Autoimmunity disorders occur when the immune system mounts an attack against the body's own tissues and organs. They are difficult to diagnose due to nonspecific initial symptoms, fluctuating symptoms, and the potential for multiple autoimmune conditions. Diagnostic methods include initial laboratory tests of inflammatory markers and autoantibodies, immunological studies, flow cytometry to analyze immune cells, cytokine studies, and examination of major histocompatibility complex genes associated with autoimmunity. A variety of autoantibodies against nuclear, cytoplasmic, and other cellular components can indicate autoimmune disease patterns and targets.
Introduction
History
Types of immunity
Tissues of immunity
Cells of immunity
Basic aspects of immunology
Major histocompatibility complex
Cytokines
Disorders of immune system
Immune responses in periodontal pathogenesis
Periodontal vaccine
Host modulation
Conclusion
References
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.
Introduction
History
Types of immunity
Tissues of immunity
Cells of immunity
Basic aspects of immunology
Major histocompatibility complex
Cytokines
Disorders of immune system
Immune responses in periodontal pathogenesis
Periodontal vaccine
Host modulation
Conclusion
References
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.
presented by HAFIZ M WASEEM
university of education LAHORE Pakistan
i am from mailsi vehari and studied in lahore
bsc in science college multan
msc from lahore
Cell mediated immunity also known as T cell immunity. it is developed by cell mediated responses and it does not involve any antibodies. Cell mediated immunity is offered by T lymphocytes and it starts developing when T cells come in contact with the antigens. In the Cell mediated immunity T cell plays one of the important role for the process of crosstalk with other immune system as well as to signal B cells to produce the antibody mediated immune response. Primary function of cell mediated response-
1) Eliminate intracellular pathogens.
2)Eliminate tumor cells.
T cells regulate proliferation and activity of other cells of the immune system : B cells, macrophages, neutrophil, etc.
presented by HAFIZ M WASEEM
university of education LAHORE Pakistan
i am from mailsi vehari and studied in lahore
bsc in science college multan
msc from lahore
Cell mediated immunity also known as T cell immunity. it is developed by cell mediated responses and it does not involve any antibodies. Cell mediated immunity is offered by T lymphocytes and it starts developing when T cells come in contact with the antigens. In the Cell mediated immunity T cell plays one of the important role for the process of crosstalk with other immune system as well as to signal B cells to produce the antibody mediated immune response. Primary function of cell mediated response-
1) Eliminate intracellular pathogens.
2)Eliminate tumor cells.
T cells regulate proliferation and activity of other cells of the immune system : B cells, macrophages, neutrophil, etc.
Dr. ihsan edan abdulkareem alsaimary
PROFESSOR IN MEDICAL MICROBIOLOGY AND MOLECULAR IMMUNOLOGY
ihsanalsaimary@gmail.com
mobile : 009647801410838
university of basrah - college of medicine - basrah -IRAQ
Immune tolerance, or immunological tolerance, or immunotolerance, is a state of unresponsiveness of the immune system to substances or tissue that have the capacity to elicit an immune response in a given organism. Immune tolerance is important for normal physiology. Central tolerance is the main way the immune system learns to discriminate self from non-self. Peripheral tolerance is key to preventing over-reactivity of the immune system to various environmental entities (allergens, gut microbes, etc.).
Studying the Adaptive Immune Response - Tools for T & B Cell Research: Host D...QIAGEN
Adaptive immunity, powered by T cells and B cells, provides specific, long-lasting protection of the host from harmful invaders. This slidedeck provides an overview of T cells and B cells and their role in cell-mediated immune responses and antibody responses, respectively, against pathogens. There is also information on tools that enable analysis of T and B cell gene expression and regulation, genotyping and signal transduction pathway activation.
An undergraduate lecture on immunologic tolerance, it's various types and how a breakdown of tolerance contributes to the pathogenesis of autoimmune diseases. Additionally a small quiz at the end to gauge the students' learning.
