The document discusses the nature of antigens and the major histocompatibility complex (MHC). It defines immunogens and antigens, noting that immunogens can trigger an immune response while not all antigens are immunogens. Antigens are usually large proteins or polysaccharides from foreign organisms. Factors like age, health, dose, and route of exposure can influence the immune response. The document also discusses epitopes, haptens, adjuvants, and the relationship of antigens to the host (autoantigens, alloantigens, heteroantigens). It provides details on MHC genes, class I and class II MHC structure and function in antigen processing and presentation to T cells.
Antigen
Antigen is a substance which binds specifically with the products (antibodies, T-cells) of the immune system.
Its ability to bind with antibodies is called antigenicity.
Immunogen
It is a substance which produces an immune response as well as binds to its products.
So, immunogen is an antigen as well but antigen need not be immunogen.
The property of producing an immune response is called immunogenicity.
Antigen
Antigen is a substance which binds specifically with the products (antibodies, T-cells) of the immune system.
Its ability to bind with antibodies is called antigenicity.
Immunogen
It is a substance which produces an immune response as well as binds to its products.
So, immunogen is an antigen as well but antigen need not be immunogen.
The property of producing an immune response is called immunogenicity.
ANTIGEN, HAPTEN, ALL TYPES OF ANTIGENS, IMMUNOGEN , ATTRIBUTES OF ANTIGENICITY, DETERMINANTS OF ANTIGENICITY,
IMMUNOLOGY KUBY, MEDICAL MICROBIOLOGY & IMMUNOLOGY OF PANIKER , LIPPINCOTT'S IMMUNOLOGY, OTHER SOURCES.
Antibodies are immune system-related proteins called immunoglobulins. Each antibody consists of four polypeptides– two heavy chains and two light chains joined to form a "Y" shaped molecule. ... This variable region, composed of 110-130 amino acids, give the antibody its specificity for binding antigen.
History
Introduction
Classification of grafts
The Immunology of Allogeneic Transplantation
Genetics of graft rejection
Types of rejection
Recognition of Alloantigens
Effector Mechanisms of Allograft Rejection
Prevention of graft rejection
Graft versus host reaction
Type II Hypersensitivity-Antibody mediated cytotoxic HypersensitivityAnup Bajracharya
Type II Hypersensitivity is antibody-mediated immune reaction in which antibodies (IgG or IgM) are directed against cellular or extracellular matrix antigens with the resultant cellular destruction, functional loss, or damage to tissues.
ANTIGEN, HAPTEN, ALL TYPES OF ANTIGENS, IMMUNOGEN , ATTRIBUTES OF ANTIGENICITY, DETERMINANTS OF ANTIGENICITY,
IMMUNOLOGY KUBY, MEDICAL MICROBIOLOGY & IMMUNOLOGY OF PANIKER , LIPPINCOTT'S IMMUNOLOGY, OTHER SOURCES.
Antibodies are immune system-related proteins called immunoglobulins. Each antibody consists of four polypeptides– two heavy chains and two light chains joined to form a "Y" shaped molecule. ... This variable region, composed of 110-130 amino acids, give the antibody its specificity for binding antigen.
History
Introduction
Classification of grafts
The Immunology of Allogeneic Transplantation
Genetics of graft rejection
Types of rejection
Recognition of Alloantigens
Effector Mechanisms of Allograft Rejection
Prevention of graft rejection
Graft versus host reaction
Type II Hypersensitivity-Antibody mediated cytotoxic HypersensitivityAnup Bajracharya
Type II Hypersensitivity is antibody-mediated immune reaction in which antibodies (IgG or IgM) are directed against cellular or extracellular matrix antigens with the resultant cellular destruction, functional loss, or damage to tissues.
Structure of antigens and receptors, Genetic control of immune response, Antigens processing by antigen presenting cell, Role of MHC and accessory molecules, Antigen-antibody interactions
Here are five things to know about coronavirus tests: PCR and antigen tests are the most common but they work differently. While antigen tests look for proteins ...
An antigen is any substance that causes your immune system to produce antibodies against it. This means your immune system does not recognize the substance, and is trying to fight it off. An antigen may be a substance from th
What is antigen
What is epitope & paratope?
Classification of antigen
Pro antigen
Superantigens
Antigenicity
Determinants of antigenicity
Test for antigen detection
An antigen is either a cell or molecule which will bind with pre exiting antibody but will not definitely cause induction of antibody production. Antigen may also be defined as ‘a macro molecular entity that essentially elicits an immune response via the formation of specific antibodies in the body of the host’. And Hapten may also be defined ‘as a substance that normally does not act as an antigen or stimulate an immune response but that can be combined with an antigen and, at a later time, initiate a specific antibody response on its own’.
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.
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Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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.
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
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
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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.
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!
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.
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.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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
2. Immunogens
macromolecules capable of triggering an adaptive immune
response
How???
by inducing the formation of antibodies or sensitized T cells in an
immunocompetent host.
can then specifically react with such antibodies or sensitized T
cells.
Antigen
refers to a substance that reacts with antibody or sensitizedT cells
What’s the difference between Immunogen and Antigen?
Immunogen is capable of triggering an immune response.
Antigen may not be able to evoke an immune response in the first place.
All immunogens are antigens, but not all antigens are immunogens.
3. Antigens
Most are proteins or large polysaccharides from
a foreign organism.
Microbes: Capsules, cell walls, toxins, viral capsids,
flagella, etc.
Nonmicrobes: Pollen, egg white , red blood cell
surface molecules, serum proteins, and surface
molecules from transplanted tissue.
Lipids and nucleic acids are only antigenic when
combined with proteins or polysaccharides.
Molecular weight of 10,000 or higher.
Hapten: Small foreign molecule that is not antigenic. Must be
coupled to a carrier molecule to be antigenic. Once antibodies
are formed they will recognize hapten.
4. FACTORS INFLUENCING THE IMMUNE RESPONSE
(1) Age
older individuals
Neonates
(2)Overall health
Malnourishment
Fatigue
Stress
(3)Dose
Generally, the larger the dose of an immunogen one is exposed to, the
greater the immune response is.
However, very large doses can result inT- and B-cell tolerance, a
phenomenon that is not well understood. It is possible that memory cells
become overwhelmed and therefore nonresponsive.
5. FACTORS INFLUENCING THE IMMUNE RESPONSE
(4)Route of Inoculation
intravenous (into a vein)
intradermal (into the skin)
subcutaneous (beneath the skin)
oral administration
Where the immunogen enters the body determines which
cell populations will be involved in the response and how
much is needed to trigger a response.
(5)Genetic Predisposition
Lastly, a genetic predisposition may be involved that allows
individuals to respond to particular immunogens.
6. In general, the ability of an immunogen to
stimulate a host response depends on the following
characteristics:
(1) macromolecular size
molecular weight of at least 10,000-- to be recognized by the
immune system,
molecular weight of over 100,000 daltons-- best immunogens
For the most part, the rule of thumb is that the greater the
molecular weight, the more potent the molecule is as an
immunogen.
(2) chemical composition and molecular complexity
Proteins and polysaccharides--are the best immunogens
Proteins
are powerful immunogens, because they are made up of a
variety of units known as amino acids.
7. Carbohydrates
are somewhat less immunogenic than protein
As immunogens, carbohydrates most often occur in the form
of glycolipids or glycoproteins.
Pure nucleic acids and lipids-- are not immunogenic by
themselves, although a response can be generated when they
are attached to a suitable carrier molecule
(3) foreignness
The immune system is normally able to distinguish between self
and nonself, and those substances recognized as nonself are
immunogenic.
8. (4) the ability to be processed and presented with MHC molecules
A substance must be subject to antigen processing, which
involves enzymatic digestion to create small peptides or pieces
that can be complexed to MHC molecules to present to
responsive lymphocytes.
If a macromolecule can’t be degraded and presented with MHC
molecules, then it would be a poor immunogen.
9. Types of antigen:
1. T-independent Antigens
• Can directly stimulate B cells to produce
antibodies
• Polysaccharides in general
• Generally more resistant to degradation
persist for longer periods of time continue to
stimulate immune system
10. 2. T-dependent Antigens
• Do not directly stimulate antibody production;
need help ofT cells
• Usually proteins
11. Epitopes
Small part of an antigen that interacts with an
antibody. 10-12 amino acids
Any given antigen may have several epitopes.
Each epitope is recognized by a different antibody.
Large molecules may have numerous epitopes, and
each one may be capable of triggering specific
antibody production or aT-cell response.
Epitopes may be repeating copies, or they may have
differing specificities.They may also be:
sequential or linear
13. Types:
1. Linear epitope – formed by a specific sequence
2. Conformational epitope – formed by a 3-D
structure
14. Schematic representation of two antibodies interacting with linear and
conformational epitopes.
a. Linear epitopes are short and continuous. After denaturation the linear
epitopes may still be able to bind the antibody.
b. Conformational epitopes are domains of proteins composed of specific
regions of protein chains. After denaturation the discontinuous epitope can
no longer bind the antibody.
15. EPITOPE
B CELL EPITOPE
• Region that is recognized by immunoglobulins
• Size can encompass 3-20 amino acids or sugar residues
• Limited to portions of the antigen that are accessible to the
antibody
16. EPITOPE
B CELL EPITOPE
Antigenic determinants are usually limited to those portions of the
antigen that are accessible to antibodies shown in black for this
iron-containing protein.
17. EPITOPE
T CELL EPITOPE
• Region recognized byT cell receptor
• 8 – 15 amino acid residues long
• recognized byT lymphocytes only after being processed and
presented in association with an MHC protein limited to
portions of the antigen that can bind to MHC proteins
18. HAPTENS
• Molecule that is not immunogenic by itself but can
react with specific antibody
• A low MW substance which by itself cannot
stimulate an immune response
• Has to be bound to a carrier molecule (immunogenic
molecule)
• Cannot activate helperT cells unable to bind to
MHC proteins since are not polypeptides
• Univalent cannot activate B cells by themselves
19.
20. An example of the latter is an allergic reaction to
poison ivy.
Poison ivy (Rhus radicans) contains chemical
substances called catechols, which are haptens.
Once in contact with the skin, these can couple with
tissue proteins to form the immunogens that give rise
to contact dermatitis.
Another example of haptens coupling with normal
proteins in the body to provoke an immune response
occurs with certain drug-protein conjugates that can
result in a life-threatening allergic response.
The best known example of this occurs with penicillin.
21. The most famous study of haptens was conducted by Karl
Landsteiner, a German scientist who was known for his discovery
of the ABO blood groups.
In his book The Specificity of Serological Reactions, published in
1917, he detailed the results of an exhaustive study of haptens
that has contributed greatly to our knowledge of antigen–
antibody reactions.
He discovered that antibodies recognize not only chemical
features such as polarity, hydrophobicity, and ionic charge, but
the overall three-dimensional configuration is also important.1,2
The spatial orientation and the chemical complementarity are
responsible for the lock-and-key relationship that allows for tight
binding between antibody and epitope.
Today it is known that many therapeutic drugs and hormones can
function as haptens.2
22. RELATIONSHIP OF ANTIGENS TO THE HOST
Antigens can be placed in broad categories according to
their relationship to the host.
Autoantigens
are those antigens that belong to the host.These do not evoke an
immune response under normal circumstances.
Alloantigens
Are from other members of the host’s species, and these are
capable of eliciting an immune response.
They are important to consider in tissue transplantation and in
blood transfusions.
Heteroantigens
are from other species, such as other animals, plants, or
microorganisms.
23. Heterophile antigens
are heteroantigens that exist in unrelated plants or animals but
are either IDENTICAL or CLOSELY RELATED in STRUCTURE so
that antibody to one will cross-react with antigen of the other.
An example of this is the human blood group A and B antigens,
which are related to bacterial polysaccharides.
anti-A antibody
normally found inType B andType O individuals is originally formed
after exposure to pneumococci or other similar bacteria.
Naturally occurring anti-B antibody is formed after exposure to a
similar bacterial cell wall product.
24. ADJUVANTS
is a substance administered with an
immunogen that increases the immune
response.
It acts by producing a local inflammatory
response that attracts a large number of
immune system cells to the injection site.1
25. EXAMPLES:
(1)Aluminum salts
are the only ones approved for clinical use in the
United States
these are used to complex with the immunogen to
increase its size and to prevent a rapid escape from
the tissues.
It must be injected into the muscle to work.
The hepatitis B vaccination is an example of
using this type of adjuvant.
26. (2)Freund’s complete adjuvant
consists of mineral oil, emulsifier, and killed
mycobacteria (0.5 mg/mL).Antigen is mixed with
adjuvant and then injected.
It is released slowly from the injection site.
Freund’s adjuvant produces granulomas, or large
areas of scar tissue, and thus is not used in
humans.
27. (3)Liposomes – defined lipid complexes
(4)Bacterial cell wall components
(5)Polymeric surfactants
(6)Cholera toxin & E. coli lymphotoxin –
potent adjuvants for IgA
28. Adjuvants are thought to enhance the
immune response by:
prolonging the existence of immunogen in
the area
increasing the effective size of the
immunogen
increasing the number of macrophages
involved in antigen processing
30. MAJOR HISTOCOMPATIBILITY COMPLEX
originally referred to as “Human Leukocyte
Antigens (HLA)”.
The French scientist Dausset gave them this name,
because they were first defined by discovering an
antibody response to circulating white blood cells.
These antigens are also known as “Major
Histocompatibility Molecules(MHC), because they
determine whether transplanted tissue is
HISTOCOMPATIBLE and thus accepted or
recognized as foreign and rejected.
31. are actually found on all nucleated cells in the body
play a pivotal role in the development of both humoral and
cellular immunity.
Their main function is to bring antigen to the cell surface
for recognition byT cells
T-cell activation will occur only when antigen is combined with
MHC molecules.
Clinically, they are relevant, because they may be involved
in transfusion reactions, graft rejection, and autoimmune
diseases.
32. Genes Coding for MHC Molecules
(HLA Antigens)
The MHC system is the most polymorphic system found in
humans.
It is thought that this polymorphism is essential to our
survival, because MHC molecules play a pivotal role in
triggering the immune response to diverse immunogens.
Genes coding for the MHC molecules in humans are found
on the short arm of chromosome 6
divided into three categories or classes.
Class I
Class II
Class III
33. GENES:
HLA-A, HLA-B, HLA-C code for class I MHC
proteins
HLA-D (DP, DQ, DR) code for class II MHC
proteins
Between the class I and class II regions on
chromosome 6 is the area of class III genes--
which code for complement proteins and
cytokines such as tumor necrosis factor.
34. Class III proteins are secreted proteins that
have an immune function, but they are not
expressed on cell surfaces.
Class I and II gene products are involved in
antigen recognition and influence the
repertoire of antigens to which T cells can
respond.
35. Structure of Class I Molecules
• Found on all nucleated cells and platelets
• Present endogenous peptides
They are highest on lymphocytes and low or undetected
on liver hepatocytes, neural cells, muscle cells, and
sperm.
