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Sugar as a defence against bacteria?

Sugar as a defence against bacteria?



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An answer on another SE site mentions that sugar "at a certain level acts as a preservative". I've always been taught that microorganisms eat sugar and expel acids, that is why sugary food are damaging to teeth. How is it that sugar acts as a preservative, then?

Googling the question I've found conflicting answers though I don't credit the sources as being especially reputable. What is the real reason that sugar can act as a preservative?


Sugar in high concentrations acts osmotic. This means that the water available in the cells is drawn towards the high concentration of a solutant (sugar), like in the image below (this is demonstrated with a plant cell, but the principle is the same for bacteria and other microorganisms):

Since microorganisms can not survive without water, they are not able to grow or reproduce. This effectively safes food. The same mechanism works when salt is used to conserve meat or fish.


Sugar participate in food preservation only at high concentrations. When microbes are introduced to high sugar concentrated environment, water inside the microbial cell diffuses out to the high sugar concentrated solute due to the phenomenon called osmosis. As water is very much needed for cell functioning and metabolism the dehydrated cells fail to perform its function and eventually die. This is called sugar curing, a food preservation technique. Also hard sugary sweet is less susceptible to microbes than soft sugar sweet because of its high sugar content that makes it intolerant for microbial growth and also the absence of moisture (important factor for microbial growth) in the hard sweet as compared to soft sweet makes it less susceptible to microbial attack.


A sweet defence against lethal bacteria

There is now a promising vaccine candidate for combating the pathogen which causes one of the most common and dangerous hospital infections. An international team of scientists from the Max Planck Institute of Colloids and Interfaces in Potsdam has developed a vaccine based on a carbohydrate against the Clostridium difficile bacterium, which is known to cause serious gastrointestinal diseases mainly in hospitals. The sugar-based vaccine elicited a specific and effective immune response in mice. Moreover, the scientists have also discovered strong indications that the substance can stimulate the human immune system to form antibodies against the bacterium.

Stimulating the immune system: on the basis of a hexasaccharide, chemists from Potsdam developed a vaccine against the Clostridium difficile bacterium, which causes serious gastrointestinal diseases in hospitals.

© MPI of Colloids and Interfaces

Clostridium difficile bacterium can turn into a life-threatening condition: a highly virulent and antibiotic-resistant strain of the spore-forming pathogen Clostridium difficile bacterium appeared in the USA and certain Western European countries some eight years ago. Since then it has been posing a major risk for hospitalised patients, in particular, who are being treated with antibiotics or have a weak immune system, such as cancer or HIV patients. Whereas no more than four per cent of healthy humans have C. difficile in their gastrointestinal system, the bacterium colonises the intestines of 20 to 40 per cent of hospitalised patients. If other bacteria in the intestinal flora are repressed by antibiotics, the rod-shaped bacterium can reproduce extremely fast. It produces toxins which cause diarrhoea and gastrointestinal inflammation, often with a lethal outcome. Surviving patients require a very costly aftercare. This new, highly virulent pathogen can produce around 20 times more toxins and significantly more spores than previously identified pathogens.

However, a carbohydrate in the bacterial cell wall now provides the team of scientists led by Peter H. Seeberger at the Max Planck Institute of Colloids and Interfaces in Potsdam a “point of attack” for a potential vaccine. “Initial testing of the sugar-based antigen synthesised by the team has already produced very promising results”, says Peter H. Seeberger, Director at the Max Planck Institute in Potsdam.

The chemists in the team first developed a synthesis for the essential component of the antigen: the hexasaccharide. To assemble the oligosaccharide, they used four different monosaccharide building blocks. An efficient and convergent approach created the exact molecule with the required arrangement of the monosaccharides. “Synthesizing complex polysaccharides is still a challenge, not least because sugar molecules can bind in several different places”, Peter H. Seeberger says. However, the chemists were able to block other reaction sites so that they could exactly control where the original saccharides bound.

The scientists then conjugated the hexasaccharide to the CRM 197 protein, which is used in many vaccines, as sugar alone, as antigen, does not elicit an effective immune response. In order to defend itself successfully against a C. difficile infection, the immune system must also use another antigen. The chemical glycoprotein conjugate triggered a very effective immune response in two mice which were injected with the substance three times, at 2-week intervals. “The fact that mice are producing antibodies against the carbohydrates is in itself a success”, Peter H. Seeberger says. “Not all carbohydrates trigger the production of antibodies.” Furthermore, the antibodies produced by the mice bound exclusively to the sugar. Thus, the antigen cannot cause an autoimmune disease.

Additionally, the scientists proved that the antibodies developed against the hexasaccharide are also part of the human immune response in the stool of hospital patients infected with C. difficile, they found antibodies against the sugar. “We can therefore expect to see that the human immune system produces antibodies against the sugar when vaccinated”, Seeberger concludes. What is more, “since the natural sugar already elicits the production of a small number of antibodies, we hope that the synthetic glycoprotein conjugate will trigger a more effective response.”

