Unit IV: Introduction to Immunology and Immune Response

General principles and practice of Immunology

Basic Principles of Immunity
Immunity is the term used to describe the defenses of the body that offer protection against foreign
pathogens, called antigens. The immune system allows an organism to respond to noninfectious
and inflammatory stimuli while it maintains a balance of reactive and counteractive responses
between the host and its surroundings. The immune system may be incompetent either because of
a failure to recognize antigens or a failure to respond effectively. When either of these
inappropriate responses occurs, the host succumbs to infection. On the other hand, when the
immune system is overactive, the protective mechanisms act in a detrimental manner, as in the
case of autoimmune diseases.
The immune system is composed of two functional components: the innate and the acquired
immune systems. The innate system requires no external stimuli to initiate a response and is
believed by some to have evolved in multicellular organisms as a way to reduce the sequelae of
established infection. By contrast, the inception of the acquired system occurs at the time of
pathogen detection and is highly specific for the microbial antigen.
A healthy immune system possesses four key qualities:
(1) the capacity to detect and fight off potential infections;
(2) the ability to recognize the host’s own cells as “self”;
(3) a retained memory from previous attacks; and
(4) the ability to limit its responses after removing the offending agent.
The cells and organs of the immune system are specifically designed to patrol the host for potential
sources of infection, recognize the challenge, and mount a counterattack. Not surprisingly, there
is a preponderance of immune cells at the most likely points of entry of invading organisms: the
skin and gastrointestinal tract. Once a challenge is detected, cellular signaling enables immune
cells to initiate, coordinate, and govern an appropriate response. All immune cells have a
tremendous capacity to communicate with each other through chemical mediators called
cytokines. Depending on the type of infection detected by the surveying cells, various amounts of
different cytokines are produced, which then change the nature of the response. In this regard, the
immune system can tailor its response according to the infection detected. Once the signals are
relayed, the immune system has immense capacity to attract effector cells to kill the offending
agent. This attack involves release of chemical stressors placed on the agent, neutralization of its
noxious properties, ingestion of the agent by the immune cells, or even mechanical disruption of
the cellular integrity of the agent.
Integrated into the ability to fight off infection is the ability of the competent immune system to
distinguish self from nonself. This attribute prevents the host’s own defenses from attacking the
very body it is designed to protect. Each cell within the body (with the exception of red blood
cells) has a molecule on its surface known as the major histocompatibility complex I (MHC I).
Except for identical twins, no two humans have exactly the same MHC I molecules. Immune cells
recognize the specific MHC I molecules as “self” and do not attack it. This fact not only keeps
cells of the immune system from attacking the host’s own tissue but also explains the biologic
phenomenon of rejection of transplanted organs, which have different MHC molecules.
The memory of the immune system enables an organism to mount an attack against pathogens
years after primary exposure, a trait that is exploited with vaccinations. Without this, each new
exposure would need the generation and proliferation of a completely new response tailored to the
stimulus. Instead, the body stores its responders in small quantities, and when an antigen is
reencountered, that specific antibody is called back and multiplied. Often, the reactivation or
secondary response is more intense than the initial one.
Last, the immune system needs to be self-limited and should be extinguished after the offending
agent is cleared. This aspect of immunology has recently been explored, and it is now thought that
a sustained overactive response to an inflammatory challenge results in the multiorgan failure and
even death that is seen following severe trauma, infection, or burn injury. In fact, it may be that
the body’s ability to limit the infection response is as important as the ability to mount the attack
in the first place.

Types of Immunity

The defense mechanisms of the body are complex. Despite constant microbial challenge from the
environment, the body prevents infections by a number of non-specific and specific mechanisms
working on their own or together (Figure 1).
 Figure 1

Nonspecific defense mechanisms

Innate or nonspecific immunity offers basic protection to disease and is composed of anatomic,
chemical, mechanical, and cellular barriers. It is not stimulated through exposure to a foreign
antigen but rather is always present and functioning. Nonspecific defense mechanisms are present
in all normal individuals. They are effective at birth and function without requiring prior exposure
to a microorganism or its antigens. They include physical barriers (e.g. intact skin and mucous
membranes), chemical barriers (e.g. gastric acid, digestive enzymes, bacteriostatic fatty acids of
the skin), phagocytic cells, and the complement system. The complement system contains several
enzymes and consists of at least 19 separate serum proteins. Complement plays a major role in
initiating the inflammatory response, clearing immune complexes, modulating immunoglobulin
production, opsonizing microbial pathogens, and killing certain gram-negative bacteria.
Specific immunity

In contrast to nonspecific defense mechanisms, specific immune defense systems are not effective
fully at birth and require time to develop after exposure to the infecting agent or its antigens.

