A. Open circulatory system 

1. Blood is pumped via a heart directly into the body coelom 

2. Examples: Arthropoda, Annelida, Mollusca 

B. Closed circulatory system--Blood is pumped via a heart(s) through a closed series of tubes.

1. Arteries carry blood AWAY from the heart. 

a) Very thick walled, highly elastic, and muscular.  

b) Arterial blood has the highest internal pressure. 

2. Arterioles--smaller arteries. 

3. Capillaries.  

a) Connect arterioles with venules.  

b) Have only an endothelium.  

c) Are the site of gas, nutrient, and waste exchange. 

d) Plasma forced out to bloodstream to form interstitial fluid and eventually lymph. 

4. Venules are small veins that receive blood from capillaries. 

5. Veins carry blood TOWARDS the heart. 

a) Thin walls compared to arteries, thinner muscle layers, not as elastic. 

b) Veins collapse without blood, whereas arteries stay open. 

c) Veins carry lowest blood pressure; have VALVES to prevent backflow or 

pooling of blood.

The heart is a 4-chambered muscular pump, whose gross structure we have discussed 

previously.

1. A brief review of human blood flow

a) The right atrium (auricle) receives blood from the superior and inferior vena 

cava. 

b) The right atrium contracts sending blood past the tricuspid valve, into the right 

ventricle. 

c) When the right ventricle contracts (ventricular systole), the tricuspid valve slams 

shut preventing the backflow of blood into the atrium, generating the pressure to 

send the blood out of the right ventricle into the pulmonary artery. 

(1) As the blood enters the pulmonary artery, it passes the pulmonary 

semilunar valve, a valve that prevents backflow of blood into the right 

ventricle when the right ventricle relaxes (ventricular diastole). 

(2) The pulmonary artery branches to send blood to both lungs. 

d) Oxygenated blood from the lungs returns to the left atrium via pulmonary veins. 

e) Blood is pumped from the left atrium to left ventricle through the mitral 

(bicuspid) valve. 

f) When the left ventricle contracts (ventricular systole), the mitral valve slams 

shut preventing the backflow of blood into the atrium, generating the pressure to 

send the blood out of the left ventricle into the aorta and the general circulation. 

a) The bicuspid valve has two flaps, and the tricuspid valve has 3 flaps. 

b) Chordae tendonae and papillary muscles prevent prolapse of the tricuspid and 

mitral valves. 

(1) The chordae tendonae are strands of connective tissue that connect the 

ventricular surface of the mitral and tricuspid valve flaps to the papillary 

muscles. 36

(2) The papillary muscles are masses of cardiac tissue (muscle) within the 

ventricles. 

(3) When the heart tissue contracts, so do the papillary muscles. 

(4) The papillary muscles along with the chordae tendonae permit the cusps of 

the mitral and tricuspid valves to slam together forming a seal that 

prevents the backflow of blood into the atria, while preventing the 

prolapse of the valves. 

c) The heart is housed within a fibrous bag called the pericardium that cushions 

and protects the heart.

The conducting system of heart is composed of “autorhythmic” cardiac muscle that is 

"leakier" to Na ions, than typical cardiac tissue.

1. The sino-atrial node (SA node) or pacemaker of heart is located in upper, lateral 

corner of right atrium. 

2. The sarcolemma of the SA node is “leaky” to Na ions 

a) The membrane gated Na ion channels are not completely closed. 

b) As Na ion trickle in, the threshold potential reached, and an action potential and 

impulse is generated. 

3. The impulse is transmitted throughout the atria for the following reasons. 

a) Cardiac cell membranes are directly connected, unlike skeletal fibers that are 

separated by a layer of connective tissue (endomysium). 

b) Intercalated discs are concentrations of gap junctions, and are found where 

cardiac fibers connect to one another. 

c) The intercalated discs of cardiac muscle facilitate impulse conduction, as 

contain gap junctions allow movement of ions across the membranes. 

d) Cardiac muscle is referred to as "functional syncytium", in that it conducts an 

impulse, as would a single cell. 

4. The two atria contract in unison. 

5. The tricuspid and mitral valve tissue creates a septum of connective tissue that 

prevents transmission of the impulse into ventricles (connective tissue is not excitable 

tissue). 

