Cells of the
Immune System
U.G. I.P Stephen
MSc in Cellular and Molecular Immunology,
BSc Biomedical science in University of Cardiff
met (UK), Higher national diploma in
biomedical science, Advanced Diploma in
Medical laboratory technology,
Dip in english British council . Higher Diploma in
English .
Immune System
A network of biological processes that protects an organism from diseases
Immunity means protection from disease and, more specifically, infectious disease
The organs, cells and molecules responsible for immunity constitute the immune system
 Immune systems response to the foreign substances is called the immune response
Immunology is the study of the body’s defense against infection
Why hematopoiesis is regulated by complex
mechanisms that affect individual cell types
 Differentiation: The regulation of hematopoiesis is crucial for the precise control of HSC
differentiation into specific blood cell types.
 Proliferation: Hematopoietic progenitor cells require signals from their microenvironment to
regulate their proliferation and survival. These signals are important for maintaining the balance
between the generation of new blood cells and the depletion of HSCs.
 Apoptosis: Hematopoiesis also involves programmed cell death, or apoptosis, of certain blood cell
types. This is important to ensure that older or damaged cells are removed from the circulation and
replaced with newer, healthier cells. Apoptosis is also tightly regulated to ensure the appropriate
balance of cell types.
 Immune response: Hematopoietic cells play a critical role in the immune response by producing
cytokines and chemokine, which are involved in the regulation of immune cell function. The
regulation of hematopoiesis is essential for the proper functioning of the immune system.
 Disease states: Abnormalities in hematopoiesis can lead to various diseases, including leukemia,
lymphoma, and anemia. The regulation of hematopoiesis is crucial for maintaining the balance
between the generation of new blood cells and the prevention of abnormal cell growth.
Cells of the Myeloid Lineage
Cells of the Immune System
 Granulocyte.
 White blood cells (leukocytes) which are classified as;
- Neutrophils,
- Basophils,
- Eosinophil's
 contain enzymes and other substances that help the granulocytes to perform their functions in the
immune system
 The cytoplasm of all granulocytes is replete with granules that are released in
response to contact with pathogens
 These granules contain a variety of proteins with distinct functions:
i. Damage pathogens directly
ii. Regulate trafficking and activity of other white blood cells
iii. Contribute to the remodeling of tissues at the site of infection
Neutrophils
 Dominant first responders to infection
 Constitute the majority (50%-70%) of circulating leukocytes
 Two types of granules in the cytoplasm
- Specific granules
- Azurophilic granules
 Granulocyte colony-stimulating factor stimulates production
 After differentiation in the bone marrow, neutrophils are released into the
peripheral blood and circulate for 7 – 10 hours before migrating into the tissues,
• Have a short life span (only a few days) within the tissues
• Predominant role – phagocytosis and pathogen killing
Neutrophils are recruited to the site of infection in response to inflammatory
molecules (eg: chemokines) generated by cells that have engaged a pathogen
• Once in tissues, neutrophils phagocytose (engulf) bacteria, and secrete a range of
proteins that have antimicrobial effects and tissue remodeling potential
• In response to infections, the number of circulating neutrophils increases
significantly, and more are recruited to tissues
• The resulting transient increase in the number of circulating neutrophils, called
leukocytosis, is used medically as an indication of infection
 Abnormalities in neutrophil levels or function can be indicative of various health conditions,
including infections, autoimmune diseases, and blood disorders.
Neutrophil vector illustration
• Derived and matured in bone marrow
• Non-phagocytic granulocytes
• Contain large granules filled with basophilic proteins
• In response to binding of circulating antibodies, basophils release the contents of their
granules
• Histamine, one of the best-known proteins in basophilic granules, increases blood vessel
permeability and smooth muscle activity.
Basophils are involved in allergic reactions and hypersensitivity responses. When exposed to an allergen, such
as pollen or certain foods, basophils release histamine, which causes symptoms such as swelling, itching, and
redness. Basophils also play a role in defending against parasites.
• Basophils (and eosinophils) are critical to our response to parasites, particularly
helminths (worms),
• But in areas where worm infection is less prevalent, histamines are best appreciated as
the cause of allergy symptoms
• Like neutrophils, basophils may also secrete cytokines that modulate the adaptive
immune response
Basophils
 Eosinophil are a type of white blood cell that play a role in the immune response.
 They are one of the five different types of white blood cells found in the human body, and they are
characterized by the presence of granules, or small structures, in their cytoplasm.
 Granules are membrane bound organelles with central crystalloid core;
• Contains major basic protein (MBP) which can damage membranes of helminths (worms)
• Induces mast cells (histamine release)
• Activates neutrophils and platelets
 Secrete cytokines that regulate B and T lymphocytes, thereby influencing the adaptive
 immune response
 • Appreciated as contributors to asthma and allergy symptoms
 Eosinophils are involved in the body's response to parasites and certain infections, as well as in allergic
reactions and asthma.
 They also play a role in certain inflammatory conditions such as eosinophilic esophagitis and eosinophilic
asthma.
 The normal range of eosinophils in the blood is typically between 0-6% of the total white blood cell count,
although this can vary depending on factors such as age, sex, and overall health.
