Innate immunity Flashcards

1
Q

Definition inflammation

A

Local accumlation of fluid, plasma proteins and leukocytes
caused by infection, injury or chemical irritation

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2
Q

Signs of inflammation

A

RCDT
rubor (redness)
calor (heat)
dolor (pain)
tumor (swelling)

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3
Q

pro-inflammatory cytokines

A

IL-1, IL-6 and TNF-alpha

adhesion. chemokines, immune cells, luid, proteins
fever, acute phase proteins, leukocyte production
septic shock

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4
Q

Effect: IL-1 and TNF-alpha

A
  • adhesion molecules on EC upregulated (permeability)
  • vasodilation in combination with other mediators (histamine, prostaglandine from mast cells)
  • chemokine expression induced
  • recruitment of immune cells, fluid and plasma proteins
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5
Q

Effect of IL-1, IL-6 and TNF-alpha

A

PROTECTIVE:
- fever: immune cell activity up, growth rate down, rest
- acute phase protein synthesis: opsonisation, complement activation

PATHOGENIC:
- systemic TNF-alpha leads to septic shock
–> HR down, permeability and vasodilation up –> BP DOWN
–> systemic blood coagulation and impaired perfusion leads to multi-organ failure

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6
Q

types of antimirobial products

A

Lysozymes
Defensins
Cathelicidins
Histatins

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7
Q

Lysozymes

A

cleave bacterial peptidoglycan in gram-positive bacteria

present in saliva, tears, paneth cells (intestinal crypts) and phagocytes

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8
Q

Defensins

A

form pores in cell membranes of microbes (e.g. gramnegative bacteria, viruses)

hydrophobic and hydrophilic end, positive charge –> allignment within the membrane and pore formation

can also bind e.g. glycoproteins and PREVENT VIRAL ENTRY

in mucosa, skin, paneth cells and phagocytes

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9
Q

Cathelicidins

A

skin, GIT and respiratory tract, phagocytes

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10
Q

Histatins

A

saliva

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11
Q

cell-associated membrane bound PRR

A

SIGNALLING: TLR, N-formyl met-leu-phe receptors

PHAGOCYTOTIC: CLR, scavenger

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12
Q

cell associated
membrane bound + signalling

A

TLR
N-formyl met-leu-phe receptors

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13
Q

cell associated
membrane bound + phagocytotic

A

CLRs
scavenger receptors

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14
Q

cell associated cytosolic PRRs

A

RLRs
STING pathway
NLRs

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15
Q

TLRs
types
activation pathway and effect

A

cell associated, membrane bound and signalling

cell surface -> 1, 2, 4, 5 and 6 -> bacterial and fungal cell wall
endosomal -> 3, 7, 8 and 9 -> nucleic acid (viral, bacterial)

Ligand binding -> dimerization -> TIR domain recruits MyD88 or TRIF -> TRAF6 activation -> inflammatory and antiviral genes

cell surface -> NFkB and AP-1 -> inflammatory genes
endosomal -> IRFs > antiviral genes

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16
Q

cell surface TLRs

A

1, 2, 4, 5 and 6
detect bacterial infections and activate NFkB and AP-1

expression of pro-inflammatory cytokines TNF-alpha, IL1 and IL6
chemoines
endothelial adhesion molecules
costimulatory molecules for adaptive immunity

Acute Inflammatory Response
Atimulation Of Adaptive Immunity

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17
Q

endosomal TLRs

A

3, 7, 8 and 9
detect viral infections
activate IRFs and expression of antviral genes

Type I IFNs –> alpha and beta

induction of the Antiviral Response

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18
Q

N-formyl met-leu-phe receptors

A

call associated
membrane bound signalling

on plasmamembranes of phagocytes

recognize peptides containing N-formyl-methionyl residues (= first AA in bacterial peptides)

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19
Q

CLRs

A

cell associated
membrane bound phagocytosing

on phagocytes
binds mannose and fructose on carbohydrates

  • Type I: DEC-205
  • Type II: dectins, DC-SIGN
  • soluble
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20
Q

Scavenger receptor

A

cell associated
membrane bound and phagocytosing

on plasmamembranes of phagocytes
binds microbial diacylglycerides

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21
Q

RLRs

A

cell associated
cytosolic signalling

recorgnizes viral RNA -> recognized intracellular viruses

RIG-1 (uncapped RNA) and MDA-5 (dsRNA)

contain CARD domain (caspase -> apoptosis and IRF)
ROBUST ANTIVIRAL RESPONSE

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22
Q

STING pathway

A

cell associated
cytosolic signalling

stimulator of IFN-genes in response to cytoslic DNA

cGAS binds DNA -> produces cGAMP -> activates STING on ER -> IRF3 and NFkB mediated type I IFN (a&b) production

