Scailyte Announces Its New Advisory Board, Composed of World Leading Clinicians and Scientists – EconomyWatch.com

March 31, 2020 medical

SURSEE, Switzerland-March 31, 2020- (Newswire.com)

Scailyte is an ETH Zurichspin-off and Top 100 Swiss Startup applying artificial intelligence to discover novel and ultra-sensitive biomarkers from single-cell data. Over the past threeyears, it has established ScaiVision, a proprietary data analytics platform for clinical research, which enables it to achieve groundbreaking discoveries in multiple disease areas. Scailyte has validated its approach by discovering its first single-cell biomarker for the detection of skin T-cell lymphoma, which it iscurrently translating into an in vitro diagnostics application that will radically improve the diagnosis and survival chances for thousands of patients suffering from this disease. Scailyteisscaling up its efforts by applying itsbiomarker discovery approach for multiple indications in oncology and womens health. In order to strengthen Scailytes discovery potential and provide strategic guidance, ithasappointed a scientific advisory board consisting of world-leading clinicians and scientists. The scientific advisory board is being led by Scailyte's co-founder, Professor Dr. Manfred Claasen.

Scailytes mission is to provide better healthcare and transform diagnostics, with particular focus on diseases with high unmet diagnostic need. With the rise of novel single-cell technologies, we are now in the unique position to leverage the potential of high dimensional single-cell data, and Scailyte is at the forefront of turning this potential into clinical applications, says Prof. Claassen

Prof. Dr. Manfred Claassen has been recently appointed as full professor in Clinical Bioinformatics at the University Hospital of Tubingen,with a focus on machine learning for single-cell biology and precision medicine. Prof. Claassen is an alumnus of the University of Tubingen and obtained his PhD from ETH Zurich. He did postdoctoral studies at Stanford University, where he pioneered research in single-cell data analysis and subsequently started his independent research group at ETH Zurich. This activity resulted in the key developments of an algorithm that paved the way for Scailytes innovative implementation of deep learning approaches for cell identity biomarker discovery.

Prof. Dr. Emmanuella Guenova is a dermatologist, specialist in cutaneous lymphoma and laboratory diagnostics of skin diseases, and appointed professor at the Faculty of Biology and Medicine of the University of Lausanne. She is a senior physician-scientist, leading the specialized cutaneous lymphoma clinic at the Department of Dermatology of the Lausanne University Hospital (CHUV). Prof. Guenova is supporting Scailyte as a clinical advisor and principal investigator in its clinical development program for cutaneous T-cell lymphoma.

Prof. Dr. Michael Mueller is a renowned gynecologist and gynecological oncologist, and managing director of the Women's Health Clinic at the University Hospital of Bern (Inselspital). Prof. Mueller is supporting Scailyte as a clinical advisor and expert in endometriosis and womens health.

Prof. Dr. Tomas Kalina is a physician and a cytometry expert currently leading a research group focused on disorders of adaptive immunity at the Charles University in Prague. Professor Kalina is supporting Scailyte as a clinical diagnostic advisor with his expertise in cytometry standardization.

Prof. Dr. Petter Brodin is a pioneer in single-cell analysis and is advising Scailyte in immunology and the application of single-cell technologies for clinical research. Prof. Brodin is based at the Karolinska Institute in Sweden and heads a research group that focuses on systems level analyses of the human immune system. Prof. Brodin is a consultant pediatrician working at the Karolinska University Hospital

Dr. Michael Stadler received training in immunology and bioinformatics from the Universities of Lausanne and Geneva. He is a scientific advisor supporting Scailytes with the development of itsdata analytics platform.After postdoctoral studies in Bern and at the Massachusetts Institute of Technology (MIT), he joined the Friedrich Miescher Institute for Biomedical Research (FMI) Basel, where he is a staff scientist and leads the computational biology group.

About Scailyte

Scailyte AG is a data-driven biomarker discovery company, founded in Luzern, Switzerland in 2017. The ETH Spin-off is using cutting edge technologies within the single-cell space and a proprietary biomarker discovery platform to develop clinical diagnostic applications in oncology and womens health. Scailyte is ranked among the Top100 Swiss Startups since 2019 and has won the MassChallenge Switzerland in 2018.

http://www.scailyte.com

Scailyte and ScaiVision are registered trademarks proprietary to Scailyte AG.

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Scailyte Announces Its New Advisory Board, Composed of World Leading Clinicians and Scientists - EconomyWatch.com

Immunology

Immunology News, Articles and Research

March 31, 2020 medical

What is Immunology?

Immunology is the branch of biomedical science that deals with the response of an organism to antigenic challenge and its recognition of what is self and what is not. It deals with the defence mechanisms including all physical, chemical and biological properties of the organism that help it to combat its susceptibility to foreign organisms, material, etc.

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Immunology News, Articles and Research

Immunology

FREE Basic Immunology Lecture Notes, Study Guide and Exam Help

March 31, 2020 medical

Basic Immunology Lecture Notes

My basic immunology exam notes were the first set of basic immunology exam notes here at this medical school that provided a FIRM BASIC UNDERSTANDING of immunology as a science, and put the deeper material of the subject into much needed context. The basic immunology exam notes previously written by other talented students here at this medical school were almost completely devoid of this basic understanding, and this rendered the deeper material contained within their pages almost completely useless for the average medical student. Though the basic knowledge of my basic immunology exam notes were incorporated at the cost of some of the deeper knowledge, this set of exam notes has already rendered several honorary students depicted on the walls of the immunology department.

