Lecture 22: Infection and innate immunity Flashcards

1
Q

What are the features of innate immunity?

A
  • First line or immediate response to pathogen invasion
  • No memory (you are born with what you have)
  • requires ability to distinguish between self and non-self
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2
Q

What are 3 process involved in innate immunity?

A
  1. Complement
  2. Myeloid cells and phagocytosis (neutrophils and macrophages)
  3. Pattern Recognition Receptors
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3
Q

What are the 3 types of pathogens?

A

Bacteria
Virus
Protozoa/Parasites

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4
Q

What are features of virus?

A

They are intracellular pathogens

Contain genetic information bound by a lipid coated protein

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5
Q

What are examples of virus?

A
Influenza
Polio
Smallpox
Varicella 
HIV
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6
Q

What are features of bacteria?

A

They are extracellular pathogens

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7
Q

What are examples of bacteria?

A
Staph aureus 
Mycobacterium tuberculosis
Strep pyogenes
Yersinia pestis (black death)
Vibrio cholerae
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8
Q

What are protozoa/parasites?

A

Complex multicellular organisms which require killing by chemical mediators released by specialist myeloid cells (basophils, eosinophils, mast cells)

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9
Q

What are two types of bacteria?

A

Gram positive and gram negative

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10
Q

What is gram positive bacteria?

A

Bacteria with a thick peptidoglycan cell wall as defence - requires phagocytosis and are not killed directly by complements

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11
Q

What is gram negative bactera?

A

Bacteria with thin peptidoglycan layer surrounded by an outer membrane. These bacteria can be broken down directly by complements.

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12
Q

How does neutrophil extravasation occur?

A

Neutrophils exit the capillaries into the interstitial fluid and navigate the fluid to the site of infection

  1. Activation
  2. Tethering
  3. Adhesion
  4. Diapadesis
  5. Chemotaxis
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13
Q

Explain the activation stage of neutrophil extravasation

A

The first step of neutrophil extravasation involves:
chemokines (e.g. anaphylotoxins) from tissue injury or inflammation activating the local endothelial cells lining an adjacent capillary wall

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14
Q

Explain the tethering stage of neutrophil extravasation

A

The second step involves:
Neutrophil tethers to the inside capillary wall (restricted movement)
This process is mediated by selectins (cell-adhesion molecules) on endothelial cells and a carbohydrate antigen on neutrophils called sialyl Lewis X

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15
Q

What are selectins?

A

Cell-adhesion enzymes upregulated in endothelial cells that tether neutrophils to capillary walls in the tethering stage

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16
Q

Explain the adhesion stage of neutrophil extravasation

A

The third step involves:
Strong binding between neutrophil integrins and ICAM-1 on the endothelium - neutrophils are completely immobilised and flattened

17
Q

Explain the diapadesis stage of neutrophil extravasation

A

The fourth step involves:

The neutrophil squeezes between endothelial cells into the interstitial space

18
Q

Explain the chemotaxis stage of neutrophil extravasation

A

The final stage involves the neutrophils migrating along a chemical gradient to the site of infection in the interstitial fluid

19
Q

How do neutrophils move in the interstitial fluid towards the site of infection?

A

They polymerise actin filaments at their leading edge and de-polymerise those filaments at trailing edge moving up the chemoattractant gradient

They have receptors that bind to the deposited complement proteins at the site of infection

20
Q

What are the 4 types of complement receptors and what do they do?

A

CR1, CR2, CR3, CR4

These receptors are found on myeloid cells and bind activated complement components deposited on pathogens by opsonisation

21
Q

What is the receptor that allows neutrophils to bind to complements?

A

CR1 allows neutrophils to bind to C3b complement

22
Q

How does FcR (antibody) mediated phagocytosis occur?

A
  1. Antibodies bind to bacterial antigens
  2. Neutrophil FcR binds to an exposed Fc region of the antibody bound to the bacteria
  3. Activates phagocytosis
  4. Membrane of neutrophil invaginates forming a phagosome
  5. Fuses with lysosome to form phagolysosome
  6. Phagolysosome acidifies and superoxides kill bacteria
23
Q

What are pattern recognition receptors?

A

These are receptors involved in the innate immunity which bind to complex molecules that are unique to pathogens (PAMPs)

24
Q

What are PAMPs?

A

Pathogen associated molecular patterns are molecules that are unique to pathogens

These are structurally very complex
Evolutionarily stable
They stimulate the power switch for the adaptive response to occur

25
Q

Name an example of a PAMP and the pattern recognition receptor for that pattern

A

Toll-like receptor 4 (TLR4) is the receptor for lipopolysaccharides (LPS)

26
Q

What is LPS?

A

Lipopolysaccharides are complex molecules found in the membrane of all gram negative bacteria

Tiny amounts of LPS induce powerful response. It is a pyrogen meaning it will cause fever