Chris Canchola, Byron Castaneda, Jonathan Tonel

The Immune System

  • Overall function
  • Major Organs
  • Function(s) of Major Organs
  • Diseases and disorders
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Introduction

The immune system enables animals to avoid or limit many infections caused by pathogens, infectious agents that cause diseases. Skin or shell serves as an animal's most basic defense by keeping out microbes that live on the body. There are then two defenses past the skin, innate immunity and acquired immunity. The innate immunity is found in all animals and responds immediately upon infection, whether it encountered that infection or not. Acquired immunity is also known as adaptive immunity/ Acquired immunity take effect after the innate immunity but develop more slowly. Acquired immunity is an immune response that is more enhanced because of previous encounters with the infecting pathogen.

Innate Immunity

Invertebrates
Innate immunity can be found in all animals, although invertebrates only have this type of immune system. Invertebrates in general have these elements that make up the innate immune system:
  • Exoskeleton
    • Made out of chitin, first defense against pathogens
  • Lysozyme
  • Hemocytes
    • Use phagocytosis to eliminate bacteria, pathogens, and other foreign materials

Fruit Fly (invertebrate)
Fruit Fly (invertebrate)


Vertebrates
Innate Defenses:
  • Barrier Defenses
    • Basically epithelial tissues like skin
    • Mucus is another example, a secretion that traps microbes and other particles
    • Saliva and tears also help immunity by preventing germs from growing on the body
    • Acidity of the skin also helps slow growth since it can range from 3 to 5 pH value due to sebaceous glands and sweat glands
  • Cellular Innate Defenses
    • Leukocytes/White Blood cells use phagocytosis to get rid of pathogens
    • Receptors called TLRs help the mammalian immune system recognize fragments of molecules characteristic of a set of pathogens
      • There are many types of TLRs that detect different foreign substances, each specialized for a different one
  • Phagocytosis
After a TLR recognizes an intruder, it alerts internal defenses. One of the first steps is calling in white blood cells to engulf microbes into them. This process is called phagocytosis. The trapped microbe is put in a vacuole. A lysosome combines with the vacuole to kill the microbe through enzymes and harmful gases. Other types of cells that also function like white blood cells are neutrophils and macrophages. For multicellular attackers, eosinophils is the phagocyte used against them. Dendritic cells are another type that help stimulate development of acquired immunity.

Antimicrobial Peptides and Proteins
Inteferons are proteins that provide innate defense against infections. Even infected cells give off interferons! Interferons inhibit viral reproduction.
The complement system consists of roughly 30 proteins in blood plasma that fight infections together. After being "waken" from a dormant state by detection of certain substances from microbes, biochemical reactions create lysis of invading cells.

Lysis, the bursting of a cell
Lysis, the bursting of a cell


Inflammatory Responses
Pain and swelling are symptoms of an inflammatory response. It is the signaling of molecules released upon injury or infection. Histamine, a molecule used for inflammatory signaling, is released to trigger nearby blood vessels to dilate and become more permeable. Activated macrophages and other cells discharge additional signaling molecules that further promote blood flow to the injured site. The diagram below goes more into depth:

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Fever is another inflammatory response. It is speculated that elevated body temperature may enhance phagocytosis and speed up chemical reactions. This allows repair and other processes to speed up.

Natural Killer (NK) Cells
These cells help recognize and eliminate certain diseased cells in vertebrates. Except for red blood cells, all cells have a protein called class I MHC molecule. When infected, the cell does not express the protein anymore. NK cells detect this and destroy the cell that is infected. This prevents or slows further reproduction.

Innate Immune System Evasion by Pathogens
Some pathogens can escape destruction or detection. Some have an outer capsule that prevents recognition. Others are too potent and cannot be broken down by the nitric gases when enclosed in lysosomes. Tuberculosis is an example.

In Acquired Immunity, Lymphocyte receptors provide Pathogen-Specific Recognition

Lymphocytes
  • B cells and T cells
  • Originate from Stem cells in the bone marrow
  • T Cells come from the thymus, organ above the heart
  • B Cells come from bone marrow
    • Both B and T detect and disable foreign invaders
    • They also have immunological memory, where they "remember" a foreign molecule from a previous encounter (like in our video)

Antigens
Any foreign molecule that is specifically recognized by lymphocytes and elicits a response from them is an antigen. There are 100,000 antigen receptors on a single lymphocyte. Epitopes are detected by the antibodies.

