17.5: Inflammation and Fever - Biology

17.5: Inflammation and Fever - Biology

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Learning Objectives

  • Identify the signs of inflammation and fever and explain why they occur
  • Explain the advantages and risks posed by inflammatory responses

The inflammatory response, or inflammation, is triggered by a cascade of chemical mediators and cellular responses that may occur when cells are damaged and stressed or when pathogens successfully breach the physical barriers of the innate immune system. Although inflammation is typically associated with negative consequences of injury or disease, it is a necessary process insofar as it allows for recruitment of the cellular defenses needed to eliminate pathogens, remove damaged and dead cells, and initiate repair mechanisms. Excessive inflammation, however, can result in local tissue damage and, in severe cases, may even become deadly.

Acute Inflammation

An early, if not immediate, response to tissue injury is acute inflammation. Immediately following an injury, vasoconstriction of blood vessels will occur to minimize blood loss. The amount of vasoconstriction is related to the amount of vascular injury, but it is usually brief. Vasoconstriction is followed by vasodilation and increased vascular permeability, as a direct result of the release of histamine from resident mast cells. Increased blood flow and vascular permeability can dilute toxins and bacterial products at the site of injury or infection. They also contribute to the five observable signs associated with the inflammatory response: erythema (redness), edema (swelling), heat, pain, and altered function. Vasodilation and increased vascular permeability are also associated with an influx of phagocytes at the site of injury and/or infection. This can enhance the inflammatory response because phagocytes may release proinflammatory chemicals when they are activated by cellular distress signals released from damaged cells, by PAMPs, or by opsonins on the surface of pathogens. Activation of the complement system can further enhance the inflammatory response through the production of the anaphylatoxin C5a. Figure (PageIndex{1}) illustrates a typical case of acute inflammation at the site of a skin wound.

During the period of inflammation, the release of bradykinin causes capillaries to remain dilated, flooding tissues with fluids and leading to edema. Increasing numbers of neutrophils are recruited to the area to fight pathogens. As the fight rages on, pus forms from the accumulation of neutrophils, dead cells, tissue fluids, and lymph. Typically, after a few days, macrophages will help to clear out this pus. Eventually, tissue repair can begin in the wounded area.

Chronic Inflammation

When acute inflammation is unable to clear an infectious pathogen, chronic inflammation may occur. This often results in an ongoing (and sometimes futile) lower-level battle between the host organism and the pathogen. The wounded area may heal at a superficial level, but pathogens may still be present in deeper tissues, stimulating ongoing inflammation. Additionally, chronic inflammation may be involved in the progression of degenerative neurological diseases such as Alzheimer’s and Parkinson’s, heart disease, and metastatic cancer.

Chronic inflammation may lead to the formation of granulomas, pockets of infected tissue walled off and surrounded by WBCs. Macrophages and other phagocytes wage an unsuccessful battle to eliminate the pathogens and dead cellular materials within a granuloma. One example of a disease that produces chronic inflammation is tuberculosis, which results in the formation of granulomas in lung tissues. A tubercular granuloma is called a tubercle (Figure (PageIndex{2})). Tuberculosis will be covered in more detail in Bacterial Infections of the Respiratory Tract.

Chronic inflammation is not just associated with bacterial infections. Chronic inflammation can be an important cause of tissue damage from viral infections. The extensive scarring observed with hepatitis C infections and liver cirrhosis is the result of chronic inflammation.

Exercise (PageIndex{1})

  1. Name the five signs of inflammation.
  2. Is a granuloma an acute or chronic form of inflammation? Explain.


In addition to granulomas, chronic inflammation can also result in long-term edema. A condition known as lymphatic filariasis (also known as elephantiasis) provides an extreme example. Lymphatic filariasis is caused by microscopic nematodes (parasitic worms) whose larvae are transmitted between human hosts by mosquitoes. Adult worms live in the lymphatic vessels, where their presence stimulates infiltration by lymphocytes, plasma cells, eosinophils, and thrombocytes (a condition known as lymphangitis). Because of the chronic nature of the illness, granulomas, fibrosis, and blocking of the lymphatic system may eventually occur. Over time, these blockages may worsen with repeated infections over decades, leading to skin thickened with edema and fibrosis. Lymph (extracellular tissue fluid) may spill out of the lymphatic areas and back into tissues, causing extreme swelling (Figure (PageIndex{3})). Secondary bacterial infections commonly follow. Because it is a disease caused by a parasite, eosinophilia (a dramatic rise in the number of eosinophils in the blood) is characteristic of acute infection. However, this increase in antiparasite granulocytes is not sufficient to clear the infection in many cases.

Lymphatic filariasis affects an estimated 120 million people worldwide, mostly concentrated in Africa and Asia.1 Improved sanitation and mosquito control can reduce transmission rates.


A fever is an inflammatory response that extends beyond the site of infection and affects the entire body, resulting in an overall increase in body temperature. Body temperature is normally regulated and maintained by the hypothalamus, an anatomical section of the brain that functions to maintain homeostasis in the body. However, certain bacterial or viral infections can result in the production of pyrogens, chemicals that effectively alter the “thermostat setting” of the hypothalamus to elevate body temperature and cause fever. Pyrogens may be exogenous or endogenous. For example, the endotoxin lipopolysaccharide (LPS), produced by gram-negative bacteria, is an exogenous pyrogen that may induce the leukocytes to release endogenous pyrogens such as interleukin-1 (IL-1), IL-6, interferon-γ (IFN-γ), and tumor necrosis factor (TNF). In a cascading effect, these molecules can then lead to the release of prostaglandin E2 (PGE2) from other cells, resetting the hypothalamus to initiate fever (Figure (PageIndex{4})).

Like other forms of inflammation, a fever enhances the innate immune defenses by stimulating leukocytes to kill pathogens. The rise in body temperature also may inhibit the growth of many pathogens since human pathogens are mesophiles with optimum growth occurring around 35 °C (95 °F). In addition, some studies suggest that fever may also stimulate release of iron-sequestering compounds from the liver, thereby starving out microbes that rely on iron for growth.2

During fever, the skin may appear pale due to vasoconstriction of the blood vessels in the skin, which is mediated by the hypothalamus to divert blood flow away from extremities, minimizing the loss of heat and raising the core temperature. The hypothalamus will also stimulate shivering of muscles, another effective mechanism of generating heat and raising the core temperature.

The crisis phase occurs when the fever breaks. The hypothalamus stimulates vasodilation, resulting in a return of blood flow to the skin and a subsequent release of heat from the body. The hypothalamus also stimulates sweating, which cools the skin as the sweat evaporates.

Although a low-level fever may help an individual overcome an illness, in some instances, this immune response can be too strong, causing tissue and organ damage and, in severe cases, even death. The inflammatory response to bacterial superantigens is one scenario in which a life-threatening fever may develop. Superantigens are bacterial or viral proteins that can cause an excessive activation of T cells from the specific adaptive immune defense, as well as an excessive release of cytokines that overstimulates the inflammatory response. For example, Staphylococcus aureus and Streptococcus pyogenes are capable of producing superantigens that cause toxic shock syndrome and scarlet fever, respectively. Both of these conditions can be associated with very high, life-threatening fevers in excess of 42 °C (108 °F).

Exercise (PageIndex{2})

  1. Explain the difference between exogenous and endogenous pyrogens.
  2. How does a fever inhibit pathogens?


Given her father’s premature death, Angela’s doctor suspects that she has hereditary angioedema, a genetic disorder that compromises the function of C1 inhibitor protein. Patients with this genetic abnormality may have occasional episodes of swelling in various parts of the body. In Angela’s case, the swelling has occurred in the respiratory tract, leading to difficulty breathing. Swelling may also occur in the gastrointestinal tract, causing abdominal cramping, diarrhea, and vomiting, or in the muscles of the face or limbs. This swelling may be nonresponsive to steroid treatment and is often misdiagnosed as an allergy.

Because there are three types of hereditary angioedema, the doctor orders a more specific blood test to look for levels of C1-INH, as well as a functional assay of Angela’s C1 inhibitors. The results suggest that Angela has type I hereditary angioedema, which accounts for 80%–85% of all cases. This form of the disorder is caused by a deficiency in C1 esterase inhibitors, the proteins that normally help suppress activation of the complement system. When these proteins are deficient or nonfunctional, overstimulation of the system can lead to production of inflammatory anaphylatoxins, which results in swelling and fluid buildup in tissues.

There is no cure for hereditary angioedema, but timely treatment with purified and concentrated C1-INH from blood donors can be effective, preventing tragic outcomes like the one suffered by Angela’s father. A number of therapeutic drugs, either currently approved or in late-stage human trials, may also be considered as options for treatment in the near future. These drugs work by inhibiting inflammatory molecules or the receptors for inflammatory molecules.

Thankfully, Angela’s condition was quickly diagnosed and treated. Although she may experience additional episodes in the future, her prognosis is good and she can expect to live a relatively normal life provided she seeks treatment at the onset of symptoms.

Key Concepts and Summary

  • Inflammation results from the collective response of chemical mediators and cellular defenses to an injury or infection.
  • Acute inflammation is short lived and localized to the site of injury or infection. Chronic inflammation occurs when the inflammatory response is unsuccessful, and may result in the formation of granulomas (e.g., with tuberculosis) and scarring (e.g., with hepatitis C viral infections and liver cirrhosis).
  • The five cardinal signs of inflammation are erythema, edema, heat, pain, and altered function. These largely result from innate responses that draw increased blood flow to the injured or infected tissue.
  • Fever is a system-wide sign of inflammation that raises the body temperature and stimulates the immune response.
  • Both inflammation and fever can be harmful if the inflammatory response is too severe.

Multiple Choice

Which refers to swelling as a result of inflammation?

A. erythema
B. edema
C. granuloma
D. vasodilation


Which type of inflammation occurs at the site of an injury or infection?

A. acute
B. chronic
C. endogenous
D. exogenous


Fill in the Blank

A(n) ________ is a walled-off area of infected tissue that exhibits chronic inflammation.


The ________ is the part of the body responsible for regulating body temperature.


Heat and redness, or ________, occur when the small blood vessels in an inflamed area dilate (open up), bringing more blood much closer to the surface of the skin.


Short Answer

Differentiate exogenous and endogenous pyrogens, and provide an example of each.

Critical Thinking

If a gram-negative bacterial infection reaches the bloodstream, large quantities of LPS can be released into the blood, resulting in a syndrome called septic shock. Death due to septic shock is a real danger. The overwhelming immune and inflammatory responses that occur with septic shock can cause a perilous drop in blood pressure; intravascular blood clotting; development of thrombi and emboli that block blood vessels, leading to tissue death; failure of multiple organs; and death of the patient. Identify and characterize two to three therapies that might be useful in stopping the dangerous events and outcomes of septic shock once it has begun, given what you have learned about inflammation and innate immunity in this chapter.

In Lubeck, Germany, in 1930, a group of 251 infants was accidentally administered a tainted vaccine for tuberculosis that contained live Mycobacterium tuberculosis. This vaccine was administered orally, directly exposing the infants to the deadly bacterium. Many of these infants contracted tuberculosis, and some died. However, 44 of the infants never contracted tuberculosis. Based on your knowledge of the innate immune system, what innate defenses might have inhibited M. tuberculosis enough to prevent these infants from contracting the disease?


Our editors will review what you’ve submitted and determine whether to revise the article.

Fever, also called pyrexia, abnormally high body temperature. Fever is a characteristic of many different diseases. For example, although most often associated with infection, fever is also observed in other pathologic states, such as cancer, coronary artery occlusion, and certain disorders of the blood. It also may result from physiological stresses, such as strenuous exercise or ovulation, or from environmentally induced heat exhaustion or heat stroke.

Under normal conditions, the temperature of deeper portions of the head and trunk does not vary by more than 1–2 °F in a day, and it does not exceed 99 °F (37.22 °C) in the mouth or 99.6 °F (37.55 °C) in the rectum. Fever can be defined as any elevation of body temperature above the normal level. Persons with fever may experience daily fluctuations of 5–9 °F above normal peak levels tend to occur in the late afternoon. Mild or moderate states of fever (up to 105 °F [40.55 °C]) cause weakness or exhaustion but are not in themselves a serious threat to health. More serious fevers, in which body temperature rises to 108 °F (42.22 °C) or more, can result in convulsions and death.

During fever the blood and urine volumes become reduced as a result of loss of water through increased perspiration. Body protein is rapidly broken down, leading to increased excretion of nitrogenous products in the urine. When the body temperature is rising rapidly, the affected person may feel chilly or even have a shaking chill conversely, when the temperature is declining rapidly, the person may feel warm and have a flushed moist skin.

In treating fever, it is important to determine the underlying cause of the condition. In general, in the case of infection, low-grade fevers may be best left untreated in order to allow the body to fight off infectious microorganisms on its own. However, higher fevers may be treated with acetaminophen or ibuprofen, which exerts its effect on the temperature-regulating areas of the brain.

The mechanism of fever appears to be a defensive reaction by the body against infectious disease. When bacteria or viruses invade the body and cause tissue injury, one of the immune system’s responses is to produce pyrogens. These chemicals are carried by the blood to the brain, where they disturb the functioning of the hypothalamus, the part of the brain that regulates body temperature. The pyrogens inhibit heat-sensing neurons and excite cold-sensing ones, and the altering of these temperature sensors deceives the hypothalamus into thinking the body is cooler than it actually is. In response, the hypothalamus raises the body’s temperature above the normal range, thereby causing a fever. The above-normal temperatures are thought to help defend against microbial invasion because they stimulate the motion, activity, and multiplication of white blood cells and increase the production of antibodies. At the same time, elevated heat levels may directly kill or inhibit the growth of some bacteria and viruses that can tolerate only a narrow temperature range.

