1. The MHC molecules present peptide antigens to T cells. Class I MHC present intracellular peptides to CD8+ T cells, while class II MHC present extracellular peptides taken up by endocytosis to CD4+ T cells.
2. Antigens are processed through different pathways depending on if they are intracellular or extracellular. Intracellular antigens are degraded by the proteasome and transported into the ER by TAP to bind class I MHC. Extracellular antigens are endocytosed and degraded in lysosomes to bind class II MHC.
3. The peptide-MHC complexes are then transported to the cell surface for recognition by T cell receptors.
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.
B cell Activation by T Independent & T Dependent Antigens-Dr C R MeeraMeera C R
During humoral immune response, Ab production is brought about by B lymphocytes. Based on the ability to induce Ab formation, antigens can be classified into T independent and T dependent antigens. Some antigens can directly induce the B cells to produce the Abs and are called T Independent Ans. However, some Ans require the help of T lymohocytes for the production of Abs from B cells. These Ans are called T Dependent Ans.
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.
B cell Activation by T Independent & T Dependent Antigens-Dr C R MeeraMeera C R
During humoral immune response, Ab production is brought about by B lymphocytes. Based on the ability to induce Ab formation, antigens can be classified into T independent and T dependent antigens. Some antigens can directly induce the B cells to produce the Abs and are called T Independent Ans. However, some Ans require the help of T lymohocytes for the production of Abs from B cells. These Ans are called T Dependent Ans.
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 ppt covers the following topic-
1.Introduction about antibody.
2. Types of antibody.
3.Genetic basis of antibody diversity.
4. Antibody diversity.
5.Light chain gene segment.
6. Mechanism of variable region DNA rearrangment.
7. Heavy chain gene segment.
8.Alternate splicing.
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 ppt covers the following topic-
1.Introduction about antibody.
2. Types of antibody.
3.Genetic basis of antibody diversity.
4. Antibody diversity.
5.Light chain gene segment.
6. Mechanism of variable region DNA rearrangment.
7. Heavy chain gene segment.
8.Alternate splicing.
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.
Major Histocompatibility Complex (MHC) plays a cardinal role in T cell-mediated immunity. Modern immunogenetics largely depends on the research on the MHC complex.
This ppts file will give the students of biochemistry or biology, in general, a brief outlook on the structure and functions of MHC, as well as its mode of action.
I hope this work will help intermediate students grasping the topic.
Comparing Evolved Extractive Text Summary Scores of Bidirectional Encoder Rep...University of Maribor
Slides from:
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Track: Artificial Intelligence
https://www.etran.rs/2024/en/home-english/
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
3. Major histocompatibility Complex
• MHC molecules are membrane proteins on APCs that
display peptide antigens for recognition by T lymphocytes.
• In all vertebrates, the MHC contains two sets of highly
polymorphic genes, called the class I and class II MHC genes.
• The human MHC, called the human leukocyte antigen (HLA)
complex, and the mouse MHC, called the H-2 complex.
• Therefore, MHC can be classified into 3 based on structure
and site of action
1. Class I MHC
encode glycoproteins expressed on the surface of nearly all
nucleated cells; the major function of the class I gene products
is presentation of peptide antigens to TC cells
2. Class II MHC
encode glycoproteins expressed primarily on antigen-
presenting cells (macrophages, dendritic cells, and B cells),
where they present processed antigenic peptides to TH cells
3. Class III MHC
encode, in addition to other products, various secreted
proteins that have immune functions, including components of
the complement system and molecules involved in
inflammation
4. Structure of MHC Molecules
Class I MHC Molecules
• Class I MHC molecules contain a 45-kilodalton (kDa) α chain associated noncovalently with a
12-kDa β2-microglobulin molecule. The α chain is a transmembrane glycoprotein encoded by
polymorphic genes within the A, B, and C regions of the human HLA complex. β 2-
Microglobulin is a protein encoded by a highly conserved gene located on a different
chromosome.
• The α chain is anchored in the plasma membrane by its hydrophobic transmembrane
segment and hydrophilic cytoplasmic tail.
• Structural analyses have revealed that the αchain of class I MHC molecules is organized into
three external domains (1, 2, and 3), each containing approximately 90 amino acids; a
transmembrane domain of about 25 hydrophobic amino acids followed by a short stretch of
charged (hydrophilic) amino acids; and a cytoplasmic anchor segment of 30 amino acids.
• The β2-microglobulin is similar in size and organization to the α3 domain; it does not contain
a transmembrane region and is noncovalently bound to the class I glycoprotein.
• The amino-terminal α1 and α2 domains of the α chain form two walls and a peptide-binding
cleft, or groove, that can accommodate peptides typically 8 to 9 amino acids long.
