Verne Jules

                                

     

  

     I  like reading Verne Jules’ books.When I went  to school,I said a friend of mine that if he could give me a book.Then he brought me some books.I looked these  books ,then I decided to read “Round The World In 80 Days” and I also decided to do my term homework with this book.It was an enjoyable term homework for me,because I like reading books so much that I didn’t want to finish my term homework.I think this book has been specially prepared to make enjoyable reading for people to whom English is second or a foreign language.An English writer never thinks of avoiding unusual words,so that the learner,trying to read the book in its original form,has to turn frequently to dictionary and so loses much of the pleasure that the book ought to give.

   Teacher!!!

  I finished my term homework.Also now you are reading my term homework,so thank you for reading my term homework and I’m sorry for all my mistakes.        

                                                                                                               Işık Yohay

                                                                                                                7/C 1092

    

                      THE   AUTHORS’ LIFE

                          

                             Verne  Jules;(1828-1905)

     

       Verne Jules;(1828-1905)

     Many writes today mix scientific facts and ideas with imaginative stories.It is a very popular mixture.Jules Verne found the secret of this mixture almost by accident.

     Jules Verne was born at Nantes,France,in 1828.He was a French writer.He was studying law when some travel stories which he wrote for a newspaper caught the public interest. When he was learning jurisprudence,he played theatre.He became a secretary for ‘Theatre-Lyrique’ and he staged some plays.They are ‘Pailles Pompues’ (1850), ‘Monseur de Chimpanze’(1860).He played a musicial theatre which  name is ‘Colin-Maillard’(1861).

    Jules Verne married with Honorine de Viane in 1857,so he became a very determined person.When he designed ‘Voyages Extraordiniaires’,he acquainted  with a woman who was an author,name was Jules Hetzel.They spoke then they decided that Jules Verne  would write forty books then they did agreement (1862).First he wrote ‘Cinq Semaines en Ballon’(1863).There are still people all over the world who enjoy them, although they  were written nearly a hundred years ago.He wrote them in French.Some people translated his books from French into many languages and some people published  most of his books on the cinema.

    Could Jules Verne see the future?In Twenty Thousand Leagues under the Sea,an imaginary ship,the Nautilus,sails under the North Pole;a real Nautilus did make the first voyage under the North Pole in 1958.

      The most popular today of Jules Verne’s books:  

1.    Voyage au  Centre de terre(1864)

2.    De La Terre a la Lune(1865)

3.    Vingt Mille Lieues Sous les Mers(1870)

4.    Le Tour du Monde en Quatre-Vingt Joterieuse(1873)

5.    I’İle Mysterieuse(1874)

6.    Michel Strgoff(1876)

7.    Un Capitanine de Quinze An(1878)

8.    La  Jandaga(1881)

9.    Mathias Sandorf(1885)

10. Nord Contre sud(1887)

            

            A little conversation about ‘Round The World In 80 Days’

·       ‘Round the world?’

·       ‘Yes, round the world.’

·       ‘In eighty days?’

·       ‘In eighty days.’

·       ‘Leaving in ten minutes’ time?’

·       ‘Just so.’

·       ‘But what about the things we are to take with us?What about packing?’

·       ‘We take nothing with us except our night clothes. . . . . . . .’

·       . . . . . . At eight  forty-five the train began to move:the journey round the world had begun. . . . . . .

     

       The Little Summary of ‘Round The World In 80 Days’

       The book is a science fiction  book.It is about oneiric novel.

When the new inventions were gaining speed,the novel’s gallant whose name is Phileas Fogg argumented with his club friends.Also the argument was crossed in his life time. . . . . . . . . . . . . . . . . . . . . .

    In the year 1872 there lived at No.7  Savile Row,london,Mr.Phileas Fogg,one of the member of  the Reform Club.As he never spoke about himself,nobody knew who he was.He was a gentleman and also he didn’t have  any job.In Reform Club,sometimes when the members of the club talked about travellers,Mr.Fogg would explain what had probably become of them.Then his explanations often proved to be  quite true,so he must have travelled everywhere.He liked playing cards.

   He didn’t have any relative.He had a servant who was John Foster,did a mistake and Mr.Fogg  didn’t like mistake,so the servant must leave him.Then, the new servant whose name was Jean Passepartout,came.Mr.Fogg went to Reform Club,then he played cards with his friends.While they were playing cards,they talked about a great bank robbery.The robber had stolen 55.000 pounds.One member of Reform Club said that where the gentleman escaped with the money.Mr.Fogg said “The World was small!,because a man would walk around the world in 80 days.His friends didn’t believe that a man would walk  around the world in 80 days.Mr.Fogg and his friends began to  claim and then Mr.Fogg said that I could walk around the world in 80 days.If he could walk around the world in 80 days,Mr.Stuart  would give him four thousand pounds.            

