Cellular component of the immune system

Cells of lymphoreticular system

1. Cells involved in immunological functions are as follows:

a. Lymphocytes.
b. Plasma cells.
c. Phagocytic cells.
 Macrophages
 Neutrophils
 Eosinophils
 Dendritic cells.

2. Structural cells.

a. Reticulum cells.
b. Endothelial cells.
c. Fibroblasts.

A. Lymphocytes

 The typical lymphocyte is a small round or club-shaped cell, 5 to 12 µm in diameter

with a spherical nucleus, densely compacted nuclear chromatin with a thin rim of
cytoplasm.
 They produce clonally distributed receptors specific for diverse antigens and are the
key mediators of adaptive immunity.
 Despite their uniform appearance, several different types of lymphocytes can be
distinguished on the basis of their functional properties and by specific surface
markers they express that may be identified using panels of monoclonal antibodies.
o The standard nomenclature for these proteins is the CD (cluster of
differentiation) numeric designation, which is used to delineate surface
proteins that define a particular cell type or stage of cell differentiation and
that are recognized by a cluster or group of antibodies
 These cells are divided into two major lineages:
o T (thymus derived) cells
o B (bone marrow derived) cells.
 The relative proportions of T and B cells vary in tissue to tissue, but in peripheral
blood they constitute 75% and 15% respectively.
 The remaining 10 percent are a special class of granular lymphocytes known as
natural killer (NK) cells.
  ‘T’ and ‘B’ lineage cells, both arise from a subset of hemopoietic stem cells in the
bone marrow or fetal liver that become committed to the lymphoid path of
development.

 There are evidences that both T and B cells, and NK cells are the descendants of a
common committed marrow progenitor cell called lymphoid stem cells.
 The growth of early lymphoid progenitors requires at least two cytokines, called
interleukin-7 (IL-7) and stem cell factor (SCF), found in both the thymic and marrow
microenvironments.
 The progeny of these putative stem cells follows divergent pathways to mature into
either T or B cell.
 Human B lymphocytes develop exclusively in bone marrow.

T cells

 T cells develop from the mature precursor that leave the marrow and travel through
the bloodstream to the thymus, where they proliferate and differentiate into mature
T lymphocytes under the influence of a number of thymic hormones.
 Mature lymphocytes leave the thymus and bone marrow in a resting state
(mitotically inactive) and are called naïve/virgin lymphocytes.
  Once they are dispersed into the bloodstream the naive (virgin) lymphocytes migrate
efficiently into various secondary lymphoid organs such as spleen, lymph nodes,
tonsils, etc.
 The secondary organs maximize the encounter between lymphocytes and foreign
substances. Most immune responses occur in these sites.
 Most virgin lymphocytes have an inherently short lifespan and are programmed to
die, within few days after leaving the marrow or thymus. However, if such a cell
receives signals that indicate the presence of foreign substance or pathogen, it may
respond through a phenomenon known as activation.

Activated or committed or sensitized cell undergoes successive cell division to form:

 memory lymphocytes which can survive for years

 effector lymphocytes, which survive only for few days, but carry out specific defence
activities against the foreign invader.

Several major subsets of T cells exist:

 helper T cells (TH cells), which express molecules called CD4

 cytotoxic T cells (TC cells), which express CD8 molecules on their surface.
 T regulatory cell (Treg cells) that possesses suppressor activity

Functions of T cells
 i. B-cell help: TH cells cooperate with B cells to enhance the production of antibodies.
Such T cells function by releasing cytokines, which provide various activation signals
for the B cells. Cytokine are soluble substances, or mediators that can regulate
proliferation and differentiation of B cells, among other functions.
ii. Inflammatory effects: On activation, certain TH cells releases cytokines that induce
the migration and activation of monocytes and macrophages, leading to
inflammatory reactions.
iii. Cytotoxic effects: TC cells become cytotoxic killer cells that, on contact with their
target cell, are able to deliver a lethal hit, leading to the death of the latter. These T
cells are termed T cytotoxic (T C) cells. In contrast with T H cells, they express
molecules called CD8 on their membranes and are, therefore, CD8+ cells.
iv. Regulatory effects: Helper T cells can be further subdivided into different functional
subsets that are commonly defined by the cytokines they release.
 These subsets (e.g., TH1, TH2) have distinct regulatory properties that are
mediated by the cytokines they release
 TH1 cells can negatively cross-regulate TH2 cells and vice versa.
v. Cytokine effects: Cytokine produced by each of the T-cell subsets (principally T H cells)
exert numerous effects on many cells, lymphoid and nonlymphoid. Thus directly or
indirectly T cells communicate and collaborate with many cell types.

