The immune system consists of lymphoid organs that produce and organize immune cells. The primary lymphoid organs, bone marrow and thymus, produce immune cell precursors and allow their maturation. The secondary lymphoid organs, lymph nodes and spleen, facilitate interactions between immune cells and initiate adaptive immune responses. All immune cells originate from hematopoietic stem cells in the bone marrow. T cells mature in the thymus, while B cells mature in the bone marrow. Natural killer cells do not require an organ for maturation. The immune cells, including T cells, B cells, natural killer cells, neutrophils, eosinophils and others, work together to provide protection from pathogens and other threats
2. Immune system
• The Immune system consists of
many different organs and tissues
that are found throughout the
body.
• These organs can be classified
functionally into two main groups.
3. Immune system
• Primary(Central) lymphoid organs -
The central lymphoid organs are the
bone marrow and the thymus, a
large organ in the upper chest.
• Secondary lymphoid organs
(peripheral) Lymph nodes,spleen
white pulp,MALT(mucosal associated
lymphoid tissue)
4.
5. Immune system
•The lymphoid organs are
organized tissues
containing large numbers
of lymphocytes in a
framework of non-
lymphoid cells.
6. Immune system
• In these organs, the interactions
lymphocytes make with non-
lymphoid cells are important
either to lymphocyte
development, to the initiation of
adaptive immune responses, or
to the sustenance of lymphocytes
7. ORIGIN OF WHITE
BLOOD CELLS
• The cells responsible for the immune
system originate in the bone
marrow, where many of them also
mature.
• Immune responses are mediated by
leukocytes, which derive from
precursors in the bone marrow.
8. ORIGIN OF WHITE
BLOOD CELLS
•They then migrate to guard
the peripheral tissues,
circulating in the blood and
in a specialized system of
vessels called the
lymphatic system.
9. ORIGIN OF WHITE
BLOOD CELLS
• The cellular elements of blood, including the
red blood cells that transport oxygen, the
platelets that trigger blood clotting in
damaged tissues, and the white blood cells
of the immune system, derive ultimately
from the same progenitor or precursor cells
the hematopoietic stem cells in the bone
marrow. They are often known as
pluripotent hematopoietic stem cells.
10. ORIGIN OF WHITE
BLOOD CELLS
• Initially, they give rise to stem
cells of more limited potential,
which are the immediate
progenitors of red blood cells,
platelets, and the two main
categories of white blood cells.
11. Hematopoiesis generates immune cells
Stem cells: 1. Self renewal
2. Totipotency
They are in bone marrow after
fetal development.
They make all myeloid and
lymphoid immune cells and
RBCs
T cell progenitors migrate to
thymus and generate T cells
B cell progenitors reside in
bone marrow to make naïve B
cells
12.
13. Lymphocytes
• The common lymphoid progenitor
gives rise to the lymphocytes.
• The lymphocytes can be broadly
subdivided into three populations—B
cells, T cells, and natural killer cells—
on the basis of function and cell-
membrane components.
14.
15. Lymphoid Cells
• Lymphocytes constitute 20%–40% of the
body’s white blood cells and 99% of the
cells in the lymph .
• These lymphocytes continually circulate
in the blood and lymph and are capable
of migrating into the tissue spaces and
lymphoid organs, thereby integrating the
immune system to a high degree.
16. THE IMMUNE CELLS
• One class differentiates on activation
into cytotoxic T cells, which kill cells
infected with viruses, whereas the
second class of T cells differentiates
into cells (Helper ) that activate other
cells such as B cells and
macrophages.
17.
18. THE IMMUNE CELLS
•T-cell progenitors differentiate
under the influence of thymic
hormones (THYMOSIN and
THYMOPOITEN)into T-cell
subpopulations
19. THE IMMUNE CELLS
• Resting B and T lymphocytes are
small, motile, nonphagocytic
cells,which cannot be distinguished
morphologically.
• B and T lymphocytes that have not
interacted with antigen—referred to
as naive, or unprimed—are resting
cells in the G0 phase of the cell cycle.
20. Naïve T- lymphocytes
• Naïve T- lymphocytes are found in
blood and constitute 60% to 70%,
and in T-cell zones of peripheral
lymphoid organs such as the
paracortical areas of lymph nodes
and periarteriolar sheaths of the
spleen.
22. Origin of T and B cells.
• Stem cells in the bone marrow (or
fetal liver) are the precursors of
both T and B lymphocytes.
• Stem cells differentiate into T
cells in the thymus, whereas they
differentiate into B cells in the
bone marrow.
23. T LYMPHOCYTES
• T-cell precursors differentiate into
immunocompetent T cells within
the thymus.
