Inflammation is one of the first responses of the
immune system to infection. The symptoms of inflammation include redness and
swelling, which are caused by increased blood flow into the tissue. Inflammation
is caused by eicosanoids and cytokines, which are released by injured or
infected cells. Common cytokines, which regulate inflammatory response, include
interleukins that are responsible for communication between white blood cells,
chemokines that promote chemotaxis, and interferons that have anti-viral
effects. See details here.
Eicosanoids include prostaglandins that produce fever and the dilation of
blood vessels and leukotrienes that attract certain white blood cells
(leukocytes). Growth factors and cytotoxic factors also regulate inflammatory
response. These cytokines and other chemicals recruit immune cells to the site
of infection and promote healing of damaged tissue following the removal of
pathogens. NFkB plays a key role in regulating the immune response to infection.
JAK/STAT pathway is also important.
The immune system protects organisms from infection with layered defenses of
increasing specificity. The innate immune system provides an immediate, but
non-specific response. It has no immunological memory and is found in nearly all
forms of life. Phagocytosis is an important feature of cellular innate immunity,
which is performed by macrophages, neutrophils, and dendritic cells that engulf
pathogens or particles.
Toll-like receptors (TLRs) are receptors that play key roles in the innate
immune system. TLRs are a type of pattern recognition receptors (PRRs) and
recognize molecules that are broadly shared by pathogens but distinguishable
from host molecules. These molecules are collectively referred to as
pathogen-associated molecular patterns (PAMPs). TLRs together with the
interleukin-1 (IL-1) receptors form a receptor superfamily, which is known as
the "Interleukin-1 Receptor / Toll-Like Receptor Superfamily". All
members of this family have a so-called TIR (Toll-IL-1 receptor) domain.
Thirteen TLRs (TLR1 to TLR13) have been identified in humans and mice
altogether. In humans, TLR1, 2, 4, 5, and 6 are cell membrane associated and
respond primarily to bacterial surface-associated PAMPs. The second group, TLR3,
7, 8, and 9 are expressed on the surface of endosomes, where they respond
primarily to nucleic acid based PAMPs from viruses and bacteria. Upon ligand
binding, TLRs activate two major signaling pathways: the NFkB and the MAPK (p38
and JNK) pathways.
In jawed vertebrates, the immune system can adapt its response during an
infection to improve the recognition of pathogens. This improved response is
called adaptive immunity, which is retained even after pathogens have been
eliminated. This kind of immunological memory allows the immune system to mount
faster and stronger responses every time a particular pathogen is encountered
again.
T cells and B cells play important roles in adaptive immune response. White
blood cells are comprised of neutrophils, eosinophils, basophils, lymphocytes
(T-cell, B-cell, and natural killer cell), monocytes, macrophages and dendritic
cells. Dendritic cells are antigen presenting cells (APC) that activate
T-lymphocytes. Both B-cells and T-cells carry receptor molecules that recognize
specific targets. B-cells are involved in the humoral immune response (HIR - the
aspect of immunity that is mediated by secreted antibodies), whereas T-cells are
involved in cell-mediated immune response. The B-cell antigen (small fragment of
the pathogen) - specific receptor is an antibody molecule on the B-cell surface
that recognizes whole pathogens without any need for antigen processing. Each
lineage of B-cells expresses a different antibody, so the complete set of B-cell
antigen receptors represents all the antibodies that the body can manufacture.
In contrast, T-cells recognize a "non-self" target, such as a
pathogen, only after antigens have been processed and presