Cell Biology 2018

Immune system

1. Immune system responses

Pathogens come in inconceivable numbers and kinds, such as bacteria,
viruses and parasites. If these are not neutralized quickly, these rapidly
dividing organisms will kill us. Our immune system consists of 3
successive lines of defense:
1. An external, non-specific defense by skin and mucous membranes.
2. A fast, internal, innate, non-specific defense by two kinds of white
blood cells or leukocytes: the phagocytes and the “natural killer” (NK)
cells. Phagocytes (macrophages and granulocytes) render bacteria
harmless by phagocytosis and NK cells kill infected cells.
3. A slow, specific response is performed by T-lymphocytes through a
cellular defense (rendering infected cells harmless) and by B-
lymphocytes that produce antibodies (humoral response). After the
infection, resistance against the specific pathogen is higher (memory).

Table 1 Immune system classification

Innate (non-specific) immunity Adaptive (specific) immunity
1st line external 2nd line internal 3rd line internal
1. Defense against classes of 1. Defense against 1 specific
pathogens pathogen
2. Fast, within hours after 2. Slow, rises a week after
infection infection

An immunological response is triggered by an antigen. Antigens are

defined as compounds capable of inducing an immunological reaction by
the body. Almost always antigens are foreign, i.e. compounds that cannot
be found anywhere in the body. Often, they are pathogens.

1.2 Innate, non-specific defense

Innate immunity plays an important role in subduing an infection. White
blood cells that play a role in this kind of defense, are not directed against
one specific compound or organism, but react to a broad spectrum of
foreign molecules (they recognize classes of pathogens). To be able to do
so, they have a number of different receptors in their membrane. These
receptors act as sensors and react with molecular patterns specific for
pathogens such as bacteria and viruses (these patterns can be certain
sugars or proteins specific for bacterial membranes, specific lipoproteins
or nucleic acid patterns specific for viruses). Different types of cells
contribute to the non-specific defense: macrophages, granulocytes,
and activated 'natural killer cells'. Upon recognition, the phagocytize
and/or kill the intruders. Innate immunity is not only important for
phagocytosis and killing of intruders, but it also plays a key role in
activating and controlling the organism's specific defense mechanisms.

Page 1 of 3
 Cell Biology 2018

1.3 Adaptive, specific defense

The humoral defense consists of
protective factors, the so-called
antibodies, also known as
immunoglobulins. These are
proteins dissolved in the bodily fluids
(blood, lymph fluid, tissue fluids).
They are produced by B-lymphocytes
that differentiate into antibody-
producing plasma cells able to react
with a specific pathogen. Check your
book 'Essential Cell Biology'
Figure 1.1 The organs essential to the pages 143, 146 and 147 to see
immune system
how antibodies are produced and
their mechanism of action.

In addition to B-lymphocytes, T-lymphocytes are part of the specific

defense system as well. T-lymphocytes differentiate within the thymus.
When a T-lymphocyte contacts a foreign antigen, it is activated and starts
dividing producing three kinds of lymphocytes: T helper cells (Th-cells)
(fig. 1.2) as well as T suppressor cells and cytotoxic T lymphocytes (Tc-
cells). T-helper cells activate B-lymphocytes by producing signaling
molecules, the cytokines. T suppressor cells suppress production of
antibodies in plasma cells. Cytotoxic T lymphocytes destroy the membrane
of a cell infected by a bacterium or a virus (through contact dependent
communication) thereby causing the infected cell to die (this is a specific
cellular response).
How does a cytotoxic T lymphocyte know what or where to attack
and when to abstain from attacking? This is because a special safety
system has been incorporated in all cells: this system is called the Major
Histocompatibility Complex (MHC), also known as the Human Leukocyte
Antigen (HLA). At the molecular level, this system certifies body cells as
being 'self'. Everything that, according to the immune system, does not
carry these MHC molecules, is considered 'non-self' and will be attacked
mercilessly. They ensure that cells infected by foreign intruders are
detected so they can be removed by T-lymphocytes.
How does a T-helper cell function? Special types of macrophages
phagocytize intruders and couple small peptides (antigens) of these
intruders to the MHC-II molecule that is presented on the outside of the
phagocyte. In the lymph nodes or lymph glands the surface of a
phagocyte is scanned by T helper-cells. When a T helper cell has a
receptor specific for the presented (bacterial) antigen bound to a MHC-II
molecule, receptor and antigen will bind, which results in activation of the
T helper cell. This produces a clone of specific T helper cells (all of which
contain the receptor specific for the peptide fragment), which in turn

Page 2 of 3
 Cell Biology 2018

induce specific B-lymphocytes to start dividing and generate antibody-

producing plasma cells (fig. 1.2).

Figure 1.2 Central role of macrophages and T helper cells in activation of the humoral immune
response.
In the lymph nodes, the surface area of a phagocyte such as a macrophage, is scanned by T
lymphocytes. If a T-lymphocyte with a proper receptor recognizes a specific bacterial antigen, it will
bind. This activates the T-lymphocyte, which will start dividing, thereby producing a T-lymphocyte
clone. Subsequently, differentiation generates activated T-lymphocytes that will activate B-
lymphocytes. For this they use cytokines, locally acting signaling molecules, which induce B
lymphocytes to start dividing and become plasma cells, which in turn will generate antibodies. These
antibodies are able to bind to the antigen, rendering it harmless.

6.2.4 Intercellular communication

An precise differentiation process is continuously active. This is only
possible with a logistical system that functions extremely well. Obviously,
this system depends to a great extent on accurate, specific
communication between the various kinds of cells and on perfect timing.
Cells achieve this by using signaling molecules, the so-called cytokines,
which initiate intracellular cascades by way of specific receptors (week 4).

Page 3 of 3