6. The impulse does, however, stimulate another mass of conducting tissue, the Atrioventricular node (AV node), located in the lower, medial portion of right atrium. 

7. A band of conducting tissue that is an extension of the AV node, called the Bundle of 

His, conducts this impulse across the connective tissue barrier to ventricular cardiac 

tissue. 

8. The Bundle of His branches into Purkinje fibers that extend throughout the ventricular 

myocardium. 

a) The conducting tissue conducts impulses more rapidly than “ordinary” cardiac 

tissue. 

b) As a result the Purkinje fibers deliver the impulse to the apex (inferior point) of 

the heart and the impulse quickly flows up towards the atria, only to be blocked 

by connective tissue separating the atria and ventricles.

9. The resulting ventricular contraction (systole) goes from the bottom-up, forcing blood 

through the aorta and pulmonary artery, which attach to the superior portion of the 

ventricles. 

10. As with the atria, the ventricles contract simultaneously.

Even though there are four chambers, the heartbeat has a two beat cadence-- the heart 

sounds are described as a “lub-dub.”

1. The "lub" is the sound created by the simultaneous closing of tricuspid and bicuspid 

valves, caused by ventricular systole. 37

2. The "dub" is the sound created by the simultaneous closing of aortic and pulmonary 

semilunar valves, caused by ventricular diastole, and the elasticity of the arteries. 

3. The heart sounds are not due to movement of blood, but the slamming of heart valves 

in response to that movement.

1. There is a slight delay between atrial contraction, and ventricular contraction. 

a) The AV node creates this delay. 

b) The delay creates time for blood to flow from the atria to the ventricles. 

2. If the SA node is damaged by disease, any of cardiac tissue has the potential to initiate 

an action potential, due to cardiac muscle’s propensity for Na ion leakiness. 

3. These “competitive” pacemakers called ectopic (which means unusual) foci, and they 

cause ectopic heartbeats that can lead to less coordinated contractions, and less 

efficient flow-- ectopic ventricular foci and heartbeats are much more serious than 

atrial problems. 

An electocardiogram (EKG or ECG) measures electrical changes generated by heart 

conduction of impulses.

1. The P wave is a record of atrial depolarization. 

2. The QRS wave is a record of ventricular depolarization. 

3. The T wave is a record of ventricular repolarization (or the ventricular refractory 

period).

Blood pressure is a measure of the hydrostatic pressure exerted on the internal surface of 

blood vessels.

1. “Systolic pressure” is a measure of arterial pressure generated during ventricular 

systole (contraction)-- normal systolic pressure for an adult male is 120 mm Hg. 

2. Diastolic pressure is a measure of the arterial pressure generated during a ventricular 

diastole (relaxation)-- normal diastolic pressure for adult male is 80 mm Hg. 

3. “Normal” blood pressure is “120/80.” 

4. Blood pressure depends on many factors including force of heart contraction; total 

volume of blood in circulation; vessel diameter, total vessel length (related to body 

weight), elasticity of vessels and other factors. 

5. Youth, being female, and fitness, all lower blood pressure values from “normal.” 

6. Cardiovascular disease, diet, stress, tobacco consumption, disposition and other factors 

all raise blood pressure from “normal.”

Clotting of blood when vessels are damaged is crucial to maintenance of homeostasis (a 

constant internal environment).

1. Many factors important to homeostasis are dependent on blood volume and pressure 

including thermoregulation, excretion, gas exchange, and others. 

2. When blood vessels and the surrounding tissue are damaged, the tissues release 

numerous clotting factors including prostaglandins, and thromboplastin into blood 

(these are considered extrinsic clotting factors since they were not produced by blood 

cells). 

3. The extrinsic clotting factors cause platelets to also release thromboplastin and other 

clotting factors into the blood plasma (these are considered intrinsic clotting factors 

because they were produced by blood cells). 

4. Prostaglandins make the platelets "sticky" causing them to stick to one another 

forming a platelet plug, which may partly or completely occlude a vessel opening. 

5. Thromboplastin acts as an enzyme, converting a plasma-clotting factor called 

prothrombin, into a different clotting factor called thrombin. 

6. Thrombin is an enzyme that converts the clotting factor fibrinogen into a tough fibrous 

protein called fibrin. 

7. Fibrin fibers attach to one another creating a dense network that is the clot (a dried clot 

is a scab). 

