MCAT Biology Pt. 2

Endocrine System

Organs; glands

Hormones: signaling molecules secreted by glands directly into bloodstream to target distant tissues

Peptide Hormones

• made up of amino acids, from small to relatively large

• must bind to extracellular receptor bc they are charged and cannot diffuse through plasma membrane

• generally rapid response but short lived

• water-soluble, can travel freely in bloodstream

Peptide Hormone Pathway

• peptide hormone is first messenger (binds to receptor) → transmission of second messenger → signaling cascade

• Amplification: binding to multiple receptors before it is degraded

• common second messengers: cAMP, IP3, calcium

Peptide Hormone - GPCR Pathway

GPCR → activate/inhibit adenylate cyclase → raise or lower level of cAMP → bind to intracellular targets like protein kinase A → phosphorylates transcription factors like CREB to exert hormone’s ultimate effect

Steroid Hormones

• derived from cholesterol

• produced primarily by gonads and adrenal cortex

• nonpolar → easily cross cell membrane so receptors usually intracellular or intranuclear

• generally slower response but longer lived

• not water-soluble, so carried in an inactive state by protein carriers that may be specific or nonspecific and must dissociate from carrier to be active

  • carrier affects levels of active hormone

Steroid Hormone Pathway

• bind to intracellular/intranuclear receptor → undergo conformational change → bind directly to DNA → increased or decreased transcription of particular genes depending on identity for hormone

Steroid Hormone Dimerization Pathway

Pairing of two receptor-hormone complexes as conformational change

Amino-Acid Derivative Hormones

• less common than peptide and steroid hormones

• epinephrine, norepinephrine, triiodothyronine, thyroxine

• derived from 1 or 2 amino acids

• catecholamines (epinephrine and norepinephrine): bind to G protein-coupled receptors

• thyroid hormones: bind intracellularly

Direct Hormones

• secreted then act directly on target tissue

• ex. insulin from pancreas causes increased uptake of glucose by muscles

Tropic Hormones

• require intermediary to act on target tissue

• GnRH from hypothalamus stimulates release of LH and FSH to act on gonads

• Usually originate from brain and anterior pituitary gland to allow for coordination of multiple processes in body

Hypothalamus

• Bridge between nervous and endocrine systems

• regulates pituitary gland through tropic hormones via paracrine release of hormones into blood portal system connecting two organs (hypophyseal portal system)

• in forebrain, directly above pituitary gland and below thalamus

• negative feedback regulation of pituitary/hypophysis gland → maintain homeostasis and conserve energy

Hypothalamus - Anterior Pituitary Interactions

• Hypothalamus release Gonadotropin-releasing hormone (GnRH) → pituitary release follicle-stimulating hormone (FSH) and luteinizing hormone (LH)

• Hypothalamus releases Growth hormone-releasing hormone (GHRH) → pituitary releases growth hormone (GH)

• Hypothalamus releases Thyroid-releasing hormone (TRH) → pituitary releases thyroid-stimulating hormone (TSH)

• Hypothalamus releases corticotropin-releasing factor (CRF) → pituitary releases adenocorticotropic hormone (ACTH)

• Prolactin-inhibiting factor (PIF) / dopamine release in hypothalamus → INHIBITION secretion of prolactin

Hypothalamus - Anterior Pituitary Interactions Negative Feedback

Axes: three-organ systems that have negative feedback

ex. hypothalamic-pituitary-adrenal axis (HPA)

Hypothalamus - Posterior Pituitary Interactions

• neurons from hypothalamus directly send axons down pituitary stalk into posterior pituitry to release oxytocin and ADH

• Oxytocin - stimulate uterine contraction and initial milk letdown during lactation, and bonding behavior

• Antidiuretic hormone (ADH)/Vasopressin: increase reabsorption of water in collecting ducts of kidneys in response to increased plasma osmolarity

Anterior Pituitary - Tropic Hormones

Tropic (FLAT)

• FSH → gonads

• LH → gonads

• ACTH → adrenal cortex

• TSH → thyroid

Anterior Pituitary - Direct Hormones

Direct (PEG)