    Mr.Fogg went to home,he collect his clothes and the servant collects his clothes.They went to the train station.That evening,at  eighty  forty-five the train began to move;the journey round the world had begun.Mr.Fogg’s programme;                                                                                                                                                                                                                                                                              

                                                                                                                                                         Londan to Suez by Calais and Brindisi                                                                                                                                  (railways and steamer).                                     .            .   7 days                                                         Suez to Bombay (steamer).                                .            . 13 days                                             Bombay to Calcutta (railway).                          .            .  3 days                                                                              Calcutta to Hong Kong (steamer).                    .            . 13 days

Hong Kong to Yokohama (steamer).                .            .  6 days

Yokohama to San Francisco (steamer).           .            . 22 days                                               San Francisco to New York (railway).             .            .  7 days                                             New York to Londan (steamer and railway)    .            .  9 days

                                                                                       +_______                            

                                                                                                 80 days            

     (Mr.Fogg)

   Seven days later,a man who wanted to catch the bank robber,name was Mr.Fix.This man was a detective and he wanted to catch Mr.Fogg,because they thought that Mr.Fogg was the man who had stolen the money from the bank and they thought that Mr.Fogg wanted to do the World Tour for escape.

                                                                 

                                                                          

Then Mr.Fix went to Suez to wait Mongolia,because Mr.Fogg was in Mongolia.When Mr.Fix watched passengers,Passepartout came and they talked.Mr.Fix said passepartout that he never had seen his master on the deck.Passepartout said that Mr.Fogg hadn’t liked mixing with other people and Mr.Fix asked that if he had known that the journey round the world in eighty days might be an excuse for something else,some secret purpose,and the servant said that he hadn’t known and he hadn’t  wanted to know about that.Then On Sunday,October 20th,when they came India,Passepartout and Mr.Fix finished the talking.The ship reached Bombay two days earlier than had been expected.Then all the people went for a walk.The servant saw  Malabar Hill.He went to it,but he didn’t take off his shoes.While he was admiring the temple from the inside,three priests threw themselves upon him a good beating.The servant was easily able to get up,knocked them down,ran.  At five minutes to eight,only a few minutes before the train left,without any shoes,he reached the railway station.Mr.Fix and Mr.Fogg were there. Mr.Frogg said his servant not to be late and Mr.Fix change his idea.Namely,he didn’t go with Mr.Frogg,because Mr.Fix could arrest them for crime which the servant entered Malabar Hill with the shoes.

   The train journey started.In the train,Mr.Fogg made friends with Sir Francis.Mr.Fogg told him the world tour and they talked about everything.The train stopped at village of Kholby,but they wanted to go Calcutta.They must find another way of getting to Allahabad.Mr.Fogg were two days early,so he wasn’t angry.The servant found an elephant and Mr.Fogg bought the elephant,but its cost was two thousand pounds.A young Indian to serviced,Mr.Fogg.Sir Francis and the servant rode the elephant.At nine o’clock they started to go.

                                            

                                                                    

Tourism Centres Of Turkey

    Turkey, whose land mass is 780.000 sq km., is a beautiful country among three continents. Three sides of it is surrounded by seas. İts population is near to 65.000.000. Iraq and Syria at the south, Iran at the east, Georgia and Armenia at the nort-east, Russia at the north, Bulgaria at the north-west and Greece at the west are the neighbours of Turkey.

   Our country has lots of tourism centers. İf you like doing things like sking or mountain climbing, you can go to Uludağ. You can ski at Moun Uludağ from December to March. İf you love visiting historic places,you should see Termessos, Perge, Aspendos, Side(in the region of Antalya) the canyon of Ihlara, the underground cities of Derinkuyu and Kaymaklı(in region of cappodocia)The Temple of Artemis at Ephesus and the remains of the seven wonders of the world at Bodrum are worth visiting. The Manastery of Sumela in Maçka, the hazel nut growes in Ordu, the cherry orchards in Giresun and the untouched naturals beauties of black sea coast are fabulous place. You can spend your holidays on the high plateaus of Trobzon. İf you are a tea addict, you can go to Rize and drink tea in the beautiful  tea gardens by the sea.I advise you to go to Kırşehir to learn the Ahi Brotherhood. İf you want to know Mevlana and his religious beliefs, you must pass by Konya. The festival of the Dancing Dervishes can be see in December. İf you like lying on the beaches all day, the Mediterranean coasts and the Aegean Coasts are most suitable places for each person. You can get a suntan on thesandy beaches in these areas.