Testicular torsion refers to the torsion of the spermatic cord structures and subsequent loss of the blood supply to the ipsilateral testicle.
Urological emergency; early diagnosis and treatment are vital.
Mainly disease of Neonates, Adolescents.
The rate of testicular viability decreases significantly after 6 hours from onset of symptoms.
There are marked variations in the incidence of gastric cancer worldwide.
The UK it is approximately 15 per 100000 per year
The USA 10 per 100000 per year
Eastern Europe 40 per 100 000 per year.
It is more common in Japan—70 per 1,00,000 population.
Common in males 2:1.
Decrease incidence in western world (Western Europe and US)—last four decades.
Urethral stricture is an abnormal narrowing or loss of distensibility of any part of the urethra as a result of fibrosis at the site of injury or inflammation.
The lymphocytes and APCs for adaptive immunity
are distributed throughout the body in the blood, lymph,
and epithelial and connective tissues. Lymphocytes are
formed initially in primary lymphoid organs (the thymus and bone marrow), but most lymphocyte activation
and proliferation occur in secondary lymphoid organs
(the lymph nodes, the spleen, and diffuse lymphoid tissue found in the mucosa of the digestive system, including
14 The Immune System
& Lymphoid Organs
INNATE & ADAPTIVE IMMUNITY 267
CYTOKINES 269
ANTIGENS & ANTIBODIES 270
Classes of Antibodies 270
Actions of Antibodies 271
ANTIGEN PRESENTATION 271
CELLS OF ADAPTIVE IMMUNITY 273
Antigen-Presenting Cells 273
Lymphocytes 273
THYMUS 276
Role of the Thymus in T-Cell Maturation & Selection 279
MUCOSA-ASSOCIATED LYMPHOID TISSUE 281
LYMPH NODES 282
Role of Lymph Nodes in the Immune Response 284
SPLEEN 286
Functions of Splenic White & Red Pulp 286
SUMMARY OF KEY POINTS 293
ASSESS YOUR KNOWLEDGE 294
CHAPTER
the tonsils, Peyer patches, and appendix). The immune
cells located diffusely in the digestive, respiratory, or urogenital mucosae comprise what is collectively known as
mucosa-associated lymphoid tissue (MALT). Proliferating B lymphocytes in the secondary structures of MALT are
arranged in small spherical lymphoid nodules
The male reproductive system consists of the testes, conducting tubules and ducts (epididymis, vas deferens, ejaculatory ducts), accessory sex glands (seminal vesicles, prostate, and bulbourethral glands), and the penis.
Evaluating Tools for Characterizing Anterior Urethral Stricture Disease A Com...Dr Abdul Qayyum Khan
We evaluated if scores generated by the LSE classification system and
the Urethral Stricture Score system are associated with intraoperative surgical
complexity and stricture recurrence risk.
The development of endourological and extracorporeal lithotripsy techniques led to an increasing
number of options for the management of renal
calculi. Each of the methods available needs to be
evaluated in terms of its stone clearance rate, potential morbidity and cost-effectiveness. Extracorporeal shock wave lithotripsy (ESWL) is an
effective, well-established method for treatment of
renal calculi. The efficacy of ESWL for treatment
of kidney stones depends on several factors
including the size, location and coposition of the
stones
Amputation is surgery to remove all or part of a limb or extremity. You may need an amputation if you’ve undergone a severe injury or infection or have a health condition like peripheral arterial disease (PAD). Many people live a healthy, active lifestyle after an amputation, but it may take time to get used to life without a limb.
The term basal nuclei is applied to a collection of masses of gray matter situated within each cerebral hemisphere.
They are the
corpus striatum,
amygdaloid nucleus,
claustrum.
The subthalamic nuclei, the substantia nigra, and the red nucleus are functionally closely related to the basal nuclei.
Bladder injuries may result from blunt,Penetrating and Iatrogenic trauma.
