Biology 211
Study Notes Exam 1
Endocrine System: a system of small glands scattered throughout the body that influences the metabolic activities of cells through hormones
- Hormones: chemical messengers released to the blood by the cells of endocrine glands that regulate the metabolic activities of other cells in the body
o Hormones signal target cells to perform specific chemical reactions
Endocrine Glands: pituitary, thyroid, parathyroid, adrenal, pineal and thymus glands.
- Organs with major functions outside the endocrine system containing endocrine tissue/cells: pancreas, gonads, hypothalamus (neuroendocrine organ)
- Tissues that produce hormones also found within: adipose cells, small intestine, stomach, kidneys, heart
Hormones:
Amino acid-based hormones: contain from a couple to many amino acidsŠ vary in size from simple amino acid derivatives (amines, thyroid hormone, peptides) to proteins (polypeptides)
Steroid hormones: synthesized from cholesterol (includes hormones from the gonads and adrenal cortex (outer region of the adrenal gland))
Eicosanoids: local hormones (paracrines); biologically active lipids released from nearly all cell membranes
- effects are highly localized, different from circulating hormones
- leukotrienes: chemicals that mediate inflammation & some allergic reactions
- prostaglandins: many targets/effectsŠ raise blood pressure, stimulate uterine contractions during birth, enhance blood clotting & inflammation
Eicosanoids are generally not considered part of the endocrine system, but will be discussed in later Chapters with the appropriate systems
Mechanisms of hormone action:
- alter plasma membrane permeability or electrical state
- stimulate synthesis of proteins within cells
- activate or deactivate enzymes
- induce secretory activity
- stimulate mitosis/cell division
- proteins and peptides cannot freely penetrate plasma membrane
- these hormones bind to a membrane receptor that starts a chain of reactions that activates an intracellular second messenger molecule
- cyclic AMP signaling:
o the hormone (first messenger) binds the membrane receptor; the receptor changes shape, which allows it to bind G protein
o G protein is activated; binds GTP & releases GDP
o activated G protein moves along membrane; binds to & activates (or inhibits) enzyme adenylate cyclase (GTP is hydrolyzed by GTPase activity of G protein)
o activated adenylate cyclase converts ATP to cyclic AMP (second messenger); if inhibited, adenylate cyclase will not catalyze its reaction
o cyclic AMP is free to circulate inside the cell; triggers activation of one to several protein kinase molecules; protein kinase phosphorylates (adds a phosphate group to) many proteins
- the phosphorylated proteins may be activated or inhibited by phosphorylation
- amplification effect: each activated adenylate cyclase can generate many cyclic AMP molecules; each protein kinase can catalyze hundreds of reactions
- the end effect depends on the target cell (in thyroid cells, binding of TSH to its receptor ends in the synthesis of thyroid hormone; in bone & muscle cells, growth hormone binding to its receptor ends in protein synthesis)
- cyclic AMP is rapidly degraded by the enzyme phosphodiesterase, but activation of protein kinase by cyclic AMP has generally already taken place
- PIP-calcium signaling mechanism:
o hormone (first messenger) binding to its receptor causes the receptor to bind inactive G protein
o G protein is activated; binds GTP & releases GDP
o activated G protein binds & activates a membrane-bound phospholipase enzyme; G protein becomes inactive
o phospholipase splits phosphatidyl inositol biphosphate (PIP2) to diacylglycerol (DAG) & inositol triphosphate (IP3); both DAG & IP3 are second messengers
o DAG activates protein kinases on the plasma membrane; IP3 triggers calcium ion release from the ER
o liberated calcium ions (also second messengers) alter activity of some specific enzymes and ion channels or bind to the regulatory protein calmodulin; calmodulin also activates specific enzymes to amplify the cellular response
- there also appear to be other second messenger systems used by some hormones that are less understood
Steroid hormones & direct gene activation:
- steroid hormones are lipid-based (synthesized from cholesterol) and can easily diffuse into target cells (no need for intracellular second messengers since the hormone can enter the cell)
- thyroid hormone also uses this mechanism
- hormone enters the nucleus; binds to & activates intracellular receptor
- the hormone-receptor complex binds a DNA-associated receptor protein, which turns on transcription & translation of the associated gene
- the protein synthesized in many cases is an enzyme that effects the metabolic activities of the cell to transmit the effects of the hormone
Hormones are specific for their target cells:
- hormones bind specific receptors; the receptor will only bind to one hormone
- the effects of the hormone depend on the blood levels of the hormone & the presence & number of receptors on the target cell
- up-regulation: increase in the # of receptors for a hormone on a target cell
- down-regulation: decrease in the # of receptors for a hormone on a target cell
The half-life of a hormone (persistence of a hormone in blood, a time indicating half its activity remaining) is brief (from a fraction of a minute to 30 minutes), but the effects of hormones can last for several minutes to hours
Control of hormone release:
Negative feedback: hormone secretion triggered by an external stimulus; as hormone levels rise, the hormones feed back to the metabolic pathway that produces them & inhibit their further release
Humoral stimuli: hormone release controlled by blood levels of specific ions and nutrients (e.g.: calcium or glucose)
Neural stimuli: nerve fibers stimulate hormone release (sympathetic neurons stimulate secretion of catecholamines (epinephrine & norepinephrine) fro the adrenal medulla))
Hormonal stimuli: other hormones regulate release of a hormone (e.g.: releasing & inhibiting hormones released by hypothalamus regulate release of hormones from pituitary)
