Lymphatic and Immune Systems

The Lymphatic and Immune Systems

• The immune system protects against viruses, bacteria, fungi, parasites, and environmental toxins

Evolution of Immune Systems

• Innate immunity quickly identifies microbial invaders with no increased response after repeated exposure
• Adaptive immunity produces receptors on white blood cells to bind foreign antigens
• Adaptive immunity stimulates lymphocytes, resulting in an increased response to specific antigens and immunological memory

The Lymphatic System

• The lymphatic system consists of lymphatic vessels and organs
• The core functions of the lymphatic system are
  • Returning excess fluid to the bloodstream
  • Transporting fats to the bloodstream via lacteals
  • Producing, maintaining, and distributing lymphocytes
• Lymphocytes combat infection and disease by responding to invading pathogens, abnormal body cells, and foreign proteins like toxins

Lymphatic Vessels

• Lymphatic vessels are a one-way system that starts with lymphatic capillaries
• These are vessels found throughout the body that take up excess tissue fluid, also known as interstitial fluid
• Lymph is the fluid located within lymphatic capillaries
• Lymph flows from capillaries to larger vessels, eventually reaching a lymphatic duct that returns lymph to the subclavian vein
• One-way valves prevent backflow

Lymphoid Organs

• Lymphoid organs include:
  • Red Bone Marrow
  • Thymus Gland
  • Spleen
  • Lymph Nodes
  • Tonsils
  • Peyer Patches
  • Vermiform Appendix
• All blood cells originate in the red bone marrow
• B cells mature in the red bone marrow
• T cells mature in the thymus gland, located between the trachea and sternum
• T cells migrate to the thymus from red bone marrow to mature
• T cells learn to recognize self and foreign molecule combinations
• Mature T cells encounter foreign molecules or cells in the bloodstream which causes them to proliferate and become activated

Lymph Nodes

• Lymph nodes capsules contain a cortex and medulla
• Macrophages concentrated in medulla cleanse lymph
• Macrophages present debris or pathogens to T cells in lymph nodes
• B and T cells in lymph nodes destroy pathogens
• Lymph nodes are named for their location

Additional Lymphoid Organs

• The spleen is located in the upper left side of the abdominal cavity just posterior to the stomach
• Macrophages remove old and defective blood cells in the Spleen
• The red pulp filters and cleanses blood in the Spleen
• Tonsils consist of patches of lymphatic tissue
• Tonsils are located in the pharynx
• Tonsils prevent entry of pathogens through the nose and mouth
• Peyer patches are located in the intestinal wall
• The vermiform appendix is attached to the cecum

Innate Immune Defenses

• Immunity is the capability of removing or killing foreign substances, pathogens, and cancer cells

• Innate immune defenses don't distinguish between types of threats

• They are fully functional without previous exposure as they activate immediately or shortly after infection

• Types of defenses:

  • Physical and chemical barriers
  • Inflammatory response
  • Phagocytes and natural killer cells
  • Protective proteins (complement and interferons)

Physical and Chemical Barriers

• Skin and mucous membranes line the respiratory, digestive, and urinary tracts
• Cilia in the respiratory tract sweep mucus and particles into the throat
• Antimicrobial molecules are in secretions of oil glands, mucous membranes, and the stomach
• Mucus contains lysozyme, an enzyme that lyses bacteria
• The acidic pH of the stomach kills microbes

Inflammatory Response

• It is a localized tissue response to injury
• Damaged and mast cells release histamine which causes capillaries to dilate and become more permeable
• Enlarged capillaries cause skin to redden
• Swelling stimulates free nerve endings, causing pain
• Neutrophils and monocytes migrate to the injury site
  • Monocytes differentiate into macrophages
  • Macrophages release colony-stimulating factors, stimulating the production and release of white blood cells
  • Neutrophils, dendritic cells (antigen presenting cells), and macrophages phagocytize pathogens
• Acute phase proteins, released by the liver in response to inflammatory mediators, make it easier for phagocytes to engulf invaders