 Elevated levels of eosinophils in the blood, known as eosinophilia, can indicate an underlying medical
condition and may require further evaluation and treatment.
Eosinophil
(LeMessurier K & Samarasinghe A,2019)
 Non-phagocytic granulocytes
 Released from the bone marrow into the blood as undifferentiated cells;
 They mature only after they leave the blood
 Can be found in a wide variety of tissues, including the skin, connective tissues ofvarious organs, and mucosal epithelial
tissue of the respiratory, genitourinary,and digestive tracts
 Contain large numbers of cytoplasmic granules that contain histamine and other
pharmacologically active substances
 Functions of Mast Cells:
 Allergic Reactions: Mast cells are best known for their role in allergic reactions. When exposed to allergens such as pollen,
pet dander, or certain foods, mast cells release histamine and other mediators, leading to allergic symptoms such as
itching, redness, swelling, and increased mucus production.
 Inflammation: Mast cells play a critical role in initiating and amplifying inflammatory responses. When tissues are damaged
or invaded by pathogens, mast cells release various inflammatory mediators that attract immune cells to the site of injury
or infection. This contributes to the recruitment of immune cells and the elimination of pathogens.
 Immune Defense: Mast cells are capable of detecting and responding to various pathogens directly, such as bacteria,
viruses, and parasites. They release antimicrobial peptides and cytokines to help combat infections.
 Angiogenesis: Mast cells contribute to the process of angiogenesis, which involves the growth of new blood vessels. This is
important for wound healing and tissue repair.
 Tissue Repair: While mast cells are associated with inflammation, they also play a role in tissue repair by releasing factors
that promote tissue remodeling and wound healing.
 Immunoregulation: Mast cells can influence the immune response by interacting with other immune cells and regulating
the balance between pro-inflammatory and anti-inflammatory signals.
Mast cells
(Noto, C.N et al 2021 )
 Myeloid antigen-presenting cells (APCs) are a type of immune cell that plays a critical role in the
adaptive immune response by presenting antigens to T cells.
 Myeloid progenitors also give rise to a group of phagocytic cells
- Monocytes & Macrophages
- Dendritic cells.
 When a pathogen invades the body, myeloid APCs engulf and digest it, and then present small
fragments of the pathogen's proteins, known as antigens, on their cell surface using molecules called
major histocompatibility complex (MHC) molecules. T cells recognize these antigen-MHC complexes and
become activated to mount an immune response against the pathogen.
 Myeloid APCs also produce cytokines and chemokine that help to recruit and activate other immune
cells, including B cells and effector T cells. Myeloid APCs are therefore critical for the initiation and
coordination of the adaptive immune response.
Myeloid antigen-presenting
Monocytes
 Monocytes are a type of white blood cell that are produced in the bone marrow and circulate in the blood. They are part
of the myeloid lineage of cells and are precursors to macrophages and dendritic cells.
 Monocytes are important components of the immune system and play a role in both innate and adaptive immunity. They
are able to recognize and engulf foreign particles, such as bacteria and viruses, and present antigens to T cells, which
triggers an immune response.
 In response to inflammation or infection, monocytes can leave the bloodstream and migrate into tissues, where they
differentiate into macrophages or dendritic cells. Macrophages are phagocytic cells that engulf and digest pathogens and
debris, while dendritic cells are specialized APCs that activate T cells and initiate adaptive immune responses.
 Overall, monocytes play an important role in coordinating immune responses and maintaining homeostasis in the body.
 Macrophages are specialized immune cells that are part of the myeloid lineage of cells. They are derived from
monocytes, which are produced in the bone marrow and circulate in the blood.
 Macrophages play a key role in the innate immune response, which is the first line of defense against invading
pathogens. They are phagocytic cells, which means that they are able to engulf and digest foreign particles, such as
bacteria, viruses, and debris.
 In addition to phagocytosis, macrophages also play a role in antigen presentation. They present antigens to T cells,
which activate and coordinate the adaptive immune response. Macrophages also produce cytokines and chemokines,
which are signaling molecules that help to recruit and activate other immune cells.
 Macrophages are found in tissues throughout the body, where they play a variety of roles. In addition to their role in
the immune system, macrophages are also involved in tissue repair and regeneration. They can promote the growth of
new blood vessels and help to remove damaged tissue.
 Overall, macrophages play a crucial role in maintaining homeostasis in the body and protecting against infection and
disease.
Macrophages
Erythrocytes (Erythroid Cells/Red Blood Cells)
 Erythrocytes, also known as erythroid cells or red blood cells (RBCs), are specialized cells that circulate in the blood and
transport oxygen from the lungs to the body's tissues.
 They are biconcave in shape, with no nucleus or organelles, which allows them to maximize their surface area and
increase their oxygen-carrying capacity.
 Erythrocytes are produced in the bone marrow from stem cells called erythroblasts.
 They contain a protein called hemoglobin, which binds to oxygen and enables the cells to carry oxygen throughout the
body. When erythrocytes become old or damaged, they are removed from circulation by the spleen and liver.