• Prior to entering the thymus, stem
cells lack antigen receptors and
lack CD3, CD4, and CD8 proteins
on their surface.
24. T LYMPHOCYTES
•During passage through the
thymus they differentiate
into T cells that can express
both antigen receptors and
the various CD proteins
25. T LYMPHOCYTES
•The stem cells, which initially
express neither CD4 nor CD8
(double-negatives), first
differentiate to express both
CD4 and CD8 (double-
positives) and then proceed to
express either CD4 or CD8.
26. T LYMPHOCYTES
•Within the thymus, T
cells become either CD4-
positive (helper) cells or
CD8-positive (cytotoxic)
cells.
27. T LYMPHOCYTES
• A double-positive cell will
differentiate into a CD4-positive
cell if it contacts a cell bearing
class II MHC proteins but will
differentiate into a CD8-positive
cell if it contacts a cell bearing
class I MHC proteins.
28. T LYMPHOCYTES
• The double-negative cells and the
double-positive cells are located in
the cortex of the thymus, whereas
the single-positive cells are
located in the medulla, from
which they migrate out of the
thymus into the blood and
extrathymic tissue.
29. T LYMPHOCYTES
• Within the thymus, two very
important processes called thymic
education occur:
• 1. CD4-positive, CD8-positive cells
bearing antigen receptors for "self"
proteins are killed (clonal deletion)
by a process of "programmed cell
death" called apoptosis.
30. T LYMPHOCYTES
•The removal of these self-
reactive cells, a process called
negative selection, results in
tolerance to our own proteins,
i.e., self-tolerance, and
prevents autoimmune
reactions
31. T LYMPHOCYTES
• 2-CD4-positive, CD8-positive cells
bearing antigen receptors that
do not react with self MHC
proteins are also killed.
• This results in a positive
selection for T cells that react
well with self MHC proteins.
32. T LYMPHOCYTES
• These two processes produce T cells
that are selected for their ability to
react both with foreign antigens via
their antigen receptors and with self
MHC proteins.
• Both of these features are required
for an effective immune response by
T cells.
33. T LYMPHOCYTES
•During their passage through
the thymus, each double-
positive T cell synthesizes a
different, highly specific
antigen receptor called the T-
cell receptor (TCR).
34. T-cell receptor (TCR).
• Each T cell expresses TCR molecules
of one structure and specificity
• TCR consists of a disulfide –linked
heterodimer made up of an α & a β
polypeptide chain, each having a
variable (antigen-binding) and a
constant region, minority composed
of γ and δ polypeptide chain
35. T-cell receptor (TCR).
•αβ TCR recognizes peptide
antigens that are displayed by
MHC molecules, γ δ TCR
recognizes peptides ,lipids and
small molecules without a
requirement for display by
MHC proteins
36. T-cell receptor (TCR).
•Each TCR is
noncovalentally linked to
CD3 (γ,δ,ε ) and dimer of
ξ (zeta) chain (5
transmembrane proteins)
37. T-cell receptor (TCR).
• The rearrangement of the variable,
diversity, and joining genes that
encode the receptor occurs early in T-
cell differentiation and accounts for
the remarkable ability of T cells to
recognize millions of different
antigens.
38. CD4 lymphocytes
•1-Help B-cell to develop into
antibody –producing plasma
cells
•2-Help CD8 T cells to become
activated cytotoxic T-cells
•3-Help macrophage to effect
delayed hypersensitivity
39. CD4 lymphocytes
Functions performed by two populations of CD4 cells
Th-1 cells – a) activate cytotoxic T-
cells by producing IL-2,
b) initiate the delayed
hypersensitivity response by
producing IL-2 and gamma
interferon
Th-2 cells -perform B-cell helper
function by producing IL-4 and IL-5
40. Comparison of Th-1cells and Th-2 cells
• IL-2 and gamma interferon
yes
• IL-4,IL-5,IL-6,IL-10 no
• Cell mediated immunity
and DTH yes
• Antibody production no
• Stimulated by IL-12 yes
• Stimulated by IL-4 no
• IL-2 and gamma interferon
no
• IL-4,IL-5,IL-6,IL-10 yes
• Cell mediated immunity
and DTH no
• Antibody production yes
• Stimulated by IL-12 no
• Stimulated by IL-4 yes
41. Regulator of balance between Th-1
and Th-2 cell
• IL-12 produced by macrophages ,increases Th-1
cells
• Gamma interferon produced by Th-1 cells activate
macrophage and inhibits the production of Th-2
cells
• IL-10 produced by Th-2 cells inhibit IL-12 production
by macrophages
• Precisely what component of microbe activates
either Th-1or Th-2 cells is unknown
42. CD8 lymphocytes
Perform cytotoxic functions
• Kill virus infected cell
• Kill tumor cells
• Kill allograft cells
They kill by two mechanisms
Release of perforins
Apoptosis
43. IEL (intraepithelial lymphocytes)
• These intraepithelial lymphocytes
(IELs) are thought to provide
protection against intestinal
pathogens.
