Drivers of biodiversity loss - IV - Over-exploitation and V - Climate change

Drivers of biodiversity loss - IV - Over-exploitation or Over- harvesting of Animals and Plants

The five important drivers of biodiversity loss are

1.      Habitat loss and degradation

2.      Pollution

3.      Invasive species

4.      Over-exploitation

5.     Climate change associated with global warming

4.      Over-exploitation or Over- harvesting of Animals and Plants

More than one- third of the world’s endangered birds, fish and mammals are threatened directly by human activities such as fishing, hunting, and trading for meat and other commodities.

Wild animals are captured as pets or for skins or other luxury items while plants are taken for gardens or as ingredients in herbal medicines.

Overfishing

For millennia, the oceans supplied fish and seafood to us without any noticeable decrease in the fish populations due to their high reproductive potential. But the industrialized fishing and exploding human populations increased the demand on fisheries that resulted in overfishing.  

Fishery collapse also affect rest of the ecosystem, such as decrease in seabirds population, increase in sea urchins population, etc.  

Consumers can play a role in reducing overfishing by buying fish and seafood wisely. Information on whether fish and seafood is being harvested sustainably can be found online in lists kept by the Blue Ocean Institute (Guide to Ocean Friendly Seafood), Environmental Defense (Oceans Alive), and the Monterey Bay Aquarium (Seafood Watch Program).

Hunting

Early humans hunted animals for food, warm clothing, and other commodities. As agriculture developed, farmed foods provided people’s diet and Hunting became a sport such as big-game hunting or trophy hunting. Favorite targets are moose, caribou, bear, and elk in North America; reindeer, elk, and wolf in Europe; tiger, leopard, elephant, and wild goat in Asia; and antelope, gazelle, zebra, leopard, lion, giraffe, rhinoceros, and elephant in Africa

Innumerable species have been hunted nearly to extinction, examples are buffalo, passenger pigeon and cheetah.

When Europeans arrived in Colonial America many animals were hunted into extinction or near extinction. The American bison or the buffalo, covered the Great Plains of the United States and Canada, with a population of about 30 million. The railroad companies paid hunters to destroy the herds so that the animals did not interfere with trains by standing on the tracks. Hunting bison was also done to prevent the sustenance of the Native American tribes who were at war with the United States. By 1890, there were fewer than 750 bison left, all in zoos or protected areas.

Passenger pigeons were hunted to the last bird. They were the most abundant bird species on Earth, they lived in enormous flocks; the largest flock, of 2 billion birds even darkened the sky for several days as it flew overhead. Because passenger pigeons lived close together and were slow flyers, they were extremely easy to hunt and their meat was so cheap and was fed to hogs and slaves. The last remaining flock, approximately 250,000 birds, was killed by sport hunters in a single day in 1896. The very last passenger pigeon died in captivity in 1914.

Species of marine mammals primarily whales, dolphins, seals, sea lions, sea otters are also being hunted to extinction or near extinction for their fur, oil, and meat.

The Marine Mammals Protection Act of 1972 bans taking (harvesting, hunting, capturing, or killing, or attempting to do so) or importing any marine mammals or mammal products in United States territorial waters and fisheries. Hunting land animals in developed nations is now highly regulated. These laws save significant populations of game animals and birds.

Professional hunters are sometimes hired to control animals in populated areas, such as bears in parks.

Wildlife Trade

The sale and exchange of wild animals and plants and the products made from them is known as the wildlife trade. Plants are gathered from the wild and sold for gardens or herbal medicines; animals are sold as pets, or for food, exotic leather products, furs, musical instruments, and medicines. Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) by the United Nations prohibits international trade in threatened or endangered organisms, which now include more than 28,000 species of plants and 5,000 species of animals.

Bushmeat

Bushmeat is commercially hunted wild animal meat, often from Africa. Recent studies show that between one and five million tons of wild animal meat are taken annually from the Congo Basin in West Africa.  This is making the wild life there unsustainable.

Of the seven great ape species, only humans are not facing extinction.  The reasons for the decline are habitat loss, pathogens, and the rise in the bushmeat trade.  Besides humans infecting apes with deadly diseases, African apes and monkeys harbor pathogens that can get transmitted into human populations. The introduction of HIV into humans has been traced to the consumption of chimpanzee meat.

China is also involved in wild animal meat. There is high demand for exotic foods such as pangolin, a slow-moving anteater.

Exotic Pet Trade

Exotic pets are animals that have not been domesticated and often do not live well with humans, and yet the trade thrives, especially in the United States, the European Union, and Japan.  Examples are baboons, chimpanzees, rhesus monkeys, tigers, lions, wolves, black bears, three-toed sloths, foxes, raccoons, snakes, tarantulas, scorpions, turtles, lizards, birds and coral reef fish.

Wild animals spread disease to domestic animals and humans.  Salmonella infection from reptiles, Herpes B virus from macaque monkeys, etc are examples

Medicinal Plants

80% of the world’s people use traditional medicine to treat illnesses which require medicinal plants. China and India are the largest markets for medicinal plants.

For more than 3,000 years, the Chinese are using natural ingredients from plants, animals, and minerals to cure everything from the common cold to fevers, arthritis, and sexual dysfunction. These medications are sold throughout China and other Asian countries and to Asians around the world. Traditional Chinese medicines use ingredients from hundreds of species of plants and animals including endangered, threatened, or protected species.  

Most medicinal plants are gathered from the wild and are an important income source.  Wild Asian ginseng cost tens of thousands of dollars per kilogram.  To protect wild medicinal plants, regulations must be enforced and cultivation of medicinal herbs should become more widespread.

