Vaccines

If nothing else watch this very short video on how different vaccines are made.

Naturally Acquired Immunity is that immunity acquired upon exposure to a specific pathogen or foreign antigen.

Artificially Acquired Immunity is that immunity obtained via vaccination with a killed or live attenuated pathogen.

Vaccine is a preparation of killed or live attenuated pathogen or of specially derived pathogen antigenic determinants that is used to induce an immune response that protects an individual to a subsequent exposure to that pathogen.

Vaccination (immunization) is a means of inducing artifically acquired immunity. The goal of vaccination is to induce antibody or cell-mediated immune responses against a pathogen, without simultaneously inducing disease.



Edward Jenner was the army surgeon who is generally credited with advancing the art of "vaccination". On May 14, 1776, Jenner purposely exposed James Phipps with cowpox virus obtained from dairymaid Sarah Nelmes. Phipps became immune to smallpox as evidenced by survival of several purposeful attempts to infect him with the virus. Benjamin Jesty claims to have done the same thing 20 years prior to Jenner. Actually, the Chinese probably were vaccinating against smallpox hundreds of years before either of these men were born.

After the introduction of the smallpox vaccine in 1778 additional vaccines were introduced such as Rabies 1885, Plague 1897, Diptheria 1923, Pertussis 1926, Tuberculosis and Tetanus 1927 and Yellow fever 1935.

TYPES OF VACCINES

Inactivated Vaccines (killed) are vaccines consisting of an inactivated whole pathogen. Because the pathogen is dead these vaccines are considered very safe. However, they usually require several booster doses of the vaccine to induce sufficient immunity. An example of an inactivated vaccine is the Salk Polio vaccine and the Influenza vaccine.

Live, Attenuated Vaccines are vaccines that are made from a live pathogen that has been weakened so it cannot cause disease. These vaccines actually result in a mild infection, thus inducing a very strong protective immune response. A disadvantage of these vaccines is that they typically cannot be given to immunosuppressed individuals. An example of a live, attenuated vaccine is the oral Sabin Polio vaccine and the smallpox vaccine.

Toxoid Vaccine is a vaccine that is made from an inactivated toxin. Many infectious bacteria produce a toxin that is the cause of disease. Toxoid vaccines are made by treating the toxin chemically or with heat to inactivate it. Examples of toxoid vaccines are Diptheria and Tetanus vaccines.

SECOND GENERATION VACCINES

These vaccines are the result of recombinant DNA techology.

Subunit Vaccines are vaccines developed from well defined antigenic fragments of a pathogen.

Recombinant subunit vaccine are obtained using recombinant DNA techniques. Yeast cells are transfected with DNA which encodes an antigenic determinant of a pathogen. The yeast cells are grown in culture and the recombinant vaccine antigen is purified from the yeast cell culture. An example of this type of vaccine is the Hepatitis B vaccine.

Recombinant vector vaccines are made by inserting pathogen genes that encode protective antigens into a virus that does not cause disease (such as the vaccinia virus) but can express the pathogen genes. Although clinical trials are being done using these vaccines, there are no currently approved recombinant vector vaccines.

Conjugate Vaccine is a vaccine that is specially designed to induce immunity in babies who have an immature immune system. These vaccines consist of a polysaccharide (bacterial surface coat antigen) which is combined with an immunogenic protein that can be recognized by the baby's immune system. An example of this type of vaccine is the Haemophilus influenzae type b (Hib) vaccine.

FUTURE VACCINES

DNA Vaccines are made of a modified form of the pathogens DNA. When this DNA is injected into an individual, the pathogen DNA enters the cells which leads to the expression of the genes in the DNA (pathogen antigens). You can read more about DNA vaccines here.

Edible Vaccines are vaccines in which the pathgen antigens are expressed in edible plants such as potatoes and tomatoes. Read more about edible vaccines here.

VACCINE SIDE EFFECTS

Vaccination can result in side effects. These are typically local side effects including pain, redness, swelling, itching or a small lump at the site of injection.

