This document provides an overview of autoimmune diseases. It defines autoimmune diseases as conditions where the immune system mistakenly attacks and destroys healthy body tissue. The causes include genetic factors, environmental triggers like infections, and defects in immunologic tolerance. Some specific autoimmune diseases discussed are rheumatoid arthritis, type 1 diabetes, Hashimoto's thyroiditis, Graves' disease, myasthenia gravis, and systemic sclerosis. The mechanisms, clinical features, pathology, and treatment options are described for each condition.
Autoimmunity and Autoimmune diseases.pptxrajmonu7858
A concise ppt about autoimmunity. It incudes information about tolerance, etiology behind autoimmune diseases, types of autoimmune diseases and few examples of diseases.
Autoimmunity and Autoimmune diseases.pptxrajmonu7858
A concise ppt about autoimmunity. It incudes information about tolerance, etiology behind autoimmune diseases, types of autoimmune diseases and few examples of diseases.
Normally, immune responses eradicate infectious pathogens without serious injury to host tissues.
However, these responses are sometimes
inadequately controlled
inappropriately targeted to host tissues
triggered by commensal microorganisms or environmental antigens that are usually harmless.
In these situations, the normally beneficial immune response is the cause of disease.
Disorders caused by immune responses are called hypersensitivity diseases.
This term , hypersensitivity , arose from the clinical definition of immunity as sensitivity, which is based on the observation that an individual who has been exposed to an antigen exhibits a detectable reaction, or is sensitive, to subsequent encounters with that antigen.
Today, we will describe the pathogenesis of different types of hypersensitivity reactions, with an emphasis on the effector mechanisms that cause tissue injury.
A variety of human diseases are caused by immune responses to non-microbial environmental antigens, and involve the type 2 cytokines interleukin-4 (IL-4), IL-5, and IL-13 produced by Th2 cells and innate lymphoid cells (ILCs), immunoglobulin E (IgE), mast cells, and eosinophils.
The antigens that elicit immediate hypersensitivity are called allergens. Most of them are common environmental proteins, animal products, and chemicals that can modify self proteins.
In the effector phase of these responses, mast cells and eosinophils are activated to rapidly release mediators that cause
increased vascular permeability
Vasodilation
bronchial and visceral smooth muscle contraction
This vascular reaction is called immediate hypersensitivity because it begins rapidly, within minutes of antigen challenge in a previously sensitized individual (immediate), and has major pathologic consequences (hypersensitivity).
Following the immediate response, there is a more slowly developing inflammatory component called the late-phase reaction characterized by the accumulation of neutrophils, eosinophils, and macrophages.
The immune system provides protection against infectious organisms and repairs tissue damage induced by infections or physical damage. Under normal conditions, an immune response cannot be triggered against the cells of one's own body. In certain cases, however, immune cells make a mistake and attack the very cells that they are meant to protect.
Autoimmunity and autoimmune diseases dr. ihsan alsaimarydr.Ihsan alsaimary
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
Normally, immune responses eradicate infectious pathogens without serious injury to host tissues.
However, these responses are sometimes
inadequately controlled
inappropriately targeted to host tissues
triggered by commensal microorganisms or environmental antigens that are usually harmless.
In these situations, the normally beneficial immune response is the cause of disease.
Disorders caused by immune responses are called hypersensitivity diseases.
This term , hypersensitivity , arose from the clinical definition of immunity as sensitivity, which is based on the observation that an individual who has been exposed to an antigen exhibits a detectable reaction, or is sensitive, to subsequent encounters with that antigen.
Today, we will describe the pathogenesis of different types of hypersensitivity reactions, with an emphasis on the effector mechanisms that cause tissue injury.
A variety of human diseases are caused by immune responses to non-microbial environmental antigens, and involve the type 2 cytokines interleukin-4 (IL-4), IL-5, and IL-13 produced by Th2 cells and innate lymphoid cells (ILCs), immunoglobulin E (IgE), mast cells, and eosinophils.
The antigens that elicit immediate hypersensitivity are called allergens. Most of them are common environmental proteins, animal products, and chemicals that can modify self proteins.
In the effector phase of these responses, mast cells and eosinophils are activated to rapidly release mediators that cause
increased vascular permeability
Vasodilation
bronchial and visceral smooth muscle contraction
This vascular reaction is called immediate hypersensitivity because it begins rapidly, within minutes of antigen challenge in a previously sensitized individual (immediate), and has major pathologic consequences (hypersensitivity).
