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Introduction to innate immunity Flashcards

1
Q

Describe innate immunity

A

Physical barriers
Chemical barriers
Phagocytes
Inflammation, acute phase response
Complement
Cytokine/chemokines

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2
Q

Describe adaptive immunity

A

T lymphocytes
B lymphocytes
Cytokines

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3
Q

Describe the specificity of the innate immune response

A

Non specific
No antigen recognition

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4
Q

Describe the specificity of the adaptive immune response

A

Involves very specific recognition of precipitating agent

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5
Q

Compare innate and adaptive immunity

A

Cells - macrophages, neutrophils, DCs (innate); lymphocytes (adaptive)
Speed - fast (innate); slow (adaptive)
Memory - none (innate); yes (adaptive)
Specificity - low (innate); very very very high (adaptive)
Receptors - host molecule, pattern recognition (innate); Ig, TCR (adaptive)
Strategy of recognition - small no of ligands, highly conserved, widely distributed, receptors evolved by natural selection (innate); every possible antigen, receptors generated randomly within individual, cannot be passed to offspring (adaptive)

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6
Q

Describe neutrophils

A

Large cells 10-20 microns
Neutral staining cytoplasmic granules containing enzymes e.g. lysozyme
Only live for 2-3 days
90% of granulocytes are neutrophils
Phagocytic - kill bacteria by microbicidal mechanisms
Most important cell in non-viral infections

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7
Q

Describe eosinophils

A

Contain prominent granules which stain red with eosin
Granules contain a crystalline core cytotoxic for parasites (eosinophil basic protein)
Important in immunity for helminth infections
Phagocytic but this is not a major function

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8
Q

Describe basophils

A

< 0.2% of WBCs are basophils
Only go into tissues during inflammation
When stimulated they release substances that promote inflammation
Important in allergy
Not thought to phagocytose

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9
Q

Describe monocytes

A

In the blood for 1-2 days
Phagocytic
They are mononuclear leukocytes

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10
Q

Describe macrophages

A

Monocytes in tissues are macrophages
Up to 10x larger than monocytes
Can live for months-years
Phagocytic
Adherent
Characteristics depend on the tissue

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11
Q

How do innate cells recognise foreign molecules?

A

Two ways:
1) Get their specificity from host molecules e.g. IgG, complement components, chemokines
2) Inherent specificity (pattern recognition) e.g. germline encoded receptors for conserved molecular patterns which detect foreign invaders or aged/damaged host cells (apoptotic)

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12
Q

What are examples of opsonic receptors?

A

FcR
CR3

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13
Q

What are examples of non-opsonic patter-recognition receptors?

A

Lectin receptors
Scavenger receptor
TLRs

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14
Q

What is the ligand for Fc receptors and the outcome of its binding?

A

Ig ligand
Outcome = phagocytosis

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15
Q

What is the ligand for complement receptors and the outcome of its binding?

A

Complement components
Outcome = phagocytosis

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16
Q

What is the ligand for 7-transmembrane receptors (G-protein-coupled) and the outcome of its binding?

A

Chemokines e.g. IL-8
Complement fragments e.g. C5a
Lipid mediators e.g. prostaglandins, leukotrienes
Outcome = Migration into tissues

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17
Q

What are the types of Fc receptors?

A

Fc gamma R
Fc alpha R
Fc epsilon R

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18
Q

What does binding to Fc receptors result in?

A

Internalisation of antibody coated antigen

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19
Q

What do Fc receptors on macrophages result in?

A

Activation and production of ROS

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20
Q

What are some types of complement receptors?

A

CR1-5
CR1
CR3
CR4

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21
Q

What do complement receptors bind?

A

Cleavage products which are bound to pathogens, immune complexes of other complement activators
They can be endocytic and activatory

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22
Q

Describe chemokine receptors

A

7 transmembrane receptors
Common family of membrane proteins
G-protein coupled

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23
Q

What do chemokine receptors do?

A

Recognise host chemokines and also microbial formyl-met peptides (starting sequence in protein synth)
Result in cell migration

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24
Q

What are the general properties of PAMPs?

A

Present only on pathogens and not on host cells
Essential for survival of pathogens
Invariant structures shared by entire class of pathogens