Full bladder is more susceptible to injury than empty bladder.
Management varies from conservative to surgical aiming to directly repair the injury.
1.Detect presence of liver disease.
2.Distinguish among different types of liver diseases.
3.Estimate the extent of known liver damage.
4.Follow the response of treatment
Classical Rabies:
Fever, Headache, Periods of mental confusion alternating with periods of normal mentation
Hydrophobia due to involvement of muscles of swallowing and breathing.
Aerophobia:blowing air on face causes spasm of muscles
Estimated 31000 deaths in Asia annually
India: 20,000 deaths annually
Pakistan 2000-5000 deaths
Disorders that perturb cardiovascular, renal, or hepatic function are often marked by the accumulation of fluid in tissues (edema) or body cavities (effusions).
Transmission-Based Precautions are the second tier of basic infection control and are to be used in addition to Standard Precautions for patients who may be infected or colonized with certain infectious agents for which additional precautions are needed to prevent infection transmission.
Negative pressure pulmonary edema (NPPE) or postobstruction pulmonary edema (POPE) is a clinical entity of great relevance in anesthesiology and intensive care. The presentation of NPPE can be immediate or delayed, which therefore necessitates immediate recognition and treatment by anyone directly involved in the perioperative care of a patient.
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
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Title: Sense of Taste
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 structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
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.
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.
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Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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
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
3. DEFINITION
• Three requirements to call it Autoimmunity :
1. The presence of an immune reaction
specific for some self antigen or self tissue.
2. Evidence that such a reaction is not
secondary to tissue damage but is of
primary pathogenic significance.
3. The absence of another well-defined cause
of the disease.
4. HISTORY
Julius Donath and Karl Landsteiner (1904)reported
autoantibodies can cause disease by showing that
autoantibodies (‘hemolysins’) caused paroxysmal
cold hemoglobinuria.
5. Introduction
• Autoimmune diseases is a group of disorders
in which tissue injury is caused by humoral (by
auto-antibodies) or cell mediated immune
response (by auto-reactive T cells) to self
antigens.
• An autoimmune disorder may result in:
The destruction of one or more types of body tissue
Abnormal growth of an organ
Changes in organ function
13. Immune tolerance
• Definition: Immunological tolerance occurs when an
immunocompetent host fails to respond to an
immunogenic challenge with a specific antigen.
• * a state of unresponsiveness specific for a given
antigen
• * It is specific (negative) immune response
• * It is induced by prior exposure to that antigen
• * While the most important form of tolerance is non-
reactivity to self antigens, it is possible to induce
tolerance to non-self antigens. When an antigen
induces tolerance, it is termed tolerogen.
14. • Immune tolerance
• * Tolerance is different from non-specific
immunosuppression and immunodeficiency. It
is an active antigen-dependent process in
response to the antigen.
• * Like immune response, tolerance is specific
and like immunological memory, it can exist in
T cells, B cells or both and like immunological
memory, tolerance at the T cell level is longer
lasting than tolerance at the B cell level.
15. TOLERANCE – GENERAL PROPERTIES
• Immature or developing lymphocyte is more
susceptible to tolerance induction than
mature one
• 1.Tolerance to antigens is induced even in
mature lymphocytes under special conditions
• 2.Tolerance of T lymphocytes is a particularly
effective for maintaining long-lived
unresponsiveness to self antigens
16.
17. Central tolerance: fates of immature
self-reactive lymphocytes
• Induced by antigen in generative lymphoid organs
(thymus for T cells, bone marrow for B cells), and high-
affinity (“strong”) recognition of the antigens
• Immature lymphocytes undergo apoptosis upon
encounter with antigens (negative selection) Eliminates
high-affinity self-reactive (potentially most dangerous)
lymphocytes
• Some self-reactive T cells that encounter self antigens
in the thymus develop into regulatory T cells and
immature B cells in the bone marrow change their
receptors (rendered harmless)
18.