B Cell Receptor
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T Cell Receptor
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MHC
Movement of the MHC molecule and bound fragment to the cell surface results in antigen presentation, the display of the antigen fragment on the cell surface. Antigen presentation can activate immune responses against the antigen or an infected cell that has the same antigen fragment. Basically, when a cell that has been invaded by a pathogen displays an antigen, it signals the immune system that it is infected.

Class I MHC molecules displaying bound antigen fragments are recognized by a subgroup of T cells called cytotoxic T cells. Class II MHC molecules are made by antigen-presenting cells such as macrophages and B cells. Antigen-presenting cells display antigens for recognition by cytotoxic T cells and helper T cells, a group of T cells that assist both B cells and cytotoxic T cells.

Major Organs and their functions

Skin
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The skin works as an animal's most basic defense against pathogens. The skin provides a significant obstacle to microbes that are present on the body.

Bone marrow
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The bone marrow is major organ of the immune system because B cells and T cells, types of white blood cells called lymphocytes originate from stem cells in the bone marrow. Lymphocytes that mature in the bone marrow develop as B cells.

Thymus
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The thymus matures lymphocytes into T cells. The lymphocytes that mature into T cells originated from the bone marrow too, but migrated from the bone marrow to the thymus, which is an organ in the thoracic cavity above the heart.

B cells and T cells recognize and inactivate foreign cells and molecules. Both types of cells also contribute to immunological memory, which is an enhanced response to a foreign substance that had been encountered before. Immunological memory is responsible for protection we obtain against chickenpox and many other diseases we previously encountered or get a vaccination for. Immunological memory can persist for many decades.

Self-Tolerance

Some lymphocytes make receptors specific to epitopes on the body. The immune system would not be able to distinguish itself from a threat if these lymphocytes were not destroyed. Antigen receptors of lymphocytes are tested as they grow. If they are self-reactive, they are destroyed by apoptosis or made nonfunctional. Failure of self tolerance leads to autoimmune diseases.

Amplification of Lymphocytes

It is rare for an antigen to find a lymphocyte with it's specific antigen receptor. Activated B and T cells divide many times, making two clones: effector cells and memory cells. Effector cells attack an antigen and pathogens making that antigen. Memory cells have receptors specific for an antigen. Memory cells last long but are not in large numbers, and Effector cells live short lives, but there are many of them. Clonal selection is the proliferation of a lymphocyte onto a clone of cells in response to binding to an antigen. The presentation of an antigen to a lymphocyte with receptors specific to that antigen makes mass cell division. The result is thousands of clones specific to that antigen. Primary immune response is the production of effector cells from a clone of lymphocytes in a first response to an antigen. Secondary immune response is the same as primary response, but faster, of greater magnitude, and more prolonged.

Defense of Body Cells and Fluids by Acquired Immunity

Acquired Immunity is basically the body's humoral response and cell-mediated response. A Humoral Response is the activation and clonal selection of effector B cells. These cells secrete antibodies that go through the body's blood and lymph. Also called the Antibody-mediated response. The Cell-Mediated Response is the activation and clonal selection of cytotoxic T cells. They find and destroy target infected cells. Helper T cells help both these responses. Acquired immunity recognizes specific traits of pathogens using their receptors. This is slower than the innate immunity response.
Humoral and Cell-Mediated Responses
Humoral and Cell-Mediated Responses

T-Cells

Helper T cells increase the power of the humoral and cell-mediated responses. They interact with antigen fragments and stimulate nearby T and B cells. Helper T cells interact with antigens by binding to them, joined by CD4. cytokines are exchanged during the interaction, which can get the antigen to stimulate the helper T cell so it can produce even more helper T cells. There are three different types of antigen presenting cells: dendritic cells, macrophages, and B cells. They all interact with helper T cells by making a primary immune response, initiating secondary immune response, and presents antigens respectively. Cytotoxic T cells destroy infected cells with secreted proteins that cause cell rupture and death. They work in cell-mediated response and are activated by helper T cells. Cytotoxic T cells use CD8 to bind to antigens. The destruction of a host cell exposes antigens to antibodies.
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T cell

B cells

B cells work with humoral response. Cytokines secreted from helper T cells activate the B cells. B cells only present the antigen that it specifically binds to, unlike other presenter cells. Activated B cells make thousands of clones of plasma cells, which each secrete around 2000 antibodies every second for four days.
A B cell and a Virus
A B cell and a Virus