The vaccine candidate must now be subjected to further testing. First, it must be established whether it can effectively prevent infection in animals. “If these tests are successful, it will probably still take one or two years before the vaccine is tested on humans”, explains Peter H. Seeberger.

The vaccine candidate against C. difficile does not contain the only immunologically effective sugar from Seeberger&aposs laboratory. Together with his colleagues, the chemist is developing sugar-based vaccines against numerous pathogens. “The current work is therefore also a proof of the progress made in glycochemistry and glycobiology”, according to Seeberger, who was awarded the 2007 Körber European Science Award for his development of a sugar synthesiser. The number of biological sugar molecules that can be produced by chemists in the laboratory is on the increase, which gives the biologists and medical scientists the opportunity to investigate their specific impacts. This fills Peter H. Seeberger with optimism: “These advances will lead to quantum leaps in related research areas, such as immunology, biology and medicine.”


Programmed cell death as a defence against infection

Eukaryotic cells can die from physical trauma, which results in necrosis. Alternatively, they can die through programmed cell death upon the stimulation of specific signalling pathways. In this Review, we discuss the role of different cell death pathways in innate immune defence against bacterial and viral infection: apoptosis, necroptosis, pyroptosis and NETosis. We describe the interactions that interweave different programmed cell death pathways, which create complex signalling networks that cross-guard each other in the evolutionary 'arms race' with pathogens. Finally, we describe how the resulting cell corpses - apoptotic bodies, pore-induced intracellular traps (PITs) and neutrophil extracellular traps (NETs) - promote the clearance of infection.

Conflict of interest statement

Competing interests statement

The authors declare no competing interests.

Figures

Pyroptosis is initiated by…

Pyroptosis is initiated by either caspases 1 or 11. Caspase 1 is…

Figure 2. Apoptosis and Necroptosis

Figure 2. Apoptosis and Necroptosis

(Left) Apoptosis can be triggered via intrinsic or extrinsic pathways,…

Figure 3. Apoptotic bodies, neutrophil extracellular traps…

Figure 3. Apoptotic bodies, neutrophil extracellular traps and pore-induced intracellular traps

Figure 4. Interactions between apoptotic, necroptotic and…

Figure 4. Interactions between apoptotic, necroptotic and pyroptotic pathways


Sugar-derived molecules kill viruses in groundbreaking new treatment

Viruses are surprisingly difficult to kill – most of the drugs and chemicals that do the job are also harmful to human health. But now, scientists have developed a new virucidal substance derived from sugar, making it deadly to a wide range of viruses but safe for us.

The vast majority of existing antiviral treatments don’t actually kill the bugs – they instead slow down their growth or reduce their ability to infect cells. While this can be an effective method of staving off illness, viruses evolve quickly, so they often mutate new defenses against these drugs.

What’s needed are new virucidal treatments that will do away with viruses properly, and ideally work against different types. Now, researchers from the University of Manchester, the University of Geneva (UNIGE) and EPFL have managed to create a promising new virucidal drug.

The team started with molecules called cyclodextrins, which are natural derivatives of glucose. They engineered these molecules to attract viruses, then cling to their surface and tear open their outer membranes, effectively destroying them.

A microscope image of a virus before and after treatment by the antiviral molecules

The researchers tested the new treatment on several types of viruses, including herpes, HIV, hepatitis C, Zika and respiratory syncytial virus, and saw strong results across the board. The molecules were tested in lab dishes of the viruses and tissue cultures, as well as in mice, and were found to be effective. Importantly they didn’t harm cells in the tissue cultures or the mice, and other tests showed that the viruses weren’t able to mutate resistance to the drug.

“We have successfully engineered a new molecule, which is a modified sugar that shows broad-spectrum antiviral properties,” says Samuel Jones and Valeria Cagno, lead researchers on the study. “The antiviral mechanism is virucidal meaning that viruses struggle to develop resistance. As this is a new type of antiviral and one of the first to ever show broad-spectrum efficacy, it has potential to be a game changer in treating viral infections.”

The team says that this molecule could be useful against viruses that have developed resistance against other treatments, and even future threats similar to the emerging coronavirus. The molecules have been patented and the team is currently setting up a spin-off company in order to bring it to market. The eventual goal is to develop them into ointments, nasal sprays and other treatments.


Defence Mechanisms and Innate Immunity

The following points highlight the top six defence mechanisms involved in innate immunity. The defence mechanisms are: 1. Physical (or Mechanical) and Chemical Barriers 2. Inflammation 3. Phagocytosis 4. The Complement System 5. Antibacterial Substances 6. Antiviral Substances.

