Molecules of the Innate Immune System Flashcards

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
Q

What is opsonisation?

A

Binding of antibodies or complement to the antigen

Increases phagocytosis since there are receptors for the antibody and complement on phagocytes.

26
Q

How is opsonisation beneficial?

A

Increases the probability of the antigen being phagocytosed since there are receptors for the antibody and complement on phagocytes.

27
Q

What molecules are involved in opsonisation?

A

Antibodies

Complement

28
Q

What are the receptors for the opsonisation molecules on phagocytes?

A

Complement receptors

Fc receptors

29
Q

What are APPs?

A

Acute phase proteins are produced under the stimulation of cytokines by the liver

Cytokines are released when PRRs recognise molecules

30
Q

What does APP stand for?

A

Acute phase proteins

31
Q

What are examples of APPs?

A

C3
C-reactive protein
Fibrinogen

32
Q

What happens to APP concentration in inflammation?

A

Increases up to 1000 fold

33
Q

What are the roles of APP?

A

Promote resolution and repair of inflammatory lesions
Enhance host resistance to infection
Minimize tissue injury

34
Q

Where are APPs made?

A

Liver

35
Q

What triggers the formation of APPs?

A

Cytokines released once PRRs recognise molecules

36
Q

What is an inflammatory lesion?

A

Lesion produced by the inflammatory response

37
Q

What are defensins?

A

Defensins small cationic antimicrobial peptides that act on bacteria to destroy them in a similar way to MAC

38
Q

Where are defensins present?

A

Everywhere. On every cell

Secreted or transmembrane forms

39
Q

What do defensins attack?

A

Bacteria and Fungi

40
Q

How do defensins eradicate pathogens?

A

Similarly to MAC

Form pore that dysregulates the membrane potential of the cell leading to cell lysis

41
Q

What are the two families of defensins?

A

a-defensins - expressed at all times

b-defensins

42
Q

What are cytokines?

A

Small, secreted proteins that act like messengers

Hormonal system of the IS

43
Q

How big are cytokines?

A

8-80 kDa

44
Q

Examples of cytokines

A

IL-1
IL-6
TNF

45
Q

Main functions of cytokines?

A

Masterful multitaskers

Regulate the immune response
Control haematopoiesis

46
Q

How do cytokines perform their functions?

A

Once cytokines bind to their receptors, they trigger intracellular singalling cascades within host cells.

47
Q

What does binding of cytokines onto their receptors cause?

A

Leads to an increase or decreased expression of genes encoding for

Cell surface molecules
Other cytokines
Cellular activities - activation and proliferation

48
Q

Important cytokines in the innate IR

A

TNFa

IL

IFN

CSF

Chemokines