Hormone Classifications and Glands

Chemical Classification of Hormones and Receptors

• Steroid hormones are derived from cholesterol and produced by the adrenal glands and gonads.
• Steroid hormones are hydrophobic and travel through the blood bound to transport proteins.
• Steroid hormones diffuse across the cell membrane and bind to intracellular receptors to activate genes in the nucleus.
• Non-steroid hormones include peptides and proteins.
• Non-steroid hormones are hydrophilic and do not require transport proteins.
• Non-steroid hormones bind to cell surface receptor proteins and activate second messenger systems to alter gene expression.
• Amino acid hormones are derived from tyrosine, including thyroid hormones (T3, T4) and catecholamines (epinephrine and norepinephrine).

Pituitary Gland and Hypothalamus

• The hypothalamus regulates the anterior pituitary gland along with monitoring body temperature, metabolism, and electrolyte balance.
• The hypothalamus communicates via vascular and neural pathways.
• The hypothalamus produces thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH), gonadotropin-releasing hormone (GnRH), and growth hormone-releasing hormone (GHRH).
• Somatostatin (GHIH) is produced in the hypothalamus to inhibit growth hormone.
• The hypothalamus produces dopamine (prolactin-inhibiting hormone).
• The anterior pituitary lobe (adenohypophysis) is derived from oral ectoderm and produces growth hormone (GH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL).
• The posterior pituitary lobe (neurohypophysis) is derived from neural ectoderm; it stores and releases antidiuretic hormone (ADH/vasopressin), which regulates water balance and oxytocin which induces uterine contractions and lactation.

Thyroid and Parathyroid Glands

• The thyroid gland, located anterior to the trachea and inferior to the larynx, consists of two lobes connected by the isthmus.
• The thyroid gland produces thyroxine (T4) and triiodothyronine (T3) to regulate metabolism, along with calcitonin which lowers blood calcium levels.
• The parathyroid glands are four small glands located on the posterior thyroid that secrete parathyroid hormone (PTH).
• PTH increases blood calcium levels by stimulating the activity of osteoclasts.

Pancreas

• The pancreas is a retroperitoneal organ with both exocrine and endocrine functions, divided into the head, uncinate process, neck, body, and tail.
• The pancreas contains the Islets of Langerhans for its endocrine function:
• Beta cells secrete insulin to lower blood sugar.
• Alpha cells secrete glucagon to raise blood sugar.
• Delta cells secrete somatostatin to inhibit GH and insulin.
• PP cells secrete pancreatic polypeptide.

Adrenal Glands

• Located on top of each kidney and secrete steroid hormones and catecholamines.
• The adrenal cortex has three zones:
• Zona glomerulosa secretes aldosterone which regulates sodium balance.
• Zona fasciculata secretes cortisol for the stress response.
• Zona reticularis secretes androgens.
• The adrenal medulla contains chromaffin cells that secrete epinephrine and norepinephrine in response to sympathetic stimulation.

Blood Supply and Regulation of Endocrine Glands

• The thyroid gland is supplied by the superior and inferior thyroid arteries.
• The parathyroid glands are supplied by the inferior thyroid arteries.
• The pancreas is supplied by the splenic and pancreaticoduodenal arteries.
• The adrenal glands are supplied by the suprarenal arteries and veins.
• Negative feedback loops include T3 and T4 inhibiting TRH and TSH production.
• Cortisol inhibits CRH and ACTH production and PTH regulates blood calcium through bone resorption.
• An example of a positive feedback loop is oxytocin during childbirth, which stimulates more contractions.

Growth Hormone (GH/Somatotropin)

• GH is produced by somatotroph cells in the anterior pituitary to regulate body growth via the hypothalamic-pituitary axis.
• The hypothalamus releases growth hormone-releasing hormone (GHRH).
• GH release is stimulated by hypoglycemia, epinephrine, estrogen, and testosterone and inhibited by increased GH, somatomedins (IGF-1), and somatostatin (GHIH).
• GH and IGF-1 inhibit GHRH and increase somatostatin in a negative feedback loop.
• Direct effects of growth hormone:
• Adipose tissue: Stimulates lipolysis for energy.
• Liver: Triggers gluconeogenesis and glycogenolysis to increase blood glucose.
• Tissues: Increases insulin resistance.
• Indirect effects of growth hormone via IGF-1:
• Muscles stimulates amino acid uptake, protein synthesis, and growth.
• Bones stimulates osteoblasts and chondrocytes for bone growth.