5. Climate change associated with global warming

Climate change has been an important factor for evolutionary processes and caused extinctions throughout Earth history. Human activities, such as fossil-fuel and forest burning results in a rapid change in Earth’s climate resulting in global warming. Amphibian species are undergoing extinction since global warming has allowed pathogens increase.

Global Warming

Since the end of the Pleistocene ice ages about 10,000 years ago, 4°C rise in global temperatures have occurred.

Each plant and animal species have an optimal climate condition to which they are adapted. Global warming alters the climatic conditions at regions which becomes intolerable for some species which may either move toward the poles or to higher elevations until it finds conditions where it can grow. Those species that cannot move or adapt to the new conditions will be extinct.

Increasing temperatures are melting glaciers and ice caps which destroys the habitat required for polar bears and northern seals. Melting ice results in rise of sea level which alter the coastal areas that habitat numerous species.

Temperature changes affect the breeding of some animal species, some populations decrease and some populations increase.

The sex of some aquatic animals, such as some turtles and fish, which are determined by water temperature and warmer water leads to all-female turtle hatchlings

Since most pathogens thrive in a warm environment, global warming increase both their survival and transmission rates.  Most disease vectors are now capable of completing their life cycle in a faster rate. About one-third of forests are affected by climate change due to increased risk of pathogen attack and problems associated with drought.

Global warming is occurring at a faster rate so that many plants and animals are not able to adapt before they suffer population decline or even extinction. The most detrimentally affected are the amphibian populations.

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References

• Emerging Consequences of Biotechnology - Biodiversity Loss and IPR Issues, Krishna Dronamraju, World Scientific Publishing Co. Pte. Ltd.
• Biosphere - Ecosystems and Biodiversity Loss, Dana Desonie, Chelsea House

Drivers of biodiversity loss -III - Invasive species

Drivers of biodiversity loss - III - Invasive species 

The five important drivers of biodiversity loss are

1.      Habitat loss and degradation

2.      Pollution

3.      Invasive species

4.      Over-exploitation

5.     Climate change associated with global warming

3.      Invasive species

Invasive species are organisms that enter into an ecosystem where they are not native.  Generally this occurs as the result of human activities.

Many alien species blend into their new habitat and actually increase biodiversity there. A few damage the local ecosystem

Species naturally enter new environments frequently, but the number and rate at which they are introduced has increased dramatically around the world.

When members of an alien species are introduced into a new ecosystem, there are three possible outcomes.

• The habitat is inhospitable and the invader perishes
• The habitat is suitable for the invader and it develops a population and increase the ecosystem’s biodiversity
• The habitat is suitable for the invader and it outcompetes the native species, its population explodes wiping out the native population – resulting in a decrease in biodiversity.

Invasive species may cause harm to native organisms in three ways

• Predation:  The Australian brown tree snake has eliminated several native bird species by eating them.
• Spreading disease: Birds introduced to Hawaii are less susceptible than the native birds.to the avian malaria parasite (this parasite is also an introduced species)
• Altering the environment: The Australian melaleuca tree is spreading through the Everglades; oil in the tree’s leaves burns easily which results in spreading fires that kill native plants.

Invasions of Aquatic Ecosystems

Alien species have damaged both marine and freshwater ecosystems.  The alien species are introduced into an aquatic ecosystem through the ballast water of a ship. Ships suck water into tanks as counterbalance to heavy loads.  This water contains as many as 300 species of organisms or their larvae.  When the ship dumps the ballast water, these organisms are expelled with it.

An example for such an alien species is the zebra mussel, a small mollusk, from the Caspian Sea which reached United States. The organism is a voracious filter feeder and reproducer and drive out native species and clog drain pipes.

Aquarium dumping is another common path for the invasion of an aquatic system by alien species.

Milfoil, a lovely aquarium plant that was released into the eastern United States formed very dense mats at the surface of a lake.  It interferes with recreational activities and power generation and prevent dissolving of oxygen into the water there by destroying the fish population.

Invasions of Terrestrial Ecosystems

Terrestrial ecosystems are also suffering from invasive species. Island animals are highly susceptible to invasive species.    Example is the dodo, a large, flightless bird lived on the island of Mauritius in the Indian Ocean had no predators to fear. When the Dutch arrived, 400 years ago, their dogs and pigs and the rats that had sneaked on their ships consumed the easy to obtain dodo eggs and in less than 100 years, the Dodo was extinct.

Invasive Species Control

We can control invasive species before they enter a new environment, early during their invasion or after they have become a serious problem.

The most effective way to keep down alien species damage in a location is to stop the aliens from entering

Once they enter a new habitat, most alien species blend into the ecosystem. Mechanical methods such as pulling off weedy plants, chopping of trees, use of herbicides to stop seedlings, etc may be adopted. Animals may be stopped by trapping or hunting.  Chemical controls such as the use poisons such as herbicides and insecticides may be employed.  Biological control, or biocontrol which uses a pathogen or a predator to control invasive species may be used to reduce the alien population density.

After habitat destruction, invasive species is the second greatest cause of biodiversity loss. The best way to avoid destruction by alien species is to stop the organisms from entering the new environment. Once they are integrated into the ecosystem, most invaders are very difficult or impossible to remove.

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References

• Emerging Consequences of Biotechnology - Biodiversity Loss and IPR Issues, Krishna Dronamraju, World Scientific Publishing Co. Pte. Ltd.
• Biosphere - Ecosystems and Biodiversity Loss, Dana Desonie, Chelsea House

Computer applications in fermentation technology

Computer applications in fermentation technology

The use of computers for control of fermentation process has increased significantly in the last decade. It is being used for both industrial fermentation and fermentation research.  A computer can be a vital instrument for process optimization and control. The first project to computerize a fermentation began in 1966 in England when direct digital control for the control of temperature, pH, air flow and form level were done in a production fermentation vessel. 

