Red soil develops on crytalline igneous rocks in areas of low rainfall in the eastern and southern part of the Deccan Plateau. Along the piedmont zone of the Western Ghat, long stretch of area is occupied by red loamy soil. Yellow and red soils are also found in parts of Odisha and Chattisgarh and in the southern parts of the middle Ganga plain.
Characteristics:
1. The soil develops a reddish colour due to a wide diffusion of iron in crystalline and metamorphic rocks.
2. It looks yellow when it occurs in a hydrated form.
3. The fine-grained red and yellow soils are normally fertile,
4. whereas coarse-grained soils found in dry upland areas are poor in fertility.
5. They are generally poor in nitrogen, phosphorous and humus.

Principles of cancer immunotherapy
Clinical oncology for students > Principles of cancer immunotherapy
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Information on authorship and revision

Last modified:
29 November 2016 09:57:06

Author(s):

    Dr Craig Gedye — Author
    Cancer Council Australia Oncology Education Committee — Co-author

      Cite this page

Contents

    1 Introduction
    2 The immune system
    3 Controlling the immune system: immune checkpoints
    4 Cancer immunosurveillance and immunoevasion
    5 Spectrum of cancer immunotherapy
    6 Active non-specific cancer immunotherapy
    7 Active specific cancer immunotherapy
    8 Passive non-specific cancer immunotherapy
    9 Passive specific cancer immunotherapy
    10 Immune checkpoint inhibitors
    11 Mechanism of action of immune checkpoint inhibitors
    12 Current examples of immune checkpoint inhibitors
    13 Side effects of checkpoint immunotherapy antibodies
    14 Managing side-effects of immune checkpoint cancer immunotherapy
    15 Managing expectations of immune checkpoint cancer immunotherapy

Introduction

Cancer immunotherapy has a long history, but has rapidly developed since 2010. The goals of cancer immunotherapy are to kill or control cancer cells by activating, or reactivating the immune system.

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The immune system

Our immune systems have evolved to a complex system involving innate and adaptive immune systems. Innate immunity starts with physical barriers (skin, mucus), and involves non-specific defences from immune cells such as neutrophils and natural killer cells. The adaptive immune system has evolved from innate immune cells, which include B-cells that produce antibodies, and is governed by lymphocytes, primarily alpha/beta, which include CD4+ helper, CD8+ killer and FOXP3+ regulatory T-cells.

The adaptive immune system is most relevant in managing the immune system, addressing viral infections, and has evolved to be the most important part of the immune system in terms of controlling and eliminating cancer.

Adaptive immune cells recognise other cells via antigen presentation. A small peptide fragment of a native, viral or cancer protein (the antigen or epitope) is “presented” on a cell surface complex made of proteins called the major histocompatibility complex (MHC). These epitopes are then recognised by proteins (e.g. the T-cell receptor, TCR) on the surface of individual T- or B-cell lymphocytes (Figure A). The repertoire of human T-cells and B-cells can recognise up to 109 individual patterns. The outcome of antigen presentation and recognition is determined by the balance of interactions between pairs of immune checkpoint costimulatory molecules (e.g. CTLA4-CD80, OX40-OX30L, CD154-CD40, PD1-PDL1; Figure B below).

Figures A and B

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Controlling the immune system: immune checkpoints

Uncontrolled immune activation leads to autoimmune diseases like ulcerative colitis, dermatitis and interstitial pneumonitis. The activity of the immune system is modulated and carefully controlled by costimulatory molecules called immune checkpoints. When antigen recognition occurs, a committee of other molecules interact on the surface of the immune cell and the target cell to determine the balance of the interaction. If the signals are largely positive, the immune cell activates and is primed to attack the antigen presented by the target cell. However if the balance of signals is negative, then the immune cell can become inactivated, sometimes permanently, and the antigen is accepted as a normal/self antigen (Figure B). Immune checkpoints of relevance to cancer include CTLA4, PD1 and PDL1 (see above).

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Cancer immunosurveillance and immunoevasion

Every cancer that becomes clinically detectable and relevant has survived elimination by the immune system. As soon as tiny cancers form, the aberrant proteins they express from mutated genes generate so-called “neoantigens” that can be recognised by the immune system by antigen presentation, targeting the aberrant cell for destruction.

Cancers are edited by this process, and may be eliminated at this point; so called immunosurveillance. Some cancers can enter a state of equilibrium with the immune system, and though present, remain clinically undetectable and irrelevant. If this balance is then later disturbed, for example by immunosuppression caused by age, illness or iatrogenic causes, the cancer can escape and evade immune control.

Cancer immunotherapies attempt to redress these escape mechanisms at many points, but a key mechanism for cancer cells to evade the immune system seems to be via negative immune checkpoint signalling (Figure C).