8. The clot seals the damaged area, stopping the loss of blood maintaining homeostasis. 

9. Other comments about clotting. 

10. Fatty diets high in cholesterol, and circulating triglycerides, can lead to fatty deposits 

on vessel walls called atherosclerosis. 

11. These fatty plaques can lead to platelet plug formation and fibrin clots, which in turn, 

may calcify the plaque and vessel wall making it inelastic-- this is arteriosclerosis. 

12. Both types of vascular disease increase blood pressure by decreasing vessel diameter. 

13. Plaques can lead to vessel swellings called aneurysms, which may burst-- typically 

these cause myocardial infarction (heart attack) or stoke. 

14. A plaque may dislodge, now forming a moving thrombus, which will eventually lodge 

in a smaller vessel causing a blockage called an embolism.

The Lymphatic (Lymph) System is an open vascular system that recovers fluid lost from the 

cardiovascular system, filters it for pathogens, and returns it to veins near the heart.

A. Plasma lost from the capillaries of the cardiovascular system becomes interstitial fluid, 

which percolates through tissues, and eventually enters lymph vessels as lymph. 

B. The lymph system is composed of a series of interconnected lymph vessels and nodes, lying 

close to the circulatory system at all times. 

C. It is an OPEN system, and the vessels have valves to prevent back up of lymph fluid. 

D. Lymph is pushed along by movement, the contraction and relaxation of skeletal muscles. 

E. Several lymph vessels typically converge on lymph nodes. 

1. Internally the lymph node is sectioned into several large spaces (or sinuses), traversed 

by a lattice of thin collagenous fibers called reticular tissue. 

2. Lymphocytes, and antigen presenting cells like dendrocytes and macrophages cling to 

the reticular fibers. 

3. As lymph percolates through the node, antigens and cellular debris will be 

phagocytized and may initiate immune responses. 

4. Lymph nodes are also sites of lymphocyte reproduction and maturation. 

5. Afferent vessels empty lymph into the nodes; efferent vessels drain lymph from the 

nodes. 

6. The tonsils and adenoids are examples of lymph nodes. 

F. The spleen and thymus, while not really nodes, have considerable lymph tissue and are 

considered lymph organs. 

G. A pair of lymph vessels near the heart returns lymph directly into the circulatory system. 

1. The Right Lymphatic Duct drains lymph from the upper right quadrant of the body, 

and empties into the junction of the Right Subclavian and Right Jugular veins 

converge to form the Right Brachiocephalic vein. 

2. The Thoracic Duct drains the remaining 3/4 of the body and empties into the junction 

of the Left Subclavian and Left Jugular veins converge to form the Left 

Brachiocephalic vein. 

H. The lymph vessels also absorb and transport lipids from the digestive tract to the 

cardiovascular system.

The body has a number of defense mechanisms to protect it against pathogens or toxins.

A. Some body defenses are non-specific in scope.

Some body defenses are non-specific in scope.

1. There is a physical barrier posed by the integument and mucous membranes.

2. There are non-specific chemical defenses.

a) Skin secretions keep the surface of the skin acidic (pH 3-5), inhibiting some

bacterial growth.

b) Non-specific humoral defense.

39

(1) Complement is a group of approximately twenty plasma proteins produced

by the liver that react to a broad spectrum of antigens--when activated

complement has the following effects.

(a) It will bind to foreign cells marking them for phagocytosis by

neutrophils or macrophages.

(b) It will cause inflammation of infected or damaged tissue.

(c) It will form a MAC’s (membrane attack complex) in the cell

membranes-- MAC’s form large pores that allow the cytoplasm to

leach out of a target (foreign) cell.

(2) Interferons are secreted by virus-infected cells and have the following

effects.

(a) They bind to receptors that are exploited by viruses to protect cells

from viral infection.

(b) They activate the immune system.

1. An antigen elicits an immune response, typically a “foreign” substance-- the epitope is

the specific part of the antigen that causes the response.

a) All cells have MHC 1.

b) Only APC’s (described below) and B cells have MHC 2.

c) The MHC’s play a role in allowing immune cells to determine whether cells are

“self” vs. “non-self” and whether to launch an immune response.