19. Mechanisms of tolerance induction
• * Clonal deletion – physical elimination of cells
from the repertoire during their lifespan
• * Clonal anergy – downregulating the intrinsic
mechanism of the immune response such as
lack of costimulatory molecules or insufficient
second signal for cell activation
• * Suppression – inhibition of cellular activation
by interaction with other cells:
• (Treg – CD4+CD25+ T lymphocytes)
20. Mechanism of tolerance induction
• Clonal deletion:
• Functionally immature cells of a clone
encountering antigen undergo a programmed
cell death, as auto-reactive T-cells are
eliminated in the thymus following interaction
with self antigen during their differentiation
(negative selection).
21. Mechanism of tolerance induction
• Clonal anergy:
• * Auto-reactive T cells, when exposed to
antigenic peptides which do not possess co-
stimulatory molecules (B7-1 or B7-2), become
anergic to the antigen.
• * Recognition of such antigens may lead to
signaling block and/or engagement of
inhibitory receptors
22.
23.
24. Mechanism of peripheral tolerance
• Ignorance: Never encounter Self Ag
• Anergy: unresponsiveness
• Self reactive T cell interact with APC but co-stimulatory signal blocked
• Immunomodulatory molecules like CTLA4 binding instead of CD 28 on T cell
• Phenotypic skewing: after activation via APC (with Self Ag)---Non
pathogenic cytokines release
• Activated self reactive Tcell---Upregulation of Fas Ligand---apoptosis
• Regulatory T cells (TREG Cells)-can down regulate self reactive T cell (by
IL-10, TGF-b)
• Sequestration of self Ag: lens protein
25. • Antigen can be Tolerogen or Immunogens
• Co-stimulatory molecules play an important
role
• Tolerance is antigen specific
26. Immune tolerance: factors that influence
immunity vs. tolerance
• * The stage of differentiation of lymphocytes
at the time of antigen confrontation
– * The site of encounter
• * The nature of cells presenting antigenic
epitopes
• * The number of lymphocytes able to respond
• * Microenvironment of encounter (expression
of cell adhesion molecules, influence of
cytokines etc.)
27. Immunologically Privileged Sites
• * Sites in the body where foreign antigens or
tissue grafts do not elicit immune responses
• * These antigens do interact with T cells, but
instead of destructive IR they induce tolerance or
a response innocent to the tissue
• Immunosuppressive cytokines such as TGF-beta
seem to be resposible for such unusual response
• * The sites include: brain, eye, testis, uterus
(fetus)
28. Failure of tolerance Autoimmunity
• Failure of Tolerance to protect host from self-
reacting lymphocytes
• Destruction of self proteins, cells, and organs
by auto-antibodies or self-reactive T cells
• 3% to 8% of individuals in the industrialized
world
29. Factors responsible for promoting
tolerance
• High dose of antigen
• Persistence of antigen
• Route of administration
• Adjuvents
• Low level of co-stimulators
• Presentation of antigen by
immature/unactivated antigen-presenting
cells (APCs)
30.
31. • All together
– Autoimmunity may be due to immunological,
Genetic, Viral, Drug induced, & hormonal
mechanisms
– Number of immunological mechanism all
leading to abnormal B or T-cell production.
– Most instances Diseases by multiple mechanism
difficulty in Rx
32.
33. Mechanisms
• Antigenic alteration
• Sequestered Ag
• Cross reacting foreign Ag
• Molecular mimicry
• Polyclonal activation of B cell
• Altered T or B cell function
35. Sequestered Ag
• Sequestered Ag: Self Ab present in closed
system not accessible to immune system
• Lens protein
• Immunological tolerance not established
during foetal life
• Penetrating injury---leak of lens protein—
immune response—injury to other eye
36. Sequestered Ag
• Sperm Ag—Puberty
• Mumps---damage to BM seminiferous
tubules—immune response---Orchitis
37. Cross reacting foreign Ag
• Similary b/w some foreign & Self Ag
• Indivisual Nerve tissue damage-antirabies
immunization of human with neural vaccine of
infected sheep brain
• Streptococcal M protein—heart ms—Heart
damage
• Nephritogenic strain streptococcus-- GN
38. Molecular mimicry
• Identical peptide sequence in epitopes b/w
microorganism & Self Ag
• HLA B27- Arthritogenic strain of S. flexneri
• Joint membrane- M. tuberculoisis
• Myocardium- Coxsackie B virus
39.