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25
Name the types of pattern recognition receptors
Mannose receptors Scavenger receptors TLRs NOD-like receptors (NLRs) RIG-like receptors 7-transmembrane receptors
26
What is the ligand and outcome for mannose receptors?
Terminal mannose and fucose Outcome = phagocytosis
27
What is the ligand and outcome for TLRs?
LPS with CD14 Lipoproteins Unmethylated CpG Flagellin dsRNA, ssRNA in endosomes Outcome = inflammation, cytokine release (TNF, IL-1, IL-12), enhanced killing, ROS & NO
28
What is the ligand and outcome of NLRs?
Peptidoglycan from gram positive and negative bacteria Some viral DNA and RNA Outcome = inflammation, cytokine release (IL-1, IL-8)
29
What is the ligand and outcome of RIG-like receptors?
dsRNA and 5/-triphospho RNA Outcome = type 1 IFN production
30
What is the ligand and outcome of 7-transmembrane receptors?
Formyl-methionine peptides Outcome = migration into tissues
31
Give an example of a lectin receptor
Mannose receptor
32
What do lectins bind?
Carbohydrates
33
Describe mannose receptor
Recognises terminal mannose and fucose which ae not present in human molecules It is a membrane bound soluble form of Mannan Binding Lectin in complement Results in phagocytosis
34
Describe scavenger receptors
Membrane bound PRRs Bind to apoptotic cells/modified self molecules Responsible for clearing up after an immune response Also bind bacterial cell walls Recognise lipoproteins
35
What is the main role of scavenger receptors?
Fine tuning TLR signalling e.g. SR-A, TLR4, TLR2 and CD36 in S. aureus and M. tb recognition
36
Name the class A scavenger receptors
SR-A I SR-A II MARCO CD163
37
Name the class B scavenger receptors
CD36 SR+BI
38
What do class A receptors have?
Collagen or C-type lectin domain
39
What do class B receptors have?
CD36 domain
40
What do class D receptors have?
LAMP domain
41
What do all of the scavenger receptors appear to have?
Clusters of cationic rsidues, centrally located May account for binding to similar ligands May be linked to FcR gamma ITAM
42
Describe TLRs
Pattern recognition molecules for bacterial and viral ligands Stimulate cytokine release
43
What are the types of TLR?
TLR1 to -9
44
Ligand for TLR1
Modulin Lipopeptides Origin = gram positive bacteria
45
Ligand for TLR2
Lipopreoteins, peptidoglycan, lipteichoic acid; origin = gram positive bacteria Mannuronic acid polymers; origin = pseudomonas aeruginosa Modulin; origin = Staphylococcus Lipoproteins, lipopeptides, lipoarabinomannan; origin = Mycobacteriae, Mycoplasmae Heat-killed bacteria; origin = Listeria Zymosan; origin = Yeast
46
Ligand for TLR3
dsRNA Origin = virus
47
Ligand for TLR4
LPS; origin = gram-negative bacteria Lipoteichoid acid, mannuronic acid polymers; origin = gram positive bacteria Taxol; origin = plant Hsp60, Hsp70, fibronectin; origin = Host
48
Ligand of TLR5
Flagellin Origin = gram negative bacteria, gram positive bacteria
49
Ligand of TLR6
Modulin Soluble tuberculosis factor Outer surface protein A lipoprotein (OspA-L) Origin = gram positive bacteria
50
Ligand of TLR7
ssRNA Small antiviral compounds Origin = virus
51
Ligand for TLR8
Small antiviral compounds
52
Ligand for TLR9
Unmethylated CpG-DNA Origin = bacteria, virus
53
What do NLRs do?
Bind dsRNA and peptidoglycan
54
What do RIG-1-like helicases do?
Recognise dsRNA intermediate of viral replication
55
What can some NLRs form?
The inflammasome
56
What is the inflammasome?
A multiprotein oligomer complex which assembles in the cytoplasm after PAMP/DAMP detection
57
What does inflammasome formation lead to?
Can lead to activation of caspase including caspase-1 which cleaves precursors to IL-1 and IL-18
58
What is the inflammasome composed of?
Several intracellular PRRs including NLRs and can be triggered by PAMPs and DAMPs
59
What does inflammasome formation lead to?
Pyroptosis Inflammatory cell death
60
What is the inflammasome linked to?
Autoimmunity (MS, diabetes) Inflammation such as atherosclerosis May be an exaggerated response to host-derived factors
61
What are some other innate cells?
NK cells NKT cells DCs Gamma delta T cells Innate lymphoid cells
62
Describe NK cells
Large granular lymphocytes 4% of WBCs are NK cells Play a role between innate and specific immunity
63
What do NK cells do?
Kill certain tumour and virally infected cells
64
What are NK cells activated by?
FcR and KIR
65
How do NK cells destroy target cells?
Target cell destruction cause by cytotoxic molecules called granzymes and perforins
66
What are NKT cells?
Express NK and T cell markers Intermediate TCR expression
67
Describe NKT cells
Restricted TCR alpha chain usage Recognises through CD1d Produces Th1 and Th2 cytokines Recognises lipids, glycolipids, hydrophobic peptides
68
What effects do NKT cells have?
Alpha-galactosylceramide and anti-tumour effect
69
Describe gamma delta T cells
Make up 10% of peripheral blood mononuclear cells but up to 70% of mucosal T cells Some express CD8 and CD4 Most are double negative Restricted through MHC molecules as alpha beta Some gamma delta T cells are restricted through other molecules such as alpha-3 butyrophilin
70
What do gamma delta T cells recognise?
A number of bacterial antigens Small aliphatic molecules (isoprenoid pyrophosphates and amines) which may represent a pattern recognition system
71
What does the gamma chain consist of?
V, J and C regions
72
What does the delta chain consist of?
V, D, J and C regions
73
What are immune lymphoid cells?
A growing family of immune cells that have similar phenotypes and functions to T cells However, they do not express acquired antigen receptors or undergo clonal selection/expansion like when stimulated like T cells do
74
Where are ILCs found?
At barrier/mucosal surfaces e.g. intestine, lungs, skin etc.
75
Name group 1 ILCs
NK cells ILC1
76
Name group 2 ILCs
ILC2
77
Name group 3 ILCs
LTi cell NCR- ILC3 NCR+ ILC3
78
Describe ILC3
Main ILC in human non-inflamed gut
79
What does ILC3 do?
Produces IL-22 in response to endothelial signals e.g. IL-23 Produces induced antimicrobial response DCs control this partly by production of IL-22BP
80
How are ILCs involved in Crohn's Disease
The ILC3 population is replaced by the ILC1 population Produces IFN-G and causes chronic inflammation
81
What are DCs?
Irregularly shaped cells in most tissues May be myeloid or lymphoid derived in tissues
82
What DCs do?
When immature they capture and engulf Ag and pass to lymphoid tissues where they mature and present antigen to T cell They direct polarisation of the immune system towards either Th1 or Th2 cells

Infection and Immunity (33 decks)

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