DENDRITIC CELLS

Dendritic cells are antigenpresenting cells that are located in tissues, and can contact external
environments through the skin, the inner mucosal lining of the nose, lungs, stomach, and intestines.
Since dendritic cells are located in tissues that are common points for initial infection, they can identify
threats and act as messengers for the rest of the immune system by antigen presentation. Dendritic cells
also act as bridge between the innate immune system and t he adaptive immune system

Since DCs have numerous cytoplasmic processes, they have a high surface area permitting intimate
contact with a large number of surrounding cells, e.g. T cells, natural killer cells, neutrophils, epithelial
cells etc

The dendritic cells in these tissues can exist as either mature cells or immature cells. The immature
dendritic cells undergo maturation in the presence of either antigens or cytokines or pathogen-
associated molecular patterns (PAMPs). Maturation of such cells activates the metabolic, cellular, and
gene transcription of the cells, causing the cells to migrate from peripheral tissues to T-dependent areas
in lymphoid organs. The process of maturation causes the loss of adhesive structures, reorganization of
the cytoskeleton, and increase in motility. It also leads to a decrease in their endocytic activity and an
increased expression of MHC-II and costimulatory molecules.

Four major types of dendritic cells are

Plasmacytoid DCs

Conventional DCs

Migratory DCs

Monocyte-DCs

MACROPHAGES

Macrophages are efficient phagocytic cells that can leave the circulatory system by moving across the
walls of capillary vessels. The ability to roam outside of the circulatory system is important, because it
allows macrophages to hunt pathogens with less limits. Macrophages can also release cytokines in order
to signal and recruit other cells to an area with pathogens.

Macrophages are a type of white blood cell that play an important role in the human immune system
and carry out various functions including engulfing and digesting microorganisms; clearing out debris
and dead cells; and stimulating other cells involved in immune function. Macrophages confer innate
immunity, which is typically the first line of defense against foreign antigens. Adaptive immunity, on the
other hand, is the subtype of the immune system that involves specialized immune cells and antibodies.
In addition to having an immune role, macrophages also secrete anti-inflammatory cytokines (i.e., small
signaling proteins) and help mediate reparative processes.
Macrophages form from monocytes, which themselves derive from the bone marrow. Monocytes
circulate through the blood for one to three days before migrating into tissues, where they become
macrophages or dendritic cells (i.e., a type of antigen presenting cell that plays a role in linking the
innate and adaptive immunity). Macrophages can be found within many organs in the body, including
the liver, brain, bones, and lungs, as well as in the blood, particularly at sites of infection.

Two illustrated macrophages, one in the first step of phagocytosis the other completing phagocytosis by
engulfing and removing a pathogen.

What are the types of macrophages?

Macrophages can largely be categorized into two main types: M1 and M2 macrophages. The M1 type,
referred to as classically-activated macrophages, are activated by pathogen invasion and play a large
role in the immune response to foreign pathogens such as bacteria. The M2 type, referred to as
alternatively-activated macrophages, play a role in wound healing and tissue repair, and have an anti-
inflammatory role.

Natural killer cells

Natural Killer cells (NK cells) are cells which do not attack pathogens directly. Instead, natural killer cells
destroy infected host cells in order to stop the spread of an infection. Infected or compromised host
cells can signal natural kill cells for destruction through the expression of specific receptors an d antigen
presentation.

Natural killer cells are initially developed within the primary lymphoid tissue of the bone marrow where
they undergo positive and negative selection to remove self-targeting cells. Once they have matured,
they move to secondary lymphoid tissues to undergo terminal maturation.

Mature NK cells possess both stimulatory and inhibitory receptors which control the activity of the cell,
for example killer cell immunoglobulin like receptors (KIR) and NKG2D. Over 20 activating receptors are
known that function to recognise proteins which are not usually present on the surface of a cell.
Inhibitory receptors mainly

Once NK cells are active they insert their lytic granules, which contain cytotoxic chemical, into the
infected cell. An immunological synapse is formed between the NK cells and the infected cell before
perforins and granzyme B are released. Perforins create pores in the membrane which allow death-
inducing enzyme granzyme B to enter the cell and induce caspase mediated apoptosis, resulting in cell
death. Activated NK cells also produce cytokines (IFN-γ and TNF-α) which recruit other members of the
immune system and activate the acquired response.
 B CELLS

B cells are a type of lymphocyte that are responsible for the humoral immunity component of the
adaptive immune system. These white blood cells produce antibodies, which play a key part in
immunity. Each B cell contains a single round nucleus.

B cells produce antibodies, or Y-shaped chromosomes that are created by the immune system to stop
foreign substances from harming the body. B cells have B cell receptors (BCRs) on their surface, which
they use to bind to a specific protein.

Once the B cells bind to this protein, called an antigen, they release antibodies that stick to the antigen
and prevent it from harming the body. Then, the B cells secrete cytokines to attract other immune cells.
They also present the antigens to T cells, which they recognize using their T cell receptors (TCRs). The T
cells destroy the antigens.When infectious agents, such as bacteria, enter the body, pieces of their
machinery can be visible on the surface of their cells. These pieces are called antigens, and B cells
activate when they encounter and recognize antigens.

B cells have B cell receptors (BCRs) on their surface, and these BCRs bind to specific antigens. Once the
cell binds to the antigens, activation begins.

T- CELLS

T cells (also called T lymphocytes) are major components of the adaptive immune system. Their roles
include directly killing infected host cells, activating other immune cells, producing cytokines and
regulating the immune response.T lymphocytes originate from haematopoietic stem cells within the
bone marrow. Some of these multipotent cells subsequently become lymphoid progenitor cells that
leave the bone marrow and travel to the thymus via the blood.

Once in the thymus, T lymphocytes undergo a selection process in which the majority of developing T
cells (called thymocytes) will not survive. During this process, thymocytes with receptors for self-
antigens receive negative signals and are removed from the repertoire.

Each T lymphocyte has a T cell receptor (TCR) which is specific to a particular antigen. T lymphocytes
that survive thymic selection will mature and leave the thymus. After that, They circulate through
peripheral lymphoid organs, ready to encounter their cognate antigens and become activated. The
thymus atrophies as we age and so produces fewer naïve T lymphocytes over time.