Anti-Bodies

There are 5 major classes of antibodies. IgM, IgG, IgA, IgD, and IgE. They each have a specialized function. IgM neutralizes and cross-links antigens. IgG neutralizes antigens and promotes opsonization and cross-linking of antigens. IgA gives a defense of local mucus membranes by cross-linking and neutralizing antigens. IgD is an antigen receptor. IgE triggers the release of histamine and other chemicals that cause allergic reactions. Antibodies can be polyclonal or monoclonal. Polyclonal means that they were made from many different b cell clones. Monoclonal means the antibodies are from one b cell clone.
An Antibody
An Antibody

Immunization

Antibodies can mess up pathogens in many ways. One of these is neutralization, where an antibody binds to a pathogen, rendering it unable to infect a host cell. Another is opsonization, antibodies bind to pathogens in a macrophage in order to increase phagocytosis. If an antigen bound to an antibody is attached to a complement protein, they will form an membrane attack complex, which fills target cells with water, causing them to lyse. natural killer cells can be called if an antibody attaches to a viral protein on the surface of an infected cell. Active immunity is immunity where clones of memory cells form to ward off infection. Passive immunity is where antibodies are immediately ready to destroy pathogens. Vaccination is a way that active immunity can be induced. Passive immunity can be induced by giving immune antibodies of an animal to another animal that is not immune. Cells from a different being of the same species can trigger an immune response. This is also true for blood. The transplanted cells and blood will be attacked and destroyed.
Vaccination
Vaccination

Transplants

In organ transplants, it is MHC genes that will trigger an immune response. The molecules are so diverse that almost no two people will have alike sets. Rejection must be minimized by doctors in a transplant. In bone marrow transplant, the donor's tissue can reject the recipient's tissue. If there is a problem with someone's bone marrow cells, it must be blasted with radiation to kill all abnormal cells. This destroys their immune system.

Acquired Immune Evasion by Pathogens

Pathogens evolve to get through an immune system. This can be seen in the disorders of the immune system.

Disorders of the Immune System

Allergies
Allergies are exaggerated response to allergens, a certain type of antigen. Antibodies of the class IgE are involved most often with allergies. When allergens enter the body, they attach to the antigen-binding sites of IgE on the surface of mast cells and cause the mast cell to release histamine and other inflammatory agents from granules (vesicles). When allergens attach to the antigen-binding sites and cause mast cells to release histamine and other inflammatory agents, this process is known as degranulation. Histamine causes dilation and also causes small blood vessels to increase permeability. Sneezing, runny nose, tearing eyes, and smooth muscle contractions that causes difficulty in breathing are typical symptoms of vascular changes caused by allergies. Drugs called antihistamines can lessen allergy symptoms by blocking histamine receptors. Exposure to an allergen can sometimes lead to anaphylactic shock, a whole body, life-threatening reaction that can occur with seconds. Anaphylactic shock happens when a widespread mast cell degranulation causes abrupt dilation of peripheral blood vessels, which then causes blood pressure to drop. Death can occur in minutes. People with severe hypersensitivities often carry around epinephrine, which counteracts anaphylactic shock.

Autoimmune diseases
An autoimmune disease happens when the immune system turns against particular parts of the body. In systemic lupus erythematosus, also known as lupus, the immune system generates antibodies against histones and DNA released by the normal breakdown of body cells. Skin rashes, fever, arthritis, and kidney dysfunction are results of the self-reactive antibodies generated by lupus. Another example of an autoimmune disease is rheumatoid arthritis, which leads to damage and painful inflammation in the cartilage and bones of joints. Gender, genetics, and environment are all factors to developing autoimmune diseases. For example, women are two to three times more likely to suffer from rheumatoid arthritis and nine times more likely to develop lupus.
Rheumatoid Arthritis
Rheumatoid Arthritis



Exertion, stress, and the immune system
Exertion and stress can also contribute to the function of your immune system. For example, you can be susceptible to the common cold and other upper respiratory tract infections. Moderate exercise can make it less likely to reduce risk of these infections and improve function of the immune system, but overexercise can lead to more frequent infections and severe symptoms. Studies have also showed that stress can disrupt the function of the immune system.

