L2: CELLS INVOLVED IN

THE IMMUNE RESPONSE

IMMUNOLOGY
MEL 1224


Lymphoid cells classes and subclasses

Biology of B and T lymphocytes

T and B cells cooperation.

Mononuclear phagocytic system and
Polymorphs.

Cytokines

Immune cells involved in the

Innate Immune system
Consist of:
 Polymorphonuclear (PMN) leukocytes
 Macrophages
 Dendritic cells
 Natural Killer cells

PMN LEUKOCYTES
Also known as granulocytes.
Including basophils, mast cells, eosinophils,
and neutrohils.
These are phagocytic cells that contain
enzyme-rich lysosomes, which facilitate
destruction of infectious microorganisms.
Granulocytes are short-lived, and played an
major role in protection against infection.

MACROPHAGES
Macrophages are phagocytes which derived
from monocytes.
Example of macrophages:
 Kupffer cells (Liver)
 Alveolar macrophages (Lung)
 Peritoneal macrophages
(white pulp of the spleen)
 Microglial cells (CNS)

 Although associated with diverse names and

locations, these macrophages shared some
common features:
 Phagocytize microorgansisms and foreign
substances that invade the bloodstream and
various tissue.
 These cells are most likely to make the first
contact with invading pathogens and
antigens.

DENDRITIC CELLS
They are long-lived and reside in an immature
state in most tissues.
Dendritic cells can be found as interdigitating
cells of thymus. Besides, they can also be
found in the skin, called Langerhans cells.
They are capable of recognizing and
phagocytize pathogens and other antigens.
Besides, direct contact will pathogens also
leads to the maturation of the dendritic cells,
forming APC.

NATURAL KILLER CELLS

Natural killer (NK)cells are cytotoxic, plays an
important role in the early stages of viral
infection or tumorigenesis before activation of
T-cells.
Unlike cytotoxic T lymphocytes which
recognize target cells in an antigen-specific
manner, NK cells lack antigen-specific
receptors.
NK cells kill potential target by determining its
MHC class I molecules (less specific)

Immune response in Innate

immunity

 Endocytosis and Phagocytosis

 Inflammation
 Killing activity of the NK-cell

ENDOCYTOSIS
Endocytosis is the ingestion of
macromolecules present in extracellular fluid
by cells.
Endocytosis can occur by:
Pinocytosis
receptor mediated endocytosis

 Pinocytosis involves only non-specific

membrane invagination.
Receptor mediated endocytosis is a process
involving selective binding of macromolecules
to the specific membrane receptors.
In both cases, endocytic vesicle is generated
which later fused with endosomes (acidic
compartments) and lysosomes (degradative
enzymes).

PHAGOCYTOSIS
Phagocytosis is the ingestion of invading
foreign individual cells such as bacteria.
It is a critical protective mechanism of the
immune system.
Phagocytic cells can detect the bacteria by:
Substances released
Opsonins (factors that make the bacteria an
easier target, eg: Ab, complement protein.)

 After ingestion, the bacteria is entrapped in

phagosome, which then fuse with lysosome
forming phagolysosomes.
The powerful enzyme in phagolysosome then
digest the bacteria.

INFLAMMATION
Damage to tissue by a physical injury (cut) or
by the entry of microorganisms triggers a
localized inflammatory response
(inflammation)
A series of events occurred (refer to the
diagram), causing the characterisitc of
inflammation: redness, edema, heat.

 Chemotactic factors are released from

pathogens, whereas chemokines are
secreted by the endothelial cells of blood
vessels and monocytes.

KILLING ACTIVITY OF THE NK CELL

As mentioned previously, NK cells kill
potential target by determining its MHC class
I molecules.
MHC class I molecules are expressed on all
normal nucleated cells.
NK cells possess receptors called killer-cell
inhibitory receptors (KIRs) which bind to
MHC class I molecules expressed on normal
cells.

 When KIRs bind to MHC class I molecules,

intracellular signals are generated and NK
cell is inhibited to destruct the target cells.
Virus-infected or transformed cells (tumour)
have significantly reduced or absent of MHC
class I molecules.
Thus, when such cells encounter NK cells,
the fail to binds with KIRs and NK-cells are
activated to destroy the target cells

Immune Cells involved in the

Adaptive Immune system
Consist of:
 B-lymphocytes
 T-lymphocytes

Development of B and T
lymphocytes
Both B-lymphocytes and T-lymphocytes are
produced in bone marrow, originating from a
common lymphoid progenitor.
B cells differentiate and mature within the
bone marrow.
In contrast, T cells differentiate only partially
within bone marrow. It undergo final
maturation within the thymus gland (primary
lymphoid organ).

 Mature B and T cells migrate through the

bloodstream and lymphatic system to the
peripheral lymphoid tissue, which is also
known as secondary lymphoid organ.
Eg of secondary lympoihd organ:
 Lymph nodes (major)
 Spleen (major)
 Tonsils
 Peyers patches

 The secondary lymphoid organs have two

major function:
 They are highly efficient in trapping and
concentrating foreign substances
 The are the main sites of production of
antibodies and induction of antigen-specific
T lymphocytes.