The Editors of Encyclopaedia Britannica This article was most recently revised and updated by Kara Rogers, Senior Editor.

6 Main Contributors to Non-Specific Resistance | Microbiology

Non specific resistance is the defense of our body from any kinds of the pathogens. It includes skin and mucous membrane, phagocytosis, inflammation, fever, production of antimicrobial substances.

1. Skin and Mucus Membranes:

Skin and mucus membranes provide the first step of defense to the body against invasion of the pathogen.

It acts both as mechanical barrier as well as chemical factors:

I. Mechanical Factors:

Skin acts as an outer barrier of keratinized epithelium to microorganisms, chemicals and non-living agents. It consists of over 15% of dry weight of the body. It contains two portions, the dermis (inner and thicker portion of skin) and epidermis (the outer thinner portion influenced by the external environment).

Epidermis comprises of tightly packed layers of epithelial cells. The upper layer of epithelial cells is dead. It protects the inner tissues. As a result of cuts, burns, wounds, etc. infection of skin and underlying tissues frequently occurs. When the skin frequently remains moist, the chances for skin infection by fungal pathogens get increased.

Mucus membranes lack the thickened layer but have the other features that provide defense. They line the gastrointestinal, respiratory, urinary and reproductive tract. The epithelial layer of mucus membrane secrets mucus which is a free moving liquid produced by globlet cells. It consists of inorganic salts, many organic molecules, loose epithelial cells and leucocytes.

Mucous prevents the tract from dessication. Some pathogens e.g., Treponema pallidum, Mycobacterium tuberculosis, Streptococcus pneumoniae, etc. attached to mucus (if are in sufficient number) can penetrate the membrane. Mucus offers less protection than the skin.

(a) Lachrymal Apparatus:

Lachrymal apparatus is found in eyes and also associated with defense against eye infection. It forms and drains away the tears. Lachrymal gland is present towards the upper and outermost part of both the eye socket. This gland produces tears which is spread over the surface of eye ball through blinking.

Continuous washing action protects the eyes from setting on eye surface. Whenever microorganisms come in contact of surface of eyes the lacrimal glands start secreting tears heavily and either dilute or wash away the microorganisms or irritating substances on eye surface.

Salivary glands produce saliva that also wash microorganisms from teeth and mucus membrane of mouth. Similarly cleansing of urethra and vagina by the flow of urine and vaginal secretion, respectively also wash microorganisms from the respective sites and provide some sorts of defense.

The mucus membrane of nose possesses mucus coated hairs that filter the air after inhaling, and trap microorganisms, dust, etc. However, the cells of mucus membrane of the lower respiratory tract are covered with dust and microorganisms which have been trapped towards the throat. This so called ciliary escalator keeps the mucus blanket moving towards the throat at the rate of 1-3 cm/h. After coughing or sneezing the escalators speed up.

Ii. Chemical Factors:

There are certain chemical factors of skin and mucus membrane that play roles in providing defense such as gastric juice, enzymes, sebum, etc. Sebaceous (oil) glands of the skin produce oily substance which is known as sebum.

Sebum prevents the hair desiccation and becoming brittle, and form a protective film over skin. Sebum contains unsaturated fatty acids and to some extent acetic acid. Sebum inhibits the growth of microorganisms. This secretion lowers down the pH between 3 and 5, and arrest the growth of many microorganisms.

Skin also possesses sweat glands that produce perspiration. Perspiration removes the wastes and wash microorganisms from skin surface and maintains body temperature. Perspiration contains the enzyme lysozyme that dissolves cell wall of Gram-positive and a few Gram-negative bacteria. The other sources of lysozyme are saliva, mucus, tears, nasal secretion and tissue fluids.

Gastric juice is secreted by the glands of stomach. It contains HCl, digestive enzymes and a little amount of mucus. Very low pH (1.2) i.e. high acidity of gastric juice of stomach kills the bacteria and bacterial toxins. However, the enteric pathogens are protected by the food particles and, therefore, enter the intestine through the gastrointestinal tract.

2. Phagocytosis:

Phagocytosis (means eat and cell) refers to ingestion of microorganisms or any particulate material by a cell. It is also a method of nutrition of some protozoa such as Amoeba, but the mechanism discussed here is related to the defense mechanism of body provided by white blood cells through phagocytosis. Before discussing the mechanism of phagocytosis we should learn the components of our blood.

Blood consists of fluid known as plasma which contains different constituents such as erythrocytes or red blood cells (RBC), leukocytes or white blood cells (WBC) and thrombocytes or platelets (Table 22.2).

The leukocytes can be divided, on the basis of granules in their cytoplasm, into granulocytes and agranulocytes. Granulocytes contain three types of blood cells (e.g. neutrophils, basophils and eosinophils) and agranulocytes contain two types of cells (lymphocytes and monocytes) (Fig. 22.1).

The granules of cytoplasm can be observed under the microscope. After staining these granules take different stains with a mixture of acidic (eosin) and basic (methylene blue) dyes the granules of neutrophils take red and blue stains respectively. Granules or basophils stain blue with methylene blue, and that of eosinophils stain red with eosin.

Neutrophils can enter an infected tissue and kill microorganisms and foreign particle. The basophils can release substances like heparin (an anticoagulant) and histamine (in inflammation and allergic responses). Eosinophils are the phagocytes. After microbial infection or hypersensitivity their number increases. In agranulocytes the granules are absent. These are of two types, lymphocytes and monocytes.

The lymphocytes are of two types, B-lymphocytes and T-lymphocytes. The B-lymphocytes derived its name from its site of maturation in the bursa of fabricius in birds. The name turned out to be apt for its major site of maturation in mammals in bone marrow. The B-lymphocytes depend on the activity of bursa tissues, whereas the T lymphocytes (derive its name from thymus) depend on the thymus for their activity.

Thymus contains T cells but not B cells similarly bone marrow consists of only B cells but not T-cells. Both the lymphocytes occur in lymphoid tissues (e.g. tonsils, lymph nodes, spleen, thymus gland, thoracic duct, bone marrow, and appendix, lymph nodes in respiratory-gastrointestinal and reproductive tracts).

The T- and B- cells cooperate in the presence of a third cell, Mechnikov macrophage. These provide immunity. Monocytes mature into macrophages and act as phagocytes. The leukocytes are derived from stem cells in bone marrow and enter the lymph system (lymph node, spleen, thymus, etc.).

I. Types of Phagocytes:

The phagocytes are of two types, granulocytes (microphages) and monocytes (macrophages). When a microbe infects granulocytes (neutrophils), monocytes move to the infected area. During migration, monocytes enlarge in size and called macrophages. Since these macrophages are migratory, they are also termed as wandering macrophages.

Some macrophages remain at a fixed position e.g. in the liver (Kupffer’s cells), lungs (aleolar macrophages), nervous system (microglial cells), branchial tissue, bone-marrow, spleen, and lymph nodes and peritoneal cavity surrounding abdominal organs. These macrophages are called fixed macrophages which constitute the mono­nuclear phagocytic system.

