2. Innate Immunity Flashcards
(104 cards)
1
Q
aim of innate immune response
A
limit spread, eliminate microorganisms and repair damage
2
Q
aim for adaptive immunity
A
to clear pathogens and produce a memory response
3
Q
Cells of the innate immune system
A
Phagocytes (neutrophils, monocytes, macrophages, mast cells, eosinophils), antigen presenting cells (monocytes, macrophages and dendritic cells) and other immune cells (NKCs, ILCs, NKTCs)
4
Q
four main types of defensive barriers/features
A
anatomical, physiological/chemical, phagocytic/endocytic, inflammatory
5
Q
examples of anatomical defence barriers
A
skin, mucosa
6
Q
how is skin used as a defence barrier
A
sloughing of dead skin, acidic (pH3-5), commensal microflora that secrete bacteriocins
7
Q
how are mucosal surfaces used a defence barriers?
A
cilia propulsion, entrapment, flow of secretions, competition by commensal bacterial, tight junctions
8
Q
examples of physiological/chemical defences
A
temperature (fever), low pH (stomach, skin), chemical mediators/antimicrobial proteins
9
Q
Protein examples
A
Lysozyme, Lactoferrin, Psoriasin, Surfactant P
10
Q
lysozyme
A
found in tears/saliva that cleaves peptidoglycans of bacterial cell walls
11
Q
Lactoferrin
A
Binds to essential nutrients, inhibiting bacterial and fungal growth
12
Q
S100 proteins e.g. Psoriasin
A
secretions and on skin, Disrupts microbial cell membranes
13
Q
Surfactant Proteins
A
respiratory tract, block bacterial surface components
by binding to them, have a lubricating function
14
Q
Peptide examples
A
Defensins, Cathelicidins, Histatin, Dermicidin
15
Q
Defensins
A
bind negatively charged microbial structures, Aggregate to form pores in cytoplasmic membrane, activate complement pathway, found in neutrophil granules
16
Q
Cathelicidins
A
disrupt microbial membranes
17
Q
what did Metchnikoff use to study phagocytosis?
A
daphnia and starfish larvae
18
Q
examples of endocytosis
A
Pinocytosis
Macro-pinocytosis
Receptor-mediated endocytosis
Phagocytosis
19
Q
which type of endocytosis is used by most cells?
A
pinocytosis and receptor-mediated
20
Q
pinocytosis
A
Cell drinking. aids osmoregulation. non-specific
21
Q
Macro-pinocytosis
A
larger gulps of cell drinking. Aids in processing of Antigens for an immune response
22
Q
Receptor-mediated endocytosis
A
specific uptake of ligand, growth factor, hormone, immune complex via a receptor. clathrin associated
23
Q
Phagocytosis
A
internalise, kill/destroy/digest particulate matter
24
Q
phagocytic cell types
A
Monocytes/Macrophages Neutrophils Dendritic cells Eosinophils B cells/Mast cells
25
stages of phagocytosis
```
1- Recognition
2- Ingestion
3- Digestion
4- Exocytosis –
also presentation
and storage
```
26
direct recognition
non-opsonic - Pattern Recognition Receptors (PRRs) on phagocytes bind to Pathogen Associated Molecular
Patterns (PAMPs) or to Damage Associated Molecular Patterns (DAMPs) on particles/microbes
27
indirect recognition
opsonic - Receptors on phagocytes bind to opsonins coating the surface of particulate matter/microbes
28
examples of PAMPs
bacteria - cell wall components, flagella. viral glycoproteins, fungi
29
examples of DAMPs
necrosing cells (ssRNA release), short-chain fatty acids in diet, apoptosing cells (PS, RNA, vitronectin)
30
C type lectin receptors
Mannose Receptor, Dectin-1, DC-SIGN
31
Mannose Receptor
* Binds to mannose/fucose/α mannan
* On surface of most Mφs and DCs
* Has 8 extracellular domains and cytoplasmic tail
32
Dectin-1
* Binds β1-3 glucan on fungi and bacteria
| * Expressed on a wide variety of myeloid lineage cells
33
DC-SIGN
• Binds mannans on bacteria, fungi and parasites
34
Scavenger receptors
SR-A and B
35
SR-A
• Found on all macrophages & some endothelial cells, binds modified low-density lipoprotein e.g. oxidised LDL
36
SR-B
• Includes CD36 found on endothelium, DC, platelets, MC & MF
• Binds variety of altered ‘self’ molecules such as
oxidised LDL or vimentin on the surface of apoptotic cells
• Also recognise some PAMPs
37
Toll-like receptors
Toll gene identified in
| Drosophila, Leucine rich repeats of external domain,
38
intracellular TLRs
detect DNA/RNA associated with viruses
and strongly induce type I interferons –
cytokines with antiviral effects
39
extracellular TLRs
expressed mainly by immune cells and are strongly
| associated with bacterial/fungal infections
40
which cell types express all TLRs?