• Prolactin → milk production in mammary glands

• Endorphins → decrease perception of pain

• Growth hormone (GH) promote growth of bone and muscle → prevent glucose uptake and stimulate breakdown of fatty acids

  • Kids excess can cause gigantism and deficit results in dwarfism

  • adults have acromegaly and large hands, feet and head

Posterior Pituitary

• contain nerve terminal of neurons with cell body in hypothalamus

• ADH and oxytocin produced by hypothalamus stored here

Posterior Pituitary - ADH

low blood volume (baroreceptors) or increased blood osmolarity (osmoreceptors) → secrete ADH → increased reabsorption of water in kidney at collecting duct

Posterior Pituitary - Oxytocin

during childbirth and suckling of breast → positive feedback loop

Thyroid

• Controlled by thyroid-stimulating hormone from anterior pituitary

Thyroid - Basal Metabolic Rate

• sets basal metabolic rate (via triiodothyronine T3 & hydroxine T4)

  • increase cellular respiration → protein and fatty acid turnover

  • negative feedback loop to anterior pituitary and hypothalamic nuclei

• both T3 & T4 produced by iodination of amino acid tyrosine in follicular cells of thyroid

• hypothyroidism: deficiency of iodine or inflammation of iodine

• cretinism: deficiency of thyroid hormones leading to intellectual disability and developmental delay

• hyperthyroidism: excess hormone from tumor or thyroid overstimulation

Thyroid - Calcium homeostasis

• promote calcium homeostasis (via calcitonin)

• C-cells/parafollicular cells produce calcitonin

• Decreases plasma calcium levels:

  • increasing calcium excretion from kidneys

  • decreasing calcium absorption from gut

  • increasing storage of calcium in bone

• stronger bones and less bone breakdown

Parathyroid Glands

• four glands posterior to thyroid

• produces parathyroid hormone (PTH):

  • antagonistic hormone to calcitonin

    • subject to feedback inhibition

  • promotes phosphorus homeostasis by increasing resorption of phosphate from bone and reducing reabsorption of phosphate in kidney

  • activates vitamin D (absorption of calcium and phosphate in gut)

Adrenal Cortex

• located at top of kidneys

• secretes corticosteroids: glucocorticoids, mineralocorticoids, and cortical sex hormones

Adrenal Cortex - Glucocorticoids

• steroid hormones that regulate glucose levels and protein metabolism

• Cortisol and cortisone:

  • raise blood glucose by increasing gluconeogenesis and decreasing protein synthesis

  • decrease inflammation and immunologic responses

• controlled by CRF → ACTH

Adrenal Cortex - Mineralcorticoids

• used in salt and water homeostasis

• aldosterone

  • increase sodium reabsorption in distal convoluted tubule and collecting duct of nephron

  • decrease reabsorption of potassium and hydrogen ions in nephron

  • under control of renin-angiotensin-aldosterone system

Adrenal Cortex - Cortical Sex Hormones

• androgens and estrogens

• ovaries much more sensitive to disorders of cortical sex hormone production bc relies more on it than testes

Adrenal Medulla

• production of catecholamine sympathetic hormones epinephrine and norepinephrine

• short-term (fast) stress responses compare to cortisol

• cortisol increases synthesis of catecholamines

Pancreas

• exocrine and endocrine functions

• exocrine: secrete substance directly into ducts

• endocrine:

  • islets of Langerhans (small clusters of hormone-producing cells)

    • alpha cell: secrete glucagon

    • beta cell: secrete insulin

    • delat cell: secrete somatostatin

• pancreas: produce large number of digestive enzymes

Pancreas - Glucagon

• secrete during times of fasting

• increase glucose production via glycogenolysis, gluconeogenesis and degradation of protein and fat

Pancreas - Insulin

• antagonistic to glucagon

• secrete when blood glucose levels are high

• induce muscle and liver cells to take up glucose and store it as glycogen for later use

• stimulate anabolic processes like fat and protein synthesis

Pancrease - Insulin Problems

Excess insulin:

