The immune system is a network designed for the homeostasis of large molecules (oligomers) and cells based on specific recognition processes.
It is the collection of cells, tissues and molecules that function to defend us against infectious microbes
IT CONTAINS THE LATEST INFORMATION ABOUT MHC MOLECULE WHICH WILL BE HELPFUL FOR B.SC /M.SC/CSIR-NET/DBT-JRF/GATE STUDENTS. THIS IS IN VERY SIMPLE AND LUCID MANNER TO UNDERSTAND AND ONE CAN EASILY OPT FOR THIS TO PREPARE NOTES.
IT CONTAINS THE LATEST INFORMATION ABOUT MHC MOLECULE WHICH WILL BE HELPFUL FOR B.SC /M.SC/CSIR-NET/DBT-JRF/GATE STUDENTS. THIS IS IN VERY SIMPLE AND LUCID MANNER TO UNDERSTAND AND ONE CAN EASILY OPT FOR THIS TO PREPARE NOTES.
MHC genes evolve through duplication, followed by diversification, co‐evolution, and sequence exchange. The focus, for HLA in transplantation, has been the specific classical class I and class II human leukocyte antigen (HLA) molecules and alleles. Importantly, anti‐HLA antibodies developed after the organ transplants play a role in acute and chronic allograft rejection, highlighting the need to detect these antibodies in a clinically relevant manner. Although the immune response to HLA antigens plays a pivotal role in allograft rejection, evidence shows that non‐HLA antigens also contribute to the pathogenesis of acute and chronic rejection, which limits long‐term graft survival of the solid organ transplants.
Major Histo compatibility Complex of Genes /certified fixed orthodontic cours...Indian dental academy
The Indian Dental Academy is the Leader in
continuing dental education , training dentists
in all aspects of dentistry and offering a wide
range of dental certified courses in different
formats.
Indian dental academy provides dental crown &
Bridge,rotary endodontics,fixed orthodontics,
Dental implants courses.for details pls visit
www.indiandentalacademy.com ,or call
0091-9248678078
In class presentation for an advanced cell biology course at KSU, fall 2017. Background knowledge includes a previous immunology course, about 6 biochemistry courses and research.
Major Histocompatibility Complex (MHC) plays a cardinal role in T cell-mediated immunity. Modern immunogenetics largely depends on the research on the MHC complex.
This ppts file will give the students of biochemistry or biology, in general, a brief outlook on the structure and functions of MHC, as well as its mode of action.
I hope this work will help intermediate students grasping the topic.
it is related to immunology .. Major histo compatibility complex - a highly polymorphic region on chromosome 6 with genes particularly involved in immune functions..
Immunity :
It is defined as the resistance exhibited by the host against any
foreign antigen including microorganisms.
Plays a major role in prevention of infectious diseases.
MHC genes evolve through duplication, followed by diversification, co‐evolution, and sequence exchange. The focus, for HLA in transplantation, has been the specific classical class I and class II human leukocyte antigen (HLA) molecules and alleles. Importantly, anti‐HLA antibodies developed after the organ transplants play a role in acute and chronic allograft rejection, highlighting the need to detect these antibodies in a clinically relevant manner. Although the immune response to HLA antigens plays a pivotal role in allograft rejection, evidence shows that non‐HLA antigens also contribute to the pathogenesis of acute and chronic rejection, which limits long‐term graft survival of the solid organ transplants.
Major Histo compatibility Complex of Genes /certified fixed orthodontic cours...Indian dental academy
The Indian Dental Academy is the Leader in
continuing dental education , training dentists
in all aspects of dentistry and offering a wide
range of dental certified courses in different
formats.
Indian dental academy provides dental crown &
Bridge,rotary endodontics,fixed orthodontics,
Dental implants courses.for details pls visit
www.indiandentalacademy.com ,or call
0091-9248678078
In class presentation for an advanced cell biology course at KSU, fall 2017. Background knowledge includes a previous immunology course, about 6 biochemistry courses and research.
Major Histocompatibility Complex (MHC) plays a cardinal role in T cell-mediated immunity. Modern immunogenetics largely depends on the research on the MHC complex.
