The immune system provides protection against infection through humoral and cellular immunity. Humoral immunity involves antibodies produced by B cells that bind to antigens. Cellular immunity is mediated by T cells that respond to antigens on host cells and mark infected cells for destruction. The immune system has the ability to recognize an almost unlimited number of antigens through clonal selection, where antigen exposure stimulates proliferation of antigen-specific lymphocytes. Memory cells generated during primary responses allow for rapid secondary responses against the same antigen. Antibody diversity is generated through somatic recombination of gene segments during B cell development.
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.
Introduction
About Drosophila
Genome of Drosophila
Life cycle
Differentiation
Development of Drosophila
* Embryonic development
* Dorsal -ventral and
* Anterior posterior development
* Body segmentation
* Homeotic gene
Conclusion
Reference
The content is about Immunology for to recall the topic " Antigen presentation and processing" - specifically about the type two pathway "Exogenous antigen presentation and processing". I just presented the content to the best of my knowledge with the reference of two books - Kuby immunology and Janeway's immunobiology. I hope this was helpful to the life science aspirants and other students in life science sector.
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.
Introduction
About Drosophila
Genome of Drosophila
Life cycle
Differentiation
Development of Drosophila
* Embryonic development
* Dorsal -ventral and
* Anterior posterior development
* Body segmentation
* Homeotic gene
Conclusion
Reference
The content is about Immunology for to recall the topic " Antigen presentation and processing" - specifically about the type two pathway "Exogenous antigen presentation and processing". I just presented the content to the best of my knowledge with the reference of two books - Kuby immunology and Janeway's immunobiology. I hope this was helpful to the life science aspirants and other students in life science sector.
The term 'segmentation gene' is a classification given to a broad class of genes that are further subdivided into three smaller classes of genes. Within the segmentation gene group, there are gap genes, pair-rule genes and segment polarity genes. They control development in this order.
cell commitment and differentiation, stem cell,types of differentiationshallu kotwal
The commitment of cells to specific cell fates and their capacity to differentiate into particular kinds of cells.
Cellular differentiation is the process in which a cell changes from one cell type to another. Usually, the cell changes to a more specialized type. Differentiation occurs numerous times during the development of a multicellular organism as it changes from a simple zygote to a complex system of tissues and cell types. Differentiation continues in adulthood as adult stem cells divide and create fully differentiated daughter cells during tissue repair and during normal cell turnover.
To determine the variation and the limitation between species, many concepts have been proposed.
When a taxonomist study a particular taxa, he/she must adopted a species concept and provide a species limitation to define this taxa.
Plant kingdom as other living kingdoms has a hierarchy structure ends mostly with species rank.
Species are one of the basic units to compare in almost all fields of biology.
A species is defined as the largest group of organisms in which two individuals are capable of reproducing fertile offspring, typically using sexual reproduction.
Definition of a species as a group of interbreeding individuals cannot be easily applied to organisms that reproduce only or mainly asexually.
If two lineages of oak look quite different, but occasionally form hybrids with each other, should we count them as different species?
Idea of a species is something that we humans invented for our own convenience.
‘‘No matter what variations occur in the individuals or the species, if they spring from the seed of one and the same plant, they are accidental variations and not such as distinguish a species permanently; one species never springs from the seed of another nor vice versa” - JOHN RAY.
Used a sexual system ‘‘natural system” for defining species - LINNAEUS.
‘‘A species is a collection of all the individuals which resemble each other more than they resemble anything else, which can by natural fecundation produce fertile individuals, and which reproduce themselves by generation, in such a manner that we may from analogy suppose them all to have sprung from one single individual” - DE CANDOLLE.
The term 'segmentation gene' is a classification given to a broad class of genes that are further subdivided into three smaller classes of genes. Within the segmentation gene group, there are gap genes, pair-rule genes and segment polarity genes. They control development in this order.
cell commitment and differentiation, stem cell,types of differentiationshallu kotwal
The commitment of cells to specific cell fates and their capacity to differentiate into particular kinds of cells.