36. • Heterodimer --made up of two noncovalently
linked polypeptide chains--polymorphic
(heavy) chain non-covalently bound to a 2-
microglobulin (chr. 15)
• Heavy chain composed of:
1. Hypervariable region – important for
recognition of self and non-self
2. Constant region – CD8+T cell binding site
37. The chain has a molecular weight of 45,000. A lighter
chain associated with it, called a β2–microglobulin, has a
molecular weight of 12,000 and is encoded by a single
gene on chromosome 15 that is not polymorphic.6
The chain is folded into three domains, 1, 2, and 3, and it
is inserted into the cell membrane via a transmembrane
segment that is hydrophobic.
38. Schematic representation depicting processing of antigens presented by class I
MHC molecules.
(1) Intracellular proteins are proteolytically degraded within proteasomes
(2) yields antigenic peptides of 9 – 11 amino acids
(3) antigenic peptides are transported into the ER
(4) bind to newly synthesized class I MHC molecules
(5) Class I MHC-antigenic peptide complexes are exported through the Golgi and
to the cell surface, for presentation of antigenic peptide to CD8+ T cells.
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39. three external domains-- 90 amino acids each
transmembrane domain--25 hydrophobic amino acids
along with a short stretch of about 5 hydrophilic amino
acids, and an anchor of 30 amino acids.
β2–microglobulin does not penetrate the cell
membrane, but it is essential for proper folding of the
chain. X-ray crystallographic studies indicate that the 1
and 2 domains each form an alpha helix and that these
serve as the walls of a deep groove at the top of the
molecule that functions as the peptide-binding site in
antigen recognition.
40. This binding site is able to hold peptides that are between 8 and 10
amino acids long.
Most of the polymorphism resides in the 1 and 2 regions, while the 3 and
2 regions are similar to the constant regions found in immunoglobulin
molecules.
The 3 region reacts with CD8 on cytotoxicT cells.
Another group of molecules called the nonclassical class I antigens are
designated E, F, and G. This group of molecules, except for G, are not
expressed on cell surfaces and do not function in antigen recognition but
may play other roles in the immune response.
G antigens are expressed on trophoblast cells during the first trimester
of pregnancy and are thought to help ensure tolerance for the fetus by
protecting placental tissue from the action of NK cells.
41. Structure of MHC Class II
CLASS II MHC MOLECULES
• Coded for by HLA-D (DP,DQ,DR)
• Heterodimer noncovalently associated chain
and chain
• Composed of:
1. Hypervariable region – responsible for polymorphism
2. Constant region – CD4T cell binding site
3. Invariant chain (Ii) – protect the binding site
• Found on APC’s
• Present exogenous antigens
42. Schematic representation depicting processing of antigens presented by class II MHC
molecules.
(1) Extracellular and integral membrane proteins are internalized into endosomes via
endocytosis
(2) Lysozomes fuse with endosomes.
3) Proteolytic degradation of endocytosed proteins resulting in the generation of antigenic
peptides
(4) A specialized subcellualr organelle containing the class II MHC molecules, invariant
chain, and DM fuses with the endolysozomal vesicle resulting in proteolytic degradation of
invariant chain to CLIP. DM then catalyzes removal of CLIP, and the empty class II MHC
molecules then bind antigenic peptides
(5) Class II MHC-antigenic peptide complexes are then exported to the cell surface, for
presentation of antigenic peptide to CD4+ T cells.
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43.
44. MHC glycoproteinsCLASS III MHC MOLECULES
• Between class I and class II; soluble proteins
• Contain immunologically important genes
encoding for:
1. Cytokines –TNF and lymphotoxin
2. Complement components – C2 and C4
• Does not have genes that code for
histocompatibility antigens
45. BIOLOGIC IMPORTANCE:
1. Antigen recognition byT cells
CD8T cells class I MHC molecules
CD4T cells class II MHC molecules
2. Autoimmune diseases occur in people who
carry MHC genes (e.g. HLA-B27 in ankylosing
spondylitis)
3. Success of organ transplants is determined by
compatibility of MHC genes of donor and
recipient.
