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Chapter 43: The Immune System
 The immune system defends against pathogens, infectious agents such as bacteria, viruses,
protists, and fungi that cause disease.
 Innate immunity includes external physical barriers and internal defenses of immune cells that
have a small group of receptor proteins that recognize a broad range of pathogens.
 Acquired immunity, also called adaptive immunity, is a line of defense in vertebrates in which
immune cells react specifically to pathogens.
- A vast array of acquired immune receptors allow recognition and response to specific
pathogens
Innate Immunity
Nonspecific Defense Mechanisms
Against a variety of microbial attacks (i.e. antigens):
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Bacteria
Viruses
Roundworms, tapeworms
Ticks
Toxins/stings
Foreign body
Pollen/allergens
Physical response:
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Skin –barrier to microbes, maintain a low pH which discourages microbe colonization
Mucus membranes in the digestive system – barrier to microbes
Saliva, tears, nostril hairs
Cilia, mucus in upper respiratory system – traps and removes microbes
Chemical response:
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Oil, sweat – due to a pH of 3-5, it kills bacteria by denaturing enzymatic reactions
Lysozyme – attacks microbial growth
Stomach acid – kills most microorganisms that reach the stomach
Interleukins and interferon – secrete cytokines which are proteins produced by infected cells
that send chemical signals to stimulates complacent proteins to bind to cells and create pores 
this results in cell fluid loss which leads to cell death
Interferons inhibit viral reproduction in cells and also activate macrophages
The complement system is a group of about 30 proteins in the blood plasma that, when
activated by contact with microbes, may lyse cells, trigger inflammation, or assist in acquired
defenses.
Cellular response:
 Toll-like receptors (TLRs) that recognize molecules that are common to a set of pathogens,
triggering phagocytosis
 White blood cells (leukocytes) including
- Phagocytes
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Macrophages- attack microbes filtered from blood in the spleen and from interstitial fluid that
flows as lymph through lymph nodes. They may migrate through the body or become
permanently attached in various organs of the lymphatic system.
- Neutrophils are the most numerous phagocytic white blood cells
- Eosinophils are leukocytes that attack multicellular parasitic invaders with destructive enzymes.
- The primary role of dendritic cells located in tissues in contact with the environment, is to
stimulate acquired immunity
*They engulf foreign particles and microbes through endocytosis, and the resulting vacuoles fuse
with lysosomes, which contain toxic gases (such as nitric oxide) and digestive enzymes
Inflammatory response:
 Characterized by redness, swelling, itchiness, and heat
 Histamines trigger:
- Increased blood flow by dilating blood vessels
- Increased phagocytes– release signals that promote blood flow to the damaged area
- Increased interstitial fluid
 It may include a fever which is triggered by toxins produced by pathogens or by pyrogens
released by macrophages
 It may lead to an allergic response: can lead to anaphalaxis
 Natural killer (NK) cells recognize an absence of a cell receptor on virus-infected or cancer cells,
attaching to them and triggering cell death
Innate Immunity of Invertebrates
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Insect defenses begin with their protective exoskeleton.
Lysozyme, an enzyme that attacks microbial cell walls, a low pH, and the chitin lining of the
intestine all protect the digestive system.
Hemocytes are circulating cells that can engulf and destroy bacteria by phagocytosis, trigger
production of chemicals that entrap multicellular parasites, and secrete antimicrobial peptides
that kill fungi and bacteria.
Different classes of pathogens bind to distinct Toll receptors that activate pathways for the
production of antimicrobial peptides effective against that group of pathogens
Innate Immune System Evasion by Pathogens
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Certain pathogens may evade the innate immune system with an outer capsule that covers their
surface molecules or by resisting breakdown in lysosomes and growing within the host’s cells
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Acquired Immunity
Specific Defense Mechanisms
*An overview:
Humoral response
Helper T cells-
Cell mediated response
B cells – produce antibodies
(=proteins)
- Attach to antigens/infected
cells and label them as
“foreign”
activate both B
and T cells
T cells – attack infected or cancer
cells using cytotoxic T cells
*2 ways to deal with antigens:
1. B CELLS: look for free antigens
 Extracellular
2. T CELLS: look for and kill infected cells
 Intracellular
*MHC complex (Major Histocompatibility complex): “self markers”
Antigen Recognition by Lymphocytes
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Lymphocytes are the key cells of acquired immunity.