Cellular differentiation is the process in which a cell changes from one cell type to another. Usually, the cell changes to a more specialized type. Differentiation occurs numerous times during the development of a multicellular organism as it changes from a simple zygote to a complex system of tissues and cell types. Differentiation continues in adulthood as adult stem cells divide and create fully differentiated daughter cells during tissue repair and during normal cell turnover.
To determine the variation and the limitation between species, many concepts have been proposed.
When a taxonomist study a particular taxa, he/she must adopted a species concept and provide a species limitation to define this taxa.
Plant kingdom as other living kingdoms has a hierarchy structure ends mostly with species rank.
Species are one of the basic units to compare in almost all fields of biology.
A species is defined as the largest group of organisms in which two individuals are capable of reproducing fertile offspring, typically using sexual reproduction.
Definition of a species as a group of interbreeding individuals cannot be easily applied to organisms that reproduce only or mainly asexually.
If two lineages of oak look quite different, but occasionally form hybrids with each other, should we count them as different species?
Idea of a species is something that we humans invented for our own convenience.
‘‘No matter what variations occur in the individuals or the species, if they spring from the seed of one and the same plant, they are accidental variations and not such as distinguish a species permanently; one species never springs from the seed of another nor vice versa” - JOHN RAY.
Used a sexual system ‘‘natural system” for defining species - LINNAEUS.
‘‘A species is a collection of all the individuals which resemble each other more than they resemble anything else, which can by natural fecundation produce fertile individuals, and which reproduce themselves by generation, in such a manner that we may from analogy suppose them all to have sprung from one single individual” - DE CANDOLLE.
Antibody (Ab) also known as Immunoglobulin (Ig) is the large Y shaped protein produced by the body’s immune system when it detects harmful substances, called antigens like bacteria and viruses. The production of antibodies is a major function of the immune system and is carried out by a type of white blood cell called a B cell (B lymphocyte), differentiated B cells called plasma cells. The produced antibodies bind to specific antigens express in external factors and cancer cells.
This presentation elaborates the economic crisis in Sri Lanka. It explains the causes of economic instability in Sri Lanka and the factors worsening it. Such miserable economic situation is presenting valuable lessons for other sister asian countries to counter their economic instability. Pakistan, a sister country of Sri Lanka is facing severe political and economic instability these days. Pakistan is learning from the Sri Lankan economic situation and tending to improve its economy but the extreme political instability is hurdling and exacerbating the economic crisis. However, policies are underway to counter the economic crisis and more probably Pakistan will escape the Sri Lankan experience.
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.
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.
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 .
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.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
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.
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.
1. Immunogenetics of Vertebrates
A basic assumption of developmental biology is that every somatic cell carries an identical set of genetic information
and that no genesare lost during development. Although this assumption holds for most cells, there are some important
exceptions, one of which concerns genes that encode immune function in vertebrates. The immune system provides
protection against infection by specific bacteria, viruses, fungi, and parasites. The focus of an immune response is an
antigen, defined as any molecule that elicits an immune reaction. Although any molecule can be an antigen, most are
proteins. The immune system is remarkable in its ability to recognize an almost unlimited number of potential antigens.
The body is full of proteins, so it is essential that the immune system be able to distinguish between self-antigens and
foreign antigens. Occasionally, the ability to make this distinction breaks down, and the body produces an immune
reaction to its own antigens, resulting in an autoimmune disease.
Disease Tissues Attacked
Graves disease, Thyroid gland
Hashimoto thyroiditis
Rheumatic fever Heart muscle
Systematic lupus erythematosus Joints, skin, and other organs
Rheumatoid arthritis Joints
Insulin-dependent Diabetes mellitus Insulin-producing cells in pancreas
Multiple sclerosis Myelin sheath around Nerve cells
The Organization of the Immune System
The immune system contains a number of different components and uses several mechanisms to provide protection
against pathogens, but most immune responses can be grouped into two major classes: humoral immunity and cellular
immunity. Although it is convenient to think of these classes as separate systems,they interact and influence each other
significantly.
