Understanding the Immune System and the Endocrine System

 

Wendy Hill Williams

Abstract

 

Understanding the complex interrelationship and workings of the immune and endocrine system is essential to understanding psychoneuroimmunology. The first paper in this assignment will discuss the intricate workings of the immune system, including the lymphatic system, organs and tissues, hematopoiesis, the numerous cell types and their functions, and various other aspects of the immune system including the complement and antigen systems. The second essays will discus the different components of the endocrine system, including the hypothalamus, the pituitary and other endocrine glands, their hormones and functions, as well as how they modulate the immune system.

The Immune System

The immune system is a complex network of interacting cells, tissues, and organs that function to protect the body against attack by foreign invaders called antigens and to eliminate damaged, or disease altered cells (Daruna, 2004; US Department of Health and Human Services [DHHS], 2003). The primary invading microbes are viruses, bacteria, protozoa, and fungi (DHHS). Anatomical barriers, such as the skin, mucus membranes, the urogenital and GI tracts, and the cilia in the respiratory tract form the first line of defense and must be penetrated before the immune system is activated (Bugl, 2001; Daruna; Delves, 2005). When a foreign agent enters the body, the immune system mounts a non-specific (innate) attack, or specific (adaptive) attack, depending on the antigen (Daruna; DHHS).This is accomplished through an intricate communications network that sets the system in motion.

Specific and Non-specific Immunity

Non-specific immunity is innate, and is a general response to invasion. Specific immunity is adaptive and acquired after birth through vaccinations or previous exposure to specific microorganisms (Bugl, 2001; Daruna, 2004; DHHS, 2003). Specific immunity has a memory of previous invaders. It is further divided into two different immune responses referred to as cell-mediated immunity derived from T-cell responses, or humoral immunity derived from B cell antibody responses (Daruna; Delves, 2005; National Cancer Institute, 2006).

Self versus Non-Self Discrimination and the Human Leukocyte Antigen System

A key factor in the immune defense is the ability of the immune system to distinguish self from non-self and attack the offending organism not the body (Daruna, 2004; Delves, 2005; DHHS, 2003). This is accomplished through the human leukocyte antigen system, and a set of specific self markers called the major histocompatibility complex (MHC), consisting of unique surface proteins found on every cell of the body that distinguishes the "self" of each individual (Daruna; Delves; NCI, 2006). Autoimmune diseases develop when the system goes awry, and the immune system mistakenly attacks the cells and tissues of the body (Daruna; DHHS).

The Organs of the Immune System and their Function in the Immune Response

Lymphoid organs are placed throughout the body and contain lymphocytes, the white blood cells involved in the immune response (DHHS, 2003). The primary organs include the bone marrow and thymus gland (Daruna, 2004; NCI, 2006). Secondary organs include the spleen, lymph nodes, tonsils, adenoids, appendix, and Peyer's patches located in the intestines. Each organ has a specific role in immune functioning (DHHS; NCI). The lymphatic vessels connect the lymphoid organs together, and play a vital role in immunity by moving lymphocyte containing lymph fluid throughout the body to combat invaders (Daruna; DHHS; NCI).

The Bone Marrow

The bone marrow is the soft spongy material located in the hallow center of the bones that manufactures red and white blood cells, and platelets. All blood cells, including the immune cells, originate from hematopoietic stem cells in the bone marrow and differentiate into specialized cells of the body (Bugl, 2001; Daruna, 2004).The white blood cells are an integral component of the immune system. Red blood cells carry oxygen throughout the body and platelets enable blood clotting after an injury (Bugl; Daruna; DHHS, 2003; NCI, 2006).

The Thymus Gland

T cells, also known as T lymphocytes travel to and mature in the thymus gland, an endocrine gland located behind the breastbone. The thymus gland also produces a hormone that stimulates T cells and the lymph nodes to produce plasma cells that create antibodies (Daruna, 2004; DHHS, 2003).

The Spleen

According to Frenkel (2005), the spleen is functionally and structurally like two organs consisting of white and red pulp. The white portion is primarily responsible for the manufacturing and maturation of B and T cells, and developing humoral antibodies from B cells. The red pulp serves a phagocytic function by removing old blood cells from the body. The spleen also stores and releases new blood when needed, and protects the body against specific bacteria (Daruna, 2004; Fenkel).Hence, individuals who have had a splenectomy are at risk for severe bacterial infections, called overwhelming post-splenectomy sepsis, and should follow recommended guidelines for vaccinations against these pathogens (Frenkel; Infectious Disease Management Program, 2007).

Lymph Nodes

Lymph nodes, like the spleen, have specialized compartments where immune cells gather and work. They are positioned along the lymphatic vessels throughout the body in the neck, armpits, groin, and abdomen (Bugl, 2001; Daruna, 2004; DHHS, 2003).

The Tonsils, Adenoids, and Appendix

These clumps of lymphoid tissue referred to as MALH or mucosa associated lymphoid tissue are scattered throughout the body and function to filter out microbes either through the nose and mouth (tonsils and adenoids) or the gastrointestinal tract (Daruna, 2004). In addition to the skin, the mucus membranes and the lining of the gut are the first major barriers against a foreign microbe or antigen (Daruna; DHHS, 2003).