Following the immediate response, there is a more slowly developing inflammatory component called the late-phase reaction characterized by the accumulation of neutrophils, eosinophils, and macrophages.
The immune system provides protection against infectious organisms and repairs tissue damage induced by infections or physical damage. Under normal conditions, an immune response cannot be triggered against the cells of one's own body. In certain cases, however, immune cells make a mistake and attack the very cells that they are meant to protect.
Autoimmunity and autoimmune diseases dr. ihsan alsaimarydr.Ihsan alsaimary
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
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.
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
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.
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
These lecture slides, by Dr Sidra Arshad, offer a quick overview of 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 leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
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. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
3. Objective
Upon completion of these materials the student will be able to:
• Describe contributive factors to autoimmune diseases
• Describe about IMMUNOLOGIC TOLERANCE and its mechanisms
• Distinguish organ specific and systemic autoimmune diseases with
examples of each
• Describe the Cause of autoimmune diseases
• Discuss about some of autoimmune diseases
4. Introduction
Autoimmune diseases
•Immune reactions against self antigens—Autoimmunity
•Autoimmune disease is the faliure in recognizing its own constituent
parts which allows an immune response against its own self and tissues.
•A condition that occurs when the immune system mistakenly attacks
and destroys healthy body tissue
•Any disease which results in such an aberrant immune response is
termed as autoimmune disease.
5. • The mere presence of autoantibodies does not indicate an
autoimmune disease
Ideally, at least three requirements should be met before a
disorder is categorized as truely caused by 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
6. IMMUNOLOGIC TOLERANCE
To function properly, your T and B cells must have two traits:
• (1) They must be able to recognize your own major
histocompatibility complex (MHC) proteins, a process known
as self-recognition, and
• (2) they must lack reactivity to peptide fragments from your
own proteins, a condition known as self-tolerance.
Loss of self-tolerance leads to the development of autoimmune
diseases
7. • Tolerance to self antigens is a fundamental property of the
immune system, and breakdown of tolerance is the basis of
autoimmune diseases.
• Self-tolerance refers to lack of responsiveness to an individual’s
own antigens, and it underlies our ability to live in harmony with
our cells and tissues
8. • Central tolerance: Immature self-reactive lymphocytes
that recognize self antigens in generative (“central”)
lymphoid organs (i.e., in the thymus for T cells and in the
bone marrow for B cells). die by apoptosis; other fates .
• Peripheral tolerance: Mature self-reactive lymphocytes
that recognize self antigens in peripheral tissues are
inactivated (anergy), killed (deletion) or suppressed.
9. MECHANISMS OF IMMUNLOGIC
TOLERANCE
Central Tolerance:
Negative selection or deletion
Receptor editing
Peripheral Tolerance:
Anergy
Suppression by regulatory T cells
Deletion by apoptosis
10.
11.
12.
13. MECHANISMS OF AUTOIMMUNITY
• Cause of autoimmune diseases is the failure of tolerance
• Autoimmunity arises from a combination of the inheritance of
susceptibility genes, which may contribute to the breakdown of
self-tolerance, and environmental triggers, such as infections
and tissue damage, which promote the activation of self-reactive
lymphocytes
14. • It is thought that susceptibility genes and environmental
triggers induce a number of changes that contribute to the
development of autoimmunity
Defective tolerance or regulation
Abnormal display of self antigens
Inflammation or an initial innate immune response
15. Defective tolerance or regulation
• Failure of the mechanisms that maintain self tolerance
Abnormal display of self antigens
• Increased expression and persistence of self antigens
that are normally cleared
• Structural changes in these antigens resulting from
enzymatic modifications or from cellular stress or
injury
Inflammation or an initial innate immune response
• Microbes or cell injury may elicit local inflammatory reactions
resembling innate immune responses, and these may be
critical inducers of the autoimmune disease.
16. ROLE OF SUSCEPTIBILITY GENES
• Most autoimmune diseases are complex multigenic disorders
Association of HLA Alleles with Disease
• Among the genes known to be associated with autoimmunity, the
greatest contribution is that of HLA genes
Association of Non-MHC Genes with Autoimmune Diseases
• Polymorphisms in a gene called PTPN22
• Polymorphisms in the gene for NOD2
• Polymorphisms in the genes encoding the IL-2 receptor(CD25)
and IL-7 receptor α chains
17.