Atatürk’s mousoleum Atatürk’s house

Ankara On a hill overlooking the Turkish capital of Ankara is the monument to the man without whom have been reduced to little more than a patch of steppeland. General Mustafa Kemal roused a people already exhausted by the Ottoman defeat in the First World War, drove the invading forces into the sea, and won back for the Turks their homeland. Taking the name Atatürk or “Father of the Turks”, Mustafa Kemal founded the modern democratic Republic of Turkey, based on Western laws. İt was Atatürk who made the strategically placed Ankara Turkey’s capital, and the city is a monument to his vision of a modern westernized state.    Even around Ankara, this path of civilization stretches back a long way; to the Hittites, a proud and warlike people who ruled an empire from the Black Sea to Phrygians, a Thracian people who dominated the Anatolian plateau in the 1.millenium B.C

The Hittite capital of Hattusas(now called Boğazkale) lies 200km.to the north-east of Ankara. The craggy hillof Hattusas was ringed by double walls and its gates were guarded by lion statues. Close to Hattusas is the Hittite open air sanctuary  of Yazılıkaya, and also nearby is the Hittite city of Alacahöyük.      To the south-west of Ankara,near Polatlı,is the site of the Phrygian capital of Gordion, where Alexander the Great cut the famous Gordion knot that gave him the key to Asia. Also at Gordion is the great eart tumulus of King Midas, famed in the legend the Golden Touch.    Mirroring the ancient civilizations of the land  is Ankara’s Museum of Anatolian Civilizations(Archaelogical Museum),with its unique collection of proto-Hittite sun discs and stg cult figures,Hittite reliefs and phrygian metalwork.

Şekil 1Dovecotes Şekil 2in the Valley of Göreme Cappadocia Violent eruptions of the volcanoes Erciyes Dağı and Hasan Dağı three million years ago, covered the surrounding plateau with tuff. From this brittle rock the wind and rain have eroded Capadocia’s spectacular, surrealist landscape of rock cones, capped pinncles and fretted ravines, in colours ranging  from warm reds and gold to cool greens and greys.    Cappadocia is one of those rare regions in the world where the works of man blend unobtrusively into the landscape. Dwelling are known to have been hewn from the rock as far back as 400B.C., when xenophon mentioned them in his Anabasis. During Byzantine times chapels and monasteries were hollowed out of the rock, and their ochre toned frescoes simply reflect the hues of the surrounding landscape. Even today, troglodyte dwellings in rock cones and village houses of volcanic tuff merge harmoniously into the landscape.

Rocky peaks of Zelve Churches of Göreme The most interesting sites of the region include the rock chapels of Göreme, the troglodyte village of Avcılar, the red-coned monastic complex of Zelve, the villages of Ortahisar and Uçhisar clustered around rock pinnacles, the canyon of Ihlara and the underground cities of Kaymaklı and Derinkuyu. In the centre of region are the town of Neşehir and the village of Ürgüp, around which are most of the region’s best hotels, many of them having swimming pools.    On the fringe of the volcanic plateau are the cities of Kırsehir, Kayseri and Nigde, all once centres of the Seljuk Turks, whose art adds a different dimension to the region. İt is intriguing that just as the region was the centre for the development of Christian monasticism in the 4th century, so too it proved a fertile area for the development of Islamic mysticism, science and art. Two humanitarian Moslem sects, the Ahi Brotherhood and the Bektasi Dervishes,originated in Kırsehir and Hacıbektas respectively, and several interesting buildings associated with these sects can still be seen.

KONYA    Fanning out from the foothills of the Taurus Mountains is the Plain of Konya, one of the cradles of civilization. Here on the grasslands, in Neolithic times, the wild bull and leopard roamed, the animals that became the cult figures of Çatal Höyük, the world’s first city. This recently excavated site of 6500 B.C., where the houses were entered from the roofs, lies 50km. south of Konya near Çumra.    İt was not until the 12th century that the Konya Plain experienced its second cultural Renaissance, when the city became the capital of the Seljuk Turks.

