Antigen processing and presentation by Dr K.Geetha, Associate Professor, Department of Biotechnology, Kamaraj College of Engineering & Technology, Near Virudhunagar, Madurai Dist.
Altering the specificity of T cell receptor (TCR) is one of the popular strategies to genetically modify T cells to enhance the tumor-killing activity of T cells. From a tumor-reactive T cell or active anti-tumor T-cell antigens, the appropriate target sequence is introduced to modify T cells to target a broad range of tumors with improved specificity. https://www.creative-biolabs.com/car-t/cellrapeutics-tcr-technology.htm
Antigen processing and presentation by Dr K.Geetha, Associate Professor, Department of Biotechnology, Kamaraj College of Engineering & Technology, Near Virudhunagar, Madurai Dist.
Altering the specificity of T cell receptor (TCR) is one of the popular strategies to genetically modify T cells to enhance the tumor-killing activity of T cells. From a tumor-reactive T cell or active anti-tumor T-cell antigens, the appropriate target sequence is introduced to modify T cells to target a broad range of tumors with improved specificity. https://www.creative-biolabs.com/car-t/cellrapeutics-tcr-technology.htm
T-Cell Activation
• Concept of immune response
• T cell-mediated immune response
• B cell-mediated immune response
I. Concept of immune response
• A collective and coordinated response to the introduction of foreign substances in an individual mediated by the cells and molecules in the immune system.
II. T cell-mediated immune response
• Cell-mediated immunity is the arm of the adaptive immune response whose role is to combat infection of intracellular pathogens, such as intracellular bacteria (mycobacteria, listeria monocytogens), viruses, protozoa, etc.
T-Cell Activation
• Concept of immune response
• T cell-mediated immune response
• B cell-mediated immune response
I. Concept of immune response
• A collective and coordinated response to the introduction of foreign substances in an individual mediated by the cells and molecules in the immune system.
II. T cell-mediated immune response
• Cell-mediated immunity is the arm of the adaptive immune response whose role is to combat infection of intracellular pathogens, such as intracellular bacteria (mycobacteria, listeria monocytogens), viruses, protozoa, etc.
The immune system refers to a collection of cells, chemicals and processes that function to protect the skin, respiratory passages, intestinal tract and other areas from foreign antigens, such as microbes (organisms such as bacteria, fungi, and parasites), viruses, cancer cells, and toxins.
Immune System - The immune system is a complex network of cells and proteins that defends the body against infection.
The immune system keeps a record of every microbe it has ever defeated so it can recognize and destroy the microbe quickly if it enters the body again.
Abnormalities of the immune system can lead to allergic disease, immunodeficiencies and autoimmune disorders.
Antigen - Any factors or agents that can enter the body and create an immune response are called antigen.
Formation of immune cells - Immune cells are produced by hematopoietic stem cell in bone marrow
Hematopoietic stem cells are self-renewing and reside in the medulla of the bone ( bone marrow ).
HSCs are divided into two main lineages, lymphoid progenitor cells or myeloid progenitor cells.
Myeloid cells - Neutrophil, Eosinophil, Basophil, Mast cells, Monocyte, Macrophage, Dendritic Cell
Lymphoid cells - B Lymphocytes,
T Lymphocyte, NK Cells
Antigen presenting cells - Professional antigen presenting
cells : Macrophage, Dendritic cell, B Lymphocyte
Non professional antigen presenting cell: Non-professional antigen presenting cells include all nucleated cell types in the body.
Proteins of immune system - Set of serum proteins that co-operate with both Innate and adaptive immune system to eliminate blood and tissue pathogen.