Mechanism # 1. Physical (or Mechanical) and Chemical Barriers:

Physical (or mechanical) barriers of the host in cooperation with chemical barriers (secretions) act as the first line of defence against pathogenic microorganisms and foreign materials. These barriers include skin, mucous membranes, respiratory system, gastrointestinal tract, genitourinary tract, eye, bacteriocins, and beta-lysin and other polypeptides.

Skin, mucous membranes, respiratory system, gastrointestinal tract, genitourinary tract, and eyes are the barriers that provide both physical and chemical defence (e.g., gastric juices, lysozyme, lactoferrin, glycoproteins, urea etc.) in cooperation. In addition, bacteriocins and beta-lysin and other polypeptides are the defensive chemicals against microorganisms.

Intact skin is a very effective physical or mechanical barrier to block the entry of microbial pathogens into the body. With few exceptions the microorganisms fail to penetrate the skin because its outer layer consists of thick, closely packed cells called keratinocytes that produce keratins.

Keratins are scleroproteins comprising the main components of hair, nails, and outer skin cells. These scleroproteins are not easily degradable enzymatically by microorganisms. They resist the entry of microbe-containing water and thus function as physical barrier to microorganisms.

In addition to direct prevention of penetration, continuous shedding of the outer epithelial cells of skin removes many of those microbial pathogens that manage to adhere on the surface of the skin.

2. Mucous membranes:

Mucous membranes of various body systems such as respiratory, gastrointestinal, genitourinary, and eye prevent invasion by microorganisms with the help of their intact stratified squamous epithelium and mucous secretions, which form a protective covering that resists penetration and traps many microorganisms.

3. Respiratory system:

An average person inhales about 10,000 microorganisms per day usually at the rate of eight microorganisms per minute. These microorganisms are deposited on the moist, sticky mucosal surfaces of the respiratory tract. The mucociliary blanket of the respiratory epithelium traps the microorganism less than 10 μm in diameter and transports them by ciliary action away from the lungs.

Microorganisms larger than 10 μm normally are trapped by hairs and cilia lining the nasal cavity which beat towards the pharynx so that the mucus with its trapped microorganisms is moved towards the mouth and expelled. Coughing and sneezing also help removal of microorganisms from the respiratory tract.

They make clear the respiratory system of microorganisms by expelling air forcefully from the lungs through the mouth and nose, respectively. Salivation also washes microorganisms from the mouth and nasopharyngeal areas into the stomach.

4. Gastrointestinal system:

Microorganisms may manage to reach the stomach. Many of them are destroyed by the gastric juice of the stomach. The gastric juice is a mixture of hydrochloric acid, proteolytic enzymes, and mucus, and is very acidic with a pH 2 to 3. This juice is normally sufficient to kill most microorganisms and destroy their toxins.

Furthermore, the normal microbial population of the large intestine is extremely significant in not allowing the establishment of pathogenic microorganisms in it.

For convenience, many commensalistic microorganisms in the intestinal tract secrete metabolic products (e.g., fatty acids) that prevent “unwanted” microorganisms from becoming established in the tract. In small intestine, however, the microbial pathogens are often killed by various pancreatic enzymes, bile, and enzymes in intestinal secretions.

5. Genitourinary system:

Kidneys, ureters, and urinary bladder are sterile under normal conditions. Kidney medulla is so hypertonic that it allows only few microorganisms to survive.

Urine destroys some microorganisms due to its low pH and the presence of urea and other metabolic end-products like uric acid, hippuric acid, mucin, fatty acids, enzymes, etc. The lower urinary tract is flushed with urine eliminating potential microbial pathogens. The acidic environment (pH 3 to 5) of vagina also confers defence as it is unfavourable to most microorganisms to establish.

The conjunctiva of eye lines the interior surface of each eyelid and the exposed surface of the eyeball. It is a specialised mucus-secreting epithelial membrane and is kept moist by continuous flushing action of tears secreted by the lacrimal glands. Tears contain lysozyme and lactoferrin and thus act as physical as well as chemical barriers.

The surfaces of skin and mucous membranes are inhabited by normal microbial flora. Of this, many bacteria synthesize and release toxic proteins (e.g., colicin, staphylococcin) under the direction of their plasmids. These toxic proteins are called bacteriocins, which kill other related species thus provide an adaptive advantage against other bacteria.

8. Beta-lysin and other polypeptides:

Blood platelets release a cationic polypeptide called beta-lysin, which disrupts the plasma membrane of certain gram-positive bacteria and kills them. Leukin, cecropins, plakins, and phagocytin are some other cationic polypeptides that kill specific gram-positive bacteria. Prostatic antibacterial factor, a zinc-containing polypeptide, is an important antimicrobial chemical secreted by the prostrate glands in males.