18.
19. ROLE OF INFECTIONS
• Autoimmune reactions may be triggered by infections
• Two mechanisms have been postulated
1.Induction of costimulators on APCs
Microbial infections with resultant tissue necrosis and
inflammation can stimulate expression of costimulatory
molecules on APCs in the tissue, thus favoring a breakdown
of T cell tolerance and subsequent T cell activation.
20.
21. 2 Molecular mimicry :
Viruses and other microbes may share cross- reacting
epitopes with self antigens, such that responses may be
induced by the microbe but may attack self tissues. e.g.
Rheumatic heart disease in which an antibody response
against streptococci cross-targets cardiac antigens.
22.
23.
24. role of inf..
• Microbes may induce other abnormalities that promote
autoimmune reactions.
• Some viruses, such as Epstein-Barr virus (EBV) and HIV, cause
polyclonal B-cell activation, which may result in production of
autoantibodies
• Tissue injury that is common in infections may release self
antigens and structurally alter these antigens so that they are
able to activate T cells that would not be tolerant to these new,
modified antigens.
25. Enviromental factors
Ultraviolet (UV) radiation causes cell death and maylead to the
exposure of nuclear antigens, which elicit pathologic immune
responses in lupus.
Smoking is a risk factor for rheumatoid arthritis, perhaps
because it leads to chemical modification of self antigens.
26. GENERAL FEATURES
Autoimmune diseases tend to be chronic, sometimes with relapses and
remissions, and the damage is often progressive
The clinical and pathologic manifestations of an autoimmune disease
are determined by the nature of the underlying immune response
The systemic diseases tend to involve blood vessels and connective
tissues, and therefore, they are often called collagen vascular diseases
or connective tissue diseases
24
28. Classification
• Depending on the principal
clinico-pathologic features of each
disease Autoimmune diseases can
be broadly divided into
• Systemic and
• Organ-specific or localised
autoimmune disorders, .
31. Autoimmune disease in which islet destruction is caused
primarily by immune effector cells reacting against endogenous
β-cell antigens
Develops in childhood, becomes manifest at puberty, and
progresses with age
Pathogenesis-
Genetic Susceptibility-
Higher concordance rates for disease in monozygotic vs dizygotic twins
genome-wide association studies have identified multiple genetic susceptibility
loci
the most important locus is the HLA gene cluster on chromosome
232
32. 90 to 95% have either an HLA-DR3 or HLA-DR4 haplotype
40% to 50% of patients combined DR3/DR4 heterozygotes
DR3 or DR4 concurrently with a DQ8 haplotype highest inherited
risks for type 1 diabetes
The first disease-associated non-MHC gene to be identified was
insulin, with variable number of tandem repeats (VNTRs) in the
promoter region being associated with disease susceptibility
Environmental Factors-
viral infections have been suggested as triggers
viruses might share epitopes with islet antigens- Molecular
mimicry
233
35. • Chronic inflammatory disorder of autoimmune origin that may
affect many tissues and organs but principally attacks the joints,
producing a nonsuppurative proliferative and inflammatory
synovitis
• Progresses to destruction of the articular cartilage and ankylosis of the
joints
• Extraarticular lesions may involve skin, heart, blood vessels and lungs
• The disease peaks in the second to fourth decades and is three times
more common in women than men.
36. Pathogenesis
• Genetic predisposition and environmental factors
• The pathologic changes are mediated by antibodies
against self-antigens and cytokine-mediated
inflammation
• CD4+ T helper (TH) cells may initiate the
autoimmune response in RA by reacting with an
arthritogenic agent
37. • Antibodies produced in lymphoid organs and in the synovium are
specific for cylic citrullinated peptides (CCPs)
• Antigen-antibody complexes containing citrullinated fibrinogen,
type II collagen, α-enolase and vimentin deposit in the joints
• 80% of patients have serum IgM or IgA autoantibodies that bind to
the Fc portions of their own IgG.
• These autoantibodies are called rheumatoid factor
• Deposit in joints as immune complexes
38. ARTHRITOGEN
• Specific HLA-DRB1 alleles are linked to rheumatoid arthritis,
• And these alleles share a common sequence of amino acids in a
polymorphic region of the β chain, which is designated the shared
epitope
• The environmental arthritogen- uncertain.