This ppts file will give the students of biochemistry or biology, in general, a brief outlook on the structure and functions of MHC, as well as its mode of action.
I hope this work will help intermediate students grasping the topic.
it is related to immunology .. Major histo compatibility complex - a highly polymorphic region on chromosome 6 with genes particularly involved in immune functions..
Immunity :
It is defined as the resistance exhibited by the host against any
foreign antigen including microorganisms.
Plays a major role in prevention of infectious diseases.
Types of immune cells
∆Lymphoid cells
-lymphocytes
constitute 20%–40% of the body’s white blood cells and 99% of the cells in the lymph
continually circulate in the blood and lymph and are capable of migrating into the tissue spaces and lymphoid organs
lymphocytes enlarge into 15 µm-diameter blast cells, called lymphoblasts; these cells have a higher cytoplasm : nucleus ratio and more organellar complexity than small lymphocytes.
Lymphoblasts proliferate and eventually differentiate into-
effector cells or into
memory cells.
* B-lymphocytes
*T-lymphocytes
* Natural killer cells
∆mononuclear phagocytes
The mononuclear phagocytic system consists of monocytes circulating in the blood and macrophages in the tissues.
-macrophages
-monocytes
∆granulocytes cells
Granulocytes are at the front lines of attack during an immune response and are considered part of the innate immune system.
Granulocytes are white blood cells (leukocytes) that are classified as neutrophils, basophils, mast cells, or eosinophils on the basis of differences in cellular morphology and the staining of their characteristic cytoplasmic granules
The cytoplasm of all granulocytes is replete with granules that are released in response to contact with pathogens.
These granules contain a variety of proteins with distinct functions:
Some damage pathogens directly;
some regulate trafficking and activity of other white blood cells, including lymphocytes
-neutrophills
-basophils
-eosinophils
-dendritic cells
-mast cells
Phagocytosis begins with adhesion of the phagocyte surface receptors to the pathogen, which then is internalized into vesicles called phagosomes.
Inside the phagocyte, the phagosome fuses to lysosomes, whose contents are released with consequent digestion and pathogen elimination.
Changes in the oxidase’s gene system components present in phagolysosome membrane lead to disability in respiratory burst and generation of reactive oxygen species (ROS).
Phagocytosis begins with adhesion of the phagocyte surface receptors to the pathogen, which then is internalized into vesicles called phagosomes.
Inside the phagocyte, the phagosome fuses to lysosomes, whose contents are released with consequent digestion and pathogen elimination.
Changes in the oxidase’s gene system components present in phagolysosome membrane lead to disability in respiratory burst and generation of reactive oxygen species (ROS).
The main effector cells of innate immunity are macrophages, neutrophils, dendritic cells, and natural killer (NK) cells .
Phagocytosis, release of inflammatory mediators, activation of complement system proteins, as well as synthesis of acute phase proteins, cytokines and chemokines are the main mechanisms in innate immunity
Immune system and its functions
The main effector cells of innate immunity are macrophages, neutrophils, dendritic cells, and natural killer (NK) cells .
The long-term preservation of the dentition is closely associated with the frequency and quality of recall maintenance. The therapist should use risk assessment and educate the patient on the need for periodontal maintenance. Supportive periodontal therapy is a lifetime effort to prevent the disease from recurring. Patients who do not return for supportive periodontal therapy lose more teeth than compliant patients.
Chronic periodontitis is an infectious disease resulting in inflammation with in supporting tissues of the teeth, progressive attachment loss and bone loss. With all emerging technologies, a successful diagnosis and treatment will only be achieved through open sharing of ideas, research findings and thorough testing .
Although there are many potential markers for periodontal disease activity and progression, numerous features still hamper the ability to use them as diagnostic tests of proven utility. After all these years of intensive research, we still lack a proven diagnostic test that has demonstrated high predictive value for disease progression.
There are many benefits to integrating orthodontics and periodontics in the management of adult patients with underlying periodontal defects. The key to treating these patients is communication and proper diagnosis before orthodontic therapy. Not all periodontal problems are treated in the same way. It should be remembered that overall success of orthodontic treatment depends on the combined effort and close monitoring of the case, by an orthodontist and a periodontist.