For a fermentation production plant the primary objective of computer control is to produce a product as economically as possible.  The computer is generally used to provide quality control, to save the operational time, to furnish automatic documentation and to decrease the per loop control cost.

The basis of any system used in monitoring and controlling a fermentation process is instrumentation.  Both computer hardware and software are required for control of fermentation process to measure and control the process variables which may be either environmental parameter or physiological parameter or based on the Biomass.  Common environmental variables are temperature, pH, dissolved oxygen, agitation speed, aeration rate and nutrient concentration.  Physiological variables are the products of metabolism and variables describing the state of metabolism.

Industrial Microbiology, Second Edition, AH Patel

The variables to be measured may be directly measured using a sensor.  For the variables which are not directly measurable gateway sensors are used.  In this technique the non-measurable parameter is extracted from a combination of measurable parameters.  The use of computer is very useful in making this type of variable measurements.

Three distinct areas of computer function in fermentation are:

1. Logging of process data. Data logging is performed by the data acquisition system which has both hardware and software components. There is an interface between the sensors and the computer. The software should include the computer program for sequential sensor signals and the procedure of data

2. Data analysis (Reduction of logged data) : Data reduction is performed by the data analysis system, which is a computer program based on a series of selected mathematical equations.  The analysed information may then be put on a print out, fed into a data bank or utilized for process control.

3. Process control. Process control is also performed using a computer program. Signals from the  computer are fed to pumps, valves or switches via the interface. In addition the computer proggram may contain instructions to display devices, to indicate alarms, etc.

The interfacing techniques used in coupling the computer with measurement and control  in a fermentation process includes the following basic components.  There will be modules providing analogue inputs, analogue outputs, digital inputs, digital outputs and interrupt inputs.

Industrial Microbiology, Second Edition, AH Patel

The computer applications in fermentation Technology are used in the automation in penicillin fermentation, fermentative production of enzymes, for fault analysis during fermentation to monitor product losses and also for fermentation research.   

There are two distinct fundamental approaches to computer control of fermenters. The first is when the fermenter is under the direct control of the computer software.  This is termed Direct Digital Control (DDC). The second approach involves the use of independent controllers to all control functions of a fermenter and the computer communicates with the controller only to exchange information. This is termed Supervisory Set-Point Control (SSC).

It is possible to analyse data, compare it with model systems and use control programs which will lead to process optimization. However, process optimization by use of computer is not a widely used procedure in the fermentation industries at present.

 

References

1. Industrial Microbiology, Second Edition, AH Patel, Trinity press
2. Principles of fermentation technology, PF Stanbury, A Whittakker, SJ Hall, 1995, Butterworth-Heinemann publications

 

Food Fermentation: Bread

Food Fermentation: Bread

Bread is known to man even from about 4,000 B.C. Today, bread is a major food of the world and it supplies over half of the caloric and Vitamins B and E intake of the world’s population.

The basic ingredients

The basic ingredients in bread-making are flour, water, salt, and yeasts. In modern bread making

Some other additives such as ‘yeast food’, sugar, milk, eggs, shortening (fat) emulsifiers, anti-fungal agents, anti-oxidants, enzymes, flavoring, and enriching ingredients are also used.

Flour, the chief ingredient of bread is produced by milling wheat.  Flour contains starch (70%), protein (7-15%), sugar (1%), and lipids (1%).

Flour proteins are of two types, the first type is soluble in water and dilute salt solutions and is non-dough forming. It forms about 15% of the total protein in flour and include albumins, globulins, peptides, amino acids, and enzymes. The second type is gluten which contributes the 85% of flour protein and they are insoluble in aqueous media and are responsible for dough formation. Gluten form an elastic structure when moistened with water and holds the starch, yeasts, gases and other components of dough.

One third portion of gluten is alcohol soluble fraction known as gladilins and two thirds of gluten is not alcohol-soluble and known as the glutenins. Gladilins are of lower molecules weight than glutenins.

Yeast used for baking is Saccharomyces cerevisiae. The ideal properties of yeasts baking are:

(a) Ability to grow rapidly at room temperature of about 20-25°C;

(b) Easy dispersability in water;

(c) Ability to produce large amounts of CO₂ rather than alcohol in flour dough;

(d) Ability to resist autolysis when stored at 20°C; Good keeping quality

(e) Ability to adapt rapidly to substrates during dough making.

(f) High invertase and other enzyme activity to hydrolyze sucrose to higher glucofructans rapidly;

(g) Ability to grow and synthesize enzymes and coenzymes under the anaerobic conditions of the dough;

(h) Ability to resist the osmotic effect of salts and sugars in the dough;

(i) High competitiveness i.e., high yielding in terms of dry weight per unit of substrate used.

The yeast amounts vary from 2.0 -  3.0% of flour weight. The amount of yeasts used during baking depends on the flour type, Very ‘strong’ flours i.e., with high protein levels, require more yeast than softer ones.  Also baking systems which involve short periods for dough formation, need more yeast.

The roles of yeasts in bread-making are leavening, flavor development and increased nutritiveness.

Yeast ‘food’ contain a calcium salt, an ammonium salt and an oxidizing agent such as iodates, bromates and peroxide. The bivalent calcium ion strengthens the colloidal structure of the wheat gluten, ammonium is a nitrogen source for the yeast and oxidizing agent strengthens gluten by reacting with the proteins and enhances the ability to hold gas releases during dough formation.

Yeast food has the following composition: calcium sulfate, 30%, ammonium chloride, 9.4%, sodium chloride, 35%, potassium bromate, 0.3%; starch (25.3%).

