Immunology, Immunity, Inflammation and Immunotherapies

Inflammation is a biological response to harmful stimuli, such as pathogens, damaged cells or irradiation. It is a protective attempt by the organism to remove injurious stimuli and to initiate the healing process. It is characterized by pain, redness, heat, swelling and disturbance of function. In order to avoid immunopathology, this system is tightly regulated by a number of endogenous molecules that limit the magnitude and duration of the inflammatory response.

The Major signs of acute inflammation include pain, heat, redness, swelling, and loss of function. Inflammation is a generic response, considered as a mechanism of innate immunity, as compared to adaptive immunity, which is specific for each pathogen.

Too little inflammation could lead to progressive tissue destruction by the harmful stimulus (e.g. bacteria) and compromise the survival of the organism. In contrast, chronic inflammation may lead to a host of diseases, such as hay fever, periodontitis, atherosclerosis, rheumatoid arthritis, and even cancer (cancer Immunology). Inflammation is therefore normally closely regulated by the body.

Cells of the innate immune system, in effect, prevent free growth of bacteria within the body; however, many pathogens have evolved mechanisms allowing them to evade the innate immune system.

Evasion strategies that circumvent the innate immune system include intracellular replication, such as in Mycobacterium tuberculosis, or a protective capsule that prevents lysis by complement and by phagocytes, as in salmonella. Bacteroides species are normally mutualistic bacteria, making up a substantial portion of the mammalian gastrointestinal flora.  Some species (B. fragilis, for example) are opportunistic pathogens, causing infections of the peritoneal cavity. These species evade the immune system through inhibition of phagocytosis by affecting the receptors that phagocytes use to engulf bacteria or by mimicking host cells so that the immune system does not recognize them as foreign. Staphylococcus aureus inhibits the ability of the phagocyte to respond to chemokine signals. Other organisms such as M. tuberculosis, Streptococcus pyogenes, andBacillus anthracis utilize mechanisms that directly kill the phagocyte.

The immune system protects the body from possibly harmful substances by recognizing and responding to antigens. Antigens are substances (usually proteins) on the surface of cells, viruses, fungi, or bacteria. Nonliving substances such as toxins, chemicals, drugs, and foreign particles (such as a splinter) can also be antigens. The immune system recognizes and destroys substances that contain antigens.

Your body's cells have proteins that are antigens. These include a group of antigens called HLA antigens. Your immune system learns to see these antigens as normal and usually does not react against them.

Immunity is the defense system with which you were born. It protects you against all antigens. Innate immunity involves barriers that keep harmful materials from entering your body. These barriers form the first line of defense in the immune response.

Cancer immunology is a branch of immunology that studies interactions between the immune system and cancer cells (also called tumors or malignancies). It is a growing field of research that aims to discover innovative cancer immunotherapies to treat and retard progression of the disease. The immune response, including the recognition of cancer-specific antigens, is of particular interest in the field as knowledge gained drives the development of targeted therapy (such as new vaccines and antibody therapies) and tumor marker-based diagnostic tests. For instance in 2007, Ohtani published a paper finding tumour infiltrating lymphocytes to be quite significant in human colorectal cancer. The host was given a better chance at survival if the cancer tissue showed infiltration of inflammatory cells, in particular those prompting lymphocytic reactions. The results yielded suggest some extent of anti-tumour immunity is present in colorectal cancers in humans.

The innate immune system, also known as the nonspecific immune system is an important part of the overall immune system that comprises the cells and mechanisms that defend the host from infection by other organisms. The innate immune system will act as the first line of defense against the invading microbial pathogens and relies on a large family of pattern recognition. Contrary to the adaptive immune system (which is found only in vertebrates), it does not confer long-lasting or protective immunity to the host.  Innate immune systems provides immediate defense against the infection, and are found in all classes of living organisms including plant and animal life. They include both humoral immunity components and cell-mediated immunity components.

Cancer immunotherapy is the use of the immune system to treat cancer. Immunotherapies can be broadly categorized into active, passive or hybrid (active and passive). These techniques exploit the fact that cancer cells often have molecules on their surface that can be identified by the immune system, known as tumour-associated antigens (TAAs); they are often proteins or other macromolecules (e.g. carbohydrates). Immunotherapy works better for some types of cancer than for others. It’s used by itself for some of these cancers, but for others it seems to work better when used with other types of treatment.

The central nervous system (CNS) regulates innate immune responses through hormonal and neuronal routes. The neuroendocrine stress response and the sympathetic and parasympathetic nervous systems generally inhibit innate immune responses at systemic and regional levels, whereas the peripheral nervous system tends to amplify local innate immune responses. These systems work together to first activate and amplify local inflammatory responses that contain or eliminate invading pathogens, and subsequently to terminate inflammation and restore host homeostasis. Here, I review these regulatory mechanisms and discuss the evidence indicating that the CNS can be considered as integral to acute-phase inflammatory responses to pathogens as the innate immune system.

