INTRODUCTION OF IMMUNOLOGY YUANDANI

DEFINITION OF IMMUNOLOGY
Immunology
is a discipline in the biomedical sciences dealing with
the mechanisms and structures in a living organism
(including man) for protection against infectious
diseases.
IMMUNOLOGY AND PHARMACEUTICS
IMMUNE SYSTEM
The immune system is a
host defense system
comprising many
biological structures and
processes within an
organism that protects
against disease
The immune system is
made up of a network
of cells, tissues, and
organs that work
together to protect the
body.
DIVISIONS OF THE IMMUNE SYSTEM

Immunity in vertebrates can be divided into different sections.

By the processes involved in the immune response, an immune system consists of:
 innate immunity and
 acquired immunity.

By the components involved in the immune response, an immune system can be

divided into:
 humoral immunity and
 Cellular immunity.

By the location of the immune response, an immune system consists of

 serosal immunity
 mucosal immunity.
ORGANS OF THE IMMUNE SYSTEM
LYMPHOID SYSTEM
CELLS OF THE IMMUNE SYSTEM
CELLS OF THE IMMUNE SYSTEM
Phagocytes

There are two types of phagocytes which differentiate based on the effectivenes of phagocytosis
by those cells :
 professional:
neutrophils, monocytes and macrophages
They are facilitated with recognition systems which allow them to bind to
microorganisms, internalize and kill them (Nagl et al. 2002).
 non-professional
These cells include epithelial cells, endothelial cells, fibroblasts and mesenchymal cell.
The cells that have undergone apoptosis, or programmed cells death are disposed of by
nonprofessional phagocytes. (Rabinovitch 1995).
CELLS OF THE IMMUNE SYSTEM
CELLS OF THE IMMUNE SYSTEM: PHAGOCYTES
Mononuclear cells
Mononuclear phagocytes are the most important group of long-lived phagocytic cells.
They are circulate in blood flow as monocytes (Takahashi 2000). Migration of these
cells from bloodstream into the tissues initiate the development of tissue macrophages
CELLS OF THE IMMUNE SYSTEM: PHAGOCYTES
Polymorphonuclear cells
The name of polymorphonuclear is generated from the common appearance of a lot of nuclei
attached. Normally, the term polymorphonuclear leukocyte often refers to neutrophil
granulocytes. The other types are eosinophils, basophils and mast cells
A. Neutrophils
Neutrophils which constitute around 70% of all blood leukocytes are the most numerous blood
leukocytes. They are the first leukocytes displayed on the site of infection with significant
antimicrobial weapon.
Neutrophils contain two types of granules:
• primary granules (lysosomes, myeloperoxidase, hydrolases)
• secondary granules (lactoferrin, collagenase).
CELLS OF THE IMMUNE SYSTEM: PHAGOCYTES
B. Eosinophil
Eosinophils are another types of granulocytes, they can engulf bacteria but they do
so weakly and inadequate to protect against bacterial infections in neutrophenic
patients. These are specialized group of leukocytes which are able to engage and
destroy large extracellular parasites (Peakman & Vergani 2009). They account in
higher numbers in two types of diseases, which include hypersensitivity diseases, such
as asthma and serum sickness and parasitic diseases, especially those caused by
nematodes.
CELLS OF THE IMMUNE SYSTEM: PHAGOCYTES
C. Basophils and mast cells
Basophils are similar to mast cells, but they are placed in different location. Basophils
circulating in the bloodstream, meanwhile mast cells are located close to the blood
vessels in all tissues, especially under the skin and in the mucosa of gastrointestinal
tract and respiratory tract (Levinson 2012). They have receptors on the cell surface
for the Fc portion of IgE heavy chain
CELLS OF THE IMMUNE SYSTEM: LYMPHOCYTES
Lymphocytes

Lymphocytes are cells that are most responsible for specific immune recognition of
pathogens, so they initiate the adaptive immune response. All lymphocytes are
originated in the bone marrow stem cells, but then they mature in different places. B
lymphocytes mature in the bone marrow, whereas T-cells mature in thymus gland
CELLS OF THE IMMUNE SYSTEM: LYMPHOCYTES
T cells

T cells account approximately 65 to 80% of all small lymphocytes and predominate

in the thymic medulla, tonsils and blood. They can be divided after stimulation by
certain mitogen, such as phytohemagglutinin or concanavalin A.
T cells are subdivided into two distinct lineages that can be differentiate by their
expression of CD4 or CD8 proteins on their surface:
Th (CD4)
Tc (CD8)
CELLS OF THE IMMUNE SYSTEM: LYMPHOCYTES
Th (CD4)

Functions of CD4 T cells:

