What is the Immune System and How Does it Work? Part Two: The Immune Response


Y-shaped antibodies at work


Physical, mechanical, chemical, and biological barriers of the human body form the primary defense against pathogens and toxins that cause infection, damage, and disease. These barriers include the skin, hair-like structures called cilia of the respiratory tract, langerhan cells of the lungs, the blood-brain barrier, blood pH, saliva, coughing, sneezing, tears, mucous, stomach acid, intestinal bacteria, the slightly acidic environment of the reproductive system, protein antimicrobial enzymes, immune cells that kill pathogens, inflammation, and the activity of hormones.
  
A secondary line of enhanced and adaptive defense is housed within the body - a dynamic and complex system that identifies and destroys foreign substances and organisms that enter the body. The immune system can distinguish between the body's own healthy tissues and foreign pathological substances. This allows cells of the immune network to identify and destroy harmful pathogens. The ability to identify a pathological microbe also permits the immune system to remember microbes (immunological memory) the body has been exposed to in the past and to initiate a faster immune response the next time any of these pathogenic microbes appear. The immune system has the ability to create an unlimited amount of different types of antibodies.


Dysfunctions of the Immune System


Immunodeficiencies occur when one or more of the components of the immune system are inactive. The ability of the immune system to respond to pathogens is diminished in both the young and the elderly, with immune responses beginning to decline at around 50 years of age. Malnutrition, obesity, alcoholism, and drug use are common causes of poor immune function. Diets lacking sufficient protein are associated with impaired cell-mediated immunity, complement activity, phagocyte function, antibody concentrations, and cytokine production. Deficiency of single nutrients such as iron, copper, zinc, selenium, vitamins A, C, D, E, B6, and folic acid (vitamin B9) also reduces immune responses. Additionally, the loss of the thymus at an early age through genetic mutation or surgical removal results in severe immunodeficiency and a high susceptibility to infection. 

Immunodeficiencies can also be inherited. Chronic granulomatous disease, where phagocytes have a reduced ability to destroy pathogens, is an example of an inherited, or congenital immunodeficiency. AIDS and some types of cancer cause acquired immunodeficiency.


Autoimmunity

Overactive immune responses comprise the other end of immune dysfunction, particularly the autoimmune disorders.  


A generally accepted explanation is that the immune system fails to properly distinguish between self and non-self, and attacks part of the body. Under normal circumstances, many T cells and antibodies react with self peptides. One of the functions of specialized cells (located in the thymus and bone marrow) is to present young lymphocytes with self-antigens produced throughout the body and to eliminate those cells that recognize self-antigens, preventing autoimmunity. It would be more productive to question why the immune system is malfunctioning in this way. 

Auto Immune diseases: Diabetes Mellitus Type 1, MS, Lupus, Rheumatoid Arthritis, Atherosclerosis, Chrohns, Myasthenia gravis, Asthma, Pernicious Anaemia, Psoriasis,  and Ulcerative Colitus. 



Hypersensitivity
Hypersensitivity is an immune response that damages the body's own tissues. They are divided into four classes (Type I – IV) based on the mechanisms involved and the time course of the hypersensitive reaction. Type I hypersensitivity is an immediate or anaphylactic reaction, often associated with allergy. Symptoms can range from mild discomfort to death. Type I hypersensitivity is mediated by antibodies, which triggers degranulation of mast cells and basophils when cross-linked by antigen. Type II hypersensitivity occurs when antibodies bind to antigens on the patient's own cells, marking them for destruction. This is also called antibody-dependent (or cytotoxic) hypersensitivity, and is mediated by antibodies. Immune complexes (aggregations of antigens, complement proteins, and antibodies) deposited in various tissues trigger Type III hypersensitivity reactions. Type IV hypersensitivity (also known as cell-mediated or delayed type hypersensitivity) usually takes between two and three days to develop. Type IV reactions are involved in many autoimmune and infectious diseases, but may also involve contact dermatitis (poison ivy). These reactions are mediated by T cells, monocytes, and macrophages.




Do You Know?

  



Chronic Stress and the Immune System


Fatigue, anger, stress and poor health affect the functioning of the prefrontal cortex, limbic system and dopamine. The brain's default setting is autopilot and the limbic system is stronger and reflex reactions overpower good intentions when there is chronic stress. There is a distinctive shift away from adaptive goal directed decision making towards habitual behaviours. Unhealthy habits and the long term neglect of basic health habits is a chronic stress for the body.

