In the immunology community, we often toss out words that may cause confusion or appear contradictory. So, I felt that a definitional reference guide applicable to humans, dogs, cats and horses (actually, all species) may be useful.
Immunity covers a spectrum from underactive to overactive. Immune competent or immunocompetent is the term referring to the state of having normal immune competence.
Immune competence is provided and maintained by two cellular systems which involve lymphocytes, produced by the body’s primary (bone marrow and thymus) and secondary (lymph nodes and spleen) lymphatic organs. They are descendants of the bone marrow’s pool of “mother” stem cells, and constitute a circulating or humoral immune system derived from B-cells (bursa-dependent or bone marrow derived), and a cellular or cell mediated immune system that derives from T-cells (thymus-dependent).
B-cell immunity includes the circulating antibodies or immunoglobulins such as IgG, IgM, IgA, IgD, and IgE. These antibodies provide an important defense mechanism against disease in healthy individuals but can become hyperactive or hypoactive in a variety of disease states. Vaccination against the so-called “core” viral diseases of dogs (canine distemper, parvovirus and hepatitis) and cats (feline panleukopenia) elicits protection by stimulating circulating B-cell humoral immunity. Serum antibody levels to these viruses, whether due to vaccination and/or prior natural exposure infection is directly proportional to their degree of protection. This is why measuring serum antibody titers against these viruses is important as a means of predicting and documenting protection.
T-cell or cell-mediated immunity is the cellular mechanism whereby T-cells act as coordinators and effectors of the immune system and its response. Cell-mediated immunity involves the lymph nodes, thymus, spleen, intestine (gut-associated lymphoid tissue), tonsils, and a mucosal secretory immunity conveyed by IgA. The major classes of T-cells are designated as helper, cytotoxic, and suppressor cells. The helper cells “help” coordinate the immune response whereas the cytotoxic cells comprise the effector network that participates in removing virus-infected cells from the body. The third class of suppressor T-cells is important in dampening the immune response when it becomes overactive or out of regulatory control. Finally, cooperation between the various T-cell classes and between T- and B-cells is an important component of the normal humoral and cellular immune response.
Immunocompromised is an all-encompassing phrase meaning an impaired immune system or immune response. The term immunocompromised is often used interchangeably with immunodeficiency, but they are not really the same. Immunodeficiency is an underperforming immune system.
An immunocompromised individual could have a dysfunctional, abnormal, or non-functioning immune system. So, someone who has an immune deficiency is immunocompromised, but a person who is immunocompromised may not have an immunodeficiency.
“Immune disorders” is the umbrella phrase that includes all conditions and diseases that affect or stem from the immune system.
Immunodeficiency is defined as an abnormality of the immune system that prevents adequate immune responsiveness. We categorize immune deficiencies into temporary acquired, primary, and acquired.
- Temporary acquired would be due to suppression of the immune system due to common viral infections such as influenza or colds in people and upper respiratory infections in pets, use of immunosuppressive drugs, cancers or chemotherapy.
- Primary immunodeficiency is congenital and more than likely inherited. Humans and animals with primary immunodeficiency states are more prone to infections. However, primary immunodeficiency is rare. As well, it does not have to be expressed clinically at birth but could develop later in life. Examples would be the immune deficiencies of grey collies, and certain basset hound and Arabian horse families.
- Acquired is also known as a secondary immunodeficiency and occurs because of a virus or another infectious agent, cancers, toxic exposures, and certain drugs. The best known acquired immunodeficiency is AIDS in people and the parallel disease in cats. Feline leukemia is another common example.
Immune deficiency states are also classified as:
Immune Defects in Mechanical Barriers
Primary ciliary dyskinesia (Immotile Cilia Syndrome, Kartagener’s Syndrome) has autosomal recessive inheritance in humans, dogs, and mice and is characterized clinically by chronic respiratory tract disease, male sterility, and middle ear infections. Heritable in Doberman pinscher, English springer spaniel, and bichon frise, although cases have been documented in several other breeds.
Defects in Non-Specific Host Defenses
- Cyclic hematopoiesis. This congenital disorder of grey Collies was originally called “cyclic neutropenia” but it is now known that all bone marrow elements are affected. A similar condition occurs in humans.
- Chediak-Higashi Syndrome is an inherited autosomal recessive condition of humans, Blue Persian cats, and Hereford cattle. Affected individuals have giant, red-colored lysosomal granules within numerous tissues including white blood cells. Affected cats have an increased susceptibility to bacterial infections, congenital cataracts, photophobia (aversion to light), and retinal changes, and there is an associated platelet dysfunction and bleeding tendency.
- Canine Granulocytopathy Syndrome is inherited as a rare autosomal recessive trait in Irish Setters with abnormal leukocyte function. Neutrophil counts can be very high and recurring pyoderma and osteomyelitis are common; lifespan is short.
