How does our immune system work, and how can we see on regular pathology tests if there are signs it's not working well, and when to be concerned about possible immune issues, whether they be potential acute or chronic causes?
How does our Immune System work?
The immune system as a whole is made up of cells, chemicals and processes that protect us from bacteria, fungi, parasites, viruses, toxins and cancer cells. Let's find out how our immune system works.
Our immune system is comprised of two parts to its defence: the innate immunity and adaptive immunity. Both sides work intimately together, but if there is a defect in any aspect, from illness, disease, or inappropriate inflammation, then autoimmune, immunodeficiency disorders and hypersensitivity reactions, can occur.
The innate and adaptive immune responses are not mutually exclusive, but rather operate together in a complementary way. Defects can occur in either side and result in inappropriate responses.
In the graphic below we can see the Innate Immune System on the left, divided by the vertical dotted line from the adaptive immune system on the right. The adaptive immune system is further divided by a horizontal dotted line separating the Cell-Mediated immune response from the Humoral immune response. What is happening in this cartoon graphic shows exactly what happens in our immune response, and is described in detail below.
Innate Immunity
Innate immunity is the first line of defence and it acts within hours of sensing an inappropriate intruder. The innate immune system uses barriers like our skin, and mucous membranes, along with body temperature, pH and chemicals to prevent entry into our bodies. It also uses cells to eat invaders (phagocytosis), as well as to release toxins and inflammatory responses (the complement system activation, pro inflammatory cytokines etc) to hinder the invaders entry into our bodies. Cells also talk to each other by communicating via cytokines and chemokine's which you may have heard of during the recent epidemic e.g. Interleukin-6, and tumour necrosis factor (TNF).
While it was once thought that the innate immune system was non-specific, approaching each pathogenic invasion as a naive experience, it is now recognised that innate immunity can be upregulated or 'trained'. This training occurs when microbe-associated molecular patterns (MAMPs) are recognised by the immune cell, allowing it to develop a memory of the pathogen, and a more rapid response to a subsequent exposure. β-glucans, which are the structural components of yeast and fungal cell walls, present as MAMPs to the innate immune cells in a similar fashion to pathogenic microbes, creating a comparable increase in cellular 'fitness' or readiness for pathogenic invasion. With all the mould exposure from heavy rainfall in Australia, it is little wonder we are seeing more immune system issues.
As well as MAMP's, the innate immune system can act the way it does by recognising receptors on pathogens (Pathogen Recognition Receptors or PRR), as well as pathogen associated molecular patterns (PAMP's). Examples could include if we had lipopolysaccharides in our gut microbiome from a fatty diet, or if we had RNA present from virus replication. There are many other examples.
The innate immune system also initiates the inflammatory response, where we see temperature increase, pain, redness, swelling, and potentially loss of function to contain the infection. All of this is controlled by the 'project manager' (who's scientific name is NF-kB) that gets initiated and sets off the pro-inflammatory response. We would see an increase in our CRP (C-reactive protein) from IL-6 release, if this response was an acute response.
Cells involved in the innate response include macrophages, monocytes, neutrophils, basophils, eosinophils, mast cells, natural killer cells (NK), and innate lymphocytes. If you see an alteration in any of these cell types on your Full Blood Count (FBC), or in lymphocyte subsets, it may mean you have an immune system imbalance. For example, often we see, chronic elevation of monocytes that live for a long time for example. Mast cells and basophil elevations can be seen with allergies or asthma. Eosinophils can highlight the presence of parasites. Elevations of Natural Killer Cells may be because they are trying to play a role in destroying cells infected by viruses.
Secretory IgA (sIgA) provides the first line of defence against pathogens, blocking adherence to the epithelial surface by binding to and trapping the pathogen in the mucous lining. The pathogen then gets discarded. We see low sIgA in all sorts of gut issues including Irritable Bowel Syndrome (IBD), and Inflammatory Bowel Syndrome (IBS), chronic stress, sleep disturbances, autoimmune diseases, after intense exercise, and from the use of some medications. The liklihood of infections, allergies and autoimmune conditions increases in low sIgA situations.
The immune system must be able to recognise us versus the pathogens. In other words 'self' versus 'non-self'. It does this by utilising major histocompatibility complexes (MHC's). MHC's are classified as either class I or class II.
MHC Class I (also termed Human Leucocyte Antigens or HLA's) are either A, B or C and are found on all cells with a nucleus. MHC Class II (or HLA DP, DQ, DR) are present on a limited number of cell types (macrophages, dendritic cells, and B lymphocytes). You may be familiar with seeing MHC testing - if you have the genetic predisposition for Coeliac Disease you will have tested positive for HLA DQ2/ DQ8. Now you have some idea what that means.