B Cells

 B lymphocytes are the only cells capable of producing antibodies; therefore, they are
the cells that mediate humoral immunity
 B lymphocyte precursors, pro-B cells, develop in the fetal liver during embryonic life
and in the bone marrow afterwards.
 B cells synthesize proteins called immunoglobulin (Ig).
o Each Ig molecule binds specifically and with high affinity with its own
molecular ligand known as antigen.
 A virgin (resting) B cell is one-stage of B cell, which has not had contact with antigen.
Each resting lymphocyte may express good number of membrane Ig on its surface.

On contact with its appropriate antigen, the mature B cell undergoes clonal proliferation:

 Some activated B cells become long-living memory cells responsible for the recall
phenomenon seen in subsequent contact with the same antigen.
o The frequency of memory cells increases with age
 The majority of the activated B cells are transformed into plasma cells (antibody
secreting cells)
 Plasma cells develop in response to antigenic stimulation in the peripheral lymphoid
organs, where they may stay and produce antibodies.
 o Small numbers of antibody-secreting cells are also found in the blood; these
are called plasmablasts.
o Some of these migrate to the bone marrow, where they mature into long-
lived plasma cells and continue to produce antibody years after the infection
is eradicated, providing immediate protection in case the infection recurs.

Effector CD4+ T cells (helper T cells) produce proteins called cytokines that activate B cells,
macrophages, and other cell types, thereby mediating the helper function of this lineage

Functions of B cells:

i. Humoral acquired immunity.

ii. Antigen processing and presenting.
iii. Production of an array of cytokines and other factors that influence the growth and
activity of other immunologically important cells
B. Phagocytic cells

phagocytic cells remove effete and foreign particle. They include:

1. Macrophages.
 The macrophages in the blood are known as monocytes or blood macrophages.
 The monocytes leave the circulation and reach various tissues and become
transformed, to macrophages with morphological and functional features
characteristic of the tissue, such as Kupffer cells in liver, alveolar macrophages in the
lungs, Langerhans’ cells in skin, osteoclasts in bone, etc.
 These macrophages proliferate and survive for months

Functions of macrophages

i. The primary function of the macrophages is phagocytosis.

 They are attracted to the area of inflammation and tissue damage by
chemotaxis.
  Foreign substances, which are sensitized by antibody (opsonin) are
phagocytosed more readily.
 The phagocytosed particles are taken inside the vacuole (phagosome), the
membrane of which fuses with the lysosome called phagolysosome.
 Lysosomal enzymes digest the particle; the remnant being extruded from the
cells. While, phagocytosis is an effective defense against most of the
organisms, bacteria such as typhoid bacilli, brucellae and tubercle bacilli
resist digestion and multiply inside the cells and are transported in them to
other locations.
ii. Antigen processing: Antigen is processed in the macrophage and the processed
antigen is presented along with major histocompatibility complex (MHC) molecule
for attraction of T lymphocytes with complementary receptors on their surface.
iii. Cytokine production: A number of biologically active substances such as hydrolytic
enzymes, binding proteins (fibronectin, transferrin), TNF (cachectin), CSF
(macrophage colony stimulating factor-regulates proliferation, differentiation and
functional activation of monocytes), IL-1 are secreted by macrophages. IL-1 acts as
endogenous pyrogen and also induces synthesis of IL-2 by activated T cells

Following migration of monocytes from the blood to various tissues, they undergo further
differentiation into a variety of histologic forms, all of which play a role in phagocytosis,
including the following:

 Kupffer cells, in the liver; large cells with many cytoplasmic projections
 Alveolar macrophages, in the lung
 Splenic macrophages, in the red pulp
 Peritoneal macrophages, free-floating in peritoneal fluid
 Microglial cells, in the central nervous tissue

Each of these macrophage populations constitutes part of the cellular members of the
reticuloendothelial system (RES), which is widely distributed throughout the body.

 The major function of the RES is to phagocytize microorganisms and foreign

substances that are in the bloodstream and in various tissues.
 The RES also functions in the destruction of aged and imperfect cells, such as
erythrocytes.
 These cells have the ability to bind and engulf particulate materials and antigens.
Their location along capillaries, makes them most likely to make first contact with
invading pathogens and antigens.

