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Immunology
Immunology
Immunology
The task of general immunology is to understand and explore the fundamental principles,
mechanisms, and components of the immune system. It encompasses a wide range of
topics related to how the immune system functions, including the following:
Immune System Components: General immunology examines the various cells,
proteins, and molecules that make up the immune system. This includes white blood
cells (leukocytes), such as T cells, B cells, macrophages, and neutrophils, as well as
antibodies and cytokines.
Innate and Adaptive Immunity: It delves into the concepts of innate immunity (the
body's immediate, non-specific defense mechanisms) and adaptive immunity (the
ability to develop specific responses to pathogens over time).
Immune Responses: The study of how the immune system recognizes and
responds to pathogens, such as bacteria, viruses, fungi, and parasites. This includes
mechanisms like phagocytosis, cytokine signaling, and the activation of immune
cells.
Antigen Recognition: Investigating how the immune system recognizes and
distinguishes between "self" and "non-self" substances through antigen recognition.
This includes the role of major histocompatibility complexes (MHC), T cell receptors,
and B cell receptors.
Immunological Memory: Understanding how the immune system forms memory
responses, allowing it to respond more effectively upon re-exposure to the same
pathogen. This is the basis of vaccination.
And more…
Innate immunity
1. List and discuss components of innate immunity.
Anatomical Defenses:
Skin: The body's largest organ serves as a physical barrier that prevents pathogens
from entering. The outermost layer of the skin is composed of dead cells and keratin,
which are inhospitable to most pathogens.
Mucous Membranes: These line the respiratory, gastrointestinal, and urogenital
tracts and secrete mucus, which traps pathogens and other foreign particles. Mucous
membranes are equipped with hair-like structures called cilia that help move trapped
particles out of the body.
Physiological Defenses:
Acidic Environments: Various bodily fluids, such as gastric acid in the stomach and
vaginal secretions, are acidic. The low pH in the stomach, for instance, helps destroy
ingested pathogens.
Enzymes: Enzymes like lysozyme, found in tears, saliva, and other secretions, can
break down the cell walls of certain bacteria.
Antimicrobial Peptides: These are small proteins with antimicrobial properties that
can directly kill or inhibit the growth of pathogens. For example, defensins are
antimicrobial peptides found in various bodily fluids.
Phagocytic Defenses:
Phagocytes: White blood cells known as phagocytes are key players in innate
immunity. Neutrophils and macrophages are examples of phagocytes. They engulf
and digest pathogens by a process called phagocytosis.
Inflammatory Defenses:
Inflammation: Innate immunity triggers an inflammatory response when it detects
infection or injury. The signs of inflammation include redness, heat, swelling, and pain
at the site of infection or injury.
● Inflammatory Mediators: Release of substances like histamines and
prostaglandins that promote inflammation.
● Increased Blood Flow: Dilation of blood vessels to enhance blood flow to
the affected area.
● Recruitment of Immune Cells: Chemotactic factors attract immune cells,
like neutrophils and macrophages, to the site of infection.
● Tissue Repair: Inflammation also initiates the repair of damaged tissues.
8. Draw and describe interaction between innate and adaptive immune responses.
Adaptive immunity
1. List and describe the central and peripheral organs of the immune system.
Central Organs:
Bone Marrow: The bone marrow is a central organ where various immune cells are
produced. It is responsible for the generation of all blood cells, including white blood
cells (leukocytes), which are critical components of the immune system.
Thymus: The thymus is a gland located in the upper chest. It is a primary central
organ of the adaptive immune system, primarily involved in the development and
maturation of T cells (T lymphocytes). T cells are essential for cell-mediated immunity
and help orchestrate immune responses.
Peripheral Organs and Tissues:
Spleen: The spleen is a peripheral organ located under the ribcage. It acts as a
blood filter and immune organ. It contains white pulp, where immune responses
against blood-borne pathogens take place. The spleen filters blood and removes
damaged red blood cells and foreign materials.
Lymph Nodes: Lymph nodes are small, bean-shaped structures found throughout
the body, connected by the lymphatic system. They filter lymph, a clear fluid
containing immune cells and cellular debris. Lymph nodes are essential for detecting
and responding to infections. They contain B cells, T cells, and other immune cells.
Lymphatic System: The lymphatic system comprises a network of vessels, nodes,
and organs that transport lymph and immune cells. Lymphatic vessels collect lymph
from tissues, carry it to lymph nodes, and ultimately return it to the bloodstream. This
system facilitates the circulation of immune cells and helps drain excess fluids from
tissues.
Mucosa-Associated Lymphoid Tissue (MALT): MALT consists of immune
structures located in mucosal tissues, such as the gastrointestinal and respiratory
tracts. It includes structures like Peyer's patches in the small intestine and tonsils in
the throat. MALT plays a crucial role in immune defense at mucosal surfaces, where
the body is most exposed to pathogens.
Gut-Associated Lymphoid Tissue (GALT): GALT is a subset of MALT found in the
gastrointestinal tract. It includes specialized immune structures like Peyer's patches
and isolated lymphoid follicles. GALT is important for protecting against intestinal
infections and maintaining immune tolerance to dietary antigens.
Bronchus-Associated Lymphoid Tissue (BALT): BALT is a component of MALT
located in the respiratory tract, specifically the bronchi and lungs. It helps protect
against respiratory infections and contributes to local immune responses.
Skin-Associated Lymphoid Tissue (SALT): SALT includes immune structures
found in the skin, such as Langerhans cells and local immune cells. These cells are
part of the body's defense against skin infections and allergens.
8. Describe and explain the interaction of immune cells in the immune response.
The immune response is a highly coordinated process involving various immune cells that
work together to recognize and eliminate pathogens. Here's an overview of how immune
cells interact during the immune response:
1. Antigen Presentation:
● The immune response begins when antigen-presenting cells (APCs), such as
dendritic cells, macrophages, and B cells, capture antigens from pathogens.