Please click on the set of exam notes of interest to start downloading them.

By the time I picked up my pencil to start writing the immunology exam notes I was on the verge of a complete psychological breakdown. The constant pressure of always having to write unparalleled exam notes in every single last major subject I was undertaking had worn me down to a shadow of myself, and at times the pencil would hardly move across the paper on which I was writing. This resulted in the 5 last questions of this set of exam notes never being written, and at several occations I was seriously considering not even appearing at the exam. However, I pulled myself together and passed the exam with dignity, and mere days later I was on my way back home to Norway. I remained in Norway for the following couple of semesters until I had regenerated sufficiently to continue my studies here at this medical school. The immunology exam notes are still one of the most cherished immunology exam notes here at this medical school, but they came to be at a much greater cost than anyone could ever have imagined on beforehand.

The original copy of these exam notes bore the following words on its cover page:

"So tired I lay down these memories,I breathe shallow deep inside of me,time has run its course with me......I'm ready to go home."

This set of lecture notes has been downloaded times.

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Immunology

Immunology | Armando Hasudungan

March 31, 2020 medical

Our body defenses help ward off damage and disease. Together these defenses make up our immune system. Functionally, the immune system can be divided into the innate and adaptive. The Innate immune system is our non-specific first line of defense and is functional already at birth. The Adaptive immune system is specific and involves recognition of foreign bodies once they breached the innate immunity defenses. The Adaptive immunity is constantly upgrading itself by learning.The immune system plays a key role in nearly all diseases and infections, but can become an unwelcome player in autoimmune diseases, hypersensitivity and some allergies.

Topics: Immune System | Medical Anatomy and Physiology | Immunology Map | Disease

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Immunology | Armando Hasudungan

Immunology

Immunology Conferences 2020 | Immunology Conferences …

March 31, 2020 medical

Scientific Sessions

The state in which the immune system of the body becomes prone to Infectious diseases and cancer or becomes incapable of fighting the foreign bodies is termed as immunodeficiency. The two kinds of immunodeficiencies are primary immunodeficiency and secondary immunodeficiency. Secondary immunodeficiency is found to be the most common type of immunodeficiency. Immunodeficiency can be tackled either by proper treatment of the infection or by enhancing the immune system. The causes of immunodeficiency differ with the type of deficiency. Some of the prime reasons are improper sanitation, genetic and malnutrition. Certain immunodeficiencies are lifelong conditions, whereas some induce early mortality.

Related conferences

Diabetes Physiology and Management Conference, Vienna (Jun 18-19, 2020); Emerging Focus in Diabetes Research Conference, Toronto (Jun 18-19, 2020); Hematology and Blood Disorders Conference, Riga (Jun 18-19, 2020); Healthcare of Pediatric Immunology and Pediatric Heart Diseases Conference, Vienna (Jun 18-19, 2020

Related societies

American Academy of Allergy, American Association of Immunologists, National Institute of Allergy & Infectious Diseases, Canadian Society for Immunology, British Society for Immunology, German Society for Immunology, Finnish Society for Immunology

2. Transplant immunology

Transplantation immunology deals with the replacement of cells, tissues or organs from one part of the body to another or from one individual to another in order to restore damaged or diseased tissues or organs. The transplant can be seen by the immune system as a threat and may get destroyed or attacked by the immune system. If this happens the organ dies in less than half an hour time period as it cannot withstand the immune system outbreak. The donor is carefully analysed and matched in order to avoid any risk of transplant rejection. Immunosuppressants are taken to prevent transplant rejection or to treat the transplant rejection. The drawback of immunosuppressive drugs is that, they may leave the patients with various side effects.

Related conferences

Allergy Vaccines in Immunology Conference, Stockholm (Jul 16-17, 2020); Clinical and Experimental Immunology Conference, Toronto (Jul 16-17, 2020); Characterization of Healthcare Data Conference, Toronto (Jul 16-17, 2020); Diabetes Research and Management Conference, Stockholm (Jul 16-17, 2020)

Related societies

British Society for Allergy and Clinical Immunology, European Academy of Allergology and Clinical Immunology, Russian Society for Immunology, European Federation of Immunological Societies, Australasian Society for Immunology, Indian Immunology Society, Korean Society for Immunology

3. Immunotherapy

Immunotherapy is a diagnostic method that involves either enhancement of the immune system or the hindering of the immune system. Immunotherapy is one of the most commonly used treatment for cancer. Immunotherapies are of two types, activation immunotherapies and suppression immune therapies. Immunotherapies have been proved to treat various kinds of tumours. Immunotherapies used in cancer are mostly biological therapies, that is, they use substances made from living organisms. Checkpoint inhibitors, adoptive cell transfer, monoclonal antibodies etc are the types of immunotherapy that are used in cancer.

