MCB 135 E Final Review Fall 2005 GSI

MCB 135 E Final Review Fall 2005 GSI: Jason Lowry

Exam Information • Monday, Dec. 19 th • 22 Warren • 5 -8 pm • • Multiple Choice (50 pts) True / False (50 pts) Short Answer (100 pts) Comprehensive exam – Majority will come from material since last midterm

New Material • Immune System • Adolescence and Puberty • Factors Affecting Sexual Behavior • Muscle Growth and Plasticity • Nutrition • Eating Disorders • Homeostasis • Hormesis

Immune System • Function of System • Tissues and Organs Involved • Cells Involved • Viral vs. Bacterial Response • Developmental Aspects • Ig Classes

Cell Types 1. Lymphocytes: derived in bone marrow from stem cells 10^12 A) T cells: stored & mature in thymus-migrate throughout the body -Killer Cells Perform lysis (infected cells) Cell mediated immune response -Helper Cells Enhance T killer or B cell activity -Supressor Cells Reduce/suppress immune activity May help prevent auto immune disease

Lymphocytes (cont. ) B) B-Cells: stored and mature in spleen • secrete highly specific Ab to bind foreign substance (antigen: Ag), form Ab-Ag complex • responsible for humoral response • perform antigen processing and presentation • differentiate into plasma cells (large Ab secretion)

2. Neutrophils- found throughout body, in blood 3. -phagocytosis of Ab-Ag CX 3. Macrophages- throughout body, blood, lymphatics -phagocytose non-specifically (non Ab coated Ag) -phagocytose specifically Ab-Ag CX -have large number of lysosomes (degradative enzyme) -perform Ag processing and presentation -present Ag to T helper cell -secrete lymphokines/ cytokines to stimulate T helper cells and immune activity 4. Natural Killer Cells-in blood throughout body -destroy cancer cells -stimulated by interferons

Macrophage Bacterial Infection

Complement Series of enzymes which are sequentially activated and result in lysis of cell membrane of infected cell at bacterium Permeablizes membrane leaky Complement binding and activation ~35 enzymes and factors involved in cascade

Viral Infection

Immune System • Antibodies – – Types Characteristics Specificity In Newborns • Development of the Immune System

5 classes of Ig Ig. G: 150, 000 m. w. most abundant in blood, cross placental barrier, fix complement, induce macrophage engulfment Ig. A: associated with mucus and secretory glands, respiratory tract, intestines, saliva, tears, milk variable size Ig. M: 900, 000 m. w. 2 nd most abundant , fix complement, induce macrophage engulfment, primary immune response

5 Classes of Ig Ig. D: Low level in blood, surface receptor on Bcell Ig. E: Binds receptor on mast cells (basophils) secretes histamine, role in allergic reactions Increased histamine leads to vasodilation, which leads to increase blood vessel permeability. This induces lymphocyte immigration swelling and redness.

Thymus Involution

ORGAN AND T-CELL DEVELOPMENT • YOLK SAC • • LIVER (4 Weeks) • • BONE MARROW (4 -5 Weeks ) • • THYMUS (7 -10 Weeks) • • • BLOOD LYMPH (14 Weeks) SPLEEN (16 Weeks) T-cells migrate and appear in tissues with development and increase in number throughout Gestation

B-CELLS • FIRST appear in immature state - Liver at 7 weeks • LATER –appear mature by 14 -20 weeks • CAN DIFFERENTIATE INTO IMMUNOLOGICALLY COMPETENT ANTIBODY-PRODUCING PLASMA CELLS

NATURAL KILLER CELLS • FIRST APPEAR IN FETAL BONE MARROW AROUND 13 WEEKS GESTATION • FOUND THROUGHOUT BODY • NK CELLS HAVE DIMINISHED ACTIVITY BEFORE BIRTH COMPARED TO ADULT • STIMULATED BY INTERFERON AFTER 27 WEEKS

COMPLEMENT PROTEINS • • ARISE FROM LIVER FIRST DETECTED 5 -6 WEEKS GESTATION INCREASE GRADUALLY IN CONCENTRATION AT ABOUT 28 WEEKS COMPLEMENT PROTEINS ARE AROUND 2/3 THAT OF ADULT CONCENTRATIONS • INDIVIDUAL VARIATION