● APCs process these antigens and present fragments of them on their cell surface
using major histocompatibility complexes (MHC).
2. Activation of Helper T Cells:
● CD4+ T helper (Th) cells recognize the antigen-MHC complex on APCs and become
activated.
● Activated Th cells release cytokines, which are signaling molecules that instruct other
immune cells.
3. B Cell Activation:
● B cells recognize antigens directly or receive help from Th cells.
● Upon activation, B cells differentiate into plasma cells, which produce antibodies
specific to the pathogen.
● Memory B cells are also formed for long-term immunity.
4. Cytotoxic T Cell Activation:
● CD8+ cytotoxic T cells (CTLs) recognize infected cells displaying antigens on their
MHC class I molecules.
● CTLs are activated and become cytotoxic, capable of killing infected cells.
5. Macrophage Activation:
● Macrophages are further activated by Th cell cytokines to enhance their phagocytic
and killing abilities.
● They play a crucial role in engulfing and destroying pathogens.
6. Natural Killer (NK) Cells:
● NK cells are activated when they detect stressed or infected cells.
● They can directly kill target cells and secrete cytokines to enhance the immune
response.
7. Inflammatory Response:
● Neutrophils are rapidly recruited to sites of infection, where they engulf pathogens.
● The release of cytokines and chemokines leads to an inflammatory response,
recruiting immune cells to the infection site.
8. Immunological Memory:
● Memory B and T cells are formed during the response.
● In future encounters with the same pathogen, memory cells provide a quicker and
more robust response.
9. Describe the interaction between innate and adaptive immunity
Recognition of Pathogens:
● Innate Immunity: Innate immune cells, such as macrophages, neutrophils, and
dendritic cells, recognize and respond to common patterns associated with
pathogens. These patterns are known as pathogen-associated molecular patterns
(PAMPs).
● Adaptive Immunity: Adaptive immune cells, like T and B cells, recognize specific
antigens on pathogens. These antigens are presented to them by antigen-presenting
cells (APCs), mainly dendritic cells.
Activation of Innate Immunity:
● Innate Immunity: Upon detecting a pathogen, innate immune cells initiate an
immediate and non-specific response. They release cytokines and chemokines,
induce inflammation, and attempt to eliminate the threat through phagocytosis and
other mechanisms.
● Adaptive Immunity: The antigens captured and presented by APCs are recognized
by helper T cells (CD4+). These T cells receive signals from innate immune cells,
promoting their activation and differentiation into effector cells.
Coordinated Response:
● Innate Immunity: The innate immune response, with its rapid actions, serves as the
first line of defense. It helps contain the pathogen while adaptive immunity is gearing
up.
● Adaptive Immunity: Once activated, helper T cells release cytokines that guide B
cells and cytotoxic T cells. B cells produce pathogen-specific antibodies, and
cytotoxic T cells eliminate infected cells. These actions are highly specific and
tailored to the pathogen.
Feedback Mechanisms:
● Innate Immunity: Innate immune responses contribute to shaping the adaptive
immune response. Innate immune cells can provide co-stimulatory signals to T cells,
guiding their differentiation.
● Adaptive Immunity: Adaptive immune responses can modulate innate immune cells.
For instance, activated T cells can enhance the function of macrophages.
Memory Formation:
● Adaptive Immunity: One of the key features of adaptive immunity is the formation of
immunological memory. Memory B and T cells are generated, which provide
long-lasting protection upon re-exposure to the same pathogen. This is not a feature
of innate immunity.
Resolution of Immune Response:
● Regulatory T cells (Tregs) play a role in dampening immune responses to avoid
excessive inflammation and tissue damage. They help regulate both innate and
adaptive immune responses.
Overall, innate immunity serves as a rapid and non-specific defense mechanism that
provides immediate protection against a wide range of threats. Adaptive immunity, on the
other hand, is specific and tailored to the pathogen, providing long-lasting immunity through
memory cells. The interactions between these two branches ensure a comprehensive and
effective response to infections and other challenges while maintaining immune balance.
10. Explain the differences between innate and adaptive immunity.
11. Compare the functional characteristics of cells of innate and adaptive immunity.
Innate Immunity Cells:
Neutrophils:
● Phagocytosis of bacteria and debris.
● Release of antimicrobial molecules.
Macrophages:
● Phagocytosis of pathogens and dead cells.
● Antigen presentation to initiate adaptive immune response.
● Secretion of cytokines to coordinate immune responses.
Natural Killer (NK) Cells:
● Detection and destruction of infected or cancerous cells.
● Release of cytotoxic granules.
Dendritic Cells:
● Antigen presentation to T cells, initiating adaptive immunity.
● Cytokine production for immune regulation.
Basophils and Mast Cells:
● Release of inflammatory mediators like histamine.
● Role in allergic reactions.
Adaptive Immunity Cells:
T Cells (CD4+):
● Helper T cells assist B cells and cytotoxic T cells.
● Regulatory T cells control immune responses.
● Memory T cells provide long-term immunity.
T Cells (CD8+):
● Cytotoxic T cells directly kill infected or abnormal cells.
● Memory T cells respond rapidly upon re-exposure.
B Cells:
● Produce antibodies (immunoglobulins) targeting specific antigens.
● Memory B cells provide long-lasting antibody production.
Plasma Cells:
● Derived from B cells, produce large quantities of antibodies.
Antigen-Presenting Cells (APCs):
● Dendritic cells, macrophages, B cells present antigens to T cells.
● Initiate adaptive immune responses.
Memory Cells:
● Remember specific pathogens for faster response upon re-infection.