Related conferences

Advances in Cellular Immunology and Allergy Research Conference, Montreal (Aug 04-05, 2020); Immunotherapy and Immunology Conference, Montreal (Aug 04-05, 2020); Latest Developments in Cellular and Molecular Immunology Conference, Montreal (Aug 04-05, 2020); Medical Immunology Analysis Techniques Conference, Montreal (Aug 04-05, 2020); Advancements in Cellular Immunology and Immunotherapy Techniques Conference, Vancouver (Aug 06-07, 2020)

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Japanese Society for Immunology, Clinical Immunology Society, Society for Immunology and Immunopathology, Turku Immunology Centre, Canadian Society of Allergy and Clinical Immunology, Cuban Society for Immunology, Norwegian Society for Immunology

4. Immunology of pregnancy

The immune system of the mother (maternal immune system) plays an important role in the completion of a healthy pregnancy. In complex terms, pregnancy is a multifaceted immunological condition. So, it is important to assess the many immunological processes during this period. A successful pregnancy needs a healthy, active and responsive immune system. The fetal and maternal survival can be directly affected by the immune responses that are associated with them. Pregnancy is also considered as a phase characterized by high risk of bacterial and viral infection. The proper development and functioning of both the placenta and fetus are governed by various cells and molecules of the immune system.

5. Microbiome and epigenetics

In the recent years the fields of human epigenetics and human microbiome research have received significant attention. The ultimate environmental trigger for development is the host-associated microbiome. It has also been proved that the gut microbiome and cancer is linked. Certain microbial species are existing more commonly in cancer tissue than in flanking normal tissue throughout the development of disease, from early cancer growth to metastasisepigenetic processes, because of its spatial site and capability to convert environmental and diet-derived compounds before they reach human cells. The relationship between the gut microbiome and disease associate both the microbiome composition in general and specific microbial species in disease.

6. Microbiology

Microbiology is a branch of science that deals with microscopic organisms, such as bacteria, viruses, archaea, fungi and protozoa. It also includes essential research on the biochemistry, physiology, cell biology, ecology, evolution and clinical aspects of microorganisms, including the host response to these agents. Microbiology is used to understand about all characteristics of the organisms in order to define how they live in their environment and how they influence their surroundings and thus other organisms around them. Microbiology has proved to be one of the most important specialties in biology, making it possible to identify how some of these organisms cause diseases, find cures for such diseases and even utilize some microbes for industrial uses etc.

7. Neuroimmunology

Neuroimmunology is an integration of neuroscience and immunology. In neuroimmunology the interactions between the nervous system and the immune system is observed at different phases. The contributions of neuroimmunology helps in the discovery of new pharmacological treatments. During infections, activated macrophages and monocytes release pro inflammatory cytokines. These pro inflammatory cytokines affect the behaviour, sleep and mood. The overall body health can be dictated by various interactions between the nervous system and the immune system.

Related conferences

Related societies

8. Immunotoxicology

Immunotoxicology can be referred to as the study of the inimical effects on the immune system by direct or indirect agents. These agents can chemical, biological and physical in nature. The immune responses to such agents can lead to adverse effects. It can be of two types. It either involves the toxic effects on the immune system or the mediation of a toxic effect by the immune system. Immune toxicity can be induced by agents like dexamethasone, cyclosporin A, azathioprine, heavy metals and air pollution. It may also result in hypersensitivity and immunosuppression.

Related conferences

Related societies

9. Immunodiagnostics

Immunodiagnostics are a group of clinical diagnostics which uses diagnostic techniques that make use of the immune system of the body. It plays a major role in understanding about various diseases in humans. These tests come in different types as they can be performed on serum. The techniques are easy to perform and decipher the diseased state of a person. New immunoassay formats and diagnostics are being introduced daily. Microfluidics is another prominent advancement in immunodiagnostics and have led to the discovery of microfluidic chips and rapid immunoassays.

Related conferences

Related societies

10. Immunosuppression

Immunosuppression is the process by which the activity of the immune system is hindered. During organ/tissue transplant, there is a chance of organ/tissue rejection by the immune system of the body. In such cases the patient is asked to take immunosuppressive drugs. Certain parts of the immune system are found to exhibit immunosuppressive effects on other regions of the immune system. Another ill effect of immunosuppressive drugs is that sometimes they leave the patient with various side effects or make them prone to different diseases. The patients undergoing immunosuppression or who takes immunosuppressive drugs are known as immunocompromised.

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Related societies

11. Cancer immunology

The role played by the immune system during various phases of cancer is referred to as cancer immunology. One of the most common application is the immunotherapy. It also includes cancer immunoediting which is the study of the interaction between the immune system and the cancer cells. The antigens in the tumours are recognised by the immune system and this in turn activates an immune response. The antigens can either be tumour specific antigens or tumour associated antigens. Usually the tumour associated antigens are found in healthy cells but they are also present in the tumour cells as well.

Related conferences

Related societies

12. Veterinary immunology

Veterinary immunology is the branch of immunology that deals with the study of all immunological aspects in animals. It is connected to both zoology and veterinary science. Some of the major researches in this field includes development of vaccines, understanding the mechanism of the animal immune system, failure of vaccines and the harmful effects caused by them. Veterinary immunology is gaining its grounds as the number of pets and farm animals are increasing at a very fast rate. It provides numerous benefits to the agricultural field by introducing new immunological techniques as farm animals are prone to various infectious diseases primarily due to the poor sanitation of their surroundings. Specially trained Vets and forest officials are appointed for the treatment of immunological diseases relating to wild animals.

