This document discusses mast cells, including their role in health and disease. It begins by describing mast cell activation through IgE receptors or other stimuli, which causes the release of mediators like histamine. These mediators contribute to wound healing, angiogenesis, and defense against infection. However, mast cell activation also causes immediate hypersensitivity reactions and exacerbates conditions like arthritis and coronary disease. The document concludes by discussing mast cell disorders like mastocytosis.
The angiogenesis process, the factors regulating it, different assays for it, a little about tumour angiogenesis, the drugs and new therapeutic approaches towards inhibiting or augmenting the process.
The angiogenesis process, the factors regulating it, different assays for it, a little about tumour angiogenesis, the drugs and new therapeutic approaches towards inhibiting or augmenting the process.
dendritic cells are part of innate immune system, antigen presenting cells in skin, activation of t cells and inducing and maintaining immune tolerance, 4 types- langerhans cells, dermal dendritic cells, merkel cells, melanocytes
various cutaneous lymphomas though having low incidence but need to be diagnosed accurately. they can be mimiced by many non neoplastic conditions of skin. so discussing both T and B cell lymphomas
Lab Diagnosis of Chronic lymphoproliferative disorders (CLPD);Flowcytometric...Dr Siddartha
Lab Diagnosis of Chronic lymphoproliferative disorders (CLPD);Flowcytometric Evaluation
Basavatarakam Indo-American Cancer Hospital and Research Institute
dendritic cells are part of innate immune system, antigen presenting cells in skin, activation of t cells and inducing and maintaining immune tolerance, 4 types- langerhans cells, dermal dendritic cells, merkel cells, melanocytes
various cutaneous lymphomas though having low incidence but need to be diagnosed accurately. they can be mimiced by many non neoplastic conditions of skin. so discussing both T and B cell lymphomas
Lab Diagnosis of Chronic lymphoproliferative disorders (CLPD);Flowcytometric...Dr Siddartha
Lab Diagnosis of Chronic lymphoproliferative disorders (CLPD);Flowcytometric Evaluation
Basavatarakam Indo-American Cancer Hospital and Research Institute
INTRODUCTION
HISTORY
CAUSES OF INFLAMMATION
CLASSIFICATION
ACUTE INFLAMMATION
CHEMICAL MEDIATORS OF INFLAMMATION
OUTCOMES OF ACUTE INFLAMMATION
CHRONIC INFLAMMATION
INFLAMMATORY DISEASES
REFERENCES
THIS SEMINAR INCLUDES DEFINATION,TYPES OF INFLAMMATIONS AND MEDIATORS OF INFLAMMATION FOLLOWED BY REGENERATION,REPAIR AND WOUND HEALING BY PRIMARY AND SECONDARY INTENTIONS OF SOFT AND HARD TISSUES.HEALING OF EXTRACTION SOCKETS AND WEEKLY CHANGES IN HEALING OF EXTRACTION SOCKET.LOCAL AND SYSTEMIC FACTORS OF INFLAMMATION ABD COMPLICATIONS OF WOUND HEALING
This is about inflammation in immunology. Types of inflammation, causes, signs, events and mechanisms are mentioned briefly and it focuses on the cytokines associated with inflammatory and anti-inflammatory responses. Inflammation topic on immunology is the focus point.
Mast cells were first discovered by Paul Erlich. Here we discuss the origin, structure, staining and applied aspects. Under applied aspects, consider its role in allergic cutaneous response, infections, psoriasis, atopic dermatitis. Mastocytosis is a disease where mast cells accumulate in one or more tissues.
Similar to Mast cells in health and disease final dr karishma (20)
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
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
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
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.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
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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
Mast cells in health and disease final dr karishma
1. Presenter :Dr Karishma A. Korgaonker
Moderator : Dr . Gauri Metkar
MAST CELLS IN HEALTH AND DISEASE
2. Introduction
Activation of mast cells
Mast cell mediators
Mast cell in health
>Wound healing
>Angiogenesis
Mast cell in disease
>Immediate hypersensitivity reaction
>Infection
>Inflammation
• Mast cell disorders
• Summary
3. Introduction
Dr Paul Ehrlich in 1878
Large mononuclear cells
Cytoplasmic membrane bound granules - contain a variety of
biologically active mediators and sulphated
glycosaminoglycans
Bone marrow–derived cells-- originate from CD34+/CD117+
multipotent hematopoietic progenitor
They are abundant near blood vessels and nerves and in
subepithelial tissues
4.