Ii. Mechanism of Phagocytosis:

After infection the number of WBC increases in blood during the initial phase of infection.

At this stage they are phagocytic in nature. As the infection progresses the number of monocytes increases. They phagocytize the remaining dead or living microbial cells. When blood and lymph containing microbial cells pass through the organs with fixed macrophages, the cells of mononuclear phagocytic system kill them through phagocytosis.

The mechanism of phagocytosis can be divided into the following four steps (Fig. 22.2):

It is a phenomenon of chemical attraction of phagocytes to microorganisms. The chemotactic chemicals which attract the phagocytes are the components of WBC, and damaged cells, peptides derived from complements and microbial products.

The plasma membrane of phagocyte gets attached to the surface of a microbe or foreign material (Fig. 22.2 A). When there is a large capsule M protein attachment can be hampered. For example M protein of Streptococcus pyogenes inhibits the attachment of a phagocyte to their site. Similarly, Klebsiella pneumoniae and Streptococcus possess a large capsule and get escaped.

However, the large sized microorganisms or foreign material is trapped in blood clots, blood vessels or fibres of connective tissues. If the cell wall of microorganisms is coated with certain plasma protein promoting the attachment of microbe to phagocytes, only then they can be phagocytized. The coat proteins are called opsonins and the process of coating of plasma protein is known as opsonization.

After attachment the plasma membrane of phagocyte extends short projections known as pseudopods which engulf the microorganisms or foreign materials. This process is known as ingestion (Fig. 22.2B). The extension of pseudopods continues until they contact and fuse, and surround the microorganism inside a sac which is known as phagocytic vacuole or phagosome (C).

After engulfment phagosome comes in the contact of lysosome that contains digestive enzymes and bactericidal chemicals (C). After making contact the membrane of phagosome and lysosome gets fused (D) and a single layered large structure is formed which is called phagolysosome (E). Within 10-30 minutes the contents of phagolysosomes degrade the microor­ganisms or foreign materials.

Lysosomes also contain lysozyme that breaks the peptidoglycan of bacterial cell wall. Lysozyme is more active at pH 4 which is an optimum pH of phagolysosomes because of production of lactic acid by phagocytes.

In addition, lysozyme also contains myeloperoxidase which binds with chloride ions to viruses and bacteria and finally kills them. After complete digestion of the foreign material the phagolysosome migrates towards the boundary of membrane and discharges the wastes (F).

Interestingly, toxin producing streptococci can kill the phagocytes and Mycobacterium tuberculosis can multiply within the phagolysosome itself and des-integrate the phagocytes. Also, the causal organism of brucellosis can remain dormant for several months or years inside the phagocytes. At this situation the role of immunity becomes vital.

3. Inflammation:

For our system the inflammatory responses are beneficial and have the following functions:

(i) Inflammation possibly destroys the harmful agents and removes them or their by-products from the infected site.

(ii) If the harmful agents are not destroyed, it wards off the injurious agents and its bye products.

(iii) It repairs or replaces the tissues damaged by the injurious agents or their bye-products. Inflammation process occurs in the three stages, vasodilation and increased permeability of blood vessels, phagocyte migration, and repair.

I. Vasodilation and Increased Permeability of Blood Vessels:

After the damage of tissue, blood vessel is dilated where damage has occurred. Permeability of blood vessels also increases. As a result of vasodilation (i.e. increase in diameter of blood vessels) flow of blood to damaged area is increased. This is the reason why damaged area turns into red, and inflammation is induced due to heat.

Vasodilation is caused by histamine, a chemical released from the damaged tissue due to injury. In blood plasma another group of chemical (kinin) is present which too causes vasodilation. Collier (1962) has discussed the role of chemical mediators (kinin) in inflammation.

Kinin after being activated attracts neutrophils to injured area. From the damaged cells a substance, prostaglandin is secreted which is also associated with vasodilation. Due to increase in permeability of blood vessels, the clotting factors are delivered to the injured area where blood clots prevent the growth of microorganisms. This results in formation of pus in a localised spot.

Ii. Phagocyte Migration:

Bretscher (1987) has given a comprehensive account of movement of phagocytes. Within an hour of inflammation, phagocytes (neutrophils and monocytes) appear and begin to stick on the inner surface of lining (endothelium) of blood vessel as the flow of blood gradually starts decreasing.

The process of sticking of phagocytes is known as margination. Thereafter, the second phenomenon, diapedesis occurs within two minutes. Diapedesis is a process of sneezing of phagocytes between the endothelial cells of blood vessels and reaching to damaged area.

Attraction of neutrophils oc­curs through chemotactic substances such as kinins, the components of complement system and secondary metabolites of microorganisms. Production and release of granulocytes from bone marrow ensures the steady stream of neutrophils.

Monocytes follow the granulocytes into the infected area as inflammation continues. In the early stage of infection granulocytes predominate but they are short lived. When monocytes are produced in tissue they undergo changes and become wandering macrophages which predominate during later stages.

They are several times larger and potential enough to phagocytize the damaged tissue, destroyed granulocytes and infectious microorganisms. After phagocytosis, the granulocytes or macrophages themselves die. After a few days the area contains dead phagocytes, damaged tissue and fluid which collectively are known as pus. Pus formation subsides later on, and gradually destroyed after a few days.

Iii. Repair:

Repair is a process through which the tissue replaces the dead cells at the end of inflammation. During the active phase of inflammation repair starts but completes after removal of dead or damaged cell, the ability of which depends on the tissues involved.

For example, skin has a high capacity for regeneration, whereas nervous tissues in the brain and spinal cord do not regenerate at all. When the stroma (supporting connective tissue) or parenchyma (functioning part of tissues) produces new cells, the damaged tissue is repaired.

4. Fever:

An abnormally high body temperature is known as fever which is caused by bacterial or viral infection or bacterial toxins. It is obvious that hypothalamus (a part of brain) controls the body temperature and, therefore, sometimes it is called the body’s thermostat as it sets the temperature normally at 37°C (98.6°F). When antigens affect hypothalamus, body’s temperature goes up.

For example, when phagocytes ingest the Gram-negative bacteria, the lipopolysaccharide of bacterial cell wall i.e. endotoxin is released that induces the phagocyte also to release interleukin-1 (endogenous pyrogens). Interleukin-1 helps the production of T-lymphocytes. In turn, interleukin induces-hypothalamus to produce prostaglandins that result the hypothalamus to a higher tempera­ture that causes fever.

Fever perists for a long duration until bacterial endotoxin or interleukin-1 is released. At high temperature the body responds with constriction of blood vessels, increased rate of metabolism and shivering (chilling). Chilling disappears after body’s temperature has reached the setting of thermostat.

Until the endotoxins are not completely removed, body’s temperature remains high. Thereafter, it is maintained normally at 37°C. In addition, fever inhibits the growth of some microorganisms in body. At high temperature body’s tissue repairs quickly, and the effect of interferon is intensified.