Migrating from the stepps of Central Asia, the Seljuks served the Byzantines with a crushing defeat in 1071 at Malazgirt, which opened the floodgates to the Turkish settlement of Anatolia. Under the enlighted rule of the Sultan Aleaddin Keykubat, Seljuk culture reached its zenith in 13th century Konya. Seljuk art strikes a pefect balance between purity of line and intricacy of decoration, as reflected by Konya’s many beautiful buildings, such as the Aleaddin Mosque, the Karatay Medresesi and the İnce Minare Medresesi.

interiorof Mevlana’s Mausoeum    İn this atmosphere where learning and art flourished, one of the great Moslem mystic movements was born. This sect, known to the West as the Whirling Dervishes of Konya, was founded by Mevlana Celaleddin Rumi, a mystic poet, whose tolerance and humanity were quite exceptional for his age. There was not a trace of fanaticism in Mevlana, and he wished to encompass all men in his faith based on love.    As the symsol of the shedding of  earth ties, Mevlana devised the whirling dance, accompanied by the ethereal sound of the reed flute. This whirling dance can still be seen in December, during the Mevlana festival. Mevlana lies buried in a striking green tiled türbe or mausoleum, which is a site of Moslem pilgrimage. Attached to the mausoleum is now a museum of articles belonging to the order.

THE PROBLEMS OF THE PLANET

The rainforests are dying, rare plant and animal species are disappearing, rivers and seas are being contaminated, crops are failing to grow, people are dying of hunger and the air being polluted. It’s time we woke up to theese problems and started repairing the damage.

One of the major problems is the destruction of the rainforests. They are home to half the world’s species and to millions of people. Moreover, the rain forests clean the air by absorbing carbon dioxide and giving out oxygen. The trees are being cut down for paper or to make room for cattle farms. As a result, birds and animals lose their homes and die. This desturiction is also bringing about changes in the climate, air pollution, flooding, drought and famine. If we continue to burn and cut down the rainfores, the earth will never be the same again.

 

Another big problem is water pollution. Factories are polluting our rivers and lakes with dangerous chemicals. Oil tankers are releasing thick, black oil into our oceans. Tons and tons of industrial and domestic waste are poured into our seas. Consequently, sea life is threatened with extinction.

Air pollution is another important issue. The cars and factories in and around our cities are giving off dangerous fumes. In the past few years, more and more peoplethan ever before have devoloped allergies and breathing problems. If we don’t do something now, our cities will become imossible to live in.

Fortunately, it is too late to solve theese problems. We have the time, the money and even the technology to prepare the way for a better, cleaner and safer future. We can plant trees and adopt animals. We can create parks endangered species. We can put pressure on those in poer to take action. Together we can save our planet. All we need to do is open our eyes and act immediately.

Only when all the rivers have run dry

And all the fish in the sea have died

Only when all the rainforests have been burnt down

And there is no food  for animals

Only when all the blue skys have been filled with smoke

And the cities of the world have choked

Will the white man understand that it’s too it’s too late to save the earth

( Native American poem)     

                                                                

               

human

Introduction

The human immune system is a truly amazing constellation of responses to attacks from outside the body. It has many facets, a number of which can change to optimize the response to these unwanted intrusions. The system is remarkably effective, most of the time. This note will give you a brief outline of some of the processes involved.

An antigen is any substance that elicits an immune response, from a virus to a sliver.

The immune system has a series of dual natures, the most important of which is self/non-self recognition. The others are: general/specific, natural/adaptive = innate/acquired, cell-mediated/humoral, active/passive, primary/secondary. Parts of the immune system are antigen-specific (they recognize and act against particular antigens), systemic (not confined to the initial infection site, but work throughout the body), and have memory (recognize and mount an even stronger attack to the same antigen the next time).

Self/non-self recognition is achieved by having every cell display a marker based on the major histocompatibility complex (MHC). Any cell not displaying this marker is treated as non-self and attacked. The process is so effective that undigested proteins are treated as antigens.

Sometimes the process breaks down and the immune system attacks self-cells. This is the case of autoimmune diseases like multiple sclerosis, systemic lupus erythematosus, and some forms of arthritis and diabetes. There are cases where the immune response to innocuous substances is inappropriate. This is the case of allergies and the simple substance that elicits the response is called an allergen.

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Fluid Systems of the Body

There are two main fluid systems in the body: blood and lymph. The blood and lymph systems are intertwined throughout the body and they are responsible for transporting the agents of the immune system.

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The Blood System

The 5 liters of blood of a 70 kg (154 lb) person constitute about 7% of the body's total weight. The blood flows from the heart into arteries, then to capillaries, and returns to the heart through veins.

Blood is composed of 52–62% liquid plasma and 38–48% cells. The plasma is mostly water (91.5%) and acts as a solvent for transporting other materials (7% protein [consisting of albumins (54%), globulins (38%), fibrinogen (7%), and assorted other stuff (1%)] and 1.5% other stuff). Blood is slightly alkaline (pH = 7.40 ± .05) and a tad heavier than water (density = 1.057 ± .009).