Nervous system modulation: the nervous system can override normal homeostatic mechanisms for hormonal control (for example, to allow more glucose for fuel to be released during excitement (³fight or flight response²))
Major Endocrine Glands:
Pituitary Gland (Hypophysis): connected to hypothalamus by stalk called infundibulum
- Anterior Pituitary (Adenohypophysis):
o Growth Hormone (GH): stimulates cell division in most cells (major targets are bone & skeletal muscle)
§ IGFs (insulin-like growth factors or somatomedins) mediate most effects of GH
§ Hypersecretion: in children, can lead to gigantism; after long bones have developed, can lead to acromegaly
§ Hyposecretion: in children, can lead to pituitary dwarfism
o Prolactin (PRL): stimulates milk production by mammary glands of breasts
o Follicle-stimulating hormone (FSH): stimulates gamete production in gonads (ovaries & testes)
o Leutinizing hormone (LH): promotes production of gonadal hormones (testosterone, estrogen & progesterone)
o Thyroid-stimulating hormone (TSH): stimulates normal development of & secretion of hormones from thyroid gland
o Adrenocorticotropic hormone (ACTH or corticotropin): stimulates release of corticosteroid hormones from adrenal cortex
- Posterior pituitary (Neurohypophysis): receives & stores hormones from hypothalamus for later release
o Oxytocin: produced by paraventricular nucleus of hypothalamus; stimulates uterine contraction during childbirth & milk ejection during nursing
o Antidiuretic hormone (ADH): produced by supraoptic nucleus of hypothalamus; stimulates kidney tubules to retain water
§ deficiency of ADH secretion leads to diabetes insipidus
Hypothalamus: secretes releasing & inhibiting hormones that regulate release of hormones from anterior pituitary
- hypophyseal portal system: network of blood vessels that delivers hormones to anterior pituitary from hypothalamus
- Growth Hormone-Releasing Hormone (GHRH)
- Growth Hormone-Inhibiting Hormone (GHIH or somatostatin)
- Prolactin-Releasing Hormone (PRH)
- Prolactin-Inhibiting Hormone (PIH or dopamine)
- Gonadotropin-Releasing Hormone (GnRH)
- Thyrotropin-Releasing hormone (TRH)
- Corticotropin-Releasing hormone (CRH)
Thyroid Gland:
- Thyroid Hormone: amino acid hormones containing 2 tyrosine molecules each bound to iodine molecules; regulates metabolic activities of all cell types, especially glucose oxidation (energy & heat production)
o Thyroxine (T4): major hormone released from thyroid follicles (contains 4 iodine molecules)
o Triiodothyronine (T3): (contains 3 iodine molecules); generally formed from T4 by cleaving an iodine molecule
- Thyroid follicles are sacs lined with follicular cells and containing a substance called colloid; colloid contains thyroglobulin (tyrosine molecules linked to iodines)
- Thyroid hormone formed by joining 2 tyrosine-iodine complexes
- simple goiter: enlargement of thyroid gland due to lack of dietary iodine (thyroid hormone precursors accumulate in gland)
- hypothyroidism in infants may be associated with cretinism (underdeveloped thyroid gland); symptoms are short, stocky stature & may lead to mental retardation
- myxedema: hypothyroidism in adults (lethargy, weight gain, hair loss, slow pulse, etc,)
- treatment for hypothyroidism is generally thyroxine therapy
- Graves¹ disease: hyperthyroidism due to enlarged & overactive thyroid gland; produces exopthalmic goiter (swelling & protrusion of eyes)
- treatment of hyperthyroidism involves thyroid gland surgery &/or radioactive iodine
- Calcitonin: produced by parafollicular cells (C cells) of thyroid gland
o lowers blood calcium levels by inhibiting osteoclasts & stimulating calcium uptake by bones
Parathyroid Glands: paired glands on posterior aspect of thyroid gland
- Parathyroid hormone (Parathormone or PTH): raises blood calcium levels by stimulating osteoclasts, enhancing absorption of calcium by kidneys, & increasing absorption of calcium by cells of intestine
o PTH activates the inactive form of vitamin D in the kidneys; vitamin D enhances absorption of calcium by intestine
Adrenal Glands (Suprarenal Glands): pyramid-shaped glands above kidneys
- Adrenal Cortex: releases corticosteroid hormones
o Mineralocorticoids: released primarily by cells of zona glomerulosa; regulate salt concentrations in extracellular fluids
§ Aldosterone: primary mineralocorticoid: enhances sodium (& water) reabsorption from kidney tubules
· Sodium ion concentration in body fluids also regulated by rennin-angiotensin system, ACTH & atrial natriuretic peptide (ANP)
o Glucocorticoids: influence metabolism of body cells & help resist stressors
§ During times of stress (injury/blood loss), glucocorticoids stimulate gluconeogenesis (glucose synthesis) & mobilize fats & proteins to be used for energy to save glucose for the brain
§ Cortisol (hydrocortisone) is major glucocorticoid (also cortisone & corticosterone)
§ Glucocorticoids also prevent water loss from cells into tissue fluids; used as anti-inflammatory agents
- Gonadocorticoids: secondary source of sex hormones; primarily androgens (testosterone), but also estrogens
o may contribute to onset of puberty
- Addison¹s disease: low level of adrenal cortex hormones resulting in bronzing of skin, low blood sugar (low energy & weak immunity) & low blood sodium (low blood pressure)
- Cushing syndrome: high level of adrenal cortex hormones resulting in high blood sugar (& possibly diabetes mellitus), high blood sodium (hypertension), swelling & obesity & possible masculinization in women
- Adrenal medulla: releases catecholamines (norepinephrine & epinephrine)
o Release is stimulated by sympathetic nervous system (³fight or flight² response)
o Epinephrine: stimulates heart rate & metabolism
o Norepinephrine: influences peripheral vasoconstriction & blood pressure
Pancreas: releases insulin & glucagon from islets of Langerhans
- Insulin: released by beta cells of islets; lowers blood glucose levels by stimulating glucose storage & uptake of glucose by cells for energy
