Immune System Notes

Immunity

• Immunity is provided by the coordinated activities of T cells and B cells in response to antigens.
• T cells are responsible for cell-mediated immunity, defending against abnormal cells and pathogens inside cells.
• B cells are responsible for humoral immunity, defending against antigens and pathogens in body fluids.

Types of Immunity

• Innate immunity is present at birth and has no relationship to previous exposure to the antigen.
• Acquired immunity is not present at birth and depends on exposure to an antigen. There are two types:
  • Active immunity
  • Passive immunity

Active Immunity

• The body makes its own antibodies in response to an antigen exposure.
  • Naturally acquired active immunity begins after birth and is continually enhanced as one ages and encounters new antigens or pathogens.
  • Induced active immunity involves artificially administered antigens under controlled conditions to produce antibodies that will prevent sickness after future infection (vaccine).

Passive Immunity

• Produced by the transfer of antibodies from another source.
  • Naturally acquired passive immunity occurs when a mother’s antibodies protect her baby by crossing the placenta or through breast milk.
  • Induced passive immunity involves administering antibodies to fight infection or disease (e.g., antibodies against the rabies virus or snake venom antidote).

Properties of Immunity

• Specificity: A specific lymphocyte will be activated by a specific antigen, producing a defense that targets that particular antigen only.
• Versatility: The immune system must be ready to confront any antigen at any time due to exposure to tens of thousands of antigens in a lifetime.
• Memory: After an infection, the immune system produces cells that attack immediately and others that remain inactive unless exposed to the same antigen in the future. This memory leads to a faster, stronger, and longer-lasting attack upon re-exposure.
• Tolerance: The immune system ignores antigens on the body's own cells and tissues due to chronic exposure (e.g., normal bacterial flora).

T Cells

• Types of T cells:
  • Cytotoxic T cells: Responsible for cell-mediated immunity. They enter peripheral tissues and directly attack antigens physically and chemically.
  • Helper T cells: Stimulate the production of other T cells and B cells when activated by an antigen.
  • Suppressor T cells: Inhibit T cell and B cell activities and moderate the immune response.

Antigen Presentation

• T cells recognize antigens by attaching to glycoproteins called MHC proteins in the plasma membranes (glycocalyx) of body cells.
• MHC proteins are genetically determined and found on regions of DNA called the major histocompatibility complex (MHC).
• There are two major classes of MHC proteins.

MHC Proteins

• Class I:
  • Located in the plasma membranes of all nucleated cells.
  • Continuously formed by the ER and Golgi apparatus.
  • Pick up small peptides in the surrounding cytoplasm.
  • If a cell is infected by a virus or bacterium, these proteins pick up “non-self” peptides from the invading organism in the cytoplasm, then broadcast the infection when sent to the plasma membrane. This activates surrounding T cells and results in the destruction of the infected body cell.
• Class II:
  • Found in membranes of only antigen-presenting cells (APCs) and lymphocytes.
  • APCs activate T cell defenses against foreign cells and proteins (e.g., monocytes, macrophages, Kupffer liver cells, microglia, Langerhans cells).
  • Engulfed pathogens or antigens are digested by the lysosomes, where the antigen fragments are bound to the MHC proteins newly formed by the ER and Golgi and sent to the plasma membrane activating surrounding T cells to destroy other similar pathogens in the area.

Antigen Recognition

• Occurs when the T cell detects non-self or antigen peptides on either a class I or class II MHC protein.
• Depends on the structure of T cell plasma membrane proteins called CD markers:
  • CD8 markers are found on cytotoxic T cells and suppressor T cells and respond to antigens presented by class I MHC proteins.
  • CD4 markers are found on helper T cells and respond to antigens presented by class II MHC proteins.

Activation of CD8 T cells

• When cytotoxic T cells encounter antigenic class I MHC proteins on infected body cells, they immediately destroy the infected cell by:
  • Releasing perforins, granzymes, or granulysins.
  • Secreting a poison called lymphotoxin.
  • Activating genes in the target cell’s nucleus that causes apoptosis.

Activation of CD8 T cells

• Suppressor T cells inhibit the response of other T cells and B cells by secreting suppression factors (inhibitory cytokines of unknown structure).

Activation of CD4 T cells

• Upon activation, CD4 T cells undergo a series of divisions that produce active helper T cells.
• The helper T cells secrete a variety of cytokines that:
  • Stimulate T cell divisions that produce memory T cells and accelerate the maturation of cytotoxic T cells.
  • Attract macrophages to the affected area and enhance their phagocytic activity.
  • Attract and stimulate NK cells.
  • Promote the activation of B cells and antibody production.