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23
Q

RIG-1

A

RLR
(cell associated, cytosolic signalling)

binds short uncapped ss or dsRNA

CARD domain -> apoptosis and IRFs
ROBUST ANTIVIRAL RESPONSE

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24
Q

MDA-5

A

RLR
(cell associated, cytosolic signalling)

binds dsRNA

CARD domain -> apoptosis and IRFs
ROBUST ANTIVIRAL RESPONSE

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25
NLRs
cell associated cytosolic signalling recognizes bacterial cell wall Leu-rich repeats for ligand bindig, NOD-domain and variable N-terminal domain CARD in NOD receptors, PYR in NLRP3
26
NOD 1&2
IkB degradation and NFkB activation NOD2 lof mutation -> Chron's disease
27
NLRP3
recognizes bacterial products and DMAPs oligomerization and adaptors and caspase 1 form inflammosome Casp1 cleaves pro-IL1b -> IL1b -> acute inflammation contributes to Gout, Alzheimers, atherosclerosis, autoinflammatoric syndromes
28
Type I IFN and viruses
produced via IFR genes -> TLRs, RLRs and STAT via NFkB -> NLRs, STING induces ANTIVIRAL STATE - induction of antiviral enzymes - activate adoptive IS (MHC I upregulation)
29
receptors activating IFR genes
TLRs RLRs/STAT
30
receptors activating NFkB
NLRs STING
31
Antiviral state
induced via type I IFN (induced by IRF or NFkB) antivral enzymes - PKR reduces viral protein sythesis - 2'5' oligo A synthesase degradation of viral RNA - Mx proteins reduce gene expression and viral assembly activate adapive IS via MHC I upregulation -> CD8+ activation
32
antiviral enzymes
PKR -> reduces viral protein synthesis 2'5' oligoA synthesis -> degradation of viral RNA Mx proteins -> reduces gene expression and virion assembly
33
Adaptive IS activation by IFN via
MHC I upregulation -> CD8+ activation
34
solubel PRRs
bind microbial structures in blood and extracellular fluids opsonization increase in inflammatory response killing acute phase proteins complement system
35
acute phase protein
soluble PRR produced by liver acute phase response initiated by IL1, Il6 and TNF alpha e.g. CRP: C-reactive protein, opsonin and activates complement, diagnostic factor for inflammations
36
CRP
C reactive protein produced by the liver acute phase protein induced by IL1, IL6 and TNFa (acute phase response) opsonin, activates complement, diagnostic factor for inflammation
37
Complement system Function
soluble PRR > 30 proteins synthesized mainly by liver circulate inactive -> proteolytic cleavage in presence of pathogens (activation) -> cascade -> MAC formation OPSONIZATION (C3b) INFLAMMATION (C3a, C5a) KILLING (C5b activates cascade -> 6,7,8,9 -> MAC)
38
Complement system Activation
soluble PRR > 30 proteins synthesized mainly by liver circulate inactive -> proteolytic cleavage in presence of pathogens (activation) -> cascade -> MAC formation ALTERNATIVE -> recognizes micorbes directly CLASSICAL -> Ab LECTIN -> mannose-binding lectin PRRS (CLRs)
39
Complement system Receptors
soluble PRR > 30 proteins synthesized mainly by liver CR1: rec. C3b, on all immune cells (innate and adaptive) CR3: iCRb (opsonin), on APCs CR4: iC3b, on APCs but mainly DCs CR2: C3dg & C3d (opsonin), on B cells and follicular T cells -> germline centers!
40
C3b function & receptors
Opsonization recognized by CR1, CR3 and CR4 (iC3b) CR2 recognizes C3dg & Cd also opsonins and recognized by B and FDCs (germline centers)
41
C3a
promotes inflammtion increased permability and chemoatraction for phagocytes
42
C5a
promotes inflammtion increased permability and chemoattrction for phagocytes
43
C5b
activates killing cascade -> C6-9 C9 essential for MAC formation and cell lysis
44
alternative pathway
complement activation via direct recognition of microbes
45
classical pathway
complement activation via recognition of Ab
46
lectin pathway
complement activtion via mannose-binding PRRs (CLRs)
47
CRP
acute phase protein opsonin activates complement diagnostic factor for inflammation (1000x elevated)
48
mast cells
innate immune cells tissue resident contain granules with pro-infl mediators express FceR1 -> bind IgE -> SENSITIZING multivalent Ag can cross-link bound IgE -> Granule content release crucial in ALLERGIC REACTIONS and their diagnosis (wheal and flare in prick test)
49
FceRI
recognizes IgE expressed by mast cells contributes to sensitizing of mast cells by IgE binding and triggering of granule release upon multivalen Ag-mediated cross-linking
50
cell essential for allergic reactions
mast cells via FceRI-IgE mediated sinsitization
51
granulocytes
innate immune cells eosinophils, neutrophils and basophils eosinophils: circulating, migration to infection and release of granule content, toxic to helminths! basophils: circulate and migrate, otherwise similar to mast cells neutrophils: phagocytosis and killing, NETosis, ADCC, regulation of T cells, ...
