3. Innate immunity Flashcards
What are the five components of innate immunity?
- Physical barriers - mechanical, chemical, biological
- Phagocytes and inflammation
- NK cells
- Circulating pattern recognition cells
- Cytokines
What are commensal flora?
“friendly bacteria”
- removes potential competition from other bacteria
What is mucous?
Water and electrolytes
- Glycoproteins and lipids
Antimicrobial compounds - transferrin, lactoferrin (absorbs iron), lysozyme
- Antibodies (IgA)
- Antioxidants - superoxide dismutase, catalase + guthathione peroxidase
How does the innate immune system provides the “early warning system” for infection?
Uses pattern - recognition receptors (PRRs) to detect microbial components which are intrinsically foreign
AND
Pathogen - associated molecular pattern (PAMPs)
- mannose (bacterial carbohydrates)
- Lipopolysaccharide (lipids)
- peptidoglycans
What do keratinocytes do?
Trigger inflammation
- cytokine production (immunological hormones)
- chemokine production (cell migration factors)
What substances are involved in the inflammatory response?
IL-1𝛃, IL-6, TNF-𝛂
What are the signs of the inflammatory response?
- Vasodilation
- Increased capillary permeability (increased fluid leakage into tissues) - oedema
- Influx of white blood cells - migration of phagocytic cell into tissues
What are the systemic effects of IL-1𝛃, IL-6 and TNF𝛂?
Hypothalamus, fever - bacterialcidal
Liver - acute phase response
Bone marrow - neutrophil and monocyte mobilisation
What is the acute phase response?
Innate body defence seen during acute illness
- increased production of acute phase proteins by cytokines released from activated macrophages + other leukocytes
What are the acute phase proteins?
C-reactive proteins + mannose - binding proteins etc. produced by cells in the liver, promote inflammation, activate complement cascade + stimulate chemotaxis of phagocytes
What is the complement system?
Found in the blood
- pro-enzyme → enzyme forming an amplification cascade
- small amount of activation is amplified to generate a large response
- similar to clotting cascade but with a different outcome and triggers
What is the complement cascade?
Foreign organism
↓
pro-enzyme → enzyme amplification
- series of serum components that are activated by foreign organisms - leads to destruction of the invading pathogen
Give an overview of the main components of the complement pathway
Activation of the complement cascade via the classical (A), lectin (B), or alternative (C) pathway results in the initiation of the terminal complement pathway - leading to the formation of membrane attack complexes
What is the activation of the alternative pathway (AP) of complement?
- C3b (C3i) binds to cell wall & other surface components of
microbes - AP protein factor B combines with C3B to form C3bB
- Factor D splits bound factor B in Bb & Ba forming C3bBb
- Serum protein properdin binds to Bb forming C3bBbP
- C3bBbP functions as a C3 convertase that can enzymatically split hundreds of molecules of C3 into C3a + C3b
- C3 is a pro-enzyme
– acts as a marker for recognition by complement receptors on phagocytic cells
– acts as an enzyme to facilitate production of the membrane attack complex
What is the membrane attack complex?
MAC punches holes in the bacterial cell wall
Bacterium swells through uptake of fluid
Organism bursts & is killed