Accompanying video lecture on Drbeen.com: https://members.drbeen.com/view/overview-innate-and-acquired-arm-1/rkhSjfCd2lW
Our immune system is a major organ system in our body that helps defend against the microorganisms trying to invade us. A majority of the patients presenting to a hospital with a complaint of fever have an underlying infection. This infection may have been caused by bacteria, viruses, fungi or parasites.
Some patients suffer from decreased immunity (e.g. HIV/AIDS), therefore they are more susceptible to infections. Other patients may have over-activation or mistargeting of their immune system which results in their immune system attacking their own tissues causing damage to their bodies. In other cases, the immune system may misidentify a non-harmful substance as being harmful and start an allergic response against it.
Functions of the immune system start at the surfaces of the body where mechanical barriers act as the first line of defense. Our skin is multilayered and keratinized. This structure prevents the entry of bacteria, fungi, and viruses from entering deeper tissues. The superficial layers of keratinization and dead cells are protective as well. Pathogens get stuck in these layers and are removed when these layers are shed. Mucous membranes of the conjunctiva, gastrointestinal tract, respiratory system, urogenital and reproductive system have surfaces with secretions covering the epithelium. The moist surfaces have chemical substances and enzymes that can attach with pathogens and prevent these pathogens from entering the deeper tissues. Cilia are also present on some of the surfaces, pathogens can become stuck on these ciliary surfaces. In these situations, pathogens are removed as the cilia propel and move the pathogens to the exit. Also of interest is that on these mucosal surfaces, there are proteins called defensins that can identify a foreign pathogen and create holes in the membrane of the pathogen to destroy it before it enters our body and harms us.
Our body is also inhabited by many non-pathogenic bacteria and fungi, which are called normal flora. They are present in the gut, throat, vagina, and pulmonary surfaces. They occupy the receptors that are potential attachment sites for pathogens. Thus the presence of normal flora protects us from infections.
Sometimes use of broad spectrum antibiotics wipes out normal flora, and pathogens attain an opportunity to attach to the mucosal surface and invade that area to enter. Another important protective mechanism is the acidic environment of the stomach and vagina. The enzymes of pathogens require an optimum pH for their function. When a pathogen enters the acidic environment of the stomach and vagina, its body becomes coagulated by the acids.
Injury to the mechanical barriers is a risk factor for infections. For example, if the skin is breached, as in surgery or trauma, the chances of infections
are increased. If the acidic environment of the stomach is altered, such as when we take proton pump inhibitors, the chances of certain infections increase. A stronger strain of bacteria may also increase the chance of infection.
Our body reacts with the pathogen after it penetrates the physical barriers. The body has dendritic cells with numerous dendrites and macrophages, which are large cells that can engulf bacteria. These cells are present across the body, mostly under the skin and mucosal surfaces. The cells recognize and breakdown foreign invaders. Macrophages, also known as phagocytes contain phagosomes and endosomes that are filled with digestive enzymes that break down the phagocytized bacteria. After the breakdown of these pathogens, macrophages and dendritic cells present antigens on their surface membrane with the help of certain proteins (i.e. MHC-II). Thus, these cells are known as antigen presenting cells. After presenting antigens on their surface for the immune system to recognize, the cells also secrete interleukins. Interleukins act as chemotactic agents for the cells of the immune system. The immune cells then come and recognize the foreign antigen. Macrophages can release IL-1, IL-6, IL-8, IL-12, tumor necrosis factor, and many other chemicals. Ultimately these antigen presenting macrophages reach the lymph nodes where, because of the interleukins, they interact with lymphocytes.
The immune system can be divided into two arms; Innate and Adaptive Immunity.
Innate immunity is the nonspecific defense mechanism that occurs immediately or within hours of an antigen’s appearance in the body. This response is activated by chemical properties of the antigen.
Adaptive immunity refers to an antigen-specific immune response. The antigen is first processed and recognized, next the adaptive immune system creates an army of its immune cells specifically designed to attack the antigen. Adaptive immunity includes specialized “memory” cells which can help aid in future immune responses to similar antigens.
Ingestion by neutrophils, macrophages and dendritic cells constitutes the innate arm of immunity. Interleukin-12 (IL-12) is the protein responsible for converting the innate response into an acquired immune response. It does so by signaling lymphocytes to be activated. Lymphocytes constitute the acquired arm of immunity. Antigen presenting cells (APCs), i.e. macrophages, dendritic cells, and B lymphocytes, create a bridge between innate and acquired immunity.
IL-12 is the chemical link between the two types of immune responses. There are two types of cells in acquired immunity: T lymphocytes form in the thymus, and B lymphocytes form in the bone marrow. A T cell is initially formed as a naïve T cell in the lymph node. On its surface, the naïve T cell contains receptors for IL-12 and IL-4. Under the influence of IL-12, the naïve T cell is converted to a helper T (TH)-1 cell.
The TH1 cell starts releasing two proteins: IL-2 and IFN-Ɣ. This constitutes the IL-12-IFN-Ɣ axis. This axis is a method by which acquired immunity reinforces the activity of macrophages since IFN-Ɣ is responsible for further activation of macrophages. Thus innate and acquired immunity both trigger each other. IL-2 also acts via an autocrine mechanism on the TH1 cell itself. Autocrine stimulation means that the cell that is stimulated by the substance is the cell that actually produced the substance.
Cytotoxic T cells are another type of T lymphocyte. Some pathogens, like viruses, enter cells and try to evade the immune system. The function of cytotoxic T cells is to kill infected cells. Cytotoxic T cells are also activated by the IL-2 produced by TH1 cells. Cytotoxic T cells recognize antigens that are presented on the surface of pathogen infected cells. These antigens are presented by MHC-I present on the surface of all nucleated cells. MHC-2 is present on all APCs. Cytotoxic T cells produce perforin and granzyme that break the membranes of the pathogens. IL-4 production also occurs, and it converts naïve T cells to TH2 cells. TH2 cells secrete IL-4 and IL-5, which are important regulators of B lymphocytes. These substances activate B lymphocytes. This leads to the formation of plasma cells from B cells. Plasma cells actively produce antibodies, which are specialized proteins that protect the body. They are produced by B lymphocytes and are the only plasma proteins that are not synthesized by the liver. These y-shaped antibodies are also called immunoglobulins. They can bind to and ultimately neutralize pathogens and their toxins.