Lymphatic and Immune Systems

Lymphatic and Immune Systems

• lymphatic vessels and organs comprise this system
• lymphatic capillaries collect excess interstitial fluid and return it to the bloodstream
• lymphatic capillaries absorb fats from the digestive tract, transporting them to the bloodstream
• lymphoid organs aid in defending the body against disease
• the white blood cells in lymphatic vessels, organs, and the blood largely carry out this function

Lymphatic Vessels

• lymphatic vessels carry lymph
• lymphatic capillaries begin as blind-ended vessels in tissues
• as lymph moves from tissues, capillaries merge into lymphatic vessels
• lymph flows into two lymphatic ducts: the thoracic and right lymphatic ducts, before emptying into subclavian veins
• the lymphatic vessel anatomy resembles veins, including valves to prevent backflow
• the movement of lymph relies heavily on skeletal muscle contraction

Lymphatic Organs

• lymphatic organs are classified as primary or secondary
• primary lymphatic organs include red bone marrow and the thymus
• secondary lymphatic organs consist of lymph nodes, spleen, and tonsils

Primary Lymphatic Organs

• red bone marrow is where blood cells are produced
• b cells (b lymphocytes) mature in the red bone marrow
• the thymus produces thymosin, which induces the maturation of T cells (T lymphocytes)
• immature t cells migrate from the bone marrow to the thymus, where they mature

Secondary Lymphatic Organs

• the spleen filters blood and is in the upper left abdominal cavity
• connective tissue divides the spleen into white and red pulp
• macrophages in red pulp remove pathogens, debris, and worn-out red blood cells
• the spleen has a thin outer capsule, making it susceptible to rupture from trauma
• lymph nodes are located along the lymphatic vessels and filter lymph
• connective tissue forms a capsule around the lymph node and divides it into compartments
• lymph nodes contain macrophages that engulf pathogens and debris
• lymphocytes, which fight infections and cancer cells, also reside in lymph nodes
• lymph nodes are named for their location, such as axillary (armpit) and inguinal (groin) nodes
• lymphatic nodules are concentrations of lymphoid tissue without a capsule
• tonsils in the pharynx function like lymph nodes, fighting infections entering through the nose and mouth
• peyer patches, found in intestinal walls and the appendix, fight infections entering via the digestive tract

Innate Immune Defenses

• immunity is the process of killing or removing foreign substances, pathogens, and cancer cells
• defenses are classified as innate (non-specific) or adaptive
• innate defenses include physical and chemical barriers, the inflammatory response, and protective proteins
• innate defenses do not recognize specific pathogens or have memory, reacting the same way to all threats

Physical and Chemical Barriers

• physical and chemical barriers represent the first line of defense against pathogens
• physical barriers include skin and mucous membranes
• the skin's keratin content makes it tough, and exfoliation removes microbes
• mucous membranes have ciliated cells that sweep away mucus with trapped pathogens
• chemical barriers include acidic secretions of sebaceous glands that kill bacteria on the skin
• sweat, saliva, and tears contain lysozyme, an antibacterial enzyme
• the acidic pH of the stomach inhibits or kills bacteria
• normal flora (microbes in the mouth and intestine) prevent potential pathogens from colonizing
• chronic antibiotic use can increase infection susceptibility by killing normal flora

Inflammatory Response

• the inflammatory response is the second line of defense against pathogens
• neutrophils and macrophages engulf pathogens during inflammation
• the four hallmark symptoms of inflammation are redness, heat, swelling, and pain
• chemicals like histamine, released by damaged tissue and mast cells, cause capillaries to dilate and become more permeable
• excess blood flow causes the skin to redden and become warm
• increased temperature inhibits pathogen growth
• increased blood flow brings white blood cells to the affected area
• wbcs move from the bloodstream into surrounding tissue
• neutrophils arrive first, phagocytizing debris, dead cells, and bacteria
• inflammation can localize infections to prevent spreading
• large numbers of dead neutrophils can form pus, a yellow-white substance
• overwhelmed neutrophils secrete cytokines, chemicals that attract more wbcs
• monocytes that enter the area become macrophages, which are powerful phagocytes