Mechanism # 2. Inflammation (Inflammatory Response):

Inflammation (L. inflammatio = to set on fire) is an innate (nonspecific) defence response of the body to pathogenic infection or tissue injury and helps localizing the infection or injury in its local area. Many of the classic features of inflammation were described as early as 1600 BC in Egyptian papyrus writings.

In the first century AD, the Roman physician Celsus described the four cardinal signs of inflammation as redness (rubor), swelling (tumor), heat (color) and pain (dolor). In the second century AD, another physician, Galen added a fifth sign: altered function (functio laesa).

1. Major events that result in cardinal signs:

Following are the major events that result in the cardinal signs of inflammation:

(i) The redness and heat (rise in temperature) of the localized area is due to vasodilation (an increase in the diameter of blood vessels) of nearby capillaries that occurs as the vessel that carry blood away from the affected area constrict resulting in engorgement of the capillary network.

(ii) Tissue swelling occurs due to accumulation of exudates in the area of infection or injury. An increase in capillary permeability facilitates an influx of fluid and cells from engorged capillaries into the tissue. The fluid that accumulates (exudate) possesses a much higher protein content than fluid normally released from the vascular system.

(iii) Pain is due to lysis of blood cells. The lysis triggers the production of prostaglandins and bradykinin, the chemical substances that alter the threshold and intensity of the nervous system response to pain. Pain probably serves a protective role as it normally causes individual to protect the infected or injured area.

2. Mechanism of defence:

Inflammatory response is a collective term representing the complex sequence of events during inflammation. It initiates when injured tissue cells release inflammatory mediators
(chemicals). Among the inflammatory mediators are various serum proteins called acute-phase proteins the principal acute-phase proteins are histamine and kinins.

The acute-phase proteins bind to receptors on nearby capillaries and venules causing vasodilation and increased permeability which results in influx of phagocytes (e.g., neutrophils, lymphocytes monocytes and macrophages) from the blood into the tissues.

The emigration of phagocytes is a multistep process (Fig. 44.14) that includes adherence of the cells to the endothelial wall of the blood vessels (margination), followed by their emigration between endothelial cells in to the tissues (diapedesis or extravasation), and finally, their migration through the tissue to the site of the invasion (chemotaxis).

As the phagocytic cells accumulate in the site of injury and begin to phagocytose microbial pathogens, during this process they release lytic enzymes that normally damage the nearby healthy cells. Dead host cells, dead phagocytic cells, dead microbial pathogens, and the body fluid collectively form a substance called pus (the inflammatory exudate).

When the acute-phase proteins bind to receptors on nearby capillaries and venules and cause vasodilation and increased permeability, the latter enable enzymes of the blood-clotting system to enter the tissue. These enzymes activate an enzyme cascade that results in the deposition of insoluble strands of fibrin, a main constituent of a blood clot.

The fibrin strands wall off the injured area from the rest of the body and serve to prevent the spread of infection. Once the inflammatory response is subsided and the pus is removed, the infected or injured area is filled with new tissues that start normal function.

Mechanism # 3. Phagocytosis:

Phagocytosis (Gk. Phagein = to eat cyte = cell and osis = a process) is a process during which large particles and microbial cells are enclosed in a phagocytic vacuole or phagosome and ingulfed. It acts a highly efficient cellular barrier against the pathogenic microorganisms and is met out by uptake and digestion of microorganisms by a variety of cells of the body’s defence system.

Besides its contribution in defence, phagocytosis helps certain cells and even organisms (e.g., protozoa) to obtain their nutrients. However, phagocytosis was a chance discovery by E. Metchnikoff (a native of Ukraine) in 1884 who suggested that the motile cells of larvae of starfish actively sought out and engulfed foreign particles present in their environment.

The following lines are devoted in the context of the role of phagocytosis in innate (nonspecific) host defence:

1. Recognition and adherence of microorganisms:

Phagocytic cells (neutrophils, monocytes macrophages, and dendritic cells) employ two fundamental molecular mechanisms for the recognition o microbial pathogens and their adherence on phgocyte’s plasma membrane:

(i) Opsonin-dependent (opsonic) recognition (called opsonization) and

(ii) Opsonin-independent (nonopsonic) recognition.

Opsonin-dependent recognition or opsonization (Gk. opson = to prepare victim for) is a process in which the phagocytic cells readily recognize the microbial pathogens that are coated by serum components (antibodies especially lgG1 and lgG3, complement C3b, and both antibody and complement C3b) called opsonins.

The opsonins function as a bridge between the microorganism and the phagocyte by binding to he surface of microorganism at one end and to specific receptors on the phagocyte surface at the other (Fig. 44.15) and enhance phagocytosis multifold. In one study for convenience, the rate of phagocytosis of a microorganism was 4000-fold higher in the presence of opsonin than in its absence.

Opsonin-independent recognition involves the mechanism which does not involve opsonins and employs other receptors on phagocytic cells that recognise structures (adhesins) expressed on the surface of different microbial pathogens (Fig. 44.16). Important ones of such receptors are lectins, polysaccharides, glycolipids, proteolycans, lypopolysaccharides (LPS), flagellin, etc.

