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ESA 2 - Infection > 3. Innate Immune Response > Flashcards

3. Innate Immune Response Flashcards

1
Q

What are the 4 main components of the innate immune response?

A

1- Complement, phagocytosis and cytokine/chemokine production

  1. Vasodilation/vascular permeability… neutrophils and monocytes
  2. Fever (via hypothalamus) and acute phase response (via liver)
  3. Local inflammation (rubor, calor, dolor and tumor)
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2
Q

What is the function of monocytes?

A

Present in blood, recruited at infection site and differentiate into macrophages

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3
Q

What is the function of macrophages?

A

Present in all organs.

  1. phagocytosis (ingest and destroy pathogens)
  2. antigen-presenting cells (to T cells) - activate adaptive immunity
  3. produce cytokines/chemokines - activate inflammation
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4
Q

What is the function of neutrophils?

A

Present in blood (increased during infection), phagocytose pyogenic bacteria (eg S. aureus and Strep. pyogenes)

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5
Q

How are neutrophils recruited? What happens to them after phagocytosis?

A
  • Recruited by chemokines to infection site.

- Die after phagocytosis, forming pus.

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6
Q

What is the function of basophils/mast cells?

A

Early regulators of inflammation via vasomodulation.

Important in allergic responses.

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7
Q

What is the function of eosinophils?

A

Defence against multi-cellular parasites (worms)

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8
Q

What is the function of natural killer cells?

A

Kills abnormal host cells (virus-infected or malignant)

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9
Q

What is the function of dendritic cells?

A

Present microbial antigens to T cells - activate adaptive immune system

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10
Q

How are pathogens recognised by the innate immune system?

A
  1. Recognition of microbial PAMPs (pathogen-associated molecular patterns) by phagocytic PRRs (pathogen recognition receptor)
  2. Pathogen opsonisation - enhances recognition and attachment of phagocytes
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11
Q

Give examples of PAMPs and their associated PRR.

A

Gram-negative bacteria:

  • lipopolysaccharide (TLR4)
  • lipoproteins and lipopeptides (TLR2)

Gram-positive bacteria:

  • peptidoglycan (TLR)
  • lipoteichoic acids (TLR4)

All mycobacteria:

  • lipoarabinomannan (TLR2)
  • mannose-rich glycans (TLR2)

Bacterial flagella:
- flagellin (TLR5)

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12
Q

What are the 2 main types of PRR?

A
  • Toll-like receptors - on phagocyte surface (bacterial recognition)
  • Nod-like receptors - intracellular (viral recognition)
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13
Q

Name examples of opsonins.

A
  1. Complement proteins (C3b, C4b)
  2. Antibodies (IgG, IgM)
  3. Acute phase proteins (CRP, MBL)
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14
Q

Which type of bacteria particularly require opsonisation to be cleared?

A

Encapsulated bacteria such as N. meningitidis, Strep. pneumoniae and H. influenza B.

(capsule prevents easy recognition by phagocytes)

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15
Q

Describe the steps involved in phagocytosis.

A
  1. chemotaxis and adherence of MO to phagocyte.
  2. phagocytosis and phagosome formatiion
  3. phagolysosome formation by fusion with lysosome
  4. enzymatic degradation of MO
  5. formation of residual body containing indigestible material
  6. exocytosis of waste materials
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16
Q

Describe the 2 phagocyte intacellular killing mechanisms.

A
  1. Oxygen-dependent pathway (respiratory burst)
    - production of toxic ROS, inc. hydrogen peroxide, hydroxyl radical and nitric oxide
  2. Oxygen-independent pathways
    - lysozyme
    - lactoferrin/transferrin
    - cationic proteins (cathepsin)
    - proteolytic and hydrolytic enzymes
17
Q

How is the complement system activated?

A
  1. LECTIN pathway: recognition of microbial surface carbohdyrates by PRRs - mannose-binding lectins (MBLs) (or L-, M- and H-ficolins).
  2. CLASSICAL pathway: binding of C1 complex directly with pathogen or to Fc component of antigen-antibody complex.
  3. ALTERNATIVE pathway: C3b binds directly to pathogen surface.
18
Q

Describe the antimicrobial actions of the complement system.

A
  1. C3a and C5a = chemoattractants - recruit phagocytes
  2. C3b = opsonin
  3. C5b-C9 = membrane-attack complex - form pores
19
Q

What are the 3 main actions of cytokines/chemokines?

A
  1. chemoattraction
  2. phagocyte activation
  3. inflammation
20
Q

Describe the effect of cytokines released by macrophages.

A

Activated macrophages release TNFa, IL-1 and IL-6.

1) Stimulate hypothalamus to produce prostaglandin… increase body temperature… fever.
2) Inflammatory actions: increase vasodilation, vascular permeability and expression of BV adhesion molecules… neutrophil recruitment and migration into tissues.
3) Stimulate neutrophil production/mobilisation in the BM via increased G-CSF (granulocyte-colony stimulating factor) production.
4) Stimulate production of proteins by the liver.

21
Q

Which liver proteins do TNFa, IL-1 and IL-6 stimulate the production of?

A
  • Opsonising proteins: C3, C4 (enhances complement activation) and CRP
  • Damage-limiting proteins: a1-antitrypsin, haptoglobin
  • Clotting factors: fibrinogen
22
Q

What are the functions of CRP?

A
  1. Opsonisation: binds surface-phospholipids of some bacteria (eg pneumococcus)
  2. Activates complement system through lectin pathway.
23
Q

How is the acute-phase response triggered and what does it involve?

A
  • Triggered by TNFa, IL-1 and IL-6 released by activated macrophages.
  • Effects:
    1. Fever by hypothalamus stimulation
    2. Liver production of: complement proteins, CRP, a1-antitrypsin and haptoglobin (damage-limiting proteins), and fibrinogen
    3. Increased neutrophil production by BM stimulated by G-CSF
    4. General activation of adaptive immune response… increase in immunoglobulins
24
Q

What is ESR? Why is it measured clinically?

A
  • ESR = erythrocyte sedimentation rate.
  • Is increased during inflammation due to increased plasma viscosity caused by increased synthesis of acute phase proteins.
  • But takes longer than CRP to become abnormal during an inflammatory response.
25
Q

How does aspirin reduce fever?

A

Blocks prostaglandin production by the hypothalamus.

ESA 2 - Infection (25 decks)

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