Lecture 22: Infection and innate immunity Flashcards
What are the features of innate immunity?
- 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
What are 3 process involved in innate immunity?
- Complement
- Myeloid cells and phagocytosis (neutrophils and macrophages)
- Pattern Recognition Receptors
What are the 3 types of pathogens?
Bacteria
Virus
Protozoa/Parasites
What are features of virus?
They are intracellular pathogens
Contain genetic information bound by a lipid coated protein
What are examples of virus?
Influenza Polio Smallpox Varicella HIV
What are features of bacteria?
They are extracellular pathogens
What are examples of bacteria?
Staph aureus Mycobacterium tuberculosis Strep pyogenes Yersinia pestis (black death) Vibrio cholerae
What are protozoa/parasites?
Complex multicellular organisms which require killing by chemical mediators released by specialist myeloid cells (basophils, eosinophils, mast cells)
What are two types of bacteria?
Gram positive and gram negative
What is gram positive bacteria?
Bacteria with a thick peptidoglycan cell wall as defence - requires phagocytosis and are not killed directly by complements
What is gram negative bactera?
Bacteria with thin peptidoglycan layer surrounded by an outer membrane. These bacteria can be broken down directly by complements.
How does neutrophil extravasation occur?
Neutrophils exit the capillaries into the interstitial fluid and navigate the fluid to the site of infection
- Activation
- Tethering
- Adhesion
- Diapadesis
- Chemotaxis
Explain the activation stage of neutrophil extravasation
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
Explain the tethering stage of neutrophil extravasation
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
What are selectins?
Cell-adhesion enzymes upregulated in endothelial cells that tether neutrophils to capillary walls in the tethering stage
Explain the adhesion stage of neutrophil extravasation
The third step involves:
Strong binding between neutrophil integrins and ICAM-1 on the endothelium - neutrophils are completely immobilised and flattened
Explain the diapadesis stage of neutrophil extravasation
The fourth step involves:
The neutrophil squeezes between endothelial cells into the interstitial space
Explain the chemotaxis stage of neutrophil extravasation
The final stage involves the neutrophils migrating along a chemical gradient to the site of infection in the interstitial fluid
How do neutrophils move in the interstitial fluid towards the site of infection?
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
What are the 4 types of complement receptors and what do they do?
CR1, CR2, CR3, CR4
These receptors are found on myeloid cells and bind activated complement components deposited on pathogens by opsonisation
What is the receptor that allows neutrophils to bind to complements?
CR1 allows neutrophils to bind to C3b complement
How does FcR (antibody) mediated phagocytosis occur?
- Antibodies bind to bacterial antigens
- Neutrophil FcR binds to an exposed Fc region of the antibody bound to the bacteria
- Activates phagocytosis
- Membrane of neutrophil invaginates forming a phagosome
- Fuses with lysosome to form phagolysosome
- Phagolysosome acidifies and superoxides kill bacteria
What are pattern recognition receptors?
These are receptors involved in the innate immunity which bind to complex molecules that are unique to pathogens (PAMPs)
What are PAMPs?
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
Name an example of a PAMP and the pattern recognition receptor for that pattern
Toll-like receptor 4 (TLR4) is the receptor for lipopolysaccharides (LPS)
What is LPS?
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