Cytokine-Producing Cells:
● Various immune cells produce cytokines to regulate immune responses.
4. Explain the role of major histocompatibility complex gene products in the immune
Response.
he Major Histocompatibility Complex (MHC) gene products play a crucial role in the immune
response, as they are responsible for presenting antigens to immune cells. There are two
main classes of MHC gene products, MHC class I and MHC class II, each with distinct roles
in the immune system:
MHC Class I Molecules:
● Function: MHC class I molecules are found on the surface of nearly all
nucleated cells in the body. Their primary role is to present endogenous
antigens, which are typically fragments of proteins derived from within the
cell. These antigens can be viral proteins, tumor antigens, or other
intracellular proteins.
● Immune Response: When a cell is infected with a virus or becomes
cancerous, it will present viral or tumor antigens on its MHC class I
molecules. Cytotoxic T lymphocytes (CTLs or CD8+ T cells) survey these
MHC class I-antigen complexes. If the antigens are recognized as foreign or
abnormal, the CTLs will destroy the infected or cancerous cell to prevent the
infection from spreading.
MHC Class II Molecules:
● Function: MHC class II molecules are primarily found on antigen-presenting
cells (APCs), including dendritic cells, macrophages, and B cells. These
molecules are responsible for presenting exogenous antigens, which are
typically derived from outside the cell, such as those from bacteria, viruses, or
environmental sources.
● Immune Response: Antigen-presenting cells internalize and process
exogenous antigens. These antigens are then presented on their MHC class
II molecules. Helper T lymphocytes (CD4+ T cells) recognize these MHC
class II-antigen complexes. When helper T cells bind to these complexes,
they initiate and coordinate various immune responses. For instance, they
can activate B cells to produce antibodies and stimulate cytotoxic T cells to
kill infected cells.
In summary, MHC gene products are critical for the immune response as they facilitate the
recognition of antigens by T cells. MHC class I molecules present antigens from within
infected or cancerous cells, allowing cytotoxic T cells to eliminate the affected cells. MHC
class II molecules present antigens from external sources to helper T cells, which then
orchestrate the immune response by activating other immune cells. The interactions
between MHC molecules and T cells are central to adaptive immunity and the body's ability
to recognize and combat pathogens and abnormal cells.
Antigens
1.Define the terms: antigen, hapten, carrier.
Antigen: An antigen is a molecule or molecular structure that is recognized by the immune
system as a foreign invader or a threat. Antigens can trigger an immune response, including
the production of antibodies, to defend the body against infections. Antigens can be found on
the surface of pathogens like bacteria or viruses, as well as on the surface of cells,
allergens, or other foreign substances.
Hapten: A hapten is a small molecule that, on its own, does not induce an immune
response. However, when it binds to a larger carrier molecule, it can become immunogenic.
Haptens are typically too small to be recognized by the immune system directly, but when
they attach to a carrier molecule, they can elicit an immune response against the entire
complex, including the carrier.
Carrier: In the context of immunology, a carrier is a larger molecule that can bind to a hapten
and make it immunogenic. By attaching to the hapten, the carrier presents the combined
structure to the immune system, which can then recognize and mount an immune response
against the hapten-carrier complex. Carriers are often proteins or other macromolecules that
can effectively present the hapten to the immune system.
Immunogenicity: Not all antigens are equally immunogenic. Some antigens are highly
immunogenic and can elicit a strong immune response, while others may be weakly
immunogenic and require the help of adjuvants or other immune-stimulating molecules to
provoke a response.
Molecular Diversity: Antigens can be composed of a wide variety of molecules, including
proteins, carbohydrates, lipids, and nucleic acids. The diversity of these molecules allows
the immune system to recognize a broad range of potential threats.
Epitopes: Antigens often contain specific regions called epitopes or antigenic determinants.
Epitopes are the parts of the antigen that are recognized by antibodies or T-cell receptors.
These epitopes can be linear sequences of amino acids in proteins or specific arrangements
of other molecular structures.
Self-Antigens: While antigens are typically thought of as foreign molecules, the immune
system also recognizes self-antigens, which are molecules derived from the body's own
tissues. Normally, the immune system is tolerant of self-antigens to avoid attacking healthy
tissues, but autoimmune diseases can result from the loss of self-tolerance.
Antigen Recognition:
● TD antigens are typically protein-based antigens. When antigen-presenting
cells (APCs), such as dendritic cells or macrophages, encounter TD antigens,
they phagocytose the antigens and process them into smaller peptide
fragments.
● These peptide fragments are presented on the surface of APCs using major
histocompatibility complex class II (MHC-II) molecules.
T Cell Activation:
● T helper (Th) cells, a subset of T lymphocytes, recognize the antigenic
peptides presented by APCs through their T cell receptors (TCRs).
● This interaction activates Th cells, leading to their proliferation and
differentiation into effector Th cells and memory Th cells.
B Cell Activation:
● Activated Th cells provide help to B cells by releasing cytokines and cell
surface interactions.
● B cells have surface receptors called B cell receptors (BCRs) that can
recognize specific antigenic epitopes.
● When BCRs on B cells bind to the TD antigen, it initiates B cell activation.
B Cell Differentiation:
● Activated B cells undergo clonal expansion and differentiation into plasma
cells.
● Plasma cells produce large quantities of antibodies (immunoglobulins)
specific to the TD antigen.
Immune Response:
● Antibodies produced by plasma cells circulate in the bloodstream and can
neutralize or mark the TD antigen for destruction by other immune cells.
● Memory B cells are also generated during this process, providing long-term
immunity upon re-exposure to the same antigen.
Antigen Recognition:
● TI antigens are often polysaccharides, molecules with repeating structures, or
other highly conserved structures.
● B cells can directly recognize and bind to TI antigens using their BCRs
without the need for T cell assistance.