Related conferences

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13. Antigens and antibodies

Antigens are foreign bodies that can create an immune response and are bound by the antibodies. Each antigen is designed in a unique way to match an antigen. Once the body is exposed to an antigen, the B cells in the immune system produces the Y shaped antibodies. The antigen binds to its antibody just the way a key fit in to the lock and the antigen gets removed from the body. The antigens present in vaccinations activate or stimulate the B lymphocytes. After the stimulation, plasma cells are formed which releases the antibody for the disease. There five kinds of antibodies and three kinds of antigens.

Related conferences

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14. Immunopathology

Immunopathology deals with the responses formed by the immune system towards a disease. The pathology of an organism or organ is studied, taking the immunological factors into consideration. It is the destructive effects caused to an organism by its own immune response. The predominant cause for which is the by restless responses of the immune system.

Related conferences

Related societies

15. Infections and vaccines

The invasion of a disease-causing agent into a host body and their multiplication and survival in the hosts tissues bring about infections. The diseases caused by these infections are called infectious diseases and they are found to transmit from one individual to the other. Infections are caused by infectious agents that include bacteria, parasites, arthropods, virus, fungi and parasites. Vaccines are used to provide active acquired immunity to a disease and the administration of vaccines is called vaccination. Vaccination is believed to be the most important aspect in prevention of diseases and is one of the safest ways to fifth and prevent various infectious diseases. Childhood vaccinations are generally safe and side effects if present will always be mild. Smallpox was eradicated with the help of vaccines.

Related conferences

Related societies

16. Autoimmune diseases and HIV

Autoimmune disease is a condition when the body sees its own tissue as a threat and attacks it. Abnormal immune responses bring about autoimmune diseases. Women are commonly affected by autoimmune diseases than men. The pathological effects of autoimmune diseases include damage of tissues, altered organ growth and changed organ function. HIV is a group of conditions that is caused as a result of the infection by human immunodeficiency virus. HIV/AIDS has affected society, both as a disease and as a source of separation. The vital cells such as T cells, macrophages and dendritic cells are infected by HIV.

Related conferences

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Immunology Conferences 2020 | Immunology Conferences ...

Immunology

Human Immunology – Journal – Elsevier

March 31, 2020 medical

Human Immunology publishes full-length, original, hypothesis-driven basic and clinical research articles as well as brief communications, reviews and editorials covering immunogenetics, transplantation immunology, autoimmunity, and immunity to infectious diseases in humans. It also publishes short population reports, which are tied to the allelefrequencies.net database, describing allele frequencies of HLA and KIR.

The journal's scope includes understanding the genetic and functional mechanisms that distinguish human individuals in their immune responses to allografts, pregnancy, infections or vaccines as well as the immune responses that lead to autoimmunity, allergy or drug hypersensitivity. It also includes examining the distribution of the genes controlling these responses in populations.

Research areas include:

Studies of the genetics, genomics, polymorphism, evolution, and population distribution of immune-related genes

Studies of the expression, structure and function of the products of immune-related genes

Immunogenetics of susceptibility to infectious and autoimmune disease, and allergy

The role of the immune-related genes in hematopoietic stem cell, solid organ, and vascularized composite allograft transplant

Histocompatibility studies including alloantibodies, epitope definition, and T cell alloreactivity

Studies of immunologic tolerance and pregnancy

T cell, B cell, NK and regulatory cell functions, particularly related to subjects within the journal's scope

Pharmacogenomics and vaccine development in the context of immune-related genes

Human Immunology considers immune-related genes to include those encoding classical and non-classical HLA, KIR, MIC, minor histocompatibility antigens (mHAg), immunoglobulins, TCR, BCR, proteins involved in antigen processing and presentation, complement, Fc receptors, chemokines and cytokines. Other immune-related genes may be considered.

Human Immunology is also interested in bioinformatics of immune-related genes and organizational topics impacting laboratory processes, organ allocation, clinical strategies, and registries related to autoimmunity and transplantation.

Original papers with new data will be given preference over uninvited reviews and meta- analyses.

As the flagship scientific publication of the American Society for Histocompatibility and Immunogenetics (ASHI), Human Immunology is primarily directed to readers with an interest in histocompatibility, immunogenetics, transplantation, anthropology/population studies, HLA disease association and pharmacogenomics. These include basic and clinical scientists as well as histocompatibility laboratory professionals.

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Human Immunology - Journal - Elsevier

Immunology

Immunology | Graduate School of Biomedical Sciences

March 31, 2020 medical

Immunology Program Guide

MERGE-INF is specifically designed to provide strong training in basic molecular and cellular immunology, the immunology of chronic diseases, as well as in-depth knowledge of the pathogenesis, diagnosis, prevention and treatment of inflammatory diseases including infections. We integrate clinical studies and patient contact throughout the training period.

The realization on the part of the scientific and medical communities that inflammation plays a role in many diseases, causing substantial morbidity and contributing to mortality, has fundamentally changed how we think about pathogenesis. Inflammation is directly involved in asthma, rheumatoid arthritis, cardiovascular disease, obesity, diabetes, osteoporosis, inflammatory bowel disease, Alzheimers disease, cancer, stroke and psychiatric disorders such as anxiety, unipolar and bipolar depression, schizophrenia, and post-traumatic stress disorder. Importantly, inflammation is involved in at least 8 of the top 10 leading causes of death in the United States today. Given the prevalence of inflammation in the human population, it is clear that research in inflammatory disease and related mechanisms should be a major scientific and medical priority.