All blood cells are manufactured by stem cells, which live mainly in the bone marrow, via a process called hematopoiesis. The stem cells produce hemocytoblasts that differentiate into the precursors for all the different types of blood cells. Hemocytoblasts mature into three types of blood cells: erythrocytes (red blood cells or RBCs),

leukocytes (white blood cells or WBCs), and thrombocytes (platelets).

The leukocytes are further subdivided into granulocytes (containing large granules in the cytoplasm) and agranulocytes (without granules). The granulocytes consist of neutrophils (55–70%), eosinophils (1–3%), and basophils (0.5–1.0%). The agranulocytes are lymphocytes (consisting of B cells and T cells) and monocytes. Lymphocytes circulate in the blood and lymph systems, and make their home in the lymphoid organs.

All of the major cells in the blood system are illustrated below.

There are 5000–10,000 WBCs per mm³ and they live 5-9 days. About 2,400,000 RBCs are produced each second and each lives for about 120 days (They migrate to the spleen to die. Once there, that organ scavenges usable proteins from their carcasses). A healthy male has about 5 million RBCs per mm³, whereas females have a bit fewer than 5 million.

Normal Adult Blood Cell Counts
Red Blood Cells		5.0*106/mm3
Platelets		2.5*105/mm3
Leukocytes		7.3*103/mm3
	Neutrophil		50-70%
	Lymphocyte		20-40%
	Monocyte		1-6%
	Eosinophil		1-3%
	Basophil		<1%

The goo on RBCs is responsible for the usual ABO blood grouping, among other things. The grouping is characterized by the presence or absence of A and/or B antigens on the surface of the RBCs. Blood type AB means both antigens are present and type O means both antigens are absent. Type A blood has A antigens and type B blood has B antigens.

Some of the blood, but not red blood cells (RBCs), is pushed through the capillaries into the interstitial fluid.

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The Lymph System

Lymph is an alkaline (pH > 7.0) fluid that is usually clear, transparent, and colorless. It flows in the lymphatic vessels and bathes tissues and organs in its protective covering. There are no RBCs in lymph and it has a lower protein content than blood. Like blood, it is slightly heavier than water (density = 1.019 ± .003).

The lymph flows from the interstitial fluid through lymphatic vessels up to either the thoracic duct or right lymph duct, which terminate in the subclavian veins, where lymph is mixed into the blood. (The right lymph duct drains the right sides of the thorax, neck, and head, whereas the thoracic duct drains the rest of the body.) Lymph carries lipids and lipid-soluble vitamins absorbed from the gastrointestinal (GI) tract. Since there is no active pump in the lymph system, there is no back-pressure produced. The lymphatic vessels, like veins, have one-way valves that prevent backflow. Additionally, along these vessels there are small bean-shaped lymph nodes that serve as filters of the lymphatic fluid. It is in the lymph nodes where antigen is usually presented to the immune system.

The human lymphoid system has the following:

• ·        primary organs: bone marrow (in the hollow center of bones) and the thymus gland (located behind the breastbone above the heart), and
• ·        secondary organs at or near possible portals of entry for pathogens: adenoids, tonsils, spleen (located at the upper left of the abdomen), lymph nodes (along the lymphatic vessels with concentrations in the neck, armpits, abdomen, and groin), Peyer's patches (within the intestines), and the appendix.

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Innate Immunity

The innate immunity system is what we are born with and it is nonspecific; all antigens are attacked pretty much equally. It is genetically based and we pass it on to our offspring.

Surface Barriers or Mucosal Immunity

1. The first and, arguably, most important barrier is the skin. The skin cannot be penetrated by most organisms unless it already has an opening, such as a nick, scratch, or cut.
2. Mechanically, pathogens are expelled from the lungs by ciliary action as the tiny hairs move in an upward motion; coughing and sneezing abruptly eject both living and nonliving things from the respiratory system; the flushing action of tears, saliva, and urine also force out pathogens, as does the sloughing off of skin.
3. Sticky mucus in respiratory and gastrointestinal tracts traps many microorganisms.
4. Acid pH (< 7.0) of skin secretions inhibits bacterial growth. Hair follicles secrete sebum that contains lactic acid and fatty acids both of which inhibit the growth of some pathogenic bacteria and fungi. Areas of the skin not covered with hair, such as the palms and soles of the feet, are most susceptible to fungal infections. Think athlete's foot.
5. Saliva, tears, nasal secretions, and perspiration contain lysozyme, an enzyme that destroys Gram positive bacterial cell walls causing cell lysis. Vaginal secretions are also slightly acidic (after the onset of menses). Spermine and zinc in semen destroy some pathogens. Lactoperoxidase is a powerful enzyme found in mother's milk.
6. The stomach is a formidable obstacle insofar as its mucosa secrete hydrochloric acid (0.9 < pH < 3.0, very acidic) and protein-digesting enzymes that kill many pathogens. The stomach can even destroy drugs and other chemicals.