• • Adolescence and Puberty Functional Changes During Adolescence Male Reproductive System Maturation Female Reproductive System Maturation

Adolescence and Puberty • Adolescence – Period between onset of reproductive function and adulthood (maturation of functions) • Puberty – Maturation of reproductive function – One of many physiologic changes occurring during adolescence

Puberty • Gonadal Function in Children Characterized by: – Very low levels of sex hormones – Very low levels of Gn. RH and FSH/LH – Testis and Ovary are differentiated • Indicates negative feedback is not functioning correctly

CNS Development and Sexual Maturation • CNS Matures progressively from birth to late childhood by: – Dendritic branching and number of synapses – Glial Cell Number – These lead to better communication, better metabolism, more efficient neurotransmissions • Due to a decreased threshold, neurons are responsive to lower stimuli levels

Experimental Evidence of Limbic System Immaturity • Immature gonads transplanted into an adult animal will mature immediately and demonstrate normal reproductive function • The pituitary taken from a prepubertal animal and transplanted into an adult will regulate normal reproductive function • Trauma to the hypothalamus will prevent the prepubertal animal from developing normal reproductive function

Functional Changes • Adult Reproductive function is established during adolescence – Female – Cyclic – Male – Tonic • Puberty Age – Female – 8 -13 – Male – 9 -14

Factors Influencing the Onset of Puberty • Hormonal • Nervous • Somatic (peak of accelerated growth/menarche) • Environmental • Social • Genetic

Precocious or Delayed Puberty True precocious puberty constitutional, cerebral Pseudoprecocious puberty secondary sex characteristics but no spermatogenesis/oogenesis Adrenal (hyperplasia tumor) Gonadal (tumor of Leydig cells or granulosa cells) Delayed Puberty Difficult to establish When menarche fails to occur by 17 years or testicular development by 20 years XO, XXY, panhypopituiarism

Changes at Puberty • Male – Genital • Penis increases length and width • Scrotum becomes pigmented and rugose • Seminal Vesicles enlarge • Prostate enlarges and secretes – Extragenital • Voice - Deepens • Hair - Increased • Behavior – More aggressive, sexual interest • Skin - Acne • Body Conformation • Females – Genital • Vagina and uterus increase in size and thickness • Menarche • Major and Minor Labia enlarge and become pigmented – Extragenital • Voice – Remains high • Hair - Increased • Behavior – Interest in opposite sex • Skin – Some Acne • Body Conformation – Hips Broader, Fat Deposition in breast/buttocks

Blood Pressure and Pulse Rate in Girls before and after menarche Systolic blood pressure Diastolic blood pressure Pulse Pressure Pulse rate

H-P-G Axis

Sex Hormones • Major Male Androgen – Testosterone • Develop and maintain male secondary sex characteristics • Exert important protein, anabolic action, and growth promoting effects • To exert inhibitory feedback on Pit LH secretion • Female Ovarian Hormones • • Estrogen – Stimulates growth and maintenance of secondary sex organs and characteristics – Stimulates ovary and follicle growth – Stimulates growth of smooth muscle and epithelial linings of reproductive tract – Stimulates bone growth and epiphyses closure • Protection against osteoporosis Progesterone – Stimulation of uterine gland secretions – Decrease contractility of uterine muscle – Feedback on hypothalamus and pituitary

Female Menstrual Cycle • Days 1 -5: – E/P levels low – Endometrial epithelium sloughs – FSH and LH increase (due to loss of P inhibition) – Follicles start to enlarge • Days 6 -7 – Dominant follicle selected • Days 7 -12 – Plasma E levels rise and endometrium proliferates • Days 12 -13 – High E induces LH secretion (positive feedback from E) – Oocyte undergoes first meiotic division and undergoes cytoplasm maturation – Follicle is stimulated to secrete lytic enzymes and prostaglandins • Day 14 – Ovulation

Menstrual Cont. • Days 15 -25 – Corpus luteum forms and secretes E/P • Secretory endometrium develops • Secretion of FSH and LH is inhibited (negative FB) • New follicles do not develop • Days 25 -28 – Corpus Luteum degenerates • Plasma levels of E/P decrease • Endometrium Sloughs • Return to Day 1 for a new cycle

