After MT3 Flashcards
1
Q
Thyroid hormone secretions cells
A
Follicular cells; form spheres that surround an inner lumen that is acellular (contains no cells) that consists of colloid (protein)
2
Q
Colloid
A
consistsmainlyofthyroglobulin, a large protein where thyroid hormone synthesis takes place.
3
Q
Thyroid hormone synthesis (IMPORTANT)
A
- Thyroid hormone is made of Tyrosine and Iodine (I).
- Iodine is an essential nutrient
- It is reduced to Iodide (I-) before absorption in the small intestine.
- It is taken up and converted into thyroid hormone by the thyroid gland.
- There are 2 active forms of Thyroid hormone:
- Tetra-iodothyronine (Thyroxine, T4)
- Tri-iodothyronine (T3)
4
Q
Lower rate of T3 and T4
A
Going to burn fewer calories
Not produce as much heat; put on more weight
Storing nutrients
5
Q
Major effects of thyroid hormone
A
- Metabolism (warm-blooded vertebrates)
Important determinant of basal metabolic rate (BMR)
INCR - Rate of O2 consumption
Calorigenic (heat producing) - INCREASE- Heart rate,strength of contraction (permissive for sympathetic NS)
- Growth (permissive for GH)
- Development of the CNS
6
Q
Thyroid hormone is lipophilic so
A
Actions at target cells via nuclear receptor
Target cells regulate deiodinase expression (T4–T3)
[ can remove iodide]
7
Q
Thyroid disease
A
As many as 1 in 10 will experience a thyroid disorder during their lifetime. Many of these conditions are life-long but treatable.
Many with thyroid problems are unaware of their condition, yet consequences can be serious, e.g. pregnant women with undiagnosed hypothyroidism risk miscarriage and fetal developmental problems.
8
Q
Hypothyroidism (too little thyroid hormone)
A
-reduced BMR
-poor tolerance of cold
-tends to increase weight (fuels stored, not burned)
-easily fatigued
-diminished alertness, poor memory
9
Q
Hyperthyroidism (too much thyroid hormone)
A
-elevated BMR
-excessive perspiration, poor tolerance of heat -reduction in body weight (fuels burned, not stored)
Burning fuel to generate heat
10
Q
Goiter
A
Enlarged thyroid gland
Can occur w BOTH hyper or hypOthyroidism
Develops when thyroid gland is overstimulated
11
Q
Causes of hypothyroidism
A
Causes:
– Primary failure of thyroid gland:
Autoimmune disease (Hashimoto’s thyroiditis)
– Secondary to a deficiency of TRH, TSH, or both
– Inadequate dietary supply of iodine
12
Q
Hypothyroidism as an adult
A
Fatigue, weight gain, weak pulse, cold intolerance, mental sluggishness and depression (goiter if due to thyroid hormone synthesis problem)
=>Reversible with thyroid hormone replacement therapy or iodine in diet
13
Q
Hypothyroidism during perinatal period (infant)
A
“Cretinism”
Short stature, poor motor skills, moderate to severe mental retardation (goiter if due to thyroid hormone synthesis problem)
=>Effects on nervous system irreversible if not corrected shortly after birth
14
Q
Cause of hyperthyroidism; elevated TH secretion
A
• Most common cause is Graves’ disease
– Autoimmune disease
– Characterized by exopthalmos (bulging eyes), goiter
– Weight loss, heat intolerance, insomnia, rapid heart rate
15
Q
Treatment for hyperthyroidism
A
Surgical removal of a portion of the over-secreting thyroid
Administration of radioactive iodine
Use of antithyroid drugs
16
Q
MAIN originate sites for immune system
A
Thymus & bone marrow
17
Q
Leukocytes
A
Collective name for all the immune cells in our body
Leukocytes fall into 2 broad categories:
-Lymphoid cells (T lymphocytes, B lymphocytes, Natural Killer cells)
-Myeloid cells (Monocytes/macrophages, granulocytes and precursors for red blood cells and platelets.