B Cell Activation:
● Binding of TI antigens to BCRs triggers signaling pathways within B cells,
leading to their activation.
Antibody Production:
● Activated B cells differentiate into plasma cells and produce antibodies
specific to the TI antigen.
Immune Response:
● Antibodies produced in response to TI antigens can neutralize the antigen or
opsonize it, making it more susceptible to phagocytosis by macrophages.
● TI antigen responses often generate weaker and shorter-lived immune
memory compared to TD antigen responses.
In summary, the key distinction between TD and TI antigens lies in the requirement for T cell
help in the immune response. TD antigens require T cell assistance to stimulate B cells
effectively, resulting in stronger and more durable immune responses, including the
formation of memory B cells. TI antigens, on the other hand, can directly activate B cells but
typically result in weaker and less durable immune responses with limited memory cell
formation.
Primary Self-Antigens:
Nature of Antigens:
● Primary self-antigens are normal, healthy self-antigens that are part of the
body's own tissues and organs.
Recognition:
● The immune system is generally tolerant of primary self-antigens and does
not mount an immune response against them.
● In a healthy individual, primary self-antigens do not typically trigger
autoimmune reactions.
Examples:
● Proteins, carbohydrates, lipids, and other molecules present in healthy cells
and tissues are considered primary self-antigens.
● Examples include the proteins in muscle cells, carbohydrates on the surface
of red blood cells, and self-antigens found in the skin.
Tolerance:
● The immune system is tolerant to primary self-antigens due to mechanisms
like central tolerance in the thymus and bone marrow, which eliminate or
inactivate autoreactive immune cells during development.
Secondary Self-Antigens:
Nature of Antigens:
● Secondary self-antigens are self-antigens that become targets of an
autoimmune response due to a breakdown in self-tolerance mechanisms.
Recognition:
● Unlike primary self-antigens, the immune system recognizes secondary
self-antigens as foreign or non-self, leading to autoimmune reactions.
● Secondary self-antigens are associated with autoimmune diseases.
Examples:
● Secondary self-antigens include self-antigens that have been modified or
presented in an abnormal context, making the immune system perceive them
as threats.
● For example, in autoimmune diseases like rheumatoid arthritis, joint tissues
contain secondary self-antigens that are recognized as foreign, triggering an
autoimmune attack on the joints.
● In type 1 diabetes, beta cells in the pancreas are targeted by the immune
system as secondary self-antigens, resulting in the destruction of these
insulin-producing cells.
Breakdown of Tolerance:
● Autoimmune diseases often result from a breakdown in the mechanisms that
maintain self-tolerance. This breakdown can occur due to genetic
predisposition, environmental factors, or infections that expose the immune
system to self-antigens in an abnormal way.
Summary of Contrast:
● Nature: Primary self-antigens are normal, healthy self-antigens, while secondary
self-antigens are self-antigens that trigger autoimmune responses.
● Recognition: Primary self-antigens are tolerated by the immune system, while
secondary self-antigens are recognized as foreign due to a loss of self-tolerance.
● Examples: Primary self-antigens include those found in healthy tissues, while
secondary self-antigens are associated with autoimmune diseases and result from
abnormal immune responses to self-components.
● Tolerance Mechanisms: Primary self-antigens are tolerated due to effective central
and peripheral tolerance mechanisms, while autoimmune diseases often result from
the breakdown of these tolerance mechanisms, leading to the recognition of
secondary self-antigens as non-self.
The development of B-lymphocytes, also known as B cells, is a complex process that occurs
primarily in the bone marrow. B cells are a critical component of the adaptive immune
system and play a central role in producing antibodies to fight infections. Here is an overview
of the development of B-lymphocytes:
Origins in Hematopoietic Stem Cells (HSCs): B cell development begins with
hematopoietic stem cells (HSCs) in the bone marrow. These stem cells have the
potential to give rise to all blood cells, including B cells.
Commitment to B Cell Lineage: Under the influence of specific signaling molecules
and transcription factors, some HSCs commit to the B cell lineage. This commitment
involves the activation of genes that specify the B cell developmental program.
Progenitor Cells: Committed HSCs differentiate into B cell progenitor cells, known
as pro-B cells. At this stage, specific genetic rearrangements occur in the DNA,
leading to the formation of a unique B cell receptor (BCR) on the cell's surface. The
BCR is a membrane-bound antibody that will allow the B cell to recognize specific
antigens.
Rearrangement of BCR Genes: During the pro-B cell stage, genes encoding the
variable regions of the BCR, which determine its antigen-binding specificity, undergo
a process called V(D)J recombination. This genetic rearrangement involves the
random joining of different gene segments (variable, diversity, and joining segments)
to generate a diverse repertoire of BCRs. This diversity is crucial for the ability of B
cells to recognize a wide range of antigens.
Checkpoint and Selection: Pro-B cells that successfully rearrange their BCR genes
undergo a selection process. Those cells with BCRs that bind to self-antigens too
strongly are eliminated (negative selection) to prevent autoimmune reactions. B cells
with functional BCRs that recognize antigens at an appropriate level proceed to the
next stage.
Maturation and Differentiation: The selected B cells continue to mature and
differentiate as they progress through various developmental stages, including pre-B
cells and immature B cells. These cells are tested for self-reactivity and further
refined.
Exit to the Periphery: Once B cells have completed their maturation and their BCRs
are properly assembled, they exit the bone marrow and enter the peripheral lymphoid
tissues, such as the spleen and lymph nodes.
Antigen Encounter and Activation: In peripheral lymphoid tissues, B cells circulate
through the bloodstream and lymphatic system. When a mature B cell encounters its
cognate antigen (the specific antigen it can bind to), it becomes activated. This
activation may occur when the BCR interacts with an antigen, often with the help of T
cells.