o Insulin deficiency may leads to diabetes mellitus
§ Insulin-dependent diabetes mellitus (IDDM): autoimmune disease where immune cells attack & destroy beta cells
§ Non-insulin-dependent diabetes mellitus (NIDDM): insulin receptors do not properly respond to insulin
- Glucagon: raises blood glucose levels by stimulating glucose removal from glycogen storage deposits in liver cells & gluconeogenesis
Gonads (ovaries & testes): produce steroidal sex hormones
- Ovaries: produce estrogens, progesterone, inhibin & relaxin
o estrogens (estrone & estradiol) & progesterone: produced by ovary cells are responsible for maturation of female reproductive organs & regulation of menstrual cycle
§ also, maintain pregnancy & prepare mammary glands for lactation
o inhibin inhibits FSH during ovarian cycle; relaxin released during pregnancy increases flexibility of pubic symphysis & helps dilate uterine cervix
- Testes: produce testosterone, an androgen (male sex hormone)
o testosterone: produced by cells of testes is responsible for maturation of male reproductive organs & sperm cell production
o inhibin inhibits FSH to regulate spermatogenesis
Pineal Gland: secretes melatonin
- pineal gland located in epithalamus of brain at roof of 3rd ventricle
- melatonin appears to be involved in maintenance or sleep/wake (day/night) cycles
o melatonin derived from the amino acid serotonin
o more melatonin released in darkness, less in light; norepinephrine from sympathetic fibers stimulate secretion of melatonin (may cause sleepiness)
o during sleep, plasma levels of melatonin increase & then decrease before awakening; therapeutic use to induce sleep still under investigation
Thymus: secretes thymopoietins & thymosins
- thymus located behind sternum superior to heart
- thymosin, thymic humoral factor (THF), thymic factor (TF) & thymopoietin involved with normal development of T cells (lymphocytes); may slow aging
Other Hormone-Producing Structures:
Heart: specialized cardiac muscle cells of atria secrete atrial natriuretic peptide (ANP), which reduces blood volume, blood pressure, & blood sodium levels
GI tract: enteroendocrine cells secrete hormones that aid in digestion
Placenta: secretes steroid hormones that help during pregnancy & human chorionic gonadotropin (hCG)
Kidney: secretes erythropoietin that stimulates red blood cell synthesis in bone marrow
Skin: secretes inactive vitamin D (cholecalciferol), which is activated by PTH in kidneys
Adipose Tissue: secretes leptin, which binds to neurons regulating appetite
control & leads to sensation of satiety
Chapter 17: Blood
Blood Functions:
- transport & distribution of oxygen & nutrients, carbon dioxide & metabolic waste, and hormones
- regulation of body temperature, normal pH and fluid volume in cells & tissues
- protection against blood loss (clotting) and infection (white blood cells)
Blood Characteristics:
- pH of blood is maintained between 7.35 and 7.45 by carbonic acid-bicarbonate ion buffer system
- blood accounts for ~ 8% body weight
- blood volume in adults is normally 5-6 L in males and 4-5 L in females
Blood Components:
- plasma & formed elements (erythrocytes, leukocytes & platelets)
- hematocrit: % of total blood volume occupied by erythrocytes (normally between 42% and 47% ± 5%)
Blood Plasma: fluid component of blood
- mostly (~ 90%) water
- contains over 100 different dissolved solutes, including:
o proteins: albumin, globulins, clotting proteins, etc.
§ albumin is majority of plasma protein; albumin is carrier molecule & contributes to plasma osmotic pressure
§ globulins include transport proteins & antibodies
o nutrients: sugars, amino acids, fatty acids, cholesterol, vitamins, etc.
o electrolytes: cations (positive ions) such as sodium, potassium, calcium & magnesium; anions (negative ions) such as chloride, phosphate & bicarbonate
o respiratory gases: oxygen & carbon dioxide
Formed Elements: erythrocytes, leukocytes & platelets
- Erythrocytes: red blood cells (RBCs)
o small cells; biconcave discs (flattened disc shape with thin, depressed centers – look like mini doughnuts)
o anucleate – RBCs have no nucleus
o function in gas transport
o most of contents of RBC (other than water) is the protein hemoglobin
§ hemoglobin is composed of 4 globin polypeptide chains each bound to a heme group
· heme is a ringlike compound with an iron atom at its center
· the iron atom in heme binds to oxygen
§ one hemoglobin molecule can bind to & transport up to 4 oxygen molecules
§ hemoglobin can also bind carbon dioxide; carbon dioxide binds to globin chain amino acids rather than heme
§ oxyhemoglobin: hemoglobin with bound oxygen
§ deoxyhemoglobin: hemoglobin with no bound oxygen
§ carbaminohemoglobin: hemoglobin with bound carbon dioxide
o hematopoiesis (hemopoiesis): blood cell formation; occurs in red bone marrow (in adults, in bones of girdles & proximal epiphyses of humerus & femur)
§ starts with stem cell called hemocytoblast (hematopoietic stem cell that is used to form all formed elements of blood)
§ erythropoiesis (erythrocyte production): hemocytoblast -> myeloid stem cell -> proerythroblast -> early erythroblast -> late erythroblast -> normoblast -> reticulocyte -> erythrocyte
· cell shrinks in size; cell accumulates hemoglobin protein during erythroblast stages; cell loses its nucleus in transition from normoblast to reticulocyte
· reticulocyte counts can be used as a rough indicator of the rate of RBC formation
· controlled hormonally by erythropoietin produced by the kidneys (responding to hypoxia (low oxygen levels))
· requires adequate supplies of iron & amino acids for hemoglobin and B vitamins (vitamin B12 and folic acid) for DNA synthesis
o since free iron is toxic, it is always transported in protein-iron complexes (such as ferritin)
o destruction of erythrocytes: RBCs last ~ 100-120 days in circulation
§ aged & damaged RBCs are broken down in small channels of the spleen, liver & marrow by macrophages