• hypoglycemia: low blood glucose concentration

Underproduction:

• diabetes mellitus/hyperglycemia: excess glucose in blood

• glucose will be present in urine b/c kidney nephron cannot reabsorb - accompanied by excess excretion of water

  • polyuria (increased frequency of urination)

  • polydipsia (increased thirst)

• Type I diabetes (insulin-dependent): autoimmune destruction of beta cells of pancreas → low or absent insulin production

• Type II diabetes (non-insulin-dependent): receptor-level resistance to effects of insulin, partially inherited and partially due to environmental factors

Pancreas - Somatostatin

• inhibitor of insulin and glucagon secretion

• high blood glucose and amino acid concentration stimulate its secretion

• produced by hypothalamus too → decrease growth hormone secretion

Gonads

Testes: secrete testosterone in response to stimulation by gonadotropins (LH and FSH)

Ovaries: secrete estrogen and progesterone in response to stimulation by gonadotropins (LH and FSH)

Pineal Gland

• deep in brain

• secrete melatonin: involved in circadian rhythms

  • receives projections from retina → release melatonin when decrease in light

  • blood levels of melatonin responsible for sleepiness

Kidney Hormones

• ADH

• erythropoietin: stimulate bone marrow to increase productions of red blood cells w/ low oxygen levels in blood

Heart Hormones

atrial natriuretic peptide (ANP):

• regulate salt and water balance if excess blood volume stretches atria cells

• promote excretion of sodium and increase urine volume

• no effect on blood osmolarity

Thymus Hormones

thymosin:

• important for proper T-cell development and differentiation

• atrophies by adulthood

Pathway of Respiratory System

nares (nose) → mucous membrane and nasal hairs (vibrissae) → pharynx behind nasal cavity and back of mouth (food + air) → epiglottis (covering of glottis) → glottis (opening of larynx) → larynx → two vocal cords → trachea → two bronchi → lungs → bronchioles → alveoli (tiny balloon like structure for gas exchange) coated with surfactant (detergent lower surface tension and prevent alveoli collapsing on itself)

Surrounding of Lung

• lungs in thoracic cavity

• pleurae: membranes that surround each lung

  • visceral pleura: surface adjacent to lung

  • parietal pleura: outer part surface along chest wall

  • intrapleural space: contain thin layer of fluid

How Lungs Fill

• not passive

• require diaphragm: skeletal muscle to generate negative pressure for expansion & divides thoracic cavity from abdominal cavity

• diaphragm under somatic control, but breathing under autonomic control

Inhalation

• active process

• use diaphragm and external intercostal muscles (layer of muscles between ribs) to expand thoracic cavity

• negative-pressure breathing:

  • diaphragm flattens and chest walls expand outward → intrathoracic volume increases → decrease in intrapleural pressure → lungs increase in volume bc higher pressure in lungs than intrapleural space → inhale air in

Exhalation

• not active process

• external intercostal muscles are relaxed → lungs decrease in volume bc lower pressure in lungs than intrapleural space → air pushed out

• internal intercostal muscles and abdominal muscles: oppose external intercostals and pull rib cage down → decrease volume of thoracic cavity → speed up exhalation

Lung Capacities and Volumes

• spirometer: instrument that measures lung capacities and volumes

Total lung capacity (TLC)

• max volume of air in lungs when one inhales completely

• usually around 6-7 liters

Residual Volume (RV)

volume of air remaining in lungs when one exhales completely

Vital Capacity VC)

difference between the minimum and maximum volume of air in the lungs (TLC - RV)

Tidal volume (TV)

Volume of air inhaled or exhaled in a normal breath

Expiratory reserve volume (ERV)

Volume of additional air that can be forcibly exhaled after normal exhalation

Inspiratory reserve volume (IRV)

Volume of additional air that can be forcibly inhale after a normal inhalation

Regulation of breathing

Ventilation center: collection of neurons in medulla oblongata that fire rhythmically to cause regular contraction of respiratory muscles