Normal flora are the microbes, mostly bacteria, that live in and on the body with, usually, no harmful effects to us. We have about 10¹³ cells in our bodies and 10¹⁴ bacteria, most of which live in the large intestine. There are 10³–10⁴ microbes per cm² on the skin (Staphylococcus aureus, Staph. epidermidis, diphtheroids, streptococci, Candida, etc.). Various bacteria live in the nose and mouth. Lactobacilli live in the stomach and small intestine. The upper intestine has about 10⁴ bacteria per gram; the large bowel has 10¹¹ per gram, of which 95–99% are anaerobes (An anaerobe is a microorganism that can live without oxygen, while an aerobe requires oxygen.) or bacteroides. The urogenitary tract is lightly colonized by various bacteria and diphtheroids. After puberty, the vagina is colonized by Lactobacillus aerophilus that ferment glycogen to maintain an acid pH.

Normal flora fill almost all of the available ecological niches in the body and produce bacteriocidins, defensins, cationic proteins, and lactoferrin all of which work to destroy other bacteria that compete for their niche in the body.

The resident bacteria can become problematic when they invade spaces in which they were not meant to be. As examples: (a) staphylococcus living on the skin can gain entry to the body through small cuts/nicks. (b) Some antibiotics, in particular clindamycin, kill some of the bacteria in our intestinal tract. This causes an overgrowth of Clostridium difficile, which results in pseudomembranous colitis, a rather painful condition wherein the inner lining of the intestine cracks and bleeds.

A phagocyte is a cell that attracts (by chemotaxis), adheres to, engulfs, and ingests foreign bodies. Promonocytes are made in the bone marrow, after which they are released into the blood and called circulating monocytes, which eventually mature into macrophages (meaning "big eaters", see below).

Some macrophages are concentrated in the lungs, liver (Kupffer cells), lining of the lymph nodes and spleen, brain microglia, kidney mesoangial cells, synovial A cells, and osteoclasts. They are long-lived, depend on mitochondria for energy, and are best at attacking dead cells and pathogens capable of living within cells. Once a macrophage phagocytizes a cell, it places some of its proteins, called epitopes, on its surface—much like a fighter plane displaying its hits. These surface markers serve as an alarm to other immune cells that then infer the form of the invader. All cells that do this are called antigen presenting cells (APCs).

The non-fixed or wandering macrophages roam the blood vessels and can even leave them to go to an infection site where they destroy dead tissue and pathogens. Emigration by squeezing through the capillary walls to the tissue is called diapedesis or extravasation. The presence of histamines at the infection site attract the cells to their source.

Natural killer cells move in the blood and lymph to lyse (cause to burst) cancer cells and virus-infected body cells. They are large granular lymphocytes that attach to the glycoproteins on the surfaces of infected cells and kill them.

Polymorphonuclear neutrophils, also called polys for short, are phagocytes that have no mitochondria and get their energy from stored glycogen. They are nondividing, short-lived (half-life of 6–8 hours, 1–4 day lifespan), and have a segmented nucleus. [The picture below shows the neutrophil phagocytizing bacteria, in yellow.] They constitute 50–75% of all leukocytes. The neutrophils provide the major defense against pyogenic (pus-forming) bacteria and are the first on the scene to fight infection. They are followed by the wandering macrophages about three to four hours later.

The complement system is a major triggered enzyme plasma system. It coats microbes with molecules that make them more susceptible to engulfment by phagocytes. Vascular permeability mediators increase the permeability of the capillaries to allow more plasma and complement fluid to flow to the site of infection. They also encourage polys to adhere to the walls of capillaries (margination) from which they can squeeze through in a matter of minutes to arrive at a damaged area. Once phagocytes do their job, they die and their "corpses," pockets of damaged tissue, and fluid form pus.

Eosinophils are attracted to cells coated with complement C3B, where they release major basic protein (MBP), cationic protein, perforins, and oxygen metabolites, all of which work together to burn holes in cells and helminths (worms). About 13% of the WBCs are eosinophils. Their lifespan is about 8–12 days. Neutrophils, eosinophils, and macrophages are all phagocytes.