2. Neutrophils.

 Neutrophils are frequently involved in the elimination and destruction of

extracellular bacteria.
  They are capable of migrating through the walls of blood vessels to areas of bacterial
infection and tissue damage, where they seek out and kill infectious bacteria.
 Neutrophil granules contain a variety of defensins and hydrolytic enzymes that help
them destroy bacteria through phagocytosis
 When many neutrophils are brought into an infected area, they can be stimulated to
release toxic molecules into the surrounding tissue to better clear infectious agents.
This is called degranulation.
 As neutrophils fight an infection, a visible accumulation of leukocytes, cellular debris,
and bacteria at the site of infection can be observed. This build-up is what we call
pus. The presence of pus is a sign that the immune defences have been activated
against an infection

3. Eosinophils

 Eosinophils are granulocytes that protect against protozoa and helminths; they also
play a role in allergic reactions.
 The granules of eosinophils, which readily absorb the acidic reddish dye eosin,
contain histamine, degradative enzymes, and a compound known as major basic
protein (MBP). MBP binds to the surface carbohydrates of parasites, and this binding
is associated with disruption of the cell membrane and membrane permeability.

4. Basophil:

 They are found in blood and tissues (mast cells).

 Their cytoplasm possesses large number of granules, which contain heparin,
histamine, serotonin and other hydrolytic enzymes.
 Degranulation leads to anaphylaxis and atopic allergy.

Antigen-Presenting Cells

The common portals of entry for microbes—the skin and gastrointestinal, respiratory, and
genitourinary tracts—contain specialized cells located in the epithelium that capture
antigens, transport them to peripheral lymphoid tissues, and display (present) them to
lymphocytes. These are the first steps in the development of adaptive immune responses
against antigens.

Macrophages and dendritic cells are antigen presenting cells

o They do not possess antigen specific receptors like lymphocytes,

o They process and present antigen to the antigen-specific receptors expressed
by T cells.
 o The APCs express a variety of cell-surface molecules that facilitate their
ability to interact with T cells e.g. the major histocompatibility complex
(MHC) molecules. MHC molecules are encoded by a set of polymorphic genes
expressed within a population.
o APCs process protein antigens intracellularly, resulting in the constellation of
peptides that noncovalently bind to MHC molecules and ultimately get
displayed on the cell surface

Dendritic cells

 These cells capture protein antigens of microbes that cross epithelial barriers and
transport these antigens to regional lymph nodes, where they display fragments of
the proteins for recognition by T lymphocytes. If a microbe has invaded through the
epithelium, it may be phagocytosed and presented by tissue macrophages.
 Microbes or their antigens that enter lymphoid organs may be captured by dendritic
cells or macrophages that reside in these organs and presented to lymphocytes.
 Dendritic cells respond to microbes by producing surface proteins, called
costimulators, which are required, together with antigen, to activate naive T
lymphocytes to proliferate and differentiate into effector cells.
 Dendritic cells express higher levels of these costimulatory proteins than do other
cell types and are thus the most potent stimulators of naive T cells and the most
efficient initiators of T cell responses.
 Other antigen-presenting cells, such as macrophages and B cells, present antigens to
differentiated effector T cells in various immune responses.
 B lymphocytes may directly recognize the antigens of microbes (either released or
on the surface of the microbes), and macrophages and dendritic cells in peripheral
lymphoid organs may also capture antigens and display them to B cells.
 A distinct type of cell called the follicular dendritic cell (FDC) resides in the germinal
centers of lymphoid follicles in the peripheral lymphoid organs and displays antigens
that stimulate the differentiation of B cells in the follicles

Natural Killer cells

 Natural killer cells are cytotoxic cells that recognise altered features of the
membranes of abnormal cells, such as those found on virus infected or cancer cells.
 NK cells are large granular lymphocytes.
 The intracellular granules contain preformed biologically potent molecules that are
released when NK cells make contact with target cells.
 Some of these molecules cause the formation of pores in the membrane of the
target cell, leading to its lysis.
  Other molecules enter the target cell and cause apoptosis (programmed cell death)
of the target cell by enhanced fragmentation of its nuclear DNA. Hence, they are
able to lyse certain virus infected cells and tumor cells without prior stimulation
 NK cells lack antigen-specific receptors. They recognize their target cells using a
mechanism involving cell–cell contact, which allows them to determine whether a
potential target cell has lost a particular self-antigen, namely, major
histocompatibility complex (MHC) class I.
o MHC class I is expressed on virtually all nucleated cells.
o NK cells express receptors called killer-cell inhibitory receptors (KIR), which
bind to MHC class I molecules expressed on normal cells.
o When ligated, KIRs inhibit downstream events that would otherwise cause
the NK cell to be activated, causing degranulation and destruction of the
target cells.
o Virus-infected or transformed (tumour) cells have significantly reduced
numbers of MHC class I molecules on their surfaces. Thus, when such cells
encounter NK cells, they fail to effectively engage KIRs and therefore become
susceptible to NK cell-mediated cytotoxicity

Reading assignment: Read about Natural Killer T cells