Week 3 Flashcards
where are CD40 and CD40L present?
CD40 - APC
CD40L - CD4 T cell
where are CD28 and CD80/86?
CD28 on T cell
CD80/86 on APC
which cytokine acts in an autocrine matter to promote T cell growth?
IL2 (3rd signal from APC)
which CD4 T cell provides CD40L?
Th1
which CD4 T cells are involved in IC and EC bacterial infections
Th1 = IC Th17= EC
what are the 3 steps in priming of CD8?
DC with increased expression of B7 activates CD8 directly
DC activates DC4 which in return enhances co-stimulatory activity in DC
activated CD4 cells secrete IL2 which directly acts on CD8
which cytokines to CTLs release?
IFNy (inhibits viral replication)
TNFa
what do the granules used in CTL contain and what do they target?
granules contain, perforin, granulysin, granzymes
intracellular targets include: caspases, nuclear DNA, mitochondrial proteins
how does acute and chronic inflammation differ? in terms of the cells involved
shift from polynuclear low nuclei cell (neutrophils)
to mononuclear cells (macrophages, lymphocytes)
what are the 3 outcomes of acute inflammation?
1- complete repair/ resolution
2- fibrosis/ scarring
3. progression to chronic inflammation
what does the recruitment of eosinophils depend on?
eotaxin - CC chemokine
causes of chronic inflammation?
persistent infection by IC bacteria
immune reactions- autoimmune
immune response to normal substances
prolonged exposure to toxic substances
role of macrophages in chronic inflammation?
produce cytokines that destroy pathogen and initiate repair
activated by cytokines from activated T cells
accumulation by increased recruitment of monocytes?
what is classical macrophage activation?
pro-inflammatory pathway
induced by microbial agents (endotoxin, IFNy)
activated macrophage produced lysosomal enzymes (NO, ROS) which enhances their ability to kill ingested organism and secrete cytokines
what is alternative macrophage activation?
anti-inflammatory
induced y IL4 and IL13 produced by T cells, mast cell and esinophils
role in tissue repair - secrete GF, increased angiogenesis, stimulate collagen synthesis
how do mast cells work in chronic inflammation?
express surface receptors that bind to Fc portion of IgE - degranulation and release of histamine
how do macrophages and lymphocytes work in a bidirectional way?`
macrophage displays Ag to T cell and produce cytokines which activates Tcell
activated T cell releases cytokines to recruit and activate macrophages which again leads to Ag presentation and more cytokine production to T cells
what does a granuloma consist of? whats its function?
macrophages
fibroblasts
giant cell (1 cell with multiple nuclei)
lymphocytes
it attempts to wall off substances it sees as foreign but is unable to eliminate it
function of epidermal GF?
mitogenic for keratinocytes and fibroblasts
stimulates keratinocyte maturation
stimulates formation of granulation tissue
function of hepatocyte GF?
enhances proliferation of heptocytes
increases cell motility
function of VEGF?
increased proliferation of endothelial cells
increases vascular permeability
function of platelet derived GF? PDGF.
chemotactic for neutrophils, macrophages, fibroblasts and SMC
activates and stimulates proliferation of fibroblasts, endothelial cells
stimulates synthesis of ECM proteins
function of fibroblast GF?
chemotactic and mitogenic for fibroblasts
stimulates angiogenesis
Stimulates ECM protein synthesis
function of TGF-beta (transforming GF-B)
chemotactic for leukocytes and fibroblasts
stimulates ECM protein synthesis
suppresses acute inflammation
where does VEGF come from?
mesenchymal cells
where does PDGF come from?
platelets, macrophages, endothelial cells, SMC
where does HGF come from?
fibroblasts, endothelial cells, stromal cells in liver
where does EGF come from?
activated macrophages, keratinocytes and salivary glands
where does FGF come from?
macrophages, mast cells, endothelial cells
where does TGF-beta come form?
platelets, T cells, macrophages, endothelial cells, SMC, fibroblasts
differentiate caseous and non-caseous granuloma/
caseous - infectious causes (TB, fungal)
non caseous - non-infectious causes - autoimmune disorders, RA, sarcoidosis
what is healing by primary intention?
injury involves 1 epithelial layer
mechanism of repair is epithelial regeneration
what is healing by secondary intention?
more extensive cell/ tissue loss
repair involved regeneration and scar formation
what is positive selection?
T cells must recognize/ bind moderately to self MCH
apoptosis of those that do not interact with HLA molecules
recognize, pMHCI and pMHCII expressed by cortical eputhelial cells
what is negative selection?
apoptosis of medullary thymocytes that recognize self peptide on MHC1/MHCII too strongly
what is central tolerance?
negative selection
what cells mediate positive selection?
cortical epithelial cells
what cells mediate negative selection?
DC, macrophages of bone marrow origin
how do effector T cells migrate from blood to tissues to perform their effecttor functions?
exit through LN efferent lymphatics or splenic vein and migrate into tissues to perform their effector functions
what happens with peptide: MHC bind in T cells?
signal transduction occurs through signalling proteins associated with TCR
Ag binding leads to phosphorylation of signalling cascades of protein: protein interactions = increased expression of genes
IL2 is the first gene switched on = its acts on itself to promote T cell growth
what cytokines do CTLs release?
IFN-y= inhibits viral replication and activates macrophages TNFa= recruitment of other inflammatory cells and promote target cell killing
what are the functions of perforin, granzymes and ganulysin?
perforin: creating pores in target cells membrane
granzymes: enter cell via perforin
granulysin: creates holes in target cell membrane and destroy it
what are acute phase proteins?
Acute-phase proteins are a class of proteins whose plasma concentrations increase or decrease in response to inflammation. This response is called the acute-phase reaction. For acute-phase reaction is characteristic fever, acceleration of peripherals leukocytes, circulating neutrophils and their precursors
GF involved in liver regeneration?
TGFa and HGF
what is the difference between central and effector memory cells?
central cells express CCR7 and remain in lymphoid tissues
effector memory cells lack CCR7 and migrate to tissues