18
Q
Macrophage vs monocyte
A
Monocyte = still IN BLOOD
Macrophage= left blood and entered tissues
19
Q
Where will the immune cells originate from
A
Stromal stem cells !
20
Q
Myeloid cells
A
Neutrophil
Basophil
Eosinophil
Monocyte/macrophage
Platelets
Red blood cells
21
Q
Lymphoid
A
T lymphocytes
B lymphocytes
Lymphoid progenitor cell
Natural killer cell
22
Q
T lymphocytes (T cells)
A
-originate in the Thymus
-necessary for cell-mediated immunity.
-uses T cell receptors
23
Q
B lymphocytes (B cells)
A
-originate in the Bursa of Fabricius (and the Bone Marrow)
-necessary for humoral immunity.
-uses B cell receptors = antibodies
24
Q
Macrophages (called monocytes in the blood)
A
-professional phagocytic cells
-scavenge our tissues in search of pathogens, dead cells and other debris
Essential for tissue maintenance
25
Granulocytes
-different types: neutrophilic, eosinophilic, basophilic, mast cells
-professional phagocytic cells that release the content of their granula as part of specific immune responses (e.g. against large extracellular parasites)
Find pathogens, engulf, die
Degranulate- encapsulate- its contents are so toxic they can overcome a bigger parasite
26
Acquired cells
T lymphocytes
B lymphocytes
27
Beta cells (receptors etc)
- Consists of 2 Heavy chain and 2 Light chains
- Linked by disulfide bonds
- Constant domain determines antibody properties
- Tip of the variable domain provide the antigen binding site
MOST of life they are UNACTIVE
28
1 specific B cell receptor will pertain to
Only 1 specific B cell
29
Antigen binding site
High affinity
Anything can be bound by B cell receptor (proteins, lipids, fat etc)
30
B cell antibody is
Unique and HIGHLY specific
- A B cell makes only kind of 1 antibody
- Each antibody is HIGHLY specific for one particular antigen (usually a part of a protein)
31
How do we generate a near infinite number of antibodies ?
Random combination of VDJ gene segments
the combinatorial power of Heavy and Light chains yields > 100 Million possible antibodies!
Many B cells make antibodies that recognize proteins of our own body (’self’). These B cells are killed off in the Bone Marrow = negative selection.
So if you are infected by a new pathogen (e.g. Sars-CoV2), you likely already have a B cell that makes just the right antibody against it.
32
How can single B cell make a difference against a pathogen?
Clonal expansion
Binding of antigen and interaction with a helper T cell stimulates the matching B cells to divide and expand the close of selected cells
Most of the new B cell clones differentiate into plasma cells, which secrete antibodies
Few of the clones differentiate into memory B cells, which respond to a later encounter with the same antigen
33
Primary antibody response
-in response to first antigen exposure
-takes a few weeks
-moderate concentration of low – medium-strength antibodies
34
Secondary antibody response
-in response to subsequent antigen exposure
-takes a few days
-high concentration of high-strength antibodies
35
Why do we vaccinate
vaccinate so that we mount a better antibody response faster!!
36
How do antibodies help fight pathogens
- Agglutination (causes antigenic cells to clump together)
- Activation of the complement pathway, a cascade of biochemical responses that ends with the formation of the Membrane Attack Complex, which kills pathogens
- Opsonization (coating of the surface of pathogens with Abs), initiating phagocytosis
- Leads to activation of Natural Killer cells
37
T cells
- Dimer of 2 TCR chains
- Tip of the variable domain provides the antigen binding site.
- Each T cell has a unique TCR, a large T cell repertoire is generated similar to B cells.
- 2 major subtypes:
- helper T cells
- cytotoxic T cells
- Helper T cells provide essential ‘help’ to B cells in mounting a humoral immune response. Without T cell help, most antibody- mediated (humoral responses) cannot take place.
- Cytotoxic T cells can kill cells via cell-cell contact. Important in the defense against virus-infected cells and cancer.