Figure C

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Spectrum of cancer immunotherapy

Cancer immunotherapies can be categorised by whether:

    they actively stimulate the immune system, or passively alter immune system signalling or cell populations, and,
    the treatment is targeted at a specific, known antigenic target, or is non-specifically stimulating the immune system.

Spectrum of cancer immunotherapy
(adapted from Davis et al., 2000)

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Active non-specific cancer immunotherapy

    Bacillus Calmette-Guerin (BCG) is one of the most commonly used and earliest discovered cancer immune therapies. This live attenuated strain of Mycobacterium tuberculosis is instilled intravesically to reduce recurrence of debulked non-muscle invasive bladder cancer. The mechanism of action is a non-specific inflammatory reaction; side effects can include dysuria and other lower urinary tract symptoms.
    Immunostimulatory cytokines such as interferon-alpha and interleukin-2 were previously mainstay treatments of metastatic renal-cell carcinoma and melanoma. Interferon-alpha was used as adjuvant therapy in resected high-risk melanoma, though the survival advantage was debatable. Interleukin-2 is still used in some countries in a limited highly restricted patient population. Treatment requires ICU admission due to severe systemic inflammatory responses and hypotension. A proportion of patients who took IL2 have experienced long-term remission of their cancer.
    Oncolytic viruses such as T-VEC (talimogene laherparepvec) and CAVATAK® (Coxsackievirus A21) are attenuated or modified viruses that can be injected directly into tumour masses or administered intravenously. Infection of tumour cells is associated with activation of an immune response, that in some patients can even spread to other, uninjected tumour sites (the “abscopal” effect). Many viruses are being explored, but none are yet in routine clinical practice.

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Active specific cancer immunotherapy

    Cancer vaccines have been trialled in many different formats, but all attempt to direct the immune system to recognise particular antigens that are then hoped to cause recognition and elimination of the cancer. Cancer vaccines can target a single peptide, a protein, or autologous or allogenic cancer cells. Unfortunately most of these vaccines have failed to improve patient outcomes. Sipeleucel-T is an allogeneic vaccine using prostate cancer cell lines that has a modest effect in prostate cancer, but is not available in Australia.
    Oncogenic virus vaccines are the most common and important form of cancer immunotherapy. Vaccines that prevent infection by the hepatitis B virus (causing hepatocellular carcinoma) or the human papillomavirus (causing cervical, ****, penile and some head and neck cancers) are internationally and numerically the most effective and most cost-effective cancer immunotherapies available.
    CAR-T-cells are autologous patient derived T-cells, that have been genetically modified to display cancer cell recognition molecules on their cell surface. In isolated cases these have generated extraordinary responses (e.g. CD19+ paediatric B-ALL) but with considerable toxicity.

पेट की आग का शमन ईश्वर (राम) भक्ति का मेघ ही कर सकता है-तुलसी का यह काव्य-सत्य समकालीन युग में भी सत्य था और आज भी सत्य है। राम को तुलसी ने घनश्याम कहा है। तुलसी प्रभु की कृपा को पेट की आग शमन के लिए आवश्यक मानते हैं। उनकी दृष्टि में ईश्वर भक्ति एक मेघ के समान है। उनकी कृपा का जल हमें चाहिए।

तुलसी का यह काव्य-सत्य इस समय का युग सत्य तब बन सकता है जब भक्ति के साथ प्रयास भी करें। केवल भक्ति करने से फल की प्राप्ति होने वाली नहीं है। प्रभु की प्रार्थना में भक्ति और पुरुषार्थ दोनों का संगम होना आवश्यक है। केवल भक्ति के बल पर बैठा रहने वाला व्यक्ति निकम्मा हो जाता है। प्रयत्न की भी बड़ी महिमा है।

पेट की आग का शमन ईश्वर (राम) भक्ति का मेघ ही कर सकता है-तुलसी का यह काव्य-सत्य समकालीन युग में भी सत्य था और आज भी सत्य है। राम को तुलसी ने घनश्याम कहा है। तुलसी प्रभु की कृपा को पेट की आग शमन के लिए आवश्यक मानते हैं। उनकी दृष्टि में ईश्वर भक्ति एक मेघ के समान है। उनकी कृपा का जल हमें चाहिए।

तुलसी का यह काव्य-सत्य इस समय का युग सत्य तब बन सकता है जब भक्ति के साथ प्रयास भी करें। केवल भक्ति करने से फल की प्राप्ति होने वाली नहीं है। प्रभु की प्रार्थना में भक्ति और पुरुषार्थ दोनों का संगम होना आवश्यक है। केवल भक्ति के बल पर बैठा रहने वाला व्यक्ति निकम्मा हो जाता है। प्रयत्न की भी बड़ी महिमा है।

The CPU is the computer hardware component that's responsible for interpreting and executing most of the commands from the computer's other hardware and software. It is used to manipulate data-is responsible for carrying out arithmetic and logic functions.

