Immunity Knowledge Base


Cellular elements of immunity



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We live in a challenging world. Life in many instances is not always so altruistic as we would wish; many organisms live by taking advantage of other forms of life, to supply a habitat, or food, or protection. When this becomes harmful to the host, it is termed an infection. Other challenges can result from non-living entities, such as foods, or pollens. These can often result in a sensitivity reaction termed an allergy. Day-to-day processes of cell repair can become altered protracted. This can often result in a phenomena called inflammation. Surprisingly, these very diverse phenomena are all controlled by the body’s immune system, which is very much under the influence of blood type.


‘Simple’ mechanisms of immunity

Most things in Nature make a habit of sticking onto other things. Not only can a simple organism hitch a free ride to a new location by doing so, attachment is the first step in the process of many infectious diseases. Thus many of the more complicated processes of the immune system in reality represent one side   trying to stick to or slide off of the other. For example, many things in Nature are ‘slimy’ because they are secreting long branching sugar molecules onto their surface so as to prevent bad guys from attaching to them. Since adhesion is so basic to life, most of the ‘older’ immune mechanisms that we employ are based on this simple framework.

The basic mechanism of adhesion is a process called agglutination, one of those few works in medicine that is not either Latin or Greek, but rather German. The word itself best describes its prime function; gluing onto things.  Most of the time agglutination results in large objects, like cells, adhering to each other. However the word is just as usable when we are describing a virus or bacteria adhering onto the tissues of our body.

Simple organisms, like plants or insects, obviously lack the advanced aspects (like blood) of higher organisms, yet still have to protect themselves from microbial intruders. It is this job that Nature apparently assigned to the agglutinating molecules that we call the lectins. This explains why lectins are so often found in the immature aspects of many simple life forms, such as the seeds and shoots of many grains. Thus to a certain degree, lectins can be considered as a primitive antibody of sorts.

We as humans have very much more sophisticated mechanisms for defending ourselves. These include purely chemical defenses, and a variety of cellular systems which given their complexity are remarkably efficient and discreet at what they do. No surprisingly, blood type is often at the forefront of many of these mechanisms.

The function of blood is to carry nutrients and oxygen to all the cells of the body. It carries waste materials  (toxins) to the kidneys and other organs for elimination. It helps to regulate the water content,  temperature, and alkalinity of the body tissues. It also transports white cells and antibodies to battle infection  and disease. In addition, it mends cuts, heals bruises and transfers hormones from the organs of production to the organs of consumption.

The average individual has about 5 quarts of blood. This may be separated into approximately 3 quarts of plasma and 2 quarts of cells. The plasma is the liquid portion of the blood, and the cells are the formed elements of the blood. The plasma is made of water, nutrients, wastes, hormones, antibodies, and enzymes.

There are three basic types of cells are leukocytes (or white blood cells), red blood cells, and platelets. The white cells are the largest in size, and consist of two major subsets – the granulocytes and the lymphocytes.  The platelets are the smallest. The red cells generally fall in size between the white blood cells and platelets, with some overlap of both populations. In quantity, however, the red blood cells greatly predominate.  For every five hundred red cells, there are approximately 30 platelets and only about 1 white cell. Though most of the time, the cells of the immune system are found in the blood stream, in situations of emergency, like an infection in a distant part of the body, they can make special chemicals which allow the lining of the blood vessels to become permeable, allowing them to pass from the blood stream into the tissues of the body.

In humans, the immune system begins to develop in the embryo. The immune system starts with hematopoietic (from Greek, "blood-making") stem cells. These stem cells differentiate into the major players in the immune system (granulocytes, monocytes, and lymphocytes). These stem cells also differentiate into cells in the blood that are not involved in immune function, such as erythrocytes (red blood cells) and megakaryocytes (for blood clotting). Stem cells continue to be produced and differentiate throughout your lifetime. 


The architecture of immunity

Although it can be quite complex, a basic understanding of the immune system is almost essential nowadays. One of the best ways to understand the different functions, chemicals and cells of the immune system is to always remember that every aspect has a particular job to do, and many cells are specialized to do very particular functions. In this respect the immune system is like a modern army. Though there are many different  arms of a modern army, each has a specific job to do, and victory  almost always depends on the ability of the commanding general to blend all their divergent functions into a balanced mix called ‘combined arms.’  For example, engineers may be required to build a bridge, while tanks may be needed to cover large amounts of territory quickly. However, if the general has not done his job well, he might have his tanks at a river without any engineers nearby to build them a bridge to cross on. The immune system is not all that different. It has a variety of  tools and soldiers trained  to do different jobs. Once you understand that each part of the immune system has a job to do, and tools to do the job with, understanding the immune system becomes as simple as fitting the particular soldier with the particular weapon to the particular task.


