Non specific immune responses

It takes 7 days from the introduction of a pathogen for a specific immune response to begin. The specific immune response engages the use of T and B cells. T-cells are activated in response to a viral pathogen and B-cells are made in response to an introduced bacteria. The cells are very good at their job, however, 7 days is plenty of time for a pathogen to make itself at home, multiply and invade, which could defeat the B and T cells if the introduced pathogen's numbers are not controlled. Our body attempts to suppress the numbers of the pathogen by presenting a counter attack on day 3.

At this time, Complement Protein Activation begins. Complement proteins are made everyday in the liver and circulate in the blood. The classical pathway of activation is as follows: C1 and C2 bond, splitting C2 into C2a and C2b. C2a floats away. 2b bonds with 4 causing 4 to split into 4a and 4b. 2b and 4a bond creating 3. 4a floats away. C3 bonds with 4b and splits into 3a and 3b. C3b then splits C5 into activated C5a and C5b. C5b then binds to C6, C7, C8 and C9 forming a Membrane Attack Complex (MAC) that has lytic capabilities, in which the complex figuratively punches holes in the membrane of the bacteria, resulting in cytolysis. Basically, these holes allow fluid to enter the cell and it explodes. Before the MAC complex is created there is another weapon that is released in the splitting process. C3a and C5a are the most potent vasodilators that have been found. Vasodilation is a major player in the process of inflammation and phagocytosis, which both help to fight invaders.

During class the issue of immunizations and specifically the flu vaccine was discussed briefly. At first I was thinking that if we decreased the use of the flu vaccine (limiting the vaccine to the elderly and children), that maybe the virus wouldn't be forced to change and modify itself. Dana explained that virus's continually evolve anyway and that limiting the vaccine probably wouldn't help. There is the other issue though of the flu vaccine being helpful anyway, since it is a 3 year process to develop it. What are the chances that it will even be the right strand? I am not against vaccines, I just believe in extreme caution in the administration of them. The conversation about vaccines, led me to the situation with antibiotics and how doctors are warning patients and their families to not abuse the medication due to bacteria learning how to modify itself so that it cannot be treated with the normal prescribed antibiotics. Call me crazy, but I have been worried about this for years. If our antibiotics are rendered useless, we are not left with much to defend ourselves against many, many infections.

Arteries and Veins

One of the major concepts that we covered in class was contrasting arteries and veins. We started with attempting to define the two and learned that we could not include the transportation of oxygenated vs deoxygenated blood into our definitions because both have one big exception. Arteries are vessels that carry oxygenated blood away from the heart, except for the pulmonary arteries which transport deoxygenated blood. Veins are blood vessels that as a majority, carry deoxygenated blood to the heart, with the same except being the pulmonary veins, which transport oxygen from the lungs to the heart.

Both arteries and veins are composed of three layers: the Tunica Intima, Tunica Media and the Tunica Externa, however, each has its own characteristics. For instance, arteries have a thicker Tunica Media, which is comprised of smooth muscle cells and elastic fibers, to help open and close the arteries. The elasticity is needed to withstand the pressure of the blood as it is pumped through. Veins on the other hand, have a much thinner Tunica Media as they do not need to handle the same amount of force. The outermost layer, the Tunica Intima contains a single layer of simple squamous epithelium (Endolithium), a basement membrane, and in the case of arteries a layer of elastic fibers. The layer of simple squamous epithelium, allows for an easy gas exchange. The outermost layer, the Tunica Externa is also found on both arteries and veins and is comprised of dense irregular connective tissue.

Another striking difference is inclusion of valves in veins. Arteries lack this feature. Valves are used in larger, deeper veins in the lower extremities to prevent the back-flow of blood due to gravity. Skeletal muscles work hard to move the blood toward the heart and valves work in conjunction to stop blood from pooling. Valves that malfunction are said to have lost their patency and varicose veins can occur.

I began wondering if the valves could ever be repaired if the person began regularly exercising so that one, the heart could more effectively pump the blood and two, so that the blood was circulated more effectively. If the patient had a strict exercise regimen, would that be enough to prevent pooling, without one or two valves, if that was all that had lost patency?

Red Blood Cell Formation and Destruction

Red blood cells live approximately 120 days and then die and then pieces are recycled. Since red blood cells dispose of their nucleus while a reticulocyte and have no organelles, the RBCs cannot repair themselves or undergo mitosis. This is not inhibitory to their function, however, since their main job is to transport oxygen. Red blood cells are very efficient at this job since they produce ATP anaerobically and thus do not use oxygen in this process. RBC's bind or hold an oxygen molecule to each Iron which is at the center of each porphyrine ring (part of the hemoglobin molecule).