The faculty of the Immunology Program is drawn from multiple departments, including Cellular and Molecular Immunology, Developmental, Molecular & Chemical Biology, Medicine, and Molecular Biology & Microbiology. This diversity is a distinct strength of the Program, as it assures the student broad exposure to research topics and approaches. It also maximizes opportunities for a student to find a research faculty advisor to serve as thesis mentor. Students begin the program in the summer with introductory courses and by pairing with clinical mentors that provide direct contact with patients, their diseases and their physicians. This is a critical part of developing translational research approaches to health-related research. Five or six cases are examined in detail and include a variety of diseases, such as endocarditis, systemic lupus erythematosus, hepatitis, scleroderma and asthma. An associated problem-based learning course provides interactive training in the analysis of pathogenesis.

During the first academic year students complete an Introductory course in immunology, biochemistry, advanced cellular immunology, signaling in cells of the immune system and the genetic analysis of immune responses. Beyond the first-year Introduction to Immunology and Biochemistry courses, all courses are based on primary sources and are taught as interactive tutorials. Interactive workshops in data analysis and informatics are part of the training. Training in fellowship grant writing is provided. Students are required to participate in classroom teaching for one semester.

Students complete four laboratory rotations in year one. These introduce the student to hands-on experience in a variety of techniques and research problems and familiarize them with potential thesis laboratories. Because of the flexibility designed into the program, a student may alter career objectives after admission.

The Immunology Program aims to provide a supportive environment that helps each student realize his or her fullest potential. Students are encouraged to work hard, be creative and have the confidence to be exploratory, yet at the same time to understand that science flourishes in an atmosphere of cooperation and collaboration.

We are looking for students with a curiosity-driven passion for research and the ability to perform laboratory-based experiments. The Immunology Program is dedicated to the premise that a diverse student body enriches the educational experience of all.

After a summer that introduces clinical aspect of inflammation and pathogenesis first year students become thoroughly immersed in immunology through foundation and advanced courses in the discipline. They also participate in journal club, seminars and research workshops, in addition to completing four laboratory rotations.

An unusual feature of this program is that students take their qualifying examination at the end of the first year, allowing them to concentrate on their thesis research going forward. The exam consists of a written research proposal and its oral defense. The purpose of this examination is to test the ability of the student to create and critically test hypotheses. A unique feature of our exam is that students are mentored by faculty to learn how real proposals are developed. Upon successful completion of the first year courses and the qualifying examination, students select a research mentor and begin their thesis work.

Thesis research experience is considered the core of a student's training. Students enter their labs at the beginning of year two. Typically, graduates of the Program generate at least two first author papers based on their research. Support to attend national meetings is available.

The Program has a student advisor who acts as an ombudsperson and student advocate.

The thesis research of four most recent PhD graduates illustrate the breadth of the work done by students in the Program:

Elizabeth showed how NEMO (NF-B essential modulator) functions in the T cell receptor activation pathway.

Michelle developed a genetic screen that allowed her to identify Klebsiella pneumoniae virulence factors, in particular, those that counter defense by neutrophils.

Bridget discovered that STING, a known detector of cytoplasmic DNA in macrophages and dendritic cells, is expressed in T cells and regulates their function.

Maria created a three-dimensional model of infection of the human intestine by Cryptosporidium parvum that for the first time allows long-term in vitro propagation of this protozoan parasite.

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Immunology | Graduate School of Biomedical Sciences

Immunology

Immunology | bioRxiv

March 31, 2020 medical

CIS checkpoint deletion enhances the fitness of cord blood derived natural killer cells transduced with a chimeric antigen receptor

Katy Rezvani, May Daher, Rafet Basar, Elif Gokdemir, Natalia Baran, Nadima Uprety, Mayela Mendt, Lucila Kerbauy, Mayra Hernandez Sanabria, Nobuhiko Imahashi, Ana Nunez, Li Li, Mohsen Fathi, Ali Rezvan, Vakul Mohanty, Pinaki Banerjee, Hila Shaim, Junjun Lu, Gonca Ozcan, Emily Ensley, Mecit Kaplan, Vandana Nandivada, Yuanxin Xi, Duncan Mak, Enli Liu, Sonny Ang, Luis Muniz-Feliciano, Jing Wang, Shahram Kordasti, Nedyalko Petrov, Navin Varadarajan, David Marin, Lorenzo Brunetti, Richard Skinner, Shangrong Lyu, Leiser Silva, Mollie Schubert, Garrett Rettig, Rolf Turk, Mark Behlke, Matthew S McNeill, Gavin Kurgan, Natalie W Fowlkes, Heng Li, Ken Chen, Marina Konopleva, Richard Champlin, Elizabeth J Shpall, Francesca Lorraine Wei Inng Lim, Yifei Shen, Mustafa Bdaiwi, Sunil Acharya, Ye Li, Xinhai Wan

bioRxiv 2020.03.29.014472; doi: https://doi.org/10.1101/2020.03.29.014472 New Results

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Immunology | bioRxiv

Immunology

Immunology Research Areas: R&D Systems

March 31, 2020 medical

Bio-Techne appreciates the critical role that you and our products and services play in research efforts to further scientific innovation and discovery. We are continually assessing our manufacturing and supplier capabilities during the COVID-19 situation and are implementing precautionary measures to ensure uninterrupted supply of products and services. Currently, and as we abide by local shelter in place orders across the world, we are fully operational and do not anticipate any material supply disruptions across our Bio-Techne brands and product lines. As the situation evolves, our goal is to utilize preventive measures to reduce the threat that COVID-19 poses to our ability to meet the needs of our customers globally.