T cells migrate to the thymus to mature, while B cells remain and mature in bone marrow.
B cells and T cells are activated by contact with foreign molecules and by cytokines, proteins
secreted by macrophages and dendritic cells after they engulf microbes.
Both B and T cells are involved in immunological memory, an enhanced response to a
previously encountered foreign molecule
Most antigens are proteins or polysaccharides, often protruding from the surfaces of microbes.
B cells and T cells have membrane-bound antigen receptors that allow them to recognize a
specific antigen.
B cells may give rise to plasma cells that secrete antibodies or immunoglobulins (Ig) which are
soluble antigen receptors.
The small region of an antigen to which a lymphocyte or secreted antibody binds is called an
epitope, or antigenic determinant
Helper T Cells: A Response to Nearly All Antigens
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Helper T cells recognize specific class II MHC molecule-antigen complexes on antigen-presenting
cells .
Signaling between the 2 cells results in the proliferation and differentiation of a clone of
activated helper T cells and memory cells.
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Activated helper T cells secrete cytokines, which stimulate both the cell mediated and humoral
responses
Cytotoxic T Cells: A Response to Infected Cells
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Cytotoxic T cells look for very specific cells: antigen-presenting cells
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They recognize nonself proteins synthesized in infected cells and bind to an MHC complex
The cytotoxic T cells make a surface protein (CD8) that greatly enhances interactions
between a target cell (aka an infected cell) and a cytoxic T cell
The cytotoxic T cells, also stimulated by cytokines from nearby helper T cells,
differentiate into active killers.
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Binding to an MHC complex on an infected cell activates a cytotoxic T cell and makes it an
active killer cell
- The activated cell secretes proteins that kill the target cell.
Pathogens released from the destroyed cell are marked by circulating antibodies for destruction
B cells: A Response to Free Antigens
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Antibodies look for “nonself” cells by recognizing cell-surface receptors
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Antibodies are very specific proteins which are secreted by plasma cells and derived
from B cells
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mRNA splicing allows a variety of antibodies to be produced
Antibodies move through the plasma of the bloodstream through the circulatory system
B cells are lymphocytes which come from bone marrow
- Part of the immune system
- Part of lymph: fluid that carries away dead cells and is moved by skeleton muscle
Each Y-shaped B cell receptor consists of four polypeptide chains: 2 identical light chains and 2
identical heavy chains, linked together by disulfide bridges.
- Both heavy and light chains have variable (V) regions at the ends of the 2 arms of the Y,
which form 2 identical antigen binding sites.
- The constant (C) regions of the molecule vary little from cell to cell.
B cells are selectively activated by antigens on the surface of bacteria.
- This activation is aided by cytokines released from helper T cells (which have also been
activated by that antigen)
Upon first binding antigen, the B cell takes in a few foreign molecules by receptor-mediated
endocytosis and presents antigen fragments in its MHC molecules to helper T cells
- Most protein antigens require the aid of helper T cells to stimulate antibody production
The activated B cell then proliferates into a clone of plasma cells and a clone of memory B cells
When certain antigens bind with multiple receptors on a single cell, a B cell response may not
involve cytokines or helper T cells
Antibody Classes
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The antigen-binding sites on the arms of an antibody allow it to identify a specific antigen.
The heavy-chain constant regions determine the antibody’s distribution in the body and its
function.
There are 5 major types of constant regions, creating 5 classes of antibodies:
IgM
IgG*
IgA*
IgD
IgE
*IgG is the most abundant antibody in blood and confers passive immunity on a fetus
*IgA is present in tears, saliva, mucus, and breast milk
Role of Antibodies in Immunity
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Antibodies label antigens for disposal by one of several mechanisms
In virus neutralization, antibodies block viruses from infecting a host cell by binding to its surface
In opsonization, antibodies coat microbes and enhance phagocytosis by macrophages
Because each antibody molecule has at least 2 antigen-binding sites, the formation of antigenantibody complexes produces clumps, which are then engulfed by phagocytes
Antibodies can secrete chemicals that create pores which increase the flow of water and ions,
causing the cell to burst.
The membrane attack complex (MAC) is what produces pores in the membrane. It is triggered
by antigen-antibody complexes on microbes which may activate the complement system by
binding with complement proteins.