However, occasionally systemic side effects can occur. These might include headache, fever, muscle aches or rashes. Very occasionally severe side effects might occur such as anaphylaxis shock.

Immunity - Lymphocytes

Lymphocytes: these are the cells that are responsible for specific immune responses. There are two distinct classes of lymphocytes:

B lymphocytes: are the cells that produce antibodies. The specific antigen receptors on B cells are membrane-bound forms of antibodies. Antibody producing B cells are called plasma cells.

T lymphocytes: do not produce antibody molecules. They produce a wide variety of molecules called cytokines that mediate immune resistance and have the capacity to directly kill other cells. There are at least three main types of T cells:

Helper T lymphocytes: (CD4+) participate in th activation and development of B lymphocytes, the activation of macrophages and the inflammatory response. They recognize foreign antigens presented by cells displaying MHC Class II molecules. You can see an animation of how this works here.






Helper T lymphocytes can be further divided into TH1 and TH2 lymphocytes.



Pathways to TH1 and TH2 lymphocyte differentiation can be seen here.

TH1 and TH2 lymphocytes are differentiated by the cytokines that they secrete. Cytokines are small protein hormones that mediate and regulate immune responses and inflammation. Learn more about cytokines here, here and here.



Cytotoxic T lymphocytes: (CD8+) are the cells that have the capacity to kill virus-infected cells, tumor cells and allografts. They can also mediated other forms of cell-mediated immunity. They recognize foreign antigens presented by cells displaying MHC Class I molecules.



Regulatory T lymphocytes: (FoxP3+) are T cells that act to suppress or regulate the activation of the immune system. These cells are probably important in preventing the expression of autoimmune diseases. These cells are a relatively recent discovery and it is not yet known exactly how they work in many cases.



Lymphocytes can also be differentiated based on the surface proteins they express called clusters of differentiation.





Here is a pretty good representation of the overall immune response to a viral infection obtained from a U. of Texas website.

Down the left side of the picture:

1) A host cell becomes infected with a virus.
2) The cell processes and presents viral antigen epitopes bound to MHC Class I molecules to the antigen receptor on a CD8+ cytotoxic T cell.
3) Activated effector viral antigen-specific CD8+ cytotoxic T cell recognizes a virally infected cell and kills it.
4) After viral pathogen is cleared some CD8+ viral specific cytotoxic T cells become memory cells.

Down the right side of the picture:

1) Lysed virally infected cell releases viral particles.
2) Viral particles are engulfed by activated macrophages, processed and presented, bound to MHC Class II molecules, to the CD4+ helper T cells.
3) CD4+ helper T cell becomes activated, proliferates, differentiates and secretes cytokines to help B cells become antibody producing plasma cells and CD8+ cytotoxic cells to become better killers.
4) Later in the response, viral specific B lymphocytes become very potent antigen presenting cells due to their antigen receptors.
5) As virus is cleared, CD4+ T cells and B cells become either die or become memory cells.

Immunity - Overview

Immune is from the latin immunitas refering to freedom from taxes or the exemption from service. We use the word to mean protection from disease, usually infectious disease.

Immunity is mediated by the immune system, a network of organs, tissues, cells and molecules. A brief introduction to the immune system can be found here.

The immune response is the collective and integrated response of the immune system to the introduction of a foreign antigen into the body.

NATURAL (INNATE) AND ACQUIRED (SPECIFIC) IMMUNITY

Natural or innate immunity are the barriers and mechanisms that mediate nonspecific resistance or defense in the body. Skin, mucous membranes, phagocytic cells and various molecules mediate innate immunity.

Acquired or specific immunity are those immune responses that are specific for distinct antigens and can increase in magnitude and capabilities with every exposure to the same antigen. An animation of specific immunity in action can be seen here.

Active Immunity is the type of specific immunity that is induced when an individual is exposed to an infectious agent or foreign antigen. This is the immunity that is generated in response to vaccination.

Passive Immunity is that immunity that can be transferred using cells or serum obtained from an immune individual. This is a means of rapidly inducing resistance to an individual.