 The production of erythrocytes is tightly regulated by the hormone erythropoietin, which is produced by the kidneys in
response to low oxygen levels in the blood. Erythropoietin stimulates the bone marrow to produce more erythrocytes,
increasing the oxygen-carrying capacity of the blood.
 Abnormalities in erythrocyte production or function can lead to a range of disorders, including anemia, sickle cell
disease, and thalassemia. Anemia is a condition characterized by a reduced number of erythrocytes or a decrease in
hemoglobin levels, which can result in fatigue, weakness, and shortness of breath.
Megakaryocytes and platelets
 Megakaryocytes are large myeloid cells that reside in the bone marrow and give rise to thousands of platelets,
 Platelets are not cells; fragments of megakaryocytes that circulate in the blood
 Contains granules, microtubules, actin-myosin filaments
 • Involve in
- Clotting
- Inflammation
When a blood vessel is damaged, platelets are the first cells to arrive at the site of injury. They become activated and
stick to the damaged area, forming a plug to stop bleeding. In addition to their role in clotting, platelets also play a role in
inflammation, wound healing, and maintaining the integrity of blood vessels.
The process of platelet formation, or thrombopoiesis, begins with the maturation of megakaryocytes. As megakaryocytes
mature, they undergo a process called endomitosis, in which their nuclei divide but the cells do not divide. This results in
megakaryocytes with multiple nuclei, which then undergo fragmentation to produce platelets.
Megakaryocytes are essential for the production of platelets and for maintaining proper blood clotting. Dysfunction of
megakaryocytes and platelets can lead to bleeding disorders, such as thrombocytopenia, or clotting disorders, such as
thrombophilia.
platelet formation
Cells of the Lymphoid Lineage
These cells are a type of immune cell that plays a crucial role in the immune response. The
common lymphoid progenitor (CLP) is a precursor cell that gives rise to various types of
lymphocytes, which are a subset of white blood cells involved in the adaptive immune
system. Common lymphoid lineage cells include:
B Cells: B cells are responsible for producing antibodies, which are proteins that help the
immune system recognize and neutralize pathogens (like bacteria and viruses). They
mature in the bone marrow.
T Cells: T cells are involved in cell-mediated immunity. They can directly attack infected or
abnormal cells and also help regulate the immune response. T cells mature in the thymus
gland.
Natural Killer (NK) Cells: NK cells are a type of lymphocyte that is important for the innate
immune response. They are capable of recognizing and destroying infected or cancerous
B cell
Characterization of B Cells:
B cells are characterized by the presence of specific surface markers, receptors, and their ability to produce antibodies.
Some of the key features of B cells include:
B Cell Receptor (BCR): B cells possess BCRs on their surface, which are specialized antigen receptors
consisting of membrane-bound immunoglobulins (antibodies) and associated signaling molecules. Each B cell
has a unique BCR that allows it to recognize a specific antigen.
CD Markers: B cells express specific cell surface markers called CD markers, which are used to identify and
classify different types and stages of B cells. For example, mature B cells are often characterized by the
presence of CD19, CD20, and CD21 markers.
Antigen-Presenting Capability: B cells are proficient antigen-presenting cells (APCs). They can internalize
antigens, process them, and present antigen fragments on their surface using major histocompatibility
complex class II (MHC II) molecules. This interaction with helper T cells is crucial for the activation of B cells.
Antibody Production: One of the primary functions of B cells is to produce antibodies. When a B cell encounters an antigen
that matches its BCR, it gets activated and undergoes differentiation into plasma cells. Plasma cells are antibody-secreting
cells that release large amounts of antibodies into the bloodstream.
Humoral Immunity: B cells are central to humoral immunity, which involves the production of soluble antibodies that
circulate in bodily fluids (like blood and lymph). This type of immunity is particularly effective against extracellular pathogens
such as bacteria and viruses that are present outside of cells.
Memory Response: B cells also generate memory cells. Memory B cells "remember" previous encounters with antigens. If
the same antigen reappears, memory B cells quickly initiate a more rapid and potent immune response, leading to faster
elimination of the pathogen.
Affinity Maturation: During an immune response, B cells undergo affinity maturation, a process where their antibodies'
binding affinity to the antigen improves over time. This is facilitated by somatic hypermutation, a mechanism that
introduces random mutations into the antibody genes, leading to the production of antibodies with higher affinities for the
antigen.
Immunoregulation: B cells can influence the immune response through immunoregulatory functions. Regulatory B cells
(Bregs) have been identified that can suppress immune responses and promote tolerance, helping to prevent autoimmune
reactions.
Antigen Presentation: B cells, as APCs, can process antigens and present them to helper T cells. This interaction is crucial for
the activation of both B cells and T cells, coordinating different arms of the immune response.
Functions of B Cells:
T cell
Characterization of T Cells:
T cells are characterized by their specific receptors, surface markers, and functions. Some key features of T cells
include:
T Cell Receptor (TCR): Like B cells, T cells also possess antigen receptors on their surface. These receptors are
known as T cell receptors (TCRs). TCRs recognize specific antigens presented by major histocompatibility complex
(MHC) molecules on the surface of other cells. There are two main types of T cells based on the type of MHC
molecules they interact with: CD4+ T cells (helper T cells) interact with MHC class II molecules, and CD8+ T cells
(cytotoxic T cells) interact with MHC class I molecules.
