3. Innate immunity Flashcards

1
Q

Innate immunity

A

Present from birth “inbuilt”
Not enhanced by 2nd exposure, no memory
Uses cellular and soluble components

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2
Q

Innate immunity timings

A

Rapid response
Mins-hours
Cooperates with and directs adaptive immunity

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3
Q

Innate immunity “pattern” recognition strategies

A

PAMP
DAMP
Natural Killer cells

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4
Q

How is PAMP a pattern recognition strategy?

A

Detect conserved microbial structures

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5
Q

How is DAMP a pattern recognition strategy?

A

Detect consequences of cell infection or injury

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6
Q

How are Natural Killer cells a pattern recognition strategy?

A

Detect ‘missing self’

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7
Q

What are the innate immunity defence barriers?

A

Anatomical (physical)
Physiological
Phagocytic
Inflammatory

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8
Q

What are the anatomical defence barriers in innate immunity?

A

Skin- mechanical barrier, acidic environment

Mucous membranes- mucous traps microorganisms, cilia expel

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9
Q

What are the physiological defence barriers in innate immunity?

A

Body temp./ fever - provides suboptimal conditions for pathogen replication
Low pH- acidic pH of stomach kills many ingested microorganisms
Chemical mediators- lysozyme, interferons, complement

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10
Q

What are the phagocytic defence barriers in innate immunity?

A

Cells ingest material

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11
Q

What are the inflammatory defence barriers in innate immunity?

A

Local vascular permeability increases

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12
Q

Cell types in innate immunity

A
Neutrophil
Eosinophil
Basophil
Monocyte/ macrophage
Mast cell
Dendritic cell
Natural killer cell
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13
Q

What do neutrophils perform?

A

phagocytosis and killing of microbes

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14
Q

What do eosinophils perform?

A

Phagocytosis
Granule release
Help B cell responses (IgA production)

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15
Q

What do basophils perform?

A

Granule release

May act as antigen presenting cell for type 2 immunity

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16
Q

What do macrophages perform?

A

Phagocytosis
Killing
Cytokine release
Act as antigen presenting cell

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17
Q

What do mast cells perform?

A

Granule release:
Histamine
Other Inflammatory mediators e.g. cytokine

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18
Q

What do dendritic cells perform?

A

Antigen capture and presentation

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19
Q

What do natural killer cells perform?

A

Lysis of infected cells

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20
Q

Major phagocytic cell types

A

Neutrophil

Macrophage

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21
Q

Describe neutrophils

A

Polymorphonuclear leukocyte
Main type of leukocyte
Short lived

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22
Q

How do neutrophils move?

A

Circulate in blood then migrate into tissues

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23
Q

Which cells are 1st to be recruited to a site of tissue damage/ infection?

A

Neutrophils

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24
Q

Describe macrophages

A

Less abundant (than neutrophils)
Dispersed throughout tissue
Signal infection by release of cytokines

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25
Q

What do neutrophils need to do to fight infection?

A

Move from circulation into infected tissue
Bind to pathogen
Phagocytose pathogen
Kill Pathogen

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26
Q

Describe the movement of neutrophils into tissue

A

Neutrophil rolls along surface of capillary, weakly binding, selection mediated
If endothelium receives sign of infection: neutrophil binds tightly to integrins on surface
Migrates through endothelium

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27
Q

Opsonisation

A

Coating of micro-organisms with proteins to facilitate phagocytosis

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28
Q

Opsonins

A

Molecules that bind to antigen, and phagocytes

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29
Q

What function as opsonins?

A

Antibodies

Complement

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30
Q

What are the 2 classes of neutrophil killing mechanisms?

A

Oxygen Independent

Oxygen Dependent

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31
Q

What are the oxygen independent killing mechanisms?

A
Enzymes (Lysozyme and hydrolytic enzymes)
Antimicrobial peptides (defensins)
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32
Q

What are the oxygen dependent killing mechanisms?

A
Respiratory burst of:
Superoxide anion
Hydrogen peroxide
Singlet oxygen
Hydroxyl radical
Nitric oxide
Reactive nitrogen intermediates
33
Q

Neutrophil Extracellular Traps (NETs)

A

Activated neutrophils release granule proteins and chromatin to form extracellular fibres.

34
Q

What is the function of neutrophil extracellular traps?

A

To trap microorganisms, allow enhanced phagocytosis by other cells and stop microorganism spreading in circulation.

35
Q

Macrophage function

A

Expresses receptors for many material constituents
Bacteria binding initiates release of cytokines (danger!= recruit more cells)
Macrophage engulfs and digests bound bacteria

36
Q

What do mast cells secrete?

A

Histamine

Other inflammatory mediators e.g. cytokines

37
Q

Where can mast cells be found?