5. Mast cells function
Participate in defence against bacterial and parasitic
infection
Develop immediate hypersensitivity reactions
Take part in reparation of tissues - angiogenesis,
production of intercellular substances
6. Introduction
Activation of mast cells
Mast cell mediators
Mast cell in health
>Wound healing
>Angiogenesis
Mast cell in disease
>Immediate hypersensitivity reaction
>Infection
>Inflammation
• Mast cell disorders
• Summary
7. Activation of mast cells
Cross-linking of high-affinity IgE Fc receptors
Complement components C5a and C3a
Mast cell secretagogues include some chemokines (e.g.,
IL-8), drugs such as codeine and morphine, adenosine,
mellitin (present in bee venom), and physical stimuli (e.g.,
heat, cold, sunlight).
8. Activation of mast cells
Mast cells express a high-affinity receptor, called FcεRI,
that is specific for the Fc portion of IgE, and avidly binds
IgE antibodies.
In the first step in this sequence, antigen (allergen) binds
to the IgE antibodies previously attached to the mast cells
The bridging of the Fcε receptors activates signal
transduction pathways from the cytoplasmic portion of the
receptors.
9. Activation of mast cells
These signals lead to mast cell degranulation with the
discharge of preformed (primary) mediators that are stored
in the granules, and de novo synthesis of secondary
mediators
16. Mast cell mediators
• Vasoactive amines:
The most important mast cell–derived amine is histamine.
= intense smooth muscle contraction,
=increased vascular permeability, and
=increased mucus secretion by nasal, bronchial, and gastric
glands.
17. Mast cell mediators
• Enzymes:
= contained in the granule matrix
= include neutral proteases (chymase, tryptase) and several
acid hydrolases.
= cause tissue damage and lead to the generation of kinins
and activated components of complement (e.g., C3a)
18. Mast cell mediators
Proteoglycans:
= include heparin (anticoagulant) and chondroitin sulfate.
= serve to package and store the amines in the granules.
19. Lipid Mediators.
are synthesized by sequential reactions in the mast cell
membranes
= lead to activation of phospholipase A2, an enzyme that
acts on membrane phospholipids to yield arachidonic
acid.
=This is the parent compound from which leukotrienes
and prostaglandins are derived by the 5-lipoxygenase and
cyclooxygenase pathways
20. Lipid Mediators.
Leukotrienes:
C4 and D4 --the most potent vasoactive and spasmogenic
agents known.
B4 --is highly chemotactic for neutrophils, eosinophils, and
monocytes.
21. Lipid Mediators.
Prostaglandin D2 :
= most abundant mediator produced in mast cells by the
cyclooxygenase pathway.
= intense bronchospasm as well as increased mucus
secretion.
22. Lipid Mediators.
• Platelet-activating factor (PAF):
= platelet aggregation, release of histamine, bronchospasm,
increased vascular permeability, and vasodilation.
=chemotactic for neutrophils and eosinophils,
=at high concentrations it activates the inflammatory cells,
causing them to degranulate.
23. Cytokines.
play an important role in immediate hypersensitivity
reactions.
The cytokines include:
>TNF, IL-1, and chemokines - promote leukocyte
recruitment
>IL-4- which amplifies the TH2 response.
24. Introduction
Activation of mast cells
Mast cell mediators
Mast cell in health
>Wound healing
>Angiogenesis
Mast cell in disease
>Immediate hypersensitivity reaction
>Infection
>Inflammation
• Mast cell disorders
• Summary
25. Woundhealingandangiogenesis
MC’s mediator influence-
All phase of wound healing
Acute inflammatory
Promote influx of inflammatory cells to injury site
Proliferative phase
Re-epithelialization & angiogenesis
Release many angiogenic factors to induce revasculaization of
damage tissue
Heparin from MC stimulates endothelial cell migration to form
new blood vessel
26. Woundhealingandangiogenesis
MC tryptase stimulates vessel tube formation & enhances growth
of microvascular endothelial cells
MC chymase promotes angiogenesis through effects of
angiotensin II
Generate growth factors : fibroblast growth factor, vascular
endothelial growth factor (VEGF), platelet-derived growth factor
(PDGF), nerve growth factor (NGF)
all growth factors induce proliferation of epithelial cells
& fibroblasts
27. Woundhealingandangiogenesis
Remodeling phase
As fibroblast expand in previous phase, they deposit
collagen & other extracellular matrix proteins molded and
remodeled into scar tissue
Hair follicle recycling
MC histamine, TNF, substance P involved are thought to
contribute in hair follicle recycling
28. Woundhealingandangiogenesis
Bone remodeling
MCs are source of osteopontin, glycoprotein component of bone
matrix, that contributes to bone resorption & calcification
In human systemic mastocytosis, bone turnover is accelerated
enhance bone loss
29. Introduction
Activation of mast cells
Mast cell mediators
Mast cell in health
>Wound healing
>Angiogenesis
Mast cell in disease
>Immediate hypersensitivity reaction
>Infection
>Inflammation
• Mast cell disorders
• Summary
30.