• CCPs are produced during inflammation (so insults such as
infection and smoking may promote citrullination of self-
proteins,creating new epitopes that trigger autoimmune
reactions)
39. MORPHOLOGY
Joints-
•Symmetric arthritis, affecting the small joints of the hand and
feet
•The synovium becomes grossly edematous, thickened, and
hyperplastic, transforming its smooth contour to one covered by
delicate and bulbous villi
40. The characteristic histologic features:
•Synovial cell hyperplasia and proliferation
•Dense inflammatory infiltrates (frequently forming lymphoid
follicles) of CD4+ helper T cells, B cells, plasma cells, dendritic cells,
and macrophages increased vascularity due to angiogenesis
•Fibrinopurulent exudate on the synovial and joint surfaces
•Osteoclastic activity in underlying bone, allowing the synovium to
penetrate into the bone and cause periarticular erosions and
subchondral cysts
41. • Together, the above changes produce a pannus: a mass of
edematous synovium, inflammatory cells, granulation tissue,
and fibroblasts that grows over the articular cartilage and
causes its erosion
• In time, after the cartilage has been destroyed, the pannus
bridges the apposing bones to form a fibrous ankylosis,
which eventually ossifies and results in fusion of the bones,
called bony ankylosis
42.
43. Skin
•Rheumatoid subcutaneous nodules- Most common lesions
occur in approximately 25% of affected individuals, usually
those with severe disease
•Arise in regions of the skin that are subjected to pressure
44. Blood vessels-
Acute necrotizing vasculitis involves small and large arteries
Segments of small arteries such as vasa nervorum and the
digital arteries are obstructed by an obliterating endarteritis
resulting in peripheral neuropathy, ulcers, and gangrene
Leukocytoclastic vasculitis produces purpura, cutaneous ulcers,
and nail bed infarction
45.
46. The diagnosis of RA is supported by
1.Characteristic radiographic findings
2.Sterile, turbid synovial fluid with decreased viscosity, poor
mucin clot formation, and inclusion-bearing neutrophils,
3.The combination of rheumatoid factor and anti-ccp antibody
(80% of patients)
48. Hashimoto’s Thyroiditis
• Autoimmune disease that results in destruction of the
thyroid gland and gradual and progressive thyroid failure
• Is characterized by the destruction of thyroid cells by various
cell- and antibody-mediated immune process.
• Caused by auto Ab of IgG & IgM type against the constituents
of thyroid gland Hashimoto’s thyroiditis
49. An association of cytotoxic lymphocyte-associated antigen 4
(CTLA4), a T cell regulatory gene, with autoimmune phenomenon in
Hashimoto’s disease has been reported.
There is initial activation of CD4+ T helper cells, which then induce
infiltration of CD8+ T cytotoxic cells in the thyroid parenchyma.
In the process, B cells are also activated to form autoantibodies,
which bring about immune destruction of thyroid parenchyma.
55. GRAVES DISEASE
• Graves disease is an autoimmune disease where the thyroid
is overactive, producing an excessive amount of thyroid
hormones
• This is caused by thyroid autoantibodies that activate the TSH-
receptor, thereby stimulating thyroid hormone synthesis and
secretion, and thyroid growth (causing a diffusely enlarged
goiter)
60. Myasthenia gravis is an autoimmune disease that is usually
associated with autoantibodies directed against acetylcholine
receptors
Prevalence of 150 to 200 per million and shows a bimodal age
distribution.
About 85% of patients have autoantibodies against postsynaptic
acetylcholine receptors
Remaining patients have antibodies against the sarcolemmal
protein muscle-specific receptor tyrosine kinase
225
61. Anti-acetylcholine receptor antibodies lead to the
aggregation and degradation of the receptors, and
also to damage of the postsynaptic membrane
through complement fixation
Autoantibodies directed against muscle-specific
receptor tyrosine kinase do not fix complement
Antibodies seem to interfere with the trafficking and
clustering of acetylcholine receptor within the sarcolemmal
membrane
226
66. Systemic sclerosis is
characterized by:
1. Chronic inflammation thought to be the result of autoimmunity,
2. Widespread damage to small blood vessels, and
3. Progressive interstitial and perivascular fibrosis in the skin and
multiple
organs
67. The skin is most commonly affected
But the gastrointestinal tract, kidneys, heart, muscles,
and lungs also are frequently involved
Diffuse scleroderma-
widespread skin involvement at onset, with rapid
progression and early visceral involvement
Limited scleroderma-
skin involvement is often confined to fingers,
forearms, and face
68. Some patients develop
CREST SYNDROME
Combination of
Calcinosis
Raynaud phenomenon
Esophageal dysmotility
Sclerodactyly
Telangiectasia
69. ETIOLOGY AND PATHOGENESIS
Autoimmunity-
CD4+ T cell responding to an unidentified antigen accumulate in the skin
release cytokines that activate inflammatory cells and fibroblasts.