‘Self’ and ‘Non-self’


Like the military, the immune system requires good intelligence; it must identify and attack the enemy, but of course it must strive to prevent casualties from ‘friendly fire.’  In immunity this is termed the concepts of ‘self’ and ‘non-self.’ Your blood type antigen is a powerful marker of self to your immune system. Simply put, most things in Nature that produce an antigen which is recognized as similar to our blood type are considered self and allowed access.

What is not commonly recognized however, is how much we view other blood types as ‘non-self.’ We do this to such a great degree that we are genetically programmed to produce an extraordinarily powerful antibody to opposing blood types, or rather microorganisms and foods, which have that particular blood type antigen. There are other mechanisms involved in self-non self recognition, but none other have as powerful a genetically programmed response.

The most basic distinction within the immune system divides its myriad of functions into  two basic branches: innate (or natural) immunity  and acquired (or memory based) immunity.


Innate Immunity: The first line of defense


Innate immunity is the body's first line of defense against infection.  It is non specific and has no memory, in other word repeated challenges  do not enhance the innate immune response.  Its elements include physical defenses such as the skin, mucous membranes and the cough reflex, and chemical elements such as stomach pH, digestive enzymes and secreted fatty acids.  Many of the physical defenses of the body are influenced by blood type: high stomach acid tends to prevent colonization of the stomach in blood type O, whereas low stomach acid may render blood type A  more liable to infection.

The normal flora (‘friendly bacteria’) can  prevent the colonization of the body's external and internal surfaces by pathogenic microorganisms often by simply crowding out the bad guys, competing for food and other necessary elements. When their habitats are disrupted by sickness or antibiotic therapy we can become susceptible to infection by such organisms as the yeast Candida albicans which are ‘opportunistic’ taking advantage of the imbalance  or weakened state of the host.  Much of the makeup of our normal flora is based upon blood type. Organisms which metabolize the antigen of a particular blood type will tend to have a ready food supply in a host of that blood type.


Acquired immunity: You must be carefully taught


The acquired immune system is made up of cells that will react with only a specific antigen displayed either on the surface of the invading organism or on the surface of an antigen presenting cell. Lymphocytes, B- & T-cells, are the sole members of this group. Precursors to lymphocytes, called stem cells, can differentiate into either T cells or B cells, depending on the microenvironment. T lymphocyte cells differentiate in the thymus, the B lymphocyte cells differentiate in the bone marrow. In addition to different areas of maturation, T cells and B cells have different functions.

Each lymphocyte will recognize and become activated by only one antigen. Therefore, if for example a Streptococcus bacteria enters the body, a lymphocyte that is specific for it must encounter either it or its processed antigen for an effective immune response to be initiated. Lymphocytes participating in the recognition process,  antibody production and killing process are   permanently committed to respond to the particular  antigen on every subsequent exposure, but to no other, and are therefore said to have "memory". In ‘backwater’ or secondary lymphoid organs such as lymph nodes, spleen and mucosal  tissues (such as the gut lining and  tonsils) lymphocytes communicate and interact with specialized antigen-presenting  phagocytes and macrophages as part of an interactive  immune response. When the antigenic stimulus is removed, the lymphocytes return  to a waiting state.


Cell Mediated versus Humoral immunity


Immunologists distinguish the two forms of acquired immunity into two basic types: ‘Cell Mediated’ and ‘Humoral.’


Cell-based killing

The term cell-mediated immunity (CMI) is used for any immune response in which phagocytic and/or cytotoxic cells play the major role, and antibody plays a minor role or no role at all.  CMI mediated by macrophages and neutrophils is extremely important in combatting bacteria, while CMI mediated by natural killer (NK) and Tc cells is essential to the elimination of virus-infected and cancer cells.  CMI mediated by eosinophils aids in the elimination of parasites or the control of allergy.


Let’s take a look at some of the principle soldiers:


Granulocytes: The ‘levy en masse’ of the immune system Granulocytes are the most numerous type of white blood cells in the body. They are classified by their ability to accept different types of dyes, based on the pH of the dye. Neutrophils are stained by neutral dyes, eosinophils by acid dyes, and basophils by basic dyes. Each class has very distinct functions in the bloodstream.