CD Markers: T cells express various cell surface markers, including CD3, CD4, and CD8. CD3 is part of the TCR
complex and is essential for signal transduction upon antigen recognition. CD4 is primarily found on helper T cells
and assists in recognizing MHC class II molecules, while CD8 is primarily found on cytotoxic T cells and assists in
recognizing MHC class I molecules.
T Cell Subtypes: T cells are broadly categorized into several subtypes based on their functions and markers. These
include helper T cells (Th), cytotoxic T cells (CTLs), regulatory T cells (Tregs), and memory T cells.
Functions of T Cells:
T cells perform diverse functions that contribute to the immune response's effectiveness:
Helper T Cells (Th cells):
Th1 Cells: These cells stimulate cell-mediated immunity, enhancing the activity of macrophages and cytotoxic T cells to target intracellular
pathogens like viruses and certain bacteria.
Th2 Cells: These cells are involved in promoting humoral immunity by aiding B cells in antibody production. They play a role in defense
against extracellular parasites.
Th17 Cells: Th17 cells are involved in immune responses against fungal and bacterial infections. They are also associated with autoimmune
responses.
Tfh Cells: T follicular helper cells are crucial for promoting B cell maturation and antibody affinity maturation in germinal centers of lymph
nodes.
Cytotoxic T Cells (CTLs):
CTLs are responsible for directly attacking and eliminating virus-infected cells, cancer cells, and cells infected by intracellular pathogens.
Regulatory T Cells (Tregs):
Tregs play a vital role in immune system regulation and preventing autoimmune reactions by suppressing excessive immune responses.
They help maintain immune tolerance to self-antigens and prevent the immune system from attacking healthy tissues.
Memory T Cells:
Similar to memory B cells, memory T cells "remember" previous encounters with antigens, leading to faster and more effective immune
responses upon re-exposure to the same antigen.
T cells are essential for orchestrating a coordinated and targeted immune response against a wide range of threats, including infections and
abnormal cells. They work in collaboration with other immune cells to maintain the body's health and immune surveillance.
Natural Killer (NK) Cells
Characterization of NK Cells:
NK cells possess certain surface markers and receptors that distinguish them from other immune cells:
CD Markers: NK cells are characterized by the presence of specific cell surface markers, including CD56 and CD16
(FcγRIIIa). CD56 is a neural cell adhesion molecule, and CD16 is a receptor for the Fc portion of antibodies. These
markers help identify and classify NK cells.
Killer Cell Immunoglobulin-like Receptors (KIRs): NK cells express receptors called KIRs, which are involved in
recognizing self-MHC class I molecules on healthy cells. These receptors help NK cells distinguish between healthy
and infected or abnormal cells.
(Islam R et al 2023)
Functions of NK Cells:
 Cytotoxic Activity: NK cells are known for their ability to recognize and directly kill virus-infected cells, tumor cells, and other
abnormal cells. They do this by releasing cytotoxic molecules such as perforin and granzymes, which induce apoptosis (cell
death) in the target cells.
 Lack of MHC Recognition: Unlike T cells, which require antigen presentation on MHC molecules for activation, NK cells can
recognize cells that have downregulated MHC class I molecules. This is a common strategy used by some infected or
cancerous cells to evade immune detection by T cells.
 Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): NK cells can also participate in ADCC. They recognize cells that are
opsonized (coated with antibodies) by binding to the Fc portion of antibodies through their CD16 receptors. This triggers
cytotoxic responses against the antibody-bound target cells.
 Cytokine Production: NK cells produce various cytokines, including interferon-gamma (IFN-γ), which plays a role in activating
other immune cells and enhancing the immune response.
 Immunoregulation: NK cells can influence the overall immune response by interacting with other immune cells. They can
interact with dendritic cells and macrophages to modulate the immune environment.
 Pregnancy and Tolerance: NK cells have specialized roles during pregnancy, particularly in the uterine lining. They help
regulate the maternal-fetal interface and play a role in ensuring maternal immune tolerance to the developing fetus.
Reference
1) Islam, R., Pupovac, A., Evtimov, V., Boyd, N., Shu, R., Boyd, R. and Trounson, A., 2021. Enhancing a natural killer:
Modification of NK cells for cancer immunotherapy. Cells, 10(5), p.1058.
2) LeMessurier, K.S. and Samarasinghe, A.E., 2019. Eosinophils: nemeses of pulmonary pathogens?. Current
allergy and asthma reports, 19, pp.1-10.
3) Noto, C.N., Hoft, S.G. and DiPaolo, R.J., 2021. Mast cells as important regulators in autoimmunity and cancer
development. Frontiers in Cell and Developmental Biology, 9, p.752350.
4) Kuby Immunology (7th edition), Owen et al, WH Freeman & Company, New
York, USA
5)Immunology, Male et al, Elsevier Ltd, Philadelphia, USA
6) Roitt’s Essential Immunology, Delves et al, Blackwell Publishing Ltd, Oxford,
7) Immunobiology, Janeway et al, Garland Science, Taylor & Francis Group, LLC
6) Cellular and Molecular Immunology, Abbas et al, Elsevier Ltd, Philadelphia,
USA
THANK
YOU

Cell of immune system.pptx

  • 1.