B Cells Sensitization and Activation

• B cells are responsible for launching a chemical attack on antigens by producing antibodies.
• This process begins with sensitization, when antigens attach to B cells and are brought into the cell via endocytosis.
• The antigen peptides are then presented on the membrane by class II MHC proteins.
• When the sensitized B cell encounters a helper T cell, the helper T cell binds to the class II MHC protein and starts to secrete cytokines that promote B cell activation.

B Cells Sensitization and Activation

• The activated B cell then divides several times, producing daughter cells that differentiate into plasma cells and memory B cells.
• The plasma cells begin synthesizing and secreting mass quantities of antibodies into the interstitial fluid (100 million antibody molecules/hr). These antibodies then search for the same antigen that was presented on the class II MHC protein.
• Memory B cells remain in reserve to deal with subsequent infections by the same antigen. When activated, they differentiate into plasma cells and secrete antibodies.

Antibody Structure

• Each antibody molecule consists of two parallel pairs of polypeptide chains: one pair of heavy chains and one pair of light chains.
• Each chain contains constant segments and variable segments.
• The constant segments form the base of the molecule and determine the way the antibody is secreted and distributed in the body.
• The variable segments contain the antigen-binding sites and bind to the antigen, forming the antigen-antibody complex.

Classes of Antibodies

• The classes are determined by the constant segments of the light and heavy chains. There are five types of antibodies, also known as immunoglobulins:
  • IgG: Largest, most diverse, and accounts for 80% of all antibodies. Responsible for resistance against many viruses, bacteria, and bacterial toxins. Able to cross the placenta and provides passive immunity to the fetus. Anti-Rh factors is an example of an IgG.
  • IgE: Attached to basophils and mast cells. When bound to an antigen, the IgE causes the cell to release histamine to accelerate the inflammatory response in the area. Important in the allergic response.
  • IgD: Attached to B cells. Binding to an antigen causes activation of the B cell.
  • IgM: The first class of antibody secreted after an antigen arrives. Attacks bacteria that are insensitive to IgG. Includes anti-A and anti-B antibodies in blood serum.
  • IgA: Found in mucus, tears, saliva, breast milk, and semen. They attack antigens before they gain access to internal tissues.

Actions of Antibodies

• Neutralization: The binding of antibodies to binding sites of a body cell, therefore preventing the binding of viruses or bacterial toxins at these sites.
• Precipitation and agglutination: Antibodies can bind to multiple antigens forming “bridges” and forming large, insoluble immune complexes.
• Attraction of phagocytes: Antigens covered with antibodies attract eosinophils, neutrophils, and macrophages to destroy it.
• Opsonization: This is the increase in the effectiveness of phagocytosis due to the coating of antibodies on an antigen, which decreases the “slipperiness” of the bacterial plasma membrane.
• Stimulation of inflammation: Antibodies may promote local inflammation (IgE).
• Prevention of bacterial and viral adhesion: Antibodies in saliva, mucus, and sweat coat epithelia, which makes it more difficult for pathogens to penetrate body surfaces.

The Primary Response

• This is the initial response to an antigen exposure.
• Because sensitization, activation, and differentiation of B cells need to take place, this response takes time.
• IgMs are first to appear in the bloodstream but are eventually replaced by the more effective IgGs.
• The antibody titer (level of antibody activity) in the plasma does not peak until one to two weeks after initial exposure. Once the individual is no longer exposed to the antigen, antibody levels start to decline due to the short life span of plasma cells and the action of suppressor T cells.

The Secondary Response

• If the body is subsequently exposed to the same antigen, the memory B cells are activated, divide, differentiate into plasma cells, and secrete mass amounts of antibodies.
• Antibody titers peak sooner and reach much higher levels than in the primary response.
• The secondary response may appear up to 20 years post-primary response due to the long life span of memory cells.

Development of Immunity

• Cell-mediated immunity can be demonstrated in the 3rd month of fetal development, humoral immunity one month later.
• The first cells that leave the fetal thymus migrate to the skin and membranes lining the mouth, GI tract, uterus, and vagina and become antigen-presenting cells, such as Langerhans cells.
• Later in development, T cells leave the thymus and populate the lymphoid organs throughout the body.
• The fetal liver and bone marrow after 4 months of development begin to form B cells.
• The fetus mostly relies on passive immunity by receiving the maternal IgGs; however, if exposed to specific antigens, it may produce its own IgM antibodies.
• In the next two months after birth, the IgG concentration in the baby dramatically decreases, so the baby relies on receiving maternal IgA antibodies via breast milk.
• During these two months, even though the baby is receiving passive immunity as IgAs, it is vulnerable to infection by bacteria and viruses that were previously overcome by the maternal antibodies.
• The baby now must produce its own IgGs in response to infections, environmental antigens, and vaccinations. B cells and T cells also increase in number.
• The child will encounter a “new” antigen every 6 weeks from birth to age 12.