Sugar is added as sucrose or fructose corn syrups,

(a) to provide additional carbon nourishment for the yeasts

(b) to sweeten the bread;

(c) for more rapid browning of the crust through sugar caramelization.  This allows greater moisture retention within the bread.

Animal and vegetable fats such as Butter, lard (fat from pork) or soy bean oil, are added as shortenings in bread-making at about 3% (w/w) of flour in order to yield

(a) increased loaf size;

(b) a more tender crumb; and

c) enhanced slicing properties.

Emulsifiers are used in conjunction with shortening to ensure a better distribution of shortening in the dough. Emulsifiers contain a fatty acid such as palmitic or stearic acid, which is bound to glycerol, lactic acid, sorbic acid or tartaric acid. Emulsifiers are added at 0.5% flour weight. Commonly used surfactants are calcium stearyl- 2-lactylate, lactylic stearate, sodium stearyl fumarate.

Milk is added to make the bread more nutritious, to help improve the crust color by sugar cearamelization and for its buffering value. Milk is added at a ratio of 1-2 parts per 100 parts of flour.

About 2% sodium chloride is usually added to bread for the following purposes:

(a) It improves taste;

(b) It stabilizes yeast fermentation;

(c) As a toughening effect on gluten;

(d) Helps minimize proteolytic activity;

(e) It participates in the lipid binding of dough.

Since salt has a retarding effect on fermentation, it is added only towards the end of the mixing.

Water is needed to form gluten, to permit swelling of the starch, and to provide a medium for the various reactions that take place in dough formation.

Amylolytic enzymes are required to breakdown the starch from flour into fermentable sugars. Flour is supplemented with malted barley or wheat to provide Alpha amylase or Fungal or bacterial amylase preparations may be added. Bacterial amy1ase from Bacillus subtilis is heat-stable and can survive the baking process. Proteolytic enzymes from Aspergillus oryzae are also used.

Mold-inhibitors (antimycotics) are added and the chief antimycotic agent added to bread to prevent fungal growth is calcium propionate, sodium diacetate, vinegar, mono-calcium phosphate, and lactic acid.

Bread is enriched with various vitamins and minerals including thiamin, riboflavin, niacin and iron.

Process of Bread-making

The processes of yeast-leavened bread-making may be divided into:

1.      Pre-fermentation (or sponge mixing): A portion of the ingredients is mixed with yeast and with or without flour to produce an inoculum. During this the yeast becomes adapted to the growth conditions of the dough and rapidly multiplies.

2.      Dough mixing: The balance of the ingredients is mixed together with the inoculum to form the dough. Maximum gluten development occurs.

3.      Cutting and rounding: The dough formed above is cut into specific weights and rounded by machines.

4.      First (intermediate) proofing: The dough is allowed to rest for about 15 minutes at about   27°C. This is done in equipment known as an overhead proofer.

5.      Molding: The dough is flattened to a sheet and then moulded and placed in a baking pan which will confer shape to the loaf.

6.      Second proofing: This consists of holding the dough for about 1 hour at 35-43°C at high humidity (89-95°C)

7.      Baking: During baking the proofed dough in the final pan is transferred to the oven where it is subjected to an average temperature of 215-235°C for 15-60 minutes. Baking is the final stage and it determines the success of all the previous steps.

8.      Cooling, slicing, and wrapping: The bread is depanned, cooled to 4-5°C, sliced (optional) and wrapped.

Baking

Bread is baked at a temperature of about 235°C for 45–60 minutes. During baking, temperature of the outside of the bread is about 195°C but the internal temperature never exceeds 100°C. The higher outside temperature leads to browning of the crust, a result of reactions between the reducing sugars and the free amino acids in the dough.  As the baking progresses and temperature rises gas production rises and various events occur as below:

•         At about 45°C the undamaged starch granules begin to gelatinize and are attacked by alpha-amylase, yielding fermentable sugars;

•         Between 50 and 60°C the yeast is killed;

•         At about 65°C the beta-amylase is thermally inactivated;

•         At about 75°C the fungal amylase is inactivated;

•         At about 87°C the cereal alpha-amylase is inactivated;

•         Finally, the gluten is denatured and coagulates, stabilizing the shape and size of the loaf.

The Three Basic Systems of Bread-making

There are three basic systems of baking that differ in the presence or absence of pre-fermentation.

(i) Sponge doughs: This is the most widely used. In the sponge-dough, a portion (60-70%) of the flour is mixed with water, yeast and yeast food in a slurry tank (or ‘ingridator’) during the pre-fermentation.  A spongy material develops due to bubbles caused by alcohol and CO₂ (hence the name). The sponge is allowed to rest at about 27°C and a relative humidity of 75-80% for 3.5 to 5 hours. During this period the sponges rises five to six times and collapses spontaneously. During the next (or dough) stage the sponge is mixed with the other ingredients. Then it is processed and baked.  

(ii) The liquid ferment system. In this system water, yeast, food, malt, sugar, salt and milk are mixed during the pre-fermentation at about 30°C and left for about 6 hours. After that, flour and other ingredients are added in mixed to form a dough. The rest is as described above.

(iii) The straight dough system: In this system, all the components are mixed at the same time until a dough is formed. The dough is then allowed to ferment at about 28-30°C for 2-4 hours and then the same process already describedfollows. The straight dough is usually used for home bread making.

The Chorleywood Bread Process is a modification of the straight dough process, which is used in most bakeries in the United Kingdom and Australia. The process is also known as CBP (Chorleywood Bread Process) where All the components are mixed together in 3-5 minutes, with added Fast-acting oxidizing agents and higher level of yeast added and no pre-fermentation time.

Role of Yeast in Bread-making

Leavening is the increase in the size of the dough induced by gases during bread-making. Leavening may be brought about in a number of ways such as Air or carbon dioxide forced into the dough, Water vapor or steam which develops during baking, Hydrogen peroxide added to release oxygen, Carbon-dioxide released by the use of decarboxylase enzymes or by the use of baking powder. Baking powder consists of 30% sodium bicarbonate mixed with leavening acids such as sodium acid pyrophosphate, monocalcium phosphate, sodium aluminum phosphate, monocalcium phosphate generate CO₂ on contact with water and this is suitable for cakes and other high-sugar leavened foods, whose osmotic pressure is too high for yeasts.

But generally bread is Leavened by yeasts.  During bread making, yeasts ferment hexose sugars mainly into alcohol and carbon dioxide and various other alcohols, esters aldehydes, and organic acids. The CO2 dissolves in the dough and the excess CO2 in the gaseous state begins to form bubbles in the dough. This formation of bubbles causes the dough to rise or to leaven. The total time taken for the yeast to act upon the dough varies from 2-6 hours.

Factors which effect the leavening action of yeasts

(i)                 The nature of the sugar available: When glucose, fructose, or sucrose are added these are utilized and when no sugar is added to the dough, the yeast utilizes the maltose in the flour. Thr most rapid leavening is achievable by using glucose.

(ii)              Osmotic pressure: High osmotic pressures inhibit yeast action. Salt is therefore added as late as possible during the dough formation process.

(iii)            Effect of nitrogen and other nutrients: The addition of minerals and a nitrogen source increases gas production. Ammonium, amino acids and peptides and thiamine act as nitrogen source.

(iv)             Effect on fungal inhibitors: Anti-mycotics added to bread are inhibitory to yeast. So the minimum level inhibitory to yeasts is used.

(v)               Yeast concentration:

Flavor development in bread

The aroma of bread is distinct from all other fermented foods because of the baking process. During baking the lower boiling point molecules escape and new compounds result from the chemical reactions taking place at the high temperature. The flavor compound found in bread are organic acids, esters, alcohols, aldehydes, ketones and other carbonyl compounds.

 

References

1. Industrial Microbiology: An Introduction, M J. Waites, N L. Morgan, J S. Rockey, G Higton
2. Modern Industrial Microbiology and Biotechnology, Nduka Okafor, Science Publishers

 

Hypersensitivity

Hypersensitivity

 Hypersensitivity reactions are pathologic processes that result from exaggerated specific interactions between antigens (exogenous or endogenous) and either humoral antibodies or sensitized lymphocytes, resulting in tissue injury. It occurs only if the host has had a previous contact with the antigen (allergen).  The initial or sensitizing dose sensitizes the immune system and the subsequent contact (shocking dose) with the same antigen or allergen causes hypersensitivity.

Hypersensitive reactions are classified based on

·         Duration between exposure of antigen and reaction – immediate type and delayed type hypersensitivity. In immediate hypersensitivity, the symptoms manifest within minutes or hours after second encounter with antigen. In Delayed-type hypersensitivity (DTH) the symptoms occur even days after exposure.

·         Immune component involved in reaction – antibody mediated and cell mediated hypersensitivity

·         Gell – Coombs classification- typeI, type II, type III and type IV

Type I -  IgE-Mediated Hypersensitivity

Antigen induces crosslinking of IgE bound to mast cells and basophils with release of vasoactive mediators.

Typical manifestations include systemic anaphylaxis and localized anaphylaxis such as hay fever, asthma, hives, food allergies, and eczema.

Type II - IgG-Mediated Cytotoxic Hypersensitivity

Antibody directed against cell surface antigens mediates cell destruction via complement activation or ADCC (Antibody-dependent cell-mediated cytotoxicity)

Typical manifestations include blood transfusion reactions, erythroblastosis fetalis, and autoimmune hemolytic anemia

Type III - Immune Complex-Mediated Hypersensitivity

Antigen - Antibody complexes deposited in various tissues induce complement activation and an ensuing inflammatory response mediated by massive infiltration of neutrophils

Typical manifestations include localized Arthus reaction and generalized reactions such as serum sickness, necrotizing vasculitis, glomerulnephritis, rheumatoid arthritis, and systemic lupus erythematosus.

Type IV - Cell-Mediated Hypersensitivity

Sensitized TH1 cells release cytokines that activate macrophages or TC cells which mediate direct cellular damage

Typical manifestations include contact dermatitis, tubercular lesions and graft rejection.

Type I -  IgE-Mediated Hypersensitivity

Type I hypersensitive reaction is induced by certain types of antigens known as allergens, and is similar to a normal humoral response. That is, an allergen induces a humoral antibody response resulting in the generation of antibody-secreting plasma cells and memory cells. But here, the plasma cells secrete IgE that binds to Fc receptors on the surface of tissue mast cells and blood basophils. Mast cells and basophils coated by IgE are said to be sensitized.

A later exposure to the same allergen cross-links the membrane-bound IgE on sensitized mast cells and basophils, causing degranulation of these cells. The IgE-antigen reaction occurring on the surface of basophils and mast cells leads to receptor cross-linking and degranulation, ie release of vasoactive amines (histamine and serotonin) and other agents (heparin, eosinophil and neutrophil chemotactic factors, platelet-activating factor, a variety of cytokines and prostaglandins and leukotrienes) from the cytoplasmic granules.  These molecules cause contraction of smooth muscle cells, vasodilation, increased vascular permeability and platelet aggregation and degranulation. These reactions can affect a single tissue or organ (as in asthma, hay fever or eczema) or multiple ones (as in generalised anaphylaxis) depending on local or general re-exposure to the allergen.

