Structure and functions of immune system

1. STUCTURE AND FUCTIONS OF
THE IMMUNE SYSTEM
A Presentation By
G. Prashanth Kumar
Department of Microbiology & Parasitology,
Faculty of Medicine, International Medical & Technological University,
Dar-Es-Salaam, Tanzania.

2. INTRODUCTION
• The lymphoreticular system is a complex organization of
cells of diverse morphology, distributed widely in
different organs and tissues of the human body, and are
responsible for immunity.
• They consist of lymphoid and reticuloendothelial
components and are responsible for immune response
of the host.
• The lymphoid cells that include lymphocytes and plasma
cells are responsible for conferring specific immunity.
• On the other hand, the reticuloendothelial system that
consists of the phagocytic cells and plasma cells is
responsible for nonspecific immunity.
• These cells kill microbial pathogens and other foreign
agents and remove them from the blood and tissue.

3. LYMPHOID SYSTEM
• The immune system is organized into several
special tissues which are collectively termed as
lymphoid or immune tissues.
• Those tissues that have evolved to a high degree of
specificity of function are termed as lymphoid
organs.
1. Lymphoid cells- lymphocytes and plasma cells.
2. Lymphoid organs
- Primary (Central )
- Secondary (Peripheral).

4. CENTRAL (PRIMARY) LYMPHOID
ORGANS.
•Thymus
•Bone marrow

5. THYMUS
• Present behind the upper part
of the sternum.
• Appearance- two lobes
surrounded by a fibrous
capsule.
• Septa divides the glands to
lobules with an outer cortex
and inner medulla.
• Cortex- actively proliferating
small lymphocytes.
• Medulla- epithelial cells and
mature lymphocytes in the
middle of which are Hassall’s
corpuscles (whorl like
aggregates of epithelial cells).

6. THYMUS
• Observations by Good (1954) of thymoma and
impaired immunity and by Miller (1961) of
immunodeficiency in thymectomised mice led to the
understanding of the pivotal role of Thymus in Cell
Mediated Immunity.
• Primary Function- Production of thymic lymphocytes.
• Lymphocytes Thymus Surface Antigen (Thy-
antigen) Thymus dependent / T-cells / T-
lymphocytes (not dependent on antigenic stimulation).

7. THYMUS

8. Effects of Thymectomy/Absent Thymus
• Decreased CMI- DiGeorge
syndrome (congenital aplasia of
thymus), ‘nude mice’
(thymectomised mice).
• Decreased antibody response to
many antigens (thymus
dependent antigen).
• ‘Thymus dependent’ region like
in the perilymphatic system
(white pulp of spleen, around the
central arterioles, and in the
paracortical areas of lymph
nodes) were found grossly
depleted.

9. BONE MARROW
• Lymphoid cells developing and maturing here are
referred to as B cells (B for Bursa of Fabricius or bone
marrow).
• Site for proliferation of stem cells and for the origin
of pre-B cells and their maturation to become
immunoglobulin-producing lymphocytes.
• Like thymic selection during T-cell maturation, a
selection process within the bone marrow eliminates
B cells with self reactive antibody receptor.

10. BONE MARROW

11. BONE MARROW

12. PERIPHERAL (SECONDARY)
LYMPHOID ORGANS
•Lymph nodes
•Spleen
•Mucosa associated lymphoid tissue

13. LYMPH NODES
• Placed along the course of lymphatics.
• Surrounded by a fibrous capsule from which
trabeculae penetrates into the nodes.
• Outer cortex- accumulation of lymphocytes (primary
lymphoid follicles) within which germinal centers
(secondary follicles) develop during antigenic
stimulation. Follicle also contain dendritic
macrophages.
• Inner medulla- lymphocytes, plasma cells and
macrophages are arranged as elongated branching
bands (medullary cords).

14. LYMPH NODES
• Lymphnode

15. LYMPH NODES
• Bursa dependent areas: The cortical follicles and medullary
cords that contain B-lymphocytes.
• Thymus dependent area: Between the cortical follicles and
medullary cords there is an ill-defined intermediate zone
(paracortical area) which contains T-lymphocytes.
• Functions:
• Filter for lymph, each group draining specific part of the body.
• Phagocytose foreign materials including microorganisms.
• Help in proliferation and circulation of T-cells and B-cells.
• They enlarge during local antigenic stimulation.