Bio-TechneWHERE SCIENCE INTERSECTS INNOVATIONTM

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Immunology Research Areas: R&D Systems

Immunology

Immunology/Introduction – Wikibooks, open books for an …

March 31, 2020 medical

Immunology is the study of the organs, cells, and chemical components of the immune system. The immune system creates both innate and adaptive immune responses. The innate response exists in many lower species, all the way up the evolutionary ladder to humans, and it acts through relatively crude means against large classes of pathogens. The adaptive response is unique to vertebrates, reacting to foreign invaders with specificity and selectivity.hb

The immune system must maintain a delicate balance, with potent defensive responses capable of destroying large numbers of foreign cells and viruses while refraining from undue destruction of the host's body. When the immune system cannot mount a sufficient defense of the host, there is an immune deficiency; this is seen in HIV infection and SCID . If, on the other hand, the immune system acts too vigorously and begins to attack the host, we have autoimmunity. This is a defiance of the integral immune system property of self/nonself recognition. That is, the immune system begins attacking or forming antibodies against the host's own body tissues. Examples of autoimmune diseases include Graves' disease, Hashimoto's thyroiditis, myaesthenia gravis and type I diabetes mellitus.

The human immune system recognizes non-self entities and mounts an effector response to neutralize the organism. A faster and stronger memory response may occur upon later exposure. The memory response has been used throughout history to confer immunity upon several populations, even previous to our understanding of the physiological basis for such a response. Thucydides wrote in his History of the Peloponnesian War that persons who had been exposed to plague previously could care for the sick without danger. In the 19th century, variolation was commonplace; this was the removal of smallpox (variola virus) skin pustules which were subsequently put into small cuts in the skin of healthy people. This was itself a crude form of vaccination, with the crusty dry pustules acting as an incubator of attenuated virus. Edward Jenner would later use the cowpox virus to vaccinate (from vacca, Latin for "cow") patients against smallpox, and Louis Pasteur attenuated rabies and injected it into a small boy, naming this substance a vaccine in honor of Jenner's earlier studies in the science of immunology.

As immunology progressed, many people began to question how these vaccines worked. Why should exposure to plague in Thucycides' time confer protection only against plague and not all disease? Why should cowpox, a similar disease to smallpox but clearly a less severe virus, give milk maids sufficient immunity to resist full smallpox infection? In short, what has caused this memory response to be relatively (yet not absolutely) specific as well as selective?

First, some vocabulary:

Note: Often, antibody and immunoglobulin are used interchangeably. antigen and immunogen are used interchangeably(but to be precise, they are not the same)

There have been several competing theories of the immune response mechanism. The instructional theory of antigen interaction postulated that the antigen itself caused antibodies to fold around the antigen in a certain way; this theory was later disproven. The selection theory states that the body creates many different sidechains on antibodies, and the antigen "selects" the correct antibody; in other words, the body creates every possible permutation of chemical sidechain-specific antibodies, and when an antigen enters the body, it is matched up with antibodies that correspond to its epitopes. The current theory of immune response is known as the clonal selection theory, which states that an individual lymphocyte (specifically, a B cell) expresses receptors specific to the distinct antigen, determined before the antibody ever encounters the antigen. Binding of Ag to a cell activates the cell, causing a proliferation of clone daughter cells.

Innate immunity is basic and nonspecific. It includes:

antigen-presenting cells (APCs))

Certain cells "eat up" foreign invaders; this is termed phagocytosis. Many of these cells are known as Antigen-Presenting Cells (APCs) because they break apart the ingested pathogen and display certain epitopes of the antigen on their surface. In this way, they localize the presentation of antigen, forming a vital link between the innate response and the adaptive response. Lymphocytes (such as B cells and T-helper cells) will have antigen presented to them, initiating the adaptive response. Monocyte-derived cells are common APCs, and they include tissue macrophages and monocytes within the blood; eutrophils are also APCs. APCs are discussed further below, in the section on cells of the immune system.

The skin contains epidermis and dermis. The epidermis contains tightly packed epithelial (cytokeratin positive) cells with keratin waterproofing. The dermis contains connective tissue blood vessels hair follicles, sweat glands, and sebaceous glands. Sebaceous glands secrete sebum; this contains fatty acids and lactic acid, lowering skin pH to 35.

Mucous membranes contain normal flora, mucus, and cilia. Mucous membranes are found in the nose, eyes, mouth, urogenital, and anal regions of the body. Flora refers to bacteria that inhabit the human body in a relative steady-state; the gastro-intestinal tract contains a large number of these bacteria, and different areas of the world contain different flora. It is for this reason that people contract Traveler's Diarrhea; in short, flora from one region of the world are more dangerous because the body has not acclimated to their presence. Mucus contains certain mucin proteins, inorganic salts, and water; it is secreted from goblet cells. Cilia acts to sway back and forth during two phases, known as the power stroke and the recovery stroke; this allows mucus to be swept out of the body, either proximodistally from the lungs up the respiratory tract, or down the GI tract through the intestines, culminating in defecation. The enteric nervous system causes contractions of the gut, moving foodstuffs, waste, and bacteria/toxins down the digestive tract. This is just one example of disparate systems of the body working together with the immune system proper. Other examples are skeletal muscles, which squeeze blood along the veins and lymph along the lymph vessels, or the nervous system, which supports a rise in body temperature in response to infection.

