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Innate immune responses Flashcards

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1
Q

What are the two main features of the innate immune response?

A

Non-specific

Rapid - initial response takes a few hours

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2
Q

What are the molecules involved in the innate immune response?

A

Antimicrobial peptides

Complement

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3
Q

What are the cells involved in the innate immune response?

A

Phagocytes

Natural Killer Cells

Interferons

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4
Q

What are the four host defences?

A

Anatomical and chemical barriers

Intrinsic

Innate immunity

Acquired immunity

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5
Q

What are the anatomical and chemical barriers preventing pathogens from causing disease?

A

Skin

Mucus

Tears

Preformed soluble molecules

Low pH

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6
Q

Which cells take part in intrinsic immunity?

A

Always present in all uninfected cells

They have the ability to prevent viruses from getting into the cell

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7
Q

Which processes form part of the intrinsic immunity?

A

Autophagy

RNA silencing

Antiviral proteins

Apoptosis

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8
Q

Examples of cellular proteins that inhibit viral replication

A

TRIM

APOBEC3

Tetherin

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9
Q

Examples of soluble mechanisms of innate immunity

A

Antimicrobial enzymes

Antimicrobial proteins

Complement

Cytokines

Acute phase proteins

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10
Q

Examples of antimicrobial proteins

A

Defensins

Cathelicidins

Histatins

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11
Q

How do defensins provide immunity?

A

Small cationic antimicrobial peptides that enter the negatively charged membrane

Form pores

Leads to a loss of small-molecule gradients

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12
Q

What are the two main structural families of defensins?

A

Alpha defensins

Beta defensins

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13
Q

Which family of defensins is constitutively expressed?

A

Alpha defensins

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14
Q

What are the two cellular responses in innate immunity in responser to danger inputs?

A

Response to threat

Communication to other immune cells

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15
Q

What are the three types of PRRs?

A

Intracellular

Cell surface

Secreted

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16
Q

Examples of DAMPs

A

Ion concentration changes

DNA

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17
Q

What type of antigens are recognised by the innate immune system?

A

Structures shared by classes of microbes

100 receptors = 100 molecules recognised

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18
Q

How many types of receptors recognise antigens that activate the innate immune system?

A

Around 100

Germline encoded

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19
Q

What type of antigens are recognised by the adaptive immunity?

A

Specific epitoptes

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20
Q

How many molecules can be recognised by the adaptive immune system?

A

> 10^7

Receptor genes undergo somatic recombination, leading to a huge diversity in the molecules recognised

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21
Q

What are the two classes of receptors making up the adaptive immune system?

A

Antibody

TCR

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22
Q

What is the main difference of the recognition potential of the adaptive immunity vs the innate immunity?

A

The adaptive immune receptors undergo somatic recombination

So although there are two main types of receptors (BCR and TCR), there is high variability in their subtypes

The innate immune receptors do not undergo somatic recombination, and the receptors they produce are used to recognise the different antigens

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23
Q

What are the two main types of PRRs?