3. Neutrophils are non-specific phagocytic leukocytes.

4. Macrophages are monocytes that have moved out of the bloodstream into the tissues.

For #4: a) They are non-specific phagocytic leukocytes.

b) They are also considered antigen-presenting cells (APC)-- APC’s present

antigens with their surface MHC 2 proteins activating an immune response.

5. Dendrocytes are derived from macrophages, and have many processes--

 they tend to

“lie in wait” in many tissues, phagocytizing what does not belong, are also APC’s.

6. B cells are a type of lymphocyte that become plasma cells when activated--

 plasma cells secrete antibodies, launching an antigen specific humoral “chemical warfare.”

a) Antibodies may mark an antigen for phagocytosis or kill the antigen-bearing cell

directly.

b) Antibodies are composed of four polypeptide chains-- two heavy chains, and

two light chains.

c) Antibodies of a specific class have a variable region, which binds the antigen

and is antigen specific, and a constant region, which will be the similar within a

class of antibodies.

d) Gamma globulins or immunoglobulins are other terms to describe antibodies.

8. T cells are a different kind of lymphocyte of which there are several types.

a) Helper T cells (TH).

(1) Helper T’s are activated when their CD-4 receptors react with antigen

bound MHC 2 proteins displayed by APCs.

(2) Helper T’s play a key role in initiating and regulating a specific immune

response.

(1) Cytotoxic T’s are activated when their CD-8 receptors react with antigen

bound MHC 1 proteins displayed by APCs, TH’s, and other cells.

40

(2) Activated Cytotoxic T’s kill cells displaying the specific antigen to which

they are sensitive-- a type of “cell to cell combat” to kill cells already

infected by a pathogen.

(2) Natural killers kill cells displaying a broad spectrum of antigens marked

for destruction by complement or interferons.

d) Suppressor T cells (TS) inhibit a specific immune response after “winning” the

battle against an antigen, may be derived from Helper T’s.

9. Memory cells 

are a select group of Helper T’s, Cytotoxic T’s, and B cells, all sensitive to the same antigen, that survive suppression of an immune response to live for the

rest on your life in lymph nodes-- they quickly respond to launch a specific immune

response should you ever be exposed to the antigen again.

a) Interleukin 1 is secreted by APC’s-- it activates Helper T’s to secrete interleukin

2 and to divide to produce a clonal population.

b) Interleukin 2 is secreted by activated Helper T cells-- it stimulates B cells to

divide and convert to plasma cells (creating a clonal population of plasma cells),

and Cytotoxic T’s to divide (creating a clonal population of Cytotoxic T’s) and

“seek and destroy” infected cells.

Specific humoral clonal response to an antigen is described below and confers “lifelong”

immunity.

1. An antigen is consumed and displayed by an APC in its MHC 2.

2. The APC will encounter and briefly bind with Helper T cells.

3. When the APC encounters a Helper T with a CD-4 receptor protein that is

complementary to its MHC 2/antigen complex, the APC secretes interleukin 1.

a) Interleukin 1 stimulates the Helper T to divide creating a clonal population of

Helper T’s all sensitive to the specific antigen.

b) Interleukin 1 also activates the Helper T’s to seek out and interact with B cells

and Cytotoxic T cells.

4. Helper T cells encounter B cells displaying the same antigen causing the Helper T’s to

secrete interleukin 2.

secrete interleukin 2.

a) Interleukin 2 causes the B cell to divide to create a clonal population sensitive to

the same antigen.

b) Interleukin 2 causes the B cell to convert to a plasma cell to begin production of

antibodies specific to the antigen.

c) The clonal population of plasma cells produces massive quantities of antibody.

d) The antibodies carry out a very effective “chemical” warfare against the antigen.

e) Antibody production is crucial to effective resistance to and recovery from

disease causing organisms-- we would not survive with only cell-to-cell combat.

5. Helper T cells encounter Cytotoxic T cells displaying the same antigen causing the

Helper T’s to secrete interleukin 2.

a) Interleukin 2 causes the Cytotoxic T cell to divide to create a clonal population

sensitive to the same antigen.

b) Interleukin 2 causes the Cytotoxic T cell to aggressively “seek and destroy”

infected cells in a “cell to cell” combat.

c) This prevents pathogens from increasing numbers by destroying their host cell.

6. At some point, as the infection is controlled and some Helper T cells are thought to

convert to Suppressor T cells.