16. SPLEEN
• Largest lymphoid organ. Capsule from which trabeculae
descends, dividing the organ into several interconnected
compartments.
• White pulp of spleen- constitute ¾th of the organ. Red pulp of
spleen.
• Functions:
• Filtering and clearing of infectious organisms.
• Serves as a ‘graveyard’ for affected blood cells.
• As a reserve tank and settling bed for blood and as a systemic
filter for trapping circulating blood borne foreign particles.
• The immunological function of spleen is primarily directed
against blood borne antigens.

17. SPLEEN

18. EFFECTS OF SPLENECTOMY
• Depends on the age at which the spleen is
removed.
• In children, splenectomy often leads to an
increased incidence of bacterial sepsis caused
primarily by Streptococcus pneumoniae, Neisseria
meningitidis, and Haemophilus influenzae.
• Splenectomy in adults has less adverse effects,
although in some, it makes the host more
susceptible to blood-borne bacterial infection.

19. MUCOSA ASSOCIATED LYMPHOID TISSUE
(MALT)
• The mucosa lining the alimentary, respiratory,
genitourinary and other lumina are endowed with a
rich collection of lymphoid cell aggregates like the
Peyer’s patches or scattered isolated follicles-
collectively called MALT.
- Gut associated lymphoid tissue (GALT): gut,
adenoids, tonsils and colon.
- Bronchus associated lymphoid tissue (BALT):
respiratory tract.

20. MUCOSA ASSOCIATED LYMPHOID TISSUE
(MALT)
• MALT contains lymphoid as well as phagocytic
cells.
• Both B and T cells are present.
• While the predominant immunoglobulin
produced in the mucosa is secretory IgA, other
immunoglobulin classes, IgG, IgM and IgE are
also formed locally.

21. CELLS OF THE IMMUNE SYSTEM
• Cells of the immune system are associated
with the lymphatic system of the body and its
specialized cells.
• Lymphocytes of the lymphatic system are
derived from stem cells of the bone marrow.
• These undifferentiated precursor cells
proliferate throughout life and replenish the
mature cells of the immune system.

22. CELLS OF THE IMMUNE SYSTEM

23. CELLS OF THE IMMUNE SYSTEM

24. LYMPHOCYTES
• Small, round cells found in peripheral blood, lymph,
lymphoid organs and in many other tissues.
• In peripheral blood it constitutes 20-45 per cent of
the leucocyte population, while in lymph and
lymphoid organs they form the predominant cell
type.
• Human body contains 10¹² lymphocytes,
approximately 109 of them being renewed daily.
• Only about 1 per cent of the total body lymphocytes
are present in the blood.

25. LYMPHOCYTES
• CLASSIFICATION:
• Depending upon where they undergo development and
proliferation:
• In the thymus (thymus derived lymphocytes, or T-cells,
and Natural Killer T, or NKT cells).
• In the bone marrow (B lymphocytes or B cells).
• By the types of receptors they possess on their cell
surface:
• TCR (T cells and NKT cells)
• BCR, or Immunoglobulins (B cells) or neither (natural
killer, or NK cells).

26. LYMPHOCYTES
• CLASSIFICATION:
• According to size:
• 1.Small (5-8 µm): most numerous, ‘hand-mirror’ form.
• 2.Medium (8-12 µm)
• 3.Large (12-15 µm)
• According to their life span:
• Short lived lymphocytes: about 2 weeks, they are the effector
cells in the immune response.
• Long lived lymphocytes: may last for 3 years or more, or even
for life, these cells are the storehouse for immunologic
memory

27. LYMPHOCYTES
• Lymphocyte Recirculation.
• Policeman on beat patrol, ceaseless wandering of
lymphocytes through the blood, lymph, lymphatic
organs and tissues.
• Mount an immune response following antigenic
introduction to any part of the body or whenever
necessary.
• One cycle completed in about one or two days.
• Recirculation lymphocytes are mainly T-cells.
• B-cells tend to be more sessile.