• contain chemoreceptors sensitive to CO2 concentration

• partial pressure of CO2 in blood increases (hypercarbia/hypercapnia) → respiratory rate increase → more CO2 exhaled

• also respond to changes in oxygen concentration but only significant during periods of significant hypoxemia (low O2 concentration in blood)

Gas Exchange

• primary function of lungs

• deoxygenated blood from body → right ventricle of heart → pulmonary arteries → capillaries → alveoli for diffusion of CO2 from blood to lungs and oxygen to blood → oxygenated blood → pulmonary veins → oxygenated blood

• driving force for gas exchange is pressure differential of oxygen down concentration gradient

Gas Exchange - higher altitudes

• less oxygen available

• breathe more rapidly to avoid hypoxia

• binding dynamics of hemoglobin to oxygen be altered too → and more RBC and blood vessel formation

Respiratory Thermoregulation

regulation of body temperature

vasodilation: increase thermal energy dissipation

vasoconstriction: decrease thermal energy dissipation and conserve them

Immune Function

• lysozyme (attack bacteria) and vibrissae present in nasal cavity

• mucociliary escalator: underlying cilia in respiratory tract to oral cavity propel mucus with gunk

• alveoli contain macrophages: digest pathogens

• lungs also contain mast cells: preformed antibodies on surfaces (cause of allergic reactions though too!)

Respiratory Control of pH

• pH balance via bicarbonate buffer system in blood

• kidneys play a role in this too by modulating secretion and resorption of acid and base within nephron → but much slower response and long-term compensation

Respiratory Control of pH - Acidemia

• acidemia: pH lower (H+ conc higher) than desired range

  • acid-sensing chemoreceptors outside BBB send signals to brain to increase respiratory rate & generate additional carbon dioxide to decrease (H+)

  • more carbon dioxide blown off and exhaled from the chemoreceptors in medulla too → shift to left as well to decrease (H+)

Respiratory Control of pH - Alkalemia

• alkalemia: blood too basic, seek to increase acidity

  • in lungs if respiratory rate slowed → more CO2 retained → shift eqn to right and make more hydrogen and bicarbonate ions → lower pH

Anatomy of Cardiovascular System

Cardiovascular system: consists of muscular four-chambered heart, blood vessels, and blood

• vasculature: arteries, capillaries and veins

• *Refer to anatomy lab drawings for details about valves, pulmonary circulation, etc.

Electrical Conduction in Heart

1. sinoatrial node (SA node): impulse initiation occurs, 60-100 signals per minute w/o neurological input → two atria contract (systole) simultaneously

   1. atrial kick: additional volume of blood from atria contracting and pushing blood to ventricles (5-30% cardiac output)

2. atrioventricular node (AV node): at junction of atria and ventricles → signal delayed to wait to fill ventricles before they contract

3. bundle of His (in intraventricular septum - wall)

4. Purkinje fibers: distribute electrical signal through ventricular muscle

• muscle cells connected by intercalated discs → contain many gap junctions directly connecting cytoplasm of adjacent cells → coordinated ventricular contraction

Contraction

• systole: ventricular contraction and closure of AV valves → blood pumped out of ventricles

• diastole: ventricles relaxed, semilunar valve are closed, blood from atria fills ventricles

• arteries are elastic to accommodate these large changes in pressure as blood is pumped through them and also maintain pressure of blood overall

Cardiac Output

• cardiac output: total blood volume pumped by ventricle in minute

• CO = HR (beats per min) x SV (stroke volume, volume of blood pumped per beat)

• humans = 5 liter per min

Vasculature

Arteries: leave heart

• much more smooth muscle than veins / elastic (rounded shape compared to floppy veins)

Vein: go toward heart

• have valves going up to keep blood from flowing back

• contain up to ¾ of our blood at any given time

Blood vessels lined with endothelial cells maintain vessel by releasing chemicals aiding in vasodilation and vasoconstriction

