Guyton 35 - M.92 - Resistance to Body Infection: Innate Immunity

Resistance to Body Infection

• The human body can resist almost all damaging organisms or toxins due to a capability called immunity.
• Innate immunity is a general defense not directed at specific disease organisms.
• Acquired/adaptive immunity is powerful, specific and develops against individual infectious agents after initial exposure.
• Weeks or months are required for adaptive immunity to develop.

Aspects of Innate Immunity

• Bacteria and invaders are phagocytized by white blood cells and tissue macrophages.
• Stomach acid secretions and digestive enzymes destroy swallowed organisms,
• The skin resists organism invasion.
• Chemicals and cells in the blood attach to and destroy foreign organisms or toxins.
• Lysozyme dissolves bacteria.
• Basic polypeptides inactivate gram-positive bacteria.
• The complement complex destroys bacteria.
• Natural killer lymphocytes destroy foreign cells, tumor cells, and infected cells.

Examples of Innate Immunity

• Humans resist some paralytic viral infections of animals, hog cholera, cattle plague, and distemper.
• Some animals resist or are immune to human diseases.

Adaptive Immunity

• Humans can develop specific immunity against lethal bacteria, viruses, toxins, and foreign tissues.
• Adaptive immunity forms antibodies and/or activated lymphocytes that attack and destroy the invading organism or toxin.
• Immunization protects against disease and toxins, toxins such as botulinum or tetanus toxins can be protected against in doses 100,000x the lethal amount without.

Types of Acquired Immunity

• Humoral immunity/B-cell immunity: Body develops antibodies (globulin molecules).
• Cell-mediated immunity/T-cell immunity: Formation of activated T lymphocytes to destroy foreign agents.
• Lymphoid tissues of the body form both antibodies and activated lymphocytes.

Types of Acquired Immunity Initiated by Antigens

• Immunity develops after invasion because the body must recognize the invasion.
• Invading organism/toxin contains specific chemical compounds (proteins or large polysaccharides) that are different from all other compounds.
• These substances are called antigens (antibody generators).
• Antigenic substances usually need a minimum molecular weight of 8000.
• Antigenicity relies on regularly recurring molecular groups called epitopes on the substance surface.

Lymphocytes

• Lymphocytes are responsible for acquired immunity.
• Those lacking lymphocytes for genetic reasons or with destroyed lymphocytes cannot develop acquired immunity.
• Lymphocytes are located in lymph nodes, spleen, submucosal areas of the gastrointestinal tract, thymus, and bone marrow.
• Lymphoid tissue intercepts invading organisms/toxins before they spread.
• Invading agents enter tissue fluids and are carried by lymph vessels to lymph nodes or other lymphoid tissue.
• Lymphoid tissue in gastrointestinal walls intercepts antigens invading from the gut.
• Lymphoid tissue of the throat and pharynx intercepts antigens entering via the upper respiratory tract.
• Lymphoid tissue in lymph nodes intercepts antigens invading the peripheral tissues of the body.
• The spleen, thymus, and bone marrow intercepts antigenic agents reaching circulating blood.

T and B Lymphocytes

• Most normal lymphoid tissue lymphocytes are divided into two major populations: T lymphocytes and B lymphocytes.
• T lymphocytes form activated lymphocytes, providing cell-mediated immunity.
• B lymphocytes form antibodies, providing humoral immunity.
• Both lymphocyte types derive from multipotent hematopoietic stem cells which form common lymphoid progenitor cells.
• These lymphocytes end up in the lymphoid tissue, further differentiated or preprocessed as follows:
• Lymphoid progenitor cells destined to form activated T lymphocytes migrate to/are preprocessed in the thymus gland, thus called T lymphocytes.
• B lymphocytes, destined to form antibodies, are preprocessed in the liver after mid-fetal life then bone marrow in late fetal life/after birth.
• B lymphocytes are named in reference to the bursa of Fabricius, location of discovery, are responsible for humoral immunity.
• Two lymphocyte systems facilitate formation of activated T lymphocytes and antibodies.

Preprocessing of T and B Lymphocytes

• Lymphocyte-committed stem cells of the embryo cannot form activated T lymphocytes or antibodies directly because they must be further differentiated in appropriate processing areas:
• T lymphocytes from the bone marrow migrate to the thymus gland, can rapidly divide and develop extreme diversity for reacting against different specific antigens, then leave.
• The thymus confirms no T lymphocytes leaving will react against proteins/antigens in the body's own tissues, otherwise lethal.
• The thymus releases T lymphocytes by mixing them with virtually all the body's own specific self-antigens, destroying/phagocytizing any T lymphocyte that reacts instead of releasing it.
• The released cells only react against outside antigens from bacteria or toxins.
• Most T lymphocyte preprocessing in the thymus occurs shortly before and a few months after birth.
• Removing the thymus beyond this period diminishes, but doesn't eliminate, the T-lymphocytic immune system.
• Liver preprocesses B lymphocytes in humans in midfetal life and bone marrow preprocesses them during late fetal and after birth.
• B lymphocytes differ from T lymphocytes because they actively secrete antibodies as reactive agents and they have greater diversity.
• After preprocessing, the B lymphocytes migrate to lymphoid tissue throughout the body to lodge near T-lymphocyte areas.
• Millions of specific types of lymphocytes are formed and lodge slightly removed from the T-lymphocyte areas.