Organs of immune cells - Spleen, Lymph node, Tonsils , MALT, Bone marrow, Thymus
Types of immunity -
Innate Immunity: Innate immune response is in born and is the first line of defense against pathogen
Adaptive immunity: Antigenic specificity. It have immunological memory
Immune Receptors - It is a specialized structures found in the cell membrane. They are mainly composed of proteins, which bind to pathogens and causes a response in immune system
The increased availability of biomedical data, particularly in the public domain, offers the opportunity to better understand human health and to develop effective therapeutics for a wide range of unmet medical needs. However, data scientists remain stymied by the fact that data remain hard to find and to productively reuse because data and their metadata i) are wholly inaccessible, ii) are in non-standard or incompatible representations, iii) do not conform to community standards, and iv) have unclear or highly restricted terms and conditions that preclude legitimate reuse. These limitations require a rethink on data can be made machine and AI-ready - the key motivation behind the FAIR Guiding Principles. Concurrently, while recent efforts have explored the use of deep learning to fuse disparate data into predictive models for a wide range of biomedical applications, these models often fail even when the correct answer is already known, and fail to explain individual predictions in terms that data scientists can appreciate. These limitations suggest that new methods to produce practical artificial intelligence are still needed.
In this talk, I will discuss our work in (1) building an integrative knowledge infrastructure to prepare FAIR and "AI-ready" data and services along with (2) neurosymbolic AI methods to improve the quality of predictions and to generate plausible explanations. Attention is given to standards, platforms, and methods to wrangle knowledge into simple, but effective semantic and latent representations, and to make these available into standards-compliant and discoverable interfaces that can be used in model building, validation, and explanation. Our work, and those of others in the field, creates a baseline for building trustworthy and easy to deploy AI models in biomedicine.
Bio
Dr. Michel Dumontier is the Distinguished Professor of Data Science at Maastricht University, founder and executive director of the Institute of Data Science, and co-founder of the FAIR (Findable, Accessible, Interoperable and Reusable) data principles. His research explores socio-technological approaches for responsible discovery science, which includes collaborative multi-modal knowledge graphs, privacy-preserving distributed data mining, and AI methods for drug discovery and personalized medicine. His work is supported through the Dutch National Research Agenda, the Netherlands Organisation for Scientific Research, Horizon Europe, the European Open Science Cloud, the US National Institutes of Health, and a Marie-Curie Innovative Training Network. He is the editor-in-chief for the journal Data Science and is internationally recognized for his contributions in bioinformatics, biomedical informatics, and semantic technologies including ontologies and linked data.
This pdf is about the Schizophrenia.
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Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
2. Definition
Antigen processing and presentation is the
process by which protein antigen is ingested
by an antigen presenting cell(APC)
partically digested into peptide fragment and
then displayed on the surface of the APC
associated with an antigen presenting
molecules such as MHC class1 or MHC
class2.
3. Antigen presenting cells have three
characteristics:-
• They are phagocytic cells which take up the
antigen by phagocytosis.
• They express class I and class II MHC
molecules.
• APCs get activated when they internalize the
pathogens, or their fractions or products.
5. Dendritic cell
• Dendritic cell or denderocytes are irregularly
shaped cell usually found in spleen and lymph
nodes.
• They are derived from the bone marrow and
the related to mononuclear phagocytic
lineage.
• Dendritic cell present in those tissues that are
in contact with the external environment.
• Such as the skin and the inner lining of the
nose, lungs, stomach and intestines.
• They are present immature state in blood.
6. Mononuclear phagocytic cells
• Macrophages are other mononuclear
phagocytes cells, play an important role in
presenting antigens, derived from extracellular
source such as bacteria and parasites.
• Macrophages ,however, do not constitutively
express class 2 MHC molecule or costimulatory
molecule.
• Macrophages have to be activated by
phagocytosis(or IFN-¥)before they can express
these two molecule required for antigen-
presenting function.
7. B.lymphocytes
• B cell are rich in class 2MHC molecule,
especially after activation
• B cell bind antigen on surface immunoglobulin
molecules , internalize, process and the present
the protein to activated TH cell.
• B cell do not constitutively express constimulator
but can be induced to express it by antibody .
• B cell unlike the other two classes of
lymphocytes , T cell and natural killer cell ,
express B cell receptor(BCR) on their cell
membrane
• B cell development from hematopoietic stem cell
that originate from bone marrow.