Immunodeficiency diseases
Immunodeficiency is a disorder where the ability of the immune system to protect against pathogens is defective or absent. A genetic or developmental defect in the immune system is an inborn immunodeficiency. An exposure to chemicals or biological agents later in life result in acquired immunodeficiency.

Antigenetic Variation
A pathogen can alter how it appears to the immune system to escape the body's defenses. The pathogen can get past the immunological memory because the immunological memory keeps a record of the foreign epitopes. The pathogen can reinfect or remain in a host if in it stops expressing the epitopes that the immunological memory kept a record of. This a major reason why the influenza, or the "flu", remains a problem to public health. The human influenza virus mutates after it replicates and infects one human host after another.

Latency
Some viruses remain in a host without activating immune defenses and stay in a largely inactive sate called latency. The viral genome stays in the nuclei of infected cells, either as a separate DNA molecule or as a copy in the host genome. One example of latency is herpes. Stimuli such as fever, emotional stress, or menstruation reactivate herpes and causes it to reappear.

HIV
HIV stands for the human immunodeficiency virus, which is the pathogen that causes AIDS. HIV both escapes and attacks the acquired immune response. HIV infects helper T cells with high efficiency once it is introduced to the body. HIV invariably escapes even though the body responds to it with an aggressive immune response. HIV persists in antigenetic variation. An untreated HIV infection not only avoids the acquired immunity, but will also abolish it in time. Even now, HIV cannot be be cured, but certain drugs can slow down HIV reproduction.


