Lymphatic System The lymphatic system represents an accessory route through which fluid can flow from the interstitial spaces into the blood. Most important, the lymphatics can carry proteins and large particulate matter away from the tissue spaces, neither of which can be removed by absorption directly into the blood capillaries. This return of proteins to the blood from the interstitial spaces is an essential function without which we would die within about 24 hours.

Terminology Interstitial fluid : (tissue fluid) a solution that bathes and surrounds the cells of multicellular animals. lymph capillaries :Tiny thin-walled vessels, closed at one end and located in the spaces between cells throughout the body, collect fluid from the tissues. Lymph: the fluid that circulates throughout the lymphatic system. The lymph is formed when the interstitial fluid is collected through lymph capillaries. It is then transported through larger lymphatic vessels to lymph nodes, where it is cleaned by lymphocytes, before emptying ultimately into the right or the left subclavian vein, where it mixes back with the blood.

consists of: lymphatic vessels 2) lymphoid tissues and lymphoid organs

Lymphatic vessels start with lymphatic capillaries lymphatic ducts lymphatic trunks lymphatic collecting vessels lymphatic capillary

The main function - collect excess large particles and tissue fluid

travel along with blood vessels. lymphatic vessels

Valves are present to prevent backflow. Lymph driven by rhythmic contractions

blockage of lymph drainage Lymphedema - swelling in tissues - due to tumor pressure, parasites, or surgery

Elephantiasis – blockage by parasitic worms

LYMPHATIC SYSTEMS consists of: lymphatic vessels 2) lymphoid tissues and lymphoid organs

Lymphoid organs can be divided broadly into central or primary lymphoid organs, where lymphocytes are generated, and peripheral or secondary lymphoid organs, where adaptive immune responses are initiated and where lymphocytes are maintained. The central lymphoid organs are the bone marrow and the thymus

The lymph nodes Afferent lymphatic vessels drain fluid from the tissues and also carry antigen-bearing cells and antigens from infected tissues to the lymph nodes, where they are trapped. In the lymph nodes, B lymphocytes are localized in follicles, with T cells more diffusely distributed in surrounding paracortical areas, also referred to as T-cell zones. Some of the B-cell follicles include germinal centers, where B cells are undergoing intense proliferation after encountering their specific antigen and their cooperating T cells B and T lymphocytes are segregated in a similar fashion in the other peripheral lymphoid tissues, and we shall see that this organization promotes the crucial interactions that occur between B and T cells upon encountering antigen.

3-The spleen is a fist-sized organ just behind the stomach 3-The spleen is a fist-sized organ just behind the stomach.The bulk of the spleen is composed of red pulp, which is the site of red blood cell disposal. The lymphocytes surround the arterioles entering the organ, forming areas of white pulp, the inner region of which is divided into a periarteriolar lymphoid sheath (PALS), containing mainly T cells, and a flanking B-cell corona.

-The gut-associated lymphoid tissues (GALT), which include the tonsils, adenoids, and appendix, and specialized structures called Peyer's patches in the small intestine, collect antigen from the epithelial surfaces of the gastrointestinal tract. In Peyer's patches, which are the most important and highly organized of these tissues, the antigen is collected by specialized epithelial cells called multi-fenestrated or M cells. The lymphocytes form a follicle consisting of a large central dome of B lymphocytes surrounded by smaller numbers of T lymphocytes .

Lymphocytes circulate between blood and lymph Lymphocytes circulate between blood and lymph. Naïve cells circulate continually from the blood into the peripheral lymphoid tissues, which they enter by squeezing between the cells of capillary walls. They are then returned to the blood via the lymphatic vessels or, in the case of the spleen, return directly to the blood. In the event of an infection, lymphocytes that recognize the infectious agent are arrested in the lymphoid tissue, where they proliferate and differentiate into effector cells capable of combating the infection

lymphoid organs site of maturation of T lymphocytes secretes hormones (thymopoietin and thymosins) - critical role in childhood Lymph Nodes Spleen Thymus

lymphoid organs Lymph Nodes Spleen Thymus Tonsils - trap and destroy bacteria

Cells of immune system

Defenses Against Pathogens 1) Nonspecific defenses 2) Specific defense

Physical barriers/Chemical barrier: The skin, cornea, and mucosa of the respiratory, GI, and GU tracts form a physical barrier. Some of these barriers also have active immune functions: •Keratinocytes in the skin secrete antimicrobial peptides (defensins), and sebaceous and sweat glands secrete microbe-acid pH substances, (eg, lactic acid, fatty acids). •Mucosa of the respiratory, GI, and GU tracts: The mucus contains antimicrobial substances, such as lysozyme, and lactoferrin. Soluble proteins including Interferon and complements found in the blood contribute to non-specific immunity. Interferons are a group of proteins made by cells in response to viral infections and has antiviral properties. Complements are also a group of serum protein made mainly by the liver, involve in the control of inflammation, the activation of phagocytic cells and lytic attack on microbial cells membrane.