Protective Proteins

• the complement system has several plasma proteins, designated by the letter C and a number
• complement proteins are involved in and amplify the inflammatory response
• some complement proteins bind to mast cells, triggering histamine release
• others attract phagocytes to the area
• some complement proteins form a membrane attack complex, creating holes in bacteria and causing them to burst
• interferons are chemicals produced by virus-infected cells, warning other cells
• interferons bind to noninfected cells, causing them to produce substances that interfere with viral replication

Adaptive Immune Defenses

• adaptive defenses come into play when innate defenses fail
• adaptive defenses overcome infection by targeting the disease-causing agent
• they establish a mechanism for the immune system to "remember" threats
• adaptive defenses can provide protection against cancer

How Adaptive Defenses Work

• adaptive defenses respond to antigens recognized as foreign
• fragments of bacteria, viruses, molds, and parasitic worms can all be antigens
• abnormal plasma membrane proteins produced by cancer cells can also be antigens
• the immune system distinguishes "self" cells from "nonself" pathogens
• adaptive immunity depends on the action of b cells (b lymphocytes) or t cells (t lymphocytes)
• b and t cells have specific antigen receptors (plasma membrane proteins that bind to certain antigens)
• each lymphocyte has only one type of receptor
• the receptor and antigen fit together like a lock and key
• two pathways of adaptive immunity: cell-mediated (t cells) and antibody-mediated (b cells)

B Cells and Antibody-Mediated Immunity

• B-cell receptors (bcr) are protein receptors on b cells
• An antigen binds to the bcr on only one type of b cell, which then clones itself
• This group of identical b cells is called a clone

Characteristics of B cells

• b cells are responsible for b immunity against pathogens
• b cells are produced and mature in bone marrow
• b cells directly recognize antigens and then undergo clonal selection
• Clonal expansion produces antibody-secreting plasma cells and memory b cells

B Cells Become Plasma Cells and Memory B Cells

• cytokines secreted by helper T(Th) cells stimulate b cells to clone during clonal expansion
• Plasma cells produce antibodies
• Memory cells remember the foreign antigen
• plasma cells undergo apoptosis (programmed cell death) if they are no longer needed after an infection has been overcome

Structure of an Antibody

• an antibody is a Y-shaped protein with two arms where each arm has a "heavy" (long) polypeptide chain and a "light" (short) polypeptide chain
• chains have constant regions, located at the trunk of the y with a fixed amino acid sequence
• antibodies are classified by the structure of their constant region
• variable regions form an antigen-binding site specific to a particular antigen
• the antigen combines with the antibody at the antigen-binding site like a lock and key
• antibodies consist of single y-shaped molecules, called monomers, or may be paired together in a dimer
• some are pentamers- clusters of 5 y-shaped molecules
• Neutralization is when antibodies coat viruses and toxins completely, “neutralizing” them and removing the threat

Classes of Antibodies

• IgG, IgM, IgA, IgD, and IgE are the 5 classes of circulated antibodies
• IgG constitutes the major types in the blood, and smaller numbers are found in lymph and interstitial fluid
• IgG binds to pathogens and toxins, and crosses the placenta to provide temporary immune protection to the fetus
• IgM are pentamers that appear first in the blood after an infection begins and disappear when the infection is over and activates the compliment system
• IgA are monomers or dimers containing the two y-shaped structures
• IgA is the main type of antibody found in body secretions like saliva, tears, mucus, and breast milk
• IgA binds to pathogens to prevent them from reaching the bloodstream
• IgD functions as antigen receptors on immature b cells
• IgE prevents parasitic worm infections and can cause allergic responses
• Monoclonal antibodies are all identical and produced by plasma cells derived from the same B cell
• They can be produced in a lab and are used for medical tests and treatments

T Cells and Cell-Mediated Immunity

• T-cell receptor (tcr) are unique receptors on the surface of each T cell
• Unlike B cells, T cells cannot recognize an antigen without help and it must be displayed to them by an antigen-presenting cell (apc) such as a macrophage (b cells have unique receptors)
• After phagocytizing a pathogen, apcs travel to the T cells in a lymph node or the spleen
• Apcs break the ingested pathogen apart in a lysosome
• A piece of the pathogen is then displayed in the groove of a major histocompatibility complex (mhc) protein on the cell's surface where there are two classes of mhc proteins: MHC I and MHC II
• Human mhc II proteins are called human leukocyte antigens (HLAs)
• HLAs are found on all body cells
• There are three general groups of HLAs: HLA-A, HLA-B, and HLA-DR, each with numerous protein variations
• Each person has a unique combination of HLAs (except identical twins)