• • • Sexualization Muscle Growth and Plasticity Nutrition Eating Disorders Homeostasis Hormesis

Sexualization • Allows: – Perpetuation of species – Genetic adaptation – Two sexes with a common goal • Successful Pregnancy: – Requires • • Mother’s Health Delivery of health child Safe environment to raise child Shared responsibility by mother, family, and society • Choosing of a mate – – Physical Attraction Behavior Chemical Attractants Cultural Influences • Sexual Orientation – Theories about homosexuality • Genes • Sensitivity to alteration of prenatal testosterone

Embryology • All muscles derive from the MESODERM of the GASTRULA Remember? Morula then Blastula then Gastrula • From its mesoderm layer: A) striated or voluntary muscles B) cardiac muscle or scalariform C) smooth muscle (of GI tract, Urinary, etc)

Importance of the Nervous System • Autonomic nervous system controls smooth and cardiac muscles • Central nervous system controls the voluntary muscles

Histology Each fiber being a multinucleated cell consists of myofibrils in bundles with a large number of mitochondria and a myoglobin (pigmented protein)

Contractility Secondary to the sliding characteristic of the 2 main proteins of the myofibrils: MYOSIN ACTIN (thinner)

TYPES of FIBERS Type 1: reddish Slow Oxidative (SO) Type 2: pale and divided into Fast Oxidative Glycolytic (FOG) Fast Glycolytic (FG)

Myoplasticity: Concept Ability of the muscle to alter the quantity and the type of its proteins in response to stimulations Modalities of stimulations: 1) Physical activities leading to an increase in its crosssectional area 2) Increase in the muscular mass with changes in the myosin type Muscle plasticity may involve: • Change in the amount of protein • Change in the type of protein • Combination of both

Myoplasticity Due to Exercise • Endurance exercise increases the oxidative metabolism of the muscle • Resistance training increases the cross-sectional area due to true hypertrophy of the single cells • Inactivity induces rapid regression

Muscle Fiber Number Virtually Fixed at Birth • The increase in mass (hypertrophy, sometimes as much as 50%) is due to increase in length and in the cross-sectional area of the muscle fibers. This is due to an increase in the number of myofibrils (from 75 to over 1000) • The capacity for regeneration and plasticity is a response to neural, hormonal and nutritional differences

The Macronutrients: Lipids • Saturated, no double bonds, usually solid • Trans-fats, from liquid to solid format (usually commercial only) • Mono-unsaturated, like olive oil • Poly-unsaturated, like most other oils • OMEGA 3, fatty acids, like many fish oils

The Micronutrients • Salt, Na+ (<5 mg/day) and K+ (deficits, excesses, need) • Ca+ (1800 mg/day), P and Fl (bone metabolism) • Fe++ (deficit and excess), Cu, Mn, and Mg • Other metals: Cr, Se, Zn and the Metalloid I • Memo the hidden aspects of hypothyroidism

Body Mass Index • Weight in kg divided by height in m 2 • NORMAL BMI : 18 to 24 years of age BMI < 18 : suspect malnutrition BMI 24 to 30 : overweight BMI 30 to 40 : obesity BMI above 40 = morbid obesity

Be familiar with: • Eating disorders – Causes, Symptoms, Treatments • Obesity – Types of obesity – Implication on health • The female athlete triad

Stress induces defense mechanisms for maintenance of homeostasis in response to environmental challenges • • • Types of stress known to stimulate the HPA axis*: • Physical Stress: hypoglycemia, trauma, exposure • to extreme temperatures, infections, heavy exercise • Contraction of spleen capsule • Psychological Stress: Acute anxiety, Anticipation • of stressful situations, Novel situations, Chronic anxiety • Exposure to stress generates: • Specific responses: varying with the stimulus and • generating different responses with each stimulus Non-Specific responses: always the same, regardless of the stimulus and mediated through stimulation of neural, endocrine & immune axes *HPA axis = hypothalamo-pituitary-adrenal axis Increased blood pressure Increased heart rate Increased force of heart contraction Increased heart conduction velocity Shift of blood flow distribution • • Increased depth and rate of respiration Mobilization of liver glycogen to glucose (glycogenolysis) Mobilization of free fatty acids from adipose tissue (lipolysis) Mydriasis (widening of pupil) Accommodation for far vision (relaxation of ciliary muscle) Widening of palpebral fissure (eyelids wide open) Piloerection Inhibition of gastrointestinal motility and secretion, contraction of sphincters Sweating (cold sweats as skin blood vessels are constricted).