Complement proteins can be activated as part of the innate or acquired defenses. In addition to
lysing microbes, activated complement proteins promote inflammation and phagocytosis.
Lymphocyte Development
Generation of Lymphocyte Diversity by Gene rearrangement
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The genes coding for the diversity of lymphocytes have numerous coding segments that are
randomly and permanently rearranged
Antigen receptors are generated by random rearrangement of DNA
Origin of Self-Tolerance
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As lymphocytes mature in bone marrow or the thymus, they are tested for self-reactivity
Lymphocytes with receptors specific for the body’s own molecules are destroyed by apoptosis,
or rendered nonfunctional.
If these self-reactive lymphocytes were not elimated or inactivated, the immune system could
not distinguish self from nonself and would attack body proteins, cells, and tissues
This self tolerance means that normally there are no mature lymphocytes that react against the
body’s own cells
Failure of self-tolerance can lead to autoimmune disorders: when the cells begin to think their
own cells are foreign so immune system attacks
Amplifying Lymphocytes by Clonal Selections
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In the body there are few lymphocytes with antigen receptors for any particular epitope
(=region on antigen where antibodies bind)
The binding of mature lymphocyte to an antigen induces the lymphocyte to divide rapidly
This proliferation of lymphocytes is called clonal selection
2 types of clones:
1. Effector cells-short lived cells that combat the antigen
2. Memory cells- long lived cells that carry receptors for that antigen
- By clonal selection, a small number of cells is selected by their interaction with a specific
antigen to produce thousands of cells keyed to that particular antigen
The body mounts a primary immune response upon first exposure to an antigen
About 10 to 17 days are required for selected lymphocytes to proliferate and differentiate to
yield the maximum response produced by effector T cells and the antibody-producing effector B
cells, called plasma cells
If the body reencounters the same antigen, the second immune response is more rapid,
effective, and prolonged
The long-lived T and B memory cells are responsible for this immunological memory
This secondary immune response provides long-term protection against a previously
encountered pathogen
Active and Passive Immunization
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Active immunity develops naturally in response to an infection
It can also develop following immunization, also called vaccination
A vaccine may be a nonpathogenic form of a virus or microbe, an inactivated toxin, or even
genes for microbial proteins
Passive immunity provides immediate, short term protection
In passive immunity, temporary immunity is provided by antibodies supplied through the
placenta to a fetus, through milk to a nursing infant, or by an antibody injection
Immune Rejection
Blood Groups
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The immune response to the chemical markers that determine ABO blood groups must be
considered in blood transfusions
It is essential to receive the same blood type during transfusions
Otherwise, the body will recognize the new blood cells as “foreign” and will produce antibodies
in response. This will induce a devastating transfusion reaction to transfused cells with matching
antigens.
Blood type = codominance:
A
B
AB *universal recipient – can get a transfusion from all
O *universal donor – can only get transfusions from O
Agglutation: clots in blood from wrong transfusion
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Rhesus factor: complete dominance
+ :
++, +–
– :
––
If a mom has Rh– blood, and her second child has Rh+ blood, then there may be potential
problems
Tissue and Organ Transplants
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Transplanted organs and tissues are rejected because the foreign MHC molecules are antigenic
and trigger immune responses
The use of closely-related donors, as well as drugs that suppress immune responses, helps to
minimize rejection.
In bone marrow transplants (used to treat leukemia and blood diseases), the graft itself may be
the source of immune rejection.
The recipient’s bone marrow cells are destroyed by irradiation, eliminating the recipient’s
immune system.
The lymphocytes in the bone barrow transplant, however, may produce a graft versus host
reaction if the MHC molecules of the donor and recipient are not well matched.
Allergies
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Allergies are hypersensitive to certain environmental antigens, or allergens
IgE antibodies created in response to initial exposure to an allergen may bind to mast cells in
connective tissue.
When allergens then bind to these cell surface antibodies, the mast cells release histamines in a
process called degranulation.
The resulting inflammatory response may include sneezing, a runny nose, and difficulty in
breathing due to smooth muscle contractions
Antihistamines are drugs that combat these symptoms by blocking receptors for histamine
Anaphylactic shock is a severe allergic response in which the abrupt dilation of peripheral blood
vessesl caused by widespread mast cell degranulation leads to a life-threatening drop in blood
pressure.