Dendritic cells are covered with a maze of membranous processes that look like nerve cell dendrites. Most of them are highly efficient antigen presenting cells. There are four basic types: Langerhans cells, interstitial dendritic cells, interdigitating dendritic cells, and circulating dendritic cells. Our major concern will be Langerhans cells, which are found in the epidermis and mucous membranes, especially in the anal, vaginal, and oral cavities. These cells make a point of attracting antigen and efficiently presenting it to T helper cells for their activation. [This accounts, in part, for the transmission of HIV via sexual contact.]

Each of the cells in the innate immune system bind to antigen using pattern-recognition receptors. These receptors are encoded in the germ line of each person. This immunity is passed from generation to generation. Over the course of human development these receptors for pathogen-associated molecular patterns have evolved via natural selection to be specific to certain characteristics of broad classes of infectious organisms. There are several hundred of these receptors and they recognize patterns of bacterial lipopolysaccharide, peptidoglycan, bacterial DNA, dsRNA, and other substances. Clearly, they are set to target both Gram-negative and Gram-positive bacteria.

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Adaptive or Acquired Immunity

Lymphocytes come in two major types: B cells and T cells. The peripheral blood contains 20–50% of circulating lymphocytes; the rest move in the lymph system. Roughly 80% of them are T cells, 15% B cells and remainder are null or undifferentiated cells. Lymphocytes constitute 20–40% of the body's WBCs. Their total mass is about the same as that of the brain or liver. (Heavy stuff!)

B cells are produced in the stem cells of the bone marrow; they produce antibody and oversee humoral immunity. T cells are nonantibody-producing lymphocytes which are also produced in the bone marrow but sensitized in the thymus and constitute the basis of cell-mediated immunity. The production of these cells is diagrammed below.

Parts of the immune system are changeable and can adapt to better attack the invading antigen. There are two fundamental adaptive mechanisms: cell-mediated immunity and humoral immunity.

 Cell-mediated immunity

Macrophages engulf antigens, process them internally, then display parts of them on their surface together with some of their own proteins. This sensitizes the T cells to recognize these antigens. All cells are coated with various substances. CD stands for cluster of differentiation and there are more than one hundred and sixty clusters, each of which is a different chemical molecule that coats the surface. CD8+ is read "CD8 positive." Every T and B cell has about 10⁵ = 100,000 molecules on its surface. B cells are coated with CD21, CD35, CD40, and CD45 in addition to other non-CD molecules. T cells have CD2, CD3, CD4, CD28, CD45R, and other non-CD molecules on their surfaces.

The large number of molecules on the surfaces of lymphocytes allows huge variability in the forms of the receptors. They are produced with random configurations on their surfaces. There are some 10¹⁸ different structurally different receptors. Essentially, an antigen may find a near-perfect fit with a very small number of lymphocytes, perhaps as few as one.

T cells are primed in the thymus, where they undergo two selection processes. The first positive selection process weeds out only those T cells with the correct set of receptors that can recognize the MHC molecules responsible for self-recognition. Then a negative selection process begins whereby T cells that can recognize MHC molecules complexed with foreign peptides are allowed to pass out of the thymus.

Cytotoxic or killer T cells (CD8+) do their work by releasing lymphotoxins, which cause cell lysis. Helper T cells (CD4+) serve as managers, directing the immune response. They secrete chemicals called lymphokines that stimulate cytotoxic T cells and B cells to grow and divide, attract neutrophils, and enhance the ability of macrophages to engulf and destroy microbes. Suppressor T cells inhibit the production of cytotoxic T cells once they are unneeded, lest they cause more damage than necessary. Memory T cells are programmed to recognize and respond to a pathogen once it has invaded and been repelled.

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Humoral immunity

An immunocompetent but as yet immature B-lymphocyte is stimulated to maturity when an antigen binds to its surface receptors and there is a T helper cell nearby (to release a cytokine). This sensitizes or primes the B cell and it undergoes clonal selection, which means it reproduces asexually by mitosis. Most of the family of clones become plasma cells. These cells, after an initial lag, produce highly specific antibodies at a rate of as many as 2000 molecules per second for four to five days. The other B cells become long-lived memory cells.

Antibodies, also called immunoglobulins or Igs [with molecular weights of 150–900 Md], constitute the gamma globulin part of the blood proteins. They are soluble proteins secreted by the plasma offspring (clones) of primed B cells. The antibodies inactivate antigens by, (a) complement fixation (proteins attach to antigen surface and cause holes to form, i.e., cell lysis), (b) neutralization (binding to specific sites to prevent attachment—this is the same as taking their parking space), (c) agglutination (clumping), (d) precipitation (forcing insolubility and settling out of solution), and other more arcane methods.