monocytes, macrophages, dendritic cells
41
which type of TLR do B cells, T cells and granulocytes express?
TLR4
42
NOD-like receptors (NLRs)
* Family of 23 members divided into 3 main groups (B,C and P)
* Interact with intracellular PAMPs and DAMPs
* Activate the NFkB pathway and autophagy
43
RIG-like receptors
* Bind viral dsRNA and so detect viral replication
| * Initiate anti-viral cytokine (type 1 interferons)
44
AIM2–like receptors (ALRs) and cGAS/STING
• Bind DNA molecules from bacteria and viruses
• Induce production of anti-viral and inflammatory
cytokines
45
inflammasome
NLRs and ALRs clump together to initiate pro-inflammatory cytokine production
46
pyroptosis
self-death by pro-inflammatory cytokines
47
pro-inflammatory cytokines
Interleukin-1 and 18
48
examples of opsonins
IgG (antibody), fragments of Complement & lectins
49
antibody receptors
Fc. Recognise the constant region
| (i.e. not antigen binding) of antibodies
50
complement receptors
Bind to components of the classical, alternative and lectin complement
pathways
51
examples of complement receptors
CR1, CR2, CR3, CR4, C3a/4a and C5aR
52
process of phagocytosis
pseudopodia form & surround particle, fuse
engulfing particle in membrane-bound vesicle. requires energy and cytoskeletal rearrangement (surface receptors need to cluster)
53
Oxygen Independent digestion
* Acidification
* Lysozyme
* Other enzymes
* Defensins
* Lactoferrin
* Cathelicidins
* S100 proteins
54
Oxygen Dependent digestion
• Reactive oxygen
intermediates
• Reactive nitrogen
intermediates
both lead to respiratory burst
55
Other oxygen independent Enzymes
• Acid hydrolases: phosphatases, sulphatases, glycosidases,
deoxyribonucleases
• Lipases: eg phospholipase A2
• Neutral proteases: collagenases, elastase, cysteine proteases
56
examples of free radical scavengers
Catalase, superoxide dismutase and glutathione
57
what can ROI and RNI damage?
proteins, lipids, DNA and cell membranes
58
how does ROI cause respiratory burst?
Rapid increase in O2 consumption, surge of targeted activity in phagosomes and
phagolysosomes, free radical reactive to microbial components
59
how does RNI cause respiratory burst?
inducible Nitric oxide synthase (iNOS)
activated by microbial products and some
cytokines, expression in vasculature and neurones, argenine oxidised to citrulline and nitric oxide within phagocytes
60
professional phagocytes
macrophages, monocytes and neutrophils
61
where are ROI/RNI found in professional phagocytes?
macrophages/monocytes - lysosomes
| neutrophils - primary and secondary granules
62
what happens to pathogens that escape digestion stages?
undergo pyroptosis or autophagy by intracellular PRR recognition
63
what happens to products of phagocytosis?
