INNATE IMMUNE SYSTEM

Cells of the innate immune system

Cells of the innate immune system include phagocytic cells (monocyte/macrophages and
polymorphonuclear leukocytes (PMNs), NK cells, basophils, mast cells, eosinophiles and
platelets.

The receptors of these cells are pattern recognition receptors (PRRs) that recognize broad
molecular patterns found on pathogens (pathogen associated molecular patterns, PAMPS).

1.Neutrophils (Polymorphonuclear cells (PMNs)- They are the most common type of white
blood cell in the bloodstream, are among the first immune cells to defend against infection.
They phagocytose invading organisms (e.g. bacteria) and other foreign cells and kill them
intracellularly. Contain granules that release enzymes to help kill and digest these cells.

Neutrophils circulate in the bloodstream and must be signaled to leave the bloodstream and enter
infected tissues. The signal often comes from the bacteria themselves , complement proteins, or
from damaged tissue, all of which produce substances that attract neutrophils to a trouble spot, a
process called chemotaxis.

Neutrophils also release substances that produce fibers in the surrounding tissue. These fibers
may trap bacteria, thus keeping them from spreading and making them easier to destroy. In
addition, PMNs contribute to collateral tissue damage that occurs during inflammation.

2. Macrophages –Develop from a type of white blood cell called monocytes after monocytes
move from the bloodstream to the tissues.

Monocytes move to the tissues when infection occurs. There, over a period of about 8 hours,
monocytes enlarge greatly and produce granules within themselves, becoming macrophages.

The granules are filled with enzymes and other substances that help kill and digest bacteria and
other foreign cells.

In addition, macrophages are capable of extracellular killing of infected or altered self target
cells. Furthermore, macrophages contribute to tissue repair and act as antigen-presenting cells,
which are required for the induction of specific immune responses.

3.Natural killer cells are called “natural” killers because they are ready to kill as soon as they
are formed. Natural killer cells attach to foreign cells and release enzymes and other substances
that damage the outer membranes of the foreign cells.

Natural killer cells kill certain microorganisms, cancer cells, and cells infected by viruses.
 Thus, natural killer cells are important in the initial defense against viral infections. These cells
are not part of the inflammatory response but they are important in nonspecific immunity to viral
infections and tumor surveillance.

Also, natural killer cells produce cytokines that regulate some of the functions of T cells, B cells,
and macrophages.

3. Eosinophils circulate in the bloodstream, can ingest bacteria but also target foreign cells that
are too large to ingest.

They contain granules that release enzymes and other toxic substances when foreign cells are
encountered. These substances make holes in the target cell's membranes.

They are however, less active against bacteria than are neutrophils and macrophages. Their main
function may be to attach to and thus help immobilize and kill parasites.

Eosinophils help destroy cancer cells. They also produce chemicals involved in inflammation
and allergic reactions (such as asthma). People with allergies, parasitic infections, or asthma
often have more eosinophils in the bloodstream than people without these disorders.

4. Basophils do not ingest foreign cells. They contain granules filled with histamine, a substance
involved in allergic reactions. When basophils encounter allergens (antigens that cause allergic
reactions), they release histamine. Histamine increases blood flow to damaged tissues. Basophils
also produce substances that attract neutrophils and eosinophils to a trouble spot.

5. Dendritic cells reside in the skin, lymph nodes, and tissues throughout the body. Most
dendritic cells ingest and break antigens into fragments (called antigen processing), enabling
helper T cells to recognize the antigen.

Dendritic cells present antigen fragments to T cells in the lymph nodes.

Another type of dendritic cell, the follicular dendritic cell, presents unprocessed (intact) antigen
that has been linked with antibody (antibody-antigen complex) to B cells.

ADAPTIVE IMMUNE SYSTEM

CELLS OF ADAPTAIVE IMMUNITY

Cells that make up the adaptive (specific) immune system include the B and T lymphocytes. After
exposure to antigen, B cells differentiate into plasma cells whose primary function is the
production of antibodies. Similarly, T cells can differentiate into either T cytotoxic (Tc) or T
helper (Th) cells of which there are two types Th1 and Th2 cells.
1. B-CELLS
The principal functions of B cells are

1. to make antibodies against antigens,

2. perform the role of antigen-presenting cells (APCs)
3. Develop into memory B cells after activation by antigen interaction.
4. B cells are an essential component of humoral immune response.
B cells do not produce antibodies until they become fully activated.

Each B cell has a unique receptor protein (referred to as the B cell receptor (BCR)) on its surface that
will bind to one particular antigen.

The BCR is a membrane-bound immunoglobulin, and it is this molecule that allows the distinction of
B cells from other types of lymphocyte, as well as being the main protein involved in B cell activation.

Once a B cell encounters its cognate antigen and receives an additional signal from a T helper cell, it
can further differentiate into either plasma B cells or memory B cells.