5. Antimicrobial Substances:

Complements and Properdin:

In classical antigen-antibody complex, certain blood proteins also get associated and complement the immune response. These serum proteins are known as complements.

Similarly three serum proteins (e.g. properdin itself, factor B and factor D) which are commonly known as properdin, play a role in alternate pathway. Both types of proteins are related to the defense system. Properdin system is composed of the above three serum proteins which altogether constitute a high proportion of serum protein.

Therefore, about 20% different types of proteins (i.e. complements) which are found in normal blood serum. These are designated as C1, C2, C3, etc. Complements are very important to both non­specific and specific defense against the microbial infection. Proteins of complement and properdin systems act in ordered sequence or cascade. The classical pathway initiates when the antibodies bind with antigens (bacteria or other microbial cells).

After a pair of antibodies recognise and bind to antigens, the C1 protein (which consists of 3 protein subunits) binds to antibodies and activated (Fig. 22.3). In turn C1 acts as an enzyme, activates C2 and C4 and splits C2 and C4 proteins (C2 into C2a and C2b, and C4 into C4a and C4b. C2a and C2b combines to form another enzyme that splits C3 into C3a and C3b.

The antibodies are not involved in the initiation of the alternate pathway, but interactions between protein properdin system and certain polysaccharides initiate this pathway. The polysac­charides are found on the cell wall of most of the bacteria, fungi and foreign RBCs of mammals. Properdin pathway interacts with Gram-negative bacteria, the cell wall of which contains lipopolysaccharide that releases lipid A (an endotoxin) and trigger the alternate pathway.

C3 is cleaved both by classical and alternate pathways into C3a and C3b C3a is an active fragment. These fragments induce the three processes, cytolysis, inflammation and opsonization.

It is a process of leaking of cellular contents of foreign cells through breaking their plasma membrane by the complements. C3b initiates a series of reactions involving C5, C6, C7, C8 and C9 which is collectively known as the membrane attack complex (MAC) (Fig. 22.3).

The activated proteins attack the microbial cell membrane and form a circular trans membrane channels (lesions). Through these lesions loss of ions and cytolysis occur. Use of the complements in this process is known as complement fixation which laid a basis for clinical test.

(ii) Inflammation:

The cleavage products, C3b and C5b, bind with mast cells (basophils) and blood platelets to trigger the release of histamine. Histamine elevates the permeability of blood. C5a fragment functions as a chemotactic factor which attracts phagocytes to the site of complement activation.

(iii) Opsonization:

Opsonization is a phe­nomenon of adsorption of certain antibodies or complement (C3 – C5 complex) specially C3b onto the surface of foreign material that results in stimulation in phagocytosis (Fig. 22.3). Opsonization is also known as immune adherence. Opsomzation is also one of the main antigen- antibody reactions associated with humoral antibodies. The two main opsonins (complement and certain antibodies) stimulate phagocytosis.

The complement stimulates T-cells to process for cell mediated immunity and release histamine from leukocytes, which in turn increases the capillary permeability and smooth muscle contraction. In general the local inflammation is caused due to these reactions. In contrast, another system (properdin system) also activates C3-C5 complex and initiates the protective responses.

The complement and properdin systems are very important in non-specific defense. The deficiency of C1, C2 and C4 causes collagen vascular disorder, consequently there develops hypersensitivity. C3 deficiency increases susceptibility to bacterial invasion and C5 deficiency (through C9) causes susceptibility to infection of Neisseria meningitidis and N. gonorrhoeae.

6. Interferon:

Viruses totally depend on their host cells for multiplication. However, during the course of multiplication the host cells may or may not be damaged. It is very difficult to check the virus multiplication without affecting the host cells. Interferons (IFN) are such class of antiviral proteins produced by certain animal cells after stimulation. Now-a-days interferons are used in causing immunity.

Interferons are host specific but not virus-specific. It means that interferons produced by human cells will show antiviral activity only in humans but not in another mammals. In contrast four interferons produced against a virus will also act against a number of other viruses. Even in humans different types of cells produce different interferons.

Human interferons are of the following three types:

(i) Alfa interferon (α-IFN or leucocyte IFN)

(ii) Beta interferon (β-IFN or fibroblast IFN), and

(iii) Gamma interferon (y-IFN or immune IFN)

With each principal group there are various subtypes of interferons. In humans interferon is produced by fibroblast in connective tissues, lymphocytes and other leukocytes.

The virus infected cells produce interferons in very low quantity which is diffused towards uninfected neighbouring cells. It reacts with plasma or nuclear membrane receptor and induces healthy cells to produce mRNA for the synthesis of the antiviral proteins.

These proteins act as enzyme and disrupt translation of viral mRNA, polypeptide chain elongation, etc. Since interferon is in low quantity, it does not badly affect the host cells. Its effect remains only for a very short duration. Interferons do not have any effect on viral multiplication in cells already infected.

Owing to its importance much emphasis is being laid on artificial production of interferon. For the first time clinical trial of interferon was done in 1981 to determine its anticancer effects. In recent years several companies have applied the recombinant DNA technology to produce interferon in certain bacteria.

Everything you need to know about inflammation

Inflammation is part of the body’s defense mechanism and plays a role in the healing process.

When the body detects an intruder, it launches a biological response to try to remove it.

The attacker could be a foreign body, such as a thorn, an irritant, or a pathogen. Pathogens include bacteria, viruses, and other organisms, which cause infections.

Sometimes, the body mistakenly perceives its own cells or tissues as harmful. This reaction can lead to autoimmune diseases, such as type 1 diabetes.

Experts believe inflammation may contribute to a wide range of chronic diseases. Examples of these are metabolic syndrome, which includes type 2 diabetes, heart disease, and obesity.

People with these conditions often have higher levels of inflammatory markers in their bodies.

In this article, find out more about why inflammation happens, its symptoms, and ways to resolve it.

Share on Pinterest A person with acute inflammation might experience pain in the affected area.

There are two main types of inflammation: acute and chronic.

Acute inflammation

An injury or illness can involve acute, or short-term, inflammation.

There are five key signs of acute inflammation:

  • Pain: This may occur continuously or only when a person touches the affected area.
  • Redness: This happens because of an increase in the blood supply to the capillaries in the area.
  • Loss of function: There may be difficulty moving a joint, breathing, sensing smell, and so on.
  • Swelling: A condition call edema can develop if fluid builds up.
  • Heat: Increased blood flow may leave the affected area warm to the touch.

These signs are not always present. Sometimes inflammation is “silent,” without symptoms. A person may also feel tired, generally unwell, and have a fever.

Symptoms of acute inflammation last a few days. Subacute inflammation lasts 2–6 weeks .

Chronic inflammation can continue for months or years. It either has or may have links to various diseases, such as:

The symptoms will depend on the disease, but they may include pain and fatigue.

Measuring inflammation

When inflammation is present in the body, there will be higher levels of substances known as biomarkers.

