Early to Late Innate Immune Response Flashcards
What do pathogens express? Hint; not found on human cells
Pathogen associated molecular patterns (PAMPs)
What do innate immune cells express? Hint; partner receptors for PAMPs
Pattern-recognition receptors (PRRs)
Where are low levels of inactive Complement System proteins found?
Extracellular fluids
What does an activated Complement System create?
A cascade (downstream) of chemical reactions that promotes: opsonisation of pathogens, direct pathogen killing, acute inflammation and leukocyte recruitment
What is the inactive precursor of the Complement System?
C3 (–> C3b + C3a)
These products activate the cascade
What triggers C3’s conversion into its active products?
Mannose binding lectin (nb mannose is not found in the human body) activates C3 convertase - there is a whole cascade of reactions that occur before C3 convertase is activated c
What does active C3b do?
Associates with other complement system proteins producing C5 convertase - cleaves inactive C5 into C5a and C5b
What does active C5b do?
Associates with other complement system proteins to produce a pore-forming channel which inserts into the pathogen membrane/cell = MAC (membrane attack complex)
When is the downstream complement pathway activated?
Only in the presence of a pathogen (is what should prevent destruction of a human cell membrane 0 they have special receptors to avoid being destroyed)
What does the MAC do?
Extracellular salts and water enter the pathogen via the pore, causing the pathogen to swell and burst
Other than C5 conversion what else does C3b do?
It is an opsonin - involved in opsonisation for pathogen phagocytosis and killing
What are C3a and C5a?
Anaphylatoxins
What do anaphylatoxins do?
Promote changes in the local vasculature, acute inflammation and leukocyte recruitment by activating mast cells or acting directly on local blood vessels
What are some features of healthy tissues?
No inflammatory mediators, normal vasculature and circulating neutrophils
What does inflammation promote?
Vascular changes, and recruitment/activation of neutrophils (transendothelial migration)
What vascular changes occur in infected/damaged tissue?
Dilation of post capillary venues (leads to vasodilation/increased blood flow), tight junctions between endothelial cells are lost (increased vascular permeability/swelling) and expression of specific adhesion molecules on the surface of endothelial cells and activation of adhesion receptors on circulating neutrophils
What do neutrophils do?
- Phagolysosomal killing and ROS-mediated killing (reactive oxygen species) as they are toxic to pathogens (double the effectiveness).
- Degranulation/releasing residual enzyme and toxins - direct killing of pathogens (causes tissue damage/systemic inflammation)
What do neutrophils do?
- Phagolysosomal killing and ROS-mediated killing (reactive oxygen species) as they are toxic to pathogens
- Degranulation/releasing residual enzyme and toxins - direct killing of pathogens (causes tissue damage/systemic inflammation)
- Neutrophil Extracellular Traps (NETs) - neutrophils kill themselves and release nets to stick to pathogens and hold them until macrophages come and ‘mop’ up the damage
What are the components of pus?
Neutrophils, NETs, dead bacteria and cellular debris
Why does fever help infection?
Raising the body temperature outside of bacteria’s narrow temperature niche helps their replication rates to drop drastically
What does C reactive protein (CRP) do?
Primes certain bacteria for destruction by the complement system (it is prognostic- rapidly increased during inflammation and very short 1/2 life so disappears once inflammation is gone)
How do virally infected cells attempt to respond to attack?
- Signal neighbouring cells to stop translation and transcription.
- Signal neighbouring cells to undergo apoptosis
- Activates immune cells - eg Natural Killer Cells
(signalling done by interferons which are host specific but not virus specific)
What do Natural Killer cells?
Specifically kill infected/abnormal cancer cells but ignore healthy tissues and cells.
What are natural killer cells?
Lymphocytes that recognise and destroy viral or cancer cells