When occlusal forces exceed the adaptive capacity of the tissues, tissue injury results. The resultant injury is termed as trauma from occlusion.
TFO refers to tissue injury, not the occlusal force. An occlusion that produces such injury is termed as traumatic occlusion.
Evolution in the pathogenesis of periodontal diseaseDrAtulKoundel
Periodontal disease (PD) is one of the most common chronic inflammatory diseases affecting humans. It is of multi-factorial origin where host, environment and bacterial factors interplay to initiate immune-inflammatory response that causes most of the soft and hard tissue destruction
Implants for the aged patient: biological, clinical and sociological considerations.
The biological considerations in treating elderly patients with dental implants is the possibility of compromised wound healing following implant placement, as well as the effect of aging on the long-term integrity of osseointegration.
Dental plaque biofilm cannot be eliminated permanently.
However, the pathogenic nature of the dental plaque biofilm can be reduced by reducing the bio burden (total microbial load and different pathogenic isolates within that dental plaque biofilm) and maintaining a normal flora with appropriate oral hygiene methods that include daily brushing, flossing and rinsing with antimicrobial mouth rinses.
This can result in the prevention or management of the associated squeal, including the development of periodontal diseases and possibly the impact of periodontal diseases on specific systemic disorders.
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.
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
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.
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.
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
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Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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
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
2. CONTENTS
• Definition
• Types of immunity
• Cells of immune system
• Complement system
• Transendothelial migration
• Leucocytes function
• Specific immune response
3. Immunity
It is defined as the resistance exhibited by the host against any
foreign antigen including microorganisms.
Plays a major role in prevention of infectious diseases.
4. Immune system
The immune system is a network designed for the homeostasis
of large molecules (oligomers) and cells based on specific
recognition processes.
It is the collection of cells, tissues and molecules that function
to defend us against infectious microbes.
7. Cells of immunity
Cells of the immune system that are important in inflammation and host defenses
include
1. mast cells
2. peripheral dendritic cells
3. neutrophils
4. monocytes/macrophages
5. T cells
6. B cells
7. natural killer cells (NK).
Other hematopoietic leukocytes, including basophils, eosinophils, erythrocytes, and
platelets, also participate in certain forms of inflammation or immune function.
10. Innate immunity or non specific immunity is the natural
immunity that a person is born with i.e, it is there at birth.
The cells of innate immunity are phagocytic cells (i.e.,
monocytes, macrophages, neutrophils), which possess a
number of inherently antimicrobial peptides and proteins
that kill many different pathogens rather than one specific
pathogen.
11. 1. Mast cells
Mast cells are important in immediate inflammation.
More recently, mast cells have been shown to express toll-
like receptors. These receptors allow the innate immune
system to adapt (e.g., express the major histocompatibility
complex (MHC) class II molecules, produce nitric oxide and so
on.
12. Mast cells feature prominent cytoplasmic granules, termed
lysosomes, which store inflammatory mediators such as
1. histamine
2. eosinophil chemotactic factor
3. neutrophil chemotactic factor
4. heparin.
Mast cells can synthesize, other inflammatory mediators, such as
1. slow-reacting substances of anaphylaxis (SRS-A)
2. tumor necrosis factor alpha (TNF-α)
3. interleukin-6 (IL-6)
4. leukotrienes C4
13. 2. Peripheral dendritic cells
Peripheral dendritic cells (DCs) are leukocytes with
cytoplasmic projections, or dendrites.
Langerhans cells are DCs that reside in the supra-basilar
portions of squamous epithelium.
14. Dendritic Cells express high levels of
1. MHC class II molecules
2. intercellular adhesion molecule-1 [ICAM-1]
3. leukocyte function–associated antigen-3 [LFA-3])
4. co-stimulatory factors.
15. 3. Neutrophils
Neutrophils, also known as polymorphonuclear
leukocytes (PMNs), are the predominant leukocyte
in blood approx. (4000-8000 cells/mm3).
They possess many lysosomes within their
cytoplasm.
