COMPONENTS OF THE IMMUNE SYSTEM

A. CELLS OF THE IMMUNE SYSTEM

Immune System

Myeloid cells Lymphoid cells

Granulocytes Mast cells Monocytes T cells B cells NK cells

Neutrophils Macrophages Helper cells Plasma cells

Basophils Kupffer cells Suppressor cells
Eosinophils Dendritic cells Cytotoxic cells
Antibodies

All cell of the immune system develops from pleuripotent stems in the bone marrow, the
soft tissue that fills most bone cavities. These cells can develop into two immune cell
precursors. The myeloid progenitor (stem) cell gives rise to erythrocytes, platelets and the
white blood cell (leukocytes), granulocytes (neutrophils, eosinophils, basophils), monocytes
that give rise to macrophages and dendritic cells and mast cells.
Macrophages are one of three types of phagocytes in the immune system and are
distributed widely in the body tissues where they play a critical part in innate immunity by
surrounding, ingesting and destroying invading bacteria and other foreign organisms in a
process called phagocytosis which is part of the inflammatory reaction. Macrophages also
play a role in adaptive immunity in that they attach to invading antigens and deliver them to
be destroyed by other components of the adaptive immune system. Dendritic cells (also a
phagocyte) are specialized to take up antigen and display it for recognition by lymphocytes.
Immature dendritic cells migrate from the blood to reside in the tissue and are both
phagocytic and macropinolytic, ingesting large amount of the surrounding fluid. Upon
encounters a pathogen, they rapidly mature and migrate to the lymph node.
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 shape nuclei. Granulocytes are relatively short lived and are produced in increased
numbers during immune response when they leave the blood to migrate to sites of infection
or inflammation. Neutrophils which are the 3rd phagocytic cell of the immune system are the
most numerous of the granulocytes and most important cellular component of the innate
immune response: hereditary deficiencies in neutrophil function lead to overwhelming
bacterial infection which is fatal if untreated. By surrounding, ingesting and destroying
invading bacteria and other foreign or garusus in a process called phagocytosis which is part
of inflammatory or macrophages also play a role in adaptor immunity in that they attach to
modifying antigens and deliver them to be destroyed by other components of the adaptive
immune system. Eosinophils are thought to be important chiefly in defense against parasite
infection because their numbers increase during a parasitic infection. The function of
basophils is probably similar and complementary to their eosinophils. Unlike neutrophils
which are phagocytes, eosinophils and basophils function by releasing their granule contents
in response to pathogens, pathogen products or damaged host cells

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Mast cells, whose blood-borne precursors are not well defined also differentiate in the
tissue. They mainly reside near small blood vessels and when activated release substances
that affect vascular permeability. Although best known for their role in orchestrating allergic
response, they are believed to play a part in protecting mucosal surface against pathogen.
The lymphoid progenitor (stern) cell generates the lymphocytes, specialized white blood cell
whose function is to identify and destroy antigens.
The Lymphoid progenitor (stem) cells generate the lymphocytes, specialized white blood cells
whose function is to identify and destroy invading antigens. Some lymphocytes mature in the
bone marrow and are called B lymphocytes. B lymphocytes, or B cells, make antibodies,
which circulate through the blood and other body fluids, binding to antigens and helping to
destroy them in humoral immune responses.
Other lymphocytes, called T lymphocytes, or T cells, mature in the thymus, a small glandular
organ located behind the breastbone. Some T lymphocytes, called cytotoxic (cell-poisoning)
or killer T lymphocytes (TC or CTL), generate cell-mediated immune responses, directly
destroying cells that have specific antigens on their surface that are recognized by the killer T
cells. CTL expresses a unique antigen on their surface called CD8. Helper T lymphocytes (TH), a
second kind of T lymphocyte, regulate the immune system by controlling the strength and
quality of all immune responses. Two types of T helper cells are produced in the thymus - the
THI cells which help the pre-cytotoxic cells to differentiate into cytotoxic T cells and T H2 which
helps B cells differentiate into plasma cells which secrete antibodies. The T H1 cells express a
unique antigen on their surface called CD4.
The Lymphoid progenitor (stem) cells also gives rise to a third class of cells - the Natural killer
(NK) cells. They lack antigen specific receptors and are part of the innate immune system.
These cells circulate in the blood as large lymphocytes with distinct cytotoxic granules. They
are able to recognize and kill some abnormal cells for example tumour cells and virus-
infected cells and are thought to be important in the innate immune defense against
intracellular pathogens.
Most contact between antigens and lymphocytes occurs in the lymphoid organs—the lymph
nodes, spleen, and tonsils, as well as specialized areas of the intestine and lungs (see Tissues
and Organs of the immune system). Mature lymphocytes constantly travel through the blood
to the lymphoid organs and then back to the blood again. This recirculation ensures that the
body is continuously monitored for invading substances.
Antigen Receptors
One of the characteristics of adaptive immunity is that it is specific: Each response is tailored
to a specific type of invading antigen. Each lymphocyte, as it matures, makes an antigen
receptor—that is, a specific structure on its surface that can bind with a matching structure
on the antigen like a lock and key. Although lymphocytes can make billions of different kinds
of antigen receptors, each individual lymphocyte makes only one kind. When an antigen
enters the body, it activates only the lymphocytes whose receptors match up with it. The
extraordinary diversity makes it likely that any chemical structure on the surface of an
invading cell will be recognized and bound by one or more antibodies. Antibody diversity is
derived from random reassembly of a set of immunoglobulin gene segments through genetic
recombination mechanism. The B-cell antigen receptor (BCR) is a membrane-bound form of
the antibody that the B-cell will secrete after activation and differentiation to plasma cells.