The clinical manifestations of type I reactions can range from life-threatening conditions, such as systemic anaphylaxis and asthma, to hay fever and eczema, which are merely irritating. So type I reactions are of two types – Anaphylaxis and Atopy

 

 The mediators can be classified as either primary or secondary.

The primary mediators are produced before degranulation and are stored in the granules and these are histamine, serotonin, proteases, eosinophil chemotactic factor, neutrophil chemotactic factor, and heparin.

The secondary mediators either are synthesized after target-cell activation or are released by the breakdown of membrane phospholipids during the degranulation process. They include platelet-activating factor, leukotrienes, prostaglandins, bradykinins, and various cytokines.

Histamine, which is formed by decarboxylation of the amino acid histidine, is a major component of mast-cell granules, and induces contraction of intestinal and bronchial smooth muscles, increased permeability of venules, and increased mucus secretion by goblet cells.

Serotonin is derived by decarboxylation of tryptophan and cause smooth muscle contraction, increased vascular permeability and vasoconstriction.

Leukotrienes and prostaglandin are formed during the mast cell degranulation and the enzymatic breakdown of phospholipids in the plasma membrane. Their effects are more pronounced and long lasting. The leukotrienes are formed through lipooxygenase pathway and mediate bronchoconstriction, increased vascular permeability, and mucus production. Prostaglandin are formed through  cyclooxygenase pathway causes bronchoconstriction.

Slow reacting substance of anaphylaxis (SRS-A) are a family of leukotrienes (LTC4, D4, E4).

Platelet activating Factor (PAF) is release from basophils and causes aggregation of platelets.

Anaphylaxis  (Ana – without and Phylaxis - protection) is a shock-like and often fatal state whose onset occurs within minutes of a type I hypersensitive reaction. This is due to the systemic vasodilation and smooth-muscle contraction brought on by mediators released in the course of the reaction. The symptoms include edema, decreased coagulability of blood, decrease in blood pressure and temperature, leucopenia and thrombocytopenia.  Tissues or organs involved are known as shock organ or target organs.

A wide range of antigens have been shown to trigger this reaction in susceptible humans, including the venom from bee, wasp, hornet, and ant stings; drugs, such as penicillin, insulin, and antitoxins; and seafood and nuts. If not treated quickly, these reactions can be fatal.

Epinephrine is the drug of choice for systemic anaphylactic reactions. Epinephrine counteracts the effects of mediators such as histamine and the leukotrienes.

Cutaneous anaphylaxis – This is a skin test for type I hypersensitivity.  When small dose of antigen is administered intradermally to a sensitized host, localized wheal and flare effect occurs with a central puffi area surrounded by area having hyperemia and erythema. 

Passive Cutaneous anaphylaxis – when small volume of antibody or serum is intradermally injected to normal animal followed by intravenous injection of antigen along with Evans Blue 4-24 hour later, bluing at the intradermal site occurs due to vasodilation and increased vascular permeability. 

In vitro anaphylaxis – when intestinal or uterine muscle strip from a sensitized animal is place in Rogers solution in presence of antigen, the muscle strip contract vigorously.  This is known as Schultz-Dale phenomenan. 

Anaphylactoid reaction – intravenous injection of peptone or trypsin provoke a reaction resembling anaphylactic shock.

In Localized anaphylaxis (atopy), (atopy means out of place / strangeness) the reaction is limited to a specific target tissue or organ, often involving epithelial surfaces at the site of allergen entry. The localized anaphylactic reactions is inherited and is called atopy. Atopic Allergies include allergic rhinitis (hay fever), asthma, atopic dermatitis (eczema), and food allergies.

Allergic Rhinitis, commonly known as hay fever results from the reaction of airborne allergens with sensitized mast cells in the conjunctivae and nasal mucosa to induce the release of pharmacologically active mediators from mast cells; these mediators then cause localized vasodilation and increased capillary permeability.

The symptoms include watery exudation of the conjunctivae, nasal mucosa, and upper respiratory tract, as well as sneezing and coughing.

Asthma -In some cases, airborne or blood-borne allergens, such as pollens, dust, fumes, insect products, or viral antigens, trigger an asthmatic attack (allergic asthma);

In other cases, an asthmatic attack can be induced by exercise or cold, apparently independently of allergen stimulation (intrinsic asthma).

Like hay fever, asthma is triggered by degranulation of mast cells with release of mediators, but instead of occurring in the nasal mucosa, the reaction develops in the lower respiratory tract. The resulting contraction of the bronchial smooth muscles leads to bronchoconstriction. Airway edema, mucus secretion, and inflammation contribute to the bronchial constriction and to airway obstruction.

Food allergies – Food allergen crosslinking of IgE on mast cells along the upper or lower gastrointestinal tract can induce localized smooth-muscle contraction and vasodilation and thus such symptoms as vomiting or diarrhea.

Mast-cell degranulation along the gut can increase the permeability of mucous membranes, so that the allergen enters the bloodstream.

Some individuals develop asthmatic attacks after ingesting certain foods. Others develop atopic urticaria, commonly known as hives, when a food allergen is carried to sensitized mast cells in the skin, causing swollen (edematous) red (erythematous) eruptions; this is the wheal and flare response, or P-K reaction (Prausnitz – Kustner reaction).  It includes swelling, produced by the release of serum into the tissues (wheal), and redness of the skin, resulting from the dilation of blood vessels (flare).

Atopic dermatitis (allergic eczema) is an inflammatory disease of skin. The allergic individual develops skin eruptions that are erythematous and filled with pus.

 Type II Hypersensitivity Antibody-Mediated Cytotoxic Hypersensitivity

Type II hypersensitive reactions involve antibody-mediated destruction of cells. Antibody can activate the complement system, creating pores in the membrane of a foreign cell  or it can mediate cell destruction by antibody dependent cell-mediated cytotoxicity (ADCC).