Neutrophils possess receptors for metabolites of
the complement molecule C3 and C5. These
receptors enable neutrophils to
1. Be recruited from the blood
2. locate offending agents
3. Ingest (phagocytose) and kill the offending
agents.
16. 4. Monocytes
Monocytes are referred to as macrophages
when they leave the blood.
They may become greater than 22 μm in
diameter.
Because macrophages differentiate and live in
the local tissues, they are suited for
communicating with lymphocytes and other
surrounding cells.
Macrophages live long enough to present
antigen to T cells. Together, macrophages and
lymphocytes orchestrate the chronic immune
response.
19. Complement (C) is an interacting network of about 30
membrane-associated cell receptors and soluble serum
glycoproteins.
Soluble components of this system account for about 5% (3-4
mg/ml) of the total serum protein.
The soluble components of the complement system were first
observed to cause bacteriolysis and cytolysis in association with
antibody, and later in the absence of antibody.
20. The complement system is a central component of
inflammation that enables endothelium and leukocytes to
recognize and bind foreign substances for which they lack
receptors. Complement promotes inflammation by
generating the following:
1. A Vasoactive substance, termed kinin-like, C2a, which induces pain
and increases vascular permeability and dilation.
2. Molecules, termed anaphylatoxins, C3a and C5a, which produce
anaphylaxis by inducing mast cell secretion.
3. A chemotaxin, C5a, which attracts leukocytes and stimulates
phagocyte secretion.
4. An opsonin, C3b, covalently bound to molecular aggregates, particles,
or cells, which enables phagocytes to ingest them.
21. C3 is the most important component of complement system.
A sequestered, internal thioester bond is the essential feature of C3, and it
shares this feature with the related molecule, C4.
Splitting of C3 forms C3a and C3b and exposes the internal thioester bond
residing within the C3b fragment.
Two main pathways result in the splitting of C3: the alternative and classical
pathways.
Both the alternative pathway and the classical pathway lead to
inflammation and phagocytosis through an enzyme that is designated a
bound C3 convertase.
The alternative pathway leads to the hydrolysis of C3b by larger structures
(designated R), including the hydroxyls and amines on macromolecules and
bacterial cell surfaces. The resulting covalent structure, C3b-R, leads to the
bound C3 convertase (R-C3bBb).
22. The classical pathway is initiated in response to the presence of some
irritant.
Irritants include antibody-antigen complexes, certain membranes, or
suspicious polymers.
This pathway involves the activation of a serine protease (e.g., C1qrs)
that has attached to an irritant.
The protease serves as a C4/C2 convertase and leads to formation of a
C3 convertase covalently bound to R (R-C4bC2b), with release of the
vasoactive kinin-like substance C2a.
23. Two main processes can occur with the formation of bound C3 convertase.
First, amplification occurs, and second, the membrane attack complex is
formed.
Amplification is an exponential increase in the formation of C3b.
Membrane attack complex is initiated after approximately 100 molecules
of C3b are formed.
These new complexes can bind and cleave both C3 and C5; thus they are
called C3/C5 convertase.
24. The C5 convertase activity is monumentally
slow (one of the slowest enzymatic activities
known).
C5 produces two important fragments, C5a
and C5b.
The C5a fragment is the main leukocyte
chemoattractant derived from complement
and is an important anaphylatoxins.
The C5b component associates with C6, C7,
C8, and C9, forming a membrane attack
complex that can kill certain bacteria and
cells by forming a large pore in the target cell
membrane.
26. Transendothelial migration is a selective interaction between leukocytes and
endothelium that results in the leukocyte pushing its way between
endothelial cells to exit the blood and enter the tissues.
The blood contains only 2% of all lymphocytes at any given time.
In a local inflammatory response, transendothelial migration occurs in the
following sequential phases
1. Rolling
2. Complement activation
3. signaling the endothelium
4. increased rolling
5. signal for rolling arrest
6. strong adhesion
7. zipper phase
8. Basement membrane degraded
9. Chemotaxis
27. Leukocytes use the lectin (a non-enzymatic carbohydrate-binding protein)
designated L-selectin to interact with carbohydrate molecules known as
vascular addressin on the luminal surface of endothelial cells.