§ heme is broken from hemoglobin; iron is salvaged & stored and the remainder of the group is degraded to bilirubin (yellow pigment), which is picked up by the liver, converted into bile & excreted
§ globin chains are metabolized are broken down into amino acids for protein synthesis
o erythrocyte disorders:
§ anemias: conditions that involve blood with a very low oxygen-carrying capacity
· caused by an insufficient number of RBCs (hemorrhagic, hemolytic & aplastic anemias), decreased hemoglobin content (iron-deficiency & athlete¹s anemia) or abnormal hemoglobin (thalassemias & sickle cell anemia)
§ polycythemia: abnormal excess of RBCs; increases blood viscosity & can impair circulation
· can be treated by diluting blood with saline
· artificial polycythemia can be induced by infusing RBCs (blood doping used by some athletes to increase available oxygenŠ considered unfair by many games committees)
- Leukocytes: white blood cells (WBCs)
o only formed elements with nucleus & normal organelles
o involved in immune responses; protect the body from damage by bacteria, viruses, parasites, toxins & tumor cells
o diapedesis: white blood cells can move out of capillaries & into tissues
§ use amoeboid motion with flowing cytoplasmic extensions to move through tissue spaces
§ positive chemotaxis: follow chemical trail of other WBCs to sites of infection
o leukocytosis: condition of increased WBC count during infection (normal response)
o Granulocytes: WBCs with membrane-bound cytoplasmic granules
§ Neutrophils: most numerous WBCs (>50% of WBC volume)
· ~ 2x size of RBCs
· very fine, lightly staining granules containing enzymes or antibiotic-like proteins (defensins)
· nucleus has from 3-6 lobes (also known as PMNs (polymorphonuclear leukocytes))
· phagocytic cells (kill bacteria & fungi by oxidation), chemically attracted to sites of inflammation
§ Eosinophils: ~ 1-4% of WBC population; about size of neutrophils
· nucleus with 2 lobes (like telephone receiver)
· large, red-staining granules with enzymes
· digest invading parasitic flatworms & roundworms with digestive enzymes
· phagocytic; ingest immune complexes during allergic reactions
§ Basophils: ~ 0.5% of WBC population (rare); about size of neutrophils
· large purplish-black-staining granules containing histamine
· histamine: inflammatory chemical - vasodilator & chemoattractant – released by basophils
o Agranulocytes: WBCs without visible granules
§ Lymphocytes: small, medium & large sizes
· large spherical nucleus occupies most of cell volume
· most lymphocytes are in lymphatic organs
· T lymphocytes: fight virus-infected cells & tumor cells
· B lymphocytes: give rise to plasma cells that produce antibodies (immunoglobulins)
§ Monocytes: largest WBCs (2-3x size of RBCs)
· Large U or kidney-shaped nucleus
· differentiate into macrophages in tissues
· macrophages are phagocytic cells that destroy bacteria & help in immune response against viruses
o Leukopoiesis: WBC production
§ Stimulated by hormones (cytokines such as interleukins & colony-stimulating factors (CSFs) from macrophages & lymphocytes
§ Hemocytoblast differentiates into either myeloid stem cell or lymphoid stem cell
· Myeloid stem cell differentiates into myeloblast or monoblast
o Myeloblast will form granulocytes
o Monoblast will form monocytes
· Lymphoid stem cell differentiates into lymphoblast, which will form lymphocytes
o Leukocyte disorders:
§ Leukemias: cancer of myeloid or lymphoid cell lines
· Leukemias can be acute (rapidly advancing) or chronic (slowly advancing)
· Treated with radiation & chemotherapy & bone marrow transplant to replace cancerous cells
§ Infectious mononucleosis: highly contagious viral infection
· caused by Epstein-Barr virus (EBV)
· symptoms (fatigue, aches, fever) last a few weeks until virus is dealt with by immune system
- Platelets: cytoplasmic fragments of megakaryocytes with granules containing blood-clotting enzymes
o sometimes referred to as thrombocytes
o stick together to form a plug to prevent blood loss in torn vessels
o platelet formation regulated by hormone thrombopoietin
o hemocytoblast differentiates into megakaryoblast, which undergoes repeated mitoses without cell division; this results in the megakaryocyte (cell with large nucleus)
o extensions of megakaryocyte in bloodstream rupture to form platelets
o Hemostasis: stoppage of bleeding from a torn blood vessel
§ Vascular spasms: result in vasoconstriction; caused by damage to smooth muscle, chemicals & reflexes
§ Platelet plug formation: in response to blood vessel injury, platelets swell & form spiked processes
· this allows them to adhere to exposed collagen fibers surrounding vessel
· release of chemicals (serotonin, ADP) enhances vascular spasms & attracts more platelets to area (positive feedback)
· PGI2 released by endothelial cells limits platelet aggregation to area of injury
§ Coagulation (blood clotting): blood transformed from a liquid to a gel
· Prothrombin activator converts the plasma protein prothrombin to thrombin
· Thrombin catalyzes joining of fibrinogen molecules in plasma to form a fibrin mesh that seals vessel
· Clotting factors enhance clot formation (several require vitamin K for formation)
· Anticoagulants inhibit clotting
o Clot retraction & repair: within 30-60 minutes after injury, platelets contract, pulling on fibrin strands to pull ends of torn vessel closer together
§ Platelet-derived growth factor (PDGF) released by platelets to stimulate division of smooth muscle cells & fibroblasts to rebuild vessel wall
o Fibrinolysis: removes unneeded clots after healing has occurred
§ Tissue plasminogen activator (tPA) activates plasma plasminogen, which is converted to plasmin
§ Plasmin is an enzyme that digests fibrin, breaking down clot
o Factors limiting clot growth/formation:
§ Anticoagulants antithrombin III, protein C & heparin work to inhibit procoagulants & thrombin
o Disorders of Hemostasis:
§ Thromboembolytic disorders: a thrombus (clot) forms in an unbroken blood vessel; if it detaches from the vessel wall, the resulting embolus can travel through the blood & block blood vessels