The Cells of the Immune System and their Function in the Immune Response

The cells of the immune system are numerous and complex, each serving a specific function in the immune response. Hematopoietic stem cells located in the bone marrow are the precursors to all the blood cells of the body. According to Daruna stem cells differentiate into various cell types due to "the switching of genes on and off [], as well as "the chemical composition of their environment" (p.25). The blood cells continuously replenish as needed through a self-regulatory process known as hematopoiesis (DHHS, 2003). Hematopoietic stem cell differentiation is shown in Figure 1 in the Appendix.

Megakaryocytes

Megakaryocytes are one of two broad categories of differentiated cells arising from hematopoietic stem cells (Daruna, 2004). Magakaryocytes are large cells that release platelets which are essential to hemostasis, blood clotting, and wound healing (DHHS, 2003). Recent research has indicated that platelets have a signaling role in innate and adaptive immunity (Weyrich, & Zimmerman, 2004).

Leukocytes

Leukocytes consist of all the white blood cells and are the other broad category of cells arising directly from hematopoietic stem cells (Daruna, 2004). Polymorphonuclear granular leukocytes (granulocytes) give rise to basopils, esonophils, and neutrophils, which are all involved in the inflammatory response (Daruna). The mononuclear leukocytes differentiate into monocytes, B lymphocytes, T lymphocytes and natural killer (NK) cells (Daruna).

Granulocytes

The granulocytes consist of the neutrophils, esonophils, and basophils. Neutrophils are phagocytes responsible for the ingestion of pathogens; esonophils are cytotoxic and effective in eliminating parasites; and basophils give rise to mast cells which are involved in the inflammatory response, and allergic reactions (Daruna, 2004; DHHS, 2003).

Monocytes

Monocytes are phagocytes; cells that ingest infectious agents through the process of phagocytosis as part of the non-specific immune response (Daruna, 2004; DHHS, 2003). Monocytes can become tissue bound and become enlarged macrophages, increasing their phagocytic ability (Daruna, 2004).

Dendritic cells

These cells are part of a group of cells known as antigen-presenting cells (APC's). APC's process and carry antigens on their surface and present it to other cells in the immune system (such as T cells) via a process of communication and chemotaxis (Delves, 2005). Dendritic cells are located in the skin and tissues throughout the body, including the lymph nodes.

Lymphocytes

The lymphocytes include T and B cells and natural killer cells. B lymphocytes provide humoral immunity in their response to antigens by producing antibody secreting plasma cells (Daruna, 2004; DHHS, 2003). Antibodies are in the protein group of immunoglobulins (Ig); each different immunoglobulin has a specific role in attacking antigens. B cells are effective outside the cell body (humoral immunity) and are not capable of attacking foreign invaders within the cell (Daruna; DHHS).

T lymphocytes

The stem cells that become T lymphocytes travel to and mature in the thymus gland (hence they are called "T" lymphocytes), where a rigorous selection process occurs and up to 95% of the T-cells are destroyed through a process known as apotosis, or programmed cell death (Daruna, 2004; DHHS, 2003; NCI, 2006).The cells that recognize non-self markers survive (Devels, 2005). T lymphocytes provide cell-mediated immunity predominately through two different types of T cells: helper T-cells, and cytotoxic (killer) T-cells (Daruna; DHHS; NCI).

Helper T-cells and cytotoxic T-cells

Helper T-cells (TH) usually posses the CD4+ marker, and are essential for all aspects of the immune response. They act as managers and help to communicate with and to activate various immune system cells and enhance their ability to perform their immune function (Daruna, 2004; DHHS, 2003; NCI, 2006). Cytotoxic T-cells (TC) carry the CD8+ marker and are so named because they are toxic to cells; they seek out and kill viral infected and cancer cells. Unfortunately, because they recognize non-self MCH molecules, they also are responsible for transplanted tissue rejection (Daruna; DHHS; NCI).

T-cell Help of Antibody Production and Cytotoxicity

Antibody production.

As noted above, B lymphocytes provide humoral immunity in their response to antigens by producing antibody secreting plasma cells (Daruna, 2004; DHHS, 2003). Although B-cells are able to be activated independent of T-cell help; according to Daruna, this response isn't always adequate to defend the organism. Therefore helper T-cell activation through cytokine release is imperative to B-cell antibody production (Daruna; Delves, 2005).

Cytotoxicity

Helper T-cells also assist in activating cytotoxic (killer) T-cells through cytokine release, causing movement of other cells to the area, in particular phagocytes and those involved in the inflammatory response. This enables killer T-cells to effectively destroy the diseased cell (Daruna, 2004; Delves, 2005; NCI, 2006)

Natural killer cells

These large lymphocytes are also cytotoxic, equipped with antibody receptors, and are capable of killing infected and distorted cells marked with antibodies; therefore, According to Daruna (2004), they are involved in " a process known as antibody-dependent cellular cytotoxicity (ADCC)" (p.34).