Autoimmune Diseases
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Sometimes the immune system turns against itself, attacking its own “self” cells
These diseases may be caused by a failure in the regulation of self-reactive lymphocytes
For example: lupus, arthritis, diabetes, and multiple sclerosis
Exertion, Stress, and the Immune System
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Exercising to exhaustion and psychological stress have been shown to impair immune system
function
Immunodeficiency Diseases
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An immunodeficiency is the inability of the immune system to protect against pathogens
An inborn immunodeficiency is a genetic or developmental defect in the immune system
May occur in any of the components of the immune system
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An acquired immunodeficiency is a defect that arises later in response to chemical or biological
agents
May be caused by drugs used against autoimmune disease or to suppress transplant rejection
Certain cancers and acquired immunodeficiency syndrome (AIDS) damage the immune system
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Chapter 45: Hormones and the Endocrine System
Hormone vs. nervous system
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Animals have 2 systems of internal communication and regulation: the nervous system and the
endocrine system.
All of an animal’s hormone-secreting cells constitute its endocrine system.
Endocrine system – long lasting but slow
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Hormones are chemical messengers that respond to stimuli such as stress, dehydration, and low
blood glucose levels
Secretes hormones with longer-acting responses in reproduction, energy metabolism, growth,
and behavior
Hormone secreting organs, called endocrine glands, are “ductless” glands because they secrete
their chemical messengers directly into extracellular fluid.
Nervous system- short lasting but fast
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Conveys high-speed signals on specialized cells called neurons to regulate other cells
Types of Secreted Chemical Signals
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Chemical signals bind to specific receptor proteins on or in target cells.
Hormones
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Endocrine cells secrete endocrine signals, or hormones, that travel through the bloodstream.
Endocrine glands are ductless secretory organs composed of groups of endocrine cells.
Hormones regulate growth, development, and reproduction, and maintain homeostasis.
Local Regulators
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Local regulators are chemical signals that reach their target cells by diffusion.
Paracrine signals act on neighboring cells
Autocrine signals act on the secreting cell itself
Neurotransmitters and Neurohormones
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Neurotransmitters are secreted by neurons at synapses with other neurons and muscles.
- Neurons conduct impulses from nerve cells to target cells
- Synaptic signaling: chemical signals to bind to receptors
Neurosecretory cells are specialized brain neurons that secret chemical signals called
neurohormones, which diffuse into and travel through blood stream to target cells
- Target cells with receptors respond
- Non target cells don’t respond
Pheromones
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Pheromones are chemical signals released into the environment that communicate between
different individuals.
They serve many functions, including marking trails leading to food, defining territories, warning
of predators, and attracting potential mates.
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Chemical Classes of Hormones
Polypeptide (protein and peptide) hormones – made of amino acids
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Polypeptides and amine hormones are made from proteins
Water soluble
Example: insulin
Steroid hormones – fused rings
- Made from lipids
- Lipid soluble
- Example: sex hormones, cortisol
Vitamin C: water soluble
Vitamin E: lipid soluble
Simple Hormone Pathways
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In many hormone pathways, endocrine cells secrete a hormone in response to a stimulus
After this stimulus, hormones are released form an endocrine cell, travel through the
bloodstream, and interact with the receptor or target cell to cause a physiological response
This type of control, called negative feedback, is typical of pathways involved in maintaining
homeostasis. In many instances, a pair of pathways provides the control system.