Constituents of gamma globulin are: IgG-76%, IgA-15%, IgM-8%, IgD-1%, and IgE-0.002% (responsible for autoimmune responses, such as allergies and diseases like arthritis, multiple sclerosis, and systemic lupus erythematosus). IgG is the only antibody that can cross the placental barrier to the fetus and it is responsible for the 3 to 6 month immune protection of newborns that is conferred by the mother.

IgM is the dominant antibody produced in primary immune responses, while IgG dominates in secondary immune responses. IgM is physically much larger than the other immunoglobulins.

Notice the many degrees of flexibility of the antibody molecule. This freedom of movement allows it to more easily conform to the nooks and crannies on an antigen. The upper part or Fab (antigen binding) portion of the antibody molecule (physically and not necessarily chemically) attaches to specific proteins [called epitopes] on the antigen. Thus antibody recognizes the epitope and not the entire antigen. The Fc region is crystallizable and is responsible for effector functions, i.e., the end to which immune cells can attach.

Lest you think that these are the only forms of antibody produced, you should realize that the B cells can produce as many as 10¹⁴ conformationally different forms.

The process by which T cells and B cells interact with antigens is summarized in the diagram below.

In the ABO blood typing system, when an A antigen is present (in a person of blood type A), the body produces an anti-B antibody, and similarly for a B antigen. The blood of someone of type AB, has both antigens, hence has neither antibody. Thus that person can be transfused with any type of blood, since there is no antibody to attack foreign blood antigens. A person of blood type O has neither antigen but both antibodies and cannot receive AB, A, or B type blood, but they can donate blood for use by anybody. If someone with blood type A received blood of type B, the body's anti-B antibodies would attack the new blood cells and death would be imminent.

All of these of these mechanisms hinge on the attachment of antigen and cell receptors. Since there are many, many receptor shapes available, WBCs seek to optimize the degree of confluence between the two receptors. The number of these "best fit" receptors may be quite small, even as few as a single cell. This attests to the specificity of the interaction. Nevertheless, cells can bind to receptors whose fit is less than optimal when required. This is referred to as cross-reactivity. Cross-reactivity has its limits. There are many receptors to which virions cannot possibly bind. Very few viruses can bind to skin cells.

The design of immunizing vaccines hinges on the specificity and cross-reactivity of these bonds. The more specific the bond, the more effective and long-lived the vaccine. The smallpox vaccine, which is made from the vaccinia virus that causes cowpox, is a very good match for the smallpox receptors. Hence, that vaccine is 100% effective and provides immunity for about 20 years. Vaccines for cholera have a relatively poor fit so they do not protect against all forms of the disease and protect for less than a year.

The goal of all vaccines is promote a primary immune reaction so that when the organism is again exposed to the antigen, a much stronger secondary immune response will be elicited. Any subsequent immune response to an antigen is called a secondary response and it has

1. a shorter lag time,
2. more rapid buildup,
3. a higher overall level of response,
4. a more specific or better "fit" to the invading antigen,
5. utilizes IgG instead of the large multipurpose antibody IgM.

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Summary

Immunity can be either natural or artificial, innate or acquired=adaptive, and either active or passive.

• Active natural (contact with infection): develops slowly, is long term, and antigen specific.
• Active artificial (immunization): develops slowly, lasts for several years, and is specific to the antigen for which the immunization was given.
• Passive natural (transplacental = mother to child): develops immediately, is temporary, and affects all antigens to which the mother has immunity.
• Passive artificial (injection of gamma globulin): develops immediately, is temporary, and affects all antigens to which the donor has immunity.

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Objectives

Know: antigen, overall properties of the immune system, allergen; major fluid systems of the body; hematopoiesis occurs in stem cells of the bone; erythrocytes, leukocytes, and thrombocytes; types of white blood cells; lymphoid system and lymph nodes; mucosal immunity and types of surface barriers to infection; normal flora; phagocytes, macrophages, antigen presenting cells, neutrophils, B cells and T cells are produced in the bone marrow and T cells are primed in the thymus, CD4+ and CD8+ cells, helper cells, memory cells, cytotoxic cells, suppressor cells; priming and clonal selection; antibody and Ig's; differences between identifying self and non-self, innate and acquired immunity, primary and secondary immunity, active and passive immunity; specificity and cross-reactivity