Fever

• Fever is the maintenance of an elevated body temperature
• A fever may be beneficial, indicating a problem
• Some bacteria or viruses may not survive as well at higher temperatures
• Some immune mechanisms work better at higher body temperatures

Phagocytes and Natural Killer (NK) Cells

• Neutrophils leave the bloodstream to phagocytize bacteria
• They also release antimicrobial peptides and bacteria-digesting enzymes & generate free radicals to kill engulfed bacteria
• Eosinophils are phagocytic
• They also attack parasites too large for phagocytosis
• Macrophages and dendritic cells engulf and destroy pathogens
• Macrophages and dendritic cells stimulate T cells in lymph nodes, initiating adaptive immune responses
• Natural killer (NK) cells are large, granular lymphocytes that kill virus-infected and cancer cells by cell-to-cell contact
• Infected cells lacking a self molecule (MHC-1) may be recognized and killed
• NK cells numbers do not increase after stimulation, unlike lymphocytes

Complement

• Complement functions as a collection of plasma proteins that complement certain immune responses
• It's activated by pathogens and destroys them in three ways:
  • Enhancing inflammation
  • Binding to pathogens coated with antibodies to ensure phagocytosis
  • Forms a membrane attack complex that produces holes in the surface of some bacteria and viruses, leading to cellular bursting by fluid entry

Interferons

• Interferons are cytokines that affect the behavior of other cells
• They are produced by virus-infected cells that bind to receptors of non-infected cells
• They cause them to produce substances that interfere with viral replication
• Interferons are used to treat certain cancers and viral infections like hepatitis C

Adaptive Immune Defenses

• Adaptive immune defenses are known as acquired immunity
• Adaptive immune defenses are not inborn
• Adaptive immune defenses take 5-7 days to become activated
• Adaptive immune defenses can last for years
• Adaptive immune defenses involve three steps
  • Recognition of an antigen
  • Response to the antigen
  • Memory of the antigen
• An antigen is any substance that stimulates the immune system to react

Lymphocytes in Adaptive Immunity

• Lymphocytes recognize and bind to specific antigens
• Lymphocytes have antigen receptors on their plasma membrane
• The receptor protein's shape allows it to combine with a specific antigen
• Pathogens, cancer cells, and transplanted tissues/organs bear antigens recognized as "nonself"

B and T Cells

• Adaptive immunity is primarily the result of B and T cells
• B-cell receptors bind directly to antigens
• B cells give rise to plasma cells that produce and secrete antibodies
• T-cell receptors bind to antigens presented by antigen-presenting cells
• Helper T cells regulate specific immunity
• Cytotoxic T cells kill virus-infected cells and cancer cells

Clonal Selection Theory

• The antigen selects which lymphocyte will undergo clonal expansion and produce more lymphocytes
• Most cloned lymphocytes become plasma cells, which produce specific antibodies
• Some become memory B cells
• Upon subsequent exposure, memory B cells quickly divide and give rise to more lymphocytes capable of producing antibodies

Antibodies

• Antibodies consist of two heavy and two light polypeptide chains in a Y shape
• They have variable and constant regions
• Antibodies neutralize pathogens by coating their antigens this prevents them from binding to receptors on cells, and attracts white blood cells that move in for the kill
• Immune complexes may be engulfed by neutrophils or macrophages or may activate the complement system
• The class of an antibody is determined by the structure of its constant region
  • IgG is the main type of antibody in circulation
  • IgA is the main type secreted in milk, tears, and saliva
  • IgM is the first antibody produced and indicates infection
  • IgE is bound to receptors on eosinophils and mast cells in tissues

T Cells and Cell-Mediated Immunity

• T-cell receptor (TCR) recognizes antigens displayed by antigen-presenting cells (APCs)

• The antigen is first linked to a major histocompatibility complex (MHC) protein in the APC’s plasma membrane