Phagocytic cells (neutrophils and monocytes in blood, macrophages and dendritic cells in tissues) ingest and destroy invading microbes by phagocytosis

Inflammation signs redness (erythema) caused by hyperemia ( blood flow) swelling (edema) caused by  capillary permeability and filtration heat caused by hyperemia pain caused by inflammatory chemicals and pressure on nerves

2) Inflammation Inflammatory chemicals - bradykinin, histamine, and leukotrienes - secreted by damaged cells, mast cells, basophils, lymphocytes, macrophages and platelets - stimulates vasodilation, increases capillary permeability, and induces pain.

Pain Causes Direct injury to nerve endings Inflammatory chemicals Tissue swelling Brandykinin, Prostaglandins, and bacterial toxins can induce pain. Brandykinin, produced from a plasma protien, is released from basophils and mast cells Pain is an important signal to tissue repair, as it signals the body to rest and not further injury itself.

3) Fever Defense mechanism: can do more good than harm promotes interferon activity accelerating metabolic rate and tissue repair inhibiting pathogen reproduction Pyrogen (fever-producing agent): - secreted by macrophages (endogenous) and microorganisms (exogenous) - stimulates anterior hypothalamus to secrete prostaglandin E which resets body thermostat higher

Specific Immunity 1) Humeral Immunity – based on B-cells and antibodies 1) Recognition 2) Attack 3) Memory 2) Cellular Immunity – uses 4 types of T cells to promote immunity, regulate attack, attack, and remember. Recognition Attack Memory

Antibodies and Antigens 1) Antibody – Y-shaped immunoglobins created to bind to various antigen-biding sites 2) Antigen – any molecule that triggers an immune response. Generally large and complex, making it distinguishable from self.

Cellular Immunity Cytotoxic T cells – attack enemy cells 1) Perforin to punch holes in cell membrane 2) Lymphotoxin attacks target cell’s DNA 3) Tumor necrosis kills tumor cells Suppressor T cells – release lymphokine that inhibit T and B cell activity, prevents the immune system from damaging self. Memory T cell – some T cells become memory after first attack. Second defense is faster like the second humeral response. Called the T cell recall response.

Immune System Disorders Hypersensitivity Autoimmune Disease Immunodeficiency Diseases

Hypersensitivity Production of antibodies to substances most tolerate, ie allergies. Type I (acute) - Most common, starts within seconds and most often ends within 30 minutes. Anaphylaxis – causes edema, mucus, and congestion Asthma – reaction to inhaled allergen. Causes massive release of histamine and spasmatic contraction of the bronchioles. Anaphylactic shock – systemic response to an injected allergen. Can cause bronchiolar constriction, circulatory shock, and possible death. Type II (antibody-dependant cytotoxic)- as in transfusion reaction. Type III (immune complex)- large antibody-antigen complexes that get trapped under the tunic interna of blood vessels and cause inflammation. Type IV (delayed)- occur 12 to 72 hours after exposure. Delay commonly associated with travel time to lymph nodes. Cosmetics and poison ivy hapten commonly do this.

Autoimmune Diseases Failure of the immune system to distinguish self from foreign antigens. Immune systems produces antibodies against bodies own tissues. Causes: - Cross reactivity – fight against a foreign antigen leds to antibodies that attack self. - Abnormal exposure to self-antigens in the blood - Changes in the structure of self-antigens

Immunodeficiency Diseases SCID – Severe combined immunodeficiency disease - congenital deficiency of both T and B cells. - susceptible to opportunistic infections. - “Bubble babies” AIDS – Acquired Immunodeficiency diseases Acquired after birth, like HIV. HIV targets helper T cells Without these cells, all 3 immune responses are hampered. Most patients with AIDS die of opportunisitic infections. HIV virus