Neutrophils are the workhorse of your body's defense against bacterial infections. Neutrophils, which are also known as polymorphonuclear leukocytes (PMN), represent 50 to 60% of the total circulating leukocytes and constitute the ''first line of defence'' against infectious agents or ''non-self'' substances that penetrate the body's physical barriers. Normally a serious bacterial infection causes the body to produce an increased number of neutrophils. Neutrophils can move out of the blood vessels into the infected tissue to attack the bacteria. The pus in a boil (abscess) is made up mostly of neutrophils.  Neutrophils are made in the bone marrow (like all the cells of the immune system ) and circulate in the bloodstream. Neutrophils can migrate toward sites of infections and destroy invaders by engulfing them (called ‘phagocytosis) or by liberating powerful inflammatory free radical chemicals to destroy them externally.  Neutrophils can increase in response to normal stresses, like exercise, pregnancy, excessive cold or heat, or emotional states. Neutrophils can also activate and contribute to inflammatory conditions, causing auto-immune problems. However, the most common cause of neutrophil activation is bacterial infections. When the ‘White Blood Count’ is low, there may not be enough neutrophils to defend you against bacterial infections.



Secretor status of healthy young volunteers in the age group of 18-22 years and having similar socio-economic background was determined by standard agglutination inhibition test of the saliva. Phagocytic response of leucocyte was worked out by in vitro suspension technique and average number of cocci engulfed by leucocytes calculated in secretors/non-secretors of each blood group. Leucocytes of non-secretors of O and AB seem to have more and highly significant ingestion power as compared to secretors. Non secretors in group A & B also show more phagocytic activity. Relatively different concentration of the components of the blood group substances in secretors/non-secretors seems to affect phagocytic activity of the leucocytes.

Type AB neutrophils appear to be the  most sensitive to reduction in phagocytic activity. A study on the interaction of different sera and polymorphonuclear cells (PMN) with reference to the ABO blood group system on the phagocytosis of a radiolabelled strain of E. coli is reported. Using untreated sera, O cells were found to be the least sensitive and AB cells the most sensitive to reduction in phagocytic activity. No reduced phagocytic capability relative to the different sera used was observed when heat-inactivated sera were applied.

Tandon OP, Bhatia S, Tripathi RL, Sharma K.  Phagocytic response of leucocytes in secretors and non-secretors of ABH (O) blood group substances. Indian J Physiol Pharmacol 1979 Oct-Dec;23(4):321-4

Melby K. Phagocytosis of 32P-labelled Escherichia coli by human polymorphonuclear cells (PMN). Effect of different sera and PMN with reference to the ABO blood group system. Acta Pathol Microbiol Scand [B] 1979 Dec;87(6):375-7

Eosinophils. Normal adult  blood contains 0 to 4 percent eosinophils. Eosinophils can migrate  between the blood vessel cells into tissue or into an area of inflammation in the same manner as neutrophils.  The most common causes of increased levels of eosinophils are drug reactions , allergy, or parasites. Many people with allergies, such as asthma and hay fever  have elevated eosinophils Both eosinophils and neutrophils  attach or ‘tether’ to microbial invaders by the use of lectin –like molecules called ‘selectins’. These selectin molecules, like their lectin cousins in nature, attach to glycoproteins on the surface of bacteria, allowing the neutrophils and eosinophils the opportunity to kill them with their free-radical chemicals.


Many foreign substances which are capable of stimulating allergic activity  by activating eosinophils  also appear to simultaneously stimulate the production of anti-blood type antibodies.

  Shekatkar AB, Chaphekar PM Changes in isoagglutinin titres following non-specific immunological stimuli. J Postgrad Med 1975 Jan;21(1):30-5


Basophils. This cell makes up about  0 to  2 percent of normal blood cells, and are characterized by abundant packets or ‘granules’ inside their bodies. Basophils are found in low numbers in the blood. Their functions are not well understood but they are known to be involved in  allergic  hypersensitivity responses. These cells have high affinity an antibody called  IgE. Attaching to  IgE causes the basophils to release heparin and histamine.  Basophils are often increased in ulcerative colitis, certain leukemias and certain forms of anemia. Unlike neutrophils and eosinophils, which have a lifespan measured in hours, basophils can apparently live for years.



Monocytes and Macrophages: The scavengers


Monocytes and macrophages are sort of the ‘Department of Sanitation’ for the immune system. They are related to each other  are intimately related to each other as they assume one type of shape (the monocyte) in the blood and another (the macrophage) in the tissues. 


Monocytes: Monocytes account for 2 to 9 percent of normal blood leukocytes. Monocytes leave the marrow when mature and enter the bloodstream, where they circulate for about 14 hours before entering tissue to transform into macrophages. Monocytes are processors of antigen for T-Lymphocytes, and, like the neutrophil, can phagocytose (or engulf)  bacteria.    They synthesize, secrete and degrade complement components, and produce  interleukin-1 (IL-1). Macrophage and monocyte cell  membranes have receptors for various antibodies complement. Particles coated with globulins are ingested in cytoplasmic vacuoles and destroyed by cytoplasmic hydrolytic enzymes.