The adaptive immune system is often classified into:

Humoral immunity which is mediated by antibodies. Go here to learn how lymphocytes make antibodies. Watch this animation on an allergic reaction that is mediated by IgE antibodies.

Cell-Mediated immunity which is mediated by T lymphocytes.

The immune response has several important features:

Specificity: immune response is specific for the antigen that induced the immune response.

Diversity: the number of antigen that can be recognized by the immune system is estimated to be 10,000,000,000.

Memory: exposure of the immune system to an antigen results in enhanced capacity to produce more antibodies or T cells to subsequent exposure to the same antigen.

Tolerance: individuals typically do not make immune responses to their own tissues. This is because the immune system is capable of discriminating self from non-self.

Self-limitation: immune responses normally decline after a period of time. This usually correlates with elimination of the antigen that originally induced the immune response.

Learn more about the immune system here and here.

A Human Endogenous Retrovirus Reconstituted

Remember those HERVs we talked about in the previous post? A group from the Aaron Diamond AIDS Research Center at The Rockefeller University has reconstituted one of them using molecular techniques. The entire article is published in PLOS Pathogens, a free, full text, on-line journal.

These investigators have reconstitute a Class II HERV, HERV-K.

A pseudo-ancestral HERV-K DNA sequence was synthesized and used to produce viral proteins and RNA that could reconstitute the HERV-K replication cycle. Thus, the replication and biology of a once-extinct retrovirus can now be studied in the laboratory. Interestingly, reconstituted HERV-K replication experiments, and comparison of the reconstituted HERV-K DNA sequence with the dead HERV-Ks in modern human DNA, suggests that HERV-K may have been extinguished in humans in part by host defenses that induce mutation of retroviral DNA and that the reconstitution of the pseudo-ancestral HERV-K reversed these changes.

This further suggests that infection with ancient retroviruses induced selective pressure on the human immune system allowing us to resist infection with certain retroviruses.

Two major components of intrinsic defense against retrovirus and retroelement replication in primate cells are the TRIM5 and APOBEC3 gene products [40–42]. Analysis of these genes in modern primates indicates that these genes have likely been under positive selection pressure for significant portions of primate evolution [12–16]. As an endogenous retrovirus that has also apparently replicated exogenously and has been active for much of Old World primate evolutionary history, HERV-K is an excellent candidate for an agent that has imposed sustained evolutionary pressure on antiretroviral defenses present in modern primates.

The Introduction and Discussion in this article is very readable. Give it a try.

Human Endogenous Retroviruses

I'm adding this post before I forget about it. We will discuss it more when we cover viruses.

Human Endogenous Retroviruses. These pieces of DNA are 'fossil's of retroviruses that were incorporated into the human germline DNA over thousands to hundreds of thousands to millions of years. They make up about 1% of the human genome. The first HERV was identified in 1981. So far, at least 20 HERV families have been identified (find free text article by M. Tristem here). There are lots of things cool about HERVs. First, they may be involved in the pathogenesis of some diseases, such as cancer, Sjogren's syndrome, Rheumatoid arthritis, Multiple sclerosis or Systemic Lupus Erythematosus, to name a few.

HERVs have been classified into 3 groups based on sequence identity with animal retroviruses.

Class I HERVs share sequence homology with infectious mammalian type C viruses. Examples would be porcine endogenous retrovirus, murine leukemia virus and baboon endogenous virus.

Class II HERVs share sequence homology to mammalian type A, B and D related retroviruses. HERV-K is a member of this group and is one of the most active HERVs. HERV-K can actually form virus-like particles.

Class III HERVs are foamy virus related HERVs and include only HERV-L. This is the oldest known genus of Retroviridae and more can be found about them here.

Why have HERVs been so successfully maintained in our genome? This person has one hypothesis. Is is possible that HERV's somehow serve the needs of the host? Also here.

Science fiction novelist Greg Bear has a series of novels in which HERV's play an important role in evolution.

