Theme 2- innate 2b Flashcards
what happens in the ingestion part of phagocytosis
what forms
what is req
- after direct or indirect recognition
- PSEUDOPODIA form and surrounds particle
- fuse particle in PHAGOSOME
- req energy and cytoskeletal rearrangement
what has to happen for cytoskeletal rearrangement to occur
- phagocyte receptors bind particle
- surface receptors are CLUSTERED
in pseudopodia formation, what helps
cytoskeletal rearrangement causes the FORCE OF FLUID to push pseudopodia out so it surrounds the particle
which organelle has a role in phagosome formation
ER
phagocytic and endocytic vesicle membranes are recycled
what are the 2 types of digestion in phagocytosis
oxygen dependent
oxygen independent
what can be involved in oxygen independent digestion
Acidification •Lysozyme •Other enzymes •Defensins •Lactoferrin •Cathelicidins •S100 proteins
what can be involved in oxygen dependent digestion
- Reactive oxygen intermediates
- Reactive nitrogen intermediates
in the RESPIRATORY BURST
how is acidification used in ox independent digestion
phagolysosome ACIDIFIES at the same time as lysosome FUSION, ENHANCING the activities of many enzymes and INHIBITING pathogen growth
how is lysozyme used in ox independent digestion
- main enzyme in lysosomes
- mediates digestion of G+ve bac cell walls
- works best with other enzymes
how are other enzymes used in ox independent digestion
acid hydrolases:
phosphatases, sulphatases, glycosidases, deoxyribonucleases
lipases: phospholipase A2
neutral proteases: collagenases, elastase, cystein proteases
how is lactoferrin used in ox independent digestion
binds to essential nutrients, inhibiting bacterial and fungal growth
how are defensins used in ox independent digestion
- +vely charged polypeptides that bind -ve PAMPs eg LPS, LTA
- specific for microbial cells
- aggregate to form pores in cytoplasmic membranes
- activate complement- classical pathway
- most abundant protein in neutrophils
how are cationic proteins used in ox independent digestion
- found in Neu granules, some in Eo
- high molecular weight and most active at alkaline pH
- damage microbial membranes, proteins
- eg elastase, cathepsin G, proteinase 3 (serine proteases)
- mostly anti-bac (cap G= also anti-fungal)
how is TNF alpha used in ox independent digestion
- secreted by macrophages
- cytotoxic to tumour cells
describe the ox dep of digestion in phagocytosis
phagocytes prod Reactive Oxygen and Reactive Nitrogen Intermediates
- damage proteins, lipids, DNA and cell membs of microorganisms
- superoxide and H2O2 released cause damage
- RNI= chort lived but act with ROI
- Catalase, superoxide dismutase and glutathione are free radical scavengers
describe ROI
- RAPID inc in O2 consumption
- involves cytoplasmic and memb associated enzymes
- O2 converted to superoxide, peroxide or hydroxyl anion w/ unpaired e-
describe RNI
- inducible Nitric oxide synthase activated by microbial prod and cytokines
- Within phagocytes = large ‘burst’ and LOTS of NO produced with potent antimicrobial activity
- Can combine with superoxide to be even more potent
most microbial mediators are prod where
where do they produce microbial mediators
MC/MFs and Neu
(professional phagocytes)
lysosomes- mc and macrophages
primary and secondary granules- neus
neutrophils are more likely to kill how
ingested microorganisms due to higher respiratory burst and higher levels of defensins
what happens if pathogens are’nt killed by RO| or RNI
can be detected by cytoplasmic PRRs and undergo autophagy or succumb to pyroptosis
what are the hallmarks of inflammation
5 hallmarks:rubor (redness) et tumor (swelling) cum calor (heat) et dolor (pain), & loss of function
acute phase response in inflammation lasts how long
0-24hours
what is the aim of inflammation
increasing blood flow, permeability of vasculature – allowing leukocyte migration to aid limiting the spread of infection, tissue damage and to promote healing
whata re the systemic effects of mediators being released from activated tissue cells
- stim release of granulocytes and monocytes from BONE MARROW
(hypothalamus-> fever)
(liver-> Acute Phase Protein production (CRP, SAA, MBL)
what are the local effects of mediators being released from activated tissue cells
inc expression of ADHESION MOLECULES on endothelial cells lining blood vessels and on leukocytes allowing endothelium attachment
Other:
- affect vascular TONE of endothelial layer allowing attached cells to pass to tissues
what are ways of destroying an organism
anti-microbial proteins/peptides (AMPS) enzymes or by respiratory burst in granules/phagolysosomes, Neutrophil Extracellular Traps (NETs)
inflammatory mediators
- produced by mast cells, basophils, macrophages
- produce: prostaglandins, leukotrienes, thromboxanes, histamine, cytokines, chemokines
also: plasma has 4 intercoonnected mediator producing systems: kinin, clotting, fibrinolytic, complement
what do cytokines do
eg
- role in inflammation
- include: Interleukin-1, 6, 8, 10, 12 (IL-1, IL-6 etc), Tumour necrosis factor a (TNF-a), Transforming growth factor β (TGF-β) and interferon γ (IFNg)
what are the alarm cytokines
IL-1, IL-6 and TNFα for acute inflammation causing local and systemic activation of fever, increased vascular permeability, production of acute phase proteins and increased adhesion molecule expression
what do anti-inflammatory cytokines do
- down reg responses inc IL-10 and transforming growth factor bets (TGF-β)
what do IL-12 and IL-18 do
induce DIFFERENTIATION of PRO INFLAMMATORY T cells
IL-8 is a potent chemokine for neutrophils
what does IFNγ do
acts in the acute phase contributing to chronic inflammation by recruiting macrophages to inf/damage
what are type I interferons
IFNalpha and beta
what do Type I interferons do
have antiviral properties
whaat are the 2 major families of chemokines
CC and CXC
what is chemokine structure
what is chemotaxis
give examples
4 cysteine residues and seq of aa
- when they bind they stimulate MIGRATION and ACTIVATION of cells towards the source along conc gradient (CHEMOTAXIS)
eg IL-8, MCP-1
Prostaglandins, Leukotrienes and Thromboxanes are all what
all Eicosanoids- INFLAMMATORY MEDIATORS-unsaturated fatty acids derived from arachidonic acid
how are prostaglandins made
by enzymes inc cyclooxygenases (COX-1, COX-2) a target of anti inflammatory pain killers
- hormone like effects
- Act on vascular permeability and leucocyte migration to tissues
- PGE2 acts on hypothalamus to induce fever
what does histamine cause
acts to inc vascular permeability and smooth muscle contraction
what is EXTRAVASATION
Movement (or migration) of white blood cells or fluid from the lumen of blood vessels into tissues