8. Macrophages
• Macrophages were first discover by Elie
Metchnikoff , a Russian bacteriologist, in 1884.
• Macrophages are the type of white blood cell
that engulf and digests cellular debris, foreign
substance ,microbes , cancer cell and any thing
else that does not have the type of protein specific
of healthy body cell on its surface in a process
called phagocytosis.
• Macrophages that encourage inflammation are
called M1 macrophages , where the those that
decrease in and inflammation encourage tissue
repair are called M2 macrophages
9. Professional antigen
presenting cell
• Professional APCs specialize in presenting
antigen to T cell and fulfill the feature of APCs
required for efficient antigen presentation.
• They are very efficient at internalizing antigen ,
either by phagocytosis or B cell , processing the
antigen into peptide fragments , and then
displaying those peptide bound to a class 2 MHC
molecules in the membrane.
• The main type of professional antigen presenting
cell are dendritic cells, macrophages and B cell.
10. Non-professional antigen
presenting cell.
• Cell such as fibroblast , glial cell , epithelial
cells , pancreatic cell and mesanthymal cell
also express class 2 MHC molecules in
response to y interferon.
• Since, these cells do not constitutively express
costimulators , it is unlikely that these non-
professional antigen presenting cell play a
central role in most T-cell response.
• It is suggested that non-professional antigen
presenting cell may play a secondary role in
cell-mediated immune response.
11. Two processing and
presentation pathways
• Antigen can be classified an Intracellular
(endogenous) and Extracellular (exogenous) antigen.
• Endogenous antigen are those that are synthesized or
introduce in cytosol of the target cell.
• For example, viral protein are synthesized in cytosol
when the virus replicate inside the cell.
• If antigen are artificially introduce directly into the
cytosol(using electroporation )they behave as
endogenous antigen.
• These endogenous antigen on class 1MHC molecule
reconized by T cytotoxic cell.
12. • These exogenous antigen presented on classes
2MHC molecule are recognized by TH cell.
• Several experimental evidences support the
existence of two processing and presentation
pathway that direct antigen fragment to either
class1 MHC or class2 MHC molecule.
1. Presentation of endogenous pathogens to
class1 MHC molecules
2.Presentation of exogenous antigen to class2
MHC molecules
Continued…
13. Presentation of endogenous pathogens
to class 1 MHC molecules
• The endogenous pathway is used to present
cellular peptide fragments on the cell surface
on MHC class 1 molecule.
• If virus had infected the cell , viral peptide
would also be presented , allowing the immune
system to recognize and kill the infected cell
• Worn out protein within the cell become
ubiquitinated , marking them for proteasome
degradition.
14. Continued…
• Proteasome break the protein up into peptide
that include some around nine amino acid long.
• Transporter associated with antigen processing
a protein that span the membrane of rough
endoplasmic reticulum, transport the peptide
into the lumen of rough (ER), transport the
peptide into the lumen of the rough ER.
• The partially folded MHC class1 molecule then
interact the TAP via tapasin.
• Once the peptide is transported into the ER
lumen, it binds to the cleft of the awaiting
MHC class1 molecule stabilizing the MHC and
allowing it to be transported to the cell surface
by golgi apparatus.
16. Presentation of exogenous antigen to
class2 MHC molecules
• The exogenous pathway is utilized by specialized
antigen presenting cell to present peptide derive
from protein that the cell has endocytosed and
degraded by acid dependent proteases in
endosome.
• The nasent MHC class 2 protein in the rough ER
has its peptide cleft blocking by li (the invariant
chain; a trimmer ) to prevent it from binding
cellular peptides or peptide from the endogenous
pathway.
• The invariant chain also facilitates MHC class2
export from the ER in a vesicles.
17. • This fuses with a late endosome with a
containing the endocytosed , degraded protein.
• The variant chain is then broken down in stage
leaving only a small fragment called “class 2-
associated invariant chain peptide”(CLIP)
which still block the peptide binding cleft.
Continued…