· Free blood clots can be treated by anticoagulants aspirin, heparin & warfarin
o Bleeding disorders:
§ thrombocytopenia
§ impaired liver function
§ hemophilia
Transfusion & Blood Replacement:
- whole blood transfusions are used to treat conditions involving massive blood loss
- packed red cells can be used to treat anemias
- Human Blood Groups: red blood cells have many (perhaps > 100) cell surface antigens – glycoproteins known as agglutinogens
o antigens determining ABO and Rh blood groups cause transfusion reactions
o ABO blood groups:
§ type A blood individuals have surface antigen A
§ type B blood individuals have surface antigen B
§ type AB blood individuals have both A & B surface antigens
§ type O blood individuals have neither A nor B surface antigens
§ individuals make antibodies (agglutinins) against the antigen(s) not present on their red blood cells (e.g.: type A blood individuals will make anti-B agglutinins); this does not require previous exposure to the antigen(s)
o Rh blood groups:
§ Humans may also have one of several Rh factors present on the surface of their red blood cells
§ An individual without Rh factor will make antibodies against Rh factor, but only after exposure to the antigen
Transfusion reactions: agglutination & hemolysis
- following infusion of mismatched blood, agglutination occurs as antibodies complex with the foreign blood group antigens
- this blocks blood vessels & hinders blood flow; reduces oxygen availability to tissues, as the RBCs are lysed, hemoglobin escapes & may precipitate in kidney tubules leading to renal failure
- treatment involves diluting agents & diuretics
- type O- blood is the universal donor
- type AB+ blood is the universal recipient
Plasma & Blood Volume Expanders:
- plasma can be temporarily used to replace some blood volume when properly typed blood is not immediately available
- also, blood volume expanders such as albumin & dextran, which draw fluid into blood, can be used temporarily
Diagnostic Blood Tests:
- differential white blood cell count: to assess infection
- platelet count: used to assess thrombocytopenia
- complete blood count (CBC) used routinely to provide counts for all formed elements & tests for clotting factors
Chapter 20: The Lymphatic System
Functions of Lymphatic System:
- Draining excess interstitial fluid: lymphatic vessels drain excess fluid from tissue spaces & return it to the blood
- Transporting dietary lipids: lymphatic vessels transport lipids & lipid-soluble vitamins (A,D,E & K) absorbed by GI tract to the blood
- Carrying out immune responses: lymphatic tissue initiates specific immune responses to microbes or abnormal cells
Lymphatic Vessels (Lymphatics): system of drainage vessels that collects excess protein-containing interstitial fluid (fluid between cells) & returns it to blood
- used to return fluid escaped from blood into tissue spaces back to blood
- lymph is interstitial fluid that has entered lymphatic vessels
- form one-way system; blood flows toward heart
- Lymph capillaries: occur almost everywhere blood capillaries occur (except bones & teeth, bone marrow, & central nervous system (uses CSF to collect fluid))
o the edges of endothelial cells in walls of lymph capillaries loosely overlap forming minivalves to prevent backflow
o collagen filaments anchor the endothelial cells to connective tissue outside, allow the flaps to open when interstitial fluid volume increases such that fluid enters the lymphatic capillaries
o lymphatic capillaries (unlike blood capillaries) can easily take up proteins, foreign cells & debrisŠ fortunately lymph is circulated through lymphoid organs with immune cells to examine the fluid for undesirables
o lacteals are specialized lymphatic capillaries in the intestinal mucosa that carry a thick white fatty lymph (chyle) to the blood
o lymph flows from lymphatic capillaries to collecting vessels, trunks, and ducts
o lymphangitis: inflammation of lymphatics
o lymphatic ducts: right lymphatic duct drains lymph from right upper arm, right side of head & thorax; thoracic duct arising from the sac-like cisterna chyli drains the rest of the body
- Lymph transport: slow transport; lymph is not pumped, but flows by smooth muscle contraction in the walls of the vessels, pressure changes in the thorax during breathing & valves to prevent backflow
o Also, bundling with blood vessels helps along with movements in adjacent tissues
Lymphoid Cells:
- Lymphocytes: T cells & B cells
o T cells direct the immune response against virally-infected cells & cancer cells
o B cells produce plasma cells that synthesize antibodies
- Macrophages: phagocytize foreign substances & help activate T cells (along with dendritic cells)
- Reticular cells: provide stroma to nourish cells of lymphoid organs
Lymphoid Tissue:
- reticular connective tissue: forms a network around macrophages & lymphocytes in lymphoid organs
- diffuse lymphatic tissue: scattered reticular tissue elements
- lymphatic nodules: tightly packed reticular elements & cells
o germinal centers: actively dividing B cells & T cells
Lymphoid Organs: lymph nodes, spleen & thymus
Thymus: bilobed organ in inferior neck extending into mediastinum
- functions in maturation of T cells; mostly in childhood
- size decreases with age as most tissue replaced by connective tissue
- thymic lobules each contain a cortex and medulla with lymphocytes (T cells); medulla contains Hassal¹s corpuscles (appear red)
- thymocytes (epithelial cells in stroma) secrete hormones (thymosins) for development of T cells
Lymph Nodes: hundreds of small organs that cluster along lymphatic vessels
- filter lymph: macrophages in lymph nodes remove debris & destroy microorganisms
- activate immune system: lymphocytes within follicles monitor lymph for foreign antigens & mount responses against them
- T cells circulate between blood, lymph nodes & lymphatic vessels for continuous exposure to foreign substances
- Lymph sinuses: large capillaries surrounded by reticular fibers with macrophages
- Structure:
