Innate Immunity Flashcards
Why do we have innate immunity?
Adaptive immune response is too slow to protect us from new pathogens (especially viruses)
Which type of immunity (adaptive or innate) provides sterile immunity?
Adaptive
Give the sites of microbe entry (7)
Conjunctiva (eyes) Insect into capillary Scratch Anus Gut infections Respiratory tract Urinogenital tract
Give the 7 components of innate immunity
Physical barriers Chemical barriers Phagocytes Inflammation Cytokines/chemokines Complement Natural killer cells
What is the purpose of the inflammatory response?
To localise and eliminate injurious agents and to remove damaged tissue components
What does the inflammatory response enhance (4)?
Permeability and extravasion, neutrophil recruitment, cell adhesion and clotting
What is the inflammatory response triggered by?
The release of pro-inflammatory cytokines and chemokines at the site of infections
What are cytokines and chemokines?
Glycoprotein hormones that affect immune response
How do cytokines act?
To modify the behaviour of cells in the immune response
What are most cytokines
Interleukins
How do chemokines act?
As chemotactic factors- creating concentration gradients that attract (or repel) specific cell types to the site of infection
What is the effect of IL-1?
Enhances response and induces acute-phase secretion
What is the effect of IL-6?
Enhances response and induces acute-phase secretion
What is the effect of IL-8/CXCL8?
Chemoattractant for neutrophils
What is the effect of IL-12?
Diverts immune response to type 1 pro inflammatory and cytokine secretion
What is the effect of TNF-alpha?
Induces changes in vascular endothelium
What is the main producer of IL-1?
Macrophages and keratinocytes
What is the main producer of IL-6?
Macrophages and dendritic cells
What is the main producer of IL-8?
Macrophages and dendritic cells
What is the main producer of IL-12?
Macrophages and dendritic cells
What is the main producer of TNF-alpha?
Macrophages and dendritic cells
What does IL-1 act upon?
Lymphocytes and liver
What does IL-6 act upon?
Lymphocytes and liver
What does IL-8 act upon?
Phagocytes
What does IL-12 act upon?
Naive T cells
What does TNF-alpha act upon?
Vascular endothelium
How do macrophages recognise microbes?
Phagocytosis receptors that bind to their microbes and components
What are the 5 types of receptors found on macrophages?
Complement Mannose Lipid Scavenger Dectin-1
How do macrophages recognise patterns?
Pathogen-associated molecular patterns (PAMPs)
What are PAMPs?
Molecules only present on pathogens that are essential for survival and are invariant structures shared by the entire class of pathogens
What is the PAMP on gram negative bacteria?
Lipopolysaccharides in the outer membrane
What is a lipopolysaccharide?
Lipid anchor with a complex polysaccharide chain floating off into the outside layer
What are the PAMPs (3) on gram positive bacteria?
Peptidoglycan, techoic acid, lipoteichoic acid
What does PRR stand for?
Pattern recognition receptors
What are PRRs?
Host factors that specifically recognise a particular type of PAMP
What are the three classes of PRR?
Extracellular, intracellular and secreted
How do secreted PRRs work?
They act to tag circulating pathogens for elimination
How do extracellular PRRs work?
They recognise PAMPs outside a cell and trigger a coordinated response to the pathogen
How do intracellular PRRs work?
Recognise PAMPs inside a cell and act to coordinate a response to the pathogen
How does the interferon system work?
The virus infects cell
Cell secretes interferon
Interferon binds to any other cells to stop them replicating (and therefore the virus replicating inside of them)
What is complement?
A system of secreted proteins made in the liver that recognise PAMPs on the surface of microbes and tag them
What are the three ways for complement to kill microbes?
Phagocytosis, opsonised or have holes punched in them
What does it mean when a cell is opsonised?
A little coat of complement has stopped pathogens being able to infect cells
What are the three ways of activating complement?
- recognition of LPS and other PAMPs
- non host glycosylation is recognised by MBP and other lectins to activate lectin pathway
- membranes that are recognised as non self activate an alternative pathway
How much of WBCs are natural killer cells?
4%
What are natural killer cells?
Large granular lymphocytes
How do natural killer cells work?
They release cytotoxic molecules called granzymes (proteases) or perforins
How do NK cells recognise pathogens
Pathogens don’t have MHC molecules on their membranes
What disease is linked to a core defect in complement?
Autoimmune diseases like lupus (…it’s never lupus)
What illness is linked to a non-core defect in complement?
Susceptibility for a specific type of pathogen like neisseria
What disease is linked to a macrophage deficiency?
Chronic granulomatous disease
What is chronic granulomatous disease?
No oxidative burst for bacterial killing
What disease is linked to an IRF8 mutation?
Susceptibility of TB
What is aicardi-goutieres syndrome associated with
Constitutive production of inflammatory cytokines
What happens if you have a lack of interferon-responsiveness?
You get a sensitivity to viral infection