38
Non self
fragment of a pathogen after degradation in the lysosomes
39
Self
refers to the Major HistoCompatibility genes (MHC), which encode a protein dimer on the cell surface that ‘presents’ this small fragment
The repertoire of MHC genes is variable between individuals
If we are looking for an organ donor ‘match’ we are looking for a donor with a similar MHC gene repertoire as the transplant recipient.
40
Cytotoxic T cells
- All cells express MHC class I
- MHC-I + peptide is recognized by TCRs on cytotoxic T cells, along with a CD8 co-receptor.
- If the peptide is ‘self’ presented in the context of ‘self’, nothing happens.
- If the peptide is ‘non-self’ (e.g. from a virus that has infected the cells) and is presented in the context of ‘self’, cytotoxic T cells with the right TCR to recognize the peptide will kill the infected cell.
41
Helper T cells
- Specific Antigen Presenting Cells express MHC class II
- MHC-II + peptide is recognized by TCRs on helper T cells, along with a CD4 co-receptor.
- If the peptide is ‘non-self’ (e.g. from a bacterium that was phagocytosed) presented in the context of ‘self’
by an antigen-presenting cells (APC), this activates the helper T cell
- Activated helper T cells can then provide help to B cells that present ’non-self’ antigen.
- Help is provided in the form of cytokines, which are soluble signaling molecules released by the helper T cells to promote proliferation (cell division) of those B cells that are activated.
42
How do helper T cells help the B cells
Helper T cells assist B cells by recognizing the antigen presented by the B cell and providing essential signals for activation. Upon antigen recognition, helper T cells release cytokines that stimulate B cell proliferation and differentiation into plasma cells, which produce antibodies. They also provide "co-stimulatory signals" through direct cell-to-cell interactions, enhancing B cell activation. In addition, helper T cells help promote the formation of memory B cells, ensuring long-term immunity against the pathogen.
LOOOK AT SLIDES
43
What role does innate immunity play
- Innate immune cells are really efficient Antigen Presenting Cells
- Without antigen presentation, there will be no acquired immune response
- Innate immune cells are also very capable of scavenging our bodies for anything damaging (foreign or self!) and clean up.
- Innate immunity provides a much faster, local response (inflammation) to a threat (damage or a pathogen). This usually takes care of the threat and promotes tissue repair.
44
How does innate immunity know to respond
- Innate immune cells recognize Pathogen-Associated Molecular Patterns (PAMPs) or Danger Signals
- PAMPs or Danger Signals broadly flag to the innate immune system that something is amiss and requires an immune response. Examples:
- Lipopolysaccharide (Gram negative bacteria)
- Unmethylated DNA (virus)
- Heat shock proteins (self), which normally never occur outside of the cell and are therefore a sign of unusual damage and cell death.
45
Disorders of the innate immune system
Genetic mutations in the signaling pathway of the PAMPs or Danger Signals lead to defects of the Innate Immune System.
- Increased susceptibility to severe and recurrent viral and bacterial infections
Over-active innate immune responses lead to auto-inflammatory diseases, usually related to the excess strength of signals that promote inflammation
46
Disorders of the acquired immune system
Rare mutations affect the ability to carry out VDJ recombination. No BCRs and TCRs can be made, causing the absence of the acquired immune system
This disorder is called Severe Combined Immuno Deficiency, is hereditary and primarily affects boys (often X-linked).
47
AIDS- acquired immune deficiency syndrome
Human immunodeficiency virus (HIV) infects and kills CD4+ helper T cells resulting in lack of B and cytotoxic T activation
48
Innate and acquired arms of immune system work together to
provide us with protection against the wide range of pathogens we might encounter over our lifetime.
If either the innate or the acquired immune system are mis- regulated, immune disorders ensue.