Transfusion Reactions

An individual possessing one type of blood-group antigen recognize other type on transfused blood as foreign and mount an antibody response. In some cases, the antibodies have already been induced by natural exposure to similar antigenic determinants on a variety of microorganisms present in the normal flora of the gut.  Antibodies to the A, B, and O antigens, called isohemagglutinins, are usually of the IgM class.  Antibodies to other blood-group antigens may also result from repeated blood transfusions and these antibodies are usually of the IgG class.

If a type A individual is transfused with blood containing type B cells, a transfusion reaction occurs in which the anti-B isohemagglutinins bind to the B blood cells and mediate their destruction by means of complement-mediated lysis.

The clinical manifestations of transfusion reactions result from massive intravascular hemolysis of the transfused red blood cells by antibody plus complement. These manifestations may be either immediate or delayed.

In the immediate type, symptoms include fever, chills, nausea, clotting within blood vessels, pain in the lower back, and hemoglobin in the urine.

Delayed hemolytic transfusion reactions generally occur in individuals who have received repeated transfusions of ABO-compatible blood that is incompatible for other antigens. The reactions develop between 2 and 6 days after transfusion.   Symptoms include fever, low hemoglobin, increased bilirubin, mild jaundice, and anemia.

Hemolytic Disease of the Newborn

Hemolytic disease of the newborn develops when maternal IgG antibodies specific for fetal blood-group antigens cross the placenta and destroy fetal red blood cells. The consequences of such transfer can be minor, serious, or lethal.

Severe hemolytic disease of the newborn, called erythroblastosis fetalis, most commonly develops when an Rh+ fetus expresses an Rh antigen on its blood cells that the Rh– mother does not express. During pregnancy, fetal red blood cells are separated from the mother’s circulation by a layer of cells in the placenta called the trophoblast. During her first pregnancy with an Rh+ fetus, an Rh– woman is usually not exposed to enough fetal red blood cells to activate her Rh-specific B cells. At the time of delivery, larger amounts of fetal umbilical-cord blood enter the mother’s circulation. These fetal red blood cells activate Rh-specific B cells, resulting in production of Rh-specific plasma cells and memory B cells in the mother.

Activation of the memory cells in a subsequent pregnancy results in the formation of IgG anti-Rh antibodies, which cross the placenta and damage the fetal red blood cells. Mild to severe anemia can develop in the fetus and conversion of hemoglobin to bilirubin cause brain damage with fatal consequences.

Hemolytic disease of the newborn can be prevented by administering antibodies against the Rh antigen to the mother within 24–48 h after the first delivery. These antibodies, called Rhogam, bind to any fetal red blood cells that enter the mother’s circulation at the time of delivery and facilitate their clearance before B-cell activation and ensuing memory-cell production can take place.

Drug-Induced Hemolytic Anemia

Certain antibiotics (e.g., penicillin, cephalosporin, and streptomycin) can adsorb nonspecifically to proteins on RBC membranes, forming a complex similar to a hapten-carrier complex. In some patients, such drug-protein complexes induce formation of antibodies, which then bind to the adsorbed drug on red blood cells, inducing complement mediated lysis and thus progressive anemia. When the drug is withdrawn, the hemolytic anemia disappears.

Immune Complex–Mediated (Type III) Hypersensitivity

The reaction of antibody with antigen generates immune complexes and these complexes are cleared by phagocytic cells.

Type III hypersensitive reactions develop when immune complexes activate the complement system and the C3a, C4a, and C5a complement products cause localized mast-cell degranulation and consequent increase in local vascular permeability. C3a, C5a, and C5b67 are chemotactic factors for neutrophils and attract neutrophils to the complex deposition site and the tissue is then injured due to granular release from the neutrophil.

Generally, complex deposition is observed on blood-vessel walls, in the synovial membrane of joints, on the glomerular basement membrane of the kidney, and on the choroid plexus of the brain.  Larger immune complexes are deposited on the basement membrane of blood vessel walls or kidney glomeruli, whereas smaller complexes may pass through the basement membrane and be deposited in the subepithelium.

·         Much of the tissue damage is due to release of lytic enzymes by neutrophils as they attempt to phagocytose immune complexes. During the process, the C3b complement component acts as an opsonin and coat immune complexes.  A neutrophil binds to a C3b-coated immune complex and since the complex is deposited on the basement membrane surface, phagocytosis is impeded, and the lytic enzymes are released during the unsuccessful attempts.

·         The  membrane-attack mechanism of the complement system also contribute to the destruction of tissue.

·         The activation of complement induce aggregation of platelets, and the resulting release of clotting factors lead to microthrombi formation.

When the complexes are deposited in tissue very near the site of antigen entry, a localized reaction develops.  When the complexes are formed in the blood, a generalized reaction develop.

Localized Type III Hypersensitivity

This is known as Arthus reaction.  When the antigen enter for the second time, at the site of antigen entry, localized tissue and vascular damage results in accumulation of fluid (edema) and red blood cells (erythema) at the site.  The severity of the reaction can vary from mild swelling and redness to tissue necrosis.

After an insect bite, a sensitive individual may have a rapid, localized type I reaction at the site.  Some 4–8 h later, a typical Arthus reaction develops at the site, with pronounced erythema and edema.

Intrapulmonary Arthus-type reactions induced by bacterial spores, fungi, or dried fecal proteins can also cause pneumonitis or alveolitis. These reactions are known as, “farmer’s lung” after inhalation of thermophilic actinomycetes from moldy hay, and “pigeon fancier’s disease” resulting from inhalation of dried pigeon feces.

