The document discusses several key mechanisms by which the immune system maintains tolerance to self-antigens to avoid autoimmunity. These include central tolerance in the thymus through negative selection which deletes self-reactive T cells, peripheral tolerance through ignorance, anergy, suppression and regulatory T cells, and the concept that tolerance is the default response unless danger signals are present to trigger an immune response. The timing of antigen exposure is also important, as antigens encountered during early development are more likely to induce tolerance.
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.
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.
introduction of adaptive immunity. classification of adaptive immunity, factor affecting it and mechanism of adaptive immunity comparison between adaptive immunity and innate immunity. characteristic of adaptive immunity . cell mediated immune responses immunoglobulins
types of immunoglobulins. functions of immunoglobulins, hypersensitivity reactions
The complement system is a part of the immune system that helps or complements the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the innate immune system, which is not adaptable and does not change over the course of an individual's lifetime.
consists of three pathways: 1. alternative
2. classical
3. lectin pathway
introduction of adaptive immunity. classification of adaptive immunity, factor affecting it and mechanism of adaptive immunity comparison between adaptive immunity and innate immunity. characteristic of adaptive immunity . cell mediated immune responses immunoglobulins
types of immunoglobulins. functions of immunoglobulins, hypersensitivity reactions
The complement system is a part of the immune system that helps or complements the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the innate immune system, which is not adaptable and does not change over the course of an individual's lifetime.
consists of three pathways: 1. alternative
2. classical
3. lectin pathway
immunological tolerance can be divided into two parts. they are central tolerance and peripheral tolerance. this slide contains information on development of central tolerance which include both B cell and T cell central tolerance.
One of the important parts in the study of Immunology.I prepared it for the sake of a seminar series competition conducted in my university. Now I thought of sharing it with others.
By DR. MANPREET KAUR BEHL.
Description of classificaton of immune system, immune cells, HLA, MHC complexes, antigen presentation, t-cell responses and b-cell responses, antibody, isotype switching, hypersenstivity reactions etc.
Biochemistry of Hair fall, A complete review of hair fall cause, Types, Current methods of treatment, Natural methods of treatment,
for more detail text see :https://iiopinion.blogspot.in/2017/01/hair-fall-scientific-way-of-treatment.html
Non-Specific Immune Response, Innate immunity, inherent immunity, Role in overall immunity of individual, Significance, components involve in Non-Specific Immune Response,
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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.
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.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
2. Our own bodies produce
some 1,00,000 different
proteins and BUT:---how the
immune system produces a
virtually universal range
while at the same time
avoiding reacting to self?
8/31/2015 6:56:30 AM
3. Definitions
We can consider two different
definitions of immunological tolerance.
The strict definition might
be that
immunological tolerance
occurs when an immuno-
competent host fails to
respond to an
immunogenic challenge
with a specific antigen.
A more operational
definition might be that
immunological tolerance
occurs when an
immunocompetent host
fails to respond to the
presence of a specific
antigen.
8/31/2015 6:56:30 AM
4. We have already seen that the adaptive immune system consists of two
distinct clonally variable repertoire expressed by T and B lymphocytes
respectively.
Thus: it is Clear that the essentially random process which
generates these repertoires will produce auto-reactive cells in both
lineages.
How does the immune system prevent the activation of these
cells?
Central Tolerance - this occurs
during lymphocyte development.
Peripheral Tolerance - occurs
after lymphocytes leave the
primary organs.
8/31/2015 6:56:30 AM
We can divide the mechanisms of immune system uses
into two main types:
5. I. Overview
• Billingham neonatal graft
experiments demonstrate
learning of tolerance
during development
• Shift of self-nonself
paradigm to “danger
theory”: immune response
generated in presence of
danger (e.g. PRRs
activated by PAMPs) and
tolerance in absence
Signal 1 vs. 2
• Signal 1
• TCR recognition of Ag
• Alone is tolerogenic,
leads to anergy or
deletion
• Signal 2
• Costimulatory molecule
engagement
• With signal 1, leads to T
cell activation
8/31/2015 6:56:30 AM
T Cell Tolerance
6. 8/31/2015 6:56:30 AM
A) Central tolerance: Mediated by negative
selection in thymus
In T cell development, the
process of –ve selection
leads to the deletion of those
thymocytes whose T cell
receptors have 'high affinity'
for self.
One aspect we did not
consider was what other
parameters influenced this
selection event?
•The only one we need to discuss is
antigen concentration.
For T cells, antigen means
the complex of specific
peptide and MHC.
so the density of any given
peptide-MHC complex is
determined by the
abundance of the peptide
and it's affinity for the
particular MHC allele.
The number of molecules of
any given peptide-MHC
complex on the surface of a
thymic APC probably varies
from 1-50K.
Now if there is only a mean
of 1 complex/cell then even
the highest affinity T cells
might fail to be deleted
whereas for the most
abundant peptide-MHC
complexes quite low affinity
T cells would be deleted.