28. LYMPHOCYTES

29. LYMPHOCYTES
• A lymphocyte that has been ‘educated’ by the central
lymphoid organs, it is an ‘Immunologically competent
cells’.
• Mature T and B cells, before they encounter antigens, are
called ‘naïve cells’, though not engaged in an
immunological response, are nevertheless fully qualified
to undertake appropriate actions.
• They sub serve the following functions:
• Recognition of antigens,
• Storage of immunological memory and
• Immune response to specific antigens.

30. LYMPHOCYTES
• ORIGIN:
• The transformation of stem cells into B-lymphocytes and T-
lymphocytes begins about the fifth month after fertilization,
and a full set is complete a few months after birth.
• These cells then migrate to the lymphoid organs in the lymph
nodes, spleen, tonsils, adenoids, and other organs of the
lymphatic system.
• To initiate the immune response, microorganisms are
phagocytized and their antigens are processed in phagocytic
cells such as macrophages.
• The antigenic determinants are displayed on the surface of
the phagocytic cells and presented to the appropriate B-
lymphocytes and T-lymphocytes to provoke an immune
response.

31. Stem cells from the yolk sac enter the abdomen of the
foetus through the umbilical cord.
Umbilical cord
Uterus
Foetus
Liver
A
B The stem cells differentiate in
the liver of the foetus.
BONE MARROW
C The hematopoietic stem cells mature in the bone
marrow.
D Stem cells then become Lymphoid
progenitors.
E Other stem cells become myeloid progenitors that
differentiate into red blood cells and most white blood
cells.
B-Lymphocyte differentiation T-Lymphocyte differentiation
F
Some lymphoid progenitors
differentiate to B lymphocytes in the
bone marrow.
G Other lymphoid progenitors differentiate to T
Lymphocytes in the Thymus.
H B Lymphocytes take up residence in
the outer cortex of a Lymph node.
I T Lymphocytes take up residence in
the inner medulla of a Lymph node.
THE ORIGIN OF B AND T
LYMPHOCYTES.

32. LYMPHOCYTES
• A number of surface antigens or markers have been
identified on lymphocytes and other leucocytes by means
of monoclonal antibodies.
• These markers reflect the stage of differentiation and
functional properties of the cell.
• At the International Workshops for Leucocytes
Differentiation Antigens order was given by comparing the
specificities of different antisera.
• When a cluster of monoclonal antibodies was found to
react with a particular antigen, it was defined as a separate
marker and given a CD (Cluster Differentiation) number.
• Over 150 CD markers have been identified so far.

33. T-CELLS
• These are Thymus derived cells.
• Key players in adaptive immunity. Governs cell mediated
immune response.
• 65-80% of the circulating pool of small lymphocytes.
• Found in the inner subcortical regions but not in the
germinal centers of the lymph nodes.
• Longer life span (months or years) than B cells.
• On exposure to certain mitogens like phytohemagglutinin
or Concavalin A, the T cells can be stimulated to divide.
• Most T cells in humans have receptors for sheep RBC on
their surface and have the ability to form rosettes with
them.

34. Development in the thymus
• All T cells originate from haematopoietic stem cells in
the bone marrow.
• Haematopoietic progenitors derived from
haematopoietic stem cells populate the thymus and
expand by cell division to generate a large population of
immature thymocytes.
• The earliest thymocytes express neither CD4 nor CD8,
and are therefore classed as double-negative (CD4‾
CD8‾) cells.
• As they progress through their development they
become double-positive thymocytes (CD4+ CD8+), and
finally mature to single-positive (CD4+CD8‾ or
CD4‾CD8+) thymocytes that are then released from the
thymus to peripheral tissues.

35. Development in the thymus
• About 98% of thymocytes die during the
development processes in the thymus by failing
either positive selection or negative selection,
whereas the other 2% survive and leave the thymus
to become mature immunocompetent T cells.
• The thymus contributes more naïve T cells at
younger ages.
• As the thymus shrinks by about 3% a year
throughout middle age, there is a corresponding
fall in the thymic production of naïve T cells, leaving
peripheral T cell expansion to play a greater role in
protecting older subjects.

36. Development in the thymus
• Positive selection selects for T cells that are
capable of recognizing self antigens through
MHC.
• Negative selection selects for T cells that bind too
strongly to self antigens.
• These two selection processes allow for Tolerance
of self by the immune system. They do not
necessarily occur in a chronological order and can
occur simultaneously in the thymus.