Generalized Type III Hypersensitivity

This is a systemic form and occurs 7-12 days after injection of foreign serum and is known as serum sickness.  Serum sickness differs from other hypersensitivities in that a single injection can serve both as sensitizing dose and shocking dose. 

When large amounts of antigen enter the bloodstream and bind to antibody, circulating immune complexes can form and they can cause tissue- damaging type III reactions at various sites.

Historically, generalized type III reactions were often observed after the administration of antitoxins containing foreign serum, such as horse antitetanus or antidiphtheria serum. In such cases, the recipient develops antibodies specific for the foreign serum protein antigens which then form circulating immune complexes with the antigens.  Within days or weeks after exposure, individual begins to manifest a combination of symptoms that are called serum sickness. These symptoms include fever, weakness, generalized vasculitis (rashes) with edema and erythema, lymphadenopathy, arthritis, and sometimes glomerulonephritis, endocarditis, vasculitis, abdominal pain, nausea, vomiting, etc.

The precise manifestations of serum sickness depend on the quantity of immune complexes formed as well as the size of the complexes and the site of their deposition.   

Formation of circulating immune complexes contributes to the pathogenesis of a number of conditions other than serum sickness. These include the following:

Autoimmune Diseases

Systemic lupus erythematosus, Rheumatoid arthritis, Goodpasture’s syndrome

Drug Reactions

Allergies to penicillin and sulfonamides

Infectious Diseases

Poststreptococcal glomerulonephritis, Meningitis, Hepatitis, Mononucleosis, Malaria, Trypanosomiasis

Type IV or Delayed-Type Hypersensitivity (DTH)

When some subpopulations of activated TH cells encounter certain types of antigens, they secrete cytokines that induce a localized inflammatory reaction called delayed-type hypersensitivity (DTH). The hallmarks of a type IV reaction are the delay in time required for the reaction to develop and the recruitment of macrophages. 

·         The development of the DTH response begins with an initial sensitization phase of 1–2 weeks after primary contact with an antigen. During this period, TH cells are activated by antigen presented together with the class II MHC molecule on an appropriate antigen presenting cell including Langerhans cells and macrophages.

·         A subsequent exposure to the antigen induces the effector phase of the DTH response. In the effector phase, TH1 cells secrete a variety of cytokines that recruit and activate macrophages and other nonspecific inflammatory cells.

·         A DTH response generally peaks 48–72 h after second contact. The delayed onset of this response is due to the time required for the cytokines to induce localized influxes of macrophages and their activation.

·         Macrophages are the principal effector cells of the DTH response. Cytokines released by TH1 cells induce blood monocytes to migrate from the blood into the surrounding tissues. During this process the monocytes differentiate into activated macrophages.

·         The heightened phagocytic activity and the buildup of lytic enzymes from macrophages  cause nonspecific destruction of cells. This intense inflammatory response develops into a visible granulomatous reaction.

·         A granuloma develops when macrophages adhere closely to one another and fuse to form epitheloid cells and then multinucleated giant cells. These giant cells displace the normal tissue cells, forming palpable nodules, and release high concentrations of lytic enzymes, which destroy surrounding tissue and blood vessels and lead to extensive tissue necrosis.

The response to Mycobacterium tuberculosis is an example for the double-edged nature of the DTH response. Immunity to this intracellular bacterium involves a DTH response in which activated macrophages wall off the organism in the lung and contain it within a granuloma-type lesion called a tubercle.  However, the concentrated release of lytic enzymes from the activated macrophages within tubercles damages lung tissue.  

 

Tuberculin type - The presence of a DTH reaction can be measured experimentally by injecting small dose of tuberculin antigen intradermally into an animal and observing whether a characteristic skin lesion develops at the injection site.  Development of a red, slightly swollen, firm lesion at the site between 48 and 72 h later indicates previous exposure. The skin lesion results from intense infiltration of cells to the site of injection during a DTH reaction; 80%–90% of these cells are macrophages.  Similar hypersensitivity is observed against fungi, viruses, parasites, allograft, etc. 

Cutaneous basophil hypersensitivity – this resembles tuberculin reaction, but it is a delayed type hypersensitivity.  Here the intradermal injection site will be infiltered with basophils.

Contact Dermatitis – contact with a allergen in a sensitized individual leads to contact dermatitis.  The allergens include formaldehyde, trinitrophenol, nickel, turpentine, and active agents in various cosmetics and hair dyes, poison oak, poison ivy, etc. Most of these substances are small molecules that can complex with skin proteins. This complex is internalized by antigen-presenting cells in the skin (e.g., Langerhans cells), then processed and presented together with class II MHC molecules, causing activation of sensitized TH1 cells. The immune reaction results in formation of macules and papules that develops to vesicles that break down resulting in raw weeping areas.

In the reaction to poison oak, a pentadecacatechol compound from the leaves of the plant forms a complex with skin proteins.  When TH cells react with this compound displayed by local antigen-presenting cells, they differentiate into sensitized TH1 cells. A subsequent exposure to pentadecacatechol will elicit activation of TH1 cells and induce cytokine production. Approximately 48–72 h after the second exposure, the secreted cytokines cause macrophages to accumulate at the site. Activation of these macrophages and release of lytic enzymes result in the redness and pustules that characterize a reaction to poison oak.

Shwartzman reaction – this is not an immune reaction.  But resembles hypersensitivity.

If Salmonella typhi culture filterate is injected intradermally followed 24 hours later by intravenous injection of same or any other endotoxin, lesion develops at the intradermal site.  There is no specificity in the reaction.  If both injections are intravenous, then the animal dies 12-24 hours after the second dose.

The initial or preparatory dose causes accumulation of leucocytes that damage capillary walls.  The second dose or provocative dose cause intravascular clotting due to necrosis of vessel walls and hemorrhage.