• The floor of the peptide-binding cleft contains amino acid residues that bind peptides for
display to T lymphocytes, and the tops of the cleft walls make contact with the T cell
receptor.
Class II MHC Molecules
• Class II MHC molecules contain two different polypeptide chains, a 33-kDa α chain and a 28-
kDa β chain, which associate by noncovalent interactions
• Each class II MHC molecule consists of two transmembrane chains, called α and β. Each chain
has two extracellular domains, followed by the transmembrane and cytoplasmic regions.
• The amino-terminal regions of both chains, called the α1 and β1 domains, contain
polymorphic residues and form a cleft that is large enough to accommodate peptides of 10 to
30 residues.
5. Cellular Distribution of the MHC Antigens
• Essentially, all nucleated cells carry classical class I molecules.
• These are abundantly expressed on lymphoid cells, less so on liver, lung and kidney, and only sparsely on brain and
skeletal muscle.
• Class II molecules are restricted in their expression, being present only on antigen presenting cells (APCs) such as B-
cells, dendritic cells and macrophages and on thymic epithelium.
• When activated by agents such as interferon g, capillary endothelia and many epithelial cells in tissues other than the
thymus, they can develop surface class II and increased expression of class I.
Properties of MHC Genes and Proteins
• MHC genes are highly polymorphic, meaning that many different alleles (variants) are present among the different
individuals in the population.
• MHC genes are co-dominantly expressed, meaning that the alleles inherited from both parents are expressed equally
• Class I molecules are expressed on all nucleated cells, but class II molecules are expressed mainly on dendritic cells,
macrophages, and B lymphocytes.
6. Inheritance Patterns of HLA Genes
• An individual inherits one haplotype from the mother and
one haplotype from the father. In outbred populations, the
offspring are generally heterozygous at many loci and will
express both maternal and paternal MHC alleles.
• The alleles are co-dominantly expressed; that is, both
maternal and paternal gene products are expressed in the
same cells.
• In an outbred population, each individual is generally
heterozygous at each locus.
• The human HLA complex is highly polymorphic and multiple
alleles of each class I and class II gene exist.
• When the father and mother have different haplotypes,
there is a one-in-four chance that siblings will inherit the
same paternal and maternal Although the rate of
recombination by crossover is low within the HLA, it still
contributes significantly to the diversity of the loci in human
populations.
• Genetic recombination generates new allelic combinations ,
and the high number of intervening generations since the
appearance
• of humans as a species has allowed extensive
recombination, so that it is rare for any two unrelated
individuals to have identical sets of HLA genes
7. Antigen Processing
and Presentation
• Recognition of a foreign antigen by a T cell requires that
peptides derived from the antigen be displayed within the
cleft of an MHC molecule on the membrane of a cell.
• The formation of these peptide-MHC complexes requires that
a protein antigen be degraded into peptides by a sequence
of events called antigen processing.
• The degraded peptides then associate with MHC molecules
within the cell interior, and the peptide-MHC complexes are
transported to the membrane, where they are displayed
(antigen presentation).
• Class I and class II MHC molecules associate with peptides
that have been processed in different intracellular
compartments.
• Class I MHC molecules bind peptides derived from
endogenous antigens that have been processed within the
cytoplasm of the cell (e.g., normal cellular proteins, tumor
proteins, or viral and bacterial proteins produced within
infected cells).
• Class II MHC molecules bind peptides derived from
exogenous antigens that are internalized by phagocytosis
or endocytosis and processed within the endocytic pathway.
• Based on the type of cell where the processing occurs and
the type of MHC the antigen processing can be classified into
1. Endogenous pathway / Cytosolic Pathway
2. Exogenous pathway / Endocytic Pathway
8. Endogenous
pathway /
Cytosolic
Pathway
This is the pathway by which endogenous antigens are
degraded for presentation with class I MHC molecules.
This occurs in four stages
1. Proteolysis of Cytosolic Proteins
2. Intake of peptides into Endoplasmic reticulum
3. Synthesis of Class I MHC and binding of peptide on it
4. Transport of Peptide-MHC Complexes to the Cell Surface
9. Proteolysis of Cytosolic
Proteins
• The peptides that bind to class I MHC molecules are derived
from cytosolic proteins following digestion by the ubiquitin-
proteasome pathway.
• Antigenic proteins may be produced in the cytoplasm from
viruses that are living inside infected cells, from some
phagocytosed microbes that may leak from or be transported
out of phagosomes into the cytosol, and from mutated or
altered host genes that encode cytosolic or nuclear proteins,
as in tumors.
• These proteins are first bind to a ubiquitin molecule which
unfolded the protein and take the molecule to proteosome.