- Pelger-Huet Anomaly is a benign condition of humans and animals not associated with a known clinical problem. It is transmitted as an autosomal dominant trait.
- Third Component of Complement Deficiency is inherited as an autosomal recessive trait in humans, Brittany Spaniels, and an inbred strain of guinea pigs. Affected dogs suffer from increased bacterial infections and septicemias.
Defects in Specific Host Defenses
- Combined Immunodeficiency occurs in humans and Arabian horses. The horse defect has a frequency of greater than 2% and is inherited as an autosomal recessive trait. It also occurs in long-haired dachshunds in Australia, and is a sex-linked trait in basset hounds that also are often co-infected with Mycobacterium (tuberculosis).
- Selective IgA deficiency occurs quite often in people, in beagles, and is commonly seen in the Chinese Shar Pei and German shepherd breeds.
- Growth Hormone and Immune Deficiency condition occurs in Weimaraners. Affected dogs are irnmunodeficient dwarfs that exhibit a wasting disease, unthriftiness, recurrent infections, and retarded growth.
- Lethal Acrodermatitis is an autosomal recessive condition of English bull terriers, and results from impaired absorption and metabolism of zinc. Affected pups are lighter in color at birth and develop diarrhea and recurrent respiratory tract and skin infections. They rarely live to adulthood.
On the flip side, we can have overactive immune responses. One would assume this is a good thing – the immune system is supercharged! But, no; that is not the case.
Tolerance is the prevention or modulation of an immune response against a particular antigen. For instance, the immune system is generally tolerant of self-antigens, so it does not usually attack the body’s own cells, tissues and organs. When tolerance is lost, disorders like immune-mediated (autoimmune) diseases, sensitivities (intolerances), or hypersensitivities (allergies) may occur. In fact, the term autoimmune disease is caused by the “failure of self-tolerance”.
- Immune-Mediated Diseases: A disease that results when the body’s immune system reacts against its own tissue. Usually, there is a genetic factor and something environmental triggers the gene such as vaccines, food, chemicals, drugs, etc. Over 80 immune-mediated diseases have been identified in humans. The immunology community is starting to replace autoimmune with immune-mediated.
- Sensitivities: Food intolerances are a classical example of this category, and are becoming more prevalent worldwide, perhaps because of the combined adverse effects of pollution, overuse of herbicides and pesticides that contaminate food and water supplies for ourselves, livestock and companion animals, and depletion of the ozone layer in the air. Sensitivities involve a spectrum of immune conditions and are measured by the antibody responses IgA and IgM, and can also include the complement system.
- Hypersensitivities: Allergies are hypersensitive reactions, typically in response to environmental inhalant or contact allergens like pollen, trees, grasses, weeds, fleas, dust, fungi, yeast, and molds. They are typically caused by the antibodies, IgD, IgE or IgG. However, we are starting to replace the term “allergies” with sensitivities (as described above for food).
Now begins the confusion. One would assume that a person with a Primary Immunodeficiency Disease (PIDD) would not have an immune-mediated disease or sensitivities to the environment or food. This is true most of the time from the data we have for sensitivities, but we know also that the data is conflicting. PIDD with concurrent immune-mediated diseases is actually common. Look at it from this perspective: The World Health Organization recognizes over 250 human PIDD’s that are caused by one or several lacking or dysfunctional cells, antibodies or proteins.
So, one antibody or cell may overcompensate for another, a miscommunication could be occurring, or one is not keeping the other one in check. Basically, this ends up sending the immune system into overdrive – i.e. autoimmunity – despite the presence of the original condition.
But, we should not forget the possibility that one with PIDD might never develop autoimmunity and vice versa, that one with an autoimmunity might never have a primary immunodeficiency.
Let’s look at IgA Deficiency, which is a protein antibody deficiency, is relatively common in humans and animals, and affects at least one out of every 500 Caucasian people (data from other ethnic groups was unavailable at the time of this writing). IgA is an antibody found in abundance in and on the mucosal surfaces such as the mouth, rest of the bowel, and nose, and in tears, sweat, and urogenital secretions. It serves as an important surface barrier to the protect against infectious agents, foreign proteins, toxins, chemicals and parasites. When it is deficient, the body cannot adequately prevent infection of these mucosal surfaces, and body secretions are functionally impaired.
IgA deficiency is a spectrum of varying degree like all immune disorders. Many of us may have some degree of IgA deficiency that goes undetected for life. We get mildly ill or otherwise, but nothing too major. Common infections include recurrent ear infections, sinusitis, bronchitis and pneumonia. Some patients also have gastrointestinal infections and chronic diarrhea, which makes sense since the mucosal barrier is depleted allows bacteria and other microbes to replicate in the gastrointestinal tract.