    Cells of the ImmuneSystem U.G. I.P Stephen MSc in Cellular and Molecular Immunology, BSc Biomedical science in University of Cardiff met (UK), Higher national diploma in biomedical science, Advanced Diploma in Medical laboratory technology, Dip in english British council . Higher Diploma in English .
  • 2.
    Immune System A networkof biological processes that protects an organism from diseases Immunity means protection from disease and, more specifically, infectious disease The organs, cells and molecules responsible for immunity constitute the immune system  Immune systems response to the foreign substances is called the immune response Immunology is the study of the body’s defense against infection
  • 5.
    Why hematopoiesis isregulated by complex mechanisms that affect individual cell types  Differentiation: The regulation of hematopoiesis is crucial for the precise control of HSC differentiation into specific blood cell types.  Proliferation: Hematopoietic progenitor cells require signals from their microenvironment to regulate their proliferation and survival. These signals are important for maintaining the balance between the generation of new blood cells and the depletion of HSCs.  Apoptosis: Hematopoiesis also involves programmed cell death, or apoptosis, of certain blood cell types. This is important to ensure that older or damaged cells are removed from the circulation and replaced with newer, healthier cells. Apoptosis is also tightly regulated to ensure the appropriate balance of cell types.  Immune response: Hematopoietic cells play a critical role in the immune response by producing cytokines and chemokine, which are involved in the regulation of immune cell function. The regulation of hematopoiesis is essential for the proper functioning of the immune system.  Disease states: Abnormalities in hematopoiesis can lead to various diseases, including leukemia, lymphoma, and anemia. The regulation of hematopoiesis is crucial for maintaining the balance between the generation of new blood cells and the prevention of abnormal cell growth.
  • 6.
    Cells of theMyeloid Lineage
  • 7.
    Cells of theImmune System  Granulocyte.  White blood cells (leukocytes) which are classified as; - Neutrophils, - Basophils, - Eosinophil's  contain enzymes and other substances that help the granulocytes to perform their functions in the immune system  The cytoplasm of all granulocytes is replete with granules that are released in response to contact with pathogens  These granules contain a variety of proteins with distinct functions: i. Damage pathogens directly ii. Regulate trafficking and activity of other white blood cells iii. Contribute to the remodeling of tissues at the site of infection
  • 9.
    Neutrophils  Dominant firstresponders to infection  Constitute the majority (50%-70%) of circulating leukocytes  Two types of granules in the cytoplasm - Specific granules - Azurophilic granules  Granulocyte colony-stimulating factor stimulates production  After differentiation in the bone marrow, neutrophils are released into the peripheral blood and circulate for 7 – 10 hours before migrating into the tissues, • Have a short life span (only a few days) within the tissues • Predominant role – phagocytosis and pathogen killing Neutrophils are recruited to the site of infection in response to inflammatory molecules (eg: chemokines) generated by cells that have engaged a pathogen • Once in tissues, neutrophils phagocytose (engulf) bacteria, and secrete a range of proteins that have antimicrobial effects and tissue remodeling potential • In response to infections, the number of circulating neutrophils increases significantly, and more are recruited to tissues • The resulting transient increase in the number of circulating neutrophils, called leukocytosis, is used medically as an indication of infection  Abnormalities in neutrophil levels or function can be indicative of various health conditions, including infections, autoimmune diseases, and blood disorders.
  • 10.
  • 12.
    • Derived andmatured in bone marrow • Non-phagocytic granulocytes • Contain large granules filled with basophilic proteins • In response to binding of circulating antibodies, basophils release the contents of their granules • Histamine, one of the best-known proteins in basophilic granules, increases blood vessel permeability and smooth muscle activity. Basophils are involved in allergic reactions and hypersensitivity responses. When exposed to an allergen, such as pollen or certain foods, basophils release histamine, which causes symptoms such as swelling, itching, and redness. Basophils also play a role in defending against parasites. • Basophils (and eosinophils) are critical to our response to parasites, particularly helminths (worms), • But in areas where worm infection is less prevalent, histamines are best appreciated as the cause of allergy symptoms • Like neutrophils, basophils may also secrete cytokines that modulate the adaptive immune response Basophils
  • 13.
     Eosinophil area type of white blood cell that play a role in the immune response.  They are one of the five different types of white blood cells found in the human body, and they are characterized by the presence of granules, or small structures, in their cytoplasm.  Granules are membrane bound organelles with central crystalloid core; • Contains major basic protein (MBP) which can damage membranes of helminths (worms) • Induces mast cells (histamine release) • Activates neutrophils and platelets  Secrete cytokines that regulate B and T lymphocytes, thereby influencing the adaptive  immune response  • Appreciated as contributors to asthma and allergy symptoms  Eosinophils are involved in the body's response to parasites and certain infections, as well as in allergic reactions and asthma.  They also play a role in certain inflammatory conditions such as eosinophilic esophagitis and eosinophilic asthma.  The normal range of eosinophils in the blood is typically between 0-6% of the total white blood cell count, although this can vary depending on factors such as age, sex, and overall health.  Elevated levels of eosinophils in the blood, known as eosinophilia, can indicate an underlying medical condition and may require further evaluation and treatment. Eosinophil
  • 14.