• This reaction, requires ATP, links several ubiquitin molecules to
a lysine-amino group near the amino terminus of the protein.
• Proteasome is composed of stacked rings of proteolytic
enzymes that degrade the unfolded proteins into peptides.
10. Binding of Peptides to Class
I MHC Molecules
In order to form peptide-MHC complexes, the peptides must be transported
into the endoplasmic reticulum (ER).
The peptides produced by proteasomal digestion are in the cytosol, while the
MHC molecules are being synthesized in the ER, and the two need to come
together.
This transport function is provided by a molecule, called the transporter
associated with antigen processing (TAP), located in the ER membrane.
TAP binds proteasome-generated peptides on the cytosolic side of the ER
membrane, then actively pumps them into the interior of the ER.
Newly synthesized class I MHC molecules, which do not contain bound
peptides, associate with a bridging protein called tapasin that links them to TAP
molecules in the ER membrane.
Thus, as peptides enter the ER, they can easily be captured by the empty class I
molecule
11. Synthesis of Class I
MHC and peptide
binding
• The α chain and β 2-macroglobulin components of the class I MHC molecule are
synthesized on polysomes along the rough endoplasmic reticulum.
• The assembly process involves several steps and includes the participation of molecular
chaperones, which facilitate the folding of polypeptides.
• The first molecular chaperone involved in class I MHC assembly is calnexin, a membrane
protein of the endoplasmic reticulum.
• Calnexin associates with the free class I α chain and promotes its folding.
• When β 2-microglobulin binds to the α chain, calnexin is released and the class I molecule
associates with another chaperone calreticulin and with tapasin.
• Tapasin (TAP-associated protein) brings the complex near to the TAP transporter and
allows it to acquire an antigenic peptide
12. Transport of Peptide-MHC Complexes to the Cell
Surface
• Peptide loading stabilizes class I MHC molecules, which are exported to the cell surface.
• Once the class I MHC molecule binds tightly to one of the peptides generated from proteasomal
digestion and delivered into the ER by TAP.
• This peptide-MHC complex becomes stable and is delivered to the cell surface.
• If the MHC molecule does not find a peptide it can bind, the empty molecule is unstable and is
eventually degraded in the ER.
13. Exogenous pathway
/ The Endocytic
Pathway
• This pathway is for antigens which are
generated outside of cell and processed by
class II MHC.
This pathway can be studied in three stages
1. Internalization and Proteolysis of
Antigens
2. Peptide Assembly with Class II MHC
Molecules
3. Transport of Peptide-MHC Complexes to
the Cell Surface
14. Internalization and
Proteolysis of Antigens
• Antigen-presenting cells can internalize antigen by phagocytosis,
endocytosis, or both.
• Once an antigen is internalized, it is degraded into peptides
within compartments of the endocytic processing pathway.
• The endocytic pathway appears to involve three increasingly
acidic compartments: early endosomes (pH 6.0–6.5); late
endosomes, or endolysosomes (pH 5.0–6.0); and lysosomes (pH
4.5–5.0).
• Internalized antigen moves from early to late endosomes and
finally to lysosomes, encountering hydrolytic enzymes and a
lower pH in each compartment.
• Within the compartments of the endocytic pathway, antigen is
degraded into oligopeptides of about 13–18 residues, which bind
to class II MHC molecules.
15. Peptide Assembly with
Class II MHC Molecules
• When class II MHC molecule are synthesized within the RER, it remains
associate with a preassembled trimer of a protein called invariant chain
(Ii, CD74).
• This trimeric protein interacts with the peptide-binding cleft of the class
II molecules, preventing any endogenously derived peptides from
binding to the cleft while the class II molecule is within the RER.
• Class II MHC–invariant chain complexes are transported from the RER to
the endocytic pathway, moving
• from early endosomes to late endosomes, and finally to lysosomes.
• As the proteolytic activity increases in each successive compartment, the
invariant chain is gradually degraded. However, a short fragment of the
invariant chain termed CLIP (for class II–associated invariant chain
peptide) remains bound to the class II molecule.
• CLIP physically occupies the peptide-binding groove of the class II MHC
molecule, preventing any premature binding of antigenic peptide.
• The CLIP molecule will be replaced by antigen peptide catalyzed by a
molecule called HLA-DM and this reaction is regulated and controlled by
HLA-DO molecule.
16. Transport of
Peptide-MHC
Complexes to the
Cell Surface
• Peptide loading stabilizes class II MHC
molecules, which are exported to the cell
surface.
• If a class II molecule binds a peptide with
the right fit, the complex is stabilized and
transported to the cell surface, where it can
be recognized by a CD4+ T cell.
• Class II molecules that do not find peptides
they can bind are eventually degraded by
lysosomal proteases