A local insult triggers the release of a variety of inflammatory signals (e.g.,
interleukin-1β, tumor necrosis factor alpha) from cells in the tissue,
especially from resident leukocytes such as mast cells.
IL-1β, TNF-α, C5a, and lipopolysaccharides can stimulate endothelial cells
to express P selectin and E-selectin on their luminal surfaces. This appears
microscopically as an increase in number of leukocytes attached to the
luminal surface of the endothelium, or increased rolling.
28. The stimulated endothelium also
releases chemokines.
Chemokines are small peptide
cytokines, first recognized for their
chemoattractant activities, which
play a fundamental role as selective
signals for leukocytes to exit the
blood. Chemokines function as a signal
for rolling arrest.
29. The interaction of a chemokine, interleukin-8 (IL-8), with the leukocyte
receptor CXCR2 causes the leukocyte to shed L-selectin and upregulate the
integrin leukocyte function–associated antigen-1 (LFA-1).
LFA-1 binds intercellular adhesion molecule-2 (ICAM-2), which is expressed
constitutively by endothelium. This results in rolling arrest because the
phagocyte becomes firmly associated with the endothelium.
CD31 (platelet-endothelial cell adhesion molecule-1) is a transmembrane
glycoprotein present at the intercellular borders of endothelial cells facing into
lumen and on all leukocytes.
Once the leukocyte locates the inter-endothelial junction, it uses its own
CD31 as a zipper.
This zipper effect has been proposed as a mechanism of minimizing the
leakage of fluid. As the endothelium unzips its CD31, the leukocyte rapidly
“zips” between the endothelial cells.
Leukocytes possess several proteases, including uro-kinase plasminogen
activator receptor (uPAR). The uPAR leads to the activation of collagenase,
which then degrdae the basement membrane and enable the leukocyte to
enter the connective tissue.
31. 1. Chemotaxis
Once the leukocyte enters the connective tissue, it must be able to locate
and migrate to the site of insult.
This is accomplished by chemotaxis, which depends on the leukocyte’s
ability to sense a chemical gradient across its cell body and migrate in the
direction of increasing concentration.
The phagocyte senses only a limited number of chemicals: chemotaxins for
which it has receptors.
The receptors for chemotaxis belong to a family called the G-protein
coupled family.
32. 2. Phagocytosis
Phagocytosis is the process by which cells ingest particles of a size visible to
light microscopy.
Neutrophils and monocytes/macrophages are the only cells efficient
enough at phagocytosis to be considered “professional phagocytes.”
Phagocytosis results of a pathogen within a membrane-delimited
structure, the phagosome.
The immune system has evolved mechanisms of coating the pathogen with
a few recognizable ligands, which enable the phagocyte to bind and ingest
the pathogen. This is referred to as opsonization.
33. Once a microbe has been ingested, it may be killed. Phagocytes kill bacteria through
two broad categories of killing mechanisms.
1. Oxidative mechanisms require
The presence of oxygen and
An oxidation reduction potential.
2. Non-oxidative mechanisms requires
phagosome-lysosome fusion
Each neutrophil possesses two main types of lysosomes, or granules:
Specific granules, designed for both extracellular and intra phago-lysosomal secretion.
Azurophil granules, designed mainly for intra phago-lysosomal secretion.
35. One of the primary challenges of the
innate system is the discrimination
of pathogens from host..
This challenge is met by recognition
of the evolutionary structures:
The PRRs.
They are primitive pattern recognition receptor.
These receptors identify specific structural patterns.
Discriminates between self and non-self.
On the basis of function PRRs are classified as:
1. Signaling PRRs
Toll-like receptors
NOD receptors (Nucleotide-Oligomerization
domain)
2. Endocytic PRRs
On the basis of location PRRs are classified as:
1. Membrane bound PRRs
2. Cytoplasmic PRRs
3. Secreted PRRs
PRRs (Pattern Recognition
Receptor)
36. TOLL-LIKE RECEPTORS
Toll-like receptors are the gate keepers of innate immunity.
These are a class of Pattern Recognition Receptor (PRRs) that recognises Microbiota
associated molecular patterns (MAMPs) and that signals cytokine secretion in innate
cells.