An example of a biomarker is C-reactive protein (CRP). If a doctor wants to test for inflammation, they may assess CRP levels.

CRP levels tend to be higher in older people and those with conditions such as cancer and obesity. Even diet and exercise may make a difference.

Inflammation happens when a physical factor triggers an immune reaction. Inflammation does not necessarily mean that there is an infection, but an infection can cause inflammation.

Acute inflammation

Acute inflammation can result from:

When the body detects damage or pathogens, the immune system triggers a number of reactions:

  • Tissues accumulate plasma proteins, leading to a buildup of fluid that results in swelling.
  • The body releases neutrophils, a type of white blood cell, or leukocyte, which move toward the affected area. Leukocytes contain molecules that can help fight pathogens.
  • Small blood vessels enlarge to enable leukocytes and plasma proteins to reach the injury site more easily.

Signs of acute inflammation can appear within hours or days, depending on the cause. In some cases, they can rapidly become severe. How they develop and how long they last will depend on the cause, which part of the body they affect, and individual factors.

Some factors and infections that can lead to acute inflammation include:

  • acute bronchitis, appendicitis and other illnesses ending in “-itis”
  • an ingrown toenail
  • a sore throat from a cold or flu
  • physical trauma or wound

Chronic inflammation

Chronic inflammation can develop if a person has:

Sensitivity: Inflammation happens when the body senses something that should not be there. Hypersensitivity to an external trigger can result in an allergy.

Exposure: Sometimes, long-term, low-level exposure to an irritant, such as an industrial chemical, can result in chronic inflammation.

Autoimmune disorders: The immune system mistakenly attacks normal healthy tissue, as in psoriasis.

Autoinflammatory diseases: A genetic factor affects the way the immune system works, as in Behçet’s disease.

Persistent acute inflammation: In some cases, a person may not fully recover from acute inflammation. Sometimes, this can lead to chronic inflammation.

Factors that may increase the risk of chronic inflammation include :

  • older age
  • a diet that is rich in unhealthful fats and added sugar
  • low sex hormones

Long-term diseases that doctors associate with inflammation include:

Inflammation plays a vital role in healing, but chronic inflammation may increase the risk of various diseases, including some cancers, rheumatoid arthritis, atherosclerosis, periodontitis, and hay fever.

The following table summarizes some key differences between acute and chronic inflammation.

CauseHarmful pathogens or tissue injury.Pathogens that the body cannot break down, including some types of viruses, foreign bodies that remain in the system, or overactive immune responses.
DurationA few days.From months to years.
OutcomesInflammation improves, or an abscess develops or becomes chronic.Tissue death, thickening, and scarring of connective tissue.

It is essential to identify and manage inflammation and related diseases to prevent further complications.

Acute inflammation can cause pain of varying types and severity. Pain may be constant and steady, throbbing and pulsating, stabbing, or pinching.

Pain results when the buildup of fluid leads to swelling, and the swollen tissues push against sensitive nerve endings.

Other biochemical processes also occur during inflammation. They affect how nerves behave, and this can contribute to pain.

Treatment of inflammation will depend on the cause and severity. Often, there is no need for treatment.

Sometimes, however, not treating inflammation can result in life threatening symptoms.

During an allergic reaction, for example, inflammation can cause severe swelling that may close the airways, making it impossible to breathe. It is essential to have treatment if this reaction occurs.

Without treatment, some infections can enter the blood, resulting in sepsis. This is another life threatening condition that needs urgent medical treatment.

Acute inflammation

A doctor may prescribe treatment to remove the cause of inflammation, manage symptoms, or both.

For a bacterial or fungal infection, for example, they may prescribe antibiotics or antifungal treatment.

Here are some treatments specifically for treating inflammation:

Nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) will not remove the cause of inflammation, but they can help relieve pain, swelling, fever, and other symptoms. They do this by countering an enzyme that contributes to inflammation.

Examples of NSAIDs include naproxen, ibuprofen, and aspirin. These are available to purchase online or over the counter. People should check first with a doctor or pharmacist to ensure they make the right choice.

People should only use NSAIDs long term if a doctor recommends them, as they can have adverse effects. Aspirin is not suitable for children.

Pain relief: Acetaminophen, including paracetamol or Tylenol, can relieve pain but does not reduce inflammation. These drugs allow the inflammation to continue its role in healing.


Corticosteroids, such as cortisol, are a type of steroid hormone. They affect various mechanisms involved in inflammation.

Corticosteroids can help manage a range of conditions, including:

They are available as pills, injections, in an inhaler, or as creams or ointments.

Long-term use of corticosteroids can be harmful. A doctor can advise on their risks and benefits.

Treatment for diseases that involve long-term inflammation will depend on the condition.

Some drugs act to repress the body’s immune reactions. These can help relieve symptoms of rheumatoid arthritis, psoriasis, and other similar autoimmune reactions. However, they can also leave a person’s body less able to fight an infection if it occurs.

People who have undergone transplant surgery also need to take immunosuppressant drugs to prevent their bodies from rejecting the new organ. They, too, need to take extra care to avoid exposure to infections.


Since endothelium appears to be the primary site of RF damage. It would be interesting to study the endothelial function in patients with acute RF, chronic rheumatic heart disease, and compare with normals.

Obtain subcutaneous nodules from patients with acute RF and study the antigen/antibody complexes, as has been done with renal biopsies in acute GN, to identify the antigen(s) responsible for RF.

Studies suggest that virulent clones of GAS organisms present in the community emerge to cause RF.[47] Proteomic/genomic study of organisms (such as M1, M3, or M18) obtained from RF epidemics or RF patients as compared to the same M type not causing RF is necessary. What are the proteomic/genomic differences between the virulent clone (causing RF) as compared to the non-virulent organism (not causing RF) which may help identify the antigenic protein(s)/glycoprotein(s).

Proteomic composition of the MV core connective tissue to be compared with the proteomic composition of the left ventricular intermyocardial connective tissue. If they are identical, it would indicate that the primary site of disease in the MV cannot be the core connective tissue since it is not involved in the left ventricle. By exclusion, the primary site becomes the endothelial layers with their basement membranes.

Study of the MV to find out the presence or absence of myosin. Since permanent damage occurs only to valves, the absence of myosin will reinforce the futility of pursuing studies involving myosin.

Evaluation of the intermediate filament and protein vimentin and the valve interstitial cells as the specific targets of streptococcal antigen. Valve interstitial cells react strongly with AS mabs. Antivimentin mabs stain cytoplasmic vimentin exactly as AS mabs. Pre-incubation of AS mabs with purified vimentin ablates valvar staining, suggesting that vimentin or valve interstitial cells may be the specific target in RF immunological damage.[13]

Cardiac valves are lined by endothelial cells on both sides. Studies indicate differences not only from the vascular endothelial cells but also between the two sides of the valve surface. Using microarray technology, adult pig aortic valves have been found to differentially express 584 genes on the aortic side as compared to the ventricular surface.[57] The difference has been felt to explain preferential calcification of the aortic surface of the valve. Hence, it cannot be assumed that the endothelial cells covering the two sides of the MV, the endothelial cells of the left atrium and of the left ventricle, continuous with the endothelium of the MV are identical in structure and function. It is necessary to study them separately. Proteomics of the endothelial cells of the

(i) left atrial endocardium, (ii) left ventricular endocardium, (iii) atrial surface of the MV, (iv) ventricular surface of the MV.

