A BASIC GUIDE TO IMMUNOLOGY
Right guys, Iâ€™ll try (being non-medic) and give you a very basic insight into immunological mechanisms. â€¦Sit up straight at the back!!, and stop munching on that bar of chocolate â€“ swallow it now!! (shouts he wearing his demon headmaster wig) - LOL
You will know doubt be familiar with allergic reactions involving IgE antibodies. For example, someone who suffers from asthma due to dust mites will suffer from what is described as an immediate Type 1 allergic reaction, sometimes also called antibody-mediated reactions because it involves the production of IgE antibodies which in turn produce inflammatory chemicals like histamine, etc.
Now there are some important immunological details (â€œthe dark sideâ€ as I sometimes call it) that are not openly communicated by GPs and are often excluded from general asthma/allergy books. Probably this is to avoid confusion due to the subject complexity.
Immune function (immunity) is split into two separate but overlapping components; Non-specific (innate) and specific immunity (adaptive). Although each of these host defences are described separately below, they are activated simultaneously and function synergistically to prevent and control infection. Host defences are regulated by T lymphocytes (T-cells) and this action is referred to as cell-mediated immunity. T-cells take their name from the Thymus gland, the point where T-cells are derived.
Non-specific immunity is the primary defence and non-specific component of the immune system such as the skin, mucous membrane and systemic defences. Non-specific immunity promotes inflammation as a defence mechanism. Generally speaking, it is only when the primary defence system has been breached that specific immunity will be signalled into action.
Specific immunity is the specific component of the immune system which initiates an immunological response when a person encounters a fungal pathogen, allergen, etc. As I said above, this does not become fully active until the non-specific defence system has been penetrated.
Specific immunity is provided by the release of antibodies (IgG, IgA, IgM, IgD & IgE) but letâ€™s not go there just now. â€¦Pay attention, please!! Antibodies are derived from B cells, also known as B lymphocytes. They take their name from the bone marrow, the point where B cells originate. B cell responses to most antigens are absolutely dependant upon T cell help.
If we look in more detail at T-cells (but still in a general sort of way), there are two main types of T-cells (there are others also). The first type are called T-helper cells (their text book name being CD4), and the second type are called T-suppressor cells (their text book name being CD8). Furthermore, T-helper cells can be broken down further into sub-populations. Does anybody know what these are called?, come on, quick, give me an answer? Much too slow. â€¦You at the back, stop peering out of the window, you will not find the answer out there!! That is not a window of opportunity!!
Okay, now where was I, â€¦yes, sub-populations â€“ The helper cell sub-populations are normally referred to using their text book names Th1 & Th2. We will not talk about what Th1 and Th2 cells do (or for that matter Th0, Th3, Tr1) we will attempt to enlighten you another day when the temperature in here is a bit chillier to stop you falling asleep.
It is noteworthy that suppressor cells also have a sub-population and these are normally referred to using their text book names Tc1 & Tc2. But as I said above, letâ€™s not go there today!
So going back to the T-cell, â€¦why are T-cells so important? ..some mumbling from someone who hasnâ€™t fallen asleep yet. Wake up you horrible lot!! Do you think I have nothing better to do than stand here sprouting forth with this medical claptrap!
T-cells are extremely important because they orchestrate and control ALL immunological functions. The T-cells work a wee bit like the engine management system in the modern car, by ensuring the correct level of immunological response is applied and withdrawn relative to the strength and potency of the invading allergen, bacteria, etc. The T-helper cells promote a vigorous immunological response (lets say by stimulating IgE production), and the T-suppressor cells hold back, slow down and taper-off the immunological response. The T-helper and T-suppressor cells work very closely together and it is this working relationship that is referred to as the T-helper/suppressor cell ratio (in text book terms CD4/CD8 ratio). In a healthy person the CD4/CD8 ratio is said to be 1:1 or even 2:1. If the ratio is changed in some way (either by an inherited characteristic or acquired) then this will affect the way in which the immunological response is applied/withdrawn. At one end of the immunological spectrum will be suppression of immune response leading to infection (possibly fungal respiratory infection) and at the other end will be hypersensitivity leading to autoimmune disease (possibly rheumatoid arthritis). And of course there is a whole range of immunological dysfunctions in between.
Well, do you know if an incorrect CD4/CD8 ration can be corrected? Come on guys, we are just about at the end of the topic for today so please show a wee bit more enthusiasm and stop slouching on your desk!
In principle it can be. This is called modulation or immunomodulation, where the ratio of CD4 to CD8 cells would artificially be adjusted/manipulated back to the nominal 2:1 ratio. The correct level of modulation is the difficult part because there are so many variables and corrections/counter-corrections going on in the body, plus this is very individual treatment and what may work well for one person may not have the desired effect on the next person.
So what treatments are available. Well guys I think the period bell is about to ring, so I will conclude this lecture by saying that treatments for T-cell modulation are very much experimental at the moment with consultants prescribing various types of immunosuppressive medicines like azathioprine, methotrexate and cyclosporin with varying degrees of success.
Cyclosporin appears to be the better option as it is a more selective immunosuppressant because its main site of action is the CD4 T helper cell population. From this, it would appear that azathioprine and methotrexate are not so selective and therefore will also suppress the T suppressor cell (CD8) population. The inference being that little (or no) modulation between CD4 and CD8 cells can be achieved using these other immunosuppressive meds. It is my opinion that immunosuppressants should not be prescribed if there is evidence that the immune system is already depressed.
Azithromycin is not an immunosuppressant but it does cause immune system modulation. Azithromycin is a macrolide antibiotic with immunomodulatory effects and this appears to be prescribed to asthmatics for its anti-inflammatory properties as well as its antibiotic properties. According to the literature, the modulatory mechanisms of azithromycin are effective but not clearly understood. It is my opinion that azithromycin should not be prescribed if there is evidence that the immune system is already depressed.
Sorry guys, but thatâ€™s it for today, and I hope you have been taking notes because I will be testing you on this next week â€“ LOL.