RBC's are phagosized in either the spleen, liver or red bone marrow. The RBC is first most broken down by macrophages into globin and heme. The globin is further broken down into amino acids and are reused for protein synthesis. The iron in the heme is then transported in the blood by a transport protein called transferrin, to the red bone marrow, where it binds to the transferritin and is stored (until used as part of Erythropoiesis). The rest of the heme is converted into biliverdin and then biliruben, enters the blood stream and travels to the liver. It is then secreted into the small intestine as bile. While in the small and large intestines, bile helps to break down large fat molecules. In the large intestine the bilirubin is converted by bacteria into urobilinogen. Some of this is converted into urobilin in the kidney and leaves the body as urine. Most of the urobilinogen is excreted in feces in the form of stercobilin.

I think the most worrisome part of this process for me is that there are some many players or places in this process where things can go awry and cause major problems for the body. And, if the body already has a disease or disorder that effects any of these elements, it becomes an even more compounded problem for the body, bringing it further and further from homeostasis. It seems like there are some naturally built in back-up systems to prepare in a way for such events. For example, if the body is suffering from liver disease and has lost some of its functioning, the macrophages can still phagosize RBCs in the spleen or red bone marrow. The liver however is still engaged in other parts of the process and I am not sure how the body adapts to this malfunction. The disfunction of one part or player in the process produces a domino effect on the rest of process, which, if I understand correctly, continues beyond just this process, effecting possibly many other processes and systems.

2nd Messanger Systems- cAMP

This messenger system begins with a hormone such as GH binding to a membrane bound receptor. Since the hormone is a protein the binding event causes a shape change in the receptor, which causes a shape change in the G-Protein complex. The G-Protein complex includes alpha, beta and gamma units, as well as an attached GDP, a low energy molecule. This shape change causes the G-Protein complex to remove the attached GDP and allows a molecule of GTP to bind. The alpha subunit and attached GTP then break away and bind to the Adenylate Cyclase. This then induces a shape change in the AC. A molecule of ATP is then recruited to the AC and is adapted into cAMP by the removal of 2 of its phosphates. It is now a 2nd messenger. The cAMP then binds to a PKA causing a shape change in the PKA which changes ATP into ADP leaving a phosphate attached to the PKA. The PKA is now able to transfer a phosphate to key enzymes. For example, in the case of GH, enzymes need the phosphate for mitosis.

Because I have a family member with liver cancer, I am interested in liver function and health. We learned that transfer proteins, specifically Albumin, transport steroidal hormones to target cells so that they can perform their function. I do not know if my family member has a low or high albumin count but I decided to read on-line to get some more information. I learned that in general, serum proteins are divided into two major categories, albumin and globulin and that the globulin can be broken down into 4 subdivisions. A general blood panel will test for the total protein, albumin. globulin and albumin/globulin ratio. I reviewed the causes for high and low amounts on all categories and it seems as if liver disfunction can cause it all. Total proteins may be increased due to liver disfunction or they may be lower than normal due to liver disease. The only category that liver disfunction did not seem to cause a change was in an increase in albumin. I did learn one interesting fact. Albumin levels can be used as strong predictors of health. Low levels of albumin suggests very poor health and a "predictor of bad outcome".

Pituitary Gland

The pituitary gland is divided into the posterior and anterior sections. The posterior pituitary releases the hormones oxytocin and ADH (Anti diuetic), however, it does not produce these hormones. The hormones are actually made in the hypothalamus and travel through a neuronal tract to the posterior pituitary gland, where it is released into the blood stream. Oxytocin stimulates mammery glands for milk secretion and stimulates the uterus for uterine contractions during child birth. ADH stimulates thirst and as a result less urine is produced to help rehydrate the body.

The Anterior Pituitary is composed of epithelial tissue and produces several different hormones. Growth hormone, prolactin and melanocyte-stimulating hormone work to stimulate a target organ directly. The others, Thyroid-stimulating hormone, ACTH, and Gonadotropin (FSH and LH) secrete hormones to effect other hormones which then stimulate a target organ or tissue. For example, Thyroid-stimulating hormone stimulates the Thyroid, triggering the release of Thyroxin, which regulates metabolic rate.