It is important to note that during opsonin-independent recognition a particular microbial species may display multiple adhesins, each recognised by a distinct receptor present on phagocytic cells.

2. Ingestion and digestion of microorganisms:

Adherence of microorganisms on phagocyte’s plasma membrane is followed by their ingestion and digestion. Adherence induces plasma membrane protrusions, called pseudopodia, 10 extent around the adhered microorganisms.

Fusion of the pseudopodia encloses the microorganisms within a membrane-bounded structure called a phagosome, which moves towards the cell interior and fuses with a lysosome to form a phagolysosome (Fig. 44.17) Lysomes contribute to the phagolysosome a variety of hydrolytic enzymes such as lysozyme, phospholipase A2, ribonuclease deoxyri- bonuclease, and proteases.

An acidic vacuolar pH favours the activity of hydrolytic enzymes. Hydrolytic enzymes digest the entrapped microorganisms. The residual contents after digestion inside the phagolysosome are then eliminated through a process called exocytosis.

Mechanism # 4. The Complement System:

The serum of the blood contains a large number (over 30) of serum proteins that circulate in an inactive state and following their initial activation by specific (adaptive) and nonspecific (innate) immunogenic mechanisms, interact in a highly regulated cascade-fashion in which the activation of one component results in the activation of next in the cascade. This cascade of scrum proteins is collectively called the complement system and the serum protein of the complement system are called complement proteins.

When the inactive forms of complement proteins are converted into active forms by various specific (adaptive) and nonspecific (innate) immunologic mechanisms, they damage the membranes of microbial pathogens either destroying them or facilitating their clearance.

Complement system may act as an effector system that is triggered by binding if antibodies to certain cell surfaces, or it may be activated by reactions between complement proteins and receptors of microbial cell walls. Reactions between complement proteins and cellular receptors trigger activation of cells of the innate or adaptive immunity.

There are three pathways of complement activation:

(i) Classical complement pathway,

(ii) Alternate complement pathway, and

(iii) Lectin complement pathway.

Although these pathways employ similar mechanisms, specific proteins are unique to the first part of each pathway. Classical pathway is involved in specific or acquire (adaptive) immunity, whereas both the alternate and lectin pathways play important role in innate (nonspecific) immunity.

Mechanism # 5. Antibacterial Substances:

Human hosts possess antibacterial substances with which they combat the continuous onslaught of bacterial pathogens. These antibacterial substances are produced either by the host itself or by certain indigenous bacteria. The important antibacterial substances are the lysozyme, bacteriocins, and beta-lysin, and other polypeptides.

Lysozyme is the enzyme that breaks the β-1, 4-glycosidic bonds between N-acetylglucosamine and N- acetylmuramic acid in peptidoglycan, the signature molecule of bacterial cell wall. This bond breakage weakens the bacterial cell wall.

Water then enters the cell, and the cell swells and eventually bursts, a process called lysis (Fig. 44.18). Lysozyme occurs in body secretions including tears, saliva, and other body fluids, and presumably functions as a major line of non-specific defence against bacterial infections.

Many of the normal bacterial flora of the host body synthesize and release plasmid-encoded toxic proteins (e.g., colicins, staphylococcin) collectively called bacteriosins that inhibit or kill closely related bacterial species or even different and may give their producers and adaptive advantage against other bacteria.

These toxic proteins are called bacteriocins to distinguish them from the antibiotics because possess a more narrow spectrum of activity than antibiotics. Bacteriocins producing genes are often present on plasmid or a transposon.

Most bacteriocins are produced by gram-negative bacteria, and are generally named after the species of the bacterial genera that produce them the bacteriocin produced by E. coli is colicin, by Bacillus subtilis is substilicin.

E. coli synthesizes colicins. Some colicins bind to specific receptors on the surface of susceptible cells and kill them by disrupting some critical cell function. For example, many colicins form channels in the plasma membrane that allows potassium ions and protons to leak out, leading to a loss of the cell’s energy forming ability. Colicin E2 (encoded by plasmid col E2) is a DNA endonuclease and cleaves DNA. Colicin E3 (encoded by plasmid Col E3) is a nuclease that cuts at a specific site in 16S rRNA and inactivates ribosomes.

Recently it has been discovered that some grain-positive bacteria produce bacteriocin-like peptides. For example, lactic acid bacteria produce Nisin A, which strongly inhibits the growth of a wide range of gram- positive bacteria.

Beta-lysin and other polypeptides:

Beta-lysin is a cationic polypeptide synthesized and released by blood platelets, and kills some gram-positive bacteria by disrupting their plasma membranes. Other cationic polypetides produced in host body include leukins, plakins, cecropins, and phagocytin. A zinc-containing polypeptide named ‘prostatic antibacterial factor’ is secreted by the prostate gland in males, and acts as an important antibacterial substance.