Helper T cells are arguably the most important cells in adaptive immunity, as they are
required for almost all adaptive immune responses. They not only help activate B cells
to secrete antibodies and macrophages to destroy ingested microbes, but they also
help activate cytotoxic T cells to kill infected target cells.
CD4 T cells perform its functions by four subpopulations of CD4 T cells:
Th-1, Th-2, Th-17 and CD4 T regulatory (Treg) cells
CELLS OF THE IMMUNE SYSTEM: LYMPHOCYTES
Tc (CD8)

cytotoxic CD8-T cells, which play cytotoxic functions such as killing virus-infected
tumor cells, cancer cells and transplanted tissues by releasing perforins, which destroy
cell membranes, or induce apoptosis. CD8 cells predominate in human bone marrow
and gut lymphoid tissue and consist about 35% of peripheral T cells
CELLS OF THE IMMUNE SYSTEM: LYMPHOCYTES
Types of T Cells
Cytotoxic T lymphocytes (CTL or Tc cell) - they are part of cell mediated immunity and perform cell killing effects(cytotoxic).
They usually target and illicit immune effector response against the self altered cells like virus or bacterial infected cells or
cancerous cells.
Helper T cells(Th cells) - they secrete low molecular weight cytokine proteins which have a regulatory function.They activate B
cells to produce antibodies,also activate macrophages and Tc cells to perform their function. They too have many subsets like
Th1,Th2,Th17 and Tfh(follicular helper cells) according to their assigned functions of regulation.
Suppressor T cells - they have role in immune tolerance.This means that they stop the function of Tc cells at the end of immune
response (works like a brake) and also suppress autoreactive T cells. This suppressor cells along with T helper cells form T
regulatory cells(Treg).
Memory T cells - they are the subset of both antigen specific Tc and Th cells which are “antigen experienced” and thus
remains for long term even after the infection is treated. They convert into effector cells when the particular infection strikes
again.
Natural killer T cells(NKT cells) - they are the link between innate and acquired immune system. They share both properties
of T cells and NK cells and perform similar function.
Some other special types of T cells include Mucosal associated invariant T cells (MAITs) and gamma Delta T cells
CELLS OF THE IMMUNE SYSTEM: LYMPHOCYTES
B cells
 B cells are responsible for humoral immunity and also known as “antibody
factories”.
After recognition of a specific antigen, B cells proliferate and differentiate into
plasma cells, which release a large number of receptor molecules in soluble form that can be secreted
which is known as antibodies (Roitt et al. 2001).
Some activated B cells forming memory cells, which can remain silent for long times but can be
activated immediately after re-exposure to antigen. In addition to produce antibodies, B cells also
have another important function to present antigen to helper T cells (Levinson 2012).
CELLS OF THE IMMUNE SYSTEM: LYMPHOCYTES
Natural killer (NK) cells

NK cells account approximately 5 to 10% of peripheral of blood lymphocytes, which

express CD16 and CD56. They are large granular lymphocytes, which are found in
lymph nodes but they are most abundant in the blood, spleen and liver. NK cells are
active without prior exposure to the virus, hence they are called as “natural” killer.
They can destroy antigen without antibody, but antibody (Ig) enhances their
effecttivenes.
 HUMORAL COMPONENTS OF THE IMMUNE SYSTEM

Complements
The complement system which consist about 30 serums proteins can be activated through several pathway.
o the alternative pathway, which is activated by a number of microorganisms spontaneuosly;
othe classical pathway, which is activated by certain antibodies bound to the pathogen surface (Chapel et al.
2006).
oThe lectin pathway is activated by the binding of plasma mannose-binding lectin (MBL) to mannose residues
in microbial proteins and polysaccharides but not in mammalian molecules
These activation generates peptide fragments which have several functions which includes opsonization of
microbes, attraction of phagocytes to sites of infection and release of further inflammatory mediators from
mast cells (Roitt et al. 2001).
Although the complement system is activated by different pathway, all of them lead to the generation of
enzyme complexes which can cleavage the third complement (C) protein C3 (Chapel et al. 2006).
HUMORAL COMPONENTS OF THE IMMUNE SYSTEM

Complement triggers the following immune functions:

Phagocytosis – by opsonizing antigens. C3b has most important opsonizing activity
Inflammation – by attracting macrophages and neutrophils
Membrane attack – by rupturing cell wall of bacteria
HUMORAL COMPONENTS OF THE IMMUNE SYSTEM

Cytokines

Cytokine is a large group of molecule which involve in signalling process between cells during immune
responses (Roitt et al. 2001).
Cytokines perform their function through the interaction with cytokine receptors that can be grouped in several
distinct families (Zidek et al. 2009).
Cytokines can be derived from any cell such as lymphocytes and monocytes/macrophages:
Cytokines which are generated from lymphocytes are called lymphokines,
monokines are cytokines produced by macrophages.
Functions:
Initially, cytokines were believed to act mainly as antiviral or antineoplastic agents. Nowadays, they are known
to be crucial to innate and adaptive immunity, cell growth and diferentiation (Spelman et al. 2006). They also
affect hematopoietic, inflammation, immediate hypersensitivities and regulate lymphocyte activities as well as
distinct population of Th cells.
HUMORAL COMPONENTS OF THE IMMUNE SYSTEM

The principal sets of cytokines are outlined below:

Interferon (IFNs).
There are several types of IFNs, i.e. IFNα, IFNβ and IFNγ which play essential role in
limiting the spread of certain viral infections by become the first line of resistance to
many viruses and being produced very early in infection.
They can be produced by cells which have become virally infected (IFNα and IFNβ)
or can released by certain activated T cells (IFNγ) (Roitt et al. 2001).
HUMORAL COMPONENTS OF THE IMMUNE SYSTEM
HUMORAL COMPONENTS OF THE IMMUNE SYSTEM

Interleukins (ILs). This is a large group of cytokines, range from IL-1 to IL-22, which have various
function, but mostly, they are involved in directing other cells to divide and differentiate. They can
be produced by T cells, mononuclear phagocytes or by tissue cells (Roitt et al. 2001).