Among the 10 human toll-like receptors identified so far, toll-like receptor-2 and
toll-like receptor-4 are the most defined members.
Toll-like receptor-2 is mostly involved in the recognition of a variety of different
bacterial cell components, such as peptidoglycans and lipoproteins.
Toll-like receptor-4 has been shown to specifically recognize lipopolysaccharide of
Gram-negative bacteria and acts in cooperation with several protein components, such
as lipopolysaccharide-binding protein and CD14.
The gingiva is constantly exposed to microbes present in plaque biofilm, toll-like
receptors signaling plays an important role in the innate immune response and
maintenance of periodontal health. However, over-production of pro-inflammatory
cytokines due to chronic stimulation of toll-like receptors, they may lead to tissue
destruction.
37.
38. TLR signaling pathway……
The Toll-Like Receptors are single-pass transmembrane proteins
characterized by an N-terminal leucine-rich recognition domain and an
intracellular C-terminal Toll/IL-1 receptor signaling domain (TIR).
TIR domains of TLRs act as a scaffold to recruit various TIR domain-
containing adaptor proteins:
1. Myeloid differentiation primary-response protein 88 (MYD88)
2. MYD88-adaptor-like protein (MAL)
3. TIR domain-containing adaptor protein inducing IFN-β (TRIF)
4. TRIF-related adaptor molecule (TRAM).
39. With the exception of TLR-3, all TLRs engage the
MyD88 adapter protein.
TLR-3 and TLR-4 uniquely interact with the
TRIF adapter protein.
Engagement of the adapter proteins at the TIR
domain of TLRs initiates signal transduction that
involves interactions between the adaptor
molecules, IL-1 receptor– associated kinases
(IRAKs) and TNF receptor–associated factors
(TRAFs).
In the case of TLR-2 localized to the plasma
membrane, MyD88-dependent downstream
activation of transforming growth factor-beta
(TGF-β), activated kinase 1 (TAK-1)
simultaneously induces mitogen- activated
protein kinase (MAPK) and nuclear factor-κB
(NF-κB) signaling.
40. NF-κB translocates to the nucleus, and MAPK cascades activate activator
protein 1 (AP-1), ultimately resulting in the expression of proinflammatory
cytokine genes.
When TLR-4 translocates to endosomes, TRIF-dependent signaling leads to the
activation of NF-κB and IFN-regulatory factor (IRF)-3, resulting in the
expression of proinflammatory cytokine and type I IFN genes.
Concerning TLR- 9 localized to the endo lysosomal membrane, MyD88-
dependendent signaling leads to the activation of IRF-7, which up-regulates
the expression of type I IFN genes.
The TLR signaling pathways highlights the potential for synergy or
amplification effects modulating the host immune response.
41. ANTIGEN PRESENTATION
Cellular interaction is very important for the recognition and
presentation of antigens to the immune system by antigen presenting
cells.
Antigens are macromolecules which are presentable and recognizable so
that the antigen processing and presenting cells digest them into smaller
fragments which are then presented on their surfaces (APCs) using MHC
molecules and CD1 clusters.
The three main professional APCs are
1. Peripheral DCs,
2. Monocyte derivatives,
3. B cells (these are both antigen receiving and presenting cells).
42. However, binding of T-lymphocytes to MHC/ or CD1 cluster alone does not activate the T-
lymphocytes into action.
So in order to become activated T-cell must receive a second signal from APC.
This second signal is called as co-stimulation. It is mediated by a variety of transmembrane
molecules of the tumor necrosis factor (TNF) superfamily.
Co-stimulation performs three functions:
1. Makes the T cell resistant to apoptosis
2. Increase the proliferation of T-cells
3. Decreases the amount of time needed to trigger the T cell response (also referred to as amplification)
B –cell also require co-stimulation to proliferate further after initial recognization and binding
to the antigen.
44. The adaptive immune system is also known as the acquired
immune system/specific immune system.
It is activated by the non specific innate immune system.
Lymphocytes (e.g., T cells, B cells) get stimulated through
their B and T cell antigen receptors (BCRs and TCRs)
present on the cell membranes which facilitates the specific
targets.
