L3: Cells of Innate Immunity Flashcards by Neasa Boyle

Summarise the Induced Inflammatory Response

1) INSULT: infection/ damage occurs in specific tissue
2) RESIDENT SENSOR CELL: macrophage/ dendritic/ epithelial cell receptors sense the damage
3) MESSENGERS RELEASED FROM RESIDENT CELLS: cytokines (IL-1, TNF) chemokines (CXCL8) and prostaglandins
4) MESSENGERS ENCOURAGE RECRUITMENT OF CELLS: monocytes become macrophages, neutrophils
5) EFFECTOR MECHANISMS: immune signalling, cytokine production, phagocytosis, antigen presentation occurs at tissue of infection
6) ADAPTIVE RESPONSE

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what cells are involved in inflammatory response?

1) resident sense cells (macrophage, denritic and epithelial) sense danger and carry out effector mechanisms (cytokines, eicosanoids, complement)
they cause increased permeability of blood stream
chemokines cause recuitment of further cells (neutrophils, monocytes, lymphocytes)

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what is hematopoiesis?

the formation of blood cellular components

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name various myeloid cells

CMP, granulocytes (neutrophils, eosinophils, basophils), mast cells, macrophages (monocytes), dendritic cell
phagocytes include neutrophils macrophages and dendritic cells

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what is phagocytosis?

highly regulated process involving rearrangment of cytoskeleton and engulfing of a substance
specialised form of endocytosis

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what is macrophage nicknamed in relation to phagocytosis?

professional phagocyte

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what is neutrophil nicknamed in relation to phagocytosis?

professional killer

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what is an APC?

Antigen presenting cell

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what is the function of APCs?

liberation of cargo, present antigens to antigen specific lymphocytes

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what phagocytic process are dendritic cells involved in?

macropinocytosis

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are all APCs phagocytes?

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what special machinery do APCs require?

MHC/ co-stim molecules

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what phagocytes are ideal APCs?

DC (professional APC)
Macrophage
B cell

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what are dentritic cells called in relation to APCs?

professional APC

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what is an example of an APC that is no phagocytic?

an infected cell
its antigens are free and expressed

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describe the shape of a macrophage

large single lobed nucleus, ruffled shape

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what cell surface markers are present on macrophage?

CD11b, DC14, F4/80, CD68

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how is the innate phagocytic capacity of macrophages increased?

expression of phagocytic receptors and PRR

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What surface markers are present on DCs?

CD11c, CD80/CD86

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what processes do DCs and Macs have in common?

Naive T-cell stimulation, antigen presentation, phagocytosis, cytotoxicity, tissue sentinel role

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what do DCs express to migrate towards lymphnodes CCL19/21?

CCR7

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Are epithelial cells phagocytic?

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how to epithelial cells reduce infection?

xenophagy

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how do epithelial cells play a role in immune system?

they express PRRs (TLRs) and are capable of cytokine/ chemokine production and therefore promotion of inflammation

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what resident/ sensing cells are present in the intestinal epithelium?

iECs (enterocytes), paneth cells and globlet cells

what do paneth cells produce?

AMPs (RegIII and defensins)

what do goblet cells produce?

mucin

what is the lack of paneth cells associated with?

IBD

what are microfold cells?

M-cells, associated with epithelium in gut, no mucin, they are exposed, they are associaed with APCs and facilitate transport of antigens

what is Transcytosis?

the vesicular transport of macromolecules from one side of a cell to the other

what type of cell is a mast cell?

myelod lineage, granulocyte

where are mast cells found?

mature tissues, v common in skin, gut and around blood vessels

what activation signal is needed for mast cells to degranulate and release contents?

C3a (innate) and IgE (adaptive)

what do mast cells produce from degranulation?

enzymes, prostaglandins, ECM proteins, histamine

what effects does the release of histamine from mast cells have in relation to inflammation?

itching, redness and swelling

what is involved in EC activation?

1) decrease tight junction expression, this allows vasdialtion 2) increase adhesion molecules enables capturing of specific cells

what processes are involved in cell recruitment to infected tissue?