Humoral immunity centers on the production of antibodies by special lymphocytes called B cells, which
mature in the bone marrow. Antibodies are proteins that circulate in the blood and other body fluids, binding to specific
antigens and marking them for destruction by phagocytic cells. Antibodies also activate a set of proteins called
complement that help to lyse cells and attract macrophages.
Cellular immunity is conferred by T cells, which are specialized lymphocytes that mature in the thymus and
respond only to antigens found on the surfaces of the body’s own cells. After a pathogen such as a virus has infected a
host cell, some viral antigens appear on the cell surface. Proteins,called T-cell receptors, on the surfaces of T cells bind
to these antigens and mark the infected cell for destruction. T-cell receptors must simultaneously bind a foreign antigen
and a self-antigen called a major histocompatibility complex (MHC) antigen on the cell surface. Not all T cells attack
cells having foreign antigens; some help regulate immune responses, providing communication among different
components of the immune system.
2. How can the immune system recognize an almost unlimited number of foreign antigens?
Remarkably, each mature lymphocyte is genetically programmed to attack one and only one specific antigen: each
mature B cell produces antibodies against a single antigen, and each T cell is capable of attaching to only one type of
foreign antigen. If each lymphocyte is specific for only one type of antigen, how does an immune response develop?
The theory of clonal selection proposes that initially there is a large pool of millions of different lymphocytes, each
capable of binding only one antigen; so millions of different foreign antigens can be detected. To illustrate clonal
selection, let’s imagine that a foreign protein enters the body. Only a few lymphocytes in the pool will be specific for
this particular foreign antigen. When one of these lymphocytes encounters the foreign antigen and binds to it, that
lymphocyte is stimulated to divide. The lymphocyte proliferates rapidly, producing a large population of genetically
identical cells—a clone—each of which is specific for that particular antigen. This initial proliferation of antigen specific
B and T cells is known as a primary immune response; in most cases, the primary response destroys the foreign
antigen. Subsequent to the primary immune response, most of the lymphocytes in the clone die, but a few continue to
circulate in the body. These memory cells
may remain in circulation for years or even
for the rest of one’s life. Should the same
antigen reappear at some time in the future,
memory cells specific to that antigen
become activated and quickly give rise to
another clone of cells capable of binding the
antigen. The rise of this second clone is
termed a secondaryimmune response.The
ability to quickly produce a second clone of
antigen-specific cells permits the long-
lasting immunity that often follows recovery
from a disease. For example, people who
have chicken pox usually have life-long
immunity to the disease. The secondary
immune response is also the basis for
vaccination, which stimulates a primary
immune response to an antigen and results
in memory cells that can quickly produce a
secondary response if that same antigen
appears in the future. Three sets of proteins
are required for immune responses:
antibodies, T-cell receptors, and the major
histocompatibility antigens. The next
section explores how the enormous diversity
in these proteins is generated.
Immunoglobulin Structure (Antibody)
The principal products of the humoral
immune response are antibodies—also
called immunoglobulins Each immunoglobulin (Ig) molecule consists of four polypeptide chains; two identical light
chains and two identical heavy Chains; which form a Y-shaped structure Disulfide bonds link the two heavy chains in
the stem of the Y and attach a light chain to a heavy chain in each arm of the Y. Binding sites for antigens are at the
ends of the two arms. The light chains of an immunoglobulin come in two basic types, called kappa chains and lambda
chains. An immunoglobulin molecule can have two kappa chains or two lambda chains, but it cannot have one of each
type. Both the light and the heavy chain has a variable region at one end and a constant region at the other end; the
variable regions of different immunoglobulin molecules vary in amino acid sequence,whereas the constant regions of
different immunoglobulins are similar in sequence. The variable regions of both light and heavy chains make up the
antigen binding region and specify the type of antigen that the antibody can bind.
