
Recognize single IgG-Ag complexes
What does expression of CD32 and CD16 allow M0 to do?
recognize multivalent immune complexes
M0 express CD71 enabling them to?
allow internalization of transferrin that has sequestered iron
What mechanisms of killing do M0 rely on?
oxidative and non-oxidative
M0 utilize the contents of what granulocyte?
N
What are the 2 subpopulations of M0?
pro-inflammatory M1 and anti-inflammatory M2
What does pro-inflammatory M1 do (Draw it)?
In the end it produces potent antimicrobial oxidants peroxynitrite and a nitrogen dioxide radical
What do M1 M0s secrete? What do these do?
IL12 and IL23 which are critical effectors for the acute phase intracellular infections
What can prolonged M1 M0 do?
damage host tissues and are involved in acute inflammatory disease (ex. gastroenteritis)
What do M2 M0s secrete?
IL10 and TGFbeta
M2 utilize arginine to produce?
ornithine then citruline
M2 appear later during infection. What do they do?
key role in wound healing and important effectors during parasitic infections
What signals M1?
IFNgamma
What signals M2?
IL4&13
How do mycobacterium Bovis and Brucells suis work against M0?
suppress M1 and promote M2 M0 differentiation facilitating their survival
M2 M0 producing what is associated with persistent bacterial infection and chronic disease?
IL10
How do M0 act as regulatory cells?
antigen presenting ability, phagocytize apoptotic N, secrete cytokines and enzymes promoting tissue remodeling and repair, secrete regulatory cytokines to stimulate acute phase responses and steer the acquired immune response
What cells are involved in steering the acquired immune response?
Th1, Th2, Th17, regulatory T-cells
What components are involved in Th1 cell steering??
IL12, IL18
What components are involved in Th2 cell steering?
IL1, IL6, IL10, IL13
What components are involved in Th17 cell steering?
TNFalpha, IL6, IL23
What components are involved in regulatory T-cell steering?
TGFbeta and IL10
M0 can become activate by? What do they differentiate into?
PAMPS and alarmins and differentiate into M1
What do M1 secrete when activated by PAMPS and alarmins?
IL12 and TNFalpha
What do IL12 and INFalpha activate?
NK cells
What do NK cells do?
secrete IFNgamma
What does IFNgamma do?
induce NOS2 gene transcription
What cells remove particles that have penetrated skin and what do they do with them?
Langerhans cells then migrate to draining lymph nodes and act as APCs interacting with T-cells
In species without lymph nodes how to cells remove particles?
Same cells but migriate to drainage lymph nodules or clear particles circulation with interaction with T-cells in secondary lymphoid tissues
What consists of secondary lymphoid tissues?
Spleen, pronephros (in fish), bursa (birds)
What is involved in the removal of ingested particles?
GI tract enzymes degrade most particles and the rest is removed by mucus flow
What is the function of M cells in the GIT?
sample particles on intestinal lumen and pass to M0 that travel to intestinal Peyer’s patches and/or mesenteric lymph nodes to interact with T cells for antigen presenting
What is involved in the removal of inhaled particles?
most stick to the mucus in the bronchi and bronchies and are pushed out
What happens to particles small enough to reach the alveoli?
they are phagocytized by alveolar M0 and removed by mucus flow
How do pigs, ruminants and horses remove circulating particles?
removed my M0 lining capillary epithelium of the lung
How do humans, rabbits and mice remove circulating particles?
via hepatic Kupffer cells and splenic M0
What occurs in the human liver to remove particles?
K-cell trap the pathogen then attract N to phagocytize and destroy them. Then there is phagocytic removal of the dying N by the K-cell
What makes the best opsonins and why?
Antibodies because they are antigen specific
K-cells rely heavily on what type of opsinization?
C3 via CD35
What do M1 differentiate into for healing?
M2
What is the function of TGFbeta?
promotes fibroblast division and enhances deposition of fibroblast proteins such as fibronectin (scaffold for ECM)
True or false - M2 M0s secrete angiogenic factors
true
When does the host inflammatory response become chronic?
when foreign particles persist for a long time or a pathogen remains elusive
Granulomas contain what?
M0 which form into giant cells to restrict spread of the pathogen or particle