Skin Tests

• Used to help determine whether an individual has previously been exposed to an antigen.
• Small quantities of antigen are placed on the skin and pricked with a pin (usually on the anterior forearm).
• If hypersensitivity to the allergen is positive, the region will become inflamed immediately or over the next 2-4 days.

Hormones of the Immune System

• Cytokines are chemical mediators of the immune response:
  • Interleukins: Promote inflammation, fever, growth and activation of T cells, mast cells, blood cells and NK cells, antibody production by plasma cells, and angiogenesis.
  • Interferons: Activate cells to prevent viral entry, inhibit viral replication, stimulates NK cells and macrophages.
  • Tumor necrosis factors: Kills tumor cells, slows tumor growth, stimulates T cells and eosinophils, inhibits parasites and viruses.
  • Phagocyte activating chemicals: Transforms monocytes into macrophages, makes macrophages more aggressive and active.
  • Colony-stimulating factors: Stimulates RBC and WBC production.

Immune Disorders

• If there is a malfunction of our immune system, mild irritations to death may result. The following are some examples of this:
  • Allergies
  • Autoimmune diseases
  • Immunodeficiency diseases
  • AIDS

Allergies

• Allergies are abnormal sensitivities to antigens in the environment. Antigens that cause allergies are called allergens. Common allergens include protein molecules on pollen, feces of dust mites, and feces of mites in animal dander (shed skin cells).
• Symptoms of an allergy occur in two stages:
  • Sensitization: The allergen enters the body and binds with the B cells. The B cells proliferate via clonal selection and secrete large amounts of antibodies to the allergen. Some of the antibodies also attach to mast cells, which are normal body cells that produce histamines to trigger the inflammatory response.
  • The second stage is where allergy symptoms begin, which is when the allergen reenters the body and binds to the antibodies on the mast cells. When this occurs, the mast cells release their histamines, which will cause sneezing, coughing, and itching. Because allergens usually enter the body in the nose or throat, the symptoms are often most prominent there.
• Anaphylactic shock is a very dangerous and life-threatening allergic reaction. Exposure to certain allergens for certain people causes a sudden release of histamines that causes the abrupt dilation of blood vessels, an extreme drop in blood pressure (shock), and the closing of the airways in the lungs. This is common in people who have allergies to peanuts, bee stings, or shellfish. It is counteracted with injections of the hormone epinephrine.

Autoimmune Disease

• One of the characteristics of our immune system is the ability to distinguish self from non-self; in other words, it is supposed to only attack foreign cells or particles and protect the body cells (due to the glycocalyx).
• However, with autoimmune diseases, the immune system attacks its own body cells. The cause of autoimmune diseases is not known; however, it is suspected that it may be due to a viral or bacterial infection, trauma, or exposure to a toxin. Examples are lupus (SLE), rheumatoid arthritis, insulin-dependent diabetes, and multiple sclerosis.

Immunodeficiency Disease

• People with these diseases lack one or more components of the immune system and as a result are susceptible to infections that would ordinarily not cause a problem.
• Severe combined immunodeficiency (SCID) causes a marked decrease of B and T cells, causing that person to have life-threatening symptoms to a little scratch (the boy in the bubble).
• Immunodeficiency may not only be genetic but also be due to leukemia, radiation and chemotherapies, and HIV infection.

AIDS

• AIDS has killed over 25M people worldwide since 1981, and more than 40M are infected today. The vast majority of infections and deaths due to AIDS are in non-industrialized nations of Asia (esp. India) and Saharan Africa.
• AIDS is caused by HIV, which attacks helper T cells, which are not only responsible for cell-mediated immune response but also humoral immune response because the helper T cells “help” to activate the antibody production by the B cells.
• The origin of HIV is unknown. Clinical symptoms may not appear until 5-10 years post-infection. It is hypothesized that it was transferred to humans as a result of hunting or the butchery of primates.

Stress and the Immune Response

• One of the normal effects of interleukin-1 secretion is the stimulation of ACTH production by the adenohypophysis, which in turn leads to the secretion of glucocorticoids (cortisol).
• The anti-inflammatory effects of glucocorticoids in a chronic stress situation can inhibit the immune response and lower resistance to disease by inhibiting the inflammatory response, activity of phagocytes, and lymphocytes.