A
Near mucosa (lung)
Near connective tissue (skin/ peritoneal cavity/ blood vessels)
38
Q

What can mast cells do to bacteria?

A

Recognise, phagocytose and kill bacteria

39
Q

How can mast cells be activated?

A

By complement products (Anaphylatoxins)

40
Q

In anaphylaxis, body wide degranulation of mast cells leads to

A

Vasodilation

Increased vascular permeability

41
Q

Describe natural killer cells (NK cells)

A

Large granulated lymphocytes: cytotoxic
Lyse target cells
Secrete the cytokine: interferon-gamma

42
Q

What proportion of peripheral blood lymphocytes are NK cells?

43
Q

Receptors on NK cells

A

No antigen-specific receptor, but express both activating and inhibitory receptors: balance of signals

44
Q

NK cells have receptors which bind to antibody-coated cells

A

So they can kill the cell (Antibody Dependent Cell-mediated Cytotoxicity)

45
Q

What are NK cells important in defence against?

A
Tumour cells
Viral infections (e.g. Herpes)
46
Q

If a cell is healthy there is ligation of inhibitory NK receptors

A

NK recognises cell as self

Inhibits killing of cell

47
Q

In an infected cell, there is ligation of activating NK receptors

A

NK recognises “missing self”

Kills target cell

48
Q

Describe Cytokines

A

Small proteins secreted for local, short-lived cell-to-cell communication
=”messengers” of immune system

49
Q

Why do cytokines have short half lives?

A

Have a biological effect at very low concentration

Need short half life to control effects

50
Q

What do cytokines bind to?

A

Specific receptors on other cells

51
Q

Types of cytokine

A
Interleukins (IL-x)
Interferons (IFN)
Chemokines
Growth factors
Cytotoxic
52
Q

Interleukin function

A

Allow communication between leukocytes

53
Q

Interferon function

A

Anti-viral effects

Interfere with virus replication

54
Q

Chemokine function

A

chemotaxis

cell movement

55
Q

Growth factor function

A

Proliferation & differentiation of cells

56
Q

Cytotoxic cytokines

A

Induce apoptosis, tumour necrosis factor (TNF)

57
Q

Proximity to other cells cytokine action

A

Most work in paracrine

58
Q

Paracrine

A

Works on nearby cell

59
Q

Name 2 alarm cytokines secreted by activated macrophages

A

IL-1

TNF-alpha

60
Q

Describe dendritic cells

A

Network of cells located at likely sites of infection
Recognise microbial patterns, secrete cytokines
Act as antigen presenting cells

61
Q

Complement system plays a major role in

A

complementing activity of specific antibody in lysing bacteria

62
Q

What is the complement system?

A

Complex series of ~30 proteins and glycoproteins that lead to a triggered enzyme cascade system

63
Q

Complement system timings

A

Rapid, highly amplified response

64
Q

Where are components of the complement system mainly produced?

65
Q

How is complement a triggered enzyme cascade system?

A

Components produced by liver are initially inactive precursors (enzymes)
Part must be cleaved to activate.
Once activated, cleaves substrate in next reaction.
Sequential activation of subsequent enzymes amplifies number of activated molecules

66
Q

What are the 3 complement activation pathways?

A

Classic
Lectin pathway
Alternative

67
Q

What is the classic complement activation pathway?

A

Antibody bound to antigen (immune complex)

68
Q

Cleaved “waste” from precursor is a pro-inflammatory molecule

A

Signals to other cells.

Binds to specific receptors on mast cells, cause degranulation (release histamine)

69
Q

What is the lectin pathway in complement activation?

A

Lectins bind to carbohydrates only on bacteria leading to activation of complement

70
Q

Lectins

A

proteins that bind to carbohydrate

71
Q

What is alternate complement activation?

A

Bacterial surfaces directly activate complement via different components

72
Q

All 3 complement pathways converge to activated C3b

A

Which opsonises antigens/pathogens.

Membrane attack complex formed that forms holes in bacterial cell membrane and causes loss of integrity

73
Q

Functions of complement

A

Lysis
Opsonisation
Activation of inflammatory response
Clearance of immune complexes

74
Q

Control of complement

A

Short half life
Dilution of components in biological fluids
Circulating and membrane bound regulatory proteins

75
Q

Local inflammatory response may be accompanied by

A
A systemic response 
"Acute phase" after 1-2 days
Fever
Increased production of WBCs 
Production of acute phase proteins in liver
76
Q

How is a systemic acute phase response induced?

A

By cytokines

77
Q

Acute-phase proteins

A

C-reactive protein (CRP)
Mannan binding lectin (MBL)
Complement
Fibrinogen (clotting)

78
Q

Which acute phase proteins activate complement?

A

C-reactive protein (CRP)

Mannan binding lectin (MBL)