Innate Immunity Flashcards
What are the three main ways in which the innate immune system can detect pathogens?
PAMPs, DAMPs and missing self
What are the main phagocytic cells? List some important features.
Neurophils – 70% of circulating WBCs – granulocytes – multilobed nucleus
Monocytes/Macrophages – signal infection by releasing cytokines
Describe how neutrophils move out of the blood vessels and into tissue.
Similar to lymphocyte extravasation.
Initial binding is weak between selectins and selectin ligands – slows down the neutrophils
Due to infection, activated macrophages release chemokines that bind to the surface of endothelial cells.
The chemokine receptor on the neutrophils binds to the chemokines and promotes the integrin to the high affinity state.
The integrin then binds with the integrin ligand which immobilises the neutrophils.
Then the neutrophils can move into the tissue.
What are the two main opsonins for neutrophils?
Antibodies and complement
Describe the action of these opsonins.
Antibodies bind to antigens on the cell surface of pathogens. Complement glycoproteins bind directly to the surface of the pathogen.
These act as adaptors and can then bind to the neutrophil, activating it and stimulating phagocytosis.
What are the mechanisms by which neutrophils kill phagocytosed pathogens?
Oxygen-dependent and oxygen-independent mechanisms.
What are cytokines? List some characteristics.
Cytokine are small secreted proteins that act as messengers. They are short-lived.
Give some examples of cytokines.
Interferons, Interleukins, Growth factors, chemokines, TNF
What are the three ways in which cytokines can act?
Paracrine, Endocrine, Autocrine
Describe the onset and consequences of septic shock.
Infection causes a massive release of alarm cytokines by activated macrophages (TNF-alpha and IL-1)
Low blood pressure + Increase in vascular permeability
What is the ‘Complement’ system?
It’s a system of soluble glycoproteins that complement the action of antibodies.
What are the three ways in which complement is activated? Explain how exactly they activate compliment.
Classical Pathway – antigen binding to antibody causes a conformational change – activates complement
Alternative Pathway – direct contact with the pathogen surface activates complement
Lectin pathway – activated by lectin (which is a PRR) binding to carbohydrates that are only found on pathogens
What happens to the cleaved fragments during the complement cascade?
They are pro-inflammatory molecules, which can bind to receptors on mast cells and cause degranulation giving rise to an inflammatory response.
Other than lysis and opsonisation, what are the two other roles of complement?
Activation of the inflammatory response (by binding to mast cells and macrophages) and clearance of immune complexes (antibody-antigen complexes must be removed before they cause inflammation of blood vessels)
What are the two types of mast cell?
Mucosal and Connective Tissue
What can activate mast cells?
Pro-inflammatory products from complement - ANAPHYLATOXINS
Describe, in full, a typical inflammatory response to a bacterial pathogen.
Bacterial infection will firstly activate tissue resident macrophages, which begin producing alarm cytokines and chemokines.
These cytokines recruit neutrophils and lymphocytes to the area of infection.
Complement is activated by the classical or alternative pathways.
The pro-inflammatory products of complement bind to mast cells and cause degranulation leading to an inflammatory response.
What acute phase proteins are involved in the systemic acute phase response?
C-reactive protein, mannan-binding lectin, fibrinogen and complement
State some basic features of NK cells.
They are large cytotoxic lymphocytes
They are granular
Secrete interferon gamma
Describe how NK cells communicate with target cells.
They don’t have antigen specific receptors.
Instead they have activating and inhibitory receptors and depending on the balance between the two signals they decide whether to attack the cell.
What are the two types of target cell recognition by NK cells? Explain how they work.
Missing Self – when infected, cells will downregulate the expression of MHC Class I, which acts as an inhibitory signal. The loss of the inhibitory signal means that NK cells are more likely to kill the target cells.
Induced Self – cells will change the pattern of their self-proteins due to stress. These stress-induced patterns will be recognised by activating receptors on NK cells and lysed.