Adaptive Immune System
The Innate Immune Response and Acute Inflammation can only hold things at bay for so long before the Adaptive Immune System is called in (a.k.a. the SAS). Dendritic cells, otherwise known as antigen presenting cells, 'show' the offender to both sides of our immune system.
The adaptive immune system kicks in when the defences of the innate system have been ineffective. The pathogen is presented by dendritic cells that have gobbled up the pathogen, and so they display 'non-self flags' to our naive T-helper lymphocyte cells. Once the naive T helper cell sees the MHC II flag, and another protective mechanism (B7) as a second alert has been triggered, the green light is given for more advanced activity to occur by our adaptive immune system.
Two sides of the Adaptive Immune system include:
T Helper 1 cells (Th1) are engaged when the pathogen is inside cells (intracellular) e.g. mostly against viruses, while T Helper 2 cells (Th2) are engaged when the pathogen is outside our cells (extracellular) by producing antibodies (IgE, IgG, IgM etc) e.g most against bacteria, fungi, parasites.
Intracellular infections –> TH1 –> cell-mediated immune response with activated APCs and cytotoxic T lymphocyte cells e.g. viruses
The fine balance between the Th1 and Th2 response is modulated by T-Regulator cells. Th17 cells are a relatively newly discovered subset and are associated with ongoing inflammatory responses like chronic infection and disease.
Some viruses have unique abilities to slip between intracellular and extracellular locations to evade being targeted by our immune system e.g. Epstein Barr Virus (EBV)
Adaptive Immunity is unique to each individual and it can remember if it has seen a pathogen before. When we vaccinate, we are calling on the memory ability of the adaptive immune system.
Diseases associated with a Depressed Immune System
Inherited (Primary) Immunodeficiencies - e.g. Severe Combined Immunodeficiency (SCID), and Common Variable Immunodeficiency (CVID)
Acquired (Secondary) Immunodeficiencies - e.g. HIV
Diseases Associated with Overactive Immune System
Type 1 - IgE Mediated Hypersensitivity from B cells e.g. Systemic Anaphylaxis, Seasonal Allergies, Food allergies, Eczema
Type II - IgG Mediated Cytotoxic Hypersensitivity from B cells e.g. Blood transfusion mismatches, autoimmune haemolytic anaemia
Type III - Immune Complex Mediated Hypersensitivity (Antigen-Antibody complexes) from B cells e.g. Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), Glomerulonephritis
Type IV- Cell Mediated Hypersensitivity from T cells where Th1 cells cause activated macrophages to accumulate at a site in the body e.g. autoimmune diseases, Multiple Sclerosis, Rheumatoid Arthritis, Contact dermatitis
Pathology Tests as Indicators of Immune Issues
As starters, regular pathology result abnormalities can be indicators of potential acute or chronic immune function issues. Do you recognise these signs of chronic, low grade inflammation?
Full Blood Count (FBC) with changes in White Cell Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Platelets
Erythrocyte Sedimentation Rate (ESR) and C-Reactive protein (CRP) elevations
Lipid studies -elevated cholesterol is actually a healing molecule, so remove the cause of inflammation and cholesterol will lower. Cholesterol is the firefighter, not the fire. There is only a minimal 10% of the population that have genetic abnormalities with cholesterol management. Elevated triglycerides. Decreased HDL is a sign of insulin resistance.
Iron Studies with % Transferrin Saturation and Total Iron Binding Capacity (TIBC) changes from poor iron regulation from Hepcidin
Vitamin B12 levels decreased
Vitamin D levels decreased
Liver Function Tests with altered Albumin and Globulin ratio, and elevated GGT levels
Thyroid Function Tests not optimal
Insulin - is elevated and with poor glucose regulation, that makes plaque in our arteries sticky like toffee. Remove simple carbohydrates from your diet, and if you've become insulin resistant unblock that first. See my blog on Metabolic Syndrome
Abdominal fat - we hold toxins in our abdominal fat. This fat build up is an inflammatory organ generating disease. Hence why we need to lose abdominal fat.
Fatty liver
Gout
Leaky gut (Intestinal Permeability) - remove the inflammation, and heal the gut
Pathogens in your microbiome - crowd out the pathogens with good bacteria, remove the pathogens and nourish your body.
Low Libido - it can be a side effect of all the above.
The immune system is complex. Pathology results give us indications as to what is going on. Ensuring you are having the results interpreted by someone qualified to look for the nuances is important for understanding the complexities of your health journey. If you would like to discuss your own personal immunity concerns, and understand potential causations, then please don't hesitate to make a booking with me.
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References:
British Society for Immunology Bio-Practica Immune System article
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