52
basophils
innate immune cell, grnaulocyte basophils: circulate and migrate, otherwise similar to mast cells
53
eosinophils
innate immune cells, granulocytes circulating, migration to infection and release of granule content, toxic to helminths!
54
neutrophils
innate immune cell, phagocyte and granulocyte phagocytosis and killig of bacteria NETosis cell-cell contact with adaptive immune cells degranulation and cytokine release effects T cells activating or suppressive contain different ytpes of granule
55
phagocytes
innate immune cells neutrophils and macrophages recruited via IL1 and TNFa (by tissue-resident MO) PRODUCTION of PRO-INF CYTO- and CHEMOKINES (IL1, IL6 and TNFa) release chemokines -> integrin activation, chemoattraction PHAGOCYTOSIS and KILLING: have phagocytotic PRRs (CLRs, scavenger), opsonin recognition (IgG, C3b, CRP) and killing via phagolysosome (oxidative burst) bacterial resistance to phagolysis or destruction
56
phagocytes recruitment
IL1 and TNFa by tissue-MO activate nedothelial cells -> upregulation of ICAM-1 and selectins bound by LFA-1 and carbohydrates on phagocytes extravasation migration along chemokine gradient
57
phagocytes function
2 main functions PRODUCTION of PRO-INF CYTO- and CHEMOKINES (IL1, IL6 and TNFa) release chemokines -> integrin activation, chemoattraction PHAGOCYTOSIS and KILLING: have phagocytotic PRRs (CLRs, scavenger), opsonin recognition (IgG, C3b, CRP) and killing via phagolysosome (oxidative burst)
58
phagocytes disease
chronic granulomatose disease mutationts in oxidase -> ROS production is impaired and therefore killing characterized by recurrent infections
59
macrophages
innate immune cell, phagocyte dominate later stages of innate immune cells (arrive after neutrophils but are longer-lived) phagocytosis, killing, cytokine production, Ag presentation tissue resident MO develop during embryonic development other develop out of monocytes when recruited to inflammations M1 and M2 subset M2 = wound-healing and repair promoting, by IL4 and IL13 (TH2 cells), also pro-tumorigenic
60
macrophages types
tissue resident -> produce IL1 and TNFa for phagocyte recruitment, developed in embryonic stages other develop out of monocytes upon recruitment M1 and M2 polarization M2 = wound-healing and repair promoting, by IL4 and IL13 (TH2 cells), also pro-tumorigenic
61
macrophages function
phagocytosis and killing cytokine production Ag presentation
62
neutrophils function
phagocytosis and killing NETosis cell-cell contact with adaptive immune cells degranulaton and cytokine release impacting T cells
63
dendritic cells
innate immune cell bridge between innate and adaptive sentinel (capture and process) and presenting PRRs: CLRs for Ag reouting into cell (Dectin) TLRs, NLRs, RLRs and CDS to mature DCs MATURATION: Ag processing and presentation, PRR signalling for co-stimulator expression, change in receptor reservoir (CCR7 upregulated for migration along CD19/21 to lymph nodes activate naive T cells in primary immune response activate mature T cells in secondary immune reponse
64
dendritic cells maturation
CLRs (dectin) mediate Ag processing and presentation TLR, NLR, RLR and DCS recognize PAMPs and initiate maturation (co-stimulator expression) change in receptor reseroir -> CCR7 to migrate along CCL19/21 to lymph nodes
65
dendritic cell function
sentinel and presenting Ag presentation of MHC I and MHC II -> cross-presentation by cDC1 possible acivation of naive T cells in primary immune response acivation of mature T cells in secondary immune response
66
dendritic cell subsets
pre-DC for conventintional, pre-pDC cDC1: Ag CROSS PRESENTATION of exogenous Ag to CD8 (MHCI) and intraclelular pathogens (MHCI) cDC2: extracellular pathogens to Cd4 on MHCII CD3: extraclelular pathogens to CD4 pDC: plasmacytoid -> produce type I IFN -> antiviral
67
cDC1
pre-DC Ag CROSS PRESENTATION of exogenous Ag to CD8 (MHCI) and intraclelular pathogens (MHCI)
68
cDC2
pre-CD extracellular pathogens to Cd4 on MHCII
69
DC3
pre-DC extraclelular pathogens to CD4 (MHCII)
70
pDC
pre-pDC plasmacytoid -> produce type I IFN -> antiviral
71
NK cells
innate immune cells KILLING of virus infected, injured or tumour cells via perforin IFNg PRODUCTION: induced by IL12 by MO -> activates MO to kill phagocytosed microbes ADCC: Ab activate NK cells - IgG binds target and FcgRIII on NK - antibody bridge - NK activation -> apoptosis
72
IFNg production by NK cells
induced by IL12 from MO activates MO to kill phagocytosed microbes
73
NK cells killing mechanism
perforin-mediated
74
ADCC
Ab activating NK cells IgG binding target and FcgRIII on NK cells -> Ab bridge NK activation and apoptosis
75
FcgRIII
on NK cells mediates ADCC IgG bindig target and FcgRIII