Proliferation and Differentiation: Upon activation, B cells undergo clonal
expansion, leading to the production of a large number of identical B cells. These
activated B cells can differentiate into plasma cells, which are antibody-producing
factories, or memory B cells that provide long-term immunity.
Antibody Production: Plasma cells are highly specialized and secrete large
quantities of antibodies into the bloodstream. These antibodies recognize and
neutralize the specific antigen encountered by the B cell.
Antigen Encounter: B cells are equipped with B cell receptors (BCRs) on their cell
surfaces. Each B cell has a unique BCR with a specific binding site. When an
antigen, such as a pathogen's protein or other foreign molecule, enters the body, it
interacts with the BCR of a B cell if the BCR matches the antigen's shape.
BCR-Antigen Binding: If the BCR on a B cell's surface matches the antigen's
shape, the antigen binds to the BCR, creating an antigen-BCR complex. This binding
is highly specific, similar to a lock and key mechanism. Only B cells with BCRs that
can recognize a particular antigen will respond.
Activation: The binding of the antigen to the BCR is the trigger for the B cell's
activation. It sets off a cascade of intracellular events, including signaling pathways,
leading to the B cell's activation.
Internalization and Antigen Processing: Once the antigen is bound to the BCR,
the B cell internalizes the antigen-BCR complex. Inside the B cell, the antigen is
processed and broken down into smaller fragments.
Antigen Presentation: B cells, like other antigen-presenting cells (APCs), present
the processed antigen fragments on their cell surface using a protein complex called
major histocompatibility complex II (MHC II). MHC II presents the antigen to other
immune cells, such as helper T cells (CD4+ T cells).
Helper T Cell Activation: Helper T cells recognize the antigen-MHC II complex
presented by B cells. When a helper T cell's T cell receptor (TCR) matches the
presented antigen, it becomes activated. The activation of helper T cells triggers a
complex immune response.
Co-Stimulation: Helper T cells require additional signals from the B cell for full
activation. This co-stimulation is usually provided by molecules known as
co-stimulatory proteins, such as CD40 on the B cell interacting with CD40L on the
helper T cell.
Clonal Expansion: Once fully activated, B cells undergo clonal expansion, where
they rapidly divide and proliferate. This results in a population of B cells, all derived
from the original antigen-specific B cell.
Differentiation: Some of the newly generated B cells differentiate into plasma cells.
Plasma cells are specialized antibody factories that produce and secrete large
quantities of antibodies specific to the antigen. These antibodies can neutralize the
pathogen and tag it for destruction by other immune cells.
Memory B Cells: In addition to plasma cells, some B cells differentiate into memory
B cells. These cells have a long lifespan and "remember" the specific antigen.
Memory B cells provide long-term immunity, ensuring a faster and stronger immune
response if the same antigen is encountered again in the future.
4. List the markers of B-cells.
Development of B-lymphocytes
1. Development of B-lymphocytes.
B-lymphocytes, or B cells, are a type of white blood cell that plays a vital role in the immune
system. The development of B-lymphocytes occurs primarily in the bone marrow and
involves several stages of differentiation and maturation. Here is an overview of the
development of B-lymphocytes:
Hematopoietic Stem Cells (HSCs): B-cell development begins with hematopoietic
stem cells (HSCs) in the bone marrow. These stem cells have the potential to
differentiate into various blood cell types, including B cells.
Early Progenitor Stage: HSCs commit to becoming lymphoid progenitor cells, which
are early precursors of both B cells and T cells. These progenitor cells migrate to
specific areas within the bone marrow known as lymphoid niches.
Expression of B-Cell Receptor (BCR): In the lymphoid niches of the bone marrow,
lymphoid progenitor cells start expressing a B-cell receptor (BCR) on their cell
surface. The BCR is a membrane-bound antibody (immunoglobulin) molecule
specific to a particular antigen.
Rearrangement of BCR Genes: One of the key events in B-cell development is the
rearrangement of the genes that encode the variable regions of the BCR. This
process is called V(D)J recombination and results in the generation of a diverse
repertoire of B cells, each capable of recognizing a unique antigen.
Expression of Pre-B Cell Receptor: Once the V(D)J recombination process is
successful and the BCR is expressed, the cells are referred to as pre-B cells. Pre-B
cells also express a surrogate light chain (SLC) to form a pre-B cell receptor
complex. This complex serves as a checkpoint to ensure that the rearranged BCR is
functional.
Positive Selection: Pre-B cells that have functional BCRs undergo positive
selection, allowing them to survive and proceed with their development.
Non-functional pre-B cells are eliminated.
Maturation and Migration: After positive selection, the pre-B cells continue to
mature and undergo further differentiation, eventually giving rise to immature B cells.
These immature B cells leave the bone marrow and migrate to secondary lymphoid
organs, such as the spleen and lymph nodes.
Encounter with Antigens: In secondary lymphoid organs, immature B cells
encounter antigens. If an immature B cell's BCR matches an antigen, it gets activated
and differentiates into either plasma cells or memory B cells.
Plasma Cells and Memory B Cells: Plasma cells are responsible for producing
antibodies specific to the encountered antigen, while memory B cells "remember" the
antigen for a faster immune response upon re-exposure.
In summary, the development of B-lymphocytes involves a series of stages in the bone
marrow, beginning with hematopoietic stem cells and culminating in the generation of mature
B cells capable of recognizing and responding to specific antigens. These B cells play a
crucial role in the adaptive immune response by producing antibodies and forming
immunological memory.
