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1. Lymphoid cells T cells 4. Mast cells
B cells
NK cells
(Null cells)
2. Mononuclear
cells
Monocytes 5. Dendritic
cells
Langerhans cells
Interstitial DC
Macrophages Interdigitating
DC
Circulating DC
3. Granulocytic
cells
Neutrophils
Eosinophil
Basophil
Cells of the immune system
III. Granulocytic cells
1. Neutrophils
2. Eosinophils
3. Basophils
Formation of Granulocytes
Myeloid stem cells (myeloblast)
Promyeloblast
Myelocyte
Metamyelocytes
Granulocytes (N, E and B)
Differentiation
Takes app 14
days
Growth
factors reqd
are
G-CSF
GM-CSF
• has a multilobed nucleus (mostly has 2-5 lobes)
• it is often called as polymorphonuclear leukocyte (PMN) (for its
multilobed nucleus)
•are the most abundant white blood cells in humans approximately
108 - 1011 are produced daily)
•they account for approximately 70% of all white blood cells
(leukocytes).
1. Neutrophils
•They have granulated cytoplasm- it stains with both acid and
basic dyes
Hematopoiesis in Bone marrow
Neutrophils formed
Released into the peripheral blood and circulate for 7–10 h
After that migrate into the tissues, where they have a life span
of only a few days.
1. Neutrophils
Granules present in neutrophils
1. Primary
2. Secondary
3. Tertiary
In the presence of Ag- degranulation occurs
(which is release of contents from granules)
Release of contents
from Granules
Ag
Proteins present in the granules
Azurophilic
granules (or
"primary
granules")
 Myeloperoxidase
 bactericidal/ permeability increasing protein (BPI)
 defensins
 the serine proteases
 neutrophil elastase
 cathepsin G
Specific
granules (or
"secondary
granules")
 Lactoferrin
 cathelicidin
tertiary
granules
 cathepsin
 gelatinase
Azurophilic
granules (or
"primary
granules")
 Myeloperoxidase
 bactericidal/ permeability
increasing protein (BPI)
 defensins
 the serine proteases
 neutrophil elastase
 cathepsin G
hCAP 18- human cathelicidin
HOBr- Hypobromous acid
HOI- Hypoiodous acid
BPI (bactericidal/ permeability increasing
protein)
is a highly cationic, 55KD protein
Is a cytotoxic protein
Found only in the cells of myeloid series
Has strong affinity for LPS, so has potent
toxicity exclusively towards gram-negative
bacteria
Azurophilic
granules (or
"primary
granules")
 Myeloperoxidase
 bactericidal/ permeability
increasing protein (BPI)
 defensins
 the serine proteases
 neutrophil elastase
 cathepsin G
Azurophilic
granules (or
"primary
granules")
 Myeloperoxidase
 bactericidal/ permeability
increasing protein (BPI)
 defensins
 the serine proteases
 neutrophil elastase
 cathepsin G
 also known as ELA2 (elastase 2, neutrophil) is a serine
protease
Secreted by neutrophils during inflammation
Hydrolyze elastin (protein present in the extracellular matrix)
Degrades outer membrane protein A (OmpA) of E. coli, and
virulence factors of organisms like Shigella, Salmonella and
Yersinia
Neutrophil elastase (or leukocyte elastase)
Cathelicidin (in secondary granules)
 Is an antimicrobial peptide
 were originally found in neutrophils, but later found to
be present in other cells including epithelial cells and
macrophages
 increased in immune cells after activation by bacteria,
viruses, fungi
 The human cathelicidin is called as hCAP-18 (Inactive
proprotein)
Specific
granules (or
"secondary
granules")
 Lactoferrin
 cathelicidin
hCAP-18 (Inactive proprotein)
Ag
active peptide (LL-37) (37 amino acids from the C-terminal) is released
exerts antimicrobial activity
Other biological
effects of LL-37
neutralizing the
biological effects of
LPS
promotion of
angiogenesis and
wound healing
angiogenesis is
physiological process
involving the growth
of new blood vessels
from pre-existing
vessels
chemotaxis of
neutrophils,
monocytes and T-
cells
Mechanism of killing by neutrophil
-Mainly phagocytosis
-Through garanule release
Neurtrophils
are the first to arrive at a site of inflammation
transient increase in the number of circulating
neutrophils, is called leukocytosis- is an
indication of infection
employ both oxygen-dependent and oxygen
independent pathways to generate
antimicrobial substances.
exhibit a larger respiratory burst and express
higher levels of defensins than macrophages
Recruitment of Neutrophils into inflamed tissue
Neutrophil extravasation- rolling, adherance---- into tissues and
elimination of pathogen in tissues
Ag
 Neutrophils are generally the first cell type to bind to
inflamed endothelium and extravasate into the tissues.
