WK 13 - Innate Immunity Flashcards
List the key differences between the innate and adaptive immune systems.
Innate system:
- phylogenetically ancient and in most multicellular organisms
- ontogenetically first (ontogeny recapitulates phylogeny)
- response in seconds/minutes
- components involved: neutrophils, eosinophils, monocytes & macrophages, natural killer cells, complement, dendritic cells
- germline (birth) encoded receptors; antigen independent; no memory
Adaptive:
- only in vertebrates
- response delayed by days
- components involved: T cells, B cells/Antibodies
- receptors generated by gene rearrangement; antigen dependent; memory develops
State examples of barriers that protect us from infection.
- skin: provides physical barrier
- cilia in respiratory system (push bugs upward until they are swallowed)
- stomach acid (kills swallowed bugs)
- tears, saliva and other secretions containing enzymes (e.g. lysozyme) that digest bugs
- defensins = cationic peptides that kill bugs by disrupting cell walls; secreted onto body’s surface
- normal flora (‘current tenants’)
What is the main function of innate immunity?
- 1st line of defines after physical and functional barriers are breached
- main functions: to control/slow down and possibly eradicate invaders and to send alarm signals
- independent of previous exposure
- sets into motion components of the adaptive immune system (as needed)
Describe the function and general
mechanisms of action of complement.
- cascade system (mostly made by hepatocytes and released into the blood)
- 3 pathways of activation
- classical pathway is activated via binding of C1 to antibodies that have bound to antigen
Functions include: - kill extracellular pathogens (membrane attack complex, MAC)
- opsonize (make tasty for phagocytes)
- chemotaxis (attract support, i.e. attract phagocytic cells)
- complement activation products C5a and C3a (protein fragments produced when C5 is split into C5a + C5b and C3 is split into C3a +C3b) are chemotactic factors for neutrophils and macrophages
- involved in inflammation
Describe the function and general
mechanisms of action of natural killer cells.
- attack cells that have intracellular disturbances, do not look like ‘normal self’ (cells infected with virus; tumor cells)
- also attack targets coated in antibody (called antibody-dependent cellular cytotoxicity (ADCC)
- NK cells respond to IL-12 produced by macrophages and secrete interferon-gamma which activates the macrophages to kill phagocytksed microbes
Describe the function and general
mechanisms of action of neutrophil (polymorphonuclear cells or PMNs).
- first cell to infiltrate (move to) site of infection
- respond to signals to “come and help” (chemotaxis)
- Kamikaze Sacrifice: activated by extracellular pathogen –> phagocytosis (cell eating) –> killing “ingested” pathogen after lysosomes (granules) fuse with phagosome –> one killing mechanism involves the oxidative burst and creation of reactive oxygen species (ROS; toxic to microbes) –> in the process they kill themselves (dying/dead neutrophils - pus)
- alarm bell: secretes pro-inflammatory signals (cytokines, e.g. TNF alpha)
Describe the function and general
mechanisms of action of monocyte (blood)/ macrophage (tissue).
Phagocytosis (‘cell eating’)
- bind opsonized targets (antibodies or complement protein fragments C3b, iC3b, C4b)
- engulfing solid particles by the cell membrane to form an internal phagosome; phagosome fuses with lysosome. Contents are subsequently degraded and either released extracellularly, or released intracellularly to undergo further processing
- macrophages also do oxidative burst and create ROS (toxic to microbes)
- macrophages phagocytose microbes and also cellular debris and dead tissue
Name the key players in protecting against extracellular pathogens.
- skin and mucosal surfaces
- complement
- neutrophils and macrophages
- B cells and antibodies
Name the key players in protecting against intracellular pathogens.
- macrophages
- NK cells
- T cells
Describe the function and general
mechanisms of action of dendritic cell.
DC = interphase between the innate and adaptive immune system
DC function:
- minimal killing
- significant phagocytosis.endocytosis, not so much to kill, but to process and present the processed part to adaptive immune system (antigen presentation)
(naive T cells need a DC to be the antigen presenting cell; i.e. the first cell that gets our long lived adaptive immune system going is the DC)
What are PAMPs (Pathogen-Associated Molecular Patterns)?
PAMPs (Pathogen-Associated Molecular Patterns) are molecular structures that:
- are present on/in numerous groups of pathogens
- stable; i.e. do not undergo frequent mutation (changes)
Describe the role of pattern-recognition receptors (esp. toll-like receptors).
PRRs (Pattern Recognition Receptors) bind PAMPs. They are expressed on many (if not most) cells of the body. But the highest number is expressed on antigen presenting cells, and amongst those, the most on DC.
Localization of PRRs predicts function. Examples:
- outside cell (e.g. TLR4 binds lipopolysaccharides, LPS) mostly recognize extracellular bacteria
- inside cell (e.g. TLR 7/8 bind RNA) mostly recognize intracellular viruses
Once bound by PAMPS, PRRs signal via their intracytoplasmic signalling ‘tail’ to activate specific pathways that lead to the immune response. It is the sum-total of these intricate signals that e.g. a DC receives and integrates into a specific message that is sent of the the rest of the immune system.
How does homeostatic regulation play a role in the immune system?
As it initiates an immune response, the innate immune system already (i.e. in parallel) starts a program that will terminate the same immune response. Signals provided by the infecting microbe (via PAMPs binding PRRs) and by the accompanying tissue destruction (‘danger signals’) result in the DC “hearing what it should do”. The signal input determines the outcome.