Antidiuretic Hormone (ADH/Vasopressin)

• ADH is produced in the paraventricular and supraoptic nuclei of the hypothalamus and stored/released from the posterior pituitary.
• Release of ADH is stimulated by increased blood osmolarity (detected by osmoreceptors) and low blood pressure (detected by baroreceptors in the carotid artery and aorta).
• Target cells and effects of ADH:
• Kidneys: Acts on the distal convoluted tubule and collecting ducts, binds AVPR2 receptors to insert aquaporin-2 water channels, and increases water reabsorption to reduce urine output.
• Blood vessels: Causes vasoconstriction to increase blood pressure.
• Increased blood pressure causes baroreceptors to inhibit the hypothalamus, decreasing ADH secretion in a negative feedback loop.

Insulin

• Insulin is produced by Beta cells in the Islets of Langerhans in the pancreas.
• Insulin release is stimulated by high blood glucose, glucagon, cortisol, and acetylcholine and inhibited by norepinephrine and somatostatin.
• Target organs and effects of insulin:
• Liver: Converts glucose to glycogen and inhibits gluconeogenesis.
• Adipose tissue: Converts fatty acids to fat.
• Skeletal muscle: Increases amino acid uptake, protein synthesis, and muscle growth.
• In a negative feedback loop, increased glucose uptake lowers blood glucose which reduces insulin secretion.

Glucagon

• Glucagon is produced by Alpha cells in the Islets of Langerhans in the pancreas.
• Glucagon release is stimulated by low blood glucose, adrenaline, and cholecystokinin.
• Glucagon release is inhibited by high blood glucose, insulin, and somatostatin.
• Target organs and effects of glucagon:
• Liver: Converts glycogen to glucose (glycogenolysis) and stimulates gluconeogenesis.
• Adipose tissue: Stimulates lipolysis (fat breakdown).
• During fasting, glucagon is secreted, while after a meal, high glucose triggers insulin release, which inhibits glucagon.

Cortisol (Glucocorticoid)

• Cortisol is produced by the Zona Fasciculata of the Adrenal Cortex.
• The hypothalamus releases CRH, stimulating ACTH release from the anterior pituitary, which stimulates cortisol production.
• Cortisol production is stimulated by stress, hypoglycemia, infection, and sleep deprivation.
• Cortisol inhibits CRH and ACTH production in a negative feedback loop.
• Target organs and effects of cortisol:
• Immune System: Suppresses inflammation and inhibits IL-2 production.
• Liver: Stimulates gluconeogenesis and glycogen storage.
• Muscles: Stimulates proteolysis to increase amino acids for gluconeogenesis.
• Adipose tissue: Stimulates lipolysis.
• Blood vessels: Increases vasoconstriction, raising blood pressure.
• Bone: Inhibits osteoblasts, reducing bone formation.

Thyroid Hormones (T3 & T4)

• T3 and T4 are produced by Follicular Cells of the Thyroid Gland.
• The hypothalamus releases TRH, stimulating TSH release from the anterior pituitary, which stimulates T3 and T4 production
• High T3/T4 inhibits TRH & TSH production in a negative feedback loop.
• Target organs and effects of T3 and T4
• All Cells: Increases Na+/K+ ATPase activity, increasing metabolic rate.
• Liver: Increases gluconeogenesis and lipolysis.
• Cardiovascular System: Increases heart rate and cardiac output.
• Growth: Essential for CNS development and bone growth.

Parathyroid Hormone (PTH)

• PTH is produced by Chief Cells of the Parathyroid Glands.
• PTH release is stimulated by low extracellular calcium and inhibited by high extracellular calcium.
• Target organs and effects of PTH:
• Bone: Stimulates osteoblasts to release cytokines that activate osteoclasts, increasing calcium release.
• Kidneys:
• Proximal Tubule: Inhibits phosphate reabsorption, lowering serum phosphate.
• Distal Tubule: Increases calcium reabsorption.
• Activates 1-alpha-hydroxylase enzyme, converting vitamin D into active form (calcitriol) to increase calcium absorption in the intestines.

Hormonal Feedback Loops

• Negative Feedback Loops:
• T3/T4 inhibit TRH & TSH secretion.
• Cortisol inhibits CRH & ACTH secretion.
• Increased glucose inhibits glucagon release.
• PTH is inhibited by high calcium levels.
• Positive Feedback Loop:
• Oxytocin stimulates uterine contractions, leading to further oxytocin release during childbirth.