Proteomics as well as genomic studies of streptococci have been done.[58,59] The studies can be utilized as reference for further studies of pathogenesis especially in relation with streptococci obtained from RF patients to identify specific differences which may help in identifying the causative antigen(s).


Body temperature increases as a protective response to infection and injury. An elevated body temperature (fever) enhances the body’s defense mechanisms, although it can cause discomfort.

A part of the brain called the hypothalamus controls body temperature. Fever results from an actual resetting of the hypothalamus's thermostat. The body raises its temperature to a higher level by moving (shunting) blood from the skin surface to the interior of the body, thus reducing heat loss. Shivering (chills) may occur to increase heat production through muscle contraction. The body's efforts to conserve and produce heat continue until blood reaches the hypothalamus at the new, higher temperature. The new, higher temperature is then maintained. Later, when the thermostat is reset to its normal level, the body eliminates excess heat through sweating and shunting of blood to the skin.

Certain people (such as alcoholics, the very old, and the very young) are less able to generate a fever. These people may experience a drop in temperature in response to severe infection.

The Case of the Recurring Fever

An elderly man had symptoms no one could explain – until Amy Berger, MD, PhD, and her team investigated.

Three panel cartoon illustration. Top panel, left, illustration of female doctor in a white coat. Text to the left reads: “An elderly man had symptoms no one could explain – until Amy Berger, MD, PhD, and her team investigated.” Three speech bubbles read: “He kept coming to the hospital with a fever. And each time, other symptoms popped up in different places. No one could find a pattern. His doctors were stymied. So I decided to take the case. I lead the UCSF Molecular Medicine Investigation Unit. We investigate underlying biology to solve tough cases.” Top panel, right side, three illustrations. First illustration is a man’s face with his hand on his head. Text above reads: “Visit 1: Fever and sores. Second illustration is of a man’s torso with a hand holding his stomach. Text above reads: “Fever and diarrhea.” Third illustration is of feet with red welts on legs. Text above reads: “Visit 3: Fever and swelling.” Top panel, right side, bottom, illustration of three scientists (two men and one woman), one looking at DNA under a magnifying glass, one looking at a test tube, and one looking in a microscope. Text below read: “Crack team of physician-scientists and trainees. Middle panel, three illustrations. First illustration is of one female scientist and one male scientist looking at a computer screen with DNA on the monitor. Text above reads: “Clue #1: Testing had revealed a blood-cell mutation.” Two speech bubbles read: “He wasn’t born with this mutation, so he must have acquired it later in life. Acquired mutations often cause cancer – but he doesn’t have cancer.” Second illustration is of a male scientist in front of a computer looking outward. Text above reads: “We dove into the scientific literature and found clue #2.” Speech bubble reads: “Here’s a recent report about children born with similar mutations who also have symptoms like our patient’s.” Third illustration is of a female scientist on a video call with a female researcher. Text above it reads: “We sent the researcher who wrote the report some of the man’s blood.” Two speech bubbles read: “This blood shows patterns of inflammation just like the children’s! So it’s an autoinflammatory disease. caused by his mutation!” Third panel, two illustrations. First is of the elderly man holding a prescription bottle with the words “Anti-inflammatory drug” pointing toward it and a speech bubble that reads: My symptoms are gone!” Second illustration is of a female scientist, Dr. Amy Berger. Speech bubble reads: “Now we’re studying the man’s cells to better understand what went wrong. There may be more patients like him who are searching for answers.”

Illustration of female doctor in a white coat. Text to the left reads: “An elderly man had symptoms no one could explain – until Amy Berger, MD, PhD, and her team investigated.”

Bottom of panel, illustration of Dr. Amy Berger with a speech bubble. Text reads: “He kept coming to the hospital with a fever. And each time, other symptoms popped up in different places. No one could find a pattern. His doctors were stymied. So I decided to take the case.” Top of panel, three illustrations. First illustration is a man’s face with his hand on his head. Text above reads: “Visit 1: Fever and sores. Second illustration is of a man’s torso with a hand holding his stomach. Text above reads: “Fever and diarrhea.” Third illustration is of feet with red welts on legs. Text above reads: “Visit 3: Fever and swelling.”

Bottom of panel, illustration of Amy Berger with a speech bubble. Text reads: “I lead the UCSF Molecular Medicine Investigation Unit. We investigate underlying biology to solve tough cases.” Right side, illustration of three scientists (two men and one woman), one looking at DNA under a magnifying glass, one looking at a test tube, and one looking in a microscope. Text below read: “Crack team of physician-scientists and trainees.”

Middle panel, three illustrations. First illustration is of one female scientist and one male scientist looking at a computer screen with DNA on the monitor. Text above reads: “Clue #1: Testing had revealed a blood-cell mutation.” Two speech bubbles read: “He wasn’t born with this mutation, so he must have acquired it later in life. Acquired mutations often cause cancer – but he doesn’t have cancer.” Second illustration is of a male scientist in front of a computer looking outward. Text above reads: “We dove into the scientific literature and found clue #2.” Speech bubble reads: “Here’s a recent report about children born with similar mutations who also have symptoms like our patient’s.” Third illustration is of a female scientist on a video call with a female researcher. Text above it reads: “We sent the researcher who wrote the report some of the man’s blood.” Two speech bubbles read: “This blood shows patterns of inflammation just like the children’s! So it’s an autoinflammatory disease. caused by his mutation!” Below, two illustrations. First is of the elderly man holding a prescription bottle with the words “Anti-inflammatory drug” pointing toward it and a speech bubble that reads: My symptoms are gone!” Second illustration is of a female scientist, Dr. Amy Berger. Speech bubble reads: “Now we’re studying the man’s cells to better understand what went wrong. There may be more patients like him who are searching for answers.”


Failures, insufficiencies, or delays at any level of the immune response can allow pathogens or tumor cells to gain a foothold and replicate or proliferate to high enough levels that the immune system becomes overwhelmed. Immunodeficiency is the failure, insufficiency, or delay in the response of the immune system, which may be acquired or inherited. Immunodeficiency can be acquired as a result of infection with certain pathogens (such as HIV), chemical exposure (including certain medical treatments), malnutrition, or possibly by extreme stress. For instance, radiation exposure can destroy populations of lymphocytes and elevate an individual’s susceptibility to infections and cancer. Dozens of genetic disorders result in immunodeficiencies, including Severe Combined Immunodeficiency (SCID), Bare lymphocyte syndrome, and MHC II deficiencies. Rarely, primary immunodeficiencies that are present from birth may occur. Neutropenia is one form in which the immune system produces a below-average number of neutrophils, the body’s most abundant phagocytes. As a result, bacterial infections may go unrestricted in the blood, causing serious complications.