Specific immunity may be acquired naturally by infection or artificially by immunization. Specific

immunity is divided into antibody-mediated and cell-mediated components. Reactions carried out
by antibodies are called humoral immune reactions. The most convenient indicator of immunity is
antibody, as antibodies are the best known of the many products of the immune system.

Antibody mediated immunity is related to B lymphocytes (or B cells), and to their direct
descendents, known as plasma cells. The plasma cells produce immunoglobulins (antibodies).
When a B cell encounters an antigen, recognized by the antibody expressed on the antigen’s
surface, the B cell is stimulated to proliferate. This leads to expansion of the number of
lymphocytes capable of secreting antibody to this antigen. Replication and differentiation of B
cells into plasma cells is regulated by contact with antigen and by interactions with T cells,
macrophages, and complement.

B lymphocytes develop in fetal liver and subsequently in bone marrow. The name “B” cell comes
from the bursa of Fabricius, a specialized organ in birds that acts as a site of B cell development.
Mammals do not possess this organ. Approximately 10% of the blood lymphocytes are B cells;
most B cells and almost all plasma cells reside in peripheral lymphoid organs, e.g. the spleen,
lymph nodes, tonsils and appendix.

Cell-mediated immunity is conferred by T lymphocytes and effected by lymphocytes and

macrophages. It involves the function of T lymphocytes (T cells) of various types and their soluble
products, lymphokines (interleukins), that act as signals for communication between different
types of cells involved in an immune response. These two components of specific immunity are
closely related to each other. T cells interact with B cells in the production of antibody against
most antigens. Specific antibodies and CMI are induced in all infections, but the magnitude and
quality of these two components varies in different infections.
Organs and Cells of the Immune System
Biologic structure dictates that cells work together to form tissue, tissues work together to form an
organ, and organs work together to form a system. For example, several types of alveolar epithelial
cells work together to form alveoli (the air exchanging portions of the lung). Alveoli coordinate to
form a functioning lung, and the lungs, together with the trachea and pharynx, form the respiratory
system. By contrast, the immune system is not physically distinct. Most of the pathogen-fighting
function of the immune system is accomplished by specific types of white blood cells known as
lymphocytes, either as individual cells or as aggregates of immune system tissue known as
lymphoid tissue. Although many lymphocytes circulate throughout the body, others are kept
separate from circulating blood or have translocated outside of the blood vessels. Several organs
and other aggregates of lymphoid tissue are needed for the genesis, development, and preservation
of these circulating effector cells.

Tissues and Organs of the Immune System

Lymphoid tissue can broadly be classified into generative and peripheral organs. The generative
or primary lymphoid organs, in which lymphocytes develop, are the bone marrow and thymus (fig.
2). The peripheral immune organs include the lymph nodes, spleen, mucosa-associated lymphoid
tissue, and the cutaneous immune system.
These aggregates of tissue respond when “effector” cells detect a foreign antigen and “present”
or “show” it to cells within a lymphoid organ. It is then that the body can mount a very specialized
and specific response to that pathogen.
Cells of the Immune System
The cells of the immune system circulate through the body from the lymphatic spaces and the skin
to the blood and lymphoid organs. This anatomic organization allows the effector cells (the
lymphocytes) to interact with antigens on any front and mount an immune response rapidly.
However, no rapid response could exist without the effector cells, the lymphocytes. There
normally are 5000 to 10,000 white blood cells per milliliter of circulating whole blood, and
lymphocytes normally constitute 20% to 40% of the total white blood cell population.
Figure 2: In adult life, hematopoiesis takes place within the bone marrow. Stem cells are pluripotent
cells that are capable of differentiating into any other cell type. The functional mature immune cells
arise from stem cells that differentiate into one of two cell lines: myeloid or lymphoid. Lymphoid
cells give rise to T or B cells and memory cells and plasma cells. Myeloid cells give rise to
erythrocytes, platelets, monocytes, and granulocytes. CTL, cytotoxic T cell; TH, T helper cell; Tc, T
cytotoxic cell.

They may be divided into three groups: B cells, T cells, and null cells. B cells mature within the
bone marrow and, when presented with a foreign antigen, express a binding receptor on the surface
that is specific for a particular region of this antigen. These receptors, called antibodies (Fig. 3),
are membrane-bound glycoproteins that recognize and bind antigens.

Figure 3: Immunoglobulins are composed of 2 light chains and 2 heavy chains. The constant portion (Fc)
anchors the antibody, whereas the variable portion (Fab) is complementary to the offending antigen.

Once antigen-antibody binding occurs, the B cell proliferates into memory cells and plasma cells.
Memory cells circulate for years, carrying the same specificity for the particular antigen as the
parent B cell. On the other hand, plasma cells produce antibody to be released into circulation.
Plasma cells have a much shorter life span than the memory cell, yet each plasma cell is capable
of producing enormous quantities of antibodies.