Heavy metals tend to be
‘stored’ and PAMPs and DAMPs once processed are often presented to the adaptive
immune response
64
5 hallmarks of inflammation
rubor (redness) et tumor (swelling) cum calor (heat) et dolor
(pain), & loss of function (functio laesa)
65
purpose of inflammation
```
increasing
blood flow, permeability of
vasculature – allowing leukocyte
migration
to aid limiting the spread of
infection, tissue damage and to
promote healing
```
66
NETs
Neutrophil Extracellular Traps
67
immune cells that produce inflammatory mediators
Mast cells, Basophils and Macrophages
68
examples of inflammatory mediators
```
• Prostaglandins, Leukotrienes,
• Histamine
- thromboxanes
• Cytokines
• Chemokines
```
69
Cytokines
movement of cells
70
interleukin
communication/messaging between white blood cells
71
Chemokines
movement towards a
| chemical
72
interconnected mediator producing
| systems
kinin, clotting, fibrinolytic and complement
73
examples of cytokines
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)
74
alarm cytokines
```
IL-1, IL-6 and TNFα
- causing local
and systemic activation of fever,
increased vascular permeability,
production of acute phase
proteins and increased
adhesion molecule expression
```
75
anti-inflammatory cytokines
IL-10 and transforming growth factor beta (TGF-β)
| - down-regulate responses
76
IL-12 and IL-18
induce the differentiation of pro-inflammatory subset of T
| cells
77
IL-8
potent chemokine for neutrophils
78
IFNγ
contributing to chronic inflammation
| by recruiting Mφs to sites of damage/infection
79
(IFNa and b)
have antiviral properties within
| infected cells
80
protein structure of chemokines
4 cysteine residues & sequence of amino
| acids involving first two of these
81
Chemotaxis
migration & activation of
| range of cells towards the source (along a concentration gradient)
82
Eicosanoids
unsaturated fatty acids derived from
arachidonic acid
- e.g. Prostaglandins, Leukotrienes and Thromboxanes
83
Kinin system
• Hageman factor (Factor XII) activated following tissue injury
• Activates pre-kallikrein to form kallikrein which cleaves kininogen
to form Bradykinin
• Bradykinin = basic protein that increases vascular permeability,
causes vasodilation, pain and contraction of smooth muscle
84
Clotting system
• Hageman factor activated following
tissue injury
• Activated by damage to blood vessels
and leads to large amounts of Thrombin
• Thrombin then acts on soluble fibrinogen….fibrin and clot
formation and fibrinopeptides which increase vascular
permeability and neutrophil chemotaxis
85
Fibrinolytic system
• Triggered by damage to endothelial cells and
activation of Hageman factor
• Removes clots from the injured tissue
• Active end product = plasmin
• Plasmin is a potent proteolytic enzyme which
breaks down the fibrin clots into degradation
products which are chemotactic for neutrophils
• Also contributes further to inflammation by activating
the classical complement pathway
• Important to block leakage & repair, must maintain
circulation – fibrinolytic system
86
3 activation pathways of complement cascade
classical, lectin and alternative
87
3 major outcomes of complement cascade
```
Opsonise particles to increase
phagocytosis
Regulate inflammatory &
immune responses
Lyse target cells and
microorganisms
```
88
MAC and its components
membrane attack complex - C5b, C6, C7, C8 and polyC9
89
activation of classical pathway
Antibody (IgG or IgM) or c reactive protein (CRP) binds to antigen and attracts C1
90
what metal ion is needed in complement cascades?
Mg2+
91
what stabilises C3bBb?
properdin
92
activation of alternative pathway
spontaneous cleavage of C3 - autohydrolysis due to being an unstable inactive precursor
93
activation of lectin pathway
mannose binding leptin associated with serine proteases
94
ILC1 + NKs
secrete pro-inflammatory TH1-like cytokines (IFNg and TNFa)
95
ILC1
immunity to
| extracellular pathogens
96
NKs
immunity to intracellular pathogens and tumour cells
97
ILC2
immunity to worms, wound healing, secrete TH2
| type cytokines that activate eosinophils
98
ILC3
lymphoid tissue development, intestinal health,
immunity to extracellular bacteria and fungi, secrete
regulatory cytokines
99
3 mechanisms of target cell killing
1. kill targets using perforins
2. express Fas ligand to induce apoptosis
3. antibody dependent cellular cytotoxicity
100
how do eosinophils kill target cells?
Granules contain Cationic peptides, Major
basic protein and Peroxidase all of which
can be released directly onto the surface
of extracellular pathogens (worms) - do not phagocytose
101
g/d T cells
Important in gut antigen recognition of bacterial antigens (particularly
lipids) through non MHC restricted means (CD1)
102
B1 cells
B cells expressing CD5 - Mainly produce low affinity antibody (IgM) mostly against
bacterial antigens (particularly carbohydrates) and are called
natural antibodies
103
receptors for opsonins
antibody receptor (Fc region), complement receptors - mainly CR1,3,4
104
acute phase protein examples
c-reactive protein, mannose binding lectin, serum amyloid a