 Neutrophils first recognize the inflamed endothelium and adhere
strongly enough so that they are not swept away by the flowing
blood.
 The bound neutrophils then penetrate the endothelial layer and
migrate into the underlying tissue.
Site of injury
The process of neutrophil extravasation are divided into
four sequential steps:
(1) Rolling
(2) activation by chemoattractant
(3) arrest and adhesion and
(4) Transendothelial migration
Site of injury
Neutrophil rolling- movie
 When there is an inflammatory response develops, various
cytokines and other inflammatory mediators act upon the
local blood vessels and induces the increased expression of
endothelial CAMs (cell adhesion molecules).
Endothelium
CAM
This neutrophil is called as activated or inflamed neutrophil
Neutrophil
Ag
Rolling (Step 1)
 During an inflammatory response,
cytokines and other mediators act
upon the local endothelium and
induces the expression of adhesion
molecules of the selectin family.
 Neutrophils attach loosely to the
endothelium by a low-affinity
interaction which involves selectins
and their Ligands.
 Selectins are a family of glycoprotein
surface adhesion molecules
 The E-selectin (expressed exclusively
on endothelial cells) and and P-
selectin (expressed on platelets and
endothelial cells) bind to mucin like
cell-adhesion molecules on the
neutrophil membrane or with a
sialylated lactosaminoglycan called
sialyl Lewisx
endothelium
Rolling:
Though Neutrophil gets attached to endothelium
Due to blood flow, it sometimes gets detached from the
endothelium, but gets attached to the selection present in the
nearby endothelium
This process is reapeated until the neurtophil gets firmly
attached to an endothelium
This is made possible by the rolling of neutrophils
Step 2 (Activation)
Chemoattractants on the endothelium
binds to its respective R on Neutrophils
Eg.,
1. Chemoattractive cytokines called as
Chemokines like interleukin 8 (IL-8)
and macrophage inflammatory
protein (MIP)
2. Other Chemoattractants like platelet-
activating factor (PAF), the
complement split products C5a, C3a,
and C5b67 and various N- formyl
peptides produced by the breakdown
of bacterial proteins during an
infection.
Chemoattractants like such as IL-8 then
binds to a G-protein–linked receptor on
the neutrophil, triggering an activating
signal.
G protein linked receptor
Step 3
This signal induces a
conformational change in
the integrin molecules,
enabling them to adhere
firmly to Ig-superfamily
molecules on the
endothelium.
G protein linked receptor
 After attachment to endothelium, the neutrophil migrates
through the vessel wall into the tissues (it is transendothelial
migration)
Eosinophils are like neutrophils- ie., are
motile phagocytic cells that can migrate
from the blood into the tissue spaces
play a role in the defense against parasitic
organisms
EOSINOPHILS
The granules contain substances like
 histamine and proteins like
 eosinophil peroxidase,
 ribonuclease (RNase),
 deoxyribonucleases,
 lipase,
 plasminogen, and
 major basic protein.
These mediators are released by a process called
degranulation following activation of the eosinophil
The secreted contents of eosinophilic granules may
damage the parasite membrane and is also toxic to the
host tissue.
Basophils are nonphagocytic granulocytes
They can be stained with basic dyes (eg toulidine blue)
Are least common (represent about 0.01% to 0.3% of
circulating white blood cells)
They function by releasing pharmacologically active substances
from their cytoplasmic granules.
BASOPHILS
 Nucleus has 2 lobes
 they contain anticoagulant heparin
 they contain vasodilator histamine (which promotes blood
flow to tissues)
 These substances play a major role in certain allergic
responses.
