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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
What do neutrophils need to do to fight infection?
Move from circulation into infected tissue Bind to pathogen Phagocytose pathogen Kill Pathogen
26
Describe the movement of neutrophils into tissue
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
27
Opsonisation
Coating of micro-organisms with proteins to facilitate phagocytosis
28
Opsonins
Molecules that bind to antigen, and phagocytes
29
What function as opsonins?
Antibodies | Complement
30
What are the 2 classes of neutrophil killing mechanisms?
Oxygen Independent | Oxygen Dependent
31
What are the oxygen independent killing mechanisms?
``` Enzymes (Lysozyme and hydrolytic enzymes) Antimicrobial peptides (defensins) ```
32
What are the oxygen dependent killing mechanisms?
``` Respiratory burst of: Superoxide anion Hydrogen peroxide Singlet oxygen Hydroxyl radical Nitric oxide Reactive nitrogen intermediates ```
33
Neutrophil Extracellular Traps (NETs)
Activated neutrophils release granule proteins and chromatin to form extracellular fibres.
34
What is the function of neutrophil extracellular traps?
To trap microorganisms, allow enhanced phagocytosis by other cells and stop microorganism spreading in circulation.
35
Macrophage function
Expresses receptors for many material constituents Bacteria binding initiates release of cytokines (danger!= recruit more cells) Macrophage engulfs and digests bound bacteria
36
What do mast cells secrete?
Histamine | Other inflammatory mediators e.g. cytokines
37
Where can mast cells be found?
``` Near mucosa (lung) Near connective tissue (skin/ peritoneal cavity/ blood vessels) ```
38
What can mast cells do to bacteria?
Recognise, phagocytose and kill bacteria
39
How can mast cells be activated?
By complement products (Anaphylatoxins)
40
In anaphylaxis, body wide degranulation of mast cells leads to
Vasodilation | Increased vascular permeability
41
Describe natural killer cells (NK cells)
Large granulated lymphocytes: cytotoxic Lyse target cells Secrete the cytokine: interferon-gamma
42
What proportion of peripheral blood lymphocytes are NK cells?
5-10%
43
Receptors on NK cells
No antigen-specific receptor, but express both activating and inhibitory receptors: balance of signals
44
NK cells have receptors which bind to antibody-coated cells
So they can kill the cell (Antibody Dependent Cell-mediated Cytotoxicity)
45
What are NK cells important in defence against?
``` Tumour cells Viral infections (e.g. Herpes) ```
46
If a cell is healthy there is ligation of inhibitory NK receptors
NK recognises cell as self | Inhibits killing of cell
47
In an infected cell, there is ligation of activating NK receptors
NK recognises "missing self" | Kills target cell
48
Describe Cytokines
Small proteins secreted for local, short-lived cell-to-cell communication ="messengers" of immune system
49
Why do cytokines have short half lives?
Have a biological effect at very low concentration | Need short half life to control effects
50
What do cytokines bind to?
Specific receptors on other cells
51
Types of cytokine
``` Interleukins (IL-x) Interferons (IFN) Chemokines Growth factors Cytotoxic ```
52
Interleukin function
Allow communication between leukocytes
53
Interferon function
Anti-viral effects | Interfere with virus replication
54
Chemokine function
chemotaxis | cell movement
55
Growth factor function
Proliferation & differentiation of cells
56
Cytotoxic cytokines
Induce apoptosis, tumour necrosis factor (TNF)
57
Proximity to other cells cytokine action
Most work in paracrine
58
Paracrine
Works on nearby cell
59
Name 2 alarm cytokines secreted by activated macrophages
IL-1 | TNF-alpha
60
Describe dendritic cells
Network of cells located at likely sites of infection Recognise microbial patterns, secrete cytokines Act as antigen presenting cells
61
Complement system plays a major role in
complementing activity of specific antibody in lysing bacteria
62
What is the complement system?
Complex series of ~30 proteins and glycoproteins that lead to a triggered enzyme cascade system
63
Complement system timings
Rapid, highly amplified response
64
Where are components of the complement system mainly produced?
Liver
65
How is complement a triggered enzyme cascade system?
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
What are the 3 complement activation pathways?
Classic Lectin pathway Alternative
67
What is the classic complement activation pathway?
Antibody bound to antigen (immune complex)
68
Cleaved "waste" from precursor is a pro-inflammatory molecule
Signals to other cells. | Binds to specific receptors on mast cells, cause degranulation (release histamine)
69
What is the lectin pathway in complement activation?
Lectins bind to carbohydrates only on bacteria leading to activation of complement
70
Lectins
proteins that bind to carbohydrate
71
What is alternate complement activation?
Bacterial surfaces directly activate complement via different components
72
All 3 complement pathways converge to activated C3b
Which opsonises antigens/pathogens. | Membrane attack complex formed that forms holes in bacterial cell membrane and causes loss of integrity
73
Functions of complement
Lysis Opsonisation Activation of inflammatory response Clearance of immune complexes
74
Control of complement
Short half life Dilution of components in biological fluids Circulating and membrane bound regulatory proteins
75
Local inflammatory response may be accompanied by
``` A systemic response "Acute phase" after 1-2 days Fever Increased production of WBCs Production of acute phase proteins in liver ```
76
How is a systemic acute phase response induced?
By cytokines
77
Acute-phase proteins
C-reactive protein (CRP) Mannan binding lectin (MBL) Complement Fibrinogen (clotting)
78
Which acute phase proteins activate complement?
C-reactive protein (CRP) | Mannan binding lectin (MBL)

Immunology (9 decks)

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