Thus we would predict that
threshold affinity of TCR for
peptide-MHC required to
produce deletion =1/ the
abundance of that peptide-
MHC complex.
Using transgenic mice and
organ culture techniques it
has been possible to provide
evidence for this hypothesis.
7. • - Autoantigen level is so
low that anti-self T cells
are not activated
• - Poor mechanism for
tolerance: deleterious T
cell is still present in
periphery
1)
Ignorance
• - Negative selection can
occur in the periphery
as well in absence of
signal 2
2) Clonal
Deletion
• - In the absence signal
2, T cell can become
anergic
• - Anergic T is
unresponsive to signals
1 + 2, but recovered by
IL-2
3) T cell
anergy
8/31/2015 6:56:30 AM
B) PERIPHERAL TOLERANCE
8. • Absence of CD4+25+ T cells
causes autoimmune disease
• These cells act by inhibiting
IL-2 production
• Other cells are also
regulatory (e.g. TH3
secretes TGF-, TR1 secretes
IL-10)
4) T regulatory
cells
• - True role of TH3 and TR1
is to negatively regulate
immune response
5)
Immunoregulation
8/31/2015 6:56:30 AM
B) PERIPHERAL TOLERANCE-cont.
9. -can be extended to inhibit
autoimmunity and therefore
promote tolerance
- Providing Ag through gut
(or lungs) can activate these
cells and mediate tolerance
challenge
8/31/2015 6:56:30 AM
Function
10. ……And also…..
Almost any other parameter which affects
the overall strength of interaction between
a clone of thymocytes and the thymic
APC also affects the positive/ negative
selection decision.
Thus the conc. of TCR and of CD4 or CD8
also influences this reaction. One
mechanism of escape for 'autoreactive'
cells into the periphery that has been seen
in TCR transgenic mice is down-regulation
of the T cell receptor, co-receptor or both.
8/31/2015 6:56:30 AM
11. During B cell development, when the complete antigen
receptor (IgM) is first expressed on 'immature' B cells & if those
cells encounter their target antigen in a form which can cross-
link their sIgM, then such cells are programmed to die (deleted
from the repertoire).
It has been discovered that injection of PCA anti-IgM from
birth prevented the development of B cells, resulting in a 'B-
less' mouse. The requirement for crosslinking means that the
antigen has to be polyvalent, the most obvious example of this
being cell-surface mol
This has been directly demonstrated by using transgenic mice
expressing rearranged Ig genes specific for natural or artificial
membrane bound molecules. Presumably other multivalent self
antigens to which immature B cells are exposed also induce
deletion of self reactive cells.
8/31/2015 6:56:31 AM
B cells
13. Peripheral Tolerance
Because many of the proteins which the body uses are not expressed in thymus or
serum, and in some cases not expressed until after the immune system has matured
there need to be some mechanisms to prevent autoreactivity of lymphocytes after they
have emigrated from the thymus/bone marrow. In fact there are several such
mechanisms:
Ignorance Suppression Anergy
Split
Tolerance
8/31/2015 6:56:31 AM
14. Ignorance
in fact both T cells and B
cells specific for
autoantigens present in
circulation.
In some cases these cells are
quite capable of making a
response but are unaware of
the presence of their
autoantigen.
This arises for 2 reasons.
the antigen may simply be
present in too low conc.
Since all lymphocytes have a
threshold for receptor
occupancy which is required
to trigger a response, then
very low conc. of antigen (in
the case of T cells these are
very low) will not be sensed.
Some antigens are
sequestered from the
immune system in locations
which are not freely exposed
to surveillance, called
immunologically
privileged sites. e.g. eye,
CNS and testis.
8/31/2015 6:56:31 AM
15. Split Tolerance=that some part of the immune
system is tolerant and some other is not.
The most frequent ex. is that where T cell tolerance has been established but
autoreactive B cells are still present.
This arises because T and B cells have different thresholds for activation and
therefore tolerance.
In this situation the B cells are 'helpless'. i.e. for most of antigens, B cells
require help from an antigen-specific T cell in order to make a response.
Thus autoreactive B cells can be present without being able to become
activated provided that there is no T cell help available.
If T cell help is provided, for example by injecting the autoantigen chemically
coupled to an immunogenic foreign carrier, then these B cells will mount a
response.
8/31/2015 6:56:31 AM
16. Experiments of this kind indicate that it takes 100 -1000 × more antigen
to tolerate B cells than T cells. As a result this type of split tolerance
situation is reasonably common for self serum proteins.
8/31/2015 6:56:31 AM
17. Anergy - T cells
As mentioned in a previous lecture, naive T cells need co-
stimulatory signals to become activated. The expression of
these co-stimulatory molecules is restricted so that most
tissue cells lack either B7.1/B7.2 or CD40 or both. Such cells
also normally lack class II MHC molecules. Thus tissue
cells normally present a spectrum of peptides from their
endogenously synthesised proteins on self MHC class I in
the absence of co-stimulation. Interaction of such cells
with autoreactive T cells leads to the T cell becoming
refractive to later encounter with the same antigen even
when co-stimulation is present. This refractory state is
termed anergy.
