The innate immune response has many synonyms: the natural, the non-specific etc. It is the body's "first line of defence" when infected. And it is crucially important.
The innate immune system can be broadly divided into the following categories, which we'll have a natter about below:
- Genetic
- Mechanical
- Molecular and
- Cellular.
A useful mnemonic I've found has been General Medical Council for GMMC. But I suppose you could come up with something a little funnier: Gretchen's Mighty and Monstrous Carp for example :P
Genetic
This is the simplest strand. It is basically that the pathogen/condition may be species specific. I.e. we are not going to suffer from a disease that just affects zebras are we?
That said, there are conditions - termed "zoonotic" - which can
jump the species barrier, as it were.
vCJD and influenza are 2 commonly named examples.
vCJD, for those who don't want to click off, is a disease originate in the bovine species that can transition to humans in very rare cases. It is a neurodegenerative condition that is ultimately fatal to humans.
Mechanical
The first, and incredibly important mechanical innate defence mechanism of the body, is the skin. Without skin (such as in the case of a burns patient), infection is very likely and very dangerous.
Secretions are the next e.g. skin, sweat and tears. They each share many pharmacologically active factors - not least lysozymes (which of course catalyse the hydrolysis of the peptidoglycan in bacterial cell walls - the characteristically unique feature of old Baccy cells).
The mucosa throughout the body (rife in mast cells with IgE surface receptors) comes next for inspection. It traps particles, debris, microorganisms etc in the trachea, GI tract and via mucociliary clearance/peristalsis is expelled from danger areas to be (a) expectorated from the oropharynx or (b) swallowed.
You should also remember that within the body are commensal organisms - as Yakult would call them, the "good bacteria". These assist in digestion and other metabolic functions, and all they ask in return is a little of the resources the body has in reserve. They also act to starve the pathogenic species entering us. This competition is keeping us safe innately - cool 'ey?
The body also has the ability to mediate inflammation and pyrexic states at a whim. Macrophages are a key player in these responses, secreting active mediating factors. Thus enabling states that are advantageous to a well oiled immune response and/or detrimental to the pathogens.
Molecular
The first thing to think of is interferon. There are 2 camps, the "specialised" and "unspecialised". Firstly, the smaller unspecialised are 15-25kDa, and secreted by most immune cells. They are termed IFN alpha and beta. The larger (30kDa on average) IFN-gamma is secreted by activated T lymphocytes only I'm afraid. Cheeky bugger.
Their functions, as IFN, is logically to interfere and prevent viral replication. As such, a large increase in the IFN family is observable on blood works during a viral infection. They also stimulate NK cells and cause the activation of the differentiation of B cells.
Enough about the interferers. There are also lysozymes, which we've touched on before, and acute phase proteins - or APPs. These are, as the name logically suggests, proteins found in large serum concs immediately after an infection has occurred.
An example of an APP is "CRP", or C-reactive protein, which is synthesised in the liver. It is only released in response to a macrophages' secretion of IL-1. At this stage, CRP is then responsible for helping to opsonise bacteria (coat in a nice sauce bacteria for phagocytosis) and also for triggering the complement cascade system.
The final molecular strand of the innate immunity is complement cascades themselves. In a brief nutshell, they are responsible for opsonisation and their terminal components lyse bacteria by literally punching a hole through their cell walls.
Cellular
The following are cells that are involved in the innate immune response:
- Macrophages: containing TLR and IgG receptors on their cell surface, they are chemotactically attracted to a site of infection. There they secrete soluble factors that are cytotoxic, and also factors that alert the rest of the immune system.
- Polymorphs: Similarly to macrophages, they possess IgG receptors, transport in the blood, exudate to infected tissue, phagocytose and secrete alerting factors to the immune system.
- Mast cells: are found in the mucosa of the body. They secrete pharmacologically active factors, e.g. histamine, that cause an increase in permeability of the endothelium of blood vessels.
- NK cells: kill tumour cells, virally infected cells and Ab coated cells.
- Dendritic cells: secrete alerting and modulatory factors to control immune responses to infections.
A little more on macrophages:
Macs are very important. I like to think of their role as 2-fold. They provide destructive and constructive elements to the innate immune response. Here's how:
They secrete factors that are cytotoxic. As well as phagocytosing cells and bringing about Oxygen dependent and independent cellular death. They also generate tissue damage through H2O2 secretions.
Constructively, they bring about inflammation, pyrexia and the secretion of modulatory cytokines. They also activate lymphocytes, process and present Ag's epitopes in their MHC structures (MHC Class I for endogenous antigens).
A final role for Mac is tissue re-organisation: factor in their use of elastinase, collagenase and angiogenic factors.