Cytokines produced- TGF-β and IL-13, stimulate transcription of genes that
encode collagen and other extracellular matrix proteins (e.G., Fibronectin) in
fibroblasts.
Other cytokines recruit leukocytes and propagate the chronic inflammation
70. Vascular damage-
Microvascular disease is consistently present early in the course,may be the
initial lesion.
Intimal proliferation is evident in the digital arteries.
Capillary dilation with leaking, as well as destruction
Nailfold capillary loops are distorted
138
71. Fibrosis
Characteristic of the disease
Culmination of multiple abnormalities including
The accumulation of alternatively activated macrophages,
Actions of fibrogenic cytokines produced by infiltrating leukocytes,
Hyperresponsiveness of fibroblasts to these cytokines, and
Scarring following upon ischemic damage caused by the vascular
lesions
72. MORPHOLOGY
Skin-
Diffuse, sclerotic atrophy of the skin
Begins in the fingers and distal regions of the upper extremities and
extends
proximally to involve the upper arms, shoulders, neck, and face
Histologically, there are edema and perivascular infiltrates containing CD4+
T cells, together with swelling and degeneration of collagen fibers
Capillaries and small arteries (150 to 500 μm in diameter)show thickening
of the
basal lamina, endothelial cell damage, and partial occlusion
73. Progression of the disease, there is increasing fibrosis of the
dermis, which becomes tightly bound to the subcutaneous
structures
There is marked increase of compact collagen in the dermis,
usually with thinning of the epidermis, loss of rete pegs,
atrophy of the dermal appendages, and hyaline thickening
of the walls of dermal arterioles and capillaries
Focal and sometimes diffuse subcutaneous calcifications
may
develop, especially in patients with the CREST syndrome
141
74. The extensive subcutaneous
fibrosis has virtually immobilized
the fingers, creating a clawlike
flexion deformity. Loss of blood
supply has led to cutaneous
ulcerations
143
75. Alimentary tract-
Affected in approximately 90% of patients
Progressive atrophy and collagenous fibrous
replacement of the muscularis develop at any level of
gut- severe in esophagus
The lower two thirds of the esophagus often
develops a rubber- hose–like inflexibility
76. The mucosa is thinned and may be ulcerated
There is excessive collagenization of the lamina
propria and submucosa.
Loss of villi and microvilli in the small bowel is the
basis for the malabsorption syndrome
77. Musculoskeletal System-
Inflammation of the synovium, associated with
hypertrophy and hyperplasia of the synovial soft tissues,
later fibrosis
Kidneys-
In 2/3rd of patients
Most prominent are the vascular lesions
Interlobular arteries show intimal thickening as a result
of deposition of mucinous or finely collagenous material
78. Lungs-
In more than 50% of individuals
Manifest as pulmonary hypertension and
interstitial fibrosis
Heart-
Pericarditis with effusion, myocardial fibrosis,
and thickening of intramyocardial arterioles occur
in one third of the patients.
148
79. SUMMARY
Autoimmunity - Breakdown in self-tolerance.
Muliple causes - genetic, environmental, nutrition, infections,
etc
Organ specific or Systemic.
Majority are caused by autoAb production
Treatment: Immunosuppressive drugs, Abs against TCR,
cytokines, adhesion molecules, etc.
80. Refreance
Kumar, V., Abbas, A. K., & Aster, J. C. (2017). Robbins basic pathology
e-book: Elsevier Health Sciences.
Robbins and Cotran Pathologic Basis of Disease 9th edition.
Harsh Mohan Textbook of Pathology, 7th edition.
Kuby Immunology 5th edition.