Molecules of the Innate Immune System Flashcards

(48 cards)

1
Q

Classes of innate immunity molecules

A
PRRs 
Fc receptors  
Cytokines 
Defensins 
Complement 
Acute phase proteins
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2
Q

What are examples of PRRs?

A

Toll-like receptors TLR-4, TLR-2 and TLR-3

Mannose receptors

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3
Q

What does TLR-4 do?

A

On most cells

Recognises Lipopolysaccharides on gram -ve bacteria

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4
Q

What does binding of LPS to TLR-4 result in?

A

Activation of the cell as binding triggers intracelllular cascades

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5
Q

What does TLR-4 recognise?

A

LPS on gram -ve bacteria

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6
Q

What does TLR-2 recognise?

A

Proteoglycans on gram +ve bacteria

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7
Q

Why are Toll-like receptors broadly specific?

A

Their targets are specific protein sequences, but these are present on many cells so they affect a large range of bacteria.

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8
Q

What does TLR-3 recognise?

A

Double stranded RNA

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9
Q

What is the difference between TLR-3 and TLR-4/2?

A

TLR-4/2 are found on CSM

TLR-3 are found intracellularly

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10
Q

What are mannose receptors?

A

Mannose are found on all cells, but usually they are blocked by other sugars

Bacteria, however have mannose as their surface sufar

Therefore, evolution has told hosts that cells with mannose as their surface sugars are non-self and should be destroyed

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11
Q

What constitutes the complement system?

A

Zymogens

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12
Q

How many molecules constitute the complement system?

A

20-30

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13
Q

How are zymogens activated?

A

By three mechanisms:

Classical - antigen-antibody interactions and C-reactive proteins
Alternative - structures on microbial cell wall
Lectin - receptors recognising sugars

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14
Q

Give an example of a lectin pathway-activating receptor

A

Mannose-binding lectin

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15
Q

What pathways are usually stimulated during infection?

A

Normally all the pathways are stimulated

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16
Q

What happens upon activation of the complement pathway?

A

C3 splits into C3a and C3b

C3b splits C5 into C5a and C5b

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17
Q

What is the role of the comlpement zymogens?

A

C3d is involved in activation of B cells

C3b and C4b opsonises molecules

C5a and C3a are acute inflammatory proteins that attract neutrophils out of the blood stream and into the tissue by releasing histamines that losen epithelium

C3a, C4a and C5a cause mast cell degranulation and enhanced permeability by the release of cytokines

C5b, C3b and C6/7/8 form MAC?

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18
Q

What is the role of C3d?

A

B cell regulation

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19
Q

What is the role of C3b and C4d?

A

Opsonisation.

Phagocytes contain membrane receptors that recognise complement and cause phagocytosis of opsonised molecules

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20
Q

What is the role of C5a and C3a?

A

Chemotactic molecules

Increase vascular permeability by the release of histamines so the neutrophils can travel from the blood to the tissues

21
Q

What is the role of C4a, C3a and C5a?

A

Mast cell degranulation and enhanced permeability by release of cytokines

22
Q

What complement zymogens form the MAC?

A

C5b, C3b, C7-9

23
Q

What is the MAC?

A

Membrane attack complex

Forms a pore in the bacteria which dysregulates the electroc potential across the membrane and causes cell lysis.

24
Q

What regulates the complement cascade?

A

T regulatory cells

25
What is opsonisation?
Binding of antibodies or complement to the antigen Increases phagocytosis since there are receptors for the antibody and complement on phagocytes.
26
How is opsonisation beneficial?
Increases the probability of the antigen being phagocytosed since there are receptors for the antibody and complement on phagocytes.
27
What molecules are involved in opsonisation?
Antibodies | Complement
28
What are the receptors for the opsonisation molecules on phagocytes?
Complement receptors | Fc receptors
29
What are APPs?
Acute phase proteins are produced under the stimulation of cytokines by the liver Cytokines are released when PRRs recognise molecules
30
What does APP stand for?
Acute phase proteins
31
What are examples of APPs?
C3 C-reactive protein Fibrinogen
32
What happens to APP concentration in inflammation?
Increases up to 1000 fold
33
What are the roles of APP?
Promote resolution and repair of inflammatory lesions Enhance host resistance to infection Minimize tissue injury
34
Where are APPs made?
Liver
35
What triggers the formation of APPs?
Cytokines released once PRRs recognise molecules
36
What is an inflammatory lesion?
Lesion produced by the inflammatory response
37
What are defensins?
Defensins small cationic antimicrobial peptides that act on bacteria to destroy them in a similar way to MAC
38
Where are defensins present?
Everywhere. On every cell Secreted or transmembrane forms
39
What do defensins attack?
Bacteria and Fungi
40
How do defensins eradicate pathogens?
Similarly to MAC Form pore that dysregulates the membrane potential of the cell leading to cell lysis
41
What are the two families of defensins?
a-defensins - expressed at all times | b-defensins
42
What are cytokines?
Small, secreted proteins that act like messengers Hormonal system of the IS
43
How big are cytokines?
8-80 kDa
44
Examples of cytokines
IL-1 IL-6 TNF
45
Main functions of cytokines?
Masterful multitaskers Regulate the immune response Control haematopoiesis
46
How do cytokines perform their functions?
Once cytokines bind to their receptors, they trigger intracellular singalling cascades within host cells.
47
What does binding of cytokines onto their receptors cause?
Leads to an increase or decreased expression of genes encoding for Cell surface molecules Other cytokines Cellular activities - activation and proliferation
48
Important cytokines in the innate IR
TNFa IL IFN CSF Chemokines