31. Immediate hypersensitivityreactions
Histamine and leukotrienes, are released rapidly from
sensitized mast cells and are responsible for the intense
immediate reactions characterized by edema, mucus
secretion, and smooth muscle contraction
32. Mast Cells vs. Allergens
Allergen detection leads to mast cell histamine
release
In skin, this leads to wheal and flare reactions.
In the gut ,leads to intestinal hyper-permeability,
smooth muscle contraction, altered water and ion
transport, and intestinal symptoms.
• In the lungs, this leads to smooth muscle
contraction, mucus production, and airway
remodeling.
33. Introduction
Activation of mast cells
Mast cell mediators
Mast cell in health
>Wound healing
>Angiogenesis
Mast cell in disease
>Immediate hypersensitivity reaction
>Infection
>Inflammation
• Mast cell disorders
• Summary
34. Mast Cells vs. Parasites
Mast cells offer a first line of defense against parasitic
pathogens.
They are preferentially located in organs targeted
by parasites, where they release proteases, recruit neutrophils,
and regulate vessel permeability.
Mast cells release antimicrobial peptides.
35. mastcell in infection
Helminth infection
MCs are activated by
helminth & MC hyperplasia
is observed in helminth
infection
36. Mast Cells vs. Bacteria
Mast cells express most TLRs on their membrane
surfaces.
TLR binding triggers distinctive patterns of mast cell
activation including the release of antimicrobial peptides
and the production of complement-mediated membrane
attack complexes.
37. mastcell in infection
Bacterial infection
MC-derived TNF, together with LTC4 & LTB4 contributed to recruitment
neutrophils to clearance Klebsiella pneumoniae, Listeria monocytogenes,
Pseudomonas aeruginosa
38. Mast Cells vs. Yeast
and Fungal Forms
Parasite antigen stimulation of TLRs) and C-type
lectin
receptors (CLRs) initiates a wide range of mast cell
IgE
receptors resulting in the release of pro-
inflammatory
cytokines, chemokines, and other pre-stored
mediators of
inflammation.
The release of pre-formed mediators of
inflammation is
39. mastcell in infection
Fungal infection
Human MCs respond to zymosan, but not peptidoglycan,
Trichoderma viridae, indoor fungus, induce MC degranulation
(high dose) but low dose enhance histamine secretion from MCs
Aspergillus fumigatus induce IgE-independent MC degranulation
40. Mast Cells vs. Viruses
Upper respiratory viral infections worsen allergic
asthma,
suggesting increased activation of mast cells during
infection.
Mast cells recognize the presence of double-stranded
viral RNA and respond by releasing: IL-29, interferon-
alpha, interferon-beta, and tumor necrosis factor
alpha.
Virally infected mast cells respond by releasing the
anti-viral
proteins.
41. mastcell in infection
41
Viral infection
This aspect is emerging field
Report from HIV-infected patients
Increased serum IgE predict worse prognosis
Israël-Biet D et al.JACI 1992 Jan;89:68-75
42. mastcell in infection
Viral infection
Dengue virus can activate MCs to release IL-1, IL-6,
RANTES, MIP-1 and MIP-1
Respiratory syncytial virus (major cause of LRT in infant &
associated with development of asthma later in life
Airway MC numbers increase in parainfluenza infection
43. Mast Cells vs. Toxins
Mast cells are known to initiate an immediate IgE-
dependent
hypersensitivity response to venoms.
Mast cells can also be activated by various
endotoxins and
exotoxins.