3. Mammals have five basic classes of immunoglobulins, known as IgM, IgD, IgE, IgG, and IgA. Each class is defined by
the type of heavy chain found in the immunoglobulin. The different classes of antibodies have different functions or
they appearat different times during animmune response or both. For example, in a primary response,all B cells initially
make IgM but, as the immune response develops, they switch to producing a combination of IgM and IgD. Later,the B
cells may switch to one of the other immunoglobulin classes.
21.16 Each immunoglobin molecule consists offour polypeptide chains_ 2 light chains and 2 heavy chains__that combine to form
a Y- shaped structure. (a) Structure of an immunoglobin. (b) Folded, space filling model
The Generation of Antibody Diversity
The immune system is capable of making antibodies
against virtually any antigen that might be encountered in
one’s lifetime: each human is capable of making about
1015 different antibody molecules. Antibodies are
proteins; so the amino acid sequencesof all 1015 potential
antibodies must be encoded in the human genome.
However,there are fewer than 1x105 genes in the human
genome and, in fact,only 3 x109 total base pairs; so how
can this huge diversity of antibodies be encoded?
The answer lies in the fact that antibody genes are
composed of segments. There are a number of copies of
each type of segment, each differing slightly from the
others. In the maturation of a lymphocyte, the segments
are joined to create an immunoglobulin gene. The
particular copy of each segment used is random and,
because there are multiple copies of each type, there are
many possible combinations of the segments. A limited
number of segments can therefore encode a huge diversity
of antibodies.
To illustrate this process of antibody assembly, let’s
consider the immunoglobulin light chains. Kappa and
lambda chains are encoded by separate genes on different
chromosomes. Each gene is composed of three types of
segments: V, for variable; J, for joining; and C, for
constant. The V segments encode most of the variable region of the light chains, the C segment encodes the constant
region of the chain, and the J segments encode a short set of nucleotides that join the V segment and the C segments
together.
The number of V, J, and C segments differs among species. For the human kappa gene, there are from 30 to 35different
functional V gene segments, 5 different J genes, and a single C gene segment, all of which are present in the germ-line
DNA (FIGURE 21.17a). The V gene segments,which are about 400 bp in length, are located on the same chromosome
4. and are separated from one another by about
7000 bp. The J gene segments are about 30 bp in
length and all together encompass about 1400 bp.
Initially, an immature lymphocyte inherits all of
the V gene segments and all of the J gene
segments present in the germ line. In the
maturation of the lymphocyte, somatic
recombination within a single chromosome
moves one of the V genes to a position next to
one of the J gene segments (FIGURE 21.17b). In
Figure 21.17b, V2 (the second of approximately
35 different Vgene segments)undergoes somatic
recombination, which places it next to J3 (the
third of 5 J gene segments); the intervening
segments are lost.
After somatic recombination has taken place, the
combined V-J-C gene is transcribed and
processed (FIGURE21.17candd). The mature
mRNA that results contains only sequences for a
single V, J, and C segment; this mRNA is
translated into a functional light chain (FIGURE
21.17e).
In this way, each mature human B cell produces
a unique type of kappa light chain, and different
B cells produce slightly different kappa chains,
depending on the combination of V and J
segments that are joined. The gene that encodes
the lambda light chain is organized in a similar
way but differs from the kappa gene in the
number of copies of the different segments. In the
human gene for the lambda light chain, there are
from 29 to 33 different functional V gene
segments and 4 or 5 different functional J and C
gene segments (each C gene segment is attached
to a different J segment). Somatic recombination
takes place among the segments in the same way
as that in the kappa gene, generating many
possible combinations of lambda light chains.