2. B lymphocytes differentiation.
The differentiation of B lymphocytes, or B cells, is a complex process that occurs primarily in
the bone marrow and results in the generation of mature B cells capable of producing
antibodies. Here is an overview of the differentiation of B cells:
Hematopoietic Stem Cells (HSCs): B-cell development begins with hematopoietic
stem cells (HSCs) in the bone marrow. These multipotent stem cells have the
potential to differentiate into various blood cell types, including B cells.
Commitment to the Lymphoid Lineage: HSCs commit to becoming lymphoid
progenitor cells, which are early precursors of both B cells and T cells. This
commitment is influenced by specific transcription factors.
Development of Pro-B Cells:
● Lymphoid progenitor cells progress to the pro-B cell stage. At this stage, they
express surface markers such as CD19, CD20, and CD22.
● One of the hallmark events in B-cell differentiation is the rearrangement of
immunoglobulin heavy chain (IgH) gene segments. This process is called
V(D)J recombination and leads to the formation of a unique B-cell receptor
(BCR).
Expression of Pre-BCR:
● Once the V(D)J recombination of the IgH gene is successful and a functional
heavy chain is produced, the pro-B cell expresses a pre-B cell receptor
(pre-BCR). The pre-BCR consists of the newly formed heavy chain and a
surrogate light chain (SLC).
● The pre-BCR plays a critical role in signaling and development, ensuring that
the BCR is functional.
Positive Selection:
● Pro-B cells with a functional pre-BCR undergo positive selection, leading to
their survival and progression to the next stage.
● Positive selection checks for the functionality of the pre-BCR and its ability to
signal the cell.
Development of Immature B Cells:
● After positive selection, the pro-B cells mature into pre-B cells and then into
immature B cells.
● Immature B cells express both IgM and IgD BCR isotypes on their surface.
Tolerance Checkpoints:
● Immature B cells undergo tolerance checkpoints in the bone marrow to
ensure that they do not react strongly to self-antigens. B cells with strongly
self-reactive BCRs are either eliminated or undergo receptor editing to modify
their specificity.
Migration to Secondary Lymphoid Organs:
● Mature, non-self-reactive B cells leave the bone marrow and migrate to
secondary lymphoid organs, such as the spleen and lymph nodes, where they
encounter antigens.
Encounter with Antigens:
● In secondary lymphoid organs, mature B cells encounter antigens. If the BCR
of a mature B cell matches an antigen, it gets activated.
Differentiation into Effector B Cells:
● Activated B cells differentiate into effector B cells, including plasma cells and
memory B cells.
● Plasma cells are responsible for producing antibodies specific to the
encountered antigen.
● Memory B cells "remember" the antigen and provide long-term immunological
memory for future encounters.
In summary, the differentiation of B lymphocytes involves multiple stages, from
hematopoietic stem cells to the generation of mature B cells. This process includes genetic
rearrangements, positive selection, tolerance checkpoints, and antigen encounter, ultimately
leading to the production of antibodies and immunological memory.
3. Markers of B-cells.
B cells, also known as B lymphocytes, are immune cells that play a central role in the
adaptive immune response. They can be identified by the presence of specific cell surface
markers or antigens. These markers are often used to characterize and distinguish B cells
from other immune cells. Some of the key markers or antigens associated with B cells
include:
CD19: CD19 is a transmembrane glycoprotein that is considered one of the most
reliable markers for identifying B cells. It is expressed throughout B-cell development,
from the pro-B cell stage to mature B cells. CD19 is a crucial component of the B-cell
receptor (BCR) complex and plays a role in B-cell signaling.
CD20: CD20 is another cell surface marker expressed on B cells. It is present on
pre-B cells and mature B cells, but not on plasma cells. CD20 is often targeted in the
treatment of B-cell malignancies, such as non-Hodgkin lymphoma, using monoclonal
antibody therapies like rituximab.
CD21 (Complement Receptor 2, CR2): CD21 is a receptor for complement
fragments, and it is expressed on mature B cells. It plays a role in B-cell activation
and antigen presentation.
CD22: CD22 is a B-cell-specific adhesion molecule and inhibitory receptor. It helps
regulate B-cell activation by modulating BCR signaling. CD22 is expressed on the
surface of mature B cells.
CD24: CD24 is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein
found on B cells. It is also expressed on other immune cells, but it can be used as a
marker for B-cell populations in combination with other markers.
IgM (Immunoglobulin M): IgM is the first immunoglobulin isotype expressed on the
surface of B cells as part of the BCR. It is associated with early B-cell development
and is present on naive B cells.
IgD (Immunoglobulin D): IgD is another immunoglobulin isotype that, like IgM, is
expressed on the surface of mature B cells as part of the BCR. It is involved in
antigen recognition.
HLA-DR (Human Leukocyte Antigen - DR isotype): HLA-DR is a major
histocompatibility complex (MHC) class II molecule that is upregulated on the surface
of B cells when they are activated. It plays a role in antigen presentation to helper T
cells.
CD38: CD38 is expressed on B cells, particularly plasma cells. It is involved in
calcium signaling and can serve as a marker for plasma cell populations.
CD138 (Syndecan-1): CD138 is a marker for plasma cells and is not typically found
on the surface of B cells. It is commonly used to identify and characterize plasma
cells in tissues.
These markers are useful for immunophenotyping and studying different stages of B-cell
development, activation, and function. Additionally, they are valuable in clinical diagnostics
and research related to B-cell disorders and immune responses
4. B-cell receptor.
The B-cell receptor (BCR) is a crucial component of B lymphocytes (B cells) and plays a
central role in the adaptive immune response. It is a membrane-bound protein complex that
allows B cells to recognize and bind to specific antigens, which are typically parts of
pathogens such as bacteria, viruses, or other foreign invaders. The BCR consists of several
key elements:
Immunoglobulin (Ig) M or IgD: The core of the BCR is an immunoglobulin
molecule, either IgM or IgD, which serves as the antigen-binding component. Each B
cell expresses surface IgM and IgD molecules with identical antigen-binding regions.