1) cytokine effector mechanism (inflammation inducer) acts on endothlial cell and promotes vasdialation 2) upregulation of adhesion molecules on EC 3) rolling: loose interactions involving CHO polymers/ selectins 4) firm adhesion: tigher specific interactions 5) chemokine gradients: promotes migration into tissue via diapedesis

why does neutrophil recruitment to infected tissues occur?

changes in surface of endothelium these changes occur due to inflammatory mediators histamine, cytseinyl-leukotrienes and cytokines

what is the advantage of microvilli?

increased surface area for recognition of infection

what are paneth cells?

specialised in AMPs defensins and RegIII

what are goblet cells?

specialised in producing mucus

what are M-cells?

found in gut epithelium, no microvilli, no mucin, exposed, associated with APCs, faciltate antigen transport allowing inflammation

what types of epithelial immune cells are there?

enterocytes (sensing) paneth (regulation of immunity) goblet (mucin production) M-cells (transport of antigen)

what happens when epithelial cells are activated during infection?

1) tight junction expression decreases, adhesion molecule increase 2) this enables fluid from blood to enter tissue 3) cell recruitment and inflammation occurs

what do mast cells produce?

histamine - driver of inflammation

is mast cell a granulocyte?

yes

during infection what is itching due to?

stimulation of the nerves

during infection what is redness due to?

vasdialation

during infection what is swelling due to?

fluid leakage

what is the key complement protein associated with mast cells?

C3a

what is the antibody associated with binding of mast cells?

IgE

what gradient is needed for the movement of cells from blood into tissue?

chemokine gradient

why do neutrophils enter the tissue as the first recruitment cell?

very early upregulation of E selectin this E selectin binds to the activated endothelial cell this binds E selectin ligand on neutrophils

after neutrophils enter the tissue, what chemokine is upregulated?

neutrophil specific CXCL8

what upregulation occurs after neutrophil entering tissue and upregulation of CXCL8?

ICAM-1 is upregulated

what upregulation occurs after neutrophil entering tissue and upregulation of CXCL8?

ICAM-1 is upregulated

what happens when ICAM-1 chemokine is upregulated?

it binds LFA-1 ligand and causes entering of monocytes

what chemokine is upregulated after upregulation of ICAM-1?

monocyte specific chemokine CCL2

upregulation of CCL2 occurs much later than CXCL8, what does this mean?

neutrophils enter first, monocytes enter much later

what is CXCL8?

A neutrophil specific chemokine

what is CCL2?

A monocyte specific chemokine

why does upregulation of CXCL8/IL8 attract neutrophils?

they are expressing CXCLR8

what do the granules in phagocytic neutrophils contain?

lytic, catabolic enzymes and AMPs

what do neutrophils produce that inhibit bacterial growth?

reactive oxygen species H2O2 via respiratory burst

describe the respiratory burst that occurs in neutrophils:

1) bacteria is internalised by phagocytosis 2) bacteria is in phagosome 3) enzyme recognises this 4) NADPH oxidase foes to phagosome and forms a full complex 5) super oxide is produced (O2-) hypochlorite and hypobromite is formed (H2O2) 6) bacteria is killed

what is the activity status of NADPH in resting cells?

inactive

what is the activity status of NADPH in resting cells?

inactive

how do neutrophils die?

degranulation followed by apoptosis followed by phagocytosis of another cell (clean up)

what is an example of a deficiency in NADPH oxidase?

chronic granulomas disease

what is the name for phagocytosis of neutrophils by macrophages?

efferocytosis

what types of macrophages are recruited for efferocytosis?

inflammatory(M1) and pro-resolving/ anti inflammatrory (M2)

what are acute/ inflammatory macrophages associated with?

increased bactericidial increased pro-inflammatory cytokines low efferocytosis

what are pro-resolving macrophages associated with?

decreased bactericidal, increased anti-inflammatory cytokines, high efferocytosis

What enzyme does M1/ inflammatory macrophage express?

INOS

What enzyme does M1/ inflammatory macrophage express?

INOS

What enzyme does M2/ anti-inflammatory macrophage express?

arginase-1

are macrophages oxidative?

yes but not as much as neutrophils

how do macrophages differ from neutrophils?

they have lysosomes not granules

what pH are macrophages and neutrophils?

3.5-4 'bactericidal'

do NK cells need to be activated?

no they are innate

what happens in NK cells when MHC is expressed?

no killing

what happens in NK cells when MHC is downregulated?

killing activated