It is not known whether mold or bacterial toxins
activate mast cell responses, but mast cells
release VEGF and MMP-9,
markers affected in biotoxin-mediated
44. Introduction
Activation of mast cells
Mast cell mediators
Mast cell in health
>Wound healing
>Angiogenesis
Mast cell in disease
>Immediate hypersensitivity reaction
>Infection
>Inflammation
• Mast cell disorders
• Summary
45. Mast cell- skin inflammation
Skin mast cells are located close to sensory nerve
endings and triggered by neuropeptides released by
dermal neurons
Acute stress releases CRH in the skin inducing local
response , increases vascular permeability
Acute stress induces redistribution of leukocytes from
the sytemic circulation into the skin and excerbates
skin delayed hypersensitivity reactions
46. Mast cell – inflammatory arthritis
Fluid aspirated from joints of patients with
arthrosynovitis contains RANTES and MCP-
1(chemoattractants)
Mast cells in the joints of RA patients express CRH
receptors
CRH and CRH receptors are increased in the joints of
inflammatory and RA patients symptoms of which
worsen by stress
47. Mast cell – Coronary inflammation
Cardiac mast cells participate in the development of
artherosclerosis , coronary inflammation, and cardiac
ishemia
Mast cells are prominent in coronary arteries during
spasm
The human mast cell proteolytic enzyme chymase is
the main cardiac source of coronary constrictor
angiotensin II
Cardiac mast cell derived histamine constrict the
coronary arteries
48. Mast Cells and
Coronary Artery Disease
People with mastocytosis or myalgic encephaplitis/chronic
fatigue syndrome are particularly prone to coronary
hypersensitivity reactions.
• Stress precipitates and worsens activation of mast cells via
activation of surface receptors by corticotropin releasing
hormone (CRH) and other hypothalamic neuropeptide
regulators.
49.
50. Mast cells and
Irritable Bowel Syndrome
Mast cell activation plays a role in post-infectious IBS.
• Mast cell degranulation associates with cytokine
alterations and intestinal hyperpermeability in patients
with IBS.
• Mast cell hyperplasia is seen in inflammatory bowel
disorders.
51. Mast Cells and the
Blood-Brain Barrier
Acute stress triggers CRH production which activates
histamine release by mast cells, which leads to increased
blood-brain barrier permeability.
This implicates mast cells in neuroinflammatory disorders
including multiple sclerosis.
53. Rolein cancer
In connective tissue of certain tumours mast cells occur in
great quantities
Cutaneous carcinomas especially basal cell cancers
Enormous accumulation of mast cells is in cutaneous
papilloma these are precancerous lesions
The moment tumour grow malignant the mast cells
disappear and escape detection
Mast cells and their products play a part in the local tissue
resistance against development and growth of the tumour
55. Introduction
Activation of mast cells
Mast cell mediators
Mast cell in health
>Wound healing
>Angiogenesis
Mast cell in disease
>Immediate hypersensitivity reaction
>Infection
>Inflammation
• Mast cell disorders
• Summary
56. MASTOCYTOSIS
A rare group of disorders
Pathological increase in mast cells in tissues
Mastocytosis can form part of other haematological
disorders, including myelodysplastic syndromes,
myeloproliferative disorders or AML.
Cutaneous mastocytosis: involve just the skin
Systemic mastocytosis: involve multiple tissues and
are associated with systemic symptoms
57. MASTOCYTOSIS
A c-kit point mutation leads to a single amino acid
substitution (Asp816Val) .
This mutation leads to ligand-independent
phosphorylation of c-Kit and a consequent clonal
expansion of mast cells.
58.
59.
60. MASTOCYTOSIS
Cutaneous manifestations
Urticaria pigmentosa is the usual presenting feature in
children and adults.
Yellowish-brown lesions,usually macular and
sometimes papular, appear in a patchy distribution.
Pruritus is common, as is flushing, and some cases
develop haemorrhagic bullous disease.
Whealing of lesions upon rubbing is known as
Darier’s sign.
61. MASTOCYTOSIS
Systemic disease
Systemic manifestations are very heterogeneous and are
secondary to mast cell mediator release.
Episodes of flushing, angioedema, or even anaphylaxis
with or without any specific trigger, can arise as a result of
systemic histamine release.
Gastrointestinal symptoms include abdominal
pain,diarrhoea, nausea and vomiting. Gastritis and peptic
ulceration may occur secondary to hyperhistaminaemia
and severe cases may develop malabsorption.
62. MASTOCYTOSIS
Osteoporosis leading to pathological fractures.