 they appear in tissues where allergic reactions are occurring
and probably contribute to the severity of these reactions
Basophils
Ig R IgE Ab
Allergens
B cells
Release IgE
Bind to R on Basophils
Degranulation of basophils occurs
Degranulation- is extracellular release of the mediators like
1.Histamine
2.Proteoglycans (like heparin and chondroitin)
3.Proteolytic enzymes (elastase, lysophospholipase)
4.Lipid mediators (leukotrienes)
5.Many Cytokines
Cause inflammation
Basopenia- is a decrease in B count
Basophilia- is a increase in B count
1. Lymphoid cells T cells 4. Mast cells
B cells
NK cells
(Null cells)
2. Mononuclear
cells
Monocytes 5. Dendritic
cells
Langerhans cells
Interstitial DC
Macrophages Interdigitating
DC
Circulating DC
3. Granulocytic
cells
Neutrophils
Eosinophil
Basophil
Cells of the immune system
Mast cells
Myeloid stem cells
Basophil Progenitor
produce either Mast Cells or Basophils
Mast cells and basophils play a central role in inflammatory and
immediate allergic reactions
 Both mast cells and basophils contain special
cytoplasmic granules which store mediators of
inflammation.
 The extracellular release of the mediators is known as
degranulation
Mast cells Basophil
usually do not circulate in the
blood stream
are the smallest circulating
granulocytes. They arise in the
bone marrow, and following
maturation and differentiation,
are released into the blood
circulation
Are present in connective tissues If they are adequately stimulated
they may settle in the tissues
MAST CELLS or mastocyte
Mast-cell precursors (in bone marrow)
(undifferentiated cell)
----------------------------------------------------------
enter to blood
Blood undifferentiated cell
---------------------------------------------------------
Tissue enter to tissue
Differentiated cell
first described by Paul Ehrlich in 1878
Tissues where mast cells are present
-Present in tissues nearby to blood vessels
1. Skin
2. connective tissues of various organs
3. mucosal epithelial tissue of the respiratory, genitourinary, and
digestive tracts.
4. Mucosa of mouth, conjunctiva and nose
cytoplasmic granules contain
1. histamine and
2. other pharmacologically active substances.
Mast cell- plays important role in
1. Allergy and
2. Anaphylaxis (a type I hypersensitivity reaction)
2 types of mediators in mast cells and basophils are
1. Preformed mediators and
2. Newly generated mediators
Preformed mediators,
These are the mediators which are stored in secretory granules
They are secreted upon cell activation by agents (eg., a biogenic
amine, histamine, proteoglycans, heparin, chondroitin sulphates
and a spectrum of neutral proteases).
Newly generated mediators
they are often absent in the resting mast cells
they are produced during IgE-mediated activation
eg of such mediators are arachidonic acid metabolites
(leukotriene C and prostaglandin D) , TNF, IL-4, IL-5 and IL-6.

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Cells of the immune system

  • 1. 1. Lymphoid cells T cells 4. Mast cells B cells NK cells (Null cells) 2. Mononuclear cells Monocytes 5. Dendritic cells Langerhans cells Interstitial DC Macrophages Interdigitating DC Circulating DC 3. Granulocytic cells Neutrophils Eosinophil Basophil Cells of the immune system
  • 2. III. Granulocytic cells 1. Neutrophils 2. Eosinophils 3. Basophils
  • 3. Formation of Granulocytes Myeloid stem cells (myeloblast) Promyeloblast Myelocyte Metamyelocytes Granulocytes (N, E and B) Differentiation Takes app 14 days Growth factors reqd are G-CSF GM-CSF
  • 4. • has a multilobed nucleus (mostly has 2-5 lobes) • it is often called as polymorphonuclear leukocyte (PMN) (for its multilobed nucleus) •are the most abundant white blood cells in humans approximately 108 - 1011 are produced daily) •they account for approximately 70% of all white blood cells (leukocytes). 1. Neutrophils
  • 5. •They have granulated cytoplasm- it stains with both acid and basic dyes Hematopoiesis in Bone marrow Neutrophils formed Released into the peripheral blood and circulate for 7–10 h After that migrate into the tissues, where they have a life span of only a few days. 1. Neutrophils
  • 6. Granules present in neutrophils 1. Primary 2. Secondary 3. Tertiary In the presence of Ag- degranulation occurs (which is release of contents from granules) Release of contents from Granules Ag
  • 7. Proteins present in the granules Azurophilic granules (or "primary granules")  Myeloperoxidase  bactericidal/ permeability increasing protein (BPI)  defensins  the serine proteases  neutrophil elastase  cathepsin G Specific granules (or "secondary granules")  Lactoferrin  cathelicidin tertiary granules  cathepsin  gelatinase