o Capsule: dense connective tissue surrounding lymph node with trabeculae that extend inward to divide the node into compartments
o Cortex: outer region of lymph node (just inside capsule) containing follicles; germinal centers of follicles contain dividing B cells
o Medulla: medullary cords from cortical tissue contain lymphocytes & plasma cells
- circulation: afferent lymphatic vessel -> subcapsular sinus -> cortical & medullary sinuses -> efferent lymphatic vessel at hilus
- lymph nodes can become inflamed when overwhelmed with foreign substances & can become secondary cancer sites
Spleen: largest lymphoid organ; located in left side of abdominal cavity just below diaphragm
- blood flows through sinuses; spleen removes aged & defective blood cells from circulation & contains macrophages to cleanse blood of foreign matter
- stores breakdown products of red blood cells for later use
- in fetus, produces erythrocytes
- stores blood platelets
- red pulp: most of mass of spleen; concerned with blood-cleansing & removal of old RBCs
- white pulp: contains lymphocytes (B cells)
- direct spleen injury can cause it to rupture; treatment = removal (splenectomy)
Tonsils: small organs around the entrance to the pharynx
- contain follicles with germinal centers with dividing B cells
- palatine tonsils: paired at posterior end or oral cavity; most likely to be infected
- lingual tonsils: at base of tongue
- tubal tonsils: at openings of auditory tubes into pharynx
Lymphoid Follicle Aggregates:
- Mucosa-associated Lymphatic tissue (MALT)
o Peyer¹s Patches in intestine (ileum)
o Appendix
Chapter 21: The Immune System: Innate & Adaptive Body Defenses
The Immune System: a functional system consisting of trillions of immune cells & molecules that inhabit lymphatic tissues & circulation providing resistance to disease (immunity).
- Surface Barriers (Skin & Mucosae)
o keratinized epithelial cells of skin & epithelial mucosae provide a physical barrier to infection
o protective chemicals secreted by cells of skin & mucosae:
§ acidic (pH 3-5) secretions of skin inhibit bacterial growth & chemicals in sebum are toxic to bacteria
§ stomach mucosa secretes concentrated HCl solution (pH 0.5-2.5) & proteases that kill microorganisms
§ saliva in oral cavity & lacrimal fluid in eyes contain lysozyme protein that kills bacteria
§ mucus of respiratory & digestive mucosae traps microorganisms
- Internal Defenses: Cells & Chemicals
o Phagocytes: cells that ingest large particles & bacteria and break them down
§ macrophages: develop from monocytes that enter tissues; most dominant phagocytes
· Free macrophages: alveolar macrophages of lungs, dendritic cells of epidermis (Langerhans¹ cells)
· Fixed macrophages: Kupffer cells of liver, microglia of brain
§ also: neutrophils, eosinophils & mast cells have phagocytic activity
§ mechanism of phagocytosis:
· microbe or foreign particle adheres to phagocyte
o adhesion is dependent on recognition of carbohydrates on surface of microbe (some bacteria with complex carbohydrate capsules do not adhere well)
o adhesion is enhanced by opsonization (foreign antigen is coated with complement & antibodies)
· phagocyte forms pseudopods that engulf particle
· particle taken into phagocyte in phagosome (phagocytic vesicle)
· phagosome fuses with lysosome, & lysosomal enzymes within phagolysosome digest particle
o respiratory burst: free radicals released to complete killing
· residual body (remaining material in phagolysosome) released from cell by exocytosis
o Natural Killer (NK) Cells: large granular lymphocytes present in blood & lymph that kill cancer cells & virus-infected cells
§ unlike T cells, NK cells are not specific for a specific virus or cancer cell type
§ like T cells, use perforins to kill target cell
o Inflammation: response to tissue injury (caused by trauma, heat, chemicals or infection)
§ prevents spread of damage
§ disposes of cell debris & pathogens
§ begins repair processes
§ 4 signs of inflammation: redness, heat, swelling & pain
§ vasodilation & increased vascular permeability: mediated by histamine, kinins, prostaglandins, complement & cytokines
· vasodilation leads to hyperemia (blood congestion) – redness & heat
· increased permeability of capillaries allows exudates (fluid with protein factors) to flow into tissue spaces causing edema (swelling) & pain (from adjacent nerves)
· swelling dilutes toxic chemicals from pathogens & speeds delivery of repair materials
· phagocytes migrate to the area:
o leukocytosis – chemicals released by injured cells draw neutrophils
o margination – neutrophils cling to walls of capillaries
o diapedesis – neutrophils move through capillary walls into tissue spaces
o chemotaxis – inflammatory chemicals draw more WBCs to the area, especially monocytes
o monocytes enter tissue spaces & develop into macrophages, which finish the disposal of microbes
o pus: mix of dead or dying WBCs & pathogens
o Antimicrobial proteins
§ Interferon (IFN): proteins released by virus-infected cells that prevent viral replication in neighboring cells
· Interferons also mobilize macrophages to area & activate NK cells
§ Complement: group of plasma proteins that, when activated, release chemical mediators that amplify inflammatory response, enhance phagocytosis (opsonization) & lyse cells
· activated by complement factors binding to antibody-antigen complex or cell wall polysaccharides of microorganisms
· membrane attack complex (MAC): group of complement proteins that inserts into cell membrane to cause cell lysis (death)
o Fever: abnormally high body temperature in response to chemicals called pyrogens secreted by leukocytes & macrophages exposed to bacteria & antigens
Adaptive (Specific) Defenses: B cells & T cells that recognize specific foreign substances & act to immobilize, neutralize & destroy them
- adaptive defenses are: antigen-specific, systemic (immune cells present throughout body), & have memory (memory cells enhance response to previously encountered antigens)
- humoral immunity (antibody-mediated immunity): mediated by antibodies in the body¹s ³humors² or fluids (blood, lymph, etc.)