49
Reproductive patterns
Internal, external fertilization
50
Oviparous
Egg laying
Fertilization internal or external
51
Viviparous
Develop in oviduct or uterus
Nourished by mother
Mostly mammals, some fish, scorpions
52
Human male reproductive system
• Includes gonads, reproductive tract, and accessory
sex glands
• Role: Make sperm - deliver sperm
MAKE AND DELIVER
53
Female reproductive functions
• Functions
– Production of ova (oogenesis)
– Reception of sperm
– Transport of sperm and ovum to common site for union
(fertilization or conception)
– Maintenance of the developing fetus until it can survive in
outside world (gestation or pregnancy)
• Formation of placenta (exchange organ between mother and
fetus)
– Giving birth to the baby (parturition)
– Nourishing infant after birth by milk production (lactation)
54
Sexual differentiation of human
Begins at 10 weeks
55
What do testes differentiate from
“Bipotential” gonads if SRY gene from Y chromosome is expressed
56
SRY gene from Y chromosome makes
Sex determining protein
Tells wolffian ducts to be maintained but also differentiate
57
What do transiently active testes secrete
Secrete testosterone (keeps Wolffian ducts alive) and Ant-Mullerian Hormone (AMH: induces loss of Mullerian ducts).
58
Testosterone tells
Wolffian dcts to become epididymus and vas deferens
59
AMH tells
Mullerian to die off
60
How are Wolffian ducts lost in FEMALES
Wollfian ducts are lost without testosterone and
Mullerian ducts become oviducts and uterus.
61
Male external genitalia formation induced by local conversion of
Local conversion of testosterone from fetal
testes to dihydrotestosterone (DHT)
62
When will external female genitalia develop
In absence of DHT
63
DHT is
Another androgen
64
What receptor does DHT act through
Acts through androgen receptor (AR)
65
Where is the AR gene located
On the X chromosome
66
CAIS: complete androgen insensitivity syndrome
(AR not functional, premature
stop codon, or can’t bind hormone or DNA)
Women: high levels of testosterone but no receptor for it
67
Dual function of testes
• Produce sperm (at puberty) within seminiferous tubules
• Secrete testosterone from Leydig cells (during development and then again at higher levels at puberty)
Descent into scrotum provides cooler environment essential for spermatogenesis
68
Spermatogonium
Sperm stem cell
69
Seminiferous tubule
Filled with sperm
70
Where is the spermatogonium close to
Edges of the seminiferous tubule
71
Where are the tails of the spermatozoa by
Lumen of the seminiferous tubule
72
Steroli cell
Location: Sertoli cells are located within the seminiferous tubules, which are the structures in the testes where sperm production occurs.
Shape and Structure: They are elongated, non-reproductive cells that extend from the basement membrane of the seminiferous tubules toward the lumen (center of the tubule). Their cytoplasm surrounds and supports developing sperm cells.
NURTURE spermatozoa
73
What do the Steroli cells produce
Produce androgen binding protein and release it into the lumen to achieve a high concentration of localized testosterone
74
Why are there tight junctions
Tight junctions are found at the apical (top) and lateral (side) regions of the Sertoli cells, where they make contact with neighboring Sertoli cells. These junctions effectively seal off the seminiferous tubule from the interstitial space outside
Create unique environment for development because the immune system has never been exposed and might attack
75
Head of spermatozoa
Includes acrosome and nucleus
76
Mid piece of sperm
Mitochondria
Provides energy for motility
77
Tail of sperm (flagellum)
Microtubules
78
Spermatogenesis
180 X106 sperm/ejaculate (below 20 X 106 infertile)
79
Epididymus and ductus deferens
- store and concentrate sperm
- increase sperm motility and fertility prior to ejaculation
80
During ejaculation: sperm are mixed with
secretions released by accessory glands
81
Secretions of seminal vesicles
supply fructose (energy source for sperm) and prostaglandins (allow female reproductive tract to contract and allow semen to advance faster through)
Provide more than half the semen
82
Prostate gland secretion
Alkaline fluid that neutralizes acidic vaginal secretions
83
Bulbourethral glands secretion
Mucus
84
Cyclic GMP
Quickly broken down
The balance between breakdown and generation determine ability to trigger erection reflex
If it is broken down too quickly, cannot achieve an erection
Viagara inhibits cGMP destruction and prolongs the erection
85
The stimulation of mechanoreceptors in glans penis sends
OPPOSING signals to parasympathetic (+) and sympathetic (-)
86
Effects of thought of sex
Can inhibit or stimulate para/sympathetic
87
Sex steroid hormone production (steroidogenesis)
Derived from cholesterol
Primarily synthesized and secreted by gonads (DHEA is secreted by the adrenal cortex)
88
Effects of testosterone
89
Adequate sperm production depends on
local estradiol
production!!!