Peripheral blood cytopenias.
Hepatosplenomegaly.
Fever, fatigue and weight loss
Symptoms of organ failure due to organ infiltration are
characteristic of aggressive systemic mastocytosis.
63. Investigations
Diagnosis usually requires histological and
biochemical confirmation
Routine investigations should include a full blood
count, liver function tests and a random serum
tryptase.
Plasma levels of soluble CD25 and CD117 (kit)
have shown promise as novel markers of mast cell
disease.
64. Investigations
Bone marrow aspiration and trephine biopsy
Mast cell aggregates can be visualized on
conventional haematoxylin and eosin-stained
sections but stand out clearly with stains such
as toluidine blue .
Immunochemistry using antitryptase
antibodies highly specific for mast cells.
Flow cytometry to look for expression of CD2
and CD25 in bone marrow mast cells may be
useful as this phenotype is not seen in
normal mast cells.
65. Investigations
Abdominal ultrasound or computerized
tomography (CT) scanning should be
performed to look for hepatosplenomegaly
and lymphadenopathy.
Plain radiography and bone densitometry can
be used to assess bone involvement and the
presence of osteoporosis.
Endoscopy and biopsy can be useful if gut
involvementis suspected
66. Treatment
No curative treatment exists for mastocytosis,
The management of which remain symptomatic
67. Prognosis
Age and disease category are the most important
determinants of outcome.
The most benign syndrome is paediatric
mastocytoma,which disappears with time in over
50% of cases. Paediatric urticaria pigmentosa
also has a good prognosis and resolves in about
one-half of the cases.
Indolent systemic mastocytosis carries a
favourable prognosis and usually persists as a
chronic low-grade disorder
68. other Mast Cells Disorders
The Most Common Forms of Mast Cell Activation
Syndrome
===Idiopathic (non-clonal) mast cell activation syndrome
(also known as nc-MCAS):
- occurs more often in women
MC triggers are usually unknown.
Idiopathic anaphylaxis and mastocytosis should be ruled
out.
69. other Mast Cells Disorders
Monoclonal mast cell activation syndrome (MMAS): ----
systemic reactions to hymenoptera stings or
-- unexplained anaphylaxis with high baseline tryptase.
Bone marrow biopsy shows monoclonal MCs but not
mastocytosis.
Thought to be rare.
70. Histamine-Overdrive Mast Cell Disorders
Histaminosis: commonly induced by exposure to
histamine from foods; rarely, an acute syndrome caused
by scromboid poisoning (due to seafood high in
histamine).
• Histamine intolerance: sensitivity to histamine from foods
and/or from reduced histamine breakdown.
71. Histamine Intolerance
Reduced central or peripheral breakdown of histamine
can lead to:
Rashes
Headaches
Fatigue
Hives or flushing
Allergies
Dysmenorrhea
Estrogen dominance
GI disturbances
Dysrhythmias
Arthritis
Central, peripheral and/or autonomic neurologic
72. Diet and Nutrition in the
Treatment of Mast Cell Disorders
Some high histamine foods
Pickles , beer, mayonnaise, nuts, wine ,chocolate,
champagne ,vinegar ,cocoa, shellfish ,dried fruits
processed meats, tofu, cheese, yeast, canned vegetables,
mushrooms food additives, egg whites, aged cheeses
, tomatoes ,spices ,spinach
73. Diet and Nutrition in the
Treatment of Mast Cell Disorders
Apples: rich in quercitin
Carrots: rich in vitamin A
Watercress: inhibits histamine release
Broccoli: H2 receptor antagonist
Ginger: H2 receptor antagonist
Thyme: anaphylaxis inhibitor
Fennel: antioxidants, antihistamine, anti-
inflammatory
Turmeric: stabilizes mast cells, inhibits histamine
release me foods with anti-histamine effects
74. Introduction
Activation of mast cells
Mast cell mediators
Mast cell in health
>Wound healing
>Angiogenesis
Mast cell in disease
>Immediate hypersensitivity reaction
>Infection
>Inflammation
• Mast cell disorders
• Summary
75. Mast Cells: The Good,
the Bad, and the Ugly
The Good
An essential player in the body’s innate immune response.
They patrol the front lines: skin, connective tissues and
mucus membranes.
They release chemical alarms to summon defenses against
pathogens, allergens, toxins, and other noxious incitants.