Mechanism # 6. Antiviral Substances:

The outcome of a virus infection is influenced by the virulence of the infecting strain and the resistance conferred by the host. Mechanisims of host resistance may be immunological or non-specific. The latter include various genetic and physiological factors such as interferons, reactive nitrogen intermediates (RNIs), defensins, and fever.

Interferons are a family of host coded proteins produced by cells on induction by viral inducers, and are considered to be the first line of defence against viral attacks. Interferon by itself has no direct effect on viruses but it acts on other cells of the same species rendering them refractory to viral infection.

On exposure to interferon, cells produce a protein (translation inhibiting protein, TIP) which selectively inhibits translation of viral mRNA without affecting cellular mRNA. Translation inhibiting protein (TIP) is actually a mixture of at least three different enzymes, namely, protein kinase, oligonucleotide synthetase, and ribonuclease (RNAse).

These enzymes together block translation of viral mRNA into viral proteins. It has also been suggested that inhibition of viral transcription may also be responsible for the antiviral activity of interferon.

Reactive nitrogen intermediates:

Macrophages (also neutrophils and mast cells) have been found recently producing reactive nitrogen intermediates (RNIs). These molecules include nitric oxide (NO) and its oxidized forms, nitrite (NO2 – ) and nitrite (NO3 – ), and are very potent cytotoxic agents.

RNIs may be either released from cells or generated within cell vacuoles. Macrophages produce RNIs from the amino acid arginine. Macrophages have been found to destruct the herpes simplex virus with the help of RNIs produced by them.

Definsins are broad-spectrum antimicrobial peptides synthesized by myeloid precursor cells during their sojourn in the bone marrow, and are then stored in the cytoplasmic granules of mature neutrophils.

Besides gram-positive and gram-negative bacteria and yeasts and moulds, defensins target some viruses. Antiviral activity of defensins involves direct neutralization of enveloped viruses non-enveloped viruses are not affected by defensins.

Fever (Elevated Body Temperature):

Fever is a physiological factor and results from disturbance in hypothalamic thermoregulatory activity leading to an increase in normal body temperature. In adult humans fever is defined as an oral temperature above 98°F (37°C) or a rectal temperature above 99.5°F (37.5°C).

In almost every instance there is a specific constituent called ‘endogenous pyrogen’ that directly triggers fever production. These pyrogens include interleukin 1 (IL-1), interleukin (IL-6), and tissue necrosis factor that are synthesized and released by host macrophages in response to pathogenic factors that include viruses, bacteria, and bacterial toxins. It has been found that fever may act as natural defence mechanism against viral infections because most viruses are inhibited by temperatures above 39°C.


Starting Points

Connecting and Relating

  • If you cut yourself, what things can you do to help prevent an infection? What part of your immune system are you helping through these actions?
  • Which cells in the immune system can you name? In what context have you heard about them before?
  • Why does a doctor feel your lymph nodes during a physical examination? Have you ever felt that your lymph nodes were sore or swollen? When have you noticed this?

Connecting and Relating

  • If you cut yourself, what things can you do to help prevent an infection? What part of your immune system are you helping through these actions?
  • Which cells in the immune system can you name? In what context have you heard about them before?
  • Why does a doctor feel your lymph nodes during a physical examination? Have you ever felt that your lymph nodes were sore or swollen? When have you noticed this?

Relating Science and Technology to Society and the Environment

  • During surgery, how is a person’s immune system exposed to pathogens? What steps do surgical teams take to avoid spreading infections during surgery?

Relating Science and Technology to Society and the Environment

  • During surgery, how is a person’s immune system exposed to pathogens? What steps do surgical teams take to avoid spreading infections during surgery?

Exploring Concepts

  • What physical barriers in the human body play an important role in the immune system?
  • What is phagocytosis? At which stage of the immune response does phagocytosis take place?
  • Where do dendritic cells originate? What is their role in the immune system?

Exploring Concepts

  • What physical barriers in the human body play an important role in the immune system?
  • What is phagocytosis? At which stage of the immune response does phagocytosis take place?
  • Where do dendritic cells originate? What is their role in the immune system?

Nature of Science/Nature of Technology

  • What do you know about how T cells were discovered? (Note: This question will require additional research.)

Nature of Science/Nature of Technology

  • What do you know about how T cells were discovered? (Note: This question will require additional research.)

Media Literacy

  • Have you heard media stories about infection outbreaks at hospitals? (e.g., MRSA, Clostridium difficile, pneumonia, influenza.) What types of infections have been reported? Why are these instances usually reported as a serious problem?

Media Literacy

  • Have you heard media stories about infection outbreaks at hospitals? (e.g., MRSA, Clostridium difficile, pneumonia, influenza.) What types of infections have been reported? Why are these instances usually reported as a serious problem?