Chemokines is a group of cytokines that attract phagocytes from the blood stream into the site of
infection (Roitt et al. 2001).

Colony-stimulating factors (CSFs) is a group of cytokines which mainly involved in differentiation of

bone-marrow stem cells and the precusors of blood leukocytes (Roitt et al. 2001).

Tumor necrosis factor (TNF) and transforming growth factor-β (TGB- β). TNF is a multipotent
cytokine which plays important role in apoptosis, cell activation, cell recruitment and differentiation.
It also increases the phagocytic ability of macrophages (Ehlers 2003; Nair et al. 2006).
 HUMORAL COMPONENTS OF THE IMMUNE SYSTEM

Antibody
Antibodies are a group of glycoproteins which are
present in serum, as well as in almost all physiological
fluids of vertebrates, as immunoglobulins (Igs).
The simplest structure of an immunoglobulin molecule
consists of two identical short polypeptide chains, the
light chains, and two identical long polypeptidechains,
the heavy chains, interconnected by several disulfide
bonds.
All antibodies consist of either κ or λ light chain
polypeptides; however, within a single antibody
molecule only one type of light chainpolypeptide
occurs.
HUMORAL COMPONENTS OF THE IMMUNE SYSTEM

Antibodies can be divided into several classes.

In humans, antibodies consist of five classes:
immunoglobulin A (IgA), immunoglobulin D
(IgD), immunoglobulin E (IgE), immunoglobulin G
(IgG), and immunoglobulin M (IgM)

The five classes of antibodies differ from each

other in the heavy chains of immunoglobulin
molecules;
for IgA, IgD, IgE, IgG, and IgM the heavy chains are α, δ,
ε, γ, and μ,
HUMORAL COMPONENTS OF THE IMMUNE SYSTEM
HUMORAL COMPONENTS OF THE IMMUNE SYSTEM

Immunoglobulin A: Immunoglobulin A, IgA, is the major secretory antibody. It is

present in dimeric form in almost all physiological fluids such as tears, saliva,
gastrointestinal fluids, milk, and other mucus fluids.
The two monomeric IgA immunoglobulin molecules are held together by a
polypeptide J chain and wrapped by a polypeptide called secretory component
(SC). SC is a portion of the IgA-receptor structure on the surface of epithelial cells
involving the secretion of this antibody. IgA is the most important antibody in mucosal
immunity. As a secreted antibody in mucosal fluids, IgA can neutralize microorganisms
and toxins before those pathogens can enter into or cross epithelia.
Furthermore, IgA in the milk can provide neonatal immunity.
HUMORAL COMPONENTS OF THE IMMUNE SYSTEM

Immunoglobulin D: IgD is found predominantly on the surface of B cells. It is present in serum with
very low concentrations (<0.1 mg/ml) and short durations (half-life <3 days). The role of IgD in the
immune response is not clear, except that it binds antigen molecules on the cell surface to stimulate
the activation of the B cells.
Immunoglobulin E: IgE is found almost exclusively on the surface of mast cells. Upon binding to
antigen molecule, IgE can cross-link with each other on the surface of the mast cell and stimulate the
release of many allergic mediaters.
Immunoglobulin G: IgG is the most predominant immunoglobulin in the serum. Normal serum contains
approximately 15 mg/ml of IgG, which is about 75% of total serum immunoglobulin.
IgG also possesses the longest half-life of all classes of immunoglobulin in the blood, i.e., 3 weeks.
IgG is capable of crossing the placenta and the immature intestinal epithelium to provide immunity
to the fetus and the newborn infant.
IgG is the most important antibody in the serosal immunity. IgG has a high affinity to the antigen and
IgG-antigen complexes can be recognized by complement factors and by Fc-receptors on the surface of
phagocytes. In both cases, IgG binding leads to the elimination of antigen-bearing cells.
HUMORAL COMPONENTS OF THE IMMUNE SYSTEM

Immunoglobulin M: IgM exists in the blood as a pentamer, and in some cases, as a hexamer.
Monomeric IgM is present on the surface of B cells.
IgM is the first antibody produced by the fetus and is also the first antibody to respond when
presented with a new antigen challenge.
In the primary response against a new antigen, the appearance of IgM in the blood precedes
that of IgG. The production of IgM decreases when the production of IgG increases.
Therefore, IgM in the serum amounts only about 1.5 mg/mL with a half-life in the blood of less
than a week.