These immunoglobulins are specific to particular antigens.
Membrane-Bound Antibodies: IgM and IgD antibodies are anchored to the B-cell
membrane, with their antigen-binding regions exposed on the cell surface. These
antibodies are identical to the soluble antibodies (immunoglobulins) secreted by
plasma cells that develop from activated B cells.
Igα and Igβ: These are accessory proteins that are associated with the
immunoglobulin molecules in the BCR complex. Igα and Igβ play a crucial role in
signal transduction. When the BCR binds to an antigen, it induces phosphorylation of
these accessory proteins, initiating intracellular signaling cascades.
5. Role of humoral immunity in immune reactions.
Humoral immunity is a critical component of the adaptive immune system responsible for
defending the body against pathogens, particularly bacteria, viruses, and toxins. It involves
the production of antibodies (also known as immunoglobulins) by B lymphocytes (B cells)
and plays several essential roles in immune reactions:
Antibody Production: B cells, activated by exposure to specific antigens,
differentiate into plasma cells. Plasma cells are specialized antibody factories that
produce large quantities of antibodies with precise antigen specificity. Each B cell
produces antibodies with a unique antigen-binding site.
Antigen Neutralization: Antibodies produced by plasma cells can directly bind to
antigens, such as proteins on the surface of bacteria or viruses. This binding process
neutralizes the infectivity of pathogens by preventing them from attaching to and
entering host cells. In the case of viruses, neutralization can also prevent viral
replication.
Opsonization: Antibodies can coat pathogens, a process known as opsonization.
This makes the pathogens more recognizable to phagocytic cells, such as
macrophages and neutrophils. Phagocytes can then engulf and digest the opsonized
pathogens more efficiently, enhancing the body's defense against infections.
Complement Activation: Antibodies can trigger the complement system, a group of
blood proteins that enhance the immune response. Activation of the complement
system leads to several immune functions, including the formation of membrane
attack complexes (MACs) that can lyse bacterial cells and the recruitment of
inflammatory cells to the site of infection.
Antibody-Dependent Cellular Cytotoxicity (ADCC): Antibodies can facilitate the
destruction of infected or abnormal cells. Natural killer (NK) cells and certain types of
white blood cells, like macrophages, have Fc receptors that can bind to the Fc region
of antibodies. When antibodies bind to the surface of target cells (e.g., virus-infected
cells or cancer cells), these effector cells can recognize and kill the target cells.
Memory Response: After the initial encounter with an antigen, some B cells
differentiate into memory B cells. Memory B cells "remember" the specific antigen,
and upon re-exposure to the same antigen, they can rapidly generate a robust
antibody response. This is the basis for immunological memory and long-term
protection against pathogens.
Variability: Humoral immunity generates a diverse repertoire of antibodies, each
specific to a particular antigen. This diversity allows the immune system to respond
effectively to a wide range of pathogens and adapt to new challenges.
Duration of Protection: Humoral immunity provides both immediate and long-lasting
protection. While antibodies are rapidly produced during an active infection, memory
B cells ensure that the immu jim ne system can respond more quickly and effectively
to subsequent exposures to the same pathogen.
In summary, humoral immunity, mediated by antibodies produced by B cells, is a crucial arm
of the immune system that targets extracellular pathogens, toxins, and abnormal cells. It
plays a pivotal role in preventing and controlling infections, providing both immediate
defense and long-term immunological memory.
6. Antigen-dependent differentiation of B-lymphocytes.
Antigen-dependent differentiation of B-lymphocytes is a crucial process in the adaptive
immune response, leading to the development of plasma cells that produce antibodies
against specific antigens. This process involves several stages:
Antigen Encounter: The activation of B-lymphocytes begins when they encounter
an antigen that matches the antigen receptors on their surface. B cell receptors
(BCRs), which are membrane-bound antibodies, play a central role in antigen
recognition. These BCRs are immunoglobulin molecules anchored to the B cell
membrane.
Antigen Recognition: When an antigen binds to the BCRs on the B cell's surface, it
triggers a series of intracellular signaling events. This antigen recognition is highly
specific, with each B cell typically recognizing a single antigen or a closely related
group of antigens.
Internalization and Antigen Processing: After binding to the antigen, the B cell
internalizes the antigen-bound BCR complex through receptor-mediated endocytosis.
Once inside the B cell, the antigen is processed into smaller peptide fragments.
These antigen fragments are then displayed on the B cell's surface bound to major
histocompatibility complex class II (MHC-II) molecules.
Antigen Presentation: B cells, like other antigen-presenting cells (APCs), can
present the processed antigen fragments to helper T-lymphocytes (T cells) bearing
CD4 receptors. This interaction occurs within secondary lymphoid organs, such as
lymph nodes and the spleen. T cells are crucial in providing additional activation
signals to B cells.
T-Cell Help: When a helper T cell recognizes the antigen-MHC-II complex presented
by the B cell, it becomes activated. The activated helper T cell releases cytokines,
particularly interleukin-4 (IL-4) and interleukin-21 (IL-21), which play essential roles in
B-cell activation and differentiation.
B-Cell Activation: With the help of cytokines from activated helper T cells, the B cell
receives the necessary signals to become fully activated. This activation leads to
B-cell proliferation and differentiation.
Differentiation into Plasma Cells: Activated B cells differentiate into plasma cells,
also known as effector B cells. Plasma cells are specialized antibody factories that
produce large quantities of antibodies with the same antigen specificity as the original
B cell receptor. Each plasma cell produces a single type of antibody.