Blood circulation order

inferior/superior vena cava → right atrium → tricuspid valve → right ventricle → pulmonary valve → pulmonary artery → lungs → pulmonary veins → left atrium → mitral valve → left ventricle → aortic valve → aorta → arteries → arterioles → capillaries → venules → vein → venae cavae → right atrium

Portal Systems

• one capillary bed connect to another before going back to heart

• hepatic portal system: blood leaving capillary beds in wall of gut pass hepatic portal vein before reaching capillary beds in liver

• hypophyseal portal system: blood leaving capillary beds in hypothalamus travels to capillary beed in anterior pituitary

• renal portal system: blood leaving glomerulus travels in efferent arteriole before surrounding the nephron in capillary network called vasa recta

Blood Composition - Erythrocyte/RBC

• oxygen transport

• contains 250 million molecules of hemoglobin which can carry 4 molecules of oxygen

Blood Composition - Leukocytes/WBC

• less than 1% total blood

• granular leukocytes/granulocytes: neutrophils, eosinophils, basophils

  • contain cytoplasmic granules toxic to invading microbes and released via exocytosis

• agranulocytes: lymphocytes and monocytes

  • lymphocytes: specific immune response like viruses and bacteria via T-cells and B-cells

  • monocytes → macrophages when leave blood cell; microglia in CNS, Langerhans cells in skin, osteoclasts in bone

Blood Composition - Thrombocytes/Platelets

• cell fragments or shards released from cells in bone marrow known as megakaryocytes

• assist in blood clotting and present in high concentrations

Blood Composition - Hematopoiesis

• hematopoiesis: production of blood cells and platelets, triggered by hormones, growth factors and cytokines

  • erythropoietin: secrete by kidney and stimulate RBC development

  • thrombopoietin: secreted by liver and kidney and stimulate platelet development

Blood Antigens

antigens: surface proteins expressed by RBC

• any specific target (protein) to which immune system can react

Blood Antigens - ABO

• A and B alleles are codominant

• O allele is recessive

• O blood: universal donors b/c blood will not cause ABO-related hemolysis in any recipient

• AB blood: universal recipient can receive blood from all blood types

• e Coli has proteins that match A and B alleles so body can make antibodies in response to that → ex. blood type A can make anti-B antibodies

Blood Antigens - Rh Factor

• Rh-positive or Rh-negative refers to presence of specific allele called D

• Rh positivity follows autosomal dominant inheritance

• Erythroblastosis fetalis: fatal to fetus bc if second child Rh+ and mom Rh-, after first child Rh+, mom already made antibodies to attack baby

Blood Pressure

• sphygmomanometer

• normal is between 90/60 and 120/80

• DeltaP (pressure differential across circulation) = CO (cardiac output) x TPR (total peripheral vascular resistance)

• atrial natriuretic peptide - ANP - lowers blood pressure

Gas and Solute Exchange - Oxygen

• carried by hemoglobin

• normal partial pressure of O2 in blood is 70-100mmHg

• oxygen saturation: percentage of hemoglobin molecules carrying oxygen - generally above 97%

• cooperative binding: easy to bind if one oxygen bound and easy to unbind if one oxygen unbinds

• Bohr effect: CO2 bicarbonate buffer make H+ with dissociation → bind to hemoglobin → lower hemoglobin affinity for oxygen → release more O2

Gas and Solute Exchange - Fluid Balance

• Hydrostatic pressure: force per unit area that blood exerts against vessel walls, by contraction of heart and elasticity of arteries towards interstitium via capillary walls

• Osmotic pressure/oncotic pressure: sucking pressure generated by solutes to draw water back into bloodstream via plasma proteins

• Starling forces: balancing of these opposing pressures

• Edema: too much excess fluid in interstitium (can be caused by blockage of lymph via thoracic duct)

Coagulation

Clots: composed of coagulation factors (proteins) and platelets

• tissue factor: protein in underlying connective tissue at site of injury exposed

• platelets see this exposed collagen and protein → release content and begin to aggregate + coagulation factors from liver sense tissue factor and initiate complex activation cascade → activation of prothrombin to form thrombin by thromboplastin → fibrinogen into fibrin → clot → plasminogen → plasmin to break down clot