40. Polyclonal activation of B cell
• Ag--- corresponding B cell activation
• Polyclonal activation of B cells:
– Chemical (2 ME)
– Bacterial product (PPD, LPS)
– Enz (Trypsin)
– Antibotics (Nystatin)
– Infection (Mycoplasma, EBV, Malaria)
41. Altered T or B cell function
• Enhanced Helper T cell
• ↓↓ Suppressor T cell function
• Defect in thymus
• Stem cell development
• Macrophage function
• Idiotype-antiidiotype network defect
52. Disease
Hashimoto’s Ds Enlargement of thyroid
Hypothyrodism or
Frank myxedma
Glandular structure-replacement
with lymphoid tissue
Ab- to thyoglobulin, acinar
colloid, Microsomal Ag,
thyroid cell surface
components
Thyrotoxicosis
(Grave’s Ds)
↑↑↑ hormone IgG Ab (to thyroid
membrane Ag) act as Long
acting thyroid stimulator
(LATS)
Addison ds Lymphocytic infiltration of
adrenal &
circulating Ab to Zona
glomerulosa
Autoimmune
orchitis
Mumps Lymphocytic infiltration of
Testes &
circulating Ab to sperm &
germinal cell
53. Disease
Myasthenia gravis Thyorid lymphoid hyperplasia
Numerous germinal center
Ab Ach Receptor on
myoneural junction of
striated Ms---impairment
of Ms Contraction
Autoimmune
Disease of eye
Phacoanaphylaxis- Cataract Sx –
intraocular inflammation
Symathetic ophthamia-
Performating injury to one
eye
Pernicious Anaemia Ab to parietal cell of gastric
mucosa- Achlorhydria, Atrophic
gastritis
Ab to Intrinsic Factor---Vit B12 def
Autoimmune
Disease of Nervous
system
Neuroparalytic accidents
following- neural vaccine—Rabies
GBS- idiopathic polyneuritis
Autoimmune ds of
Skin
Pemphigus vulgaris- Ab to
intracellular adhesion protein
desmoglein
Bullous pemphigoid- Ab
dermoepidermal junction
Ab in Dermatitis
herpetiformis
54.
55.
56. – Variety of AutoAb
• Nuclei
• Intracytoplasmic cell constituents
– LE cell- Neutrophils containing LE Bodies (large
pale homogenous body) almost filling cytoplasm
– Antinuclear Ab (ANA)—Sensitive but not specific
• Pattern: homogenous, Peripheral, speckled, nucleolar
– Anti DNA Ab- ds
57.
58.
59.
60.
61.
62.
63.
64.
65. • The diagnostic methods of autoimmune
diseases includes,
• Initial laboratory evolution
• Immunological studies
• Inflammatory markers
• Flowcytometry
• Cytokine studies
• Major histocompatibility complex
66.
67.
68.
69. • Q: Why are autoimmune diseases challenging to
diagnose?
• A: Diagnosis is challenging for several reasons:
• 1. Patients initially present with nonspecific symptoms such
as fatigue, joint and muscle pain, fever, and/or weight
change.
• 2. Symptoms often flare and remit.
• 3. Patients frequently have more than 1 autoimmune
disease.
• According to a survey by the Autoimmune Diseases
Association, it takes up to 4.6 years and nearly 5 doctors for
a patient to receive a proper autoimmune disease diagnosis