Transcript Final Review - Molecular and Cell Biology

MCB 135E
Final Review
Fall 2005
GSI: Jason Lowry
Exam Information
• Monday, Dec. 19th
• 22 Warren
• 5-8 pm
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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
• 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
-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
Bacteria
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
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Types
Characteristics
Specificity
In Newborns
• Development of the
Immune System
5 classes of Ig
IgG: 150,000 m.w.
most abundant in blood, cross placental barrier,
fix complement, induce macrophage engulfment
IgA: associated with mucus and secretory glands,
respiratory tract, intestines, saliva, tears, milk
variable size
IgM: 900,000 m.w.
2nd most abundant , fix complement,
induce macrophage engulfment, primary
immune response
5 Classes of Ig
IgD: Low level in blood, surface receptor on Bcell
IgE: 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
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YOLK SAC
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LIVER
(4 Weeks)
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BONE MARROW
(4-5 Weeks )
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THYMUS
(7-10 Weeks)
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BLOOD LYMPH
(14 Weeks)
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SPLEEN
(16 Weeks)
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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
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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 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
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
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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
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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
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Mother’s Health
Delivery of health child
Safe environment to raise child
Shared responsibility by
mother, father, family, and
society
• Choosing of a mate
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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 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
Stress induces defense mechanisms for
maintenance of homeostasis in response to
environmental challenges
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Types of stress known to stimulate the HPA axis*: •
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Physical Stress:hypoglycemia, trauma, exposure
to extreme temperatures, infections, heavy
exercise
• Contraction of spleen capsule
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Psychological Stress: Acute anxiety, Anticipation
of stressful situations, Novel situations, Chronic
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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
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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 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
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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