One not uncommon occurrence in pregnancy is ABO haemolytic disease, caused by sensitization of the mother’s immune system to the blood type antigens of the fetus she is carrying. In most cases the mother’s antibodies against blood group antigens A or B  of the fetus are able to sensitize its red blood cells for destruction by monocytes.  

Brouwers HA, Overbeeke MA, Ouwehand WH, Keuning K, van Ertbruggen I, van Leeuwen EF, Stoop JW, Engelfriet CP Maternal antibodies against fetal blood group antigens A or B: lytic activity of IgG subclasses in monocyte-driven cytotoxicity and correlation with ABO haemolytic disease of the newborn. Br J Haematol 1988 Dec;70(4):465-9


Macrophages: Macrophages are an example of antigen presenting cells that take in the invading organism (bacteria, virus, fungi, etc.), break it down, and present it to T-lymphocyte cells. If the T-cell is specific for the antigens found in the bacterium (there are many potential antigens in each organism), it becomes activated and begins secreting cytokines that activate other cells. Macrophages secrete many immunomodulatory substances, such as cytokines, some of which can increase the activity of the immune system to the extent of causing excess activity,  resulting in auto-immune diseases.  One of the most important molecules used by macrophages to kill microorganisms is nitric oxide. When macrophages encounter bacteria and interferon, the gene responsible for the production of nitric oxide   is made in large numbers. When a macrophage  encounters a site of infection or inflammation the gene encoding Inducible Nitric Oxide Synthase is activated and the amino acid arginine is converted to citrulline,  releasing free nitric oxide.



Evidence exists which appears to indicate that those who carry a B antigen (blood types AB and B) may have some difficulty in controlling the activity of nitric oxide. This may help explain why blood  type B has been associated with chronic, lingering viral infections

The blood group A and H antigens  have been shown to block the interaction macrophages and a serum factors which inhibits their migration. It is suggested that the BGS mimic the natural macrophage receptor

this inhibitory factor and by doing so enhance the activity of macrophages which incorporate the blood type antigens onto their surface.

McFadzean J, et al.  Nitric oxide ABO blood group difference in children Lancet. 1999 Apr 24;353(9162):1414-5

Fox RA, MacSween JM, McGuire RL. Potentiation of the macrophage response to migration inhibition factor from fetal calf serum by blood group substances with human H activity. Scand J Immunol 1976;5(8):941-7



NK cells: The ‘Pac-Men’ of the immune system


NK cells are a subset of T lymphocytes which function as a first line of defense against cancer cells and viral infection. Their primary function is called ‘cytotoxicity,’ which basically can be thought of as the ability to cause spontaneous cell destruction of either a cancer or viral-infected cell. This cytotoxicity or overall activity level of NK cells (usually expressed as Lytic Units or LU) is far more important than the total quantity or overall number of cells.

However, NK cells do not kill indiscriminately. NK cells have several very specialized lectin-like receptors that recognize major histocompatibility complex (MHC) class I molecules expressed on normal cells. The lack of expression of one or more HLA class I alleles leads to NK-mediated target cell lysis.

As a rule of thumb, poor lifestyle habits decrease NK cell activity, while good lifestyle habits are associated with increased activity. In a Japanese study, researchers investigated the association between lifestyle habits in healthy males and NK cell activity. The researchers divided individuals into groups based upon whether they maintained good, moderate, or poor lifestyles according to their responses on a questionnaire regarding eight health practices (tobacco smoking, alcohol consumption, hours of sleep, physical exercise, eating breakfast, balanced nutrition, hours of work habits, and mental stress). Demonstrating the cumulative power of lifestyle habits, individuals with the most good lifestyle habits were found to have the highest NK cell activity with their NK levels being significantly higher than the NK cell activity in those reporting poorer lifestyle choices.


Lifestyle habits associated with increased NK activity

Increased intake of meat (type O)      

Increased intake of green vegetables

Increased intake of soybean products (type A)

Regular meals

Regular Sleep (greater than 7 hours per night)

Proper body weight


Modest use of alcohol (males)

Moderate work hours

Increased intake of milk, dairy products (Type B)


Nakachi K, Imai K. Environmental and physiological influences on human natural killer cell activity in relation to good health practices. Jpn J Cancer Res 1992;83:798-805.