46. Important Features of Some Human
MHC Gene Products
Class I Class II
Genetic loci (partial
list)
HLA-A, -B, and –C HLA-DP, -DQ, and
–DR
Polypeptide
composition
MW 45,000 + 2M (MW
12,000)
chain, chain, and Ii
chain
Cell distribution All nucleated somatic
cells
Antigen-presenting
cells, activatedT cells
Present peptide
antigens to
CD8+T cells CD4+T cells
Size of peptide
bound
8 – 11 residues 10 – 30 or more residues
47. Comparison of Class I and Class II MHC Proteins
Feature
Class I
MHC
Class II
MHC
Present antigen to CD4+ T cells No Yes
Present antigen to CD8+ T cells Yes No
Found on surface of all nucleated cells Yes No
Found on surface of professional APCs Yes Yes
Encoded by genes in the HLA locus Yes Yes
Expression of genes is codominant Yes Yes
Multiple alleles at each gene locus Yes Yes
Composed of 2 peptides encoded in HLA
locus
No Yes
Composed of one peptide encoded in the
HLA locus & a 2-microglobulin
Yes No
48. Structure of Class II Molecules
The occurrence of class II MHC molecules is much more restricted than that of class I, because they are found primarily on antigen-presenting cells, which include B
lymphocytes, monocytes, macrophages, and dendritic cells.
The major class II molecules—DP, DQ, and DR—consist of two noncovalently bound polypeptide chains that are both encoded by genes in the MHC complex.
DR is expressed at the highest level, as it accounts for about one-half of all the class II molecules on a particular cell.
The DR gene is the most highly polymorphic, as 18 different alleles are known at this time.
Both the chain, with a molecularweight of 33,000, and the chain, with a molecularweight of 27,000, are anchored to the cell membrane.11 Each has two domains, and it is
the 1 and the 1 domains that come together to form the peptide-binding site, similar to the one found on class I molecules7,10 (see Fig. 3–5).
However, both ends of the peptide-binding cleft are open, and this allows for capture of longer peptides than is the case for class I molecules. At least three other class II
genes have been described—DM, DN, and DO, the so-called nonclassical class II genes. Products of these genes play a regulatory role in antigen processing.7
The main role of the class I and class II MHC molecules is to bind peptides within cells and transport them to the plasma membrane, where T cells can recognize them in the
phenomemon known as antigen presentation.
T cells can only “see” and respond to antigens when they are combined with MHC molecules. While one individual can express only a small number of MHC molecules, each
molecule can present a large number of different antigenic peptides to T cells.
It is thought that the two main classes of these molecules have evolved to deal with two types of infectious agents:
those that attack cells from the outside (such as bacteria)
and those that attack from the inside (viruses and other intracellular pathogens).
Class I molecules mainly present peptides that have been synthesized within the cell to CD8 (cytotoxic) T cells, while class II molecules present antigen to CD4 (helper) T
cells.
Class II molecules mainly bind exogenous proteins—those taken into the cell from the outsideand degraded.13,14
Class I molecules are thus the watchdogsof viral, tumor, and certain parasitic antigens that are synthesized within the cell, while class II molecules stimulate CD4 T cells in
the case of bacterial infections or the presence of other material that is endocytosed by the cell.13,15
In either case, for a T-cell response to be triggered, peptides must be available in adequate supply for MHC molecules to bind, they must be able to be bound effectively,
49. and they must be recognized by aT-cell receptor.16
Some viruses, such as herpes simplex and adenovirus, have
managed to block the immune response by interfering with one
or more processes involved in antigen presentation.
These viruses are able to maintain a lifelong presence in the host
(see Chapter 22 for details).
The difference in functioning of the two molecules is tied to the
mechanisms by which processed antigen is transported to the
surface.