All non-essential physiological systems shut down, our stress hormones (adrenaline/noradrenaline) kick in and there is an increase of blood pressure, heart rate, a release of glucose for a burst of energy and an increase of blood and oxygen to muscle tissue in response to a threat. Our stress response of flight or fight was originally designed to be brief and to help us in an immediate physical emergency only. 



But to a surprising extent, we humans turn on the same sort of response when feeling stressed out about the mortgages or relationships or our own mortality, and at those times the stress-response is anything but helpful, states Robert Sapolsky, Professor of Neurobiology at Stanford University and a research associate at The National Museum of Kenya.
When people burdened with stress start to feel bad physically, it is not just in their minds. Emotional crisis bring on specific changes in the body. If those responses are prolonged or set in motion too often, the resulting wear and tear can lead to alteration throughout all organ systems, concludes Dr. Sapolsky. Immune, cardiovascular, nervous, digestive, hormonal and reproductive systems, and the brain are altered. Damage to chromosomes, premature aging, inhibition of insulin production, and major depression can result, and chronic stress is making us more vulnerable to disease. 
Some side effects of over-stimulation and production of stress hormones includes: palpitations, arrhythmia, anxiety, headaches, tremors, hypertension and pulmonary edema. 



Hormones and the Immune System


When the body’s hormones are either too high, or too low, the immune system can be adversely impacted, so it is imperative to keep hormone levels properly balanced.

Adrenal  The adrenal glands have a significant influence on immunity.  They produce hormones that are vital to several metabolic functions, including DHEA, progesterone, testosterone, cortisol, and epinephrine.

Specifically, the adrenal gland’s production of cortisol is essential to maintain immunity. However, the overproduction of cortisol weakens the immune system by suppressing neutrophil function. (Neutrophil’s - white blood cells critical for immune response.)

Thyroid  A strong immune system needs an active production of Natural Killer Cells (NK or NKCs - part of the immune system’s first line of defense) to fight off foreign intruders. Researchers found that NK cells were more active among individuals with optimal levels of thyroid hormones.

Low thyroid levels can hamper the body’s response to viruses, and also cause a sluggish response to inflammation.

Estrogen  Extremely high or low estrogen levels affect the immunity. Excessive production of estrogen can suppress the thyroid, as well as reduce the activity levels of NK cells and interleukin 2.  Interleukin 2 is produced by T-cells (a type of white blood cell) to stimulate the immune system.

Furthermore, high levels of estrogen decrease the size of the thymus gland, which depresses immune activity by causing a reduction in thymus hormone levels in the blood.

In contrast, postmenopausal women that are estrogen-deprived also have weakened immunity. Low estrogen levels decrease NK cell, B lymphocyte, and T helper cell activity (all essential for proper immune response), while increasing the body’s inflammatory response.

Progesterone  Low levels of progesterone has been linked to some autoimmune diseases.  Correct progesterone balance affects proper T-cell and NK cell activity.
It has also been observed that progesterone aids immune system development in the fetus, during pregnancy.

Testosterone  When testosterone levels are low, T-cell production multiplies. T-cells fight against infections, but overproduction can lead to autoimmune diseases.

In contrast, testosterone levels that become too high significantly increase corticosterone levels, which suppress immune activity. Testosterone also regulates production of monocytes and lymphocytes - white blood cells that are essential to immunity.

Other hormones appear to regulate the immune system as well, most notably prolactin, growth hormone and vitamin D.

When a T-cell encounters a foreign pathogen, it extends a vitamin D receptor. This is essentially a signaling device that allows the T-cell to bind to the active form of vitamin D, the steroid hormone calcitriol. T-cells have a symbiotic relationship with vitamin D. Not only does the T-cell extend a vitamin D receptor, in essence asking to bind to the steroid hormone version of vitamin D, calcitriol, but the T-cell expresses the gene  which is responsible for converting the pre-hormone version of vitamin D, calcidiol into the steroid hormone version, calcitriol. Only after binding to calcitriol can T-cells perform their intended function. Other immune system cells that are known to express this gene and thus activate vitamin D, are dendritic cells, keratinocytes and macrophages.