76. Mast Cells: The Good,
the Bad, and the Ugly
The Bad
Over-activation of mast cells can lead to:
• Allergic disease/Asthma/Anaphylaxis
• Eczema/atopic dermatitis
• Migraines/neurological disorders
• Autoimmune disorders
• Gastrointestinal disorders
• Unexplained multi-symptom illnesses
Histamine is only one of many inflammatory elements
released by mast cells. Excess release of mast cell-derived
chemicals results in mast cell-related inflammation.
77. Mast Cells: The Good,
the Bad, and the Ugly
The Ugly
Abnormal mast cell proliferation results in mastocytosis,
which can lead to mast cell tumors and severe forms of
cutaneous or systemic disease.
Systemic mastocytosis commonly results in an
unexplained multi-system, multi-symptom illness
with damage to multiple organ systems that can go
unrecognized in multiple medical settings.
78. Take Home Message
Mast cells are functionally diverse cells that have a constitutive
presence at mucosal surfaces and elaborate impressive array of
mediators, making them an attractive therapeutic target.
Mast cell proteases,their well-documented ability to alter
intestinal permeability, is a key factor in several GI
autoimmune/inflammatory pathologies
79. Take Home Message
Mast cells have emerged as unique immune cells that
can be activated by many immune and nonimmune
triggers, including acute stress through CRH
Inhibition of mast cell activation by CRH, therefore,
is a novel target for the development of new treatments
for inflammatory and autoimmune disease
80. References
Robbins and Cotran pathologic basis of disease ,
Eighth Edition p.198-202
A. Victor Hoffbrand ,Daniel Catovsky MD, Edward
G.D. Tuddenham MD, Postgraduate Haematology,
Fifth edition 2005;p-775-778
Beaven M. Our perception of the mast cell from Paul
Ehrlich to now. European Journal of Immunology.
2009 Jan;39(1):11-25.
Moon TC, et al. Advances in mast cell biology: new
understanding of heterogeneity and function.Mucosal
Immunology. 2010;3:111-128.
81. References
Metz M, Maurer M. Mast cells: key effectors in
immune response. Trends in Immunology.
2007;28:234-241.
Theoharis C. Theoharides,and Dimitrios
Kalogeromitros The Critical Role of Mast Cells in
Allergy and InflammationAnn. N.Y. Acad. Sci. 1088:
78–99 (2006). C 2006 New York Academy of
Sciences.doi: 10.1196/annals.1366.025
Gustav Asboe-hansen Mast cells in health and disease
New Understanding Of Mast Cell surasarit Khawlaor
Editor's Notes
(production of IgE antibodies in response to an antigen, binding of IgE to Fc receptors of mast cells, cross-linking of the bound IgE by the antigen and release of mast cell mediators)
. Although the production of PAF is also triggered by the activation of phospholipase A2, it is not a product of arachidonic acid metabolism
The inflammatory cells that are recruited by mast cell–derived TNF and chemokines are additional sources of cytokines and of histamine-releasing factors that cause further mast cell degranulation.
As is evident from this figure, mast cells are capable of signalling to all other immune cells and other cells, the presence of a pathogen.
Mast cells are highly adaptible in nature. Very heterogeous and phenotypically malleable. Originally classified based on staining patterns as mucosal or connective tissue mast cells. These so called types actually differ in their phenotype, their granule composition. For eg. Mucosal mast cells show a different range of proteases than connective tissue mast cells. This composition is further affected based on the stimuli for eg. A cytokine signal that it receives. And based on this stimuli, the response is also quite differently modulated. These features allow mast cells to respond to different pathogens entering different tissues in different ways.
Mast cells functions by virtue of their mediators include increasing vascular permeability and oedema, immune cell recruitment like neutrophils and eosinophils, DCs, T cells and others. Producing antimicrobial peptides and reactive o2 species that have direct bactericidal properties. By its abbility to interact with smooth muscle cells, nerve cells and mucosal cells it can impede colonization of pathogens, and even its physical expulsion for eg. Diarrhoea in response to bacterial toxins. They further activate and modulate Ag presentation of DCs. Mast cells also influence cell trafficking to draining lymph nodes and lymphocyte retention, thus increasing the chances of induction of rare Ag-specific lymphocytes.
With all these functions that mast cells are capable of, they become an attractive addition to vaccines since the clearly enhance the asaptive response by serving as an adjuvant. It was shown 48/80.