Sertoli cells express a
low level of aromatase
90
Leydig cell
Stimulated by LH
PRODUCES TESTOSTERONE
91
Testosterone in endocrinology
From leydig cells
Leads to masculinizing effects
A STEROID HORMONE
Inhibits hypothalamus and selectively inhibits LH secretion
92
Steroli cell stimulated by
FSH
Testosterone
93
Steroli cell leads to/releases…
Leads to spermatogenesis
Secretes; INHIBIN
94
Inhibin
Selectively inhibits FSH secretion in gonadotrope
95
Inhibin is a _____ hormone
Peptide
96
Ovaries
Primary female reproductive organs
• Secrete female sex steroid hormones beginning at puberty
– Estrogen
– Progesterone
as well as inhibin, a peptide hormone
• Produce ova (oogenesis)
97
How many primary oocytes at birth
1-2 X 106 primary oocytes arrested in meiosis
98
Primary oocytes by puberty
300,000
99
How many oocytes are ovulated by puberty
400-500 ovulated until about age 50 (menopause)
(assuming 1 per 28 day cycle)
100
What completes meiosis
Fertilization
101
Female stem cell
Oogonium
102
When is the first Meiotic division completed
just PRIOR to ovulation
103
Whats the purpose of the polar bodies
Just used to object excess DNA
104
When is second Meiotic division completed
After fertilization
105
What cells surround the primary oocytes
Single layer of granulosa cells at the beginning of
106
What happens to the primary follicle that randomly starts to mature
Granulosa cells start to thicken
107
Follicular cells
Granulosa and thecal cells
108
Zona pellucida
Thick layer of connective tissue like material
109
Ovulated ovum (secondary oocyte)
Jumps out of ovum and breaks through the ovarian surface
110
Corpus luteum
After ovulation, when a mature egg is released from the ovarian follicle, the remaining cells of the ruptured follicle transform into the corpus luteum.
This transformation is stimulated by luteinizing hormone (LH), which is released from the pituitary gland after ovulation.
Secretes progesterone; which helps prepare the endometrium (lining of the uterus) for potential implantation of a fertilized egg
Estrogen also prod
111
Preovulation
Follicular phase
112
LH surge
Induces ovulation
Induces corpus luteum formation
113
LH has effect on
Thecal cells
114
What do thecal cells help do
Help convert cholesterol to androgen (TESTOSTERONE)
115
How and why does testosterone get from thecal cells to granulosa cells
It is lipophilic so it cannot be contained; therefore it diffuses into granulosa cells start
116
What does FSH stimulate
Granulosa cells
117
What do granulosa cells help do
Convert testosterone to estrogen (estradiol)
118
Impact of estrogen
Further stimulates granulosa cells, so almost all testosterone produced by thecal cells is quickly converted to estrogen by nearby granulosa
- gets secreted into blood
-remains in follicle
119
Importance of difference in levels of LH and FSH
Early follicular phase
FSH is inhibited more strongly by BOTH estrogen and Inhibin than LH
120
Late follicular phase to ovulation
Continued exposure of the
hypothalamus and pituitary to rising
levels of estradiol leads to a switch from
weak negative to strong positive
feedback on GnRH and LH secretion
Estrogen potently activates AVPV and stimulates LH secretion when it reaches a high threshold
121
Kisspeptin
Protein
key activator of the gonadotropin-releasing hormone (GnRH) neurons,
leads to the release of GnRH, which stimulates the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
122
Luteal phase
Egg is available and pregnancy could occur
123
What maintains the corpus luteum
LH stimulates development and maintenance of corpus luteum
124
What does the corpus luteum secrete
Secretes progesterone and estrogen
125
What happens as LH starts to gradually decline
LH sustains corpus l. So if it declines so does corpus luteum
Without corpus, there is a decline in progesterone and estrogen
126
What happens as progesterone declines