Some bacteria can attach to mucous membranes via fimbriae or pili, which attach to special glyoproteins/glycolipids on the epithelial cells of mucous membranes.

Several antimicrobial compounds mediate the innate response.

peptidoglycan in bacterial cell walls

cells (it is a paracrine factor), inducing a generalized antiviral state

pathogen cell membranes

their lipid membranes or agglutinating them

via pattern recognition to certain classes of molecules; TLR4, for example, recognizes lipopolysaccharide (LPS) on gram-negative bacteria

Classical biology puts several characteristics together as an inflammatory response. These included redness (erythema, rubor), heat (calor), swelling (edema, tumor), pain (dolor), and loss of function (functio laesa). The physiological processes that bring about these symptoms are central to the innate immune response.

Erythema results from constriction of post-capillary venules in tissue beds and vasodilation in pre-capillary arterioles/metarterioles. This results in an increase of hydrostatic pressure in the capillary bed, overcoming the osmotic pressure of the interstitial fluid and causing exudate (high-protein fluid with acute-phase proteins like C-reactive protein and macrophages) to flow into the interstitial tissue. This flowing of exudate also allows the factors of the clotting cascade to enter areas of tissue damage, forming clots and, eventually, scars. Certain inflammatory factors also cause phagocytic cells to enter the damaged tissue. The now-permeable capillaries are traversed by these phagocytes in response to chemotaxis, the release of factors that lure the cells to the site of injury. The cells first approach the side of a capillary (margination), move through the spaces between capillary endothelial cells (diapedesis), and then enter the tissue itself. Histamine helps to mediate this response, and certain factors (such as bradykinin and possibly prostaglandins) stimulate skin pain receptors. Thus, blood flows into the tissue, causing redness, warmer steady-state temperature, swelling, and pain; loss of function is a secondary effect of these four states.

Adaptive immunity occurs in response to antigen exposure. It is specific, and it shows memory. As long as an antigen is made of the normal chemical elements we experience in biological systems (e.g. Carbon, Nitrogen, Sulfur, Hydrogen, Oxygen), we can form an adaptive response to it. This is how we fight off new diseases, and it has even been shown that we can create antigens in the laboratory that have never before existed on Earth, only to have animals mount competent immune reactions to them. As stated earlier, the adaptive immune system's specificity is tempered with an ability to differentiate between self and non-self antigen; simply put, the body doesn't attack its own cells, unless they have been invaded by virus and ask to be sacrificed for the sake of the host. When the immune system does attack the body, this is a disease state: autoimmunity.

The primary response takes 56 days, but the memory (secondary) response will be swifter and deadlier. It includes:

Blood cells are made in the bone marrow of adults. Leukocytes are white blood cells (WBCs). This includes monocytes (which become myriad cell types in the body, most importantly macrophages), granulocytes (neutrophils, basophils, eosinophils), and lymphocytes. Of all the leukocytes, the lymphocyte class are the most preeminent in the adaptive immune response. On a peripheral blood smear, lymphocytes are approximately the size of erythrocytes (red blood cells, RBCs), although they can be larger if activated and have a characteristic "clock-face" nucleus if they are B cells. Lymphocytes are so named because fewer than 1% are present in the circulating blood; the rest lie in the lymph nodes, spleen and other lymphoid organs. T lymphocytes leave the bone marrow, travelling to the thymus gland, where they mature and gain their specificity for the diverse antigens the body might come into contact with; additionally, any T cells that react against the body's own epitopes are selected against (killed) in the thymus, in an effort to stop any possible autoimmunity. A similar process occurs in the bone marrow in the case of B lymphocytes. B cells are conveniently named ("B for bone marrow"), but this is just a coincidence; it turns out that they are named B cells after the Bursa of Fabricius, a small pouch in the cloaca (lower large intestine, cloaca Latin for "sewer") of birds.

B cells leave the bone marrow with their specific membrane bound Ig (antibody) already specified. The Ig itself is made up of two medial heavy chains (both identical) with two lateral light chains (also identical) attached to the "top" of the heavy chains, which form a Y shape. Before they encounter antigen, B cells are known as "naive." Once they encounter antigen, the naive B cells will undergo clonal expansion; an activated B cell will form some daughter memory B cells and some plasma cells. The memory cells will lie in wait for a second encounter with the antigen, while the plasma cells will begin a massive secretion of antibody (Ig). B cells can bind to antigen when it is free and unprocessed in the body, much like APCs can.

Before moving on to T lymphocytes, it should be noted that certain cell surface molecules distinguish each person's unique immune system profile. The Major Histocompatibility Complex (MHC, or HLA) is a type of protein expressed on the surface of host cells that interacts with T-cell receptors (TCRs) of T cells. Virtually all the body's cells, including APCs, express class I MHC (MHC-I) on their surface. Only APCs express class II MHC (MHC-II). Thus, most body cells express MHC-I, while APCs express both MHC-I and MHC-II. When antigen enters a body cell and is broken down, the products of this breakdown are sent to the surface of the cell coupled with MHC-I. This forms the MHC-I/Ag complex, and usually occurs when a virus or bacterium enter a cell and are broken down by intracellular defenses. This can also occur in APCs, but APCs additionally process the antigen that they phagocytose, presenting it as an MHC-II/Ag complex on the surface of their cells.

