Regulatory T cells (Tregs) suppress anti-tumor immune responses, allowing cancers to evade detection. Tregs are overrepresented in cancers like melanoma, helping the tumor establish an immunosuppressive microenvironment. Blocking Treg activity through antibodies against CTLA-4 prevents Treg proliferation while pushing other T cells towards an anti-tumor Th17 profile, limiting Treg differentiation and freeing up interleukin-2 (IL-2) for cytotoxic T cell expansion. Combining CTLA-4 blockade with IL-2 therapy could activate cytotoxic CD8+ T cells to destroy tumors by inducing granzyme and perforin expression for lysis of cancer cells.
T helper 17 cells (Th17) are a subset of T helper cells producing interleukin 17 (IL-17). They are developmentally distinct from Th1 and Th2 cells.
They create inflammation and tissue injury in autoimmune disease
T helper 17 cells (Th17) are a subset of T helper cells producing interleukin 17 (IL-17). They are developmentally distinct from Th1 and Th2 cells.
They create inflammation and tissue injury in autoimmune disease
Slideshow is from the University of Michigan Medical
School's M1 Immunology sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M1Immunology
Slideshow is from the University of Michigan Medical
School's M1 Immunology sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M1Immunology
THIS SEMINAR HAS BRIEF ABOUT T CELLS , TYPES, FUNCTIONS, CLUSTER OF DIFFERENTIATION, MHC MOLECULE, TOLERANCE , ROLE OF T CELLS IN PROGRESSION AND PREVENTION, T CELL IMMUNODEFICIENCY DISORDERS
By DR. MANPREET KAUR BEHL.
Description of classificaton of immune system, immune cells, HLA, MHC complexes, antigen presentation, t-cell responses and b-cell responses, antibody, isotype switching, hypersenstivity reactions etc.
T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response and are distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface.
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system.. B cells produce antibody molecules.
In mammals, B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricus.
B cells present antigens (they are also classified as professional antigen-presenting cells (APCs)) and secrete cytokines.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Triangles of Neck and Clinical Correlation by Dr. RIG.pptx
Déjà vu blame it on the tregs
1. Déjà vu.. Blame it on the Tregs!!!!!!
As I reevaluate my theory, I have come full circle in my research and came across the
research paper entitled:
The Role of Regulatory T Cells in Cancer
Tai-You Ha*
Department of Immunology, Chonbuk National University Medical School, Chonju,
Chonbuk, Korea
<A HREF="https://www.box.net/shared/ygz27ma9vn">The Role of Regulatory T Cells
in Cancer</A> <BR>
I postulate that the T regulatory cells may be the major stumbling block in the whole
immunotherapy.
Recent studies have shown that CD4+CD25high FoxP3+ Treg cells are
overrepresented in human metastatic lymph nodes with a 2-fold increased frequency
compared with both tumor-free lymph nodes and that advanced melanoma is associated
with increased numbers of circulating Treg cells and Dendritic Cells (DCs) and suggested
that melanoma induces immunosuppressive DCs and Treg cells in the systemic
circulation of the patients . Vence et al also showed the presence of tumor antigen-
specific CD4+ Treg cells in the blood of patients with metastatic melanoma.
This means the host (you) may already have the correct antigen, but the tumor and
microenvironment may be suppressing the immune response by secreting suppressive
cytokines like TGF- beta , IL-10, and IL -6 and or proliferating the suppressive Tregs.
Nicholaou et al most recently showed in patients with melanoma that although strong
antibody responses were mounted, the generation of delayed-type hypersensitivity
1
2. response was significantly impaired and patients with advanced melanoma had a
significantly higher proportion of circulating CD4+ CD25+FoxP3+ Treg cells
compared with those with minimal residual disease. So we now can blame the tolerance
of our immune system to cancer on the T Regulatory Cells (Tregs).
It has been reported that the large number of different cell types that are claiming to be
directly targeted by FoxP3+ Treg cells are CD4+, CD8+ T cell, dendritic cells, B
cells, marophages, osteoblasts, mast cells, NK cells, and NKT cells.
No wonder our immune system can’t raise an attack on the Melanoma. The tumor is like
a castle in the middle ages. The castle (tumor) is surrounded by a moat the (suppressive
cytokines) and the walls and towers are the Tregs. If you take out walls and tower, the
castle becomes vulnerable.
2
3. These Tregs when activated, upregulate the CTLA-4, CD25 (IL-2), and other receptors.
So if you control the function of the Tregs, you may be able to break the tolerance of the
immune system. This can be done by blocking receptors on the Treg cells
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4. It was also noted as the tumor burden increased, so did the Tregs in the peripheral which
makes it harder to eradicate tumors in the advanced stage of Melanoma.
Wieczorek et al found that Treg cell numbers are significantly increased in the peripheral
blood of patients with IL-2-treated melanoma. IL-2 stimulates CXCR4 expressed on the
Tregs enables the Tregs to migrate CxCL12 in the tumor microenvironment increasing
the Treg accumulation.
So we need to deplete, block and limit the expansion of the Tregs. We also want to limit
the concentration of Interluekin-2 at the early stage of the CD4+ T-cell expansion. This
can be done in a number of ways, but why not use an antibodies that can indirectly
accomplish both tasks at once. By using anti-CTLA-4 blockage we keep the activation
going, causing a free for all for the cytokine IL-2 that is secreted.