• Their antigen receptors and surface
proteins are different from those of
thymus-derived lymphocytes.
44. T LYMPHOCYTES
•Some T lymphocytes,
perhaps as much as 40% of
the total, do not develop in
the thymus but rather in
the "gut-associated
lymphoid tissue" (GALT).
45. T LYMPHOCYTES
• IELs cannot substitute for thymus-
derived lymphocytes because
patients with DiGeorge's
syndrome who lack a thymus are
profoundly immunodeficient and
have multiple infections.
46. T LYMPHOCYTES
• The thymus involutes in adults, yet T
cells continue to be made. Two
explanations have been offered for this
apparent paradox.
• One is that a remnant of the thymus
remains functional throughout life and
the other is that an extrathymic site
takes over for the involuted thymus.
48. B cells
•10 -20% of circulating
peripheral lymphocyte
population
•Also present in peripheral
lymphoid organs such as
,lymph nodes ,spleen ,tonsils
and extralymhatic organs
such as gastrointestinal tract
49. B cells
• Lymph node superficial cortex
• Spleen white pulp
• B –cells are located in follicles
• Maturation of B-cell has two phases
Antigen independent phase
Antigen dependent phase
50. B cells
Stem cell,
pro-B cell---ü chain (cytoplasm),CD10,CD19,
pre-B-cell--- ü chain +light chain,CD10,CD19
immature B-cell----CD10,CD19 ,CD20,SIg(IgM)
mature B-cell
, Activated B-cell
memory B cell
plasma cell
51. B cells
Markers- (BCR) IgM or IgD, Igα/Igβ
–(hetrodimer of nonpolymorphic
transmembrane proteins,donot
bind antigen like CD3 but essential
for signal transduction through
antigen receptor
MHC class I,MHC class II,B7,CD40,
CD10,CD19, surface receptors for
FcγR, complement receptor(CD21)
53. Differences of T-cell and B-cell
• Thymus
• IgM on surface no
• CD3 on surface yes
• Immunoglobulin synthesis
no
• IL-2,IL-4,IL-5,gamma
interferon yes
• Effector of cell mediated
immunity yes
• Bone marrow
• IgM on surface yes
• CD3 on surface no
• Immunoglobulin synthesis
yes
• IL-2,IL-4,IL-5,gamma
interferon no
• Effector of cell mediated
immunity no
54. Natural Killer cell
• Innate host defense
• Make up 10% to 15% of the peripheral blood
lymphocytes
• Kill virus infected cell and tumor cell by
Cytotoxins ( perforin, granzymes )
Fas-FasL mediated apoptosis
• Large granular lymphocyte
• Contain abundant azurophilic granules
55. Natural Killer cell
• Do not mature in thymus
• lack CD3 protein and surface IgM or IgD
• CD16 and CD56
• Active without exposure
• Not enhanced by exposure
• Not specific for any virus
• Can kill without antibody
56. Natural Killer cell
•IL-2 and gamma interferon
are potent activator of NK
cell
•No immunological memory
•No T-cell receptor
•Killing does not require
recognition of MHC proteins
57. Natural Killer cell
•NK cell have receptors that
detect the presence of class I
MHC proteins on the cell
surface
•NK cell detect presence of
cancer cell by recognizing a
protein called MICA that is not
found on normal cells
58. THE IMMUNE CELLS
•Myeloid Progenitor
•The myeloid progenitor is the
precursor of the
granulocytes,macrophages,
dendritic cells, and mast cells
of the immune system.
59. THE IMMUNE CELLS
• The granulocytes are so called
because they have densely staining
granules in their cytoplasm; they are
also sometimes called
polymorphonuclear leukocytes
because of their oddly shaped nuclei.