  • 8. Azurophilic granules (or "primary granules")  Myeloperoxidase  bactericidal/ permeability increasing protein (BPI)  defensins  the serine proteases  neutrophil elastase  cathepsin G
  • 9. hCAP 18- human cathelicidin HOBr- Hypobromous acid HOI- Hypoiodous acid
  • 10. BPI (bactericidal/ permeability increasing protein) is a highly cationic, 55KD protein Is a cytotoxic protein Found only in the cells of myeloid series Has strong affinity for LPS, so has potent toxicity exclusively towards gram-negative bacteria Azurophilic granules (or "primary granules")  Myeloperoxidase  bactericidal/ permeability increasing protein (BPI)  defensins  the serine proteases  neutrophil elastase  cathepsin G
  • 11. Azurophilic granules (or "primary granules")  Myeloperoxidase  bactericidal/ permeability increasing protein (BPI)  defensins  the serine proteases  neutrophil elastase  cathepsin G  also known as ELA2 (elastase 2, neutrophil) is a serine protease Secreted by neutrophils during inflammation Hydrolyze elastin (protein present in the extracellular matrix) Degrades outer membrane protein A (OmpA) of E. coli, and virulence factors of organisms like Shigella, Salmonella and Yersinia Neutrophil elastase (or leukocyte elastase)
  • 12. Cathelicidin (in secondary granules)  Is an antimicrobial peptide  were originally found in neutrophils, but later found to be present in other cells including epithelial cells and macrophages  increased in immune cells after activation by bacteria, viruses, fungi  The human cathelicidin is called as hCAP-18 (Inactive proprotein) Specific granules (or "secondary granules")  Lactoferrin  cathelicidin
  • 13. hCAP-18 (Inactive proprotein) Ag active peptide (LL-37) (37 amino acids from the C-terminal) is released exerts antimicrobial activity Other biological effects of LL-37 neutralizing the biological effects of LPS promotion of angiogenesis and wound healing angiogenesis is physiological process involving the growth of new blood vessels from pre-existing vessels chemotaxis of neutrophils, monocytes and T- cells
  • 14. Mechanism of killing by neutrophil -Mainly phagocytosis -Through garanule release
  • 15. Neurtrophils are the first to arrive at a site of inflammation transient increase in the number of circulating neutrophils, is called leukocytosis- is an indication of infection employ both oxygen-dependent and oxygen independent pathways to generate antimicrobial substances. exhibit a larger respiratory burst and express higher levels of defensins than macrophages
  • 16. Recruitment of Neutrophils into inflamed tissue Neutrophil extravasation- rolling, adherance---- into tissues and elimination of pathogen in tissues Ag
  • 17.  Neutrophils are generally the first cell type to bind to inflamed endothelium and extravasate into the tissues.  Neutrophils first recognize the inflamed endothelium and adhere strongly enough so that they are not swept away by the flowing blood.  The bound neutrophils then penetrate the endothelial layer and migrate into the underlying tissue. Site of injury
  • 18. The process of neutrophil extravasation are divided into four sequential steps: (1) Rolling (2) activation by chemoattractant (3) arrest and adhesion and (4) Transendothelial migration Site of injury
  • 20.  When there is an inflammatory response develops, various cytokines and other inflammatory mediators act upon the local blood vessels and induces the increased expression of endothelial CAMs (cell adhesion molecules). Endothelium CAM This neutrophil is called as activated or inflamed neutrophil Neutrophil Ag
  • 21. Rolling (Step 1)  During an inflammatory response, cytokines and other mediators act upon the local endothelium and induces the expression of adhesion molecules of the selectin family.  Neutrophils attach loosely to the endothelium by a low-affinity interaction which involves selectins and their Ligands.  Selectins are a family of glycoprotein surface adhesion molecules  The E-selectin (expressed exclusively on endothelial cells) and and P- selectin (expressed on platelets and endothelial cells) bind to mucin like cell-adhesion molecules on the neutrophil membrane or with a sialylated lactosaminoglycan called sialyl Lewisx endothelium
  • 22. Rolling: Though Neutrophil gets attached to endothelium Due to blood flow, it sometimes gets detached from the endothelium, but gets attached to the selection present in the nearby endothelium This process is reapeated until the neurtophil gets firmly attached to an endothelium This is made possible by the rolling of neutrophils
  • 23.