45. 1. T Cells
T cells are responsible for cell mediated immunity.
T cells recognize diverse antigens using a low-affinity
transmembranous complex, the T-cell antigen receptor (TCR).
The T cells are of the following types:
1. Helper T cells (CD4 cells).
2. Cytotoxic T cells (CD8 cells).
3. Regulatory (Suppressor).
4. Memory T cells.
5. Natural killer T cells (NK T cells).
46. Helper T cells/ CD4 cells are responsive to MHC class II molecules found on
the dendritic cells, macrophages and B lymphocytes.
Cytotoxic T cells/CD8 cells are cytotoxic and kills virus infected cells eg. HIV
infected CD4+ T cells, cells infested with bacteria or protozoa, allograft eg.
Transplanted kidney, heart, lungs, etc. and cancer cells.
Regulatory/ suppressor T cells maintain immunological tolerance and
regulate effects and continuation of the immune response.
Memory T cells live for a long time after an infection has been settled. Upon
re-exposure by the same microbe, they quickly expand the number of
effector T cells and effects the specific immune response.
Natural Killer T cells/ NKT cells are a heterogeneous group of T cells that
share properties of both T cells and Natural killer cells. Dysfunction or
deficiency of NKT cells is believed to lead to the development of autoimmune
diseases eg. Diabetes, cancer, etc.
47. 2. B Cells
B cells are primarily responsible for humoral immunity.
B cells work chiefly by secreting soluble substances called antibodies into
the body fluids.
B cells recognize diverse antigens using the B-cell antigen receptor (BCR),
which is a high-affinity antigen receptor.
The high-affinity interaction between BCR and antigen enables the B cell
to bind and ingest the antigen without antigen presentation. Ingested
antigen is degraded and presented to T cells.
48. 3. Natural Killer (NK) Cells
• NK cells recognize and kill certain tumor and virally infected cells.
• The NK cells possess several classes of antigen receptors, including killer
inhibitory receptor (KIR) and killer activating receptor (KAR).
• NK cells have small granules containing proteases, perforin, etc in their
cytoplasm.
• These receptors also recognizes the antigens.
49. SPECIFIC IMMUNE RESPONSES
Following events that take place are:
1. Clonal selection – selection and activation of specific lymphocytes which are
capable of recognizing specific Antigen.
2. Clonal expansion – increase in the number of activated lymphocytes (up to
5000 times).
3. Clonal contraction – apoptosis of activated lymphocytes after completing
their job.
4. Memory – maintenance of these activated lymphocytes in small number till
the time body encounters the same antigen again. These cells will cause
rapid immune response (secondary immune response).
When the body encounters the same antigen again the memory cells
will induce clonal expansion at a rapid phase (1 to 3 days).
50. T-CELL RESPONSES
After receiving co-stimulation, cytokines receptors are activated and
produce cytokines. Once activated, the T cell undergoes proliferation and
differentiation, leading to one of several possible mature T-cell
phenotypes.
51. B-CELL RESPONSES AND ANTIBODIES
B cells produce immunoglobulins at the site of infection from local and systemic
tissue sources.
An immunoglobulin that binds a known antigen is known as antibody.
Immunoglobulin accounts for about 20% to 25% (15 mg/ml) of the total serum
protein (60-70 mg/ml).
Humans possess nine genetically distinct isotypes of immunoglobulins: IgM, IgD,
IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, and IgE.
The ability of B cells to respond to antigen depends on the B-cell antigen receptor
(BCR). The BCR is formed partly by immunoglobulin molecules on the B-cell
surface, which serve as highly specific antigen receptors.
52. B cells are capable of responding to certain antigens in the absence of T cells.
This is referred to as T-independent B-cell antibody response.
However, in some situations B-cells are activated by the T-cells. This is known
to be T cell dependent antibody response.
In this pathway B cell bind soluble antigens and then they are ingested and
processed. Thus mechanism of binding antibody to antigen results in
protection via:-
1. Neutralization
2. Agglutination
3. Opsonization
4. Complement activation
5. Enhanced NK cells