Clonal Expansion

• Clonal expansion produces many copies of the activated T cell
• Clonal expansion occurs when a macrophage presents an antigen to a T cell, the specific tcr will bind to the particular antigen
• This process activates the T cell, causing it to undergo clonal expansion
• Some T cells become cytotoxic T cells, and some become helper T cells

Cytotoxic T Cell

• Cytotoxic T cells have storage vacuoles containing perforins and enzymes called granzymes
• After binding to a virus-infected or tumor cell, it releases perforins, which punch holes in the plasma membrane and form a pore
• Cytotoxic T cells then deliver granzymes into the pore, causing the cell to undergo apoptosis and thus are responsible for cell-mediated immunity

Helper T Cells

• Helper T cells secrete cytokines that enhance the response of all types of immune cells
• Helper T Cells are required for B-cell activation and HIV infects T-cells

Characteristics of T cells

• T cells are defined by cell-mediated immunity against virus-infected and cancer cells
• They are produced in bone marrow and mature in the thymus
• Cytotoxic T cells destroy nonself antigen-bearing cells
• Helper T cells secrete cytokines that control the immune response

Acquired Immunity

• Immunity is brought about naturally through an infection or artificially through medical intervention
• Immunity includes active vs passive immunity

Active Immunity

• Active immunity is when an individual's body makes antibodies against a particular antigen
• Active immunity can happen through natural infection or through immunization involving vaccines

Passive Immunity

• Passive immunity is when an individual is given antibodies to combat a disease and it is only temporary

Cytokines and Immunity

• Cytokines are signaling molecules produced by T lymphocytes, macrophages, and other cells
• They regulate wbc formation and function
• Interferon and interleukins are cytokines used in various medical treatments

Hypersensitivity Reactions

• Hypersensitivity Reactions occur when the immune system overreacts and causes harm to the body
• Hypersensitivity Reactions include allergies, receiving an incompatible blood type, tissue rejection, or autoimmune disease

Allergies

• Allergies are hypersensitivity to allergens such as pollen, food, or animal hair, which are normally harmless
• The Immediate allergic response occurs within seconds of contact with the antigen
• Immediate allergic response is caused by IgE antibodies attached to receptors on mast cells and basophils, which release histamine when they bind allergens
• Anaphylactic shock represents an immediate allergic response
• Anaphylactic shock is characterized by a sudden, life-threatening drop in blood pressure due to increased permeability of the capillaries by histamine
• Delayed allergic responses are initiated by memory T cells at the location of contact with the allergen

Other Immune Problems

• Rejection of transplanted tissue occurs when the recipient's immune system recognizes the transplanted tissue is not "self"
• Cytotoxic T cells attack the transplanted tissue and, can be controlled with immunosuppressive drugs and by transplanting organs that have the same mhc proteins in the donor and the recipient
• Immunosuppressive drugs act by inhibiting the production of cytokines
• Xenotransplantation is transplanting organs from an animal
• Severe combined immunodeficiency disease features inadequate/lacking antibody and cell-mediated immunity
• Acquired immune deficiencies can be caused by infections, chemical exposure, or radiation
• Acquired immunodeficiency syndrome (aids) results from infection with the human immunodeficiency virus (hiv)
• Aids patients are more susceptible to infections and have a higher risk of cancer
• Autoimmune disease is when cytotoxic T cells or antibodies attack the body's own cells as if they were foreign
• An example of an autoimmune disease is Rheumatic fever, where antibodies induced by a streptococcal bacterial infection of the throat also react with heart muscle
• Rheumatoid arthritis is when antibodies bind against joints, and Systemic lupus erythematosus is when there are high levels of anti-DNA antibodies
• Plasma cells form; b cell divides; b cell activates; antigen binds to bcr