  • 24. Step 2 (Activation) Chemoattractants on the endothelium binds to its respective R on Neutrophils Eg., 1. Chemoattractive cytokines called as Chemokines like interleukin 8 (IL-8) and macrophage inflammatory protein (MIP) 2. Other Chemoattractants like platelet- activating factor (PAF), the complement split products C5a, C3a, and C5b67 and various N- formyl peptides produced by the breakdown of bacterial proteins during an infection. Chemoattractants like such as IL-8 then binds to a G-protein–linked receptor on the neutrophil, triggering an activating signal. G protein linked receptor
  • 25. Step 3 This signal induces a conformational change in the integrin molecules, enabling them to adhere firmly to Ig-superfamily molecules on the endothelium. G protein linked receptor
  • 26.  After attachment to endothelium, the neutrophil migrates through the vessel wall into the tissues (it is transendothelial migration)
  • 27. Eosinophils are like neutrophils- ie., are motile phagocytic cells that can migrate from the blood into the tissue spaces play a role in the defense against parasitic organisms EOSINOPHILS
  • 28. The granules contain substances like  histamine and proteins like  eosinophil peroxidase,  ribonuclease (RNase),  deoxyribonucleases,  lipase,  plasminogen, and  major basic protein. These mediators are released by a process called degranulation following activation of the eosinophil The secreted contents of eosinophilic granules may damage the parasite membrane and is also toxic to the host tissue.
  • 29. Basophils are nonphagocytic granulocytes They can be stained with basic dyes (eg toulidine blue) Are least common (represent about 0.01% to 0.3% of circulating white blood cells) They function by releasing pharmacologically active substances from their cytoplasmic granules. BASOPHILS
  • 30.  Nucleus has 2 lobes  they contain anticoagulant heparin  they contain vasodilator histamine (which promotes blood flow to tissues)  These substances play a major role in certain allergic responses.  they appear in tissues where allergic reactions are occurring and probably contribute to the severity of these reactions
  • 31. Basophils Ig R IgE Ab Allergens B cells Release IgE Bind to R on Basophils Degranulation of basophils occurs
  • 32. Degranulation- is extracellular release of the mediators like 1.Histamine 2.Proteoglycans (like heparin and chondroitin) 3.Proteolytic enzymes (elastase, lysophospholipase) 4.Lipid mediators (leukotrienes) 5.Many Cytokines Cause inflammation
  • 33. Basopenia- is a decrease in B count Basophilia- is a increase in B count
  • 34. 1. Lymphoid cells T cells 4. Mast cells B cells NK cells (Null cells) 2. Mononuclear cells Monocytes 5. Dendritic cells Langerhans cells Interstitial DC Macrophages Interdigitating DC Circulating DC 3. Granulocytic cells Neutrophils Eosinophil Basophil Cells of the immune system
  • 35. Mast cells Myeloid stem cells Basophil Progenitor produce either Mast Cells or Basophils Mast cells and basophils play a central role in inflammatory and immediate allergic reactions
  • 36.  Both mast cells and basophils contain special cytoplasmic granules which store mediators of inflammation.  The extracellular release of the mediators is known as degranulation Mast cells Basophil usually do not circulate in the blood stream are the smallest circulating granulocytes. They arise in the bone marrow, and following maturation and differentiation, are released into the blood circulation Are present in connective tissues If they are adequately stimulated they may settle in the tissues
  • 37. MAST CELLS or mastocyte Mast-cell precursors (in bone marrow) (undifferentiated cell) ---------------------------------------------------------- enter to blood Blood undifferentiated cell --------------------------------------------------------- Tissue enter to tissue Differentiated cell
  • 38. first described by Paul Ehrlich in 1878 Tissues where mast cells are present -Present in tissues nearby to blood vessels 1. Skin 2. connective tissues of various organs 3. mucosal epithelial tissue of the respiratory, genitourinary, and digestive tracts. 4. Mucosa of mouth, conjunctiva and nose cytoplasmic granules contain 1. histamine and 2. other pharmacologically active substances.
  • 39. Mast cell- plays important role in 1. Allergy and 2. Anaphylaxis (a type I hypersensitivity reaction)
  • 40. 2 types of mediators in mast cells and basophils are 1. Preformed mediators and 2. Newly generated mediators Preformed mediators, These are the mediators which are stored in secretory granules They are secreted upon cell activation by agents (eg., a biogenic amine, histamine, proteoglycans, heparin, chondroitin sulphates and a spectrum of neutral proteases). Newly generated mediators they are often absent in the resting mast cells they are produced during IgE-mediated activation eg of such mediators are arachidonic acid metabolites (leukotriene C and prostaglandin D) , TNF, IL-4, IL-5 and IL-6.