• There are three types of granulocyte,
all of which are relatively short lived
60. THE IMMUNE CELLS
•Neutrophils, which are the
third phagocytic cell of the
immune system, are the most
numerous and most important
cellular component of the
innate immune response:
61. Neutrophils
• 60% of leukocyte count
• Half-life 6-7hrs in blood and 1-2 days
in tissue space
• Important phagocytic cell
• No antigen presentation because no
MHC class II proteins on their surface
62. Neutrophils
• Important cell of acute inflammation
• Multilobate nucleus
• Stem cell → myeloid stem
cell→myeloblast→promyelocyte
→myelocyte→metamyelocyte→
bandshape→neutrophil
65. Eosinophils
•Bilobed and 1-5% of total
leukocytes
•Size 12-17üm in diameter (red
granules with wright stain)
•Half life 6-12 hours
•Several days in tissue
67. Eosinophils
•Do not present antigen to
helper T-cell
• Are activated by
C3b,C4b,C5a,LTB4,IL-3,
• The growth and differentiation of
eosinophils is stimulated by IL-5
69. Eosinophils
• mitigate effects of hypersensitivity
reaction due to histaminase enzyme
• Eosinophils contain leukotrienes and
peroxidases which can damage tissue
and cause inflammation.
• Diseases caused by protozoa are
typically not characterized by
eosinophilia
70. Basophils
•0.2-1% of total leukocytes
•5-7üm in diameter
•Granules appear blue when
stained with wright stain
•Circulate in blood
71. Basophils
• Histamine ,protease ,
proteoglycans, leukotrienes
,prostaglandins
• Receptors for IgE,C3a,C5a,and
C3b
• Play role in hypersensitivity
reactions type 1
72. THE IMMUNE CELLS
• Macrophages are one of the
three types of phagocyte in the
immune system and are
distributed widely in the body
tissues, where they play a critical
part in innate immunity.
73. THE IMMUNE CELLS
•They are the mature form of
monocytes, which circulate in
the blood and differentiate
continuously into
macrophages upon migration
into the tissues.
75. Macrophage
•Is derived from stem cell
•Take part in initiation of T-cell
activation by processing and
presenting antigen
•Destroy bacteria by
phagocytosis
•Phagocytose apoptotic cells
76. Macrophage
•Recognizes bacteria by pattern
recognition receptors
•PRR recognize pathogen
associated molecular patterns
•Recognition of bacteria by
macrophage Toll – like
receptors
77. Macrophage Function
• Phagocytosis
• Macrophage ingest bacteria, virus and
foreign particles.
• Surface Fc-receptor interact with FC
portion of IgG
• Receptors for C3b -------opsonin
Ingestion and killing of microbes in
phagolysosomes.
78. Macrophage Function
killing caused by reactive
oxygen intermediates such as
superoxides,reactive nitrogen
intermediates such as nitric
oxide,and lysosomal enzymes
such as proteases,nucleases
and lysozyme
81. Macrophage
•Macrophages are involved in
the induction of cell mediated
immune response
•Are also important in the
effector phase of humoral
immunity
82. THE IMMUNE CELLS
•Dendritic cells are
specialized to take up
antigen and display it
for recognition by
lymphocytes.
84. THE IMMUNE CELLS
• Immature dendritic cells migrate from
the blood to reside in the tissues and are
both phagocytic and macropinocytic,
ingesting large amounts of the
surrounding extracellular fluid.
• Upon encountering a pathogen, they
rapidly mature and migrate to lymph
nodes.
86. Interdigitating dendritic cell
• Antigen presenting cells for initiating
primary immune responses against
protein antigens
• Are primarily located under the skin and
the mucosa e.g. ,Langerhans cells in the
skin
• Express many receptors TLRs and
Mannose receptors
87. Interdigitating dendritic cell
• Express class II MHC protein and
costimulatory proteins B7-1 and
B7-2
• Present antigen to CD4-positive T-
cell
• Express chemokine receptors as
do naïve T-cell
88. Follicular dendritic cell
•located in B-cell containing
germinal centers of the
follicles of spleen and lymph
nodes
• They do not present antigen to
helper T-cell because they do not
produce class II MHC protein
89. Follicular dendritic cell
•Bear Fc receptors for IgG
and receptors for C3b
and can trap antigen
bound to antibodies or
complement proteins
90. Follicular dendritic cell
•The antigen antibody
complexes are then detected
by activated B-cell
•FDCs produce chemokines
that attract B-cells to the
follicles in the spleen and
lymph nodes
91. THE IMMUNE CELLS
•Mast cells, whose blood-
borne precursors are not
well defined, also
differentiate in the
tissues.
92. Mast cells
• Mast cells mediate inflammatory
responses such as hypersensitivity
and allergic reactions. ... Upon
stimulation by an allergen, the mast
cells release the contents of their
granules (a process called
degranulation) into the surrounding
93. Mast cells
• They mainly reside near small blood
vessels and, when activated, release
substances that affect vascular
permeability .
• They are believed to play a part in
protecting mucosal surfaces against
pathogens.