Symptoms Symptoms

Familial Mediterranean fever (FMF) is characterized by recurrent episodes of fever accompanied by pain in the abdomen, chest, joints, pelvis, and/or muscles. Episodes may also be associated with a skin rash or headache, and rarely, pericarditis and meningitis . [1] [2] [3] Amyloidosis, which can lead to kidney failure, is the most severe complication which can occur if FMF is not treated. In some cases, amyloidosis is the first sign of the condition in a person who otherwise has no symptoms. [3]

Episodes usually last for about one to three days, and the time between episodes can vary from days to years. [4] [2] The first episode usually occurs during childhood or the teenage years. In some cases, the first episode occurs much later in life. [1] The majority of people with FMF experience their first episode by age 20. [4] People tend to be symptom-free between episodes. [2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Dean D. Metcalfe, M.D.

The mast cell is the focus of the Mast Cell Biology Section (MCBS) research effort. This multifunctional inflammatory cell is involved in both innate and acquired immunity and plays a central role in the induction of allergic inflammation. An integrated program investigating mast cell biology includes studies into the growth and differentiation of mast cells, mast-cell signal transduction, and the products generated by mast cells that lead to disease. The MCBS program emphasizes basic research that may be translated into the clinic and from the clinic to the bench, where protocols include studies on the pathogenesis of anaphylaxis, physical urticarias and clonal mast cell disorders. Research efforts have contributed to the identification of mutations in mast cell disease, understanding signaling through KIT and the high affinity IgE receptor, and how alterations in the control of mast cell mediator production affect human disease.

Dr. Metcalfe received his M.D. at the University of Tennessee and an M.S. in microbiology at the University of Michigan, where he also did a residency in internal medicine. Dr. Metcalfe then trained in allergy and immunology during a fellowship at NIAID, followed by training in rheumatology while a Fellow in Immunology at the Robert Brigham Hospital in Boston. In 1995, he was appointed as the first Chief of the newly created Laboratory of Allergic Diseases at NIAID, a position he continued for 22 years until stepping down as Laboratory Chief in 2017. He is a past president of the American Academy of Allergy, Asthma, and Immunology, and a past chair of the American Board of Allergy and Immunology. Dr. Metcalfe is a Fellow of the American Academy of Allergy, Asthma, and Immunology and a member of the Association of American Physicians, Collegium Internationale Allergologicum, and American Clinical and Climatological Association. Dr. Metcalfe is a recipient of numerous awards including the Commendation, Outstanding Service and Meritorious Service Medals of the USPHS, an Outstanding Alumnus Award from University of Tennessee College of Medicine Alumni, the Distinguished Scientist Award from the Association the American Academy of Allergy and Asthma and Immunology, the Distinguished Scientist Award from the World Allergy Organization, the Lifetime Mentorship Award from the AAAAI and the ECNM Researcher of the Year.

Dean D. Metcalfe, M.D., Section Chief
Ana Olivera, Ph.D., Staff Scientist (Associate Scientist)
Melody Carter, M.D., Staff Clinician (Senior Research Physician)
Hirsh D. Komarow, M.D. , Staff Clinician (Associate Research Physician)
Linda M. Scott, C.R.N.P., Nurse Practitioner
Hyejeong Bolan, R.N., Study Coordinator
A. Robin Eisch, R.N., Study Coordinator
Geethani Bandara, Ph.D., Biologist
Yun Bai, M.S., Biologist
Yuzhi Yin, Ph.D., Biologist
Guido Falduto, Ph.D., Visiting Fellow
Annika Pfeiffer, Ph.D., Visiting Fellow
Andrea Luker, Ph.D., Post-doctoral IRTA Fellow
Arnold S. Kirshenbaum, M.D., Special Volunteer
Ayelet Makovoz, B.A., Post-Baccalaureate IRTA

Back row, L to R: Ayelet Makovoz, B.A,. Post-Baccalaureate IRTA Yun Bai, M.S., Biologist Linda Scott, C.R.N.P., Nurse Practitioner Dean D. Metcalfe, M.D., Chief Guido Falduto, Ph.D., Visiting Post-Doctoral Fellow Hirsh Komarow, M.D., Staff Clinician
Front row, L to R: Geethani Bandara, Ph.D., Biologist Annika Pfeiffer, Ph.D., Visiting Fellow Andrea Luker, Ph.D., Post-doctoral IRTA Fellow Ana Olivera, Ph.D., Staff Scientist Melody Carter, M.D., Staff Clinician Robin Eisch, R.N., Nurse Study Coordinator Hyejeong Bolan, R.N., Senior Research Nurse (Nurse Study Coordinator)

Boyden SE, Desai A, Cruse G, Young, ML, Bolan HC, Scott LM, Eisch AR, Long RD, Lee CR, Satorius CL, Pakstis AJ, Olivera A, Mullikin JC, Chouery E, Megarbane A, Medlej-Hashim M, Kidd KK, Kastner DL, Metcalfe DD, Komarow HD. Vibration-induced mast cell degranulation caused by a mutation in ADGRE2. N Engl J Med 2016 374: 656-663. PMID: 26841242

Cruse G, Yin Y, Fukuyama T, Desai A, Arthur GK, Bäumer W, Beaven MA, Metcalfe DD. Exon-skipping of FcεRIβ eliminates FcεRI expression in mast cells with therapeutic potential for allergy. Proc Natl Acad Sci USA 2016: 113:14115-14120. PMID: 27872312.

Carter MC, Desai A, Komarow HD, Bai Y, Clayton ST, Clark AS, Ruiz-Esteves KN, Long LM, Cantave D, Wilson TM, Scott LM, Simakova O, Jung MY, Hahn J, Maric I, Metcalfe DD. A distinct biomolecular profile identifies monoclonal mast cell disorders in patients with idiopathic anaphylaxis. J Allergy Clin Immunol 2018 141:180-188. PMID: 28629749.

Kim DK, Cho YE, Komarow H, Bandara G, Song BJ, Olivera A, Metcalfe DD. Mastocytosis-derived extracellular vesicles exhibit a mast cell signature, transfer KIT to stellate cells and promote their activation. Proc Natl Acad Sci USA 2018115(45):E10692-E10701. doi: 10.1073/pnas.1809938115. Epub 2018 Oct 23. PMID 30352845.

Carter MC, Bai Y, Ruiz-Esteves KN, Scott LM, Cantave D, Bolan H, Eisch R, Sun X, Hahn J, Maric I, Metcalfe DD. Detection of KIT D816V in peripheral blood of children with cutaneous mastocytosis suggests systemic disease. Br J Haematol 2018 183:775-782. PMID: 30488427.

Watch the video: Acute Phase Reactants APRs ESR and CRP (July 2022).


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