Review of the innate immune system Flashcards
What is the importance of innate immunity as the first line of defence when encountering new pathogens
For a new pathogen, the adaptive immune response is too slow and so innate immunity exists to buy time for survival
Innate immunity is the first line of defence against pathogens and is critical for preventing the spread of infection and protecting the host from disease.
It acts rapidly upon encountering a pathogen, providing immediate protection before the adaptive immune response is fully activated.
Innate immunity includes physical barriers such as the skin and mucous membranes and cellular components such as phagocytic cells and natural killer (NK) cells that can quickly recognise and eliminate pathogens.
What are the general principles of recognition of pathogens and what is the role of pattern recognition receptors in the innate immune system?
Pattern recognition receptors (PRR) are host factors expressed on the surface of innate immune cells and can recognise conserved patterns on pathogens known as pathogen-associated molecular patterns (PAMPs)
PRRs are germ-line encoded (do not rearrange unlike T-cells receptors), several classes of PRR:
- Extracellular - recognise PAMPs outside of a cell
- Intracellular/cytoplasmic - recognise PAMPs inside a cell
- Secreted - act to tag circulating pathogens for elimination
PAMPs are only present on pathogens and not on host cells, it’s essential for the survival of pathogens and are invariant structures shared by the entire class of pathogens (bacteria, viruses, fungi and parasites) E.g.:
- Gram-negative bacteria: Lipopolysaccharides (LPSs)
- Gram-positive bacteria: teichoic acid, lipoteichoic acid, peptidoglycan
- Bacterial flagellin
- Abnormal protein glycosylation
- Viruses - abnormal nucleic acid (double-stranded RNAs)
When a PRR recognises a PAMP, it triggers a signalling cascade that leads to the activation of innate immune cells and the production of cytokines and chemokines that recruit additional immune cells to the site of infection.
What are the components to innate immunity?
1) The inflammatory response
- A generic defence mechanism whose purpose is to localise and eliminate injurious agents and remove damaged tissue components
- Triggered by the release of pro-inflammatory cytokines (IL-1, INF-γ) and chemokines (chemo-contractor signals) at the site of infection
- Enhanced permeability and extravasation
- Neutrophil recruitment (by chemokines)
- Enhanced cell adhesion (adhesins on surface of cells) and clotting
2) Phagocytes - Monocytes/granulocytes/neutrophils
- Recognise infection in order to produce cytokines and chemokines
- Recognise PRR
- Recognise phosphatidylserine on surface of cells undergoing apoptosis
- Detects atypical sugars on cell surfaces
- Scavenger receptors
- Complement receptors
- Peptides from broken-down pathogens can be presented through MHC and promote the development or recall of adaptive T-cell response
3) Complement - soluble proteins made and secreted by the liver
- binds to pathogen
- Acts as secreted PRRs
4) Glycoprotein immune hormones; Cytokines, chemokines and anti-microbial peptides (AMPs):
- cytokines act to modify the behaviour of cells in the immune response, most are called interleukins
- Chemokines act as chemotactic factors - i.e. they create concentration gradients which attract specific cell types to a site of production/infection
- Interferons are the main anti-viral cytokines (Type 3 = respiratory), produced and secreted by infected cells to act on neighbouring cells, growth arrest, cell death mRNA degradation, translational arrest, ↑antigen presentation, ↑adhesion molecules
- AMPs are secreted short peptides, usually work by disrupting cell wall leading to lysis, some are induced by bacterial infection, offers broad protection
5) Natural Killer cells (NK cells) detect lack of MHC
- Large granular lymphocytes, kill certain tumours & virally infected cells. Target cell destruction is caused by cytotoxic molecules called granzymes & perforins
- Selectivity is conferred by LOSS of ‘self’ MHC molecules on target surfaces and up-regulation of activating ligands (ligand on infected cells)
Describe the importance of innate immunity in triggering an appropriate adaptive immune response
Innate immunity provides signals that activate and shape the adaptive immune response, e.g. dendritic cells and macrophages, 2 types of innate immune cells, can engulf and process pathogens and present pathogen-derived peptides (antigens) on their surface to T cells, aka, antigen presentation. Critical for activating naive T cells and initiating the adaptive immune response.
Additionally, innate immune cells produce cytokines and chemokines that can activate and shape the adaptive immune response, influencing the differentiation and function of T and B cells
Compare innate and adaptive immune system
The innate and adaptive immune systems differ in their speed of response, specificity, and memory.
Innate immunity involves macrophages, neutrophils and DCs using PRR to recognise small numbers of microbial ligands that are highly conserved between pathogens (PAMPs) in order to provide rapid, non-specific antigen recognition and involves recognition of broadly conserved features of different classes of pathogens thus does not require prior exposure to the pathogen. Germ-lined encoded receptors, evolved by natural selection
The adaptive immune system includes T and B cells (lymphocytes) that can recognise specific antigens with Ig receptors or TCR, undergo clonal expansion, and differentiate into effector cells that can eliminate the pathogen. Additionally, the adaptive immune system can generate immunological memory, which provides long-term protection against future infections with the same pathogen. Receptors generated randomly within individuals; cannot be inherited