T cells can be subdivided into two broad types: T helper cells and T cytotoxic cells. T helper cells express a T-Cell Receptor (TCR) that will interact with APC surfaces. Specifically, they interact with the MHC-II/Ag complex on the surface of APCs, and the TCR is stabilized in its binding by a CD4 receptor. CD stands for "cluster of differentiation," and is simply a class of cell receptor which occurs predominantly on T cells. T helper cells contain CD4 receptors and T cytotoxic cells contain CD8 receptors. Upon binding, T helper cells release cytokines, which act as chemotactic agents to call for more T helper cells, T cytotoxic cells, APCs, and B cells.

T cytotoxic cells encounter body cells that have been invaded and are presenting MHC-I/Ag on their surface. Tc cells extend their TCR to the MHC-I/Ag complex and stabilize this interaction with their CD8 receptor arms. Upon binding, the CD8+ cells differentiate, much like naive B cells, into memory T cells and cytotoxic T lymphocytes (CTLs), effector cells that cause the MHC-I/Ag-presenting cell (the "altered self cell") to die (apoptose). CTLs trigger apoptosis by secreting a perforin that allows the entry of a serine protease (Granzyme B) which activates intracellular executioner caspases. It should be noted that cancer cells can also become altered self cells, and CTLs are very important in the destruction of cancerous cells. T cells can interact with antigen only after it has been processed, either by a normal body cell (MHC-I) or by an APC (MHC-II).

Difference between the two types of T cells:

presented on MHC-II, via binding with TCR and CD4.

proteins), broken down by lysosomes in many types of body cells, presented on MHC-I, via binding with TCR and CD8.

Note that it is both the antigen and the MHC that is presented to T cells; each person has a unique MHC. This is why we must type for bone marrow transplantswe don't want people producing tons of new immune cells in bone marrow that think every MHC in the body is actually just antigen; when this does occur, it is called graft-vs.-host disease. Not only would the new bone marrow make cells that attacked every body cell's MHC, but when the body did present Ag on MHC, the lymphocytes from the transplant would not be able to recognize this MHC-I/Ag complex (although the MHC-II complex cells would be made in the new bone marrow, and thus APCs could, in some cases, still present). Unfortunately, these APCs would be very busy presenting the host's own body cells; clearly MHC typing (also known as HLA typing) for bone marrow transplants is a necessary result of the elegant self-nonself recognition of the human immune system. It is also worth noting that we are only as good as our presenting molecules. Some people have MHC genes that are not as good at presenting antigen, and thus some people have more vigorous immune respones than others.

The cellular and humoral responses of the adaptive immune system are linked via the T helper cell-B cell interaction. The T helper cell secretes cytokine factors to encourage chemotaxis of B cells to the site of infection as well as B cell differentiation and growth. B cells themselves, in their effector plasma B cell form, release antibodies into the blood.Antigens, or foreign substances that enter the body,are very harmful to the Immune System. But when specific antibodies are produced to bind with an antigen, the foreign substance becomes harmless and is delivered to the lymph. Antibodies are also very important in the complement system; this is an example of the vertebral adaptive immune response making good use of the relatively primitive innate immune response. Antibodies to the body's own cells are a very real danger. Type I diabetes may be caused by an autoimmune response, where the body makes antibodies to its own Beta cells in the pancreatic Islets of Langerhans. Graves' disease is a condition where the body produces antibodies to receptors in the follicular cells of the thyroid; these Ab keep the cells constantly activated, giving the patient hyperthyroidism and increasing their metabolism, to adverse effect. The interesting counterpoint to this is Hashimoto's thyroiditis; here the body makes antibodies to thyroid follicular cells' receptors, but in this case the cells are shut down by the Ab, and the patient endures hypothyroidism.

Autoimmunity due to antibody overreaction (hypersensitivity) is a huge problem, and it is a much greater problem in women than in men. Women tend to have a higher titer of immunoglobulin (antibody), and thus they exert a stronger (and sometimes overwhelming) immune response. For example, for every one man who gets Graves' disease, 8 women will contract it.

Antibodies are often given to produce a short-lived humoral immunity in emergency situations. Many antivenoms are actually horse immunoglobulin, produced in order to bind the venom until it can be cleared from the body.

It should be noted that all of the above-mentioned immune responses result in the destruction or agglutination of foreign pathogen. The goal of the immune response is three-fold:

The immune responses listed above show the intimate interaction between the innate and adaptive immune systems, as well as the subclasses of adaptive responses. The clonal selection theory of immune response, introduced above, is clear in the action of lymphocytes. Clonal selection simply means that antigen is presented to many circulating naive B and (via MHC) T cells, and the lymphocytes that match the antigen are "selected" to form clones of themselves, both memory and effector. This mass production of daughter cells is termed clonal expansion, and it is essential in the understanding of the theoretical basis of immunology. Not only this; clonal selection is used negatively in the lymphoid organs. Here, the body's own epitopes are presented to the infant lymphocytes; those that react are recognized as traitors and destroyed before they (and their future cloned daughters) can leave and wreak havoc in the body.

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