Teaching Suggestions

  • This article supports teaching and learning in Biology and Human Health related to the immune system, structure and function of the immune system, and the immune response. Concepts introduced include pathogens, macrophages, phagocytosis, innate immunity, adaptive immunity, dendritic cells and T cells.
  • Before reading this article, teachers could provide students with a Vocabulary Preview to help engage prior knowledge and introduce new terms. Ready-to-use Vocabulary Preview learning strategy reproducibles are available in [Google doc] and [PDF] formats.
  • To help consolidate and extend learning, teachers could have students watch one or more of the videos from the Learn More section. To organize and compare the information from these resources, students could complete a Print-Video Venn Diagram learning strategy. Ready-to-use Print-Video Venn Diagram reproducibles for this article are available in [Google doc] and [PDF] formats.
  • In addition, after reading this article and/or viewing the videos, teachers could have students create a graphic organizer that clearly illustrates the levels of defence of the immune system and the structures and cellular processes involved at each level. Students could use an online infographic creator to convey this information in a creative and unique digital format.

Teaching Suggestions

  • This article supports teaching and learning in Biology and Human Health related to the immune system, structure and function of the immune system, and the immune response. Concepts introduced include pathogens, macrophages, phagocytosis, innate immunity, adaptive immunity, dendritic cells and T cells.
  • Before reading this article, teachers could provide students with a Vocabulary Preview to help engage prior knowledge and introduce new terms. Ready-to-use Vocabulary Preview learning strategy reproducibles are available in [Google doc] and [PDF] formats.
  • To help consolidate and extend learning, teachers could have students watch one or more of the videos from the Learn More section. To organize and compare the information from these resources, students could complete a Print-Video Venn Diagram learning strategy. Ready-to-use Print-Video Venn Diagram reproducibles for this article are available in [Google doc] and [PDF] formats.
  • In addition, after reading this article and/or viewing the videos, teachers could have students create a graphic organizer that clearly illustrates the levels of defence of the immune system and the structures and cellular processes involved at each level. Students could use an online infographic creator to convey this information in a creative and unique digital format.

Bony encasements

Bony encasements, such as the skull and the thoracic cage, protect vital organs from injury and entry of microbes.

Mechanical removal is the process of physically flushing microbes from the body. Methods include:

  1. Mucus and cilia: Mucus traps microorganisms and prevents them from reaching and colonizing the mucosal epithelium. Mucus also contains lysozyme to degrade bacterial peptidoglycan, an antibody called secretory IgA that prevents microbes from attaching to mucosal cells and traps them in the mucus, lactoferrin to bind iron and keep it from from being used by microbes, and lactoperoxidase to generate toxic superoxide radicals that kill microbes. Cilia on the surface of the epithelial cells propel mucus and trapped microbes upwards towards the throat where it is swallowed and the microbes are killed in the stomach. This is sometimes called the tracheal toilet.
  2. The cough and sneeze reflex: Coughing and sneezing removes mucus and trapped microbes.
  3. Vomiting and diarrhea: These processes remove pathogens and toxins in the gastrointestinal tract.
  4. he physical flushing action of body fluids: Fluids such as urine, tears, saliva, perspiration, and blood from injured blood vessels also flush microbes from the body.

Bacterial Antagonism by Normal Microbiota

Approximately 100 trillion bacteria and other microorganisms reside in or on the human body. The normal body microbiota keeps potentially harmful opportunistic pathogens in check and also inhibits the colonization of pathogens by:

  1. Producing metabolic products (fatty acids, bacteriocins, etc.) that inhibit the growth of many pathogens
  2. Adhering to target host cells so as to cover them and preventing pathogens from colonizing
  3. Depleting nutrients essential for the growth of pathogens and
  4. Non-specifically stimulating the immune system.

Destruction of normal bacterial microbiota by the use of broad spectrum antibiotics may result in superinfections or overgrowth by antibiotic-resistant opportunistic microbiota. For example, the yeast Candida, that causes infections such as vaginitis and thrush, and the bacterium Clostridium difficile, that causes potentially severe antibiotic-associated colitis, are opportunistic microorganisms normally held in check by the normal microbiota.

In the case of Candida infections, the Candida resists the antibacterial antibiotics because being a yeast, it is eukaryotic, not prokaryotic like the bacteria. Once the bacteria are eliminated by the antibiotics, the Candida has no competition and can overgrow the area.

Clostridium difficile is an opportunistic Gram-positive, endospore-producing bacillus transmitted by the fecal-oral route that causes severe antibiotic-associated colitis. C. difficile is a common healthcare-associated infection (HAIs) and is the most frequent cause of health-care-associated diarrhea. C. difficile infection often recurs and can progress to sepsis and death. CDC has estimated that there are about 500,000 C. difficile infections (CDI) in health-care associated patients each year and is linked to 15,000 American deaths each year.