37. T-CELLS ACTIVATION

38. TYPES OF T-CELLS
• T helper cells / TH cells / CD4+ T cells.
• Cytotoxic T Cells / Tc cells / CLT / CD8+ T cells.
• Memory T cells.
• Regulatory T cells / Treg cells also formerly
known as Suppressor T cells.
• Natural Killer T cells / NKT cells.
• gd T cells / gamma delta T cells.

39. TYPES OF T-CELLS

40. HELPER ( CD4+ ) T CELLS
• About 65% of peripheral T cells
• Found mainly in the thymic medulla, tonsils
and blood.
• Recognize a nonpeptide-binding portion of
MHC Class II molecules.
• Hence CD4 T cells are restricted to the
recognition of pMHC Class II complexes.

41. HELPER ( CD4+ ) T CELLS
• These cells are also known as CD4+ T cells because they
express the CD4 protein on their surface.
• Helper T cells become activated when they are presented
with peptide antigens by MHC class II molecules that are
expressed on the surface of Antigen Presenting Cells (APCs).
• Once activated, they divide rapidly and secrete small proteins
called cytokines that regulate or assist in the active immune
response.
• These cells can differentiate into one of several subtypes,
including TH1, TH2, TH3, TH17, or TFH which secrete different
cytokines to facilitate a different type of immune response.
• The mechanism by which T cells are directed into a particular
subtype is poorly understood, though signaling patterns from
the APC are thought to play an important role.

42. HELPER ( CD4+ ) T CELLS
• Involved in the induction and regulation of immune response. They
perform the following helper functions:
i. They help B cells to be transformed to plasma cells.
ii. CD8 T cells to become activated cytotoxic T cells, and
iii. Macrophages to mediate delayed type Hypersensitivity reactions.
• Main functions:
1. Help in the antigen specific activation of B cells and effector T cells.
2. Th-1 cytokines activates cytotoxic inflammatory and delayed
hypersensitivity reactions.
3. Th-2 cells help in the production of interleukins which encourage
production of antibodies especially IgE.
4. Th-2 cytokines are associated with regulation of strong antibody and
allergic response.

43. CYTOTOXIC (CD8+ ) T CELLS
• Account for approximately one-third of all
mature CD3+ cells.
• Found mainly in the bone marrow and gut
lymphoid tissue.
• Recognize a nonpeptide-binding portion of MHC
Class I molecules (which is present on the
surface of nearly every cells of the body).
• Hence, CD8 T cells, also known as cytotoxic T
cells are restricted to the recognition of pMHC
Class I complexes.

44. FUNCTIONS OF CD8 T-CELLS
• They kill: Virus-infected cells, Allograft cells, Tumor cells.
• T-cell mediated cytotoxicity is an apoptotic process that
appears to be mediated by two separate pathways:
i. Involving the release of proteins known as Perforins,
which insert themselves into the target cell membranes
forming channels. These channels allow the diffusion of
enzymes (granzymes) into the cytoplasm. Granzyme-
induced apoptosis is calcium dependant.
ii. Signal delivery by cytotoxic cells to the target cells which
require cell-to-cell contact. This pathway is calcium
independent.

45. Difference between helper T cells
(CD4) and cytotoxic T (CD8) cells
Helper T cells Cytotoxic T cells
Carries CD4 marker Carries CD8 cells
Helps or induce immune response. Predominantly cytotoxic
Recognizes antigens in
association with class II MHC
Recognize antigens in association
with class I MHC
APCs are activated to kill
intracellular microorganisms by
secreting cytokines.
Destroy virus-infected and tumor
cells directly

46. MEMORY T CELLS
i. Memory cells live for many years or have the capacity to
reproduce them.
ii. A large number of memory cells are produced, and so
secondary response is enhanced and is greater than the
primary response (‘memory against past infection’).
iii.They are activated by small quantities of antigens and require
less co-stimulation than do the naïve and unactivated T cells.
iv.Activated memory cells produce greater amounts of
interleukins than do naïve T cells when they are first
activated.
• Comprise two subtypes: Central memory T cells (TCM cells)
and Effector memory T cells (TEM cells). Memory cells may be
either CD4+ or CD8+.