    (LeMessurier K &Samarasinghe A,2019)
  • 15.
     Non-phagocytic granulocytes Released from the bone marrow into the blood as undifferentiated cells;  They mature only after they leave the blood  Can be found in a wide variety of tissues, including the skin, connective tissues ofvarious organs, and mucosal epithelial tissue of the respiratory, genitourinary,and digestive tracts  Contain large numbers of cytoplasmic granules that contain histamine and other pharmacologically active substances  Functions of Mast Cells:  Allergic Reactions: Mast cells are best known for their role in allergic reactions. When exposed to allergens such as pollen, pet dander, or certain foods, mast cells release histamine and other mediators, leading to allergic symptoms such as itching, redness, swelling, and increased mucus production.  Inflammation: Mast cells play a critical role in initiating and amplifying inflammatory responses. When tissues are damaged or invaded by pathogens, mast cells release various inflammatory mediators that attract immune cells to the site of injury or infection. This contributes to the recruitment of immune cells and the elimination of pathogens.  Immune Defense: Mast cells are capable of detecting and responding to various pathogens directly, such as bacteria, viruses, and parasites. They release antimicrobial peptides and cytokines to help combat infections.  Angiogenesis: Mast cells contribute to the process of angiogenesis, which involves the growth of new blood vessels. This is important for wound healing and tissue repair.  Tissue Repair: While mast cells are associated with inflammation, they also play a role in tissue repair by releasing factors that promote tissue remodeling and wound healing.  Immunoregulation: Mast cells can influence the immune response by interacting with other immune cells and regulating the balance between pro-inflammatory and anti-inflammatory signals. Mast cells
  • 16.
    (Noto, C.N etal 2021 )
  • 17.
     Myeloid antigen-presentingcells (APCs) are a type of immune cell that plays a critical role in the adaptive immune response by presenting antigens to T cells.  Myeloid progenitors also give rise to a group of phagocytic cells - Monocytes & Macrophages - Dendritic cells.  When a pathogen invades the body, myeloid APCs engulf and digest it, and then present small fragments of the pathogen's proteins, known as antigens, on their cell surface using molecules called major histocompatibility complex (MHC) molecules. T cells recognize these antigen-MHC complexes and become activated to mount an immune response against the pathogen.  Myeloid APCs also produce cytokines and chemokine that help to recruit and activate other immune cells, including B cells and effector T cells. Myeloid APCs are therefore critical for the initiation and coordination of the adaptive immune response. Myeloid antigen-presenting
  • 18.
    Monocytes  Monocytes area type of white blood cell that are produced in the bone marrow and circulate in the blood. They are part of the myeloid lineage of cells and are precursors to macrophages and dendritic cells.  Monocytes are important components of the immune system and play a role in both innate and adaptive immunity. They are able to recognize and engulf foreign particles, such as bacteria and viruses, and present antigens to T cells, which triggers an immune response.  In response to inflammation or infection, monocytes can leave the bloodstream and migrate into tissues, where they differentiate into macrophages or dendritic cells. Macrophages are phagocytic cells that engulf and digest pathogens and debris, while dendritic cells are specialized APCs that activate T cells and initiate adaptive immune responses.  Overall, monocytes play an important role in coordinating immune responses and maintaining homeostasis in the body.
  • 19.
     Macrophages arespecialized immune cells that are part of the myeloid lineage of cells. They are derived from monocytes, which are produced in the bone marrow and circulate in the blood.  Macrophages play a key role in the innate immune response, which is the first line of defense against invading pathogens. They are phagocytic cells, which means that they are able to engulf and digest foreign particles, such as bacteria, viruses, and debris.  In addition to phagocytosis, macrophages also play a role in antigen presentation. They present antigens to T cells, which activate and coordinate the adaptive immune response. Macrophages also produce cytokines and chemokines, which are signaling molecules that help to recruit and activate other immune cells.  Macrophages are found in tissues throughout the body, where they play a variety of roles. In addition to their role in the immune system, macrophages are also involved in tissue repair and regeneration. They can promote the growth of new blood vessels and help to remove damaged tissue.  Overall, macrophages play a crucial role in maintaining homeostasis in the body and protecting against infection and disease. Macrophages
  • 20.
    Erythrocytes (Erythroid Cells/RedBlood Cells)  Erythrocytes, also known as erythroid cells or red blood cells (RBCs), are specialized cells that circulate in the blood and transport oxygen from the lungs to the body's tissues.  They are biconcave in shape, with no nucleus or organelles, which allows them to maximize their surface area and increase their oxygen-carrying capacity.  Erythrocytes are produced in the bone marrow from stem cells called erythroblasts.  They contain a protein called hemoglobin, which binds to oxygen and enables the cells to carry oxygen throughout the body. When erythrocytes become old or damaged, they are removed from circulation by the spleen and liver.  The production of erythrocytes is tightly regulated by the hormone erythropoietin, which is produced by the kidneys in response to low oxygen levels in the blood. Erythropoietin stimulates the bone marrow to produce more erythrocytes, increasing the oxygen-carrying capacity of the blood.  Abnormalities in erythrocyte production or function can lead to a range of disorders, including anemia, sickle cell disease, and thalassemia. Anemia is a condition characterized by a reduced number of erythrocytes or a decrease in hemoglobin levels, which can result in fatigue, weakness, and shortness of breath.