Interestingly, 25-33% of those people with an IgA Deficiency were diagnosed with an immune-mediated disorder like rheumatoid arthritis. 10-15% were diagnosed with a hypersensitivity (allergy), which is disproportionately greater than seen in the general population.
If you are wondering about dogs…As many as 80% of all Chinese Shar Pei have IgA deficiency. A survey of 278 dogs of 32 common breeds with suspected immunodeficiency found 56% of them to have selective IgA deficiency. These dogs also had recurrent staphylococcal dermatitis, demodectic mange, thyroid disease, external ear infections, flea allergy, cystitis, food intolerance, bronchitis and atopy (inhalant allergy).
Vaccines and Immunity
Indeed, time and again, we know that giving humans and animals – who already have an immune deficiency, autoimmune disease or immune dysfunction – a vaccine may, in fact, cause the disease it is trying to prevent.
The debate remains controversial. Can vaccines trigger immune-mediated diseases in the general population or in patients with PIDD? While young babies, puppies, ponies or kittens exposed frequently to polyvalent vaccine antigens may not demonstrate overt adverse effects, their relatively immature immune systems may be temporarily or more permanently harmed from such antigenic exposures.
Consequences in later life may be the increased susceptibility to chronic debilitating diseases. Some veterinarians trace the increasing current problems with allergic and immunological diseases to the introduction of MLV vaccines some 20 years ago. While other environmental factors no doubt have a contributing role, the introduction of these vaccine antigens and their environmental shedding may provide the final insult that exceeds the immunological tolerance threshold of some individuals.
From my 50-year perspective as a veterinary immunologist and hematologist which included my being the Executive Secretary of the New York State Council on Human Blood and Transfusion Services, vaccines can trigger these diseases. The caveat is that affected individuals must first have the genetic predisposition to have vaccine-associated disorders.
Overall, we have to remember:
- Immunity is a functional spectrum.
- Humans and animals that appear outwardly healthy could still be relatively immunocompromised.
- We know that certain vaccines are considered unsafe for humans and animals that have an immunodeficiency or immune dysfunction so we avoid giving vaccines to this population.
- Vaccines alter and can suppress the immune system and should not be given to any individual currently taking immunosuppressive medications or undergoing cancer treatment.
- Any vaccine can produce a mild or severe side effect, which means the body is overreacting.
- We often do not know the exact causes or triggers of immune-mediated diseases, and there could be one or multifactorial.
- It has been postulated that certain vaccines could prevent or modify rather than cause or exacerbate immune-mediated diseases.
Accordingly, clinicians need to be aware of this potential and offer alternative approaches for preventing infectious diseases in susceptible animals. Appropriate alternatives to current vaccine practices include: measuring serum antibody titers; avoidance of unnecessary vaccines or over-vaccinating; caution in vaccinating ill, geriatric, debilitated, or febrile individuals, and tailoring a specific minimal protocol for dogs or families of breeds known to be at increased risk for immunological reactions. The accumulated evidence indicates that vaccination protocols should no longer be considered as a “one size fits all” program.
As I stated, this is multifactorial. In my opinion, why vaccinate an animal or human that has sufficient immunity to a disease, if the risk of infection is low and the symptoms are not life-threatening, particularly if we know that adverse effects can happen.
Inherently, we want to boost the immune system of an individual with an immunodeficiency. However, during an immune-mediated or sensitivity flare up, we want to “suppress” or down-regulate that portion of the immune system. This is an important point to make: people often assume that immune support or boosters will correct an immune-mediated disease. However, this may actually exacerbate the problem. It is quite a balancing act for all conventional and holistic medical professionals, because we want to boost one side of the immune system but down-regulate the other side.
The good news though is that standard conventional treatments such as corticosteroids and other immune suppressant drugs used for immunologic disorders can often be replaced or augmented with holistic alternatives and homeopathic remedies.
Immune Disorder: An umbrella phrase for dysfunction of the immune system which can be either overactive or underactive.
Immune-Mediated (Autoimmune) disease: A disease that results when the body’s immune system reacts against the individual’s own tissue(s).
Immunocompromised: A state in which an individual’s immune system is absent, weakened or dysfunctional.
Immunodeficiency: A state of either a congenital (present at birth) or an acquired (secondary) abnormality of the immune system that prevents adequate immune responsiveness.
Immunomodulator: A chemical agent, drug, or other substance that modifies the immune response or the functioning of the immune system.
Immunosuppression: Suppression of natural immune responses.
Vaccine: A substance that contains components from an infectious organism or other antigen (protein) which stimulates an immune response in order to protect against subsequent exposure to that organism or antigen.
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