Types of B cells
Plasma B cells are large B cells that have been exposed to antigen and produce and secrete large
amounts of antibodies (immunoglobulins) which assist in the destruction of microbes by binding to
them and making them easier targets for phagocytes and activation of the complement system.

These are short lived cells and undergo apoptosis when the inciting agent that induced immune
response is eliminated.

Memory B cells are formed from activated B cells that are specific to the antigen encountered
during the primary immune response. These cells are able to live for a long time, and can respond
quickly following a second exposure to the same antigen.

B-cell activation

1. T cell-dependent activation These are antigens that activate B cells with the help of T-cell. They are
named as such because they are unable to induce a humoral response in organisms that lack T cells. Once
a BCR binds a T dependent antigen, the antigen is taken up into the B cell through receptor-mediated
endocytosis, degraded, and presented to T cells as peptide pieces in complex with MHC-II molecules on
the cell membrane. T helper (TH) cells, typically follicular T helper (TFH) cells, that were activated with
the same antigen recognize and bind these MHC-II-peptide complexes through their T cell receptor (TCR).
Following TCR-MHC-II-peptide binding, T cells express the surface protein CD40L as well as
cytokines such as IL-4 and IL-21. CD40L serves as a necessary co-stimulatory factor for B cell
activation by binding the B cell surface receptor CD40, which promotes B cell proliferation,
immunoglobulin class switching, and somatic hypermutation as well as sustains T cell growth and
differentiation.

The whole process takes a minimum of 10-14 days. Subsequent exposure to the microbe results in
activation of the memory B cells leading to more rapid production of antibody, often within 1-2 days

2 T cell-independent activation . These are antigens that activate B cells without T cell help are.
They include foreign polysaccharides and unmethylated CpG DNA. They are named as such
because they are able to induce a humoral response in organisms that lack T cells. B cell
response to these antigens is rapid, though antibodies generated tend to have lower affinity and are
less functionally versatile than those generated from T cell-dependent activation. As with T
dependent antigens, B cells activated by T independent antigens need additional signals to
complete activation, but instead of receiving them from T cells, they are provided either by
recognition and binding of a common microbial constituent to toll-like receptors (TLRs) or
by extensive crosslinking of BCRs to repeated epitopes on a bacterial cell.

1. T lymphocytes
A T cell, or T lymphocyte, is a type of lymphocyte that plays a central role in cell-mediated
immunity. With 70-80% of circulating lymphocytes in blood while 90% of lymphocytes in the
thoracic duct.

T cells can be distinguished from other lymphocytes, such as B cells and natural killer cells, by
the presence of a T-cell receptor on the cell surface. They are called T cells because they mature
in the thymus.

They are classified as

1. T helper cells (CD4+

T helper cells (TH cells) assist other white blood cells in immunologic processes, including
maturation of B cells into plasma cells and memory B cells, and activation of cytotoxic T cells and
macrophages.

These cells are also known as CD4 cells because they express CD4+ glycoprotein on their
surfaces.

They also express T-cell receptor that binds to MHC class II in association with APC.

Helper T cells become activated when they are presented with peptide antigens by MHC class II
molecules, which are expressed on the surface of antigen-presenting cells (APCs).

Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or
assist in the active immune response.

These cells can differentiate into one of several subtypes, including TH1, TH2, TH3, TH17, TH9,
which secrete different cytokines to facilitate different types of immune responses.

2. T cytotoxic cells CD8+

Cytotoxic T cells (TC cells, CTLs, T-killer cells, killer T cells) destroy virus-infected cells and
tumor cells, and are also implicated in transplant rejection.

These cells are also known as CD8+ T cells since they express the CD8 glycoprotein at their
surfaces and T-Cell receptor.

Viral antigens enter the eukaryotic cells (host’s cells), through the rough endoplasmic Reticulum and
get processed to act as an effective antigen. Later, it enters the Golgi Body gets processed further and
integrate therein with MHC-I class of membrane proteins and are then expressed over cell membrane.

A second way of introduction of viral peptide is the synthesis (by transcription and translation)
of viral peptide itself by the viral DNA and from there on similar cascade follows.

The eukaryotic cell is ready with the processed antigens. The next task that is performed is to summon
the T-Cytotoxic cells. The host cell plays this role probably by secreting various types of cytokines
and even interferons (gamma-interferon), which serve to inhibit the growth of virus. The T-Cytotoxic
cells approach the infected host cell as well as tumour cells and kill them after they bind to them
because they possess a TCR and CD8 which is specific for MHC-I found over host cells.

3. Memory T cells
May be either CD4+ or CD8+. Memory T cells typically express the cell surface protein CD45RO.

Memory T cells comprise three subtypes:

1. central memory T cells (TCM cells),

2. effector memory T cells (TEM cells and TEMRA cells) and
3. resident memory T cells (TRM)