3.1 Introduction to Immunity

We are exposed to many potentially dangerous pathogens every day, and the defenses coordinated by our immune responses keep us from being harmed by these substances most of the time. Bacteria, virus, fungi, cancer, and even our own normal cells can stimulate an immune response. For a review of the types of immune responses and the types of cells involved, please watch the following video.

3.1 – Resource 01 – “Introduction to the immune system”Osmosis is licensed under Fair Use

3.2 Types of Immunity

3.2.1 Innate (Non-specific) Immunity

Innate immunity is a very generally first-line defense against any kind of cell or substance that the body recognizes as potentially harmful or not belonging to the body. Skin, mucosa, and secretions such as sweat, tears, and stomach acid are included in this category. These barriers and fluids are nonspecific, that is, they react in the same way to any potential pathogen, such as bacteria, virus, or fungal cells. Innate immunity does not include the production or storage of memory cells, so every time a foreign substance tries to enter the body, the innate immune response is the same. Neutrophils, monocytes, macrophages, inflammatory mediators (basophils, mast cells, eosinophils) and natural killer cells are active in the innate immune response. Phagocytosis is the major form of destruction of non-self or foreign cells in the innate response.

3.2.2 Passive Immunity(Specific; no memory cells formed):

Passive immunity occurs in one of two ways. (1)Antibodies are passed from mother to fetus through the placenta and in breast milk in natural passive acquired immunity. Antibodies or sensitized lymphocytes can be injected in the form of an inoculation, as in the case of treatment for rabies or antivenom for snake bite, in the process of artificial passive acquired immunity. In both kinds of passive immunity, no memory cells are formed, so there will be no lasting immunity for the individual. Immunity only lasts until the specific antibodies are processed and/or eliminated by the body.

3.2.3 Acquired or Adaptive (Specific) Immunity

In acquired, or adaptive, immunity, B-cells and T-cells are activated and go through a process by which B-cells become memory cells. This is useful, because these memory cells “remember” antigens they have seen before and mount a defense more quickly with subsequent exposure. Other B-cells (plasma cells) create antibodies, which reside on the surfaces of memory cells. T-cells either assist in the creation of antibodies and memory cells (helper T-cells) or directly kill cells that are recognized as non-self or unwanted, such as cells infected by a virus or cancer cells.

3.2.3.1 Active Acquired Immunity

is a term used to describe the gaining immunity through one of two ways: (1) experiencing the disease or condition, which is called natural immunity, or (2)vaccination, which is called artificial acquired immunity. Vaccinations usually involve dead or attenuated (weakened) forms of the pathogens, so that the vaccinated individual does not actually experience symptoms of the disease but does mount an immune reaction to the antigen. Both natural and artificial acquired immunity create memory cells to protect for a long period of time, in many cases, a lifetime.

3.2.3.2 Acquired or Adapted Immunity:  Humoral and Cell-Mediated Responses

There are two distinct and connected responses that occur in acquired,  or specific, immunity. In the humoral response, B lymphocytes, or B-cells, are the main players. They become activated when they engulf an antigen for which they have a matching antigen-receptor. The antigen is broken apart inside the B-cell, and fragments of this antigen are displayed on the outer surface of the B-cell. This attracts a helper T-cell (TH) to attach to the activated B-cell, and this interaction causes the T-cell to release cytokines. The cytokines help the B-cell to mature into plasma cells, which produce antibodies, or memory cells, which recognize future antigen invasions of the same type, and quickly initiate the immune response to destroy them.

In the cell-mediated response, T-cells are a major component in destroying cells that are infected with a virus or intracellular bacterium, cancer cells and transplanted cells. T-cells must come into direct contact with infected cells (target cells) to become activated. The three types of T-cells that are involved in the cell-mediated response include helper T-cells (CD4 cells), cytotoxic T-cells (CD8 cells) and suppressor T cells. Helper T-cells enhance the activity of other T-cells, B-cells, and macrophages through the production and secretion of cytokines. Cytotoxic T-cells kill target cells, such as cancer cells, infected cells and transplanted cells. Suppressor T-cells suppress the activity of other T-cells and B-cells. They effectively “turn off” the immune response when it is no longer needed.

 

3.2 – Resource 01 – “Types of immune responses: Innate and adaptive, humoral vs. cell-mediated | NCLEX-RN | Khan Academy” by Khan Academy is licensed under Fair Use

 

3.2 – Resource 02 – “Review of B cells, CD4+ T cells and CD8+ T cells | NCLEX-RN | Khan Academy” by Khan Academy is licensed under Fair Use

3.3 Factors Affecting Immunity

Immunity is affected by many factors. We are all born with certain immune predispositions, which are controlled by our genetics. Some environmental trigger could be required to activate a particular immune response, positive or negative. For example, exposure to the leaves of the poison ivy plant causes a severe immune response in some individuals, but no response in others. Likewise, some people appear to have a genetic predisposition for autoimmune conditions, such as Type 1 diabetes mellitus, where the immune system attacks the body’s own insulin-producing beta cells in the pancreas. It is unclear what might cause the body to set up detrimental immune responses to its own cells, but it is believed an environmental trigger, such as a virus, might be involved.

Age, also, plays a role in immunity. The very young and very old generally elicit less robust immune responses than do people in other age groups. Individuals who have several co-morbidities are more likely to produce inadequate immune responses to pathogens. For this reason, it is important that all PTAs are careful not to expose any patients to possible pathogens or allergens. Careful attention to hygiene, personal protective equipment and aseptic technique is essential in the health care setting.

Other aspects of personal health and well-being that appear to affect immune response include lifestyle choices, such as diet, exercise, sleep patterns, stress response, obesity, and alcohol and drug use. Availability of adequate preventative, secondary, and tertiary is also important in maintaining appropriate immune responses in the individual and general community health.

One more important factor affecting immunity is medication. Some drugs are designed to suppress the immune response for good reason, but they are also detrimental to normal immune responses during exposure to common pathogens, such as bacteria and viruses present in the community. Patients who have received organ transplantations are prescribed medications that decrease the immune response to foreign cells to reduce the likelihood of rejection. Patients who are on chemotherapy or radiation for cancer treatments are often very immunosuppressed, as the treatments targeted for cancer cells can also destroy normal cells that are active in the immune response. Any patient taking steroidal medications is also at risk for immunosuppression, as steroid drugs interact with the cells that are involved in inflammation and immunity. Many patients take steroid medications for extended periods for inflammatory conditions such as arthritis, asthma, and sepsis, or to help decrease the effects of autoimmune conditions. Patients who have transplanted organs are often taking steroids, as well. Prednisone, hydrocortisone, prednisolone, and methylprednisolone are glucocorticoid drugs that are in this category.

Because there are many factors affecting the immune response, it is important that all PTAs are careful not to expose themselves or any patients to possible pathogens or allergens. Careful attention to hygiene, personal protective equipment and aseptic technique is essential in the health care setting.

3.4 Exercise and Immunity

It has been demonstrated that moderate exercise helps boost immune response, but a temporary decrease in immune function is noted in the case of extreme exercise. After the body recovers from bouts of unusually long or difficult exercise sessions, the immune response appears to return to its normal level of function.

3.5 Autoimmune disease

Sometimes the immune response acts on cells that are the body’s own functioning cells. For some reason, the immune cells seem to not recognize some cells as “self.” An immune response is triggered, which is detrimental to body function. Why this happens, in most cases, is unknown. It is believed that most autoimmune conditions are caused by a genetic predisposition plus an inciting environmental factor. A brief explanation of a few examples of autoimmune conditions are listed below. These disorders will be discussed in greater detail in other chapters.

3.5.1 Type 1 Diabetes Mellitus:

Beta cells in the Islets of Langerhans of the pancreas, where insulin is normally produced are destroyed. Without insulin, glucose in the blood is unable to get into the body’s cells and blood glucose levels go unchecked. Because of the lack of energy being supplied to the cells, symptoms of Type 1 Diabetes include fatigue and lethargy, and sometimes, confusion. The excess glucose attracts water molecules in the body, and the kidneys are overwhelmed with the excess glucose and fluid; this causes other symptoms, including polyuria, glucosuria, and increased thirst.

3.5.2 Rheumatoid Arthritis:

Rheumatoid arthritis is a systemic disease affecting the joint capsule and cartilage in synovial joints. The effect is inflammation, which causes the joints to become warm, swollen, stiff and painful. Over time, joint destruction occurs as the capsule, ligaments, and articular cartilage are destroyed. Other organs can also be involved in rheumatoid arthritis. These include the skin, lungs, heart, and blood vessels.

3.5.3 Systemic Lupus Erythematosus (SLE):

SLE causes the immune system to attack connective tissue throughout the body. Symptoms include joint pain and stiffness, skin rashes, fever, malaise and fatigue. As the disease progresses, the heart, blood vessels, lungs, and kidneys can be adversely affected by the disease.

Refer to Physiopedia for more information on lupus. Pay particular attention to the section on physical therapy.

 

3.5.4 Graves’ disease:

Graves’ disease is the most common cause of hyperthyroidism. In Graves’ disease, body produces antibodies for the receptors for thyroid stimulating hormone in the thyroid gland. This leads to many symptoms, including increased heart rate and blood pressure, weight loss, insomnia, tremor, diarrhea, thyroid eye disease, and goiter.

3.5.5 Myasthenia gravis:

The acetylcholine receptors in the neuromuscular junction are destroyed in the condition known as myasthenia gravis or MG. This causes muscle weakness, often most noticeable in muscles of the eyes, face, and the muscles of swallowing.

3.5.6 Multiple Sclerosis (MS):

In MS, the myelin sheaths covering the motor and sensory nerves in the brain and spinal cord are destroyed in an autoimmune process, causing motor weakness and sensory loss. Visual deficits and disruptions in the autonomic nervous system are also common.

3.6 Types of Immune Hypersensitivity Reactions

3.6.1 Type I:

Hay fever, asthma, allergies to food or medication, and anaphylactic reaction are examples of Type I immune hypersensitivity reactions. The initial exposure to the allergen (antigen) results in B cells producing IgE antibodies to the antigen, which, when activated, bind to mast cells and basophils. This causes the cell degradation and symptoms associated with these types of allergies: vasodilation, smooth muscle contraction, mucous production and tear production. Type 1 reactions occur quickly, usually within minutes of exposure, and can be mildly irritating and localized (e.g., hay fever or hives) to systemic and life-threatening (anaphylactic shock).

3.6.2 Type II:

In Type II (cytotoxic) reactions, antibodies are created which bind to antigens on the surfaces of the body’s own cells and cause inflammation and ultimately, cell death. This type of reaction is responsible for the symptoms found in myasthenia gravis, Graves’ disease, and mis-match of blood type in blood transfusions. Type II reactions develop over hours or days.

3.6.3 Type III:

The accumulation of immune complexes, or antigen-antibody complexes, is the hallmark of type III reactions. In these reactions, many small antigen-antibody complexes build up over time, and the phagocytic cells are unable to clear them. These complexes become embedded in blood vessel walls, joints, and in other organs, causing inflammation. This process can occur over days, weeks or months. SLE, RA, serum sickness, and post streptococcal glomeruli-nephritis are examples of type III reactions.

3.6.4 Type IV:

Type IV reactions occur in conditions such as skin reactions to poison ivy, Type 1 diabetes mellitus, MS, and irritable bowel syndrome. These are delayed reactions that generally take more than a day, and often much longer, to develop. The reactions are cell-mediated and do not involve the production of antibodies. Activated T-cells destroy the target cells.

 

3.6 – Resource 01 – “Hypersensitivity ( I, II, III, IV): An Introduction (FL-Immuno/82)” by Frank Lectures is licensed under Fair Use

3.7 Immunodeficiency

3.7.1 Primary (Congenital):

There are several congenital disorders that can cause immunodeficiency. Some affect T-cells, some B-cells, some the complement system, and some the affect the production of all immune cells in the bone marrow. These conditions are rare, and most become apparent early in life, either through prenatal or post-natal screenings, or frequent infections in a young child.  Bone marrow transplant and gene therapy, prenatally or postnatally, are the most effective long-term treatments for these disorders.

3.7.2 Secondary (Acquired):

Secondary immunodeficiencies are much more common than primary immunodeficiencies.  These can occur for many reasons: viral infection, such as HIV-AIDS, environmental factors, such as malnutrition or exposure to toxins, and immunosuppressive therapy, as is necessary in organ transplants and in some forms of cancer. Even age is a factor, as the very young have underdeveloped immune responses, and the very old often have poorly functioning immune responses.

3.7.3 Human Immunodeficiency Virus (HIV)

is the most common infectious immunodeficiency. It is transmitted through unprotected sexual activity, intravenous drug use, mother-to-child via placenta and breast milk, and contact with blood or body fluids. The progression of HIV infection to Acquired Immunodeficiency Syndrome (AIDS) follows three distinct stages: Acute HIV infection, Clinical Latency/ Asymptomatic, and AIDS.

Stage 1: Acute HIV infection: The symptoms of this stage occur 2-4 weeks following the initial infection, and can include fever, rash, myalgia, arthralgia, and headaches. This is a stage where transmission is most likely, as many people mistake their symptoms for the flu, not realizing that HIV is rapidly reproducing within their bodies and their T-cell (specifically CD4 cell) count is dropping. They are highly contagious.

Stage 2: Clinical Latency/Asymptomatic: In this stage, outward symptoms can be minimal or non-observable. Most patients are on retroviral therapy in this stage. People who are taking antiretroviral drugs during this stage live for several decades without much change in the quality of life. Even without antiretroviral therapy, people stay in this stable stage for approximately 10 years.

Stage 3: AIDS: The clinical determination of entry to Stage 3 is the CD4 count dropping below 200 cells/mm3 and the presence of opportunistic infections or other defining symptoms. Without treatment, life expectancy is around 3 years. With treatment, life expectancy is variable, but once opportunistic infections become evident, life expectancy diminishes.

Most people who have AIDS succumb to opportunistic infections. Other causes of death include cancer, cardiopulmonary disorders, and neurological conditions.

 

The Immune Response Resources

General Resources:

Goodman, Catherine and Fuller, Kenda. Pathology: Implications for the Physical Therapist. 5th ed. Elsevier. 2020.

Section 3.1

Resource 01 – “Introduction to the immune system”Osmosis is licensed under Fair Use

Section 3.2 

Resource 01 – “Types of immune responses: Innate and adaptive, humoral vs. cell-mediated | NCLEX-RN | Khan Academy” by Khan Academy is licensed under Fair Use

Resource 02 – “Review of B cells, CD4+ T cells and CD8+ T cells | NCLEX-RN | Khan Academy” by Khan Academy is licensed under Fair Use

Section 3.3

Section 3.4

Section 3.5

Section 3.6

Resource 01 – “Hypersensitivity ( I, II, III, IV): An Introduction (FL-Immuno/82)” by Frank Lectures is licensed under Fair Use