Innate immunity to infection
LO: Describe how pattern recognition receptors recognise microbe-associated molecular patterns
Innate immune recognition
- Microbes recognised through highly conserved and essential features different from those of our bodies
- Cell walls - peptidoglycan
- Nucleic acids - CpG DNA
- Sugars - liposaccharides, mannan
- Flagella
- Microbe/pathogen-associated molecular patterns (M/PAMPs)
Pathogen-associated molecular patterns (PAMPs)
- Recognised by toll-like receptors on macrophages, neutrophils, dendritic and epithelial cells
Damage-associated molecular patterns (DAMPs)
- Endogenous danger molecules produced in cellular damage/stress
- Contain multiple types of molecules normally hidden from immune system
- Sterile inflammation
LO: Discuss the function of the complement system
Complement system
- 30 different proteins, 4% of the proteins in the blood
- Lyse bacteria in 30 seconds
- Classical pathway - activated by antibodies
- Lectin pathway - activated by microbial sugars
- Alternative pathway - constant low-level hydrolysis of C3
- Promotes microbial killing and phagocytosis
Diseases
- Rheumatoid and osteoarthritis - enhanced complement activation
- Atypical haemolytic uraemic syndrome
- Dense deposit disease
- Hereditary angiodema - C1 inhibitor
- Tumours - upregulation of membrane bound complement inhibitors
LO: Describe the mechanism of phagocytosis
- Microbes are killed by phagocytic cells
- Broken up into components that are presented to the adaptive immune system
- Opsonisation: Binding of microbes to immunoglobulin or complement (C3b) enhances phagocytosis
- Pathogen debris detected by immune system
- Pathogens are killed by reactive oxygen species (ROS), acid and proteases
| Neutrophils | Macrophages |
| Lasts only a few days and die after phagocytosis | Lasts for weeks/months and can phagocytose many times |
| Circulate in blood | Reside in tissues |
| First to arrive | Arrive later than neutrophils |
| Do not present antigens | Presents antigens |
NETosis
- Reactive oxygen species releases nuclear elastase (NE) from granules
- NE goes to nucleus and triggers release of DNA and antimicrobial proteins
LO: Describe the innate immune system's barriers against infection and common defects in innate immunity and the resulting diseases
Acute phase response
flowchart LR
A[Inflammation, cytokines, interferon] --> B[IL-6, IL-1, TNF]
B --> C[CRP and other positive acute phase proteins increase]
B --> D[Negative acute phase proteins decrease]
Function
Positive acute phase proteins (ACPs)
- Microbial defence (opsonisation): CRP and serum amyloid A (SAA) bind to microbial surfaces marking them for destruction via phagocytosis
- Coagulation and pathogen trapping: fibrinogen forms blood clots that wall off microbes
- Scavenging free radicals and iron: haptoglobin binds free haemoglobin from damaged red blood cells, starving invaders of nutrients and prevents oxidative tissue damage
- Neutralising proteases: alpha-1-antitrypsin and alpha-2-macroglobulin inhibit destructive enzymes released by white blood cells during intense inflammation, protecting healthy tissue
Negative ACPs
- Conserving amino acids: reduce production of proteins like albumin and transfer amino acids so the liver can prioritise making high demand defence proteins