Innate Immunity Flashcards
What are the components of the innate immune system?
• Physical barriers Skin and mucous surfaces • Chemical barriers pH and secreted factors • Phagocytes Macrophages, Monocytes, granulocytes and neutrophils • Inflammation • Cytokines and chemokines • Complement • Natural killer cells
Adaptive immune response is too slow to protect us from some new pathogens
- Once a microbe has infected you it takes around 3.5 days before any T-cell response and 5 days before antibodies are produced.
- However, some pathogens (such as influenza replicate very quickly), long before any T-cell and antibody response.
- The innate immune response is activated very quickly to essentially buy you time for you to produce any T-cells and antibody response.
Why is phagocytosis in innate immunity very ancient?
- Virtually all multicellular animals have means to recognise and phagocytose debris and infected cells undergoing apoptosis
- Carried out in humans (and other vertebrates) by macrophages, dendritic cells and neutrophils
What is the purpose of inflammation?
What is it cause by?
Other effects?
- A generic defence mechanism whose purpose is to localize and eliminate injurious agents and to remove damaged tissue components
- Triggered by the release of pro-inflammatory cytokines and chemokines at the site of infection
- Enhanced permeability and extravasation
- Neutrophil recruitment
- Enhanced cell adhesion
- Enhance clotting
Cytokines and Chemokines are glycoprotein hormones, what are there function?
Cytokines
• Act to modify the behaviour of cells in the immune response
• Most of these are called interleukins (eg. IL-1)
Chemokines
• Act as chemotactic factors – i.e. they create concentration gradients which attract (or occasionally repel) specific cell types to a site of production/infection
How do host cells see microbes?
Macrophages have phagocytic receptors that bind microbes and their components - sampling, scavenging
What is gram-positive and what is gram-negative?
Gram-negative bacteria; lipopolysaccharides (LPSs) found in outer membrane
e.g Gram-positive bacteria; teichoic acid, lipoteichoic acid, peptidoglycan found in outer membrane
Other PAMPs include:
• Bacterial flagellin
• Abnormal protein glycosylation
• Abnormal nucleic acids - viruses
Pattern recognition receptors (PRRs) are germ-line encoded, but how are they functionally separated?
Extracellular – they recognise PAMPs outside of a cell and trigger a co-ordinated response to the pathogen
Intracellular (cytoplasmic) – they recognise PAMPs inside a cell and act to co-ordinate a response to the pathogen
Secreted – they act to tag circulating pathogens for elimination
what are complements?
A system of secreted proteins made in the liver that recognise PAMPs on the surface of microbes and “decorate” or “tag” them. The microbes are then cleared by phagocytosis, “opsonised” or they have holes punched in them
Three ways of activating:
(i). Recognition of LPS and other PAMPs by the C1q component of “classical” pathway
(ii). Non-host glycosylation is recognised by MBP and other lectins to activate the “lectin” pathway
(iii). Membranes that are recognised as “non-self” activate the “alternative” pathway
Complement activation involves a proteolytic cascade
Describe natural killer cells
% white blood cells
• Lymphocyte-like but larger with granular cytoplasm
• Kill certain tumour & virally infected cells
• Target cell destruction is caused by cytotoxic molecules called granzymes & perforins
NK cells possess the ability to recognise and lyse virally infected cells and certain tumour cells.
Selectivity is conferred by LOSS of “self” MHC molecules on target cell surfaces, AND up-regulation of activating ligands
There are many diseases associated with inherited defects in Innate Immunity
- Complement – core defects (e.g. C3) linked to development of autoimmune diseases such as lupus
- Complement – non-core defects linked to suseptibility to specific types of pathogens such as Neisseria
- Macrophage deficiencies - Chronic granulomatous disease (CGD); No oxidative burst for bacterial killing
- Macrophage deficiencies – IRF8 mutations linked to susceptibility to TB
- Aicardi–Goutières syndrome associated with constitutive production of inflammatory cytokines
- Lack of interferon-responsiveness – sensitivity to viral infection (e.g. measles)