CD4+ T cells regulate immune responses by producing various cytokines upon antigen
stimulation. Naive CD4+ T cells have limited cytokine responses and secrete only IL-2
before they differentiate into various effector cell types CD4+ T cells regulate immune
responses by producing various cytokines upon antigen stimulation. Each cell type is
competing for a limited amount of IL-2 secreted by a small subset of the T helper cells.
Naive T cells stimulated with antigen in the presence of IL-4 differentiate into Th2 cells
secreting IL-4, IL-5, IL-10, and IL-13, whereas IL-12 induces the differentiation of naive
cells into Th1 cells secreting IL-2, IFN-γ, and lymphotoxin.
4
5. FROM:
Autoimmunity: IL-21: a new player in Th17-cell differentiation
Elissa K Deenick and Stuart G Tangye
WWW.Nature.com
Ribas and Restifo et al found that if you use Anti-CTLA-4 blockade the native T-cell is
pushed towards the Th17 differentiation. This causes less interleukin-2 to be produced by
the CD4+ T-cells causing a shortage of IL-2 in the microenvironment for the expanding
T-cells thus limiting the differentiation to Tregs. It is well known that in the presence of
TGF-beta and IL-2, the Native T-cell differentiates into T Regulatory Cells.
Also the activation and differentiation of Naïve CD8+ T cells require IL-2 provided by
activated CD4+ T cells at the initial priming stage within 0–2.5 hours after stimulation.
Thers is
critical IL-2 signal from CD4+ cells is mediated through the IL-2R (receptor) of Naïve
CD8+ cells. This activation of IL-2 signaling advances the restriction point of the cell
5
6. cycle, and thereby expedites the entry of antigen-stimulated Naïve CD8+ T-cell into the S
phase of the cell cycle.
The cell cycle has four stages:
1. G1 phase when the cell increases in size and gets ready to replicate its DNA.
2. S phase when the cell synthesizes or copies its chromosomes
3. G2 phase in which the cell prepares to divide
4. M phase when mitosis occurs.
If no IL-2 is available to Naïve CD8+ T-cells, they never get a chance to expand and
differentiate into Ctotoxic T Lymphocytes (CTLs) Killer T-cells.
Besides promoting cell proliferation, IL-2 stimulation increases the amount of IFNγ and
granzyme B produced by CD8+ T cells.
Activation and Differentiation of (CTLs) Cytotoxic T Lymphocytes
Naïve CD8+ T-cells are referred to as CTL-precursors (CTL-Ps), which are incapable of
performing any function other then recognizing the class I MHC-antigen complex on the
Tumor cells through the (TCR) T Cell Receptor. For activation, the CTL-P needs at least
three signals:
1. Antigen specific signal transmitted by the MHC I peptide/TCR complex for the
recognition of the Antigen
2. The Costimulatory signals transmitted by the CD28 receptor and the B7 molecule
of the Antigen Presenting Cells (APCs)
3. Cytokine induced signal, IL-2 interaction with the IL-2r (receptor) on the CTL-P
leading to activation and differentiation of the CTL-P into effector CTL
The Cytokine IL-2 came from the(CD4+) TH1 cells which means the CTL-P is IL-2
limited and can only be activated by the secreted IL-2 if there is any to be had or by
introducing IL-2 through IL-2 therapy. Now you know the reasoning behind using the
IL-2 therapy as the second part of the combinatorial Therapy. If there is not enough IL-2
in the host environment, you will only get partial expansion of the CTLs. It may not be
enough to eradicate large bulky tumors.
6
7. The Interluekin-2 plays another role in this Melanoma Maze. In a study by Janas et al, Il-
2 increases the expressions of the perforin and granzyme A, B and C genes in the CD8+
T-cells. This increase expression causes the CD8+ T-cells to mature into Cytoxic T
Lymphocytes (CTLs). The exogenous IL-2 is required for the granzyme proteins. CTLs
have cytoplasmic granules that contain the proteins perforin and granzymes. A dozen or
more perforin molecules insert themselves into the plasma membrane of target cells
forming a pore that enables granzymes to enter the cell. Once in the tumor cell, these
enzymes are able to breakup (lyse) the cell and destroy it. This is the beginning of the end
for the cancer cells. The tumors begin to shrink and the rest is history.
Research suggests that the primary mode of the destruction of the tumors by CTL is by
initiating death through the Fas-FasL pathway. Studies have shown that CTLs store
Cytotoxic proteins in the form of granules in their cytoplasm. These proteins belong to
two categories:
1. Perforins: involved in pore formation
2. Granzymes: responsible for hydrolysis of the cellular products.
Granzymes breaks down the tumors cells just like your detergent enzymes in your
laundry detergent.
Immediately following a CTL contact with the tumor cell, the Golgi sacks load with
granules and granzymes which create pores to allow the granzymes to enter and destroy
the tumors cells.
So now you know why Anti-CTLA-4 blockage and HD Interluekin-2 go hand and hand.
Timing of the addition of IL-2 can make or break the immune response. And without
suppressing the Tregs, your chances to mount an immune response may be slim at best.
Your Immune System is a well Orchestrated system of events; we just need the
Knowledge on how to harvest its potential on eradicating cancer.
7
8. The beginning of knowledge is the discovery of something we do not understand.
~Frank Hebert~
A critically acclaimed and commercially successful American science fiction author
8
9. The beginning of knowledge is the discovery of something we do not understand.
~Frank Hebert~
A critically acclaimed and commercially successful American science fiction author
8
10. The beginning of knowledge is the discovery of something we do not understand.
~Frank Hebert~
A critically acclaimed and commercially successful American science fiction author
8