A Hormone Cell



It is conjectured that a progressive decline in hormone levels with age is partially responsible for weakened immune responses in aging individuals. Conversely, some hormones are regulated by the immune system, notably thyroid hormone activity. The age-related decline in immune function is also related to dropping vitamin D levels in the elderly. As people age, two things happen that negatively affect their vitamin D levels. First, they stay indoors more due to decreased activity levels. This means that they get less sun and therefore produce less cholecalciferol via UVB radiation. Second, as a person ages the skin becomes less adept at producing vitamin D. 




The Latest Research Regarding Auto Immune Disease and Treatment

New findings are challenging the traditional view that the immune system in auto immune disease is targeting it’s own healthy cells and tissue. New research supports the belief that the immune system is generating antibodies in response against metagenomic communities of pathogenic microbes and that those microbes cause the systemic dysfunction often associated with auto immune diagnosis.

Pathogenic microbes share similarities to human antibody proteins and can contribute to autoantibody production. Human antibodies are polyspecific and when created to target pathogens may mistakenly target human proteins causing unintentional collateral damage. Pathogens have evolved to slow the defences of the innate immune system, disabling antibody receptor sites, deregulating hormones and releasing debris and toxins from microbial death and infection into the bloodstream, causing immune system overload and exhaustion, dysfunction and increasing successive infection. When a stalemate occurs between invading organisms and the body’s resistive forces, chronic conditions prevail.

Chronic inflammatory auto immune disease is traditionally treated with immune suppressors but the body naturally reacts by generating antibodies in response to pathogens. Immunostimulation rather than suppression is more likely to facilitate the reversal of chronic conditions.




New Discovery: Intestinal Bacterial Flora

In the early 1900s, scientists discovered that each person belonged to one of four blood types. Now they have discovered a new way to classify humanity: by bacteria. Each human being is host to thousands of different species of microbes. Yet a group of scientists now report just three distinct ecosystems in the intestines of people they have studied.

Blood type, meet bug type.





Healthy Bacteria of the Intestine



The researchers, led by Peer Bork of the European Molecular Biology Laboratory in Heidelberg, Germany, found no link between what they called enterotypes and the ethnic background of the European, American and Japanese subjects they studied.

Nor could they find a connection to sex, weight, health or age. They are now exploring other explanations. One possibility is that the intestines of infants are randomly colonized by different pioneering species of microbes.

The microbes alter the digestive tract so that only certain species can follow them.

Whatever the cause of the different enterotypes, they may end up having discrete effects on people’s health. Bacterial flora of the intestine aid in food digestion and synthesize vitamins, using enzymes our own cells cannot make.

Dr. Bork and his colleagues have found that each of the types makes a unique balance of these enzymes. Enterotype 1 produces more enzymes for making vitamin B7 (also known as biotin), for example, and Enterotype 2 more enzymes for vitamin B1 (thiamine).

The discovery of the blood types A, B, AB and O had a major effect on how doctors practice medicine. They could limit the chances that a patient’s body would reject a blood transfusion by making sure the donated blood was of a matching type. 


Doctors might be able to use enterotypes to find alternatives to antibiotics, which are becoming increasingly ineffective. Instead of trying to wipe out disease-causing bacteria that have disrupted the ecological balance of the gut, they could try to provide reinforcements for the good bacteria.

The discovery of enterotypes follows on years of work mapping the diversity of microbes in the human body - the human microbiome, as it is known. The difficulty of the task has been staggering. Each person shelters about 100 trillion microbes.For comparison, the human body is made up of only around 10 trillion cells, 10:1 ratio. These studies offered glimpses of a diversity akin to a rain forest’s. Different regions of the body were home to different combinations of species. From one person to another, scientists found more tremendous variety. Many of the species that lived in one person’s mouth, for example, were missing from another’s.

Scientists wondered if deeper studies would reveal a unity to human microbiomes. Over the past few years, researchers have identified the genomes - the complete catalog of genes - of hundreds of microbe species that live in humans. Now they can compare any gene they find with these reference genomes.

They can identify the gene’s function, and identify which genus of bacteria the microbe belongs to. And by tallying all the genes they find, the scientists can estimate how abundant each type of bacteria is.

The scientists then searched for patterns. We didn’t have any hypothesis, Dr. Bork said. “Anything that came out would be new.” Still, Dr. Bork was startled by the result of the study: all the microbiomes fell neatly into three distinct groups.