Review of The Innate Immune System Flashcards
Why do we need innate immunity?
The adaptive immune response is too slow to protect us from some new pathogens (the cytotoxic T cells take about 3-4 days to kick in), which is a problem as we are being exposed to new pathogens every day.
If the pathogen replicates relatively slowly, you’ll be fine as the adaptive immune system will kick in before the number starts to get too high.
However, if the pathogen replicates at a high level, they could rapidly overwhelm you if you don’t have a rapid immune response.
Thus, innate immunity kicks in very early.
It buys you time long enough for the adaptive immune system to respond to the pathogen.
What is the specificity of the innate immune response as compared to the adaptive immune system?
Adaptive immunity involves very specific recognition of infectious agents (usually sees a protein = antigen).
Innate immunity involves no specific antigen recognition.
Innate involves recognition of broadly conserved features of different classes of pathogens.
What does innate immunity consist of?
- Phagocytosis – engulfing foreign bodies
- The Inflammatory Response
- Cytokines, Interferons and Antimicrobial peptides (AMPs)
- Complement – enhancing the way that antibodies work
- Intrinsic Defences – “the hostile cell” – cells have evolved to be environments that are hostile to the replication of the pathogen
- NK cells
Describe phagocytosis.
It is carried out in vertebrates by dendritic cells, macrophages and neutrophils.
Phagocytosis clears pathogens but also presents peptides on MHCs – this promotes development or reactivation of the adaptive immune response.
Describe dendritic cells, macrophages and neutrophils.
The major role of dendritic cells is to detect the pathogen, take it up, then they traffic to lymph nodes, where they break down the pathogen they’ve taken up. They then present its peptides to MHC Class II (sometimes Class I) and our lymph nodes educate the adaptive immune response, so they help select and stimulate division of naïve T and B cells.
Macrophages are found in most tissues, and they have many functions. Along with presenting antigens, they also can reactivate memory, and clear and repair damage. Most of them are tissue-resident, so they stay there.
Neutrophils are rarely tissue-resident; they circulate around the body. When an infection is triggered, you get recruitment to the site of infection, and a massive increase in the number of neutrophils.
Ultimately, it is the neutrophils that do most of the phagocytosis. It is advantageous that they can remove pathogens, but disadvantageous that they will destroy anything.
What are the role of macrophages in innate immunity?
Macrophages have two distinct roles in innate immunity:
- phagocytosis; material is destroyed in lysosomes
- captured material can trigger macrophage activation - activated macrophages produce cytokines and chemokines to stimulate both innate and adaptive immune responses – this triggers the inflammatory response and can promote a local anti-microbial state
Describe the inflammatory response.
It is a generic defence mechanism whose purpose is to localize and eliminate injurious agents and to remove damaged tissue components.
It:
- enhances permeability and extravasation
- recruits neutrophils
- enhances cell adhesion
- enhances clotting
Briefly, recap the inflammatory response by a macrophage.
When a macrophage is infected, it will release signals such as cytokines and chemokines. They chemicals increase the permeability of the surrounding blood vessels, allowing the neutrophils and other immune system cells to pass through and localise at the site of infection. Neutrophils and macrophages arrive that help deal with and clear up the remaining infection.
What is the difference between cytokines and chemokines?
They are both glycoprotein hormones that affect the immune response.
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 phagocytes know what to eat?
Material to be “eaten” is recognised in a number of ways:
- by detecting phosphatidyl serine on exterior membrane surface (cells undergoing apoptosis)
- by scavenger receptors (they target bacterial cell walls) (mainly)
- by some Toll-Like Receptors (TLRs)
- by passive sampling
Describe PAMPs (Pathogen-Associated Molecular Patterns).
These molecules present only on pathogens and not on host cells.
They are essential for the survival of pathogens, so the organism cannot mutate it away.
It is an invariant structure shared by entire class of pathogens.
List some examples of PAMPs.
- Gram-negative bacteria: lipopolysaccharides (LPSs) found in outer membrane
- Gram-positive bacteria: teichoic acid, lipoteichoic acid, peptidoglycan found in outer membrane
- Bacterial flagellin (conserved throughout bacteria)
- Abnormal protein glycosylation
- Abnormal nucleic acids – viruses (since they don’t have cell walls)
Describe PRRs (Pattern Recognition Receptors).
They are host factors that specifically recognise a particular type of PAMP.
They are germ-line encoded (they encode for the exact same thing no matter which cell they are expressed in).
There are several classes of PRR, but functionally they are either:
- 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
Describe the complement system.
It was originally described as a heat-sensitive component of serum that could augment the ability of antibodies to inactivate antigen.
It was originally thought to be a biochemically complex antibody-dependent effector mechanism leading to:
- opsonisation
- recruitment of phagocytic cells, vasoactive function
- punches holes in target membranes (MAC)
The complement system is an evolutionarily ancient system, which predates the development of the adaptive response.
The use as an effector mechanism for the latter is therefore an adaptation grafted onto the original purposes of complement as a vital part of innate immunity.
Complement proteins act as secreted Pattern recognition receptors (PRRs) and can be activated by a range of PAMPs, and can also be activated by “altered self”.
What are the three pathways of complement?
CLASSICAL: This is the antigen-antibody pathway. The triggering protein is C1q, which can recognise polysaccharides.
LECTIN PATHWAY: This one can recognise abnormal glycosylation.
ALTERNATIVE PATHWAY: any pathogen surface that is not of host origin will lack complement control proteins on the surface, which will activate complement.