47. REGULATORY T-CELLS
• Formerly known as suppressor T cells, are crucial for the
maintenance of immunological tolerance. Their major role is to
shut down T cell-mediated immunity toward the end of an immune
reaction and to suppress auto-reactive T cells that escaped the
process of negative selection in the thymus.
• Two major classes of CD4+ regulatory T cells have been described,
including the naturally occurring Treg cells and the adaptive Treg
cells.
• Naturally occurring Treg cells arise in the thymus, whereas the
adaptive Treg cells may originate during a normal immune response.
• Naturally occurring Treg cells can be distinguished from other T cells
by the presence of an intracellular molecule called FoxP3.
Mutations of the FOXP3 gene can prevent regulatory T cell
development, causing the fatal autoimmune disease IPEX

48. NATURAL KILLER T-CELLS
• NKT cells are a special kind of lymphocyte that bridges
the adaptive immune system with the innate immune
system.
• Unlike conventional T cells that recognize peptide
antigen presented by major histocompatibility complex
(MHC) molecules, NKT cells recognize glycolipid antigen
presented by a molecule called CD1d.
• Once activated, these cells can perform functions
ascribed to both TH and TC cells (i.e., cytokine production
and release of cytolytic/cell killing molecules).
• They are also able to recognize and eliminate some
tumor cells and cells infected with herpes viruses.

49. gd T-CELLS
• Gamma delta T cells represent a small subset of T cells that
possess a distinct T cell receptor (TCR) on their surface.
• A majority of T cells have a TCR composed of two glycoprotein
chains called α- and β- TCR chains.
• However, in gd T cells, the TCR is made up of one g-chain and
one d-chain.
• This group of T cells is much less common (2% of total T cells)
than the αβ T cells, but are found at their highest abundance
in the gut mucosa, within a population of lymphocytes known
as intraepithelial lymphocytes (IELs).
• The antigenic molecules that activate gd T cells are still widely
unknown.
• However, gd T cells are not MHC restricted and seem to be
able to recognize whole proteins rather than requiring
peptides to be presented by MHC molecules on antigen
presenting cells.

50. T-CELL RECEPTOR / TCR
• Consists of two polypeptides: alpha and beta, and they are
associated with CD3 proteins.
• Each T cell has a unique TCR on its surface, thereby implying
that hundreds and millions of different T cell occur in each
person.
• T cell alpha and beta polypeptides show many similarities to
immunoglobulin heavy chain in following ways:
i. There are V (variable), D (diversity), J (joining), and C
(constant) segments that rearrange to provide diversity,
thereby resulting in more than 107 different receptor proteins.
ii. RAG-1 and RAG-2 are the two genes that encode the
recombinase enzymes that catalyze these gene
rearrangements and are similar in T and B cells.

51. T-CELL RECEPTOR / TCR
• However differ to
immunoglobulins by
i. Having two chains
rather than having four
in immunoglobulins and
ii. Recognizing antigens
only in conjunction with
MHC proteins, whereas
immunoglobulins can
recognize free antigens.

52. EFFECTOR FUNCTIONS OF T CELLS
• Cytotoxicity.
• Cytotoxicity of virus-infected cells:
a. By inserting perforins and granzymes.
b.By the Fas-Fas ligand (FasL) interaction
c. By Antibody Dependant Cellular Cytotoxicity
(ADCC).
• Role in graft (allograft) rejection.
• Delayed Hypersensitivity.

53. REGULATORY FUNCTIONS OF T CELLS
• Regulation of antibody production.
• Stimulation of Helper and Cytotoxic T cells
to participate in the Cell Mediated Immunity.
• Suppression of certain immune response by
Suppressor T cells.

54. B-CELLS
• Pro B cells produced from foetal liver during
embryonic life.
• Afterwards bone marrow throughout life.
• Nearly 30% of circulating small lymphocytes.
• Short life span of days or weeks.
• Nearly 109 B cell produced daily.
• These are found in the germinal centers of
lymph nodes, in the white pulp of spleen, and
in the MALT.

55. B-CELLS
• Play a large role in the humoral immune response.
• THE PRINCIPAL FUNCTIONS OF B CELLS:
• Differentiate into plasma cells and produce antibodies against
antigens.
• Perform the role of antigen-presenting cells to Helper T cells,
and
• Eventually develop into memory B cells after activation by
antigen interaction.
• B cells are an essential component of the adaptive immune system.
• The abbreviation "B", in B cell, comes from the bursa of Fabricius in
birds. In mammals, immature B cells are formed in the bone
marrow, which is used as a acronym for the cells' name.
• Express immunoglobulins and class II MHC molecules on their
surface.