• After the TCR binds to the antigen, the T cell undergoes clonal expansion

• Types of T cells in Adaptive Immunity

  • Cytotoxic T Cells
  • Helper T Cells
  • Memory T cells

• The majority of T cells undergo apoptosis after the immune response has been successful, and Some T cells remain as memory T cells

• Key Functions of Cytotoxic T Cells

  • Destroy antigen-bearing cells
  • Storage vacuoles containing perforins and granzymes

• Helpful T Cells activate other T cells and B cells Regulate immunity by secreting cytokines (signaling molecules)

• Memory T cells persist after a successful immune response

• Memory T cells provide protection if the same antigen is encountered again

HIV

• The primary host for HIV is a helper T cell
• The host produces viruses that destroy more helper T cells
• At first, an individual can stay ahead of the virus by producing enough of said T cells
• The HIV count rises and the helper T-cell count drops
• Affected patients become vulnerable to opportunistic infections, which becomes characteristic during the AIDS diagnosis
• Stage A: No symptoms or very mild symptoms
• Stage B: opportunistic infections, such as candidiasis, shingles, and diarrhea
• Stage C: Characterized by more severe opportunistic infections and clinically described as AIDS

Cytokines

• Cytokines are a soluble protein that acts as a signaling molecule
• Cytokines (interleukins) are produced by white blood cells and stimulate other white blood cells
• Interleukins might awaken the immune system and lead to the destruction of the cancer
• IL-2 is being used to treat some forms of melanoma and kidney cancer
• Tumor necrosis factor (TNF) is a cytokine produced by macrophages
• TNF promotes the inflammatory response and causes the death of cancer cells
• Anti-TNF monoclonal antibodies are being developed as potential treatments for inflammatory diseases

Active vs Passive Immunity

• Active Immunity occurs when an individual produces their own immune response
• Active immunity involves injecting a vaccine, which are is a substance that contains an antigen to which the immune system responds
• Active immunity is dependent on memory B and T cells
• Passive Immunity is occurs when an individual receives another person’s antibodies in order to combat a disease
• Example: Newborns passing down antiobodies from the mother’s blood
• Passive immunity lasts for a short period of time
• Can be used to prevent illness in a patient that has recently been exposed to infectious agents or toxins, like
  • Rabies
  • Tetanus
  • Botulism
  • Snake Bites
• Cells of the immune system may be transferred to a patient that is receiving a bone marrow transplant

Immune System Disorders and Hypersensitivity Reactions

• Immunodeficiencies result in increased susceptibility to infection
• Primary immunodeficiencies are genetic
• Severe Combined Immune Deficiency (SCID) occurs when neither T nor B cells function
• Untreated SCID infants die by 3 months when the antibodies obtained from the mother have been degraded
• Treatment can include a bone marrow transplant
• X-Linked Agammaglobulinemia (XLA) is caused by a mutation in a gene on the X chromosome that's necessary to develop B cells properly

Allergies

• Allergies are hypersensitivities to substances that ordinarily would not harm the body
• Immediate vs Delayed Allergic Responses
  • Immediate = IgE antibodies, release of histamine, causes asthma or anaphylactic shock
  • Delayed = regulated by cytokines, involves memory T cells, causes contact dermititis

Autoimmune Disease

• Immune system attacks body's own cells
• There appears to be a genetic tendency for developing autoimmune diseases
• Immune system cant distinguish between self and nonself antigens
• Examples of autoimmune diseases:
  • Rheumatoid arthritis (inflammation in synovial joints)
  • Myasthenia gravis
  • Systemic lupus erythematosus (lupus)

Transplants

• Antibodies and cytotoxic T cells cause destruction of transplanted foreign tissues
• System is correcting distinguishing between self and nonself antigens (transplant rejection)
• Xenotransplantation is the animal to human tissue transplant
• This action is considered a potential way to alleviate human donor organ shortage problems
• Animal organs can be engineered by removing MHC antigens
• Tissue engineering may eliminate rejection issues by producing human organs from stem cells