The document provides background information on primary immunodeficiency diseases (PIDs) and discusses their approach and management. It notes that over 350 PIDs have been identified so far. PIDs are classified based on the component of the immune system involved, such as combined antibody and T-cell deficiencies. Clinical markers for specific PIDs include recurrent infections, eczema, hair abnormalities, and organ involvement. Case scenarios demonstrate examples of SCID, LAD, CGD, agammaglobulinemia, and SCN. Screening tests and CBC findings are discussed to rule out certain PIDs. Management involves hematopoietic stem cell transplantation or IVIG replacement depending on the disorder.
Primary immune deficiency diseases( PID) comprise a heterogeneous group of genetic disorders that affects distinct components of the innate and adaptive immune system such as:
-neutrophils
-macrphages
-dendritic cells
-natural killer cells
-T and B lymphocytes
-complement components
More than 200 distinct PID disorders have been identified and 276 gene have been associated with these diseases.
Spectrum of these diseases can vary from mild presentation to lethal disorders. Lethality is due to increase susceptibility to infections and malignancies.
Primary immune deficiency diseases( PID) comprise a heterogeneous group of genetic disorders that affects distinct components of the innate and adaptive immune system such as:
-neutrophils
-macrphages
-dendritic cells
-natural killer cells
-T and B lymphocytes
-complement components
More than 200 distinct PID disorders have been identified and 276 gene have been associated with these diseases.
Spectrum of these diseases can vary from mild presentation to lethal disorders. Lethality is due to increase susceptibility to infections and malignancies.
Contents- Introduction to Immunodeficiency | Types | SCID | LAD
Immunodeficiency is the inability to produce an adequate immune response because of insufficiency or absence of antibodies, immune cells or both.
SCID & LAD are the two immunodeficiencies from primary immunodeficiency.
This presentation is about chronic infections in patients and earlier diagnosis of immunodeficiency. The goals of the presentation are:
1. Understand the role of innate and adaptive immune systems in the defense against infection
2. Recognize the common presentations of common primary immunodeficiencies
3. Be able to identify patients in an ENT practice that may have a primary immunodeficiency
Presentation by: Dr. Richard L. Wasserman and Dr. Scott Manning
Contents- Introduction to Immunodeficiency | Types | SCID | LAD
Immunodeficiency is the inability to produce an adequate immune response because of insufficiency or absence of antibodies, immune cells or both.
SCID & LAD are the two immunodeficiencies from primary immunodeficiency.
This presentation is about chronic infections in patients and earlier diagnosis of immunodeficiency. The goals of the presentation are:
1. Understand the role of innate and adaptive immune systems in the defense against infection
2. Recognize the common presentations of common primary immunodeficiencies
3. Be able to identify patients in an ENT practice that may have a primary immunodeficiency
Presentation by: Dr. Richard L. Wasserman and Dr. Scott Manning
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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.
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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.
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Stay informed, stay safe, and get your flu shot today!
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Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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
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MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
4. History
● The first PID was discovered 70 years ago —> CGD (around 1950)
● Then SCID—> WAS and Bruton’s agammaglobulinemia
● The introduction of immunoglobulin replacement (1952) and bone marrow
transplantation (1957
● Around 2010, PID discovered was around 150
● Now its more than 350 diseases described—> expansion in understanding immune basis
and genetic etiology.
5. Background- “Inborn Errors of Immunity”
Primary immunodeficiency diseases (PIDs) are inherited disorders that
impair the immune response, leading to increased risk of infections,
immune dysregulation, autoimmune phenomena, inflammation, and
malignancy.
>1 million cases in India; 6 million people —> PIDs worldwide, of which only
27,000–60,000 have been diagnosed
Approximate incidence : 1 in 2000 to 1: 10,000
For now more than 344 gene defects and 354 disease identified and it is
increasing….
Primary Immunodeficiency Disorders in India—A Situational ReviewAnkur Kumar Jindal, Rakesh Kumar Pilania, Amit Rawat and Surjit Singh*Allergy
Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
6. Primary Immunodeficiency Disorders in India—A Situational ReviewAnkur Kumar Jindal, Rakesh Kumar Pilania, Amit Rawat and Surjit Singh*Allergy
Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
7. Basics –Immunity
Innate Immunity Adaptive Immunity
Lag time Short Long
Active Always active Activated after antigen exposure
Specificity Non-specific Specific
Eg., Skin epithelium,GI and
Respiratory mucosa
Cells Neutrophils,Eosinophils,Basoph
ils,Monocytes and NK cells
Pattern recognition receptors
B and T lymphocytes,
Plasma cells—>antibody
8. Cells of adaptive immunity
B cells T cells
Produced in Bone Marrow Bone Marrow
Mature in Bone Marrow Thymus
Lymph node Follicles Para-follicular
Spleen Follicles Per—arteriolar region
Immune system Humoral —> antibody
mediated
Cell mediated—>
CD4/CD8 T cells
13. 10 warning signs…
● The overall significance of having any of the 10 warning signs to suspect
PID showed that
● When at least one warning sign was exhibited, the sensitivity was 100,
specificity was 26%.
● Meeting at least two criteria of the 10 warning signs led to a sensitivity
of 94% specificity of 64%.