8/31/2015 6:56:31 AM
19. Anergy - B cells
As implied from the section on split tolerance, there is a
mechanism for tolerising B cells to soluble antigens if they are
present at sufficiently high concentration. The general rules for
this tolerance mechanism were worked out using mice
transgenic for rearranged immunoglobulin molecules and a
transgenic soluble protein whose concentration in serum could
be regulated. It is apparent that the critical parameter is receptor
(surface Ig) occupancy. When more than 5%* of the sIgM
molecules are normally occupied by monomeric soluble antigen
the B cell becomes anergic. This anergic state can be recognised
in the case of B cells by the downregulation of surface IgM.
Note the level of surface IgD remains unaffected and the precise
explanation for why such B cells are refractory to stimulation
even when T cell help is available is not known.
8/31/2015 6:56:31 AM
21. Suppression
In some cases there are autoreactive T cells present
which are capable of reacting to their cognate antigen
as presented within the host
[ ie. they are not anergic or ignorant], yet do not express
this reactivity in the normal intact animal.
These cells appear to be prevented from reacting by
the presence of other T cells, a phenomenon which has
been termed Dominant Regulation or Suppression.
The mechanism is again obscure, but the following
experiments make it likely that this form of tolerance
is at least as important as anergy.
8/31/2015 6:56:31 AM
23. Timing
Some 50 years ago, Owen observed two types of non-identical twin cattle,
those that had shared a haemopoietic system in utero were tolerant of blood
cells from each other and those who had not, were not cross-tolerant.
Burnet postulated that there was a temporal window of tolerance such
that antigens encountered while the immune system was immature
tolerised the relevant lymphocytes.
Medewar subsequently investigated the effects of transferring haemopoietic
cells from histoincompatible mice at different times after birth.
He found that if the cells were transferred in the first few days of life (but not
later) the recipient mouse acquired lifelong tolerance to the antigens of the
donor.
8/31/2015 6:56:31 AM
25. Timing is an important parameter on the
tolerisability of the immune system
In essence bone marrow stem
cells establish chimaerism of
the host.
Some of these cells
differentiate into APC and
migrate to the thymus where
they tolerate developing
thymocytes by deletion
(central tolerance).
Lifelong chimaerism is
needed to maintain tolerance
and even a low level of
chimaerism is sufficient.
8/31/2015 6:56:31 AM
26. Timing is an important parameter on the
tolerisability of the immune system
For the first few days of the mouse's life there are
too few post-thymic T cells to sustain a response
and these are tolerised either by peripheral
deletion or some other mechanism.
If the transfer is done later the number and
maturity of the peripheral T cell pool is
sufficient to destroy the donor stem cells before
they can engraft.
Even antigens which cannot establish
chimaerism can establish a state of tolerance in
neonatal mice, this is less permanent however.
8/31/2015 6:56:31 AM
27. The Danger Hypothesis - Matzinger versus
Medewar?
Matzinger has proposed that
“there is not a special window
for tolerance during neonatal
life
but the fact that whether
encounter with an antigen
results in tolerance or an
immune response is
determined by whether the
prevailing host environment
promotes a response via
nonspecific cues 'sensing'
danger.
She has further suggested that the
controlled death process of apoptosis is
critical in preventing autoimmunity when
old or surplus cells are disposed off.
The notion that the normal, default
pathway of the immune system is
tolerance rather than response is not a
new idea to immunologists - antigens
usually fail to elicit a response unless
given with adjuvants, whose purpose is
probably to generate stimulatory cues
(cytokines).
8/31/2015 6:56:31 AM
28. The Danger Hypothesis - Matzinger versus
Medewar?....contd
Recent experiments have shown that not only can adults be tolerised
under certain circumstances, but that neonates can make effective
immune responses if the antigen is presented in sufficiently
immunogenic form.
I believe that the supposed conflict between Matzinger and Medewar
is rather 'hyped up' and essentially a matter of detail. Neonatal T cells
are not intrinsically tolerisable but the systemic neonatal environment
does predispose to tolerance. Nevertheless, I think that her hypothesis
has drawn the attention of a wider audience to current ideas about
tolerance induction and the factors determining immune
responsiveness.
Which of the 4 mechanisms of peripheral tolerance referred to above
do you think might be inducible by inhalation of peptide?
blockade of B7 (B7.1 and B7.2)?
What factors can you list which would influence the effectiveness
(immunogenicity) of a new subunit (purified protein) vaccine?
8/31/2015 6:56:31 AM
Editor's Notes
The general answer that is emerging from a variety of studies is that these harmful or useless types of B and T cells are actually eliminated from the animal by a variety of processes. This process of weeding out the harmful or useless clones is called “selection”, and there are thought to be two types (see Fig. 10-5). Negative selection is removal of self-reactive B or T cells. Positive selection is the process of eliminating T cells bearing receptors that (probably) recognize non-self MHC plus antigen, and retention of only the T cells that can recognize self-MHC plus foreign antigen.