7. Suppressor T cells trigger apoptosis of Helper T cell, plasma cell and Cytotoxic T cell

clones.

41

8. Some Helper T cell, plasma cell and Cytotoxic T cell clones survive and become

Memory cells in the lymph tissue.

9. This ends what is considered the primary response to an antigen.

10. The memory cells will respond much more rapidly to a repeated exposure to the

antigen in what is called a secondary response.

11. There is mutagenic mechanism at work in the Helper T cells, B cells, and Cytotoxic T

cells affecting antigenic receptor proteins that generates new types of cells, sensitive to

“new” antigens.

12. The key to resisting infection is having Helper T cells, B cells and Cytotoxic T cells

that are sensitive to a specific antigen, and they being able to respond to the pathogen

before it has done irreparable harm.

Vaccination protects an individual from disease.

1. Active immunity is an artificially induced primary infection, which lends secondary

protection--the host is making its own antibodies.

a) Live attenuated vaccines use a live organism that will trigger an immune

response without causing disease-- the organism may be genetically modified or

a close relative of the pathogen.

b) Some vaccines contain killed pathogens-- the organisms cannot reproduce, but

the antigens are present to initiate an immune response.

c) Epitopic vaccines are highly purified solutions that contain the antigenic agent.

d) Nucleic Acid Vaccines—as the name implies, genes from viruses or other

pathogens introduced into the bloodstream in plasmids; how they work is not

entirely known, thought that immune transformed and produce proteins

intracellularly; HIV, malaria, influenza vaccines being developed this way.

a) Since the vaccine contains no antigenic agent, an immune response is not

launched.

b) Passive immunity is temporary, lasting only as long as the antibodies exist in the

body, and it lends no secondary protection.

E. Self vs. non-self.

1. One of the keys to initiation of an immune response is the immune system deciding

whether a molecule is yours (self) or foreign (non-self).

a) Self-antigens must be ignored.

b) Non-self antigens are evidence of a potential pathogen and will be destroyed.

2. The MHC 1 proteins are important in this process.

3. The Thymus gland screens lymphocytes for their sensitivity to self-antigens.

a) Lymphocytes that bind too strongly or weakly to self-antigens are destroyed.

b) Lymphocytes that moderately bind to self-antigens live.

c) An infant is exposed to a variety of antigens early in life, newly derived

lymphocytes may be sensitive to self antigens and must be screened--as a result

the infant thymus is huge, and shrinks as we age.

d) One of the best ways to ensure the infant immune system does not develop

hypersensitivities to self or foreign antigens is to breast feed for as long as

possible.

4. Autoimmune disorders are those in which the immune system reacts to self-antigens--

diabetes mellitus, and lupus erythrematosis are examples.

F. The danger theory.

1. Self vs. non-self does not explain all behaviors of immune response.

2. It appears that in addition to the self vs. nonself trigger, a second signal is required to

initiate an immune response.

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3. This second signal has sometimes been described as the danger signal-- in other words

it is not enough that an antigen is foreign; it must also be demonstrating some danger

to our health in the form of tissue damage.

a) Maternal nonreaction to the foreign fetus growing within her.

b) Carefully dissected tissue transplants trigger less immune response than those

with more tissue damage.

c) Autoimmune disease onset occurs most frequently after an illness-- it seems a

self-antigen is confused with a dangerous antigen.

d) Many vaccines are more effective when the epitope is combined with an

adjuvant of ground up foreign tissue.

5. The specifics of the role of the danger signal are largely unknown-- this is a relatively

new, but intriguing spin on immune responses.

G. Inflammation is tissue response to injury, which acts to isolate the area to prevent the spread

of infectious agents, dispose of cell debris and pathogens, and begin the healing process.

1. Damaged tissue secretes several chemicals including histamine and prostaglandins.

2. They cause vasodilatation and increased capillary permeability.

3. This leads to plasma loss from capillaries causing edema of the tissue.

4. The edema contains clotting factors, which isolates fluid in the area, dilutes pathogens,

and creates scaffolding for tissue repair.

5. Macrophages and other immune cells are attracted to the area possibly launching an

immune response.

6. The swelling and prostaglandins also irritate nociceptors.

7. The hallmarks of inflammation are redness, swelling, heat, and pain.