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immunology xy2011 > innate immunity and inflammation 2 > Flashcards

innate immunity and inflammation 2 Flashcards

1
Q

where do myeloid cells originate from

A

bone marrow

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2
Q

what is the primary function of dendritic cells

A

allows constant sampling of tissue environment by phagocytosis and macropinocytosis

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3
Q

when do dendritic cells mature

A

upon engagement of PRRs with PAMPs/DAMPs

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4
Q

what are the secondary functions of dendritic cells

A
  • migrate to lymph nodes to act as messenger cells
  • present antigen to T cells
  • recruit cells of the adaptive immune response
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5
Q

what are natural killer cells

A

large lymphocyte like cells with highly granular cytoplasm and are found in peripheral tissues

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6
Q

what do natural killer cells lack

A

antigen receptors but express innate receptors

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7
Q

what is the function of natural killer cells

A

respond to cellular stress and infections by specific viruses
- early defence against viruses by programmed cell death

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8
Q

what granules do natural killer cells contain

A
  • granzyme - serine protease
  • perforin - pore forming protein
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9
Q

what are the functions of granules in natural killer cells

A
  • released onto surface of virally infected or malignant cells
  • penetrate cell and induce programmed cell death (apoptosis)
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10
Q

what is the TRAIL mechanism

A

TNF-related apoptosis inducing ligand

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11
Q

what are the steps in the TRAIL mechanism

A

interacts with death receptors (DR4 and DR5) expressed by cells
- activates pro enzyme of capsule 8 resulting in apoptosis

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12
Q

what stimulates granule release in natural killer cells

A

binding of antibody to Fc receptors on neural killer cells

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13
Q

what occurs with a natural killer cell deficiency

A

susceptible to herpes virus and other viral infections

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14
Q

what type of B cell makes up the majority

A

B2 cells

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15
Q

where are B1 cells formed

A

fetal liver

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16
Q

what do B2 cells do

A

adaptive immunity, antibody producing

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17
Q

what do B1 cells do

A

part of innate immune system

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18
Q

where are B1 cells found

A
  • peritoneal
  • pleura cavities
  • lymphoid tissue
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19
Q

where are B2 cells formed

A

bone marrow

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20
Q

what are the functions of B1 cells

A
  • recognise capsular polysaccharide antigens - protection against bacteria and viruses
  • produce IgM
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21
Q

what happens to mice lacking B1 cells

A

don’t produce anti-phosphocholine antibodies so they are susceptible to staph.pneumoniae

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22
Q

where does chronic lymphoid leukaemia originate from

A

B1 cells

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23
Q

where are pattern recognition receptors found

A

on phagocytes and other leukocytes

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24
Q

where are soluble pattern recognition receptors found

A

throughout body in plasma, lymph and interstitial fluid

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25
what do pattern recognition molecules do
- relatively non specific but bind a limit range of molecules - can trigger destruction of organisms - can make cells more efficient at destroying organisms
26
what happens when PRRs send information
via proinflammatory cytokines to immune system about nature of threat
27
what are the types of pattern recognition molecules
plasma membrane associated - TLR, C-type lectin and scavenger receptors cytoplasmic - RIG-1, cytoplasmic DNA and NLRs receptors
28
when does single PRRs engage
low level or distant infection
29
when do multiple PRRs engage
- binding/ phacoytonsis of single bacterium - robust response warranted - synergistic activation of signalling pathways
30
what happens when 2 or more signals in tandem are delivered
activates particular response
31
what is the ectodomain of TLRs
many leucine rich repeats and is C or ? shaped
32
where are transmembrane glycoproteins found in TLRs
plasma membrane or endosome membrane
33
what is the cytoplasmic domain of TLRs
- Toll/IL-1 receptor domain - interacts with other types
34
where do TLRs reside
plasma and endosome membranes
35
what do TLR initiate
- engagement with PAMPs - activate intracellular signalling cascade - transcription factors NF-kb and IRF - NF-kB and IRF enter the nucleus and bind to promotors
36
where are C type lectin receptors found
macrophages and dendritic cells
37
what do C type pectin receptors do
- mostly transmembrane proteins - trigger intracellular activation signals
38
what do scavenger receptors do
- recognise various molecules eg. anionic polymer and acetylated low density lipoproteins
39
what does structural diversity of scavenger receptors allow
allows recognition of wide range of modified molecules
40
what do modified molecules do
central to the pathogenesis of atherosclerosis and beta amyloid fibres in Alzheimers
41
what do scavenger receptors also exist as
TLR4- bound form
42
what to TLR4- bound do
- bind LRP in gram negative bacteria - expressed by monocytes and macrophages
43
what do retinoid acid inducible gee 1 receptors do (RIG1)
- intracellular sensor of ssRNA from ssRNA viruses - discriminates between host and viral RNA due to 5'end differences in dsRNA transcripts
44
what are the steps in RIG1 activation
- unbound RIG1 is autoinhibiteed - RIG1 activated by 5' uncapped viral RNA - activated form binds to MAVS on mitochondrial membrane
45
where are STING receptors found
ER membrane
46
what do STING receptors do
- recognises bacterial cyclic dinucleotides - bacterial 2nd messengers - binding to STING recruits proteins to lead to type 1 interferon expression - similar to TLR3 signalling mechanism
47
what occurs due to a sting deficiency in mice
increased susceptibly to herpesvirus
48
where are NLRs found
cytoplasm
49
what are NLRs
NOD-like receptors - family of soluble protein
50
what do NLRs do
- expressed mostly in epithelial cells (macrophages and dendritic cells) - centrally located nucleotide binding oligomeristaion domain - ligans bind to C- terminal leucine rich repeats
51
what are the intracellular bacterial ligands
- NOD1 recognises γ-glutamyl diaminopimelic acid (iE-DAP) - NOD2 recognises muramyl dipeptide (MDP)
52
what do NLRs lead to
nuclear localisation of NF-kB - cytokine expression - production of NO - toxic to bacteria and intracellular parasites
53
how does Crohn's disease occur
- NOD2 - LRR domain mutation leading to loss of function mutations
54
how does early onset sarcoidosis (Blau syndrome) occur
- NOD2 - gain of functional mutation - activation of signalling without ligand binding
55
what are the types of NRLs
- NLBB - baculovirus inhibitory repeat domain - NLRC/A - capase recruitment domain - NLRP - pyrin domain - all determine signalling cascade
56
what does NOD1 protect us against
protozoa
57
what does NOD2 protect us against
viruses - strongly expressed in paneth cells in the gut - antimicrobial peptides - regulates expression of alpha and beta defensins
58
what activates NLRP3
- requires 2 signals - crystalline uric acid - extracellular ATP - released by damaged cells - K+ efflux - pore forming toxins - ROS - reactive oxygen, rupture of phagolysosome - mitochondrial DNA
59
where is NLRP3 inflammasomes expressed
- monocytes - macrophages - granulocytes - dendritic cells - epithelial cells
60
why is NLRP3 metabolically expensive
mitochondria plays central role I NLRP3 activation
61
what is pyroptosis
highly inflammatory form of cell death
62
what is the function of pyroptosis
- bacteria can't grow in dead cells - removes intracellular reproduction niches - releases large quantities of IL-1beta and IL-18 - recruits large numbers of fresh immune cells - release large quantities of DAMPs

immunology xy2011 (9 decks)

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