4.5 Innate Immunity Flashcards
What are the three pillars of the innate immune response? Barriers, proteins and cells?
- Fixed and induced defences
- Barriers (physical, chemical and cellular)
- Specialised proteins (complement, chemokines, cytokines)
- Specialised cells (neutrophils, macrophages, NK cells)
How is the innate immune response activated?
- Receptor molecules on cells and in serum recognise PAMPs (activation)
- Can use specialized cells (NK cells) to detect altered self glycoproteins
What is the role of epithelial cells in innate immunity?
More than an important physical barrier, they also produce microbicidal and inhibitory molecules
What are the three specialised plasma factors mediating innate immunity?
C reactive protein, Mannose binding lectin, Complement proteins
What does the C-reactive protein do as part of the innate immune system?
- Binds capsule of several bacteria, aids phagocytosis, triggers the complement cascade
- Acts as soluble pattern recognition receptors
What does mannose binding lectin do as part of the innate immune system?
- Binds mannose residues on pathogens, triggers the complement cascade
What do complement proteins do as part of the innate immune system?
- Pro-enzymes (C1, C2 etc) which are triggered after binding a pathogen to produce a cascade of reactions which generate effector molecules against the pathogen
- These and others are termed acute phase proteins - rapidly produced in infection (eg CRP, C3, C4)
What does the term complement refer to?
The term complement refers to a large group of constitutively produced plasma proteins which interact with pathogens to mark them for killing
How is the complement system activated?
- No matter how the cascade is activated, breakdown of C3 is the critical step in the cascade
- Complement activation involves an enzyme “cascade”
- Exist as inactive proenzymes but cleaved products of enzyme cascade are given terms a for smaller fragment as b for larger fragment
What are the stages of complement action?
What are the outcomes of the complement cascade?
- migration of phagocytes to site of infection
- phagocytosis of microorganisms
- lysis of microorganisms
What three pathways lead to the cleavage of C3 in the complement cascade?
What does the cleavage of C3 lead to in the complement cascade?
What does this show?
- Release C5b allows recruitment of C6 and 7 and 8
- Form structure on the membrane which makes a pore and results in lysis
- Does not occur on the surface of self cells
- Our own cells have proteins that stop this cascade but microbes do not have defence mechanism
How are these cells divided?
- Bloodstream vs tissues
- Contains granules they release in response to activation
Which of these are the PAMPs?
What are the classes of Pattern Recognition Receptors?
- TLR (toll like receptors) membrane bound on surface or endosome, they recognise RNA and DNA as pathogens unpack and expose nucleic acid
- NOD (nucleotide binding oligomerisation domain) bind to peptidoglycan
- RIG (retinoic acid inducible gene), collectins, etc.,
- Some of these also bind danger associated molecular patterns (DAMPs) which are the rsult of metabolic products or products produced in excess when cell is in distress
What are the different outcomes of pattern recognition receptor and PAMP ligation?
- Ligation of soluble receptors such as MBL leads to phagocytosis
- Ligation of cell bound receptors such as mannose receptor and scavenger receptor leads to phagocytosis
- Ligation of TLRs and NODs may results in
- expression of different cell surface receptors
- production of chemokines and cytokines
- production of defensins
- Ligation of RIGs associated with anti-viral immunity
What are cytokines?
- a protein secreted by cells that interacts with and affects the behaviour of nearby cell bearing the appropriate receptors
- Affect multiple functions (regulate innate immunity, adaptive immunity, haematopoiesis and more)
What are some types of cytokines?
Multiple names – interleukins (IL-), interferons (IFN-), colony stimulating factors (CSF’s) , tumor necrosis factors (TNF’s),
What are chemokines?
A secreted protein that attracts cells bearing the appropriate receptors
What are the two groups of chemokines?
- Two groups of receptors, both of which contain two cysteine molecules
- CCR
- CXCR
What are the two types of phagocytes?
Polymorphonuclear neutrophils
- most numerous, but short lived cells, found in circulation.
Mononuclear phagocytes (macrophages, monocytes)
- long lived cells, found in circulation and tissues
What is the function of phagocytes?
- Enter an infected site from the circulation, where they:
- bind , engulf, and kill a wide variety of microbial agents
- produce immunomodulatory substances, eg. cytokines, chemokines, which regulate the immune response
- act as a first line defence against infection
What sort of receptors do macrophages express?
Many different pattern recognition receptors
What bioactive products do macrophages express when activated?
How does inflammation occur?
How do macrophage and complement proteins induce nuetrophil migration from blood to tissues?
How does the binding strength compare?
What are the steps of phagocytosis?
What are some phagocyte killing mechanisms?
Lactoferrin scavenge iron away from the bacteria
What are cytotoxic cells?
- Target infected or altered cells, and release granules whose contents are toxic.
- Natural killer (NK) cells (kill tumour, virus infected cells)
- Eosinophils (kill antibody coated parasites)
- Macrophages (release cytotoxic mediators)
What are basophils and mast cells?
- Release granules containing inflammatory mediators to augment the action of immune cells,
- But this increases inflammation and mediates unwanted hypersensitivity reaction such as allergies
What is the outcome of the response to microorganism invasion by the innate defences?
- Removal of the invading microorganisms leads to resolution of infection.
- Persistence and replication of microorganism.
- because some microorganisms evolved to overcome the defences of the innate immune system - Pathogens
- Resolution of infection of infections by pathogens requires additional effector mechanisms. These are provided by the more recently evolved Adaptive Immune System.