Mechanism of Lymphocytes

• Specific antigens that come into contact with T and B lymphocytes in lymphoid tissue activate some T and B lymphocytes and become antibodies.
• The activated T cells and antibodies specifically react against the antigens that initiated their development.
• Millions of preformed B and T lymphocytes can form highly specific types of antibodies or T cells.
• Each of these lymphocytes only forms one type of antibody/one type of T cell.
• Only the specific type of antigen can activate the lymphocyte.
• Once activated by the antigen, the lymphocyte over multiplies forming tremendous numbers of duplicate lymphocytes.
• If it is a B lymphocyte, progeny will secrete the antibody and circulate throughout the body.
• If a T lymphocyte, progeny are specific sensitized T cells, released into the lymph and then circulated through all the tissue fluids and back into the lymph.
• A clone of lymphocytes are the different lymphocytes capable of forming one specific antibody or T cell.
• Lymphocytes in each clone are alike, derived from one or a few early lymphocytes.
• A few hundred and a few thousand genes code for the millions of different types of antibodies and T lymphocytes.
• The whole gene for forming each type is never present in the original stem cells from which the functional immune cells are formed, but there are hundreds of segments.
• During preprocessing the gene segments mix in random combinations, finally forming whole genes.
• Millions of cell gene types occur because there are several hundred gene segment types, as well as millions combinations.
• Gene structure codes for only one antigen specificity for each functional T or B lymphocyte.
• These mature cells then become highly specific T and B cells, populating the lymphoid tissue.
• Each clone responds to a single type of antigen/similar antigens because the B lymphocytes each have 100,000 antibody molecules on the cell surface membrane to react with one antigen type.
• When the appropriate antigen comes along, it attaches to the antibody in the cell membrane, leading to activation process.
• T lymphocytes have molecules of surface receptor proteins, called T-cell receptors, which are on the T-cell membrane and are highly specific for an activating antigen.
• Macrophages are present in the same tissue along with lymphoid tissue lymphocytes.
• Macrophages line the lymph nodes, spleen, and other lymphoid tissue sinusoids and lie in apposition to lymph node lymphocytes.
• Invading organisms are phagocytized and partially digested by the macrophages, and the antigenic products are liberated into macrophage cytosol.
• Macrophages pass antigens by cell to cell contact to the lymphocytes, leading to activation of the lymphocyte clones.
• The macrophages also secrete the activating substance interleukin-1 to promote growth and reproduction of lymphocytes.
• Some T cells formed are called T-helper cells to secrete specific substances (lymphokines) that activate the B lymphocytes and quantity of created antibodies.

Specific Attributes

• Clones of B lymphocytes remain dormant in the lymphoid tissue before exposure to a specific antigen.
• Entry of a foreign antigen causes macrophages in the lymphoid tissue to phagocytize the antigen and present it to adjacent B lymphocytes.
• Antigens are presented to T cells; activated T-helper cells contribute and activate B lymphocytes.
• The B lymphocytes immediately enlarge, transforming into lymphoblasts, then some lymphoblasts differentiate to form plasmablasts, precursors of plasma cells.
• The cytoplasm expands, and the rough endoplasmic reticulum proliferates in plasmablasts, then the plasmablasts then divide, giving a total population of 500 cells/ original plasmablast in 4 days.
• Mature plasma cells produce gamma globulin antibodies and secrete them into the lymph at an extremely rapid rate, then the antibodies will be carried to the circulating blood.
• The process continues for several days/weeks until the plasma cells are exhausted.
• A few lymphoblasts formed by activation of a clone of B lymphocytes form moderate numbers of new B lymphocytes similar to the original clone, also circulate throughout the body.
• These memory cells are dormant until activated again by a new quantity of the same antigen causing a more rapid and potent antibody response
• Primary antibody response occurs on first exposure to an antigen versus the secondary response that occurs after second exposure.
• The primary response has a 1wk delay with weak potency but the secondary response begins rapidly, forms antibodies for a longer duration.