A

Soluble molecules

Cell associated molecules

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24
Q

Examples of soluble PRRs

A

Pentraxins

Ficolins

Collectins

Complement proteins

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25
Examples of cell associted PRRs
C-type lectins TLR Scavenger receptors NOD like receptors RIG-like receptors c-GAS
26
What is the difference between different cell associated PRRs?
Found in different locations on the cell Cell surface = C-type lectins, TLR Inside endosomes = TLR Cytosolic = NOD like receptors, RIG-like receptors
27
How are soluble PRRs useful?
Recognise presence of a pathogen in the circulation
28
Describe the specificity of PRRs
Different PRRs recognise different patterns Elicit specific responses upon binding to a pattern
29
Describe TLR signalling
1. Ligand engages TLR 2. Association of protein kinases to adaptor proteins 3. Activation of transcription factors 4. Formation of respiratory bursts, cytokines, chmokines, MMPs, antimicrobial peptides
30
What is the function of IRF?
Interferon regulatory factor Generally antiviral
31
What is the function of NFkB?
Generally inflammatory
32
What are the 3 major classes of cytosol PRRs?
NOD like receptors RIG like receptors Cytosolic DNA sensors
33
What do NOD like receptors recognise?
NOD1/2 recognise the bacterial cell wall
34
What do RIG like receptors recognise?
Viral RNA
35
What do cytosolic DNA sensors recognise?
Microbial DNA in the cytoplasm
36
What are the cells of the innate immunity?
Macrophages Dendritic cells Neutrophils Eosinophils Basophils Mast cells Natural killer cells
37
What is special about neutrophils, eosinophils and basophils?
They are polymorphonuclear leukocytes Contain granules that stain in different ways to allow for identification
38
What happens to macrophages and DCs once stimulated by PRRs?
Increase their antigen presenting capacity Lead to the development of the adaptive immunity
39
Describe the process by which phagocytosis destroys pathogens
1. Chemotaxis 2. Adherence via PAMP recognition 3. Cell activation via PRR 4. Initiation of phagocytosis 5. Phagosome formation 6. Phagolysosome formation 7. Bacterial killing and digestion 8. Release of degradation products
40
What is the main purpose of opsonisation?
Allows the process of phagocytosis to function more efficiently
41
How do cells carrying out phagocytosis recognise the microbe?
The microbe is bound to antibodies The FcR of the phagocytosing cell recognises the Fc portion of the antibody
42
What three main processes lead to bacterial killing in the phagolysosome?
Enzymes Reactive oxygen species Reactive nitrogen species
43
Examples of ROS
Hydroxyl radical Superoxide
44
Oxygen-independent mechanisms of pathogen destruction
Damage to microbial membrane by - cathepsin G - defensins - cationic proteins - bacteriidial permeability increasing proteins Splitting of mucopeptide in the bacterial cell wall by lyzosymes Complex with iron through lactoferrin Digestion of killed organisms through proteolytic and hydrolytic enzymes
45
What is phagocytosis?
Ingestion and killing of extracellular microbes
46
Which cells carry out phagocytosis?
Neutrophils Monocytes Macrophages
47
From which cells are macrophages derived from?
Monocytes
48
Which are the first cells to respond to infection?
Neutrophils
49
What type of cell are natural killer cells?
Large granular lymphocytes
50
Where are natural killer cells found?
In the circulation
51
What percentage of circulating leykocytes do NK cells make up?
5-20%
52
NK cells destroy bacteria TRUE or FALSE
FALSE Recognise changes in self cells
53
What do NK cells respond to?
Cells with missing self antigens Stressed cells Viral haemagglutinins Antibody-coated cells
54
What are the two responses evoked by NK cells?
Cytotoxicity IFNy release
55
What are NK cells an important source of?
Interferon gamma
56
Describe what is meant by 'NK cells react to cells with abnormal self receptors'
Cells express activator proteins as well as MHC I MHC I binds to the inhibitory receptors on NK cells, preventing them from causing cell death In cancer or infected cells, they can overexpress activatory proteins or reduce expression of MHC I This is detected by NK cells, which cause death of these abnormal cells
57
What are the mechanisms of NK cell killing?
Granzymes enter target cell via perforin pore or endocytosis Activation of apoptotic pathways
58
Which cell links the adaptive and innate immune responses?
Dendritic cells
59
Which scientist first described Dendritic cells?
Langerhans
60
What are the two states dendritic cells are found in?
Immature Mature
61
Compare the MHC expression between mature and immature DCs
Mature DCs express MHC highly Immature has low surface MHC
62
Do mature or immature DCs have high phagocytic activity?
Immature DCs are highly phagocytic
63
How do DCs become mature?
Through detection of microbial products Inflammatory cytokines Damaged host cells
64
Give a brief overview of the role of DCs in the innate immune response
Immature DCs are found in many tissues Mature in inflamed tissues following cytokine signals and antigen capture Mature DCs migrate to lymph nodes and present antigenic peptides to T cells
65
What type of cells are dendritic cells?
Professional antigen presenting cells Activate naive T cells
66
How do NK cells carry out cell death the activation of apoptotic pathways?
FASL on NK cells binds to Fas on target cell FADD becomes activated upon binding, which turns procaspase-8 into caspase-8 Caspase-8 activates Caspase-3 Caspase-3 leads to apoptosis
67
What is the marker for mature dendritic cells?
CCR7 Immature DCs are also CCR7+, but also express CCR2,5,6

IMM005 (17 decks)

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