Teratoma

A teratoma is a tumor derived from pluripotent stem cells. The word teratoma is from the Greek meaning monstrous tumor. Teratomas are derived from germ cells, sperm and ova and thus can form tissue from endoderm, mesoderm and ectoderm. Thus these tumors can contain hair, bone and even teeth. Rarely, a more developed organ such as an eyeball or hand can be formed. Some forms of teratomas, Fetus in fetu and fetiform teratoma, can even resemble a malformed fetus. Pictures of these types of teratomas can be found here and can be quite shocking.

Here is a link to ovarian teratomas. There are two different kinds of ovarian teratomas. Mature teratomas which are benign and immature teratomas that are cancerous. A short review on teratomas can also be found here.

Pressure Ulcers

There is a worthwhile article on pressure ulcers (bedsores) in todays New York Times Science section. An excellent review of this condition can be found at massage therapy. More information can be found here and here.

Cancer Biopsy and Risk of Metastases

Last year someone asked if biopsy of a tumor could result in the spread of the cancer. There are a few unathorative websites that claim this is the case. Those sites also happen to be touting "alternative" treatments for cancer.

A recent publication The impact of preoperative breast biopsy on the risk of sentinel lymph node metastases: analysis of 2502 cases from the Austrian sentinel node biopsy study group by Peters-Engl et al (full free text here) concluded that:

based on the present data, is that preoperative breast biopsy does not cause artificial tumour cell spread to the SLN, with possible negative impact on the prognosis of breast cancer.

These results disagreed with those of Hansen et al in a paper titled Manipulation of the Primary Breast Tumor and the Incidence of Sentinel Node Metastases From Invasive Breast Cancer (summary here).

But go here and read what Dr. Hansen has to say about her study before you make a decision about the safety of cancer biopsy.

"This study does not link biopsy with spread [of breast cancer]," Hansen tells WebMD via email. "We have not changed our practice and do not plan to. We still prefer to perform a needle biopsy to confirm the diagnosis of cancer and then will proceed at another time to definitive surgical management."

Neoplasms

For an excellent easily understood review about cancer proceed to this National Cancer Institute website and click through all 61 slides.




TERMS

Neoplasm: (neo= new; plasm= form) an uncontrolled growth of new cells, may be benign or malignant

Tumor: a mass; a neoplasm

Cancer: any kind of malignant neoplasm

Malignant: capable of spreading throughout the body and causing death

Carcinoma: a malignant neoplasm of epithelial cells

Sarcoma: a malignant neoplasm of mesenchymal (tissue derived from mesoderm) tissue

Our bodies are constantly shedding dead cells and growing new cells. Remember that a neoplasm is and uncontrolled growth of new cells. It is not normal growth.



Normal cell growth is controlled by proto-oncogenes. These genes generally encode proteins which control normal cell growth. But when proto-oncogenes undergo mutation, they may become oncogenes. You can learn much more about oncogenes here.



The body has evolved mechanisms to repair damaged DNA.

Cancer is caused by mutation of somatic cells. Some individuals have inherited genetic mutations that predispose them to develop certain types of cancer. It may take as few as 3 and as many as 20 mutations for a proto-oncogene to become an oncogene. Thus, cancers are frequently found in aged individuals.

How does DNA become damaged? Chemical carcinogens, ionizing radiation and viral infection have all been linked to DNA injury. Many, many more causes and risk factors for cancer can be found at this NIH website.

Does fluoridated water cause cancer? Experts at NIH say there is no evidence that it does.

In 1993, the Subcommittee on Health Effects of Ingested Fluoride of the National Research Council, part of the National Academy of Sciences, conducted an extensive literature review concerning the association between fluoridated drinking water and increased cancer risk. The review included data from more than 50 human epidemiological studies and six animal studies. The Subcommittee concluded that none of the data demonstrated an association between fluoridated drinking water and cancer (5). A 1999 report by the CDC supported these findings. The report concluded that studies to date have produced “no credible evidence” of an association between fluoridated drinking water and an increased risk for cancer (2).

However, if you do a google search you will find over 2.5 million links claiming differently. Could there really be a conspiracy to cover up the effects of fluoride treatment on cancer? I doubt it.