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    Megakaryocytes and platelets Megakaryocytes are large myeloid cells that reside in the bone marrow and give rise to thousands of platelets,  Platelets are not cells; fragments of megakaryocytes that circulate in the blood  Contains granules, microtubules, actin-myosin filaments  • Involve in - Clotting - Inflammation When a blood vessel is damaged, platelets are the first cells to arrive at the site of injury. They become activated and stick to the damaged area, forming a plug to stop bleeding. In addition to their role in clotting, platelets also play a role in inflammation, wound healing, and maintaining the integrity of blood vessels. The process of platelet formation, or thrombopoiesis, begins with the maturation of megakaryocytes. As megakaryocytes mature, they undergo a process called endomitosis, in which their nuclei divide but the cells do not divide. This results in megakaryocytes with multiple nuclei, which then undergo fragmentation to produce platelets. Megakaryocytes are essential for the production of platelets and for maintaining proper blood clotting. Dysfunction of megakaryocytes and platelets can lead to bleeding disorders, such as thrombocytopenia, or clotting disorders, such as thrombophilia. platelet formation
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    Cells of theLymphoid Lineage These cells are a type of immune cell that plays a crucial role in the immune response. The common lymphoid progenitor (CLP) is a precursor cell that gives rise to various types of lymphocytes, which are a subset of white blood cells involved in the adaptive immune system. Common lymphoid lineage cells include: B Cells: B cells are responsible for producing antibodies, which are proteins that help the immune system recognize and neutralize pathogens (like bacteria and viruses). They mature in the bone marrow. T Cells: T cells are involved in cell-mediated immunity. They can directly attack infected or abnormal cells and also help regulate the immune response. T cells mature in the thymus gland. Natural Killer (NK) Cells: NK cells are a type of lymphocyte that is important for the innate immune response. They are capable of recognizing and destroying infected or cancerous
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    B cell Characterization ofB Cells: B cells are characterized by the presence of specific surface markers, receptors, and their ability to produce antibodies. Some of the key features of B cells include: B Cell Receptor (BCR): B cells possess BCRs on their surface, which are specialized antigen receptors consisting of membrane-bound immunoglobulins (antibodies) and associated signaling molecules. Each B cell has a unique BCR that allows it to recognize a specific antigen. CD Markers: B cells express specific cell surface markers called CD markers, which are used to identify and classify different types and stages of B cells. For example, mature B cells are often characterized by the presence of CD19, CD20, and CD21 markers. Antigen-Presenting Capability: B cells are proficient antigen-presenting cells (APCs). They can internalize antigens, process them, and present antigen fragments on their surface using major histocompatibility complex class II (MHC II) molecules. This interaction with helper T cells is crucial for the activation of B cells.
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    Antibody Production: Oneof the primary functions of B cells is to produce antibodies. When a B cell encounters an antigen that matches its BCR, it gets activated and undergoes differentiation into plasma cells. Plasma cells are antibody-secreting cells that release large amounts of antibodies into the bloodstream. Humoral Immunity: B cells are central to humoral immunity, which involves the production of soluble antibodies that circulate in bodily fluids (like blood and lymph). This type of immunity is particularly effective against extracellular pathogens such as bacteria and viruses that are present outside of cells. Memory Response: B cells also generate memory cells. Memory B cells "remember" previous encounters with antigens. If the same antigen reappears, memory B cells quickly initiate a more rapid and potent immune response, leading to faster elimination of the pathogen. Affinity Maturation: During an immune response, B cells undergo affinity maturation, a process where their antibodies' binding affinity to the antigen improves over time. This is facilitated by somatic hypermutation, a mechanism that introduces random mutations into the antibody genes, leading to the production of antibodies with higher affinities for the antigen. Immunoregulation: B cells can influence the immune response through immunoregulatory functions. Regulatory B cells (Bregs) have been identified that can suppress immune responses and promote tolerance, helping to prevent autoimmune reactions. Antigen Presentation: B cells, as APCs, can process antigens and present them to helper T cells. This interaction is crucial for the activation of both B cells and T cells, coordinating different arms of the immune response. Functions of B Cells:
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    T cell Characterization ofT Cells: T cells are characterized by their specific receptors, surface markers, and functions. Some key features of T cells include: T Cell Receptor (TCR): Like B cells, T cells also possess antigen receptors on their surface. These receptors are known as T cell receptors (TCRs). TCRs recognize specific antigens presented by major histocompatibility complex (MHC) molecules on the surface of other cells. There are two main types of T cells based on the type of MHC molecules they interact with: CD4+ T cells (helper T cells) interact with MHC class II molecules, and CD8+ T cells (cytotoxic T cells) interact with MHC class I molecules. CD Markers: T cells express various cell surface markers, including CD3, CD4, and CD8. CD3 is part of the TCR complex and is essential for signal transduction upon antigen recognition. CD4 is primarily found on helper T cells and assists in recognizing MHC class II molecules, while CD8 is primarily found on cytotoxic T cells and assists in recognizing MHC class I molecules. T Cell Subtypes: T cells are broadly categorized into several subtypes based on their functions and markers. These include helper T cells (Th), cytotoxic T cells (CTLs), regulatory T cells (Tregs), and memory T cells.