Antibiotic-associated colitis is especially common in older adults. It is thought that C. difficile survives the exposure to the antibiotic by sporulation. After the antibiotic is no longer in the body, the endospores germinate and C. difficile overgrows the intestinal tract and secretes toxin A and toxin B that have a cytotoxic effect on the epithelial cells of the colon. C. difficile has become increasingly resistant to antibiotics in recent years making treatment often difficult. There has been a great deal of success in treating the infection with fecal transplants, still primarily an experimental procedure. Polymerase chain reaction (PCRs) assays, which test for the bacterial gene encoding toxin B, are highly sensitive and specific for the presence of a toxin-producing Clostridium difficile organism. The most successful technique in restricting C. difficile infections has been the restriction of the use of antimicrobial agents.

  1. A patient is given large doses of broad spectrum antibiotics and subsequently develops a Candida albicans infection of the vagina. Discuss why this might happen in terms of immediate innate immunity. Why didn't the antibiotic kill the Candida albicans too?
  2. Often during intestinal infections drugs are given to suppress diarrhea. Discuss why this may not always be a good idea, especially with microbial infections that cause ulceration of the intestines.

Questions

Study the material in this section and then write out the answers to these questions. Do not just click on the answers and write them out. This will not test your understanding of this tutorial.

  1. State what color Gram-positive bacteria appear after the Gram stain procedure. (ans)
  2. Describe the structure and appearance of a Gram-positive cell wall. (ans)
  3. State the beneficial function to the bacterium of the following components of the gram-positive cell wall:
    1. peptidoglycan (ans)
    2. teichoic acids (ans)
    3. adhesins (ans)
    4. invasins (ans)

    Lecture notes

    6.3.1 Define pathogen: an organism or virus that causes disease

    6.3.2 Explain why antibiotics are effective against bacteria but not viruses

    • antibiotics block specific metabolic pathways found in bacteria, but not eukaryotic cells
    • because viruses reproduce using the host cell (eukaryotic) metabolic pathways, they are unaffected by antibiotics
    • antibiotics have produced great benefits world-wide in the control of bacterial diseases
      • Staphylococcus infections controlled
      • STD's, such as gonorrhea and syphilis controlled

      6.3.3 Outline the role of skin and mucous membranes in defense against pathogens

      • 1st line of defense = nonspecific
      • skin:
        • tightly bound barrier of dead, keratin-rich epidermal cells
          • tough, elastic, waterproof surface
          • linings of intestinal tract, respiratory tract, eyes, genitals
          • mucous traps microbes
          • lysozymes: antibacterial enzymes
          • cilia: clear respiratory tract
          • acidity:
            • stomach: pH = 2
            • vagina pH = 5-6

            6.3.4 Outline how phagocytic leucocytes ingest pathogens in the blood and in body tissues:

            • damage to tissues allows invasion across 1st line of defense
              • microbes successfully invade body fluids or tissues
              • damaged cells release histamine and other chemicals initiating inflammation
              • phagocytes recognize microbes as foreign by antigen recognition
              • variety of phagocytic cells: neutrophils (65% of WBCs), monocytes (4% of WBCs, macrophages (derived from monocytes))
              • digested microbe fragments are displayed on cell membrane
              • phagocytes with microbe fragments displayed = antigen-presenting cells: APCs

              6.3.5 Distinguish between antigens and antibodies

              • antigen: a molecule recognized as foreign by the immune system it elicits an immune response
              • antibody: =immunoglobulin
                • a globular protein
                • recognizes an antigen by its complementary shape and charge
                • thus allowing it to attach to the antigen specifically
                • marking it for attack by the immune system

                6.3.6 Explain antibody production = Humoral response:

                • macrophages:
                  • following phagocytotic digestion, display antigen on surface
                  • becoming antigen-presenting cells = APCs
                  • only T-lymphocytes with receptor proteins specifically matching the antigen of the APCs
                  • only those B-lymphocytes with antibodies specifically matching helper T-lymphocytes receptor proteins are activated
                  • produces a large population of B-lymphocytes
                    • plasma cells
                    • memory cells
                    • by protein synthesis
                    • releasing antibodies by exocytosis
                    • into the surrounding humors
                      • blood
                      • tissue fluids
                      • lymph
                      • marking them for phagocytosis by macrophages
                      • B-lymphocytes & helper T-lymphocytes
                      • reside in the lymph nodes
                      • upon subsequent exposure to the antigen
                        • produce a rapid and intense response
                        • = secondary response

                        6.3.7 Outline the effects of HIV on the immune system

                        • reduction in the number of active lymphocytes
                        • loss of the ability to produce antibodies

                        6.3.8 Discuss the cause, transmission and social implications of AIDS


                        References

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