Introduction to the Immune System

• The immune system protects the body from pathogens (bacteria, viruses, fungi, parasites), through organs, cells, and molecules that coordinate immune responses.
• The immune system has two primary branches:
• Innate Immune System: Fast, non-specific, no memory.
• Adaptive Immune System: Specific, slower, memory-based.
• Components of the immune system:
• White Blood Cells (Leukocytes):
• Myeloid cells: Neutrophils, basophils, eosinophils, monocytes (macrophages, dendritic cells).
• Lymphocytes: T cells, B cells, Natural Killer (NK) cells.

Innate Immune Response

• The innate immune response is the first line of defense, it is rapid and non-specific.
• Recognizes invaders through pattern recognition receptors (PRRs).
• It responds the same way to repeated infections (no memory).
• Cells of the innate immune system:
• Neutrophils: First responders, phagocytose pathogens, destroy pathogens through phagolysosome formation and oxidative burst.
• Macrophages: Phagocytose pathogens, release cytokines to signal other immune cells and present antigens to activate T cells.
• Dendritic Cells: Found in skin and mucosal tissues, phagocytose pathogens, process antigens, migrate to lymph nodes, present antigens to T cells.
• Natural Killer (NK) Cells: Target virus-infected cells and cancer cells, kill through perforin and granzymes, recognize the absence of MHC I molecules on infected cells.

Adaptive Immune Response

• Slower but highly specific.
• Generates memory cells for stronger future responses.
• B Cells: Mature in the bone marrow, when activated, they become plasma cells that produce antibodies.
• The B cell antibodies function by:
• Neutralizing pathogens.
• Marking pathogens for destruction (opsonization).
• Activating complement system.
• T Cells:
• T-Cell Receptor (TCR) binds antigen presented on MHC molecules.
• CD4 Helper T Cells bind MHC II and activate the immune responses.
• CD8 Cytotoxic T Cells bind MHC I and kill infected cells.
• Helper T Cells (CD4+): Support immune functions by secreting cytokines, activate B cells, macrophages, and cytotoxic T cells, recognize MHC II molecules from antigen-presenting cells (APCs).
• Cytotoxic T Cells (CD8+): Kill infected cells by binding MHC I molecules, release perforin (punches holes) and granzymes (triggers apoptosis).

Major Histocompatibility Complex (MHC) Molecules

• MHC I Molecules: Found on all nucleated cells, present antigens to Cytotoxic T Cells (CD8+), signal infected or cancerous cells for destruction.
• MHC II Molecules: Found on antigen-presenting cells (APCs) (macrophages, dendritic cells, B cells), present antigens to Helper T Cells (CD4+), activate helper T cells to coordinate immune responses.

T Cell Activation & Clonal Expansion

• Two-Signal Requirement for T Cell Activation:
• Antigen Recognition: TCR binds to antigen on MHC molecule.
• Co-stimulation: CD28 on T cell binds B7 on APC.
• Lack of co-stimulation leads to T cell anergy (inactive state).
• Clonal Expansion of T Cells:
• Activated Helper T Cells secrete IL-2.
• IL-2 binds IL-2 receptors on activated T cells leading to rapid proliferation.

Immunological Memory

• After infection, memory T and B cells persist, providing faster and stronger responses upon re-exposure.
• Vaccines work by creating memory cells without causing disease.

Immune Response to Pathogens

• Bacterial Infections:
• Macrophages & neutrophils phagocytose bacteria.
• Dendritic cells present antigens to T cells.
• CD4+ Helper T cells activate B cells, then plasma cells secrete antibodies that opsonize bacteria for destruction.
• Viral Infections:
• Infected cells display viral antigens on MHC I.
• Cytotoxic T cells (CD8+) kill infected cells.
• Natural Killer cells attack cells lacking MHC I.
• Antibodies neutralize extracellular viruses.