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    Functions of TCells: T cells perform diverse functions that contribute to the immune response's effectiveness: Helper T Cells (Th cells): Th1 Cells: These cells stimulate cell-mediated immunity, enhancing the activity of macrophages and cytotoxic T cells to target intracellular pathogens like viruses and certain bacteria. Th2 Cells: These cells are involved in promoting humoral immunity by aiding B cells in antibody production. They play a role in defense against extracellular parasites. Th17 Cells: Th17 cells are involved in immune responses against fungal and bacterial infections. They are also associated with autoimmune responses. Tfh Cells: T follicular helper cells are crucial for promoting B cell maturation and antibody affinity maturation in germinal centers of lymph nodes. Cytotoxic T Cells (CTLs): CTLs are responsible for directly attacking and eliminating virus-infected cells, cancer cells, and cells infected by intracellular pathogens. Regulatory T Cells (Tregs): Tregs play a vital role in immune system regulation and preventing autoimmune reactions by suppressing excessive immune responses. They help maintain immune tolerance to self-antigens and prevent the immune system from attacking healthy tissues. Memory T Cells: Similar to memory B cells, memory T cells "remember" previous encounters with antigens, leading to faster and more effective immune responses upon re-exposure to the same antigen. T cells are essential for orchestrating a coordinated and targeted immune response against a wide range of threats, including infections and abnormal cells. They work in collaboration with other immune cells to maintain the body's health and immune surveillance.
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    Natural Killer (NK)Cells Characterization of NK Cells: NK cells possess certain surface markers and receptors that distinguish them from other immune cells: CD Markers: NK cells are characterized by the presence of specific cell surface markers, including CD56 and CD16 (FcγRIIIa). CD56 is a neural cell adhesion molecule, and CD16 is a receptor for the Fc portion of antibodies. These markers help identify and classify NK cells. Killer Cell Immunoglobulin-like Receptors (KIRs): NK cells express receptors called KIRs, which are involved in recognizing self-MHC class I molecules on healthy cells. These receptors help NK cells distinguish between healthy and infected or abnormal cells. (Islam R et al 2023)
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    Functions of NKCells:  Cytotoxic Activity: NK cells are known for their ability to recognize and directly kill virus-infected cells, tumor cells, and other abnormal cells. They do this by releasing cytotoxic molecules such as perforin and granzymes, which induce apoptosis (cell death) in the target cells.  Lack of MHC Recognition: Unlike T cells, which require antigen presentation on MHC molecules for activation, NK cells can recognize cells that have downregulated MHC class I molecules. This is a common strategy used by some infected or cancerous cells to evade immune detection by T cells.  Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): NK cells can also participate in ADCC. They recognize cells that are opsonized (coated with antibodies) by binding to the Fc portion of antibodies through their CD16 receptors. This triggers cytotoxic responses against the antibody-bound target cells.  Cytokine Production: NK cells produce various cytokines, including interferon-gamma (IFN-γ), which plays a role in activating other immune cells and enhancing the immune response.  Immunoregulation: NK cells can influence the overall immune response by interacting with other immune cells. They can interact with dendritic cells and macrophages to modulate the immune environment.  Pregnancy and Tolerance: NK cells have specialized roles during pregnancy, particularly in the uterine lining. They help regulate the maternal-fetal interface and play a role in ensuring maternal immune tolerance to the developing fetus.
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    Reference 1) Islam, R.,Pupovac, A., Evtimov, V., Boyd, N., Shu, R., Boyd, R. and Trounson, A., 2021. Enhancing a natural killer: Modification of NK cells for cancer immunotherapy. Cells, 10(5), p.1058. 2) LeMessurier, K.S. and Samarasinghe, A.E., 2019. Eosinophils: nemeses of pulmonary pathogens?. Current allergy and asthma reports, 19, pp.1-10. 3) Noto, C.N., Hoft, S.G. and DiPaolo, R.J., 2021. Mast cells as important regulators in autoimmunity and cancer development. Frontiers in Cell and Developmental Biology, 9, p.752350. 4) Kuby Immunology (7th edition), Owen et al, WH Freeman & Company, New York, USA 5)Immunology, Male et al, Elsevier Ltd, Philadelphia, USA 6) Roitt’s Essential Immunology, Delves et al, Blackwell Publishing Ltd, Oxford, 7) Immunobiology, Janeway et al, Garland Science, Taylor & Francis Group, LLC 6) Cellular and Molecular Immunology, Abbas et al, Elsevier Ltd, Philadelphia, USA
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