Key Terms & Definitions


Pathogens: infectious agents that cause disease
Innate Immunity: defensive responses that are active immediately upon infection and are the same whether or not the pathogen has been encountered previously
Lysozyme: an enzyme that digests microbial cell walls
Phagocytosis: the ingestion and digestion of bacteria and other foreign substances
TLR (Toll-like receptor): receptors on cells that recognize fragments of molecules characteristic of a set of pathogens
Neutrophils: Most abundant type of white blood cell. Destroys foreign invaders.
Macrophages: A phagocytic cell present in many tissues that functions in innate immunity by destroying microbes and in acquired immunity as an antigen-presenting cell
Eosinophils: A type of white blood cell with low phagocytic activity that is thought to play a role in defense against parasitic worms by releasing enzymes toxic to these invaders
Dendritic Cells: An antigen-presenting cell, located mainly in lymphatic tissues and skin, that is particularly efficient in presenting antigens to helper T cells, thereby initiating a primary immune response
Inteferon: A protein that has antiviral or immune regulatory functions. A and B help nearby cells resist viral infection. Interferon Y helps activate macrophages
Complement System: A group of about 30 blood proteins that ma amplify the inflammatory response, enhance phagocytosis, or directly lyse extracellular pathogens
Inflammatory Response: An innate immune defense triggered by physical injury or infection of tissue involving the release of substances that promote swelling, enhance the infiltration of white blood cells, and aid in tissue repair and destruction of invading pathogens
Histamine: A substance released by mast cells that causes blood vessels to dilate and become more permeable in inflammatory and allergic responses
Mast Cells: A vertebrate body cell that produces histamine and other molecules that trigger inflammation in response to infection and in allergic reactions
Natural Killer (NK) Cells: A type of white blood cell that can kill tumor cells and virus-infected cells as part of innate immunity
Lymphocytes: A type of white blood cell that mediates acquired immunity. The two main classes are B cells and T cells
Thymus: A small organ in the thoracic cavity of vertebrates where maturation of T cells is completed
T Cells: The class of lymphocytes that mature in the thymus and that includes both effector cells for the cell-mediated immune response and helper cells required for both branches of adaptive immunity
B Cells: The lymphocytes that complete their development in the bone marrow and become effector cells for the humoral immune response
Cytokines: Any group of proteins secreted by a number of cell types, including macrophages and helper T cells, that regulate the function of lymphocytes and other cells of the immune system
Antigen: A macromolecule that elicits an immune response by binding to receptors of B cells or T cells
Antigen Receptors: The general term for a surface protein, located on B cells and T cells that binds to antigens, initiating acquired immune responses. The antigen receptors on B cells are called B cell receptors, and the antigen receptors on T cells are called T cell receptors
Antibody/Immunoglobulin (Ig): A protein secreted by plasma cells that binds to a particular antigen; also called immunoglobulin. All antibody molecules have the same Y-shaped structure and in their monomer form consist of two identical heavy chains and two identical light chains
Epitope: A small, accessible region of an antigen to which an antigen receptor or antibody binds; also called an antigenic determinant
B Cell Receptor: The antigen receptor on B cells
Heavy Chains: One of the two types of polypeptide chains that make up an antibody molecule and B cell receptor; consists of a variable region which contributes to the antigen-binding site, and a constant region
Light Chains: One of the two types of polypeptide chains that make up an antibody molecule and B cell receptor
T Cell Receptor: The antigen receptor on T cells
Major Histocompatibility Complex (MHC): A family of gens that encode a large set of cell-surface proteins that function in antigen presentation
Antigen Presentation: The process by which an MCH molecule binds to a fragment of an intracellular protein antigen and carries it to the cell surface, where it is displayed and can be recognized by a T cell
Class I MHC Molecules: A type of MHC molecule found on the surface of nearly all nucleated cells and that functions in identification of infected cells by cytotoxic T cells
Cytotoxic T Cells: A type of lymphocyte that, when activated, kills infected cells as well as certain cancer cells and transplanted cells
Class II MHC Molecules: A type of MHC molecule restricted t o a few specialized immune cell types (dendritic cells, macrophages, and B cells) that serve as antigen-presenting cells
Antigen-presenting Cells: A cell that upon ingesting pathogens or internalizing pathogen proteins generates peptide fragments that are bound by class II MHC molecules and subsequently displayed on the cell surface to T cells. Macrophages, dendritic cells, and B cells are the primary antigen-presenting cells
Helper T Cells: A type of T cell that, when activated, secretes cytokines that promote the response of B cells (humoral response) and cytotoxic T cells (cell0mediated response) to antigens
Effector Cells: Muscle cell or gland cell that performs the body’s response to stimuli as directed by signals from the brain or other processing center of the nervous system. A lymphocyte that has undergone clonal selection and is capable of mediating an acquired immune response
Memory Cells: One of a clone of long-lived lymphocytes, formed during the primary immune response, that remains in a lymphoid organ until activated by exposure to the same antigen that triggered its formation
Clonal Selection: The process by which an antigen selectively binds to and activates only those lymphocytes bearing receptors specific for the antigen. The selected lymphocytes proliferate and differentiate into a clone of effector cells and a clone of memory cells specific for the stimulating antigen.
Primary Immune Response: The initial acquired immune response to an antigen, which appears after a lag of about 10 to 17 days
Plasma Cells: The antibody-secreting effector cell of humoral immunity; arises from antigen-stimulated B cells
Secondary Immune Response: The acquired immune response elicited on second or subsequent exposures to a particular antigen. The secondary immune response is more rapid, of greater magnitude, and of longer duration than the primary immune response
Humoral Immune Response: The branch of acquired immunity that involves the activation of B cells and that leads to the production of antibodies, which defend against bacteria and viruses in body fluids
Cell-Mediated Immune Response: The branch of acquired immunity that involves the activation of cytotoxic T cells, which defend against infected cells
CD4: A surface protein, present on most cytotoxic T cells, that binds to class II MHC molecules, enhancing the interaction between the T cell and an antigen-presenting cell
CD8: A surface protein, present on most helper T cells, that binds to class I MHC molecules, enhancing the interaction between the T cell and a target cell
Monoclonal Antibodies: Any of a preparation of antibodies that have been produced by a single clone of cultured cells and thus are all specific for the same epitope
Active Immunity: Long-lasting immunity conferred by the action of B cells and T cells and the resulting B and T memory cells specific for a pathogen. Active immunity can develop as a result of natural infection or immunization
Passive Immunity: Short-term immunity conferred by the transfer of antibodies, as occurs in the transfer of maternal antibodies to a fetus or nursing infant
Immunization: The process of generating a state of immunity by artificial means. In active immunization, also called vaccination, an inactive or weakened form of a pathogen is administered, inducing B and T cell responses and immunological memory. In passive immunization, antibodies specific for a particular microbe are administered, conferring immediate but temporary protection
Vaccination: *active immunization
Allergens: The exaggerated responses to certain antigens
Autoimmune Disease: An immunological disorder in which the immune system turns against self
Immunodeficiency: A disorder in which the ability of an immune system to protect against pathogens is defective or absent
Acquired Immunodeficiency Syndrome (AIDS): Caused by the pathogen HIV. Infects helper T cells with high efficiency. The HIV virus is highly adapted due to a mutation rate.