The gene that encodes the immunoglobulin
heavy chain is arranged in V, J, and C segments,
but this gene also possesses D (for diversity)
segments. Somatic recombination taking place in lymphocyte maturation joins one D gene segment to one J gene
segment, and then a Vgene segment is joined to this combined D-Jgene segment (FIGURE21.18a and b). Transcription
and RNA processing of this gene produces a mRNA that encodes only one particular type of heavy ch36ain (FIGURE
21.18c–e).
Thus, many different types of light and heavy chains are possible. Somatic recombination is brought about by RAG1
and RAG2 proteins, which generate doublestrand breaks at specific nucleotide sequences called recombination signal
sequences that flank the V,D, J, and C gene segments. DNA repair proteins then process and join the ends of particular
segments together (FIGURE 21.19).
In addition to somatic recombination, other mechanisms add to antibody diversity. First, each type of light chain can
potentially combine with each type of heavy chain to make a functional immunoglobulin molecule, increasing the
amount of possible variation in antibodies. Second, the recombination process that joins V, J, D, and C gene segments
in the developing B cell is imprecise, and a few random nucleotides are frequently lost or gained at the junctions of the
5. recombining segments. This junctional diversity greatly enhances variation among antibodies. Third, a high rate of
mutation, called somatic hyper mutation (the cause of which is unknown), is characteristic of the immunoglobulin genes.
T-Cell-Receptor Diversity
Like B cells, each mature T cell has genetically determined specificity for
one type of antigen that is mediated through the cell’s receptors. T-cell
receptorsare structurally similar to immunoglobulins (FIGURE 21.20) and
are located on the cell surface; most T-cell receptors are composed of one
alpha and one beta polypeptide chain held together by disulfide bonds. One
end of eachchain is embedded in the cell membrane; the other end projects
away from the cell and binds antigens. Like the immunoglobulin chains,
eachchain of the T-cell receptorpossessesa constant region and a variable
region (see Figure 21.20); the variable regions of the two chains provide
the antigen-binding site.
The genes that encode the alpha and beta chains of the T-cell receptor are
organized much like those that encode the heavy and light chains of
immunoglobulins: each gene is made up of segments that undergo somatic
recombination before the gene is transcribed.For example, the human gene
for the alpha chain initially consists of 44 to 46 V gene segments,50 Jgene
segments, and a single C gene segment. The organization of the gene for
the beta chain is similar, except that it also contains D segments. Random
combination of alpha and beta chains and junctional diversity takes place,
but there is no evidence for somatic hypermutation in T-cellreceptor genes.
Major Histocompatibility Complex Genes
When tissues are transferred from one species to another or even from one
individual member to another within a species, the transplanted tissues are
usually rejected by the host animal. The results of early studies demonstrated
that this graft rejection is due to an immune response that occurs when
antigens on the surface of the grafted tissue are detected and attacked by T
cells in the host organism. The antigens that elicit graft rejection are referred
to as histocompatibility antigens, and they are encoded by a cluster of genes
called the major histocompatibility complex.
T cells are activated only when the T-cell receptor simultaneously binds both
a foreign antigen and the host cell’s own histocompatibility antigen. The
reason for this requirement is not clear; it may reserve T cells for action
against pathogens that have invaded cells. When a foreign body, such as a
virus, is ingested by a macrophage or other cell, partly digested pieces of the
foreign body containing antigens are displayed on the macrophage’s surface
(FIGURE 21.21). Through their T-cell receptors, T cells bind to both the
histocompatibility protein and the foreign antigen and secrete substancesthat
either destroy the antigen-containing cell or activate other B and T cells or
both.
The MHC genes are among the most variable genes known: there are more
than 100 different alleles for some MHC loci. Because eachperson possesses
five or more MHC loci and because many alleles are possible at each locus,
no two people (with the exception of identical twins) produce the same set of
histocompatibility antigens. The variation in histocompatibility antigens
provides each of us with a unique identity for our own cells, which allows
our immune systems to distinguish self from nonself. This variation is also
the cause of rejection in organ transplants.