Negative feedback loops
Insulin/Glucagon – maintain glucose homeostasis
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These hormones are produced by the pancreas, in clusters of endocrine cells called islets of
Langerhans
- Within each islet are alpha cells that secret glucagon and beta cells that secrete insulin
They are antagonistic hormones:
- Insulin: lowers glucose levels
- Glucagon: raises glucose levels
Homeostasis
Falling blood glucose levels:
insulin released  liver
takes up glucose and stores
it as glycogen  raises
glucose levels
Rising blood glucose levels:
glucagon released  liver
breaks down glycogen and
releases glucose into the
blood  lowers glucose
levels
Parathyroid hormone/calcitonin – maintain blood Ca+2 levels
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Ca+2 is in bones, stored in the sarcoplasmic reticulum, and is involved in muscle contractions
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Parathyroid hormone (PTH): raises blood Ca+2 levels
- released by parathyroid glands
Calcitonin: lowers blood Ca+2 levels
Homeostasis
Falling blood Ca+2 levels:
PTH  stimulates uptake
of Ca+2 in kidneys, bones,
intestines  raises blood
Ca+2 levels
Rising blood Ca+2 levels:
calcitonin  stimulates
depostion of Ca+2 in
kidneys and secretion by
kidneys  raises blood
Ca+2 levels
Positive Feedback Loops
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FSH = follicle stimulating hormone: stimulates egg growth in follicles of ovaries from immature
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to mature
Estrogen: builds up the uterine lining
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Progesterone: keeps uterine lining intact
Oxytocin: induces contraction of smooth muscle which delivers the baby; also allows delivery
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of milk to the mammary glands
Prolactin: makes milk which is released after oxytocin kicks in
HCG = human chrionic gonadotropin: looked for in pregnancy tests
Glands
Endocrine (=ductless)
Exocrine (=duct)
Thyroid
Parathyroid gland
Pituitary
Hypothalamus
Adrenal
Pancreas
(Stay in body)
Salivary
Sweat
(leave the body)
Coordination of Endocrine and Nervous Systems in Vertebrates
The Hypothalamus and Pituitary Gland
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The hypothalamus, situated in the lower rain, plays a key role in integrating the endocrine and
nervous systems.
In response to nerve signals it receives from throughout the body, the hypothalamus sends
endocrine signals to the pituitary gland located at its base
The pituitary gland has 2 discrete parts that develop separately and have different functions.
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1. The posterior pituitary, or neurohypophysis, is an extension of the hypothalamus that grows
downward during embryonic development
*It stores and secretes 2 hormones that are produced by the hypothalamus: ADH and
oxytocin
2. The anterior pituitary, or adenohypophysis, develops from the roof of the embryonic mouth
*The hypothalamus regulates secretion of hormones by the anterior pituitary
Posterior Hormones
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The posterior pituitary stores and releases 2 neurohormones that are produced by and
delivered from neurosecretory cells of the hypothalamus.
Oxytocin: induces uterine contractions during birth and milk ejection during nursing
Both of these actions are under positive feedback
Antidiuretic hormone (ADH): increases water retention by the kidneys and thus decreases urine
volume
Anterior Hormones
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Some hypothalamic neurosecretory cells produce releasing hormones and inhibiting hormones
that regulate the hormones of the anterior pituitary.
- For example, thyrotropin releasing hormone (TRH) stimulates the anterior pituitary to
secrete thryotropin, or thyroid stimulating hormone (TSH)
These hypothalamic hormones are released into capillaries at the base of the hypothalamus and
travel via a short portal vessel to capillary beds in the anterior pituitary
Hormone Cascade Pathways
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In a hormone cascade pathway:
1. A stimulus triggers a sensory neuron on the hypothalamus
2. The hypothalamus secretes a hormone that targets the anterior pituitary. It either
stimulates or inhibits release of an anterior pituitary hormone.
3. In response to this anterior hormone, the endocrine gland secretes a hormone that travels
to target cells, where it induces a response to the stimulus.
Other Anterior Hormones
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Growth hormone – stimulates growth (especially bones) and metabolic functions
Prolactin – stimulates milk production and secretion
FSH – stimulates production of ova and sperm
Adrenal Hormones: Response to Stress
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Stressful stimuli cause the hypothalamus to activate the adrenal medulla via nerve impulses
(short term) and the adrenal cortex via hormonal signals (long term)
The adrenal medulla mediates short-term responses to stress by secreting the catecholamine
hormones epinephrine and norepinephrine
The adrenal cortex controls more prolonged responses by secreting cortisols
Short term stress response
Effects of epinephrine and norepinephrine:
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Glycogen broken down to glucose  increased blood glucose
Increased blood pressure
Increased breathing rate (increased oxygen delivery)
Increased metabolic rate
Change in blood flow patterns, leading to increased alertness and decreased digestive,
excretory, and reproductive system activity
Long term stress response
Effects of cortisols:
1. Kidneys retain sodium ions and water
2. Increased blood volume and pressure
3. Increased blood glucose (as proteins and fats are broken down into sugars)
4. Immune system may be suppressed
“Fight or flight response”
Nervous system response: quick action of the nervous system in danger (secretes adrenaline/
epinephrine)
Endocrine response: increased blood pressure, decreased blood to digestive, excretory, or reproductive
organs, increased blood to muscles and brain
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