Tumor suppression genes can be thought of as genes that provide a "stop" signal. If these genes are mutated normal cell growth can become uninhibited. Much more about tumor suppressor genes here.

An important consideration in cancer biology is the speed of tumor growth. Go to this website to learn about cell growth and doubling time.



Angiogenesis is the process of growing a new blood supply. It's very important in tumor biology. There is a slide presentation on understanding the role of angiogenesis in cancer at this NCI website.

Grading and staging of neoplasms are done to aid in treatment decisions. Cancer grading is a pathologic exercise that determines the degree of differentiation of a tumor. Cancer staging is a clinical exercise that evaluates the behavior of a neoplasm. Learn more about grading and staging at this website.

Early detection of cancer is important for the most effective treatment. Learn about early detection of some cancers here, here and here.

Want further training in understanding cancer in general and specific tumors? Go to this government training website to continue your training.

Vaccination Via Tattoo

German scientists have reported that vaccines delivered using a tattoo needle produce antibody responses 16 times greater than those delivered by intramuscular injection.

Hemodynamics - Thrombosis, Embolism, Shock

A thrombus is a stationary mass of blood elements that remains attached to its place of origin along the wall of a blood vessel.

Thrombi are not clots although they are partially made up of clotted blood. Unlike most clots, a thrombus is always the result of a pathologic event. Clots are normal (usually) and occur outside a blood vessel.

The formation of a thrombus is not initially dependent on the clotting process. Thombi begin endothelial injury and an initial platelet clump. Layers of platelets are added followed by the adherence of white blood cells. A clot then adds volume as the thrombus grows.

You can find a full text article concerning deep vein thrombosis here and another full text article here.



An embolus is an intravascular object (air, tumor fragment, broken off thrombus, calcium fragments) that circulates in the bloodstream until it becomes lodged in a vessel obstructing the blood flow.

Ischemia is a lack of oxygen supply to a tissue usually due to obstruction of blood flow.



Lack of oxygen supply to a tissue can result in a tissue death called an infarct

See photos of an infarct of the heart here.

Shock is a state of systemic low blood flow. It can occur due to a loss of blood or because cardiac output is reduced.

Cardiogenic shock occurs when the heart is incapable of maintaining blood pressure. You can read much more about cardiogenic shock here.

Hypovolemic shock is a result of an underfilled vascular space, usually the result of hemorrhage. It can also be caused by fluid loss in cases of severe burns or diarrhea. Read more about hypovolemic shock here.

Septic shock is associated with systemic bacterial infections (sepsis) usually gram-negative bacterial infections. It is due to a massive inflammatory response to the infection. Read more about septic shock here.

Hemodynamics - Edema

Above figure from Heartzine.Go there to learn about circulatory system.

To review your anatomy of the circulatory system go to this great website at the Texas Heart Institute.

60% of the human body is water. So an average person of 155 lbs is made up of 93 lbs of water and 62 lbs of solids. The 42 liters of water can be broken down this way:

Extracellular
Interstitial (space outside the blood vessels and in between cells) 8 liters
Plasma 3 liters
Cerebrospinal fluid and other 6 liters
For a total of 17 liters

Intracellular
A total of 25 liters (including Red Blood Cells)

Blood pressure is the force of blood pushing against the walls of arteries. It's expressed as the number of millimeters it can force a column of mercury upwards.

Normal blood pressure is a reading of 120/80 or lower. High blood pressure is a reading of 140/90 or greater.

Another type of pressure is osmotic pressure. Osmotic pressure is the amount of hemodynamic pressure that must be applied on the side with low water concentration to prevent water from passing into the saltier side.

Go to this Colorado State osmotic pressure simulator site and you can see the effects of increasing or decreasing solute on either side of a permeable membrane.

You can learn about osmotic pressure here (interactive) and here (physics).

Edema is a shift of water from the vascular space into another compartment, usually the interstitial compartment. Here is one website that discusses edema in general.