56. ORIGIN OF B CELLS
• B cell precursor during embryogenesis develop in the foetal
liver, bone marrow (main site for maturation in adults)
• After reaching the IgM+ immature stage in the bone marrow,
these immature B cells migrate to the spleen, where they are
called transitional B cells, and some of these cells
differentiate into mature B lymphocytes.
• They do not require thymus for maturation.
• B cells mature in two phases:
• i. The antigen independent phase that consists of stem cells
and pre-B cells and
• ii. The antigen dependant phase that consists of activated B
cells and plasma cells.

57. B-CELLS
• B cell development occurs through several stages, each
stage representing a change in the genome content at
the antibody loci.
• An antibody is composed of two identical light (L) and
two identical heavy (H) chains, and the genes specifying
them are found in the 'V' (Variable) region and the 'C'
(Constant) region.
• In the heavy-chain 'V' region there are three segments;
V, D and J, which recombine randomly, in a process
called VDJ recombination, to produce a unique variable
domain in the immunoglobulin of each individual B cell.
• Similar rearrangements occur for light-chain 'V' region
except there are only two segments involved; V and J.

58. Stage Heavy chain Light chain Ig
IL-7
receptor
CD
19
Progenitor (or
pre-pro) B cells
germline germline - No No
Early Pro (or pre-
pre)-B cells
undergoes D-J
rearrangement
germline - No No
Late Pro (or pre-
pre)-B cells
undergoes V-DJ
rearrangement
germline - No Yes
Large Pre-B cells is VDJ rearranged germline
IgM in
cytoplasm
Yes Yes
Small Pre-B cells is VDJ rearranged
undergoes V-J
rearrangement
IgM in
cytoplasm
Yes Yes
Immature B cells is VDJ rearranged VJ rearranged
IgM on
surface
Yes Yes
Mature B cells is VDJ rearranged VJ rearranged
IgM and IgD
on surface
Yes Yes
The list above describes the process of immunoglobulin formation
at the different stages of B cell development.

59. B-CELLS
• Mature B cells are distinguished from other lymphocytes
by the synthesis and display of membrane bound
immunoglobulin (antibody) molecules.
• Each of the approximately 1.5 X 105 molecules of
antibody on the membrane of a single B cell has an
identical binding site for antigen.
• B cell has surface IgM which acts as a receptor of
antigens.
• Some B cells also carry surface IgD as receptor for
antigens.
• Many other molecules expressed on the surface are
B220, Class II MHC molecules, CR1 and CR2, CD40 etc.

60. Mechanism of Action
• A critical difference between B
cells and T cells is how each
lymphocyte recognizes its
antigen.
• B cells recognize their cognate
antigen in its native form.
• They recognize free (soluble)
antigen in the blood or lymph
using their BCR or membrane
bound-immunoglobulin.
• In contrast, T cells recognize
their cognate antigen in a
processed form, as a peptide
fragment presented by an
antigen presenting cell's MHC
molecule to the T cell receptor. T cell-dependent B cell activation, showing
a TH2-cell (left), B cell (right), and several
interaction molecules

61. ACTIVATION
• Cooperation of cells in the
immune response
• Antigen-presenting cells (e.g.
dendritic cells) present
processed antigen to virgin T
cells, thereby priming them.
• B cells also process the
antigen and present it to the T
cells. They then receive signals
from the T cells that cause
them to divide and
differentiate.
• Some B cells form antibody-
forming cells while a few form
B memory cells.

62. EFFECTOR FUNCTIONS OF B CELLS
• Production of plasma cells is the end result of activation
of B cells.
• The plasma cells in turn produce large amounts of
immunoglobulins specific for the antigen.
• Some activated B cells also produce Memory cells, most
memory B cells have surface IgG that acts as the antigen
receptor, but some have surface IgM.
• Memory T cells produce interleukins that facilitate
antibody production by the memory B cells. The
presence of these cells is responsible for the rapid
appearance of antibody in the secondary immune
response.