o B cells produce plasma cells that release antibodies that bind antigens
- cellular immunity (cell-mediated immunity): mediated directly by T cells
o T cell receptors recognize & bind to antigens on virus-infected cells & cancer cells
- antigens: substances that can provoke an immune response
o most antigens are molecules that are not normally present in the body (nonself)
o immunogenicity: the ability of an antigen to stimulate proliferation of lymphocytes & antibody production
o reactivity: the ability of an antigen to react with the lymphocytes & antibodies
o haptens: small molecules that are reactive but not immunogenic unless attached to a protein carrier
o antigenic determinants: immunogenic regions of antigen
o self antigens: antigens that are not immunogenic to an individual but strongly immunogenic to others
§ MHC (major histocompatibility complex) proteins: self antigens involved in cellular immunity
· In humans, called HLA (human leukocyte antigen) molecules
· Class I MHC proteins: on surface of nearly all cells
· Class II MHC proteins: only on surface of professional antigen-presenting cells (APCs)
- Lymphocytes: produced from lymphoid stem cells in bone marrow
o must become immunocompetent (able to bind antigen); where cell becomes immunocompetent determines whether it is a T cell or B cell
o B cells become immunocompetent in bone marrow
o T cells become immunocompetent in thymus
§ Self-tolerance: T cells that strongly bind self-antigens or are not immunocompetent are weeded out & destroyed (negative selection), while T cells that weakly bind self antigens continue to develop (positive selection)
- antigen-presenting cells: one of several cell types that engulfs & digests antigens & presents part of them on its plasma membrane bound to MHC molecules for recognition by T cell receptors
o antigen presentation by APCs is essential for the cellular immune response
o professional APCs include dendritic cells, macrophages & activated B cells, but most cell types can function as APCs
Humoral Immune Response: B cells stimulated by antigen; leads to production of antibodies by plasma cells
- Clonal selection of B cells: immunocompetent but naïve B cell is activated by antigen binding its receptor, & forms a clone (population of identical cells)
o most cells of clone differentiate into plasma cells, which secrete antibodies
o some cells become memory B cells that can mount an immediate response to another encounter with the same antigen
- Immunological memory:
o Primary immune response: clonal selection & differentiation outlined above
§ takes approximately 3-6 days to start antibody production
o Secondary immune response: rapid response to subsequent exposure to same antigen
§ within 2-3 days, a much higher level of antibody is produced than is generated during primary response
- Active & Passive Humoral immunity:
o Active immunity: response by our own B cells to antigen(s)
§ naturally acquired: antigens from bacteria & viral infections
§ artificially acquired: antigens from vaccines
o Passive immunity: antibodies harvested or delivered from immune serum (from human or other animal)
§ naturally acquired: antibodies pass from mother to child via placenta
§ artificially acquired: antibodies acquired from injection of immune serum
- Antibodies (immunoglobulins or Igs): gamma globulin component of blood serum
o Y-shaped proteins produced by activated B cells & plasma cells in response to antigen
§ composed of 2 identical heavy (H) chains & 2 identical light (L) chains
§ each chain has a variable (V) region & constant (C) region
§ variable regions of 1 H chain & 1 L chain make up antigen-binding site; each antibody has 2 antigen-binding sites
§ constant region of H chains make up complement binding site & macrophage binding site
o 5 classes of antibodies:
§ IgD: B cell antigen receptor
§ IgM: monomer & pentamer forms
· monomer – B cell antigen receptor
· pentamer – circulates in blood plasma; first Ig class secreted; potent agglutinating agent
§ IgG: most abundant circulating antibody; protects against bacteria, viruses & toxins; fixes complement; primary antibody of primary & secondary responses; confers naturally acquired passive immunity
§ IgA: monomer & dimer forms
· monomer: small amounts in plasma
· dimer: found in secretions (mucus, saliva, sweat intestinal juice, milk), helps to prevent pathogens from entering body
§ IgE: normally rarely in plasma (levels rise during allergic reaction), secreted by plasma cells in skin, mucosae of digestive & respiratory tracts, & tonsils; when activated by antigen, binds to mast cells & basophils & causes release of histamine & other mediators of inflammation
o antibody diversity: genes for H & L chain proteins contain segments of DNA that are ³shuffled² by somatic recombination, & V regions are hot spots for mutation; the result is an enormous variation in the antigen specificity of the antibodies produced
§ also, plasma cells can produce more than 1 class of antibody (³switch² from producing IgM to IgG)
- Antibody functions: antibodies bind to antigens to form antigen-antibody complexes that inactivate antigens or target them for destruction
o Precipitation: large antigen-antibody complexes formed that settle out of solution; makes easier targets for macrophages
o Lysis: antibodies bind to antigens on surface of bacteria & mismatched red blood cells; complement binding site of antibody binds complement, which triggers complement fixation & cell death
o Agglutination: IgM binds to antigens on surface of mismatched red blood cells & forms large complexes (clumping)
o Neutralization: antibody binds to active site of toxin (from virus or bacteria) & inactivates it
o Monoclonal antibodies: pure antibody preparations produced from a B cell clone used in clinical applications
Cell-mediated immune response: T cells stimulated by antigen; leads to lysis of virus-infected cells or cancer cells &/or elevation of immune response
