Immune System is one single force that is responsible for our survival in a hostile environment of bacteria, viruses and parasites. It is fully responsible for the longevity and happiness of life by constantly proof-reading our DNA. In contrary to skin, hair or eyes, immunity does not have a single visible organ in the body except for lymph nodes that sometimes can be felt for on the neck – the immune cells are everywhere and are involved in multiple body functions. In my opinion that is the main reason people usually are not that worried about immunity when they experience headaches, back pain, memory problems, or indigestion. Yet, many of the symptoms can be a giveaway of malfunctioning immunity.

Medical conditions that are caused by low functioning of the immune system are immunodeficiency. This can be an inherited condition (SCID, Wisckott-Aldrich syndrome) when low immune defenses are caused by a genetic break in the chromosome. Immunodeficiency can be caused by certain drugs on purpose (high doses of steroids that are given during bone marrow transplant), or as a side effect – (certain biological treatments that are used for cancer treatment or autoimmune diseases).

Recently more attention is brought to the health problems caused by immune system “going hair wire” – hyperactivity. Common allergy is an example very known to everyone.allergy In this state of aggressiveness immune system somehow starts attacking proteins that were historically a part of normal exposure to surrounding life and elements. Signals that immune cells give to the whole system change from “accept and tolerate” to “attach and destroy”. In a way, our immunity is just trying to protect us from dangerous intruders, unfortunately these proteins are vital to us and abandon in our daily life (like food, metals, or pets). There is almost no difference in the way immune cells will try to destroy viruses, parasites or these “new” offenders like pet dander or wheat. That is why clinical problems that develop as a result of “confused” immune system actions will feel just like getting sick with cold, or having food poisoning. The bigger problem is inability of immune system to destroy cat hair that got into the nose or corn protein that is added to almost every food we eat. As the “war” continues for a prolong periods of time, the whole body starts overusing resources and showing the signs of systemic malfunctions on all the other aspects of immune works (regeneration, protection from the infections, health maintenance)

Here are 7 early warning signs we find as highly predictive and pointing to hyperactive immune system:chronic-fatigue

  1. New onset of allergies or intolerances to pollen, pets, contact chemicals or foods
  2. Increased number of colds and infections, prolonged recovery time
  3. Unusual infections and rashes
  4. Increasing fatigue, “feeling old and rundown”
  5. Nervous system dysfunctions – anxiety, depression, panic attacks
  6. Problems with digestive system – indigestion, bloating, constipation
  7. Signs of slow regenerations – arthritis, low back pain, slow healing, cancer
  • Adv Immunol. 2009;102:95-133. doi: 10.1016/S0065-2776(09)01202-4.

How the immune system achieves self-nonself discrimination during adaptive immunity.Jiang H1, Chess L.Author information


We propose an “Avidity Model of Self-Nonself Discrimination” in which self-nonself discrimination is achieved by both central thymic selection and peripheral immune regulation. The conceptual framework that links these two events is the understanding that both in the thymus and in the periphery the survival or the fate of T cells is determined by the avidity of the interactions between T cell receptors (TCRs) on T cells, specific to any antigens and MHC/antigen peptides presented by antigen-presenting cells (APCs). We envision that the immune system achieves self-nonself discrimination, during adaptive immunity, not by recognizing the structural differences between self versus foreign antigens, but rather by perceiving the avidity of T cell activation. Intrathymic deletion of high avidity T cell clones responding to the majority of self-antigens generates a truncated peripheral self-reactive repertoire composed of mainly intermediate and low but devoid of high avidity T cells compared with the foreign-reactive repertoire. The existence of intermediate avidity self-reactive T cells in the periphery represents a potential danger of pathogenic autoimmunity inherited in each individual because potentially pathogenic self-reactive T cells are included in the pool of intermediate avidity T cells and can often be functionally activated to elicit autoimmune diseases. The distinct composition of peripheral T cell repertoires to self versus to foreign antigens provides a unique opportunity for the immune system to discriminate self from nonself, in the periphery, by selectively downregulating intermediate avidity T cells to both self and foreign antigens. Selective downregulation of the intermediate avidity T cell populations containing the potentially pathogenic self-reactive T cells enables the immune system to specifically control autoimmune diseases without damaging the effective anti-infection immunity, which is, largely, mediated by high avidity T cells specific to the infectious pathogens. In this regard, it has been recently shown that Qa-1-restricted CD8(+) T cells selectively downregulate intermediate avidity T cells, to both self and foreign antigens, and as a consequence, specifically dampen autoimmunity yet optimize the immune response to foreign antigens. Selective downregulation of intermediate avidity T cells is accomplished via specific recognition, by the Qa-1-restricted CD8(+) T cells, of particular Qa-1/self-peptide complexes, such as Qa-1/Hsp60sp, which function as a common surrogate target structure and preferentially expressed on the activated intermediate avidity T cells. This regulatory pathway thus represents one example of the peripheral mechanisms that the immune system evolved to complete self-nonself discrimination that is achieved, imperfectly, by thymic negative selection, in order to maintain self-tolerance. The conceptual framework of the “Avidity Model” differs from, but contains intellectual wisdom of certain conceptual elements of, the “Tunable Activation Thresholds Hypothesis,” the “Danger Model,” and the “Ergotypic Regulation Phenomenon.” It provides a unified and simple paradigm to explain various seemingly unrelated biomedical problems inherent in immunological disorders that cannot be uniformly interpreted by any currently existing paradigms. The potential impact of the conceptual framework of the “Avidity Model” on our understanding of the development and control of commonly seen autoimmune diseases is also discussed.