MCB 135EFinal Review

Fall 2004

GSI: Jason Lowry

Exam Information

• Monday, Dec. 20th

• F-295 Haas• 5-8 pm• Multiple Choice (50pts)

• 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• Cell mediated vs.

Humoral Immunity• Tissues and Organs

Involved• Cells Involved• Viral vs. Bacterial

Response

                                                                          

                                                        

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 CellsEnhance T killer or B cell activity

-Supressor CellsReduce/suppress immune activityMay help prevent auto immune disease

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)

Lymphocytes (cont.)

2. Neutrophils- found throughout body, in blood-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

Bacterial Infection

Macrophage

Bacteria

ComplementSeries 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

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

• 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

Know these slides from reader

• 18-7: – Age differences in

heart rate

• 18-8:– Growth in vital

capacity with age

• 18-9:– Basal Metabolism with

age

• 18-10:– Change in basal metabolic

rate during childhood

• 18-11– Changes in blood pressure

• 18-12– Changes in diastolic blood

pressure

• 18-13:– Age changes in metabolic

response to severe excercise

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 GnRH 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

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

Factors Influencing Onset

• Hormonal

• Nervous

• Somatic– Menarche follows peak growth

• Environmental

• Social

• Genetic

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, father, family, and society

• Choosing of a mate– Physical Attraction

– Behavior

– Chemical Attractants

– Cultural Influences

• Sexual Orientation– Theories about

homosexuality• Feminine Genes?

• Sensitivity to alteration of prenatal testosterone

Sexualization

• Puberty– Brain turns on adult cycles of gonad function

– Gonads begin production of adult levels of sex hormones

– Sex hormones stimulate adult body type

– Sex hormones stimulate reproductive behavior

– Status becomes a primary goal

– Desire for independence

– Skills for attracting sexual partner

– Peer pressure

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: ConceptAbility 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 cross-

sectional area2) Increase in the muscular mass with changes in the

myosin typeMuscle 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

Caloric production

• FATS : 1 gm = 9 kcal

• PROTEINS : 1 gm = 4 kcal

• CHO : 1 gm = 4 kcal

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 m2

• 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• Increased blood pressure• Increased heart rate• Increased force of heart contraction• Increased heart conduction velocity• Shift of blood flow distribution • Contraction of spleen capsule• 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 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

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

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 activityInsulin secretion

Access to energy storage is facilitated & energy storage steps are reversed:

glucocorticoid secretionEpinephrine/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 mmHg•Diastolic blood pressure: ≥ 83 mmHg

•Waist-hip ratio: ≥ 0.94•Total cholesterol-High Density Lipoprotein ration: ≥ 5.9

•Total glycosylated hemoglobin level: ≥ 7.1%•Urinary cortisol level: ≥ 25.7mg/g creatinine

•Urinary epinephrine level: ≥ 5 mg/g creatinine•Urinary norepinephrine level: ≥ 48mg/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

– Remember the web-site• Embryonic Stages• Hormones of pregnancy• Nervous system development• Fetal Growth• The newborn (normal/at risk / assessment tests)• Lactation• GI Funciton• Liver • Kidney

Other Material

• Study guides

• Previous exams

• Web-site material