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The T-cell antigen receptor (TCR) is related to Ig but is quite distinct from it as it is especially
adapted to detect antigens derived from proteins or pathogens that have entered into the
host cell.
Antigen-Presenting Cells
When an antigen enters a body cell, certain transport molecules within the cell attach
themselves to the antigen and transport it to the surface of the cell, where they “present”
the antigen to T lymphocytes. These transport molecules are made by a group of genes
called the Major histocompatibility complex (MHC) and are therefore known as MHC
molecules. In humans the MHC proteins are collectively called Human Leukocyte Antigens or
HLA. MHC proteins mediate the detection of protein antigens in host cells. They bind
polypeptide fragments of protein (cellular and viral) digested in cell and present them to the
outside surface of the cell. There are two classes of MHC proteins which differ in their
distribution among cell type and in the source of digested protein whose peptides they
display.
Class 1 MHC proteins
 Are found on the surface of virtually all vertebrate cells.
 Consist of two polypeptide chains, a membrane embedded alpha chain encoded in the
MHC gene region and a smaller peptide called Beta-2- microglobulin (β2m) encoded by a
non-MHC gene.
 There are countless variants in the human population placing them among the most
polymorphic of proteins.
 Because each individual produces up to six class 1 MHC protein variants, any two
individuals are unlikely to have the same set
 Polymorphisms in MHC proteins are the major antigenic barriers for tissue
transplantation from one individual to another; tissue transplants not matched for MHC
identity are recognised as non-self and rejected.
 Class I MHC proteins present antigens to Killer T cells
 Each TC cell has many copies of only one T-cell receptor that is specific for a particular
class of class 1 MHC protein-peptide complex
Class II MHC proteins
 Occur on the surfaces of specialized cells (Antigen presenting cells, APC, which includes
dendritic cells, macrophages, and B lymphocytes).
 Consist of two covalently linked polypeptides called α and β. Like class 1 α-chain these
polypeptides are embedded in the cytoplasmic membrane and project outwards from
the cell surface
 Like class I MHC, the class II proteins are highly polymorphic with many variants in the
human population
 Each human is capable of producing 12 variants and thus it is unlikely that any two
individuals have an identical set.
 The class II MHC proteins bind and display peptides derived NOT from cellular proteins
but from external proteins ingested by the cells.
 The Class II MHC proteins present antigens to helper T cells