Circulation of lymph and fate of

antigen after penetration through:

Blood stream

Skin

GI tract or
respiratory
tract

Immune response in Adaptive

immunity
In cell-mediated immunity:
 Helper T- cells (TH)
 Cytotoxic T- cells (TC)

What is MHC molecules?

They are cell surface glycoproteins
There are 2 main types of MHC molecules:
 MHC class I
(can be found on almost all nucleated body
cells)
 MHC class II
(can be found on specialized cell types eg:
macrophages, B cells, activated T-cells, etc.)

 In immune response, MHC molecules

function display the antigen fragments
present in the infected cells on cell surface,
forming Antigen Presenting Cells.
TH have receptors that bind to antigen
fragments displayed by MHC Class II
molecule .
Tc have receptors that bind to antigen
fragments displayed by MHC Class I
molecule .

Function of Helper T-Cell in both CELLMEDIATED and HUMORAL immune

response

1. Macrophages engulf a bacterium and

transports the fragment to the cell surface and
displayed by MHC class II molecule, forming
APC.
2. A specific TH cell is activated by binding to
the MHC-antigen complex.
3. The activated TH cell proliferates, giving rise
to a clone of identical cells . These cells
secrete cytokines.
4. The cytokines further stimulate the TH cells
and also help activate B cells and TC cells.

Function of Cytotoxic T-Cell in cell-mediated

immune response

1. An infected cell (or cancer cell) displays an

antigen fragment on its surface by MHC class
I molecule.
2. A specific TC cell is activated by binding to
the MHC-antigen complex.
3. The activated TC cell discharges perforin
molecules, which function to create pores in
the membrane of the infected cells
4. Water and ions flow into the infected cell, and
the cell lyses.

Cytokines
History of Cytokines
The activity of cytokines was first discovered
in 1960s.
At that time, cytokines was believed to be
present with the presence of antigen, to
elevated the proliferative responses of T-cells
Soon afterward, it was determined that this
factor was produced by T cells, and also by
monocytes and macrophages.

 Several names were given to cytokines

produced by different cells.
For example:
 T-cell growth factor (TCGF)
 Lymphocyte-activating Factor (LAF)
 Lymphokines
 Interleukins (IL)
 Interferon (IFN)
 Monokines (monocytes and macrophages)
 Chemokines
 Tumour Necrosis Factor (TNF)

GENERAL PROPERTIES OF CYTOKINES

Most cytokines have very short half lives.
Cytokines facilitate communication between
cells at very low concentrations
Cytokines may act:
 Locally
(autocrine; paracrine)
 Systematically
(endocrine)

 Autocrine: act on
the same cell that
secreted it
Paracrine: act on
other cells
Endocrine:
systematically

General properties of Cytokines

Cytokines exert their functional effects by
binding to specific receptor on target cells.
Hence, the target cell must be expressing the
receptor for cytokines.
The response of the target cell depends on the
quantity and the type of cytokines which it is
exposed to.
Some cytokines behave antagonistically:
inhibiting each others action on a target cell.

CATEGORIES AND FUNCTIONS OF

CYTOKINES
Cytokines can be divide into:
 Cytokines that faciliate innate immune
responses
 Cytokines that promote inflammatory
responses
 Cytokines that regulate adaptive immune
responses
 Cytokines that affect leukocyte movement
 Etc.

 Cytokines that faciliate innate immune

responses
 Eg: IL-1, IL-6, TNF-
 They are produced by phagocytes, and are
capable of causing fever, promoting
inflammation, enhancing phagocytosis
(opsonin)
 Elevated body temperature is beneficial to
host defenses: pathogens grow less
efficiently at raised temperature, intensing
adaptive immune responses.

 Cytokines that promote inflammatory

responses
 Eg: IL-1, IL-6, IL-23, TNF-
 They cause increased vascular
permeability, leading to swelling and
redness associated with inflammation.

 Cytokines that regulate adaptive immune

responses.
 Eg: IL-1, IL-2
 Depending on the cytokines involved, the
regulation can be positive or negative.
 Ultimately, cytokines regulate the intensity
and duration of immune responses.
 Cytokines tend to act on antigen-activated
lymphocytes .

 Cytokines that affect leukocyte movement.

 Chemokines: attractors for various
leukocytes.
 Eg: IL-8
 IL-8 is produced by macrophages, T-cell,
etc.
 It activates and attracts neutrophils to the
site of tissue, promoting inflammatory
response and wound healing.

ROLES OF CYTOKINES AND CYTOKINE

RECEPTORS IN DISEASE
Cytokines have complex regulatory properties.
Hence, over-expression or under-expression
of cytokines or cytokine receptors have been
implicated in many disease:







Toxic-shock syndrome
Bacterial septic shock
Cancers (Follicular lymphoma)
Autoimmunity (SLE)
Asthma