Many people in my family (including sibling and both parents) have hypothyroidism and so I decided to research this condition on-line. I learned that the disorder is a result of low levels of the hormones produced by the Thyroid gland, mostly, T3 and T4 and since most T4 is converted into T3 in the blood, this is the hormone of interest. The job of T3 is to regulate the metabolism of cells. The releases of thyroid hormones is regulated by a negative feedback system involving the hypothalamus, the pituitary gland and then the thyroid. The hypothalamus relases Thyrotropin releasing hormone which triggers the release of Thyroid-Stimulating hormone from the Pituitary Gland, which in turn sends a signal for the Thyroid gland to release its hormones. A disruption in any of these levels can result in a low production of Thyroid hormones.

The most common cause of this disorder is Hoshimoto's Thyroiditis Disease, an inherited disease, marked by an enlarged Thyroid gland that has difficulty producing its hormones. It is an autoimmune disease in which the body attacks the tissue of the gland. Other causes include a severe iodine difficiency or medications. Some medications used to treat hyperthyroidism actually have a dramatic effect by causing hypothyroidism. The treatment includes taking synthetic T-4 for the length of life of the patient. T4 is used instead of T3 because it effect is longer lasting and is converted into T3 easily.

Autonomic Nervous System, Part II

All Autonomic impulses are afferent, meaning that they travel from the CNS to the PNS. The ANS can be broken down into two major divisions, the Parasympathetic and the Sympathetic divisions. The Parasympathetic division is responsible for all of the feed-and-breed or rest-and-digest functions of the body and is the restorer of homeostasis. The preganglionic axon is long and the post ganglionic axon is short. The Sympathetic division can be seen as the parasympathetic divisions opposite. The Sympathetic division carries out the fight-or-flight responses in our body. In this division, the preganglionic axon is shot and the post ganglionic axon is long. In both divisions, the target cells are smooth muscle, cardiac muscle and glands. Another commonality is that all preganglionic neurons release Ach and all receptors on the post ganglionic neurons are thus nicotinic.

There are two different categories of receptors for the ANS. Cholinergeric, which includes both Nicotinic and Muscarinic receptors and Adrenergic receptors. Nicotinic receptors always cause excitation or activation and perform as both the receptor and channel. They also only bind Ach. Muscarinic receptors can either cause excitation of inhibition and use either a PKA pathway or a PKC pathway to allow chemicals to enter the neuron. Both pathways utilize G-Proteins. Adrenergic receptors also utilize these pathways and are broken down into a1, a2, b1, b2, b3 receptors. The 1's refer to impulses that cause constriction or contraction and the 2's refer to impulses that cause dilation. B3 is the odd man out and its impulse causes heat production. Muscarinic and Adrenergic receptors are found on the cells of terminal targets.

I understood from lecture that the Adrenal gland, a gland that sits on top of the kidneys, is part of the sympathetic nervous system. This gland produces both epinephrine and norepinepherine by diffusing the hormones into the blood stream. This direct link into the blood stream allows for a fast regulation of the hormone throughout the body. That was as much as I was able to retain from lecture, so I researched a little more on the Internet. I learned that adrenal medulla is the central core of the Adrenal gland. The neurons within it (called Chromaffin cells) produce the hormones that are released into the blood stream instead of producing an impulse as all of the other neurons that we have learned about do. These hormones aid in the fight-or-flight response by increasing blood pressure, metabolic rate and or glucose concentration. The neurons in the Adrenal Medulla also produce dopamine, which low-levels of this hormone has been linked to Parkinson's diseases.

Automonic Nervous System

There are two motor neurons in an autonomic motor pathway. The first neuron is called a preganglionic neuron and its cell body is located in the brain or spinal chord. Its axon (very long) leaves the CNS and extends (as part of a spinal or cranial nerve) to an autonomic ganglion. The second neuron is called the post ganglionic neuron and its axon is short. The preganglionic neurons pass along nerve impulses from the CNS to the autonomic ganglia and the postganglionic neurons relay the impulse from the autonomic ganglia to the terminal target, which could be smooth muscle, cardiac muscle or a gland. The neurotransmitter that is released is always excitatory and is always Ach. The #2 neuron always produces an action potential. Wether the terminal target becomes excited depends on its receptors. They are usually cholinergeric and thus are either Nicotinic (excitatory) or muscarinic (inhibitory).

After browsing the internet, I learned that a malfunction in the autonimic system is called autonomic failure and is a result of the imbalance between the sympathetic and parasympathetic divisions of the autonomic nervous system. Signs that there is an imbalance include orthostatic hypotension and postprandial hypotension. These can cause dizzyness or lightheadedness. Elderly people are most likely to suffer from this condition and the drop in blood pressure is usually a result of the onset of a disease (diabetes, stroke) and the medications that are used to treat them. There is no cure for autonomic disorders, however there are medications that can treat the low blood pressure and the uncomfortableness that accompanies the episodes.