Stress, Homeostasis, and Allostasis An organism must vary all parameters of its internal milieu and match them appropriately to environmental demands through: Homeostasis: steady state and optimal set-points are achieved; it is obtained by repeated fluctuation s of various physiological systems (allostasis) and/or long-term exposure to elevated levels of physiologic activity Allostasis: emphasis is on optimal operating ranges of physiologic systems; it represents stability obtained through change Allostatic load: the cumulative, multi-system view of physiologic toll that may be exacted on the body through attempts at adaptation

Pathophysiologic Responses During and After Stress During Stress Energy storage ceases because: Sympathetic activity Parasympathetic activity Insulin secretion Access to energy storage is facilitated & energy storage steps are reversed: glucocorticoid secretion Epinephrine/norepinephrine secretion Glucagon secretion After Stress If physiologic responses are insufficient and adaptation is incomplete, symptoms of poor health are registered (e. g. loss of energy when freeing energy from storage and returning to storage) Examples of consequences: Muscle wasting, Diabetes (Type 2), ulcers, colitis, diarrhea Inhibition of growth (in childhood), Osteoporosis (in old age) LHRH, testosterone

Risk Factors (Allostatic Load) Endangering Health & Shortening Life Span Elevated Physiologic Indices (at risk) • Systolic blood pressure: ≥ 148 mm. Hg • Diastolic blood pressure: ≥ 83 mm. Hg • Waist-hip ratio: ≥ 0. 94 • Total cholesterol-High Density Lipoprotein ration: ≥ 5. 9 • Total glycosylated hemoglobin level: ≥ 7. 1% • Urinary cortisol level: ≥ 25. 7 mg/g creatinine • Urinary epinephrine level: ≥ 5 mg/g creatinine • Urinary norepinephrine level: ≥ 48 mg/g creatinine Lowered Physiologic Indices (at risk) • HDL cholesterol level: ≤ 1. 45 mmol/L • DHEA (Dehydroepiandrosterone) level: ≤ 2. 5 micro mol/L

Hormesis • Hormesis: the beneficial action (s) resulting from the response of an organism to a low-intensity stressor • The term “Hormesis” was first utilized by T. D. Luckey in 1991 in a book entitled Radiation Hormesis. • High doses of radiation increase mortality and shorten life; small doses of radiation prolong life (as compared to the non-irradiated animals).

Hormesis & Chaperones • The beneficial effects of moderate stress on the resistance to extreme and prolonged stresses, and the promotion of longevity, may be due to their action in stimulating the production of “heat-shock proteins” (HSP) (also known as “stress proteins”). • HSP are type of “chaperone” protein – Chaperones ubiquitin, glucose related proteins, endoplasmic reticulum chaperones.

Hormesis & Chaperones • During stress, HSP level increases and protects the normal assembly of proteins by promoting their appropriate folding • In C. Elegans it has been shown that upon stress, there is increase levels of HSP together with a longer life.

In Humans, Practical Limitations of Prescribing Stress as a Pro-Longevity Treatment • Complexity of human biology • Difficulty in quantifying stress responses (from mild to severe) • Difficulty in adjusting levels of mild stress to age-related changes in stress sensitivity • Difficulty in predicting precisely under which conditions hormesis will occur • Variability among individuals that increases with age • Determining the biological significance of relatively small hormetic effects that may or may not have large beneficial effects during the entire lifespan

Early Material • • • Male/Female Reproductive Systems Gametogenesis Fertilization – Including web-site material Embryonic Stages Hormones of pregnancy Nervous system development Fetal Growth The newborn (normal/at risk / assessment tests) Lactation GI Funciton Liver Kidney