So, I was reminded yet again how little people actually know about immunology, so before I write a post on the role of the immune system in any disease, I figured I should write this first. Most people I have met know very little of the adaptive immune system, and if you ask a random person on the street about the innate immune system, well, don’t, it’s depressing. So I’m going to start off with a brief introduction into innate immunity. It is a bit of a simplification, and if you want to know more, buy an immunology book, I recommend this one.
We have two types of immunity which do, somewhat, overlap. The innate immune system has several parts. Complement, granulocytes (I include Mast Cells here, too), and Natural Killer cells (NK cells) are the portions which are truly innate requiring no antibodies to the target proteins or cells, although bound antibodies can and do enhance these responses.
NK cells destroy non-self tissue (and are potentially, along with CD8+ T cells, a major component of immune system mediated transplant rejection) when they fail to bind an MHC class I molecule which is normally a result of viral downregulation of the MHC class I gene. As opposed to CD8+ T-cell cytolitic activity which is in the default “do not kill” state, the “default” state for an NK cell is “kill” unless it is given the “stop” signal by binding MHC class I.
The complement system is initiated in one of three pathways, Classical, Alternative, or Mannose Binding Lectin (MBL). Classical is actually part of the adaptive immune system as it requires antibodies to bind antigen (IgG or IgM antibodies, specifically) and a protein called C1q binds to the Fc (functional) region of the antibodies (IgG or IgM) which are bound to the antigen. The alternative pathway is started by random dissociation of a molecule (C3) into it’s two byproducts. The MBL pathway, as the name suggests, binds mannose (and fucose) in a specific arrangement as found on many pathogenic cells rather than binding to antibodies which are attached to antigen. You really only need to know two things about this: C3b and Membrane Attack Complex (MAC). C3b is an opsonizing agent (it coats the target cell and signals to phagocytes “EAT ME!!!”) while the MAC forms a pore allowing all the insides of the cell to diffuse to the outside as well as the other way around, thus killing the target cell. I see no need to get much more detailed than this with the complement system.
The final major parts of the innate immune system are the cells. These include the granulocytic and phagocytic cells. Neutrophils are both, but mast cells, eosinophils, and basophils are granulocytes, as while the macrophages is phagocytic. Eosinophils, basophils, neutrophils, and mast cells contain granules (hence the name: granulocyte) which contain chemicals utilized for destruction of target cells and recruitment of additional cells. Macrophages and neutrophils are capable of phagocytizing pathogens.
The innate immune system responds the same way to the same type of pathogen every time. One Streptococcus infection is treated just like any other, at least by the innate immune system, until the adaptive response enhances and directs the parts of the innate response..
The adaptive immune system has two major components which need to be remembered: T-cells and B cells. Each of these can be subdivided, CD8+ and CD4+ T cells (as well as γδ T cells and others, but let’s ignore these) and Plasma, Memory, Follicular, and other B cells. Put simply, T-cells play a role in cell-mediated immunity while B-cells produce antibodies. When you or I receive a vaccine, these are the types of cells which are being activated. I say activated because (short of a genetic disorder or cancer treatment) you have thousands of each type of cell which vary considerably in the antigen they bind to. When these cells bind the antigen, they proliferate (and undergo hypermutation (lots of mutations in the binding region of the immunoglobulin), and then activate.
CD8+ T-cells interact with MHC class I molecules and the peptide which is presented by the MHC molecule. The peptide which is bound by the MHC molecule is the antigen which is presented to T-cells. If the (CD8+) T cell (presently naive) is capable of tightly binding the MHC and peptide, it undergoes clonal expansion, i.e. it will proliferate several thousand fold, and these daughter cells are “activated.” Once activated, the same MHC class I/peptide combination results in the T-cell killing the target cell. CD4+ T cells, on the other hand, respond to MHC Class II molecules and only signal other cells when it binds its target MHC/Peptide combination.
B-cells produce the immunoglobulins which are found on the surface of B-cells (IgD, IgM), in mucosal areas (IgA), and serum (all of the above plus IgE and IgG). Different immunoglobulans have different Fc regions which elicit various responses. IgE is responsible for the degranulation of Mast Cells. IgG and IgM activate the complement system and opsonize pathogens. IgA prevents pathogens from colonizing mucosal areas. In truth, their roles and interactions are a bit more complex than this, but for the purposes of an introduction to the immune system, it will suffice.