Innate Immunity/Nonspecific Immunity

composed of defenses always active against infection by lack ability to target specific invaders

Adaptive/Specific Immunity

• Defenses that target specific pathogen

• slower to act but can maintain immunological memory of infection to mount faster attack on subsequent infections

Anatomy of Immune System

bone marrow → leukocytes (WBC)

• Spleen → location of blood storage and activation of B cells → plasma cells to produce antibodies (act in blood = humoral immunity)

• thymus → location of T-cells maturation in front of pericardium (cell-mediated immunity = act in cell directly killing viral cells)

• lymph nodes → immune cells communicate and mount attack → B cells activated here too

• gut-associated lymphoid tissue (GALT): tonsils & adenoids in head, Peyer’s patches in small intestine, lymphoid aggregates in appendix

Innate Immune System - Noncellular Nonspecific Defenses - Skin

• Skin (integument):

  • physical barrier

  • defensins: antibacterial enzymes on skin

  • sweat: antimicrobial properties

Innate Immune System - Noncellular Nonspecific Defenses - Mucus

• trap particulates like smoke and dirt

• prevent bacteria and viruses from gaining access to lung tissue below

• lysozyme: nonspecific bacterial enzyme around eye and oral cavity, secreted in tears and bacteria

Innate Immune System - Gastrointestinal Tract

• stomach secrete acid that kills pathogens

• gut flora in intestine → does not allow too many other bacteria to invade and grow

Innate Immune System - Complement

• number of proteins in blood that act as nonspecific defense against bacteria

• classical pathway: require binding of antibody to pathogen

• alternative pathway: does not require antibodies

• punch holes in cell walls of bacteria to make them osmotically unstable

Innate Immune System - Interferons

proteins that prevent viral replication and dispersion, produced by infected cells

• responsible for many flu-like symptoms

• upregulate MHC class I and class II easier to antigen presentation

• decrease permeability of neighboring cells

• decrease production of viral and cellular protein in neighboring cells

Innate Immune System - Macrophages

• agranulocyte residing within tissues

• from blood borne monocytes and can become resident population within tissue

Innate Immune System - Macrophages Pathway

1. phagocytizes the invader through endocytosis

2. digests invader using enzymes

3. presents little pieces of invader (mostly peptides) to other cells using protein called major histocompatibility complex (MHC) → bind to pathogenic peptide called antigen → carries it to cell surface → recognized by cells of adaptive immune system

4. macrophage also release cytokines: chemical substances stimulating inflammation and recruiting additional immune cells to the area

Innate Immune System - MHC Class I Molecules

• loaded onto MHC-1 and presented on surface of cell

• only infected cells would present unfamiliar (nonself) protein on surfaces

• endogenous pathway: binds antigens that come from inside cell

• can be killed then by T-Cells

Innate Immune System - MHC Class I Molecules

• displayed by professional antigen-presenting cells like macrophages, dendritic cells in skin, some B-cells and certain activated epithelial cells

• antigen: substance (pathogenic protein) that can be targeted by an antibody

• exogenous pathway: antigens originated outside of cell

  • presentation of antigen by immune cell result in activation of both innate and adaptive immune systems

Innate Immune System - Pattern Recognition Receptors

macrophage and dendritic cell also have special receptors: pattern recognition receptors (PRR) / toll-like receptors (TLR): recognize category of invader and produce appropriate cytokines to recruit right type of immune cells

Innate Immune System - Natural Killer Cells (NK)

viruses can cause downregulation of MHC molecules → harder for T-cells to recognize presence of infection

NK cell: nonspecific lymphocyte detecting downregulation of MHC via these viruses and even some cancers and induce apoptosis in these virally infected or cancerous cells

Innate Immune System - Granulocytes - Neutrophils

• most populous leukocyte in blood, very short lived

• phagocytic

• follow bacteria with chemotaxis (movement of organism via chemical stimuli)

• detect bacteria once they have been opsonized (marked with antibody from B-cell)