Additional Information About Immunity

• Long-lived plasma cells provide rapid protection and reside in tissues such as the bone marrow and gut-associated lymphoid tissue and can continue producing antibodies for many years providing lifelong immunity against infectious diseases.
• High titers of smallpox-specific antibodies have been detected in vaccinated subjects from their childhood decades after, as well as virus-neutralizing antibodies shown after 90yrs to older survivors of the 1918 influenza virus pandemic.
• Antibodies are gamma globulins called immunoglobulins (Igs) with molecular weights between 160,000-970,000, composed of combinations of light and heavy polypeptide chains (two light and two heavy chains).
• A designated end of each light and heavy chain, the variable portion, is different for each specific antibody and attaches to a particular antigen and the remaining chain is the constant portion depending on biological properties.
• Antibodies are specific for a particular antigen due to the unique structural organization of amino acids in the variable portions of the chains allow for rapid and tight mirror image fit between the antibody and antigen. Bonding sites make antibody-antigen coupling quite strong with different noncovalent/covalent bonds.
• There are five classes of antibodies with different names, however IgG, IgE, and IgM are particularly important.
• IgG constitutes 75% and and is a bivalent antibody.
• IgE constitutes a little percentage but is involved in allergies.
• A large number of generated during primary response are of type IgM. They also have exceedingly effective sites however present in smaller number.
• Antibodies act to protect the body by directly attacking the invader or activating the complement system.

Direct Action and Invading Agents

• Antibodies can inactivate invading agents in these ways:
• Agglutination: Large particles with antigens are bound together.
• Precipitation: A molecular complex of soluble antigen and antibody becomes very insoluble.
• Neutralization: Antibodies cover the toxic sites of antigenic agents.
• Lysis: Potent antibodies can sometimes directly attack membranes of cellular agents to cause a rupture.
• The complement system often amplifies protection, through opsonization and phagocytosis.

Complement System and Antibody Action:

• The main function is to enhance the actions of antibodies and phagocytic cells in neutralizing and destroying pathogens, removing damaged cells from the body and promoting inflammation. Complement is a system of about 20 proteins is described used.
• Enzymes are formed for those proteins to help prevent damage caused by the invading organism or toxin and among the more important of the effects include:
• Opsonization and phagocytosis C3b that activates facilitates neutrophils and macrophages allowing them to engage in phagocytizing through complex formations, hundreds being destroyed versus original counts.
• Lysis: The membrane attack complex inserts itself into lipid bilayer of the cell membrane which is a combination of 5b6789 factors designated pores forming osmotic rupture on invader surfaces.
• Agglutination complements also shift the area creating a promoting adhesion.
• Neutralizaion virulent structures of product are often altered and cause the viruses enzyme to become non-virulent. Chemotaxis-5A initiates a number on phagocytes into being more adjacent.
• Activation fragments that activate the mast and basophils triggering fluid blood flow leakage and proteins for inactivation.

The T Lymphocyte System: Activated T Cells and Cell-Mediated Immunity

• Release of activated T cells from the Lymphoid results when upon exposure to the proper antigen, the lymphocytes Proliferate and release a number of specifically reacting T cells while the major releases include:
• Activated release into the Lymph and then distributed along capillary walls with continuous body exposure to blood again in months/years.

T antigen-Presenting Cells, and receptors

• T-Cell response are antigen sensitive for those reasons T-Cells and antibodies in defence have been assisted, T Cells are usually regulated because they are molecules bounding called MHC (in tissue) and T-Lymphocytes responding to those bounds in the major types, macrophages and denritic are present.

Different types of T Cells with their functions

• T-Cells are classified into 3 groups with the suppression of regulatory portions.
• The helper is the most well known and are usually around 75% of of the volume, because the system of the functions will need help.
• Stimulation of growth in order to form what is B-Cell and antibody.
• Activation Macrophage the macrophage, slowing and stopping in order to receive feedback to trigger activation which allows agent stimulation to act as amplifers.
• Cytotoxic which kills micro organisms and are able to be removed, the attack causes inflammation as fluid is often swelling into the space.
• Regulatory with help of the suppression cause a excessive immune reaction that can damage other structures.

The T and B role immunity to the body

• The Tolerance develops when most pre processing happens during lymphocytes or bone marrows, to the point when the body can become exposed due to self antigen however damage can also often happen and may then lead to be autoimmune.

Immunity Injection of antigens

• The Immunitzation has been used for acquired properties to prevent against diseases as some in the injection for the antigens are dead which cause many other types of anti-biotics that come.
• Immunity can be achieved when chemical treatment destroys toxins while in place chemical antigens.

Allergy and Hypersensitivity

• There is a side effect when in under certain conditions such an allergeic factor such as a delayed reaction to the allergy due to T cells that aren't caused. In the cases such has caused a immune reaction for substance in where the damage has accrued is not available.
• Atopic allergies with excesses which have the tendency with allergy that is hereditary with IGE proteins.