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B. MOLECULES OF THE IMMUNE SYSTEM
1. ANTIMICROBIAL PEPTIDES (From Prescott)
Cationic Peptides
Antimicrobial cationic peptides appear to be highly conserved through evolution. There are
three generic classes of cationic peptides whose biological activity is related to their ability to
damage bacterial plasma membranes. This is accomplished by electrostatic interactions with
membranes—the formation of ionic pores and/or transient gaps thereby altering membrane
permeability.
The first group of cationic peptides includes those that are linear, alpha-helical peptides that
lack cysteine amino acid residues. An important example is cathelicidin, a peptide that arises
from a precursor protein having a C-terminus bearing the mature peptide of some 12 to 80
amino acids. Cathelicidins are produced by a variety of cells (e.g., neutrophils, respiratory
epithelial cells, and alveolar macrophages) and there is substantial heterogeneity between
cathelicidins made by various cells.
A second group, the defensins, is composed of peptides that are open-ended, rich in arginine
and cysteine, and disulfide linked. The group is composed of various structural motifs with an
approximate average molecular weight of 4,000 Daltons. In mammals, defensins have anti-
parallel beta sheet structures with beta hairpin loops containing cationic amino acids. Two
types of defensins have been reported in humans—alpha and beta. Alpha defensins tend to
be peptides of 29 to 35 amino acid residues while beta defensins are usually 36 to 42 amino
acids in length and are found in the primary granules of neutrophils, intestinal Paneth cells,
and in intestinal and respiratory epithelial cells.
A third group contains larger peptides that are enriched for specific amino acids and exhibit
regular structural repeats. Histatin, one such peptide isolated from human saliva, has
antifungal activity. Histatin is a 24 to 38 amino acid peptide, heavily enriched with histidine,
that does not appear to form ionic channels, but rather translocates to the fungal cytoplasm
where it targets mitochondria.
Bacteriocins
The first line of defense against microorganisms is the host’s anatomical barrier, consisting of
the skin and mucous membranes. These surfaces are colonized by normal microbiota, which
by themselves provide a biological barrier against uncontrolled proliferation of foreign
microorganisms. Many of the bacteria that are part of the normal microflora synthesize and
release toxic proteins (e.g., colicin, staphylococcin) called bacteriocins that are lethal to
other strains of the same species as well as other bacterial species. Bacteriocin peptides
range from 900 to 5,800 Daltons and can be cationic, neutral, or anionic. Bacteriocins may
give their producers, which are naturally immune to antibacterial products they make, an
adaptive advantage against other bacteria. Ironically, they sometimes increase bacterial
virulence by damaging host cells such as mononuclear phagocytes. Bacteriocins are
produced by gram-negative and gram-positive bacteria. For example, E. coli synthesizes
bacteriocins called colicins, which are encoded by genes on several different plasmids
(ColB, ColE1, ColE2, ColI, and ColV). Some colicins bind to specific receptors on the cell
envelope of sensitive target bacteria and cause cell lysis, attack specific intracellular sites
such as ribosomes, or disrupt energy production. Other examples include the lantibiotics
produced by the genera Streptococcus, Bacillus, Lactococcus and Staphylococcus. It is now

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widely recognized that these antimicrobial peptides act as defensive effector molecules
protecting the bacterial flora and its human host.

2. CYTOKINES
Cytokines are soluble protein or glycoprotein released by one cell population that acts as an
intercellular (between cells) mediator or signaling molecule. Cytokines are required for
immunoregulation of both of these immune responses.
 When released from mononuclear phagocytes, these proteins are called monokines;
 when released from T lymphocytes they are called lymphokines;
 when produced by a leukocyte and the action is on another leukocyte, they are
interleukins;
 and if their effect is to stimulate the growth and differentiation of immature leukocytes
in the bone marrow, they are called colony-stimulating factors (CSFs).
Cytokines have been grouped into the following categories or families:
 chemokines,
 hematopoietins,
 interleukins, and
 members of the tumor necrosis factor (TNF) family.
Cytokines can affect the same cell responsible for their production (an autocrine function) or
nearby cells (a paracrine function), or they can be distributed by the circulatory system to
distant target cells (an endocrine function).
Their production is induced by nonspecific stimuli such as a viral, bacterial, or parasitic
infection; cancer; inflammation; or the interaction between a T cell and antigen. Cytokines
produce biological actions only when they bind to specific, high-affinity receptors on the
surface of target cells. The affinity of cytokine receptors for their cytokine ligands is very
high, and consequently cytokines are effective at very low concentrations .
3. COMPLEMENT (To be sent as a separate chapter)

C. TISSUES AND ORGANS OF THE IMMUNE SYSTEM

The lymphoid organs are organized tissues containing large number of lymphocytes in a
framework of non-lymphoid cells. Based on function, the organs and tissues of the immune
system can be divided into primary or central lymphoid organs where lymphocytes are
generated and secondary or peripheral lymphoid organs where adaptive immune responses
are initiated and where lymphocytes are maintained.
The primary lymphoid organs are the bone marrow and thymus a large organ in the upper
crest. Both B and T lymphocytes originate in the bone marrow but only B lymphocytes
mature there; T lymphocytes migrate to the thymus to undergo their maturation. Once they
have completed their maturation, both lymphocytes enter the blood stream from which they
migrate to the periphery lymphoid organs.
The secondary organs and tissues serve as areas where lymphocyte may encounter and bind
antigen whereupon they proliferate and differentiate into fully active, anitigen specific
effector cells. The spleen is a secondary lymphoid organ while the lymph node and mucous-
associated lymphoid tissues, MALT, consisting of GALT, gut-associated lymphoid tissues
(includes tonsil, adenoids, appendix) and SALT, skin-associated lymphoid tissues, are the

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secondary lymphoid tissues. A less well organized MALT occurs in the respiratory system and
is called bronchial-associated lymphoid tissue, BALT.
The spleen, a large organ in the abdominal cavity, specializes in filtering the blood and
trapping blood borne micro-organisms and antigens.
The lymph nodes fitter out harmful micro-organisms and antigen from the lymph. The
mucosa-associated lymphoid tissues interact with antigens and micro organisms from the
gut skin, the bronchial mucosa tissues and other mucosa membranes.
The primary role of the lymphoid tissues is to efficiently organize and increase interactions
between the innate and the acquired arms of the immune response.