• dead neutrophil → pus

Innate Immune System - Granulocytes - Eosinophils

• bright red-orange granules

• involved in allergic reactions and invasive parasitic infection

• release a lot of histamine: inflammatory mediator → vasodilation and leakiness of blood vessels → additional immune cells to move out of bloodstream and into tissue

Innate Immune System - Granulocytes - Basophils

• large purple granules

• allergic responses

• least populous leukocyte

• Mast cells: closely related to basophils but smaller granules and exist in tissues, mucosa and epithelium

• release a large amount of histamine in response to allergens

Humoral Immunity

• production of antibodies (immunoglobulins Ig)

• take up to a week to become fully effective

• antibodies specific to antigens of invading microbe

• antibodies produced by B-cells, which are lymphocytes that originate and mature in bone marrow and activate in spleen and lymph nodes

Humoral Immunity - Function of antibodies

1. once antibodies bound to specific antigen, antibodies may attract other leukocytes to phagoytize antigens immediately (opsonization)

2. antibodies may cause pathogens to clump together (agglutinate), forming large insoluble complexes that can be phagocytized

3. antibodies can block ability of pathogen to invade tissues, essentially neutralizing it

• when antigen binds to cell-surface antibodies on B-cell → proliferation of B-cells and formation of plasma and memory cells

• when antigen binds to antibodies on surface of mast cell → degranulation (exocytosis of granule contents) → release histamine → inflammatory allergic reaction

Humoral Immunity - Structure of antibodies

• two identical heavy chains inside and two identical light chains parallel to heavy chains, make a Y shape (V) domain and C domain

• antigen binding region/variable region/domain: at end of Y

• hypermutation: mutation of antigen-binding region for B-cell, trying to find best match for antigen

  • clonal selection: only best affinity antibody survive

• constant region (C) domain: cells like NK cells, macrophages, monocytes and eosinophils have receptors for to initiate complement cascade

• isotype switching: cells change which isotype of antibody they prduce when stimulated by specific cytokines

  • IgG, IgA, IgM, IgD, and IgE

Humoral Immunity - Types of B cells

• naive B-cells (note yet exposed to antigen) wait in lymph nodes for particular antigen to come along → then produce two daughter cells

  • Plasma cells: produce large amount of antibodies

  • memory B cells: stay in lymoh node, awaiting reexposure to same antigen

• primary response: initial activation of the two types of daughter cells, 7-10 days

• secondary response: rapid and robust, re-exposed to previous antigen

• Vaccination: development of lasting memory cells basis for efficacy of vaccines

Cytotoxic Immunity

• positive selection: allowing only maturation of cells that can response to presentation of antigen on MHC, apoptosis of those that don’t react to MHC

• Negative selection: causing apoptosis in cells that are self-reactive (activated by proteins produced by organism itself)

Cytotoxic Immunity: Types of T cells

• helper T-cells (Th) CD4+ T-cells: coordinate immune response by secreting other immune cells (plasma cells, cytotoxic T-cells, macrophages)

  • loss of these cells = HIV / AIDS

• cytotoxic T-cells (Tc) CTL or CD8+ T-cells: capable of directly killing virally infected cells by injecting toxic chemicals for apoptosis of infected cells

  • respond to antigen on MCH-I molecules

• Suppressor or regulatory T-cells (Treg): express CD4 but differentiated bc also express Foxp3

  • tone down immune response once infection adequately contained

  • self-tolerance: turn off self-reactive lymphocytes to prevent autoimmune disease

• memory T-cells: similar to memory B-cells, wait until next exposure to same antigen

Bacterial (Extracellular Pathogen) Infections

macrophage engulf bacteria and release inflammatory mediators → digest bacteria and present antigens in conjunction with MHC-II → cytokines → inflammatory cells (neutrophils and other macrophages and mast cells) → histamine release and leakiness of capillaries → dendritic cell goes to lymph node to present antigen to B-cells to make plasma cells and memory cells → tag bacteria for instruction + dendritic cells → antigen to T-cells to activate helper T cells