Summary of Key Immune Cells & Functions

• Neutrophils: Phagocytosis & oxidative burst, targetting bacteria
• Macrophages: Phagocytosis and cytokine secretion, targetting bacteria and fungi
• Dendritic Cells: Antigen presentation to T cells, targetting various pathogens
• Natural Killer Cells: Kill virus-infected & cancer cells targeting infected cells
• Helper T Cells (CD4+): Activate immune cells targeting antigen-presenting cells
• Cytotoxic T Cells (CD8+): Kill infected cells targeting cells with MHC I
• B Cells: Produce antibodies targeting pathogens in blood

Overview of the Lymphatic System

• Functions:
• • Fluid Balance: Returns excess interstitial fluid to the bloodstream.
• • Immune Surveillance: Houses lymphocytes (T & B cells) to detect and fight pathogens.
• • Fat Absorption: Transports dietary lipids from the intestines.
• Components:
• • Lymph: Clear fluid containing immune cells.
• • Lymphatic Capillaries: Smallest vessels, collect excess interstitial fluid.
• • Lymphatic Vessels: Transport lymph through lymph nodes.
• • Lymphatic Trunks & Ducts which include the:
• -- Right Lymphatic Duct: drains right upper body into the venous system and the
• -- Thoracic Duct: Drains lymph from the rest of the body into the venous system.

Lymphoid Organs & Immune Function and their functions they include:

• Primary Lymphoid Organs that: includes the:
• • Bone Marrow; which: Produces B cells & T cell precursors.
• • Thymus; which is the: Site of T cell maturation & selection.
• Secondary Lymphoid Organs:
• • Lymph Nodes: Filter lymph and detect pathogens, while they; Contain B & T cells, dendritic cells, macrophages.
• • Spleen:
• -- White pulp; Filters blood for pathogens, activates immune responses.
• -- Red pulp: Destroys old RBCs, stores platelets.
• • Tonsils; works to: Trap inhaled/ingested pathogens.

Innate Immune System: First Line of Defense Key

• Characteristics include:
• • Non-specific: Targets broad pathogen categories.
• • Fast-acting: Immediate response (minutes to hours).
• • No Memory and responds the same way every time.
• Physical & Chemical Barriers by:
• • Skin & Mucous Membranes Prevents pathogen entry.
• • Tears & Saliva; has content that: Contain lysozymes that break down bacterial walls.
• • Stomach Acid Kills ingested microbes
• • Cilia in Airways; functioning to: Trap and remove inhaled pathogens.
• Macrophages; these are:.
• • First responders, found in tissues
• • They Recognize Pathogen-Associated Molecular Patterns (PAMPs) and
• -- Perform Phagocytosis: Engulf and digest microbes, while using
• -- Cytokine Secretion: To Recruit immune cells. With the goal being to:
• ---Oxidative Burst: Uses reactive oxygen species (ROS) to kill microbes.
• Neutrophils:
• • Most abundant WBC in blood.
• • Phagocytosis & oxidative burst to destroy pathogens.
• • Are Short-lived, rapidly recruited to infection sites.
• Denritic Cells are a: Bridge between innate and adaptive immunity with with goal to:
• • Capture antigens, migrate to lymph nodes, and activate Cells in the Body
• Natural Killer (NK) Cells
• • Destroy virus-infected & cancerous cells with the intent to:
• --Recognize absence of MHC I molecules.
• --Use perforin & granzymes to induce apoptosis.
• --Mediate Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC).

Complement System Functions

• Opsonization: Marks pathogens for phagocytosis.
• Inflammation: Recruits immune cells via C3a & C5a.
• Direct Pathogen Lysis: Forms Membrane Attack Complex (MAC).
• Pathways to Complement Activation include three sections which are:.
• -Classical Pathway: Is: Triggered by antibodies (IgG or IgM) bound to antigens.
• --C1 binds antibodies which activate C2 & C4 which then Forms C3 convertase.
• • Lectin Pathway these are :Triggered by mannose-binding lectin (MBL) binding mannose on bacterial walls.
• ---Leads to C convertase formation and which :are Amplifies immune response by forming C3 convertase. Alternative Pathway: Triggered by direct C3b binding to microbial surfaces.
• Formation of Membrane Attack Complex (MAC) steps:
• -C3 convertase cleaves C3 which Produces C3b, Then ,
• -C5 convertase forms cleaves C5 into C5a & C5b follows which,
• --C5b binds C6, C7, C8, and multiple C9 molecules which Forms MAC and then the ,
• --- MAC creates a pore in bacterial membranes, causing lysis and death.

Inate to Adaptive Immunity

• -Immediate response (minutes to hours) vs which causes a: Delayed response (days to weeks)
• -Non-specific vs Highly specific (recognizes unique antigens)
• -No memory vs Memory cells allow faster future responses
• -Macrophages, Neutrophils, NK cells, Complement system
• The B cells Adaptive Immunity are involved in the: Antibody Production with the ,T cells and the: (CD4/CD8 involved in the Activation)