Antibody Production: The newly formed plasma cells release antibodies
(immunoglobulins) into the bloodstream. These antibodies circulate throughout the
body, binding to the specific antigen for which they were activated. Antibodies play
essential roles in immune defense, such as neutralizing pathogens, opsonizing them
for phagocytosis, activating the complement system, and facilitating
antibody-dependent cellular cytotoxicity (ADCC).
Memory B Cells: Alongside the generation of plasma cells, a subset of activated B
cells differentiates into memory B cells. Memory B cells "remember" the antigen and
remain in the body for a prolonged period. If the same antigen is encountered in the
future, memory B cells can quickly differentiate into plasma cells, resulting in a rapid
and robust antibody response.
Antigen-dependent differentiation of B-lymphocytes is a highly coordinated and specific
process that ensures the production of antibodies tailored to the encountered pathogen. This
process is a fundamental mechanism of adaptive immunity, allowing the immune system to
mount specific and memory responses to a wide range of antigens.
Five Major Types of Antibodies: Antibodies are classified into several types or classes,
each with distinct roles in the immune response. The five major types of antibodies include:
IgG (Immunoglobulin G): IgG is the most abundant antibody class in the
bloodstream, accounting for approximately 75-80% of all antibodies. It is highly
versatile and is involved in a broad range of immune functions, including neutralizing
pathogens, opsonization (marking pathogens for phagocytosis), and activating
complement proteins. IgG can cross the placenta, providing passive immunity to the
fetus.
IgM (Immunoglobulin M): IgM is the first antibody class produced during an initial
immune response. It is large and primarily found in the bloodstream. IgM is efficient
at agglutinating (clumping) pathogens, making them easier to clear from the body. It
is also a critical component of the B-cell receptor complex.
IgA (Immunoglobulin A): IgA is predominantly found in mucosal areas, such as the
respiratory and gastrointestinal tracts. It plays a vital role in mucosal immunity by
preventing pathogen attachment to mucosal surfaces and protecting against
infections. IgA is often found in secretions like saliva, tears, and breast milk.
IgE (Immunoglobulin E): IgE is associated with allergic reactions and immune
responses against parasitic infections. It binds to mast cells and basophils, triggering
the release of histamines and other inflammatory mediators when exposed to
allergens. This causes allergic symptoms, such as itching and swelling.
IgD (Immunoglobulin D): IgD is primarily found on the surface of B cells as a
receptor. It plays a role in B cell activation and maturation. IgD is less common in
circulation, and its specific functions are not as well understood as the other antibody
classes.
2. Describe the structure of an antibody monomer and state what part of it binds to
Antigens.
● Antibody Monomer Structure:
● Antibodies, also known as immunoglobulins (Ig), have a monomeric structure.
● Each antibody monomer is shaped like a "Y."
● The Y-shaped structure consists of two identical heavy chains and two
identical light chains.
● Binding Site for Antigens:
● The part of the antibody responsible for binding to antigens (foreign
substances) is located at the tips of the "Y."
● This region is referred to as the "antigen-binding site" or "paratope."
● The antigen-binding site is composed of the variable regions of both the
heavy chain and the light chain.
● Within these variable regions, there are three hypervariable regions called
CDRs (complementarity-determining regions).
● The CDRs, especially CDR3 at the junction of the V and C regions, exhibit the
greatest variability in amino acid sequences.
● This diversity allows antibodies to recognize and bind to a wide range of
specific antigens.
● The binding of an antibody to its specific antigen initiates immune responses,
including antigen neutralization, opsonization, and immune cell activation.
Remember that the specific amino acid sequences in the CDRs of the variable regions
determine the antibody's unique ability to recognize and bind to specific antigens.
3. Name and explain the functions of the Fab and Fc fragments of immunoglobulins.
The Fab (Fragment Antigen-Binding) and Fc (Fragment, Crystallizable) fragments of
immunoglobulins have distinct functions:
Fab Fragment (Fragment Antigen-Binding):
● Function: Binds to antigens (foreign substances, pathogens).
● Composition: Contains one constant and one variable domain from both
heavy and light chains.
● Specific Role: Shapes the antigen-binding site, also known as the paratope,
located at the amino terminal end of the monomer.
● Mechanism: The two variable domains, one from each heavy and light chain,
interact with specific epitopes on their corresponding antigens.
● Result: This binding initiates immune responses against the recognized
antigens.
Fc Fragment (Fragment, Crystallizable):
● Function: Modulates immune cell activity and mediates various physiological
effects.
● Composition: Comprises two heavy chains, contributing two or three constant
domains, depending on the antibody class.
● Key Roles:
● Protein Binding: Binds to specific proteins, ensuring the appropriate
immune response for a given antigen.
● Cell Receptor Interaction: Interacts with various cell receptors, such as
Fc receptors on immune cells.
● Interaction with Immune Molecules: Also binds to other immune
molecules, including complement proteins.
● Physiological Effects: Mediates effects like opsonization (enhancing
phagocytosis), cell lysis (cell destruction), and degranulation of
immune cells like mast cells, basophils, and eosinophils.
5. List and describe features of the structure and functions of the major classes of
Immunoglobulins.
6. Describe ways in which an antibody acts against an antigen.
Neutralization: Antibodies can bind to antigens, such as viruses or toxins, and block their
harmful effects. By neutralizing these antigens, antibodies prevent them from infecting cells
or damaging tissues.
Opsonization: Antibodies can enhance the process of phagocytosis, where immune cells
called phagocytes (e.g., macrophages and neutrophils) engulf and destroy pathogens.
Antibodies attach to antigens, making them more visible to phagocytes and improving the
efficiency of pathogen clearance.
Complement Activation: Antibodies can trigger the complement system, a group of
proteins that form pores in the membranes of pathogens. This process leads to cell lysis
(bursting) and the destruction of the pathogen.
7. Provide examples of using monoclonal antibodies in therapy.