Lecture 28 - Innate Immunity 1 Flashcards

1
Q

What are the major features of innate immunity?

A
  • Present at birth
  • Rapid response
  • No memory
  • Non specific

Components:
• Physical barriers
• Chemical defences
• Cells

Responding to change in equilibrium: not necessarily infection. Can be, for example, a response to a bruise

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2
Q

What are the chemical defences of innate immunity?

A
  • Fatty acids
  • Low pH
  • Pulmonary surfactant
  • Defensins
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3
Q

Which cells play a role in innate immunity?

A
  • Granulocytes: neutrophils, eosinophils, basophils
  • Monocytes / macrophages
  • Mast cells
  • DCs
  • NK cells
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4
Q

What is the stem cell line of innate immune cells?

A

CMP: common myeloid progenitor

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5
Q

Describe the innate defences in the skin

A
  1. Mechanical
    • Epithelial cells w/ tight junctions
    • Longitudinal flow of air or fluid
2. Chemical
 • Fatty acids
 • β defensins
 • Lamellar bodies
 • Cathelicidin
  1. Microbiological
    • Normal microbiota
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6
Q

Describe the innate defences in the gut

A
  1. Mechanical
    • Epithelial cells w/ tight junctions
    • Longitudinal flow of air or fluid
2. Chemical
 • Low pH
 • Enzymes (pepsin)
 • α-defensins (cryptidins)
 • Cathelicidin
 • RegIII (Lecticidins)
  1. Microbiological
    • Normal microbiota
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7
Q

Describe first line of defence in lungs

A
  1. Mechanical
    • Epithelial cells w/ tight junctions
    • Mucociliary escalator
  2. Chemical
    • Pulmonary surfactant
    • α-defensins
    • Cathelicidin
  3. Microbiological
    • Normal microbiota
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8
Q

Describe the innate barriers in the ear/nose and oral cavities

A
  1. Mechanical
    • Epithelial cells w/ tight junctions
    • Tears
    • Nasal cilia
  2. Chemical
    • Lysozyme in tears and saliva
    • Histatins
    • β defensins
  3. Microbiological
    • Normal microbiota
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9
Q

What is the general life span of the following cells:
• Granulocytes
• Monocytes / macrophages

A

Neutrophils: short lived (8-10 hours to days)

Monocytes / macrophages: long lived

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10
Q

What is the function of the following cells:
• Neutrophils
• Eosinophils
• Basophils

A

Neutrophils:
• Phagocytosis of extracellular pathogens
• Activation of bactericidal mechanisms

Eosinophils:
• Killing of antibody coated parasites

Basophils:
• Promotion of allergic response
• Anti-parasitic immunity

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11
Q

Which cell is responsible for chronic granulomatous disease?

A

Neutrophils

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12
Q

Where are neutrophils normally found?

A

In the blood

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13
Q

Which diseases can neutrophils cause?

A

Chromic granulomatous disease
• Mutations in NADPH oxidase
• Cannot kill phagocytosed bacteria

Myeloid leukaemias

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14
Q

Describe the process of neutrophil extravasation

A
  1. Rolling adhesion
    • Selectin mediated
  2. Tight binding
    • Integrin mediated
  3. Diapedesis
    • PECAM1
  4. Migration
    • Chemokines
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15
Q

Describe phagocytosis by neutrophils

A
  1. Microbe binds receptors on the surface of neutrophils
  2. RME
  3. Microbe in phagosome
  4. Fusion of lysosomes with phagosomes
  5. ROS burst and NADPH oxidase activation
  6. Intracellular killing of the pathogens
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16
Q

Describe NET formation

A

Effector function of neutrophils

  1. Neutrophil engages extracellular bacterium
  2. Release of molecules (DNA etc.)
  3. DNA precipitates with many other proteins
  4. Bacteria become entangled and thus opsonised
  5. Macrophages come and phagocytose these bacteria
17
Q

What are the two types of granules in eosinophils?

A

Toxic granules containing:
• Arginine-rich basic protein

Microbicidal:
• Toxic proteins
• Radicals

Immunomodulatory:
• Leukotrienes
• Prostaglandins
• Cytokines

18
Q

Where are eosinophils found?

A

Mainly in tissues

Small numbers in the blood

19
Q

Describe effector function of eosinophils

A

Parasite immunity

Granule release
• Microbicidal
• Immunomodulatory

Killing of antibody coated parasites

Role in allergic disease

20
Q

What is the important structural feature of eosinophils?

A

Many granules visible in the cytoplasm

21
Q

To which other cells do basophils have a similar function?

A

Eosinophils
Mast cells

(possibly)

22
Q

Describe the function of basophils

A
  • Recruitment to site of IgE-mediated allergic reactions
  • Release of histamine and cytokines (IL-4, IL-13)
  • Involved in ‘helper’ T cell differentiation
  • Important role in allergic diseases
23
Q

Where are basophils found?

A

Circulation

24
Q
Compare location of the following cells:
 • Neutrophils
 • Eosinophils
 • Basophils
 • Monocytes / macrophages
 • Mast cells
 • NK cells
 • DCs
A

Neutrophils: circulation

Eosinophils: tissues (also some in circulation)

Basophils: circulation (?)

Monocytes: circulation

Macrophages: tissues

Mast cells: connective tissues

NK cells: * (?)

DCs: tissue resident

25
Q

What is NADPH oxidase?

A

Complex of enzymes that become auto-catalytically activated

Generate oxygen radicals

Found in neutrophils to kill phagocytosed microbes

26
Q

Which cytokines do basophils release?

A

IL-4

IL-13

27
Q

Which is usually the first cell to arrive in an area of injury?

A

Neutrophils

normally within 10 minutes

28
Q

What is pus made of?

A

80% Neutrophils

29
Q

What are the functions of macrophages?

A

Phagocytosis: clearance of:
• Microbes
• Debris
• Dead cells

Presentation of antigen

Orchestration of immune responses

30
Q

Describe the function of Mast cells

A

Histamine release:
• Increased VP

Sensitisation with IgE
• IgE binds Ig(e)R on Mast cells
• Cross linking once antigen binds
• Toxic granule release

31
Q

Which other cell is really important for Mast cell function?

A

B cells

The B cells produce the Ab that sensitise mast cells and allow them to perform their main function

32
Q

What is the ‘concerted inflammatory response’?

What are the cardinal signs?

A

Involvement of all the components of the innate immune response

Cardinal signs:
 • Calor
 • Dolor
 • Rubour
 • Tumour
 • Function laesa