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Infection and Immunity > Introduction to innate immunity > Flashcards

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
Q

Name the types of pattern recognition receptors

A

Mannose receptors
Scavenger receptors
TLRs
NOD-like receptors (NLRs)
RIG-like receptors
7-transmembrane receptors

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26
Q

What is the ligand and outcome for mannose receptors?

A

Terminal mannose and fucose
Outcome = phagocytosis

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27
Q

What is the ligand and outcome for TLRs?

A

LPS with CD14
Lipoproteins
Unmethylated CpG
Flagellin
dsRNA, ssRNA in endosomes
Outcome = inflammation, cytokine release (TNF, IL-1, IL-12), enhanced killing, ROS & NO

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28
Q

What is the ligand and outcome of NLRs?

A

Peptidoglycan from gram positive and negative bacteria
Some viral DNA and RNA
Outcome = inflammation, cytokine release (IL-1, IL-8)

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29
Q

What is the ligand and outcome of RIG-like receptors?

A

dsRNA and 5/-triphospho RNA
Outcome = type 1 IFN production

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30
Q

What is the ligand and outcome of 7-transmembrane receptors?

A

Formyl-methionine peptides
Outcome = migration into tissues

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31
Q

Give an example of a lectin receptor

A

Mannose receptor

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32
Q

What do lectins bind?

A

Carbohydrates

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33
Q

Describe mannose receptor

A

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
Q

Describe scavenger receptors

A

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
Q

What is the main role of scavenger receptors?

A

Fine tuning TLR signalling
e.g. SR-A, TLR4, TLR2 and CD36 in S. aureus and M. tb recognition

36
Q

Name the class A scavenger receptors

A

SR-A I
SR-A II
MARCO
CD163

37
Q

Name the class B scavenger receptors

A

CD36
SR+BI

38
Q

What do class A receptors have?

A

Collagen or C-type lectin domain

39
Q

What do class B receptors have?

A

CD36 domain

40
Q

What do class D receptors have?

A

LAMP domain

41
Q

What do all of the scavenger receptors appear to have?

A

Clusters of cationic rsidues, centrally located
May account for binding to similar ligands
May be linked to FcR gamma ITAM

42
Q

Describe TLRs

A

Pattern recognition molecules for bacterial and viral ligands
Stimulate cytokine release

43
Q

What are the types of TLR?

A

TLR1 to -9

44
Q

Ligand for TLR1

A

Modulin
Lipopeptides
Origin = gram positive bacteria

45
Q

Ligand for TLR2

A

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
Q

Ligand for TLR3

A

dsRNA
Origin = virus

47
Q

Ligand for TLR4

A

LPS; origin = gram-negative bacteria
Lipoteichoid acid, mannuronic acid polymers; origin = gram positive bacteria
Taxol; origin = plant
Hsp60, Hsp70, fibronectin; origin = Host

48
Q

Ligand of TLR5

A

Flagellin
Origin = gram negative bacteria, gram positive bacteria

49
Q

Ligand of TLR6

A

Modulin
Soluble tuberculosis factor
Outer surface protein A lipoprotein (OspA-L)
Origin = gram positive bacteria

50
Q

Ligand of TLR7

A

ssRNA
Small antiviral compounds
Origin = virus

51
Q

Ligand for TLR8

A

Small antiviral compounds

52
Q

Ligand for TLR9

A

Unmethylated CpG-DNA
Origin = bacteria, virus

53
Q

What do NLRs do?

A

Bind dsRNA and peptidoglycan

54
Q

What do RIG-1-like helicases do?

A

Recognise dsRNA intermediate of viral replication

55
Q

What can some NLRs form?

A

The inflammasome

56
Q

What is the inflammasome?

A

A multiprotein oligomer complex which assembles in the cytoplasm after PAMP/DAMP detection

57
Q

What does inflammasome formation lead to?

A

Can lead to activation of caspase including caspase-1 which cleaves precursors to IL-1 and IL-18

58
Q

What is the inflammasome composed of?

A

Several intracellular PRRs including NLRs and can be triggered by PAMPs and DAMPs

59
Q

What does inflammasome formation lead to?

A

Pyroptosis
Inflammatory cell death

60
Q

What is the inflammasome linked to?

A

Autoimmunity (MS, diabetes)
Inflammation such as atherosclerosis
May be an exaggerated response to host-derived factors

61
Q

What are some other innate cells?

A

NK cells
NKT cells
DCs
Gamma delta T cells
Innate lymphoid cells

62
Q

Describe NK cells

A

Large granular lymphocytes
4% of WBCs are NK cells
Play a role between innate and specific immunity

63
Q

What do NK cells do?

A

Kill certain tumour and virally infected cells

64
Q

What are NK cells activated by?

A

FcR and KIR

65
Q

How do NK cells destroy target cells?

A

Target cell destruction cause by cytotoxic molecules called granzymes and perforins

66
Q

What are NKT cells?

A

Express NK and T cell markers
Intermediate TCR expression

67
Q

Describe NKT cells

A

Restricted TCR alpha chain usage
Recognises through CD1d
Produces Th1 and Th2 cytokines
Recognises lipids, glycolipids, hydrophobic peptides

68
Q

What effects do NKT cells have?

A

Alpha-galactosylceramide and anti-tumour effect

69
Q

Describe gamma delta T cells

A

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
Q

What do gamma delta T cells recognise?

A

A number of bacterial antigens
Small aliphatic molecules (isoprenoid pyrophosphates and amines) which may represent a pattern recognition system

71
Q

What does the gamma chain consist of?

A

V, J and C regions

72
Q

What does the delta chain consist of?

A

V, D, J and C regions

73
Q

What are immune lymphoid cells?

A

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
Q

Where are ILCs found?

A

At barrier/mucosal surfaces
e.g. intestine, lungs, skin etc.

75
Q

Name group 1 ILCs

A

NK cells
ILC1

76
Q

Name group 2 ILCs

A

ILC2

77
Q

Name group 3 ILCs

A

LTi cell
NCR- ILC3
NCR+ ILC3

78
Q

Describe ILC3

A

Main ILC in human non-inflamed gut

79
Q

What does ILC3 do?

A

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
Q

How are ILCs involved in Crohn’s Disease

A

The ILC3 population is replaced by the ILC1 population
Produces IFN-G and causes chronic inflammation

81
Q

What are DCs?

A

Irregularly shaped cells in most tissues
May be myeloid or lymphoid derived in tissues

82
Q

What DCs do?

A

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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