Theme 2- innate 2b

Question 1

what happens in the ingestion part of phagocytosis
what forms
what is req

Answer 1

• after direct or indirect recognition
• PSEUDOPODIA form and surrounds particle
• fuse particle in PHAGOSOME
• req energy and cytoskeletal rearrangement

Question 2

what has to happen for cytoskeletal rearrangement to occur

Answer 2

• phagocyte receptors bind particle

- surface receptors are CLUSTERED

Question 3

in pseudopodia formation, what helps

Answer 3

cytoskeletal rearrangement causes the FORCE OF FLUID to push pseudopodia out so it surrounds the particle

Question 4

which organelle has a role in phagosome formation

Answer 4

ER

phagocytic and endocytic vesicle membranes are recycled

Question 5

what are the 2 types of digestion in phagocytosis

Answer 5

oxygen dependent

oxygen independent

Question 6

what can be involved in oxygen independent digestion

Answer 6

Acidification
•Lysozyme
•Other enzymes
•Defensins 
•Lactoferrin
•Cathelicidins
•S100 proteins

Question 7

what can be involved in oxygen dependent digestion

Answer 7

• Reactive oxygen intermediates
• Reactive nitrogen intermediates

in the RESPIRATORY BURST

Question 8

how is acidification used in ox independent digestion

Answer 8

phagolysosome ACIDIFIES at the same time as lysosome FUSION, ENHANCING the activities of many enzymes and INHIBITING pathogen growth

Question 9

how is lysozyme used in ox independent digestion

Answer 9

• main enzyme in lysosomes
• mediates digestion of G+ve bac cell walls
• works best with other enzymes

Question 10

how are other enzymes used in ox independent digestion

Answer 10

acid hydrolases:
phosphatases, sulphatases, glycosidases, deoxyribonucleases

lipases: phospholipase A2

neutral proteases: collagenases, elastase, cystein proteases

Question 11

how is lactoferrin used in ox independent digestion

Answer 11

binds to essential nutrients, inhibiting bacterial and fungal growth

Question 12

how are defensins used in ox independent digestion

Answer 12

• +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

Question 13

how are cationic proteins used in ox independent digestion

Answer 13

• 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)

Question 14

how is TNF alpha used in ox independent digestion

Answer 14

• secreted by macrophages

- cytotoxic to tumour cells

Question 15

describe the ox dep of digestion in phagocytosis

Answer 15

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

Question 16

describe ROI

Answer 16

• RAPID inc in O2 consumption
• involves cytoplasmic and memb associated enzymes
• O2 converted to superoxide, peroxide or hydroxyl anion w/ unpaired e-

Question 17

describe RNI

Answer 17

• 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

Question 18

most microbial mediators are prod where

where do they produce microbial mediators

Answer 18

MC/MFs and Neu
(professional phagocytes)

lysosomes- mc and macrophages
primary and secondary granules- neus

Question 19

neutrophils are more likely to kill how

Answer 19

ingested microorganisms due to higher respiratory burst and higher levels of defensins

Question 20

what happens if pathogens are’nt killed by RO| or RNI

Answer 20

can be detected by cytoplasmic PRRs and undergo autophagy or succumb to pyroptosis

Question 21

what are the hallmarks of inflammation

Answer 21

5 hallmarks:rubor (redness) et tumor (swelling) cum calor (heat) et dolor (pain), & loss of function

Question 22

acute phase response in inflammation lasts how long

Answer 22

0-24hours

Question 23

what is the aim of inflammation

Answer 23

increasing blood flow, permeability of vasculature – allowing leukocyte migration to aid limiting the spread of infection, tissue damage and to promote healing

Question 24

whata re the systemic effects of mediators being released from activated tissue cells

Answer 24

• stim release of granulocytes and monocytes from BONE MARROW
  (hypothalamus-> fever)
  (liver-> Acute Phase Protein production (CRP, SAA, MBL)

Question 25

what are the local effects of mediators being released from activated tissue cells

Answer 25

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

Question 26

what are ways of destroying an organism

Answer 26

anti-microbial proteins/peptides (AMPS) enzymes or by respiratory burst in granules/phagolysosomes, Neutrophil Extracellular Traps (NETs)

Question 27

inflammatory mediators

Answer 27

- 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

Question 28

what do cytokines do | eg

Answer 28

- 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)

Question 29

what are the alarm cytokines

Answer 29

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

Question 30

what do anti-inflammatory cytokines do

Answer 30

- down reg responses inc IL-10 and transforming growth factor bets (TGF-β)

Question 31

what do IL-12 and IL-18 do

Answer 31

induce DIFFERENTIATION of PRO INFLAMMATORY T cells | IL-8 is a potent chemokine for neutrophils

Question 32

what does IFNγ do

Answer 32

acts in the acute phase contributing to chronic inflammation by recruiting macrophages to inf/damage

Question 33

what are type I interferons

Answer 33

IFNalpha and beta

Question 34

what do Type I interferons do

Answer 34

have antiviral properties

Question 35

whaat are the 2 major families of chemokines

Answer 35

CC and CXC

Question 36

what is chemokine structure what is chemotaxis give examples

Answer 36

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

Question 37

Prostaglandins, Leukotrienes and Thromboxanes are all what

Answer 37

all Eicosanoids- INFLAMMATORY MEDIATORS-unsaturated fatty acids derived from arachidonic acid

Question 38

how are prostaglandins made

Answer 38

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

Question 39

what does histamine cause

Answer 39

acts to inc vascular permeability and smooth muscle contraction

Question 40

what is EXTRAVASATION

Answer 40

Movement (or migration) of white blood cells or fluid from the lumen of blood vessels into tissues