Immunotherapeutic action of natural killer cells on cancer

According to the National Cancer Institute (NCI, 2006), there are more than 100 types of cancer, all of which begin from a single cell. Cancers are named according to their cell of origination and form when the cells of the particular tissue are damaged, mutate, and multiply uncontrollably (Daruna, 2004). Natural killer cells engage in constant surveillance of the body, seeking out and destroying microbial organisms and neoplasms, and hence, are one of the body's natural defenses against cancer (Delves, 2005; NCI). When a cell becomes malignant, the surface antigens of the cancer cell change and pieces of antigen are shed into the blood stream. This stimulates chemotaxis, or movement of immune cells toward the damaged cells. Natural killer cells are the first line of defense against these damaged or mutated cells (Smyth, Hayakawa, Takeda, & Yagita, 2002). NK cells are filled with potent lethal chemicals and kill the malignant cell on contact (DHHS, 2003; NCI).

Unfortunately, sometimes this system breaks down, and the cells continue to multiply, divide, and possibly form a tumor. Malignant cells have the ability to metastasize and invade other parts of the body and crowd out and destroy normal body tissue (NCI, 2006). Metastatic cancer is potentially lethal; therefore cancer specialties are constantly researching new ways to prevent and treat malignancies.

According to Delves (2005), immunotherapeutics are "Therapeutic agents that use or modify immune mechanisms" (Immunotherapeutics 1). Over the past 20 years, natural killer cells have been studied extensively in this regard, and major progress has been made in harnessing their innate immune capacities to treat previously fatal malignancies (Moretta, Locatelli, & Moretta, 2008; Smyth, et al., 2002 ). Researchers and clinicians have enhanced NK effectiveness through administering cytokines (various interleukins) and other immune substances. This treatment has shown promise with renal cell carcinoma, lung and liver cancers, malignant melanoma, and recently a study included the treatment of breast cancer (Smyth, et al.). In addition, bone marrow transplants are a treatment often used with virulent leukemias and other malignancies; putting the patient in a severely compromised immune condition. However, according to Moretta et al., utilizing alloreactive NK cells in this population of leukemia patients has the potential to cure, and even eradicate previously fatal leukemias. Thus NK cell immunotherapy in the treatment of malignancies is very promising.

Additional Components of the Immune System

Cytokines

Cells secrete proteins known as cytokines that enable the cells of the body to communicate with each other, to either act on the cell itself (autocrine) or a nearby paracrine cell (Daruna, 2004; Delves, 2005; DHHS 2003). Cytokines are not antigen specific, although specific antigens activate secretion of cytokines; hence they are capable of assisting in both adaptive and innate immunity (Delves). Cytokines include the interleukins, interferons, growth factors, tumor necrosis factor, and many other chemical messengers essential to the inflammatory and immune response (Daruna; Delves; NCI, 2006). Cytokines are also the powerful chemical messengers that trigger the stem cells to differentiate into specific type of immune cells (DHHS).

The complement system

Simply put, "The complement system is an enzyme cascade that helps defend against infection" (Delves, 2005, Complement System). The complement system includes numerous proteins that are produced in and released primarily from the liver into the bloodstream. The enzymes have numerous immune functions, but primarily bridge innate and adaptive immunity, assist antibodies in their attack on bacteria, and are involved in inflammatory responses (Daruna, 2004; Delves; DHHS, 2003; NCI, 2006). The complement cascade is activated through a complement molecule encountering an antibody-antigen complex, setting off a sequenced chain of events (DHHS; NCI).

Clusters of differentiation (CD markers)

Lymphocytes are differentiated and identified through antigen specific surface molecules and receptors referred to as CD markers (Daruna, 2004; Delves, 2005). The Clusters of Differentiation nomenclature system was created in Paris in 1982 at the first International Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA). The CD molecules are given a number based on the order of discovery. There are currently over 300 known and identified CD markers (Daruna; Delves). This is significant because every lymphocyte has the capacity to recognize a specific antigen through their CD markers (Delves), thus furthering the understanding of the immune system and treatments of immune disorders.

Conclusion: The Immune System and Response

The immune system is a highly complex, sophisticated network of interacting cells, tissues, chemical substances, and organs, designed to protect the body from foreign invaders or internal dysregulation. The immune response begins on an anatomical level when a microbe attempts to invade the body (Daruna, 2004; Delves, 2005; DHHS, 2003; NCI, 2006). The skin, coughing and sneezing reflex, mucous secretions, and acids of the GI tract all provide the first defense including secretion of IgA antibodies. If this barrier is successfully crossed, the body mounts a non-specific attack involving phagocytes, natural killer cells, granulocyctes, and complement cells. A specific immune response follows this level, involving antibodies and cytotoxic T cells equipped with precise receptors to attack the particular microbe (Daruna; Delves; DHHS; NCI). In addition, the immune system is prepared to mount an attack against internal cell mutations, such as those that occur in malignancies (Daruna; Delves; DHHS; NCI). Sometimes the immune system goes awry and the body attacks its own tissue resulting in autoimmune disorders. Thus, in order to be successful, the complex workings of the immune response must first be activated, regulated, and ultimately resolved (Delves).