Question : Palk strait and Gulf of Mannar separate which two countries?

Chapter: India Size and Location
A n s w e r:
Palk strait and Gulf of Mannar separate India and Srilanka.

The basic rights of women are explained below:

(i) Woman is born free and remains equal to man in rights.

(ii) The goal of all political associations is the preservation of the natural rights of woman and man. These rights are liberty, property, security and above all resistance to oppression.

(iii) The source of all sovereignty resides in the nation, which is nothing but the union of woman and man.

(iv) The law should be the expression of the general will, all female and male citizens should have a say either personally or by their representatives in its formulation.

(v) No woman is an exception, she is accused, arrested and detained in cases determined by law, woman, like man, obey this rigorous law.

(i) The revolutionary ideas of the French Revolution i.e. equality and liberty changed the clothes people wore, the language they spoke and the books they read. Laws were passed to translate these ideals into everyday practice.
(ii) One important law that came into effect soon after the storming of the Bastille in 1789 was the abolition of censorship. In the Old Regime all written material and cultural activities could be published or performed only after they had been approved by the censors of the king.
(iii) Now the "Declaration of the Rights of Man and Citizen" proclaimed freedom of speech and expression to be a natural right. As a result, newspapers, pamphlets, books and printed pictures flooded the towns of France from where they travelled rapidly into the countryside. They all described and discussed the events and changes taking place in France.
(iv) Freedom of press also meant that opposing views of events could be expressed. Each side sought to convince the others of its position through the medium of print.
(v) Plays, songs and festive processions attracted large numbers of people. The visual and oral art forms became very popular among the common mass which could not read and write in the 18th century.
(vi) The majority of men and women could now easily understand the ideas ofequality, liberty and justice.
Thus, the everyday life of the French people was deeply affected by the revolution.

• Before the French Revolution in 1789, France had three colonies of the Caribbean - Martinique, Guadeloupe and San Domingo under its control. These places were major suppliers of sugar, coffee, indigo and tobacco.
•  The triangular slave trade between Europe, Africa and America began in the 17th century.
•  Merchants sailed from the French ports to the African coast where they bought Negroes, who are natives of Africa, from the local chieftains.
•  Port cities like Bordeaux and Nantes were flourishing economically because of the slave trade.
•  The National Convention voted to abolish slavery in all the French colonies on February 4, 1794.
•  Slavery was reintroduced in the French colonies by Napoleon Bonaparte. Slavery was finally abolished in 1848 by the French Second Republic.

• Women were active participants in the French Revolution. Women in France were not empowered.
• Most of the women of the third estate had to work to earn their livelihood. They worked as seamstresses, sold flowers and vegetables or worked as domestic servants in the houses of wealthy families.
• Women started their own clubs in order to raise their own voices. A famous women’s club was the Society of Revolutionary Republican Women. This club demanded that women be given the same political rights as men. Women till now had no right to vote.
• In the beginning, many laws were implemented to improve the condition of women in French society. Schooling was made compulsory for all girls. Fathers could no longer marry off their daughters without obtaining their consent. Divorce was made legal, and women began to be trained for various jobs.
• Olympe de Gouges was politically active in revolutionary France. She protested against the Constitution and the Declaration of Rights of Man and Citizen because they did not even give basic political rights to women
• During the Reign of Terror, many laws were issued which ordered the closing of women’s clubs. Many women were tried and guillotined. 
• Women’s struggle to demand equal voting rights however continued. The French women were finally granted voting rights in 1946.

Verbal communication is any communication that uses words to share information with others. These words may be both spoken and written.

If we consider poor democracies and all dictatorships for the fifty years between 1950 and 2000, dictatorships have higher rate of economic growth. The inability of democracy to achieve higher economic development is a matter of worry. When we compare record of dictatorial regimes with democracies in poor countries, then we find them in upper hands.

The leaden heart of the Happy Prince and the dead swallow are the two most precious things mentioned in the story.

They are precious because the Happy Prince was kind and served the poor and the needy by providing them with the last resource of his statue to bring back a little happiness in their lives. The bird was always been his faithful messenger and helped him helping the unprivileged. When God asks an angel to bring two precious things in the city, it brings him the leaden heart of the Happy Prince and the dead swallow.

A rule is an explicit statement that tells an employee what he or she can and cannot do. Rules are “do” and “don't” statements put into place to promote the safety of employees and the uniform treatment and behavior of employees. For example, rules about tardiness and absenteeism permit supervisors to make discipline decisions rapidly and with a high degree of fairness. Hence this plan is least flexible.