Both types of molecules, however, must be capable of presenting
an enormous array of different antigenic peptides toT cells.The
chemistry of the MHC antigens controls what sorts of peptides fit
in the binding pockets.These two pathways are discussed here.
50. Role of Class I Molecules
Both class I and class II molecules are synthesized in the rough endoplasmic reticulum, and for a
time they remain anchored in the endoplasmic reticulum membrane.
Class I molecules, however, actually bind peptides while still in the endoplasmic reticulum.7 In
fact, binding helps to stabilize the association of the chain of class I with the B2–microglobulin.16
However, before binding with antigen occurs, newly synthesized chains freely bind a molecule
called calnexin.This 88-kd molecule is membrane-bound in the endoplasmic reticulum, and it
keeps the chain in a partially folded state while it awaits binding to B2–microglobulin.13,18
When 2–microglobulin binds, calnexin is released, and three other chaperone molecules—
calreticulin, tapasin, and ERp57—are associated with the complex and help to stabilize it for
peptide binding17,18
(Fig. 3–6).
Peptides that associate with the class I molecules are approximately eight to ten amino acids in
length and are derived from partial digestion of proteins synthesized in the cytoplasm.
These intracellular peptides may include viral, tumor, or even bacterial antigens.12 Such peptides
may be newly made proteins that fail to fold correctly andhence are defective.
51. These are called defective ribosomal products (DRiPs).12 Twenty to 70 percent of all proteins synthesized in a cell may fall into this
category.8,19 Digestion of these defective or early proteins is carried out by proteases that reside in large cylindrical cytoplasmic
complexes called proteasomes.
13
Proteasomes are a packet of enzymes that play a major role in antigen presentation.13
Peptides must be unfolded before entering the cylindrical chamber of the proteosome, and then they are cleaved into the proper size for
delivery to class I molecules. Once cleaved, the peptides must then be pumped into the lumen of the endoplasmic reticulum by
specialized transporter proteins.7,15
These two proteins, transporters associated with antigen processing (TAP1 and TAP2), are responsible for the adenosine
triphosphate–dependent transport, from the cytoplasm to the lumen of the endoplasmic reticulum, of peptides suitable for binding to
class I molecules.8,17,18 TAP1 and TAP2 are most efficient at transporting peptides that have 12 amino acids or less.15,17
Tapasin brings the TAP transporters into close proximity to the newly formed MHC molecules and mediates interaction with them so
that peptides can be loaded onto the class I molecules.13,15 Once the chain has bound the peptide, the MHC I-peptide complex is rapidly
transported to the cell surface (see Fig. 3–6).6
Of the thousands of peptides that may be processed in this manner, only a small fraction of them (1 percent or less) actually induce a T-
cell response.15 Binding is based on interaction of only two or three amino acid residues with the class I binding groove. Different class I
molecules will have slightly different binding affinities, and it is these small differences that determine to which particular antigens one
individual will respond.
It is estimated that a single cell may express about 105 copies of each class I molecule, so many different peptides can be captured and
expressed in this manner.10 As few as 10 to 100 identical antigen-MHC I complexes can induce a cytotoxic response.15 In healthy cells,
most of these MHC I complexes contain self-peptides that are ignored by the T cells, while in diseased cells, peptides are derived from
viral proteins or proteins associated with cancerous states.
52. Display of hundreds of class I molecules
complexed to antigen allows CD8T cells to
continuously check cell surfaces for the
presence of nonself-antigen.
If it recognizes an antigen as being foreign,
the CD8T cell produces cytokines that cause
lysis of the entire cell (Fig. 3–7).