As progesterone declines, the inhibition of FSH GOES AWAY
NO MORE INHIBITION, FSH increases again
NOW allow next cycle’s follicle to mature
127
What do high levels of progesterone inhibit
Inhibit BOTH LH and FSH (***) from gonadotrope
Kiss1 neuron in ARC nucleus
128
In luteal phase, Progesterone exerts a strong
negative feedback on GnRH and LH (and FSH)*
129
A certain level of LH is
Required for corpus luteum survival
130
No pregnancy =
corpus luteum degenerates,
estradiol and progesterone levels fall
131
What is also made by the corpus luteum
Some Inhibin (a different form)
132
Systemic effects of estrogen (major one: estradiol)
1. Uterus: growth of endometrium
2. Secondary sex characteristics: Mammary
gland growth
3. Fusion of growth plates, maintenance of
bone density
4. Permissive for actions of progesterone
(induces progesterone receptors)
133
How does estrogen act as mitogen
“Mitosis “-mito
Induces cell division of endometrial and mammary gland cells
134
Uterine cycle
Proliferative phase (Preovulation)
Secretory phase (Post-ovulation)
Menstrual Phase
135
Systemic effects of progesterone
1. Uterus: INHIBITS estrogen induced growth
Induces endometrial environment conducive to implantation (glycogen)
Inhibits uterine contractions
Cervix: Induces thick mucous secretion that opposes sperm entry (cervical plug)- (avoid 2 pregnancies of different ages)
2. Maintain health of endometrium: endometrial lining collapses and is lost via menstruation without adequate progesterone
136
What causes breakdown of endometrium/menstrual flow
Withdrawal of hormonal support
Low progesterone
137
How does birth control work
Mimic luteal phase
FSH stay inhibited, no more follicles mature so no ovulation thus no pregnancy
Suppress ovulation
138
How could male bc work
Intervention of local concentration of testosterone in the Steroli cell/seminiferous tubule
Block local testosterone action, local only
139
Leydig and thecal cells
BOTH make testosterone under influence of LH
140
Steroli and granulosa cells
• Make inhibin under influence of FSH
• Nurse gametes
• Produce steroid binding proteins that concentrate testosterone in seminiferous tubules and estrogen in antrum
141
Site of fertilization
Oviduct
142
When should fertilization occur
Must occur within 24 hours after ovulation
– (Note: sperm usually survive about 48 hours but can survive up to 5 days)
143
Travel of sperm
Sperm deposited in vagina travel through cervical canal, uterus, and to upper
third of oviduct
144
What percent of ejaculated sperm make it to fertilization site
.001
From 20 million to 200 sperm
145
What happens when the sperm make contact with the egg
acrosomal vesicle bursts open to help dissolve the zona pellucida, all help to break it down so just 1 can fully break through
146
Cortical granules
Cortical granules release enzymes that modify the zona pellucida, creating a barrier to prevent multiple sperm from fertilizing the egg.
release of cortical granule contents is triggered by a rise in intracellular calcium levels following sperm entry.
ONLY 1 IN
Meiosis 2 completed
147
Time from fertilization to implantation
About 1 week
148
Early stages of development after fertilization
Cleavage
Morula
Blastocysts
149
Inner cell mall of blastocyst becomes
Fetus
150
Trophoblast
Accomplishes implantation and develops into fetal portions of placenta
Surface layer of cells of blastocyst
151
Implanted embryonic trophoblast cells secrete
a peptide hormone- chorionic gonadotropin (hCG)
• Structurally related to LH
• Maintains corpus luteum and estradiol/progesterone secretion
• Placenta develops at ~10th week and takes over from “corpus luteum of pregnancy”
152
Placental progesterone suppresses
myometrial contractions, maintains healthy pregnancy
153
Peak of hCG
@ ab 2-3 months
154
What induces expression of testis determining factor from the SRY gene
hCG