● When at least three criteria of the 10 warning signs were fulfilled, the
sensitivity was 77% ,the specificity was 86%
The most common asymptomatic PID –
Selective IgA deficiency (1:223 to 1:1000)
The most common symptomatic PID –
Antibody deficiency
16. Based on component of immune system involved
1. Combined T-cell and B-cell immunodeficiencies- SCID
2. Predominantly antibody deficiencies –CVID, X-linked
agammaglobulinemia
3. Other well defined immunodeficiency syndromes- DiGeorge, Ataxia
telengiectasia, WAS
4. Diseases of immune dysregulation-HLH
5. Congenital defects of phagocyte number and function – LAD, CGD
6. Defects in innate immunity- MSMD, CMC
7. Auto-inflammatory disorders- FMF
8. Complement deficiencies( C1 inhibitor deficiency- hereditory
angioedema)
27. Case scenario 1
● Karuppasamy, 3 months old male child presented with fever , respiratory distress for 3
days; worsened very rapidly ; expired due to septic shock within a day.
● ALC-3000; previous 3 sibling death at similar age; consanguinity present
● Previous child workup for complement and Ig profile was normal.
29. SCID
● Usually present within first six months of life with failure to thrive, chronic
diarrhea, persistent oral thrush, skin rash, pneumonia, and sepsis
● Disseminated BCG infection is commonly seen in patients with SCID
● Lymphopenia is commonly seen with patients with SCID
● >22 groups of SCID is present. ADA deficiency, X-Linked SCID , Artemis
deficiency , PNP deficiency etc.,
● Less than 2 years + Less than 20% CD3 T cells/ALC<3000/mm3/one
defined mutation Diagnose SCID
32. Case scenario 2
● Kavish, 7 months old male child presented with increase in head size and umbilical
discharge.
● Consanguinity present; delayed umbilical cord fall present.
● Recurrent hospital admissions for non-healing omphalitis / required more than 2 months
of iv antibiotics
● His total count at admission was 85000
● He had brain abscess too which was evacuated and craniectomy was done.
35. Leukocyte adhesion deficiency
● Recurrent infection + neutrophilia
● Delayed seperation of umbilical cord
● No pus formation
● No signs of inflammation
● LAD-1 : CD11/CD18 low
● LAD-2 : CD 15 /Normal CD11 and CD18
● LAD-2 associated with Bombay blood group
● LAD-3 Associated with Glanzman thrombasthenia like bleeding disorder
● HSCT can be tried in LAD 1 and LAD 3
38. Case 3
● 18 months old boy; Recurrent otitis media and pneumonia since 8 months of
age
● Absent tonsils and Lymph node
● Consanguinity present
● IgA-16 mg/dL (40-200)
● IgG-184 mg/dL (490-1610)
● IgM- 9 mg/dL (50-299)
39. Agammaglobulinemia
● Absent B cells and Reduced Ig levels are
suggestive of Agammaglobulinemia
● X-Linked or AR inheritance
● 1952 Colonel Ogden Bruton found reduced
immunoglobulin levels in a boy with recurrent
infections .He was the first to give Ig (im)
● Basic defect: Pro B cell to mature B cell –
Btk gene expression defective
● More than 50% will have serious infection by 2
years of age
● Marked reduction in all types of
Immunoglobulin
41. B cell defects
● Reduced Ig with normal to low B cells with abnormal specific antibody responses
common variable immunodeficiency (CVID)
● Markedly low IgG and IgA with normal to elevated IgM levels s/o Hyper IgM syndrome
● Antibody deficiency- best approach to diagnosis Serum specific antibody titers
(usually IgG) in response to vaccine antigens (tetanus toxoid and pneumococcus)
● Pre and post immunization levels will be diminished or absent
● In many PIDs, antibody responses to these antigens are absent.
42. Case 4
● 1 1/2 year old boy was admitted from Feb,12 to March
8,2021–> Presented with fever for 20 days; Multiple
swellings for 20 days;Not responding to oral antibiotics for 2
months—> worked up for Primary Immunodeficiency Ig
profile-Normal;Bone marrow-Paucity of myeloid series of
cells/No blasts;TBNK profile was normal.
● The child had issues 1.Left cervical abscess 2.Right
Otomycosis 3.Oral Candidiasis
● His ANC counts never raised >1000
44. Severe congenital neutropenia
● Mutation in ELANE, HAX 1 and G6PC3
● More prone for Staphylococcus, E.coli and
Pseudomonal infections
● Cyclical neutropenia – once in 21 days
● Monocytosis is common during Neutropenic phase
● Treatment –G-CSF
● Defintite management HSCT
45. Some well known immunodeficiency syndromes
1. Wiscott Aldrich Syndrome
2. Ataxia Talengectasia
3. Di-george anomaly
4. Hyper IgE Syndromes(HIES)/AD (Jobs Syndrome)
46. ● 4 year old boy Recurrent pneumonia and Otitis media ; eczema over
trunk and Thrombocytopenia
● PS was s/o Microplatelets
● Triad of Atopic dermatitis; Infections and Thrombocytopenia
● X-linked
● No autoimmunity
● WAS gene
Case 5
48. CBC in PID:
Neutrophil Normal Rules out LAD/
Neutropenia
Lymphocyte Normal Rules out T-cell defect
Platelet Normal Rules out WAS
Howel Jolly bodies Present Asplenia
50. Rule of 2/3 rd’s
● For a child less than 3 years
o 2/3 of WBC should be lymphocytes
o 2/3 of lymphocytes should be T cells
o 2/3 of T cells should be CD4 cells
• For a child more than 3 years
o 2/3 of WBC should be neutrophils
o 2/3 of lymphocytes should be T cells
51. Screening tests for PID
B Cell defect Antibody levels(Ig)
Antibody titres to vaccination
(Protein and Polysaccharide)
T cell defect ALC
Flow cytometry (for naïve T cells)
Phagocytic defect ANC
Respiratory burst assay
Complement deficiency CH50
AH50