Low protein edema also called a transudate, occurs when there is excess venous pressure (hydrostatic edema) or low plasma osmotic pressure. Each of these conditions allows water to leave the vascular spaces and enter the tissue spaces.

One example of low protein edema is varicose veins due to excess venous pressure. Read more about varicose veins here.

Osmotic edema is another type of low protein edema. It occurs when plasma albumin levels are abnormally low allowing water to escape from the vascular space to the interstitial space. Osmotic edema is often associated with liver disease because the liver is the primary producer of albumin.

Generalized edema (anasarca) is another example of low protein edema.

High Protein Edema is the fluid accumulation seen in inflammation. Inflammatory edema would be seen in a sprained joint.

Lymphedema is due to obstucted lymphatics. See more here.



Cerebral and pulmonary edema can be fatal. Swelling of the brain results in increased pressure on the brain. Pulmonary edema can impair gas transport and exchange or encourage bacterial growth.

William Harvey and Blood Circulation

William Harvey is the 17th century physician who hypothesized that blood moved in a circle. This was quite different from the accepted view of the time. Galen had postulated 1700 years previously that there were two kinds of blood, arterial and veinous, each with their own pathway to the tissues where it was consumed.

Harvey wrote: Since all things, both argument and ocular demonstration, show that the blood passes through the lungs and heart by the force of the ventricles, and is sent for distribution to all parts of the body, where it makes its way into the veins and porosites of the flesh, and then flows by the veins from the circumference on every side to the centre, from the lesser to the greater veins, and is by them finally discharged into the vena cava and right auricle of the heart, and this in such a quantity or in such a flux and reflux thither by the arteries, hither by the veins, as cannot possibly be supplied by the ingesta, and is much greater than can be required for mere purposes of nutrition; it is absolutely necessary to conclude that the blood in the animal body is impelled in a circle, and is in a state of ceaseless motion.
That is one hell of a sentence!

Harvey knew blood moved in a circle but he was unable to determine exactly how. He did not have the technology to observe the small capillaries that connected the arterial and veinous vessels.

Harvey was one of the first to use the scientific method in his work. He said:

I profess to learn and teach anatomy not from books but from dissections,not from the tenets for Philosophers but from the fabric of Nature.

You can learn more about William Harvey here.

Repair: Recovery from injury

After injury and inflammation comes repair. Repair is the restoration of normal structure and function to injured tissue.

Read about it here.

Tissue regeneration requires an intact supporting stromal framework.

One element of this framework is the extracellular matrix. Read about extracellular matrix here.

The other stromal framework element is the basement membrane.


Photomicrograph from here.

Without the support of the extracellular matrix and basement membrane, tissues cannot return to normal and scarring occurs.

Angiogenesis is the growth of new blood vessels into the wound. View this NIH tutorial on angiogenesis in relation to tumor metastasis. It's a slide show, so just keep clicking on the arrow in the upper right corner.

There is also an entire issue of Nature devoted to angiogenesis with free text available here. This article is especially good.

Scar development follows angiogenesis. Read about scar development here.

What about tissue repair of the perineal region that is torn during childbirth?
You can read about this at these links here, here and here. Or you can listen to an NPR report on the topic here.

Stem Cells

Above image from here.

Stem cells are primative, undifferentiated cells that have the capacity to proliferate and differentiate into more mature types of cells.

Some forms of tissue regeneration require stem cells.

You can go here to see animations about stem cells (you need Flash Player installed).

There is also stem cell information in lay terms at the NIH Stem Cell Information website.

Embryonic stem cells are obtained from human fertilized eggs called blastocysts. These stem cells are often refered to as "totipotent stem cells".

You can view an animated tutorial on human embryonic stem cells at this website and also at this website.

Adult stem cells are multipotent and are normally obtained from the bone marrow. A bone marrow transplant can be considered a stem cell transplant.

More recently, stem cells have been obtained from umbilical cords of recently born babies.

Stem cells were first cultured at my Alma Mater, The University of Wisconsin by James Thomson (paper cited above). Lots of stem cell info at this UW website.