Kusaka Y, Kondou H, Morimoto K. Healthy lifestyles are associated with higher natural killer cell activity. Prev Med 1992 Sep;21(5):602-15

Kusaka Y, Kondou H, Morimoto K. Healthy lifestyles are associated with higher natural killer cell activity. Prev Med 1992 Sep;21(5):602-15

Kusaka Y, Morimoto K. Does lifestyle modulate natural killer cell activities? Nippon Eiseigaku Zasshi 1992 Feb;46(6):1035-42 [Article in Japanese]




In another Japanese study, researchers similarly found a strong correlation between NK cell activity and healthy lifestyle. Food choices such as selecting for more green vegetables, increased quantity of meat, dairy, or soy products and the regular consumption of meals were critical. Lifestyle choices of non-smoking, modest alcohol use, and regular sleep showed strong associations with good NK activity. These researchers also found that in women, a daily workload of less than 3 hours per day favored good NK cell activity.

Nakachi K, Imai K. Environmental and physiological influences on human natural killer cell activity in relation to good health practices. Jpn J Cancer Res 1992 Aug;83(8):798-805


Evidence also suggests differences exist between NK activity in males and females with males having on average slightly higher NK cell activity.  This male/female difference is present at birth and persists through adulthood.  Within scientific circles, the age-dependence of NK cell activity has been a matter of debate and controversy. Some evidence suggests it improves as we age while other evidences suggests NK activity declines with aging and these immune cells lose some of their ability to destroy cancer cells and viral-infected cells

Albright JW, Albright JF. Age-associated decline in natural killer (NK) activity reflects primarily a defect in function of NK cells. Mech Ageing Dev 1985 Sep;31(3):295-306


Although this controversy is unlikely to go away, proper lifestyle habits along with the correct type of physical exercise for your type are your best investments in keeping your NK cell levels up.



A relative contribution of genetics might influence NK cell activity. Studies have consistently shown that the level of NK cell activity in humans can vary widely between individuals. Clearly many factors are involved in this variation; however, several researchers have proposed that genetic factors contribute to this variability.

Lowered NK cell activity has been shown to have a familial association in melanoma and chronic fatigue syndrome, suggesting a possible genetic contribution. A significant relationship with Lewis antigen expression and resistance to NK cell cytotoxicity is found on target cells (meaning that the Lewis antigens being present on a cell, make it a less likely target for NK cell lysis.

Cell surface A and H antigens also increase resistance to lysis, while precursor structures (T and Tn antigens) increase the sensitivity of tumor cells to be destroyed by NK cells. So, blood type antigen expression on target cells certainly influences the ability of a NK cell to bind and destroy cells. Although information is not unequivocal, higher NK activity has been associated with AB blood group when compared either against blood Type A, or Type A, B, and O taken together as a group. In general, the lowest NK cell activity has been associated with A blood group. Why would type AB have higher levels of NK activity than the other blood types? My suspicion is that it is a sort of compensation for type AB lacking any antibodies against ‘other blood types’ which renders them more susceptible infections by organisms with either A or B antigenicity.


Rh blood type might also influence NK cell activity. While some studies have not found an association, other researchers have observed a higher natural NK cytotoxicity against target cells in individuals with Rh- blood type. 

Blottiere HM, Burg C, Zennadi R, et al. Involvement of histo-blood-group antigens in the susceptibility of colon carcinoma cells to natural killer-mediated cytotoxicity. Int J Cancer 1992;52:609-18.

Blottiere HM, Burg C, Zennadi R, et al. Involvement of histo-blood-group antigens in the susceptibility of colon carcinoma cells to natural killer-mediated cytotoxicity. Int J Cancer 1992;52:609-18.

Lasek W, Jakobisiak M, Plodziszewska M, Gorecki D. The influence of ABO blood groups, Rh antigens and cigarette smoking on the level of NK activity in normal population. Arch Immunol Ther Exp (Warsz) 1989;37(3-4):287-94

Pross HF, Baines MG. Studies of human natural killer cells. I. In vivo parameters affecting normal cytotoxic function. Int J Cancer 1982 Apr 15;29(4):383-90

Pross HF, Baines MG. Studies of human natural killer cells. I. In vivo parameters affecting normal cytotoxic function. Int J Cancer 1982 Apr 15;29(4):383-90

Lasek W, Jakobisiak M, Plodziszewska M, Gorecki D. The influence of ABO blood groups, Rh antigens and cigarette smoking on the level of NK activity in normal population. Arch Immunol Ther Exp (Warsz) 1989;37(3-4):287-94

Hersey P, Edwards A, Trilivas C, et al. Relationship of natural killer-cell activity to rhesus antigens in man. Br J Cancer 1979 Mar;39(3):234-40




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