If you’re preparing for the MCAT exam, you’ll want to begin by revising the subjects listed in the MCAT syllabus. The immune system is one of the key MCAT topics included in the syllabus and forms part of the Biological and Biochemical Foundations of Living System sections of the exam. This comprehensive overview is designed to provide you with everything you need to know about the immune system for the MCAT exam.
The immune system is the basis behind how humans and other species protect themselves from diseases and eradicate diseases that have entered the body. It recognizes foreign organisms such as bacteria, viruses, parasites and fungi amongst others and works to kill them or disable them in order to prevent them from causing harm to the body or to reduce the harm they have already caused. The immune system also works to kill mutated, cancerous cells to reduce the impact of cancer, as well as being the basis behind autoimmune and autoinflammatory conditions in the body.
The immune system is divided into two main concepts: the innate immune system and the adaptive immune system. The innate immune system is the part of the immune system that works as soon as a pathogen enters the body. It is non-specific, with the primary goal being to kill organisms regardless of what type of organism it is. It is responsible for the initial phagocytosis of organisms by cells such as natural killer cells and macrophages, after which point, phagocytic cells can present the antigens that existed on the invading pathogen that has now been digested. From this, antibodies on B cells can adapt to these specific pathogens. At this point, the adaptive immune system is important. It is composed initially of B cells that have previously encountered the pathogen and are specialized against it, known as memory B cells. These memory B cells massively increase the numbers of T cells and macrophages so that they can specifically affect this pathogen, meaning that the organism can often be eradicated before symptoms occur, or if not, can prevent severe symptoms and side effects of the disease from occurring.
Macrophages are one of the main cells involved in the innate immune system. They describe a series of cells, including microglia that exist in the central nervous system as well as Kupffer cells in the liver and alveolar macrophages in the lungs amongst others. They are known as agranulocytes, which means that unlike certain blood cells such as neutrophils, they lack granules within their cytoplasm. They work to ingest pathogens through endocytosis, digest them within the cell and present the antigens of the pathogen on the Major Histocompatibility Complex. Macrophages can also release cytokines, which are small proteins that can cause inflammatory reactions and help to recruit more macrophages alongside other immune cells to the site of the infection.
Phagocytes describe a group of immune cells that are capable of phagocytosis. These include monocytes (of which several immune cells are derived), neutrophils, dendritic cells, and macrophages. When they come across a foreign pathogen, they will extend out to be able to surround the pathogen and ingest it, and the pathogen will be stored in an intracellular compartment known as a phagosome. These phagosomes will fuse with a lysosome to form a phagolysosome for the pathogen to be digested. It is estimated that there are around 6 billion phagocytes that exist per liter of blood, therefore on average, there are about 30 billion phagocytes in one adult human.
T-lymphocytes are one of the most important cells involved in the adaptive immune system and are split into 3 main categories. Killer T cells, otherwise known as cytotoxic T cells (TC cells), are CD8+ T cells that are responsible for killing entire cells instead of direct pathogens. This means that they are responsible for killing cells that have been infected with viruses, as well as mutated, cancerous cells. The other main categories of T cells are the T helper cells and the T regulatory cells, which both have important, though indirect effects on the immune system. T helper cells (TH cells) are a type of T cell that is responsible for the activation of B cells, meaning that antibodies can be released, and memory cells can be formed. They are CD4+ cells, and also have a role in the autoactivation of other T cells to increase the population of TC cells in the body. The final type of T cell, the regulatory T cell (Treg cell) is a type of T cell that is responsible for the differentiation of T cells. It prevents T cells from recognizing self-antigens as foreign as well as regulating the migration of T cells around the body.
B-lymphocytes describe a type of immune cell that is activated by T cells and is responsible for the production of antibodies to specifically target a specific pathogen. B cells have antibodies that have different subtypes, and a branch of them, known as plasma B cells, can undergo a process known as somatic hypermutation. This describes when the antibodies on the B cells mutate rapidly until an antibody is formed that perfectly fits the antigen that exists on the pathogen. The B cells can then replicate, and that exact antibody is multiplied massively. The memory B cells are a further subtype of B cells which have a very long lifespan, and these are responsible for containing a memory of the pathogen so that if the organism is reinfected, the memory B cells can trigger the plasma B cells to produce large quantities of the specific antibody to eliminate the pathogen before a significant effect is triggered.
The bone marrow is an essential site of differentiation of several immune cells, as they arise from one common haemopoietic stem cell that exists only in the bone marrow. Red blood cells are also created in the bone marrow, specifically at the ends of the long bones, for instance, the femur. The most important immune cells that rely on the bone marrow are the B cells, which undergo differentiation here before being released and circulated in the blood during infections.
The bone marrow is responsible for the differentiation of B cells; however, T cells differentiate in the thymus. This is a gland in the anterior mediastinum composed of two lobes, which gradually degenerate into fatty tissue as the organism ages. Two processes in the maturation of T cells occur in the thymus: positive selection and negative selection. Positive selection describes where T cells are presented with different MHC complexes (either MHC I or MHC II) and from this, they differentiate into either Tc cells or TH cells. Negative selection is where these same cells are introduced to host antigens. If they attack host antigens, they degenerate, however, if they do not react to host antigens, they become mature T cells.