- Clonal selection of T cells: immunocompetent but naïve T cell is activated by binding of its T cell receptor (TCR) to antigen-MHC protein complex on cell surface of antigen-presenting cell, & forms a clone (population of identical cells)
o most cells of clone differentiate into mature T cells
§ cytotoxic T cells (CD8 cells or TC cells) lyse target cells
§ helper T cells (CD4 cells or TH cells) release chemicals called cytokines that amplify immune response (stimulate production of more B cells & T cells, mobilize phagocytes & attract more WBCs to area)
§ some cells become memory T cells that can mount an immediate response to another encounter with the same antigen
- T cell activation:
o Antigen recognition & MHC restriction: T cell receptors recognize & bind to antigen-MHC protein complex on cell surface of APC
o T cell receptors must recognize both self (MHC) & foreign (antigen) molecules in complex on the surface of APC
o TC cell receptors bind to short peptides from endogenous antigens (foreign/viral proteins inside cell) in complex with MHC Class I molecule
o TH cell receptors bind to longer peptides from exogenous antigens (foreign/bacterial proteins/allergens phagocytized from outside cell in blood/plasma) in complex with MHC Class II molecule
o Costimulation: T cell must be exposed to costimulatory signal to continue activation
§ signal can be binding to additional receptor on APC surface (B7 on macrophages binds CD28 on T cell) or cytokine stimulation
§ if no signal, T cell will halt activation & may become tolerant to antigen (anergy)
- Cytokines: hormone-like glycoproteins released by activated T cells & macrophages
o interleukins (IL-1 & IL-2) act as costimulators of T cells & T cell proliferation
o include cell toxins (perforin), inflammatory factors
- Specific T cell roles:
o helper T cells (TH cells): in most cases, required for adaptive immune responses
§ release cytokines that:
· activate B cells bound to certain antigens (T cell-dependent antigens)
· mobilize immune cells & macrophages
· attract more WBCs to area (chemotaxis) & enhance nonspecific defenses
o cytotoxic T cells (TC cells): also called killer T cells, directly attack & kill APCs with recognized foreign antigen/MHC complex on cell surface
§ mainly target virus-infected cells, but also target some bacteria, parasites, cancer cells & foreign RBCs
§ once bound to target cell & activated by helper T cells, release perforin (or lymphotoxin) to lyse target APC (similar to complement lysis)
o other T cells:
§ suppressor T cells (TS cells): release cytokines that suppress activity of T & B cells; may be involved in ending/cleaning up response
§ delayed-type hypersensitivity cells (TDH cells): release cytokines to activate macrophages in delayed hypersensitivity reactions
§ gamma-delta T cells: small intestinal population of T cells
Organ Transplants & Prevention of Rejection: cytotoxic T cells will normally target & kill foreign tissue
- both ABO blood group antigens & MHC antigens are typed to match (slight mismatches in MHC antigens are often tolerable)
- immunosuppressive therapy kills activated & circulating immune cells (as well as other rapidly dividing cells)
Immunodeficiencies: conditions where the production or function of immune cells, phagocytes or complement is impaired or abnormal
- severe combined immunodeficiency syndrome (SCID): congenital (present from birth) condition resulting from deficits in both T and B cells
o can be caused by nonfunctional interleukin receptors, defective adenosine deaminase (toxic to T cells)
o fatal if untreated (due to any infection), but can be treated with bone marrow transplant
- acquired immunodeficiency syndrome (AIDS): infection with human immunodeficiency virus (HIV) destroys helper T cells
o viral surface proteins target/bind to CD4 protein on helper T cells
o if untreated, over time helper T cell populations diminish & the condition can be fatal due to any type of infection
o treatments are available that inhibit viral replication/synthesis, but must be continuous as the virus is not eliminated by the treatment
o since these treatments only prevent new viral production, new research is aimed at treatments to prevent viral binding to/entry into helper T cells & specific removal of infected T cells
Autoimmune diseases: condition in which the body produces antibodies & activated cytotoxic T cells that target & destroy (self) body tissues
- causes include improper negative selection of self-directed lymphocytes in bone marrow & thymus during development, appearance of new antigens on cells, or foreign antigens that resemble self antigens
- examples are systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) & multiple sclerosis (MS)
- treatments include anti-inflammatories to control symptoms & antibodies/chemicals to suppress lymphocyte activity
Hypersensitivities:
- Immediate hypersensitivities:
o Type I (anaphylaxis): contact with allergen sensitizes individual; second contact results in immediate symptoms (swelling caused by IgE binding to allergen & causing release of histamine from mast cells & basophils)
§ Produces symptoms of asthma - treated with antihistamines
§ In rare cases, may cause anaphylactic shock due to loss of blood plasma (hypotensive shock); can be fatal - treated with epinephrine
§ Atopy: rarely symptoms may appear without initial sensitization
- Subacute hypersensitivities: mediated by IgG & IgM
o Type II (cytotoxic) reactions: antibodies bind to antigens on cell surfaces (bacteria or foreign red blood cells) & stimulate phagocytes & complement-mediated lysis (example: transfusion reactions)
o Type III (immune complex) reactions: insoluble antigen-antibody complexes form resulting in intense inflammatory reaction (example: autoimmune diseases)
- Delayed hypersensitivities:
o Type IV reactions: slower to appear (1-3 days); mediated by T cells (cytotoxic & delayed hypersensitivity) (example: allergic contact dermatitis)