Temperature Regulation

The human body can regulate its core temperature to between 98 and 100 degrees F. If skin temperature drops below 37 degrees C. the body attempts to conserve heat by constricting the blood supply to the body surface. Shivering is the bodys attempt to produce more heat through muscle activity. Because no external work is performed during shivering, all the energy released is in the form of heat. Here is a short review on body temperature regulation. Also here.

Hypothermia (stage 1) occurs when the body temperature reaches 95 degrees or lower. Read about hypothermia at this Coast Guard website.

Hyperthermia occurs when the body produces more heat than it can dissipate. Body temperatures above 104 degrees F are life threatening. You can listen to scientist talk about how the human body copes with heat at this NPR website.

Fever (pyrexia)is an increase in body temperature as a response to bacterial or viral infection or to tissue injury. It's a temporary elevation in the bodies thermoregulatory setpoint. Generally, fever is not an illness because it's a defense response against infections. Body temperature can also increase due to hard exercise; ovulation; excess thyroid secretions and central nervous system damage. Cancer can also induce fever. More about fevers here.

Inflammation

All disease is due to cell injury. Cell injury results in inflammation. The cardinal signs of inflammation were first described by Cornelius Celsus. You can actually read a translation of Celsus' De Medicina here.



You can learn a lot about Acute Inflammation at this website; chronic inflammation and healing and repair.

The pathogenesis of inflammation involves the leukocyte adhesion cascade. You can learn more about this process here.

This process is very important. Leukocyte Adhesion Deficiency Syndrome is a very rare genetic disorder caused by lack of, or deficiency in production of the cell surface molecule CD18.



Persistent injury can result in chronic inflammation. The above is one example. A Nobel Prize was awarded for this disovery.



The process of inflammation is very complex. There are many molecules involved and a few of them can be seen in the above figure showing airway smooth muscle mediators of inflammation.

More on molecular mediators of inflammation can be found HERE.

Plasma-derived mediators of inflammation:

Clotting system - read this.

Complement system - read this. We will discuss the complement system further under immunity. But the complement system generally has an under appreciated role in inflammation.

Kinin system - read this. [pdf available]

Cell-derived mediators of inflammation:

Vasoactive amines - read this and this.

Cell membrane factors - read this and this.

Cytokines (here and here)and Chemokines (here and here).

Reactive oxygen compounds - read this and this.

Chronic inflammation differs from acute inflammation. Read about it here.

Mitochondrial Diseases

Yes there are diseases due to malfunctioning mitochondria. You can find an introduction here at the United Mitochondrial Disease Foundation. Many of these diseases are due to mutations in the mitochondrial DNA.

If you are really interested I found a free full text article about mitochondria and mitochondrial diseases here (but you have to register).

Healing Powers of Hyperbaric Oxygen

Several diseases can be treated with hyperbaric oxygen. Read about some of them here at the Medical College of Wisconsin.

As for the use of hyperbaric oxygen therapy in cancer, there doesn't seem to be any firm evidence that it is useful. There is a fair bit of literature on the subject but I couldn't find any clinical trials that show the effectiveness of HBO treatment on cancer.

Necrosis

Go here to see examples of coagulative necrosis and resulting infarcts both at the gross level and histological level. Keep clicking the 'right' arrow to see more examples. What is the most common cause of coagulative necrosis?

Examples of liquefactive necrosis can be seen starting here. Notice the photo of the macrophages cleaning up debris from an area of liquefactive necrosis in the brain.



Examples of fat necrosis start here.





Next is, you got it, the cheesy caseous necrosis seen in TB infected lung.



The Mycobacteria need to create these extensive areas of necrosis so they can be coughed out of the lungs and passed on to another individual.

Gangrene is next. Don't click on the link if you are feeling ill. The photo is of disembodied toes. We all know what can happen if you get frostbite.



Fibrinoid necrosis in hypertension.



Remember we talked about accumulation of abnormally folded proteins. Check out this photo of amyloid accumulation.

Then there is aging. Wear and tear (growing old) results in the accumulation of lipochrome in the liver. This is cellular debris that is sequestered within the cytoplasm.