53. Role of Class II Molecules
Unlike class I molecules, class II molecules must be transported from the endoplasmic reticulum (ER) to an
endosomal compartment before they can bind peptides.7
Dendritic cells are the most potent activators ofT cells, and they are excellent at capturing and digesting
exogenous antigens such as bacteria.Class II molecules in the endoplasmic reticulum associate with a protein
called the invariant chain (Ii), which prevents interaction of the binding site with any endogenous peptides in the
endoplasmic reticulum.7,13
The invariant chain is a 31-kd protein that is made in excess so that enough is available to bind with all class II
molecules shortly after they are synthesized. Ii may be responsible for helping to bring and chains together in the
ER lumen and then moving them out through the Golgi complex to the endocytic vesicles, where digested antigen
is found.16
Because the open structure of class II molecules would permit binding of segments of intact proteins within the ER,
Ii serves to protect the binding site.20
Once bound to the invariant chain, the class II molecule is transported to an endosomal compartment, where it
encounters peptides derived from endocytosed, exogenous proteins.Antigen processing may help to unfold
molecules and uncover functional sites that are buried deep within the native protein structure.3The invariant
chain is degraded by a protease, leaving just a small fragment called class II invariant chain peptide (CLIP) attached
to the peptide-binding cleft.14,21 CLIP is then exchanged for exogenous peptides. Selective binding of peptides is
favored by the low pH of the endosomal compartment.16 HLA-DM molecules help to mediate the reaction by
removing theCLIP fragment. 6,10,21
Generally, peptides of approximately 13 to 18 amino acid residues can bind, because the groove is open on both
ends, unlike class I molecules, which have a closed end.10,14,22,23Within a central core of 13 amino acids, 7 to 10
residues provide the major contact points.10
54. Hydrogen bonding takes place along the length of the
captured peptide, in contrast to class I molecules, which
only bond at the amino and carboxy terminal ends.23,24
There are also several pockets in the class II proteins that
easily accommodate amino acid side chains.
This gives class II proteins more flexibility in the types of
peptides that can be bound.23,24
Once binding has occurred, the class II protein-peptide
complex is stabilized and is transported to the cell surface
(see Fig. 3–6). On the cell surface, class II molecules are
responsible for forming a trimolecular complex that occurs
between antigen, class II molecule, and an appropriateT-
cell receptor. If binding occurs with aT-cell receptor on a
CD4T cell, theT helper cell recruits andtriggers a B-cell
response, resulting in antibody formation (Fig. 3–8).
55. Clinical Significance of MHC
Testing for MHC antigens has typically been done, because both class I and class II molecules can induce a
response that leads to graft rejection.
Testing methodology has changed from serological principles to molecular methods, which are much more
accurate.The role of the laboratory in transplantation is presented in Chapter 17.
MHC antigens also appear to play a role in development of autoimmunediseases.The link between MHC antigens
and autoimmune diseases is discussed more fully in Chapter 14.
However, the evidence that both class I and class II moleculesplay a major role in antigen presentation has more
far-reaching consequences.They essentially determine thetypes of peptides to which an individual can mount an
immune response. Although the MHC molecules typically have a broad binding capacity, small biochemical
differences in these proteins are responsible for differences seen in the ability to react to a specific antigen.12 It is
possible that nonresponders to a particular vaccine such as hepatitis B do not have the genetic capacity to respond.
On the other hand, presence of a particular MHC protein may confer additional protection, as the example of HLA
B8 and increased resistance to HIV infection shows.8Therefore, it will be important to know an individual’s MHC
type for numerous reasons.
Much of the recent research has focused on the types of peptides that can be bound by particular MHC molecules.
23–25 Future developments may include tailoring vaccines to certain groups of such molecules. As more is learned
about antigen processing, vaccines containing certain amino acid sequences that serve as immunodominant
epitopes can be specifically developed.This might avoid the risk associated with using live organisms. Additionally,
if an individual suffers from allergies, knowing a person’s MHC type might also help predict the types of allergens
to which they may be allergic, because research in this area is attempting to group allergens according to amino
acid structure.25 It is likely that knowledge of the MHC molecules will affect many areas of patient care in the
future.