63. PLASMA CELLS
• Originate from terminally differentiated B cells.
• Oval or egg-shaped structure characterized by a
stellate nucleus, non-staining Golgi and basophilic
cytoplasm.
• Found in the bone marrow and
perimucosal lymphoid tissue.
• Short life span of 30 days.
• Function: Produce and secrete all the classes of
immunoglobulins into the fluids around the cells.
• Secreting thousands of antibodies per second,
which are specific to the antigen.

64. NATURAL KILLER CELLS
• Large granular lymphocytes.
• 5-10% of peripheral lymphocytes and are found in spleen and
peripheral blood.
• Lack T cell receptor, CD3 proteins, and surface IgM and IgD,
but possess killer activation receptors and killer inhibition
receptors.
• Thymus not required for development.
• Does not carry antigen receptors of any kind, but can
recognize antibody molecules and destroy target cells using
the same mechanism as T cell cytotoxicity (ADCC).
• The IL-12 and gamma interferons are potent activators of NK
cells
• Number remains normal in severe combined
immunodeficiency, in which mature T cell and B cells are
absent.

65. Functions of NK cells
i. Kill virus infected cells and tumor cells.
ii. Non-specific killing of virus infected cells and tumor
cells.
iii.Killing is independent of antigen presentation by MHC
proteins.
iv.Mechanism of killing is by perforins and granzymes.
v. Killing is activated by failure of a cell to present antigen
with class I MHC proteins on the cell surface.

66. RETICULOENDOTHELIAL SYSTEM

67. RETICULOENDOTHELIAL SYSTEM
• The aggregate of the phagocytic cells, including certain cells of the
bone marrow, lymphatic system, liver, and spleen, that have
reticular and endothelial characteristics and function in the
immune system's defense against foreign bodies.
• Collection of cells united by the common property of phagocytosis.
• Phagocytosis is part of the natural, or innate, immune process, and
is not an adaptive immune process.
• Phagocytosis in man is carried out primarily by three groups of
cells:
A. mononuclear phagocytes
B. neutrophils
C. eosinophils (to a minor extent)
• The term MONONUCLEAR PHAGOCYTIC SYSTEM has been
suggested to replace the Reticuloendothelial System, since it is the
mononuclear phagocytes that play the major role in the
phagocytosis of foreign material.

68. PHAGOCYTIC CELLS
Include macrophages and dendritic
cells

69. MACROPHAGES
• The mononuclear phagocytic system consists of monocytes
circulating in the blood and macrophages in the tissue.
• Differentiation of a monocyte to a tissue macrophage involves
a number of changes as follows
• i. Cell enlarges five to ten fold.
• ii. Intracellular organelles increase in number and complexity.
• iii. It acquires increased phagocytic abilities.
• iv. Produces higher level of hydrolytic enzymes.
• v. Begins to secrete a variety of soluble factors.
• Interferon gamma is a potent activator of macrophages.

70. MACROPHAGES
• Macrophages are named according
to tissue location to
• (a). Alveolar macrophages in the
lungs
• (b). Histiocytes in connective
tissues
• (c). Kupffer cells in the liver
• (d). Mesangial cells in the kidneys
• (e). Microglial cells in the brains,
and
• (f). Osteoclasts in the bones.

71. IMPORTANT FEATURES OF MACROPHAGES
FEATURES MECHANISMS
Phagocytosis Ingestion and killing of
microbes in
phagolysosomes.
Antimicrobial and cytotoxic
activities
Oxygen dependent killings:
by superoxides, NO, H2O2
Oxygen independent killings:
by TNF, lysozymes,
hydrolytic enzymes.
Antigen processing Phagocytic antigen

72. DENDRITIC CELLS
• Dendritic cells named because of their many long, narrow processes
that resemble neuronal dendrites, which make them very efficient in
making contacts with foreign materials.
• Primarily present in the skin (e.g., Langerhans cells) and the mucosa.
• Four types are known:
• 1. Langerhans cells
• 2. Interstitial dendritic cells
• 3. Myeloid cells, and
• 4.Lymphoid dendritic cells.
• Features:
• important for presentation of the antigens to T cells during primary
immune response. They are bone marrow derived cells that express
class II MHC proteins and present antigens to CD4 T cells.
• little or no phagocytic activity.