The spleen is another primary lymphoid organ and resides in the upper right quadrant of the abdomen. It is responsible for the breakdown and recycling of different blood components, including red blood cells and B cells covered in antibodies. The two main components of the spleen are the red pulp (75% of the spleen) and the white pulp (25%), surrounded by a capsule. The red pulp is the part of the spleen that works to filter the blood by removing red blood cells and antigens, while the white pulp is a large mass of lymphoid tissue that contains several macrophages, T lymphocytes and B lymphocytes that are involved in adaptive immunity.
Lymph nodes are the most common immune tissue in the body, existing in several different locations around the body. They are responsible for the filtration of waste products from different tissues around the body, making them vital for the normal function of the organisms in which they exist. Different lymph nodes drain different parts of the body; however, they all end up draining into the thoracic duct, which in turn drains into the vena cava for the blood to be filtered out in the kidneys. Due to their extensive supply, several cancers metastasize through the lymph nodes, resulting in an easy, but often predictable, route of spread of cancers. Lymph nodes themselves consist of kidney-shaped, encapsulated structures that are full of different lymphocytes that can then be distributed to different tissues in order to fight infection. In states of illness, infection or disease, they can become inflamed, known as lymphadenopathy.
Clonal selection refers to the differentiation and expansion of both B and T lymphocytes in the blood. In this process, antigens are presented to all the B and T lymphocytes that are circulating in the bloodstream. These B and T cells are slightly different in their structure, therefore will bind slightly differently to the antigen. When the lymphocytes that bind to the antigen with the highest affinity are found, they will rapidly reproduce and clone themselves to enable them to fight off the infection the fastest.
The ability to recognize self-antigens (antigens that are produced by the host) as autoantigens as opposed to pathogenic or harmful antigens is very important in the human body, as without it different disorders, especially autoimmune and autoinflammatory disorders, can result. This is because the body will then make autoantibodies against its autoantigens, resulting in different cells being recognized as pathogens and therefore broken down. This is the mechanism behind what happens in Type 1 diabetes (the body sees insulin-producing β cells as foreign and kills them), as well as Coeliac disease (crypts in the small intestine are broken down and the body cannot digest gluten), rheumatoid arthritis (bone is broken down, affecting the joint spaces), amongst others.
The difference between antigens and antibodies is a concept that is difficult for many people to remember as the words are very similar. Antigens are primarily peptide molecules that are expressed on pathogens, however, some autologous antigens exist in the blood as a result of certain physiologies such as blood type. They are how the body can recognize and differentiate between pathogens, as well as acting as the binding site through which the body can lyse, disable, or phagocytose these pathogens. Antibodies are immunoglobulins that are proteins in the shape of a ‘Y’. They are produced by B lymphocytes in the body to attach to antigens as markers so that different immune cells and immune complexes can bind to the antigen and therefore cause damage to the pathogen.
The basic structure of an antibody consists of a Fab region, composed of 2 doublets of chains (one heavy and one light) connected via a disulfide bond, which then joins at the hinge region to meet the Fc region, composed of the remainder of the heavy chains of the Fab region, also connected through a disulfide bond. The Fab region is known as the variable region, meaning that it can change and adapt depending on the antigen, and this is the area of the antibody that attaches to the epitope of the antigen on the pathogen. This is known as ´class switching´. The Fc region, however, is a constant region, meaning that it cannot change, and this region is either left free or attached to the B cell from which it has been composed.
Image source: https://commons.wikimedia.org/wiki/File:Antibody_basic_unit.svg
The functioning of the adaptive immune system relies heavily on the ability of pathogens to express antigens, and for these antigens to be presented to different immune cells to produce the proper antibodies and eliminate the pathogen. This presentation is done on antigen presenting cells (APCs), which consist of every cell that has a nucleus after the pathogen has been broken down within the cell. They are presented on the Major Histocompatibility Complex, and this is then recognized by T cells. Helper T cells can also assist in this recognition by presenting these antigens to B cells, and it is a mixture of this alongside some other cellular signals that result in the activation of B cells and then antibody class switching on the B cells.
Different antigen-presenting cells, often phagocytotic cells, will absorb a pathogen, break it down and then present the antigen on their surface via the MHC. This will be specifically presented to lymph nodes, Peyer's patches or other sites containing immature T and B cells to elicit a response. For the APC to elicit a response from TH cells, CD40 on the APC must bind to CD40L (CD40 ligand) on the TH cell. For the TC cell, a ligand, such as CD28, on the APC must bind to a T cell receptor on the surface of the TC cell. This triggers the activation of the two different types of T cell and these T cells can then, in turn, activate B cells. The B cells will undergo class switching and clonal selection with the assistance of cytokines released by the T cells, and through this, the most suitable antibodies are produced.
The major histocompatibility complex (MHC) is a complex present on all nucleated cells in some form, that allows for antigens to be presented on the cell surface. There are two main types of MHC: I and II. It is the most common type of MHC and is expressed on nearly all cells. It presents non-self-antigens which are picked up by CD8 on TC cells, and these antigens are all endogenous antigens. MHC II, however, is only present on APCs and presents to TH cells through a CD4 costimulatory signal. This presents both self-antigens and non-self-antigens, with the non-self-antigens being exogenous antigens.
Hopefully this information has been helpful in supporting your understanding of the immune system for the MCAT. To support your revision further, we’ve produced blogs covering a wide variety of MCAT topics, including the digestive system, the excretory system, and meiosis for the MCAT. For everything you need to know about the exam, including the MCAT test dates and fees, the exam format and how to prepare for the MCAT, check out our MCAT Guide.