Active cellular therapies usually involve the removal of immune cells from the blood or from a tumor. Those specific for the tumor are cultured and returned to the patient where they attack the tumor. Cell types that can be used in this way are natural killer cells, lymphokine-activated killer cells, cytotoxic T cells and dendritic cells. The only US-approved cell-based therapy is Dendreon's Provenge, for the treatment of prostate cancer.

Immune system disorders cause abnormally low activity or over activity of the immune system. In cases of immune system over activity, the body attacks and damages its own tissues (autoimmune diseases). Immune deficiency diseases decrease the body's ability to fight invaders, causing vulnerability to infections.

In response to an unknown trigger, the immune system may begin producing antibodies that instead of fighting infections, attack the body's own tissues. Treatment for autoimmune diseases generally focuses on reducing immune system activity

Immunotherapy is treatment that uses certain parts of a person’s immune system to fight diseases such as cancer. This can be done in a couple of ways:

Stimulating your own immune system to work harder or smarter to attack cancer cells. Giving you immune system components, such as man-made immune system proteins. Some types of immunotherapy are also sometimes called biologic therapy or biotherapy.

In the last few decades immunotherapy has become an important part of treating some types of cancer. Newer types of immune treatments are now being studied, and they’ll impact how we treat cancer in the future.

Immunotherapy includes treatments that work in different ways. Some boost the body’s immune system in a very general way. Others help train the immune system to attack cancer cells specifically.

Immunotherapy works better for some types of cancer than for others. It’s used by itself for some of these cancers, but for others it seems to work better when used with other types of treatment.

The adaptive immune system, also known as the acquired immune or, more rarely, as the specific immune system, is a subsystem of the overall immune system that is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogen growth. The adaptive immune system is one of the two main immunity strategies found in vertebrates (the other being the innate immune system). Adaptive immunity creates immunological memory after an initial response to a specific pathogen, leads to an enhanced response to subsequent encounters with that pathogen. This process of acquired immunity is the basis of vaccination. Like the innate system, the adaptive system includes both humoral immunity components and cell-mediated immunity components.

Anatomical barriers include physical, chemical and biological barriers. The epithelial surfaces form a physical barrier that is impermeable to most infectious agents, acting as the first line of defense against invading organisms. Desquamation of skin epithelium also helps remove bacteria and other infectious agents that have adhered to the epithelial surfaces. Lack of blood vessels and inability of the epidermis to retain moisture, presence of sebaceous glands in the dermis provides an environment unsuitable for the survival of microbes. In the gastrointestinal and respiratory tract, movement due to peristalsis or cilia, respectively, helps remove infectious agents. Also, mucus traps infectious agents. The gut flora can prevent the colonization of pathogenic bacteria by secreting toxic substances or by competing with pathogenic bacteria for nutrients or attachment to cell surfaces. The flushing action of tears and saliva helps prevent infection of the eyes and mouth

Vitamins have properties to help fight off a variety of illnesses and protect the body from damage to cells. Many foods contain vitamins that protect the immune system. Although many dietitians recommend getting vitamins from the diet, taking vitamin supplements can be a helpful and easy way to absorb the vitamin into the body if particular foods are not available. Some vitamins have more immune protection power than others.

Getting continuous amounts of vitamin C helps with wound healing. Vitamin C has antioxidant properties to block damage from oxidation that can lead to inflammatory conditions, heart disease and cancer. Vitamin C also protects against toxic chemicals and air irritants. Vitamin D plays vital roles in strengthening immune function and reducing inflammation. The vitamin generally absorbs into the body from sunlight. Many people get enough sun exposure for adequate doses of vitamin D.

Antioxidants are the best vitamins for immune system support. A diet rich in antioxidant vitamins and nutrients can help maintain healthy immunity to help your body to fight off infection. The three major antioxidant vitamins are: beta-carotene (vitamin A), vitamin C, and vitamin E. You’ll find them in colorful fruits and vegetables – especially those with purple, blue, red, orange, and yellow hues. To get the biggest benefits from antioxidants, eat these foods raw or lightly steamed.

The innate immune system plays an important role systemically and locally in infectious and inflammatory diseases. Vaccines, vaccine adjuvants and anti-inflammatory drugs were developed by understanding mechanisms of the innate immune system and causative factors of infection and inflammatory diseases. Pattern-recognition receptors, such as Toll-like receptors, retinoic acid-inducible gene I (RIG-I)-like helicases and nucleotide-binding oligomerization domain(NOD)-like receptors, and their downstream signals have great potential as targets of therapeutics because they are involved in numerous diseases. Furthermore, proteolytic systems such as autophagy and immunoproteasomes play important roles in the innate immune system, making them potential therapeutic targets also. By taking advantage of the immune system, humankind has made a great effort to develop new therapeutic and preventive medicines. Accordingly, we have reported several studies on the development of vaccines and adjuvant based on novel mechanistic strategies. Additionally, we have elucidated the mechanism underlying an interaction between innate immunity and the endocrine system. This review introduces the possible use of innate immune molecules for the development of immunomodulatory drugs and the involvement of the immune system in endocrine metabolic diseases to discuss future applications of innate immune molecules to therapeutics of various inflammatory diseases.

Innate immunity is the first line of defence against invading microorganisms in vertebrates and the only line of defence in invertebrates and plants. Plants are invaded by an array of pathogens of which only a few succeed in causing disease. The attack by others is countered by a sophisticated immune system possessed by the plants. The plant immune system is broadly divided into two. microbial-associated molecular-patterns-triggered immunity (MTI) and effector-triggered immunity (ETI). MTI confers basal resistance, while ETI confers durable resistance, often resulting in hypersensitive response. Plants also possess systemic acquired resistance (SAR), which provides long-term defense against a broad-spectrum of pathogens. Salicylic-acid-mediated systemic acquired immunity provokes the defense response throughout the plant system during pathogen infection at a particular site. Trans-generational immune priming allows the plant to heritably shield their progeny towards pathogens previously encountered. Plants circumvent the viral infection through RNA interference phenomena by utilizing small RNAs.

In the case study, we describe the effects of a particular individual's concentration/meditation technique on autonomic nervous system activity and the innate immune response. The study participant may be a women or a men or an animal with regard to tolerating extreme cold and hot weather conditions that  influence the autonomic nervous system and thereby the innate immune response.

Cell-mediated immunity is an immune response that does not involve antibodies, but rather involves the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. Historically, the immune system was separated into two branches: humoral immunity, for which the protective function of immunization could be found in the humor (cell-free bodily fluid or serum) and cellular immunity, for which the protective function of immunization was associated with cells. CD4 cells or helper T cells provide protection against different pathogens. Cytotoxic T cells cause death by apoptosis without using cytokines, therefore in cell-mediated immunity cytokines are not always present.

Immunomodulators help the body to produce extra cytokine molecules. Cytokines are “messengers” that tell the immune system how to react to certain things. For instance, your cytokines may tell your immune system that there is a virus present and with how much aggression it should attack. Part of the attack is producing a certain amount of inflammatory cytokines to help take care of invaders, viruses, bacteria, infections or disease. Immunomodulators help the immune response to be more “appropriate” or “efficient”.

Therapies that reduce an immune response to treat allergy or autoimmune disease, for example, are referred to as suppression immunotherapies. Suppression immunotherapy may also be used to prevent tissue/organ rejection in patients who receive a transplant. Immunotherapy is treatment that works by triggering, improving or suppressing the body’s immune response. Therapies that induce or amplify an immune response are referred to as activation immunotherapies and these are used in vaccines or to treat cancer.

Bacteria (and perhaps other prokaryotic organisms), utilize a unique defense mechanism, called the restriction modification system to protect themselves from pathogens, such as bacteriophages. In this system, bacteria produce enzymes, called restriction endonucleases, that attack and destroy specific regions of the viral DNA of invading bacteriophages. Methylation of the host's own DNA marks it as "self" and prevents it from being attacked by endonucleases. Restriction endonucleases and the restriction modification system exist exclusively in prokaryotes.

Invertebrates do not possess lymphocytes or an antibody-based humoral immune system, and it is likely that a multicomponent, adaptive immune system arose with the first vertebrates. Nevertheless, invertebrates possess mechanisms that appear to be precursors of these aspects of vertebrate immunity. Pattern recognition receptors are proteins used by nearly all organisms to identify molecules associated with microbial pathogens. Toll-like receptors are a major class of pattern recognition receptor, that exists in all coelomates (animals with a body-cavity), including humans. The complement system, as discussed above, is a biochemical cascade of the immune system that helps clear pathogens from an organism, and exists in most forms of life. Some invertebrates, including various insects, crabs, and worms utilize a modified form of the complement response known as the prophenoloxidase (proPO) system. 

Today, antibodies have been developed to treat an increasing number of cancers that affect a larger proportion of patients and make a significant contribution to overall or disease-free survival as part of a combination regimen with established cytotoxic chemotherapies. The vast majority of antibodies are given as part of a combination chemotherapy regimen to realize their full potential. Enhancement approaches are designed to create more potent antibodies that work better in combination or possibly as single agent therapy. Humanized monoclonal antibodies have changed the cancer treatment landscape over the past decade. Both in hematologic and solid tumors, antibodies have become an integral component of treatment regimens that have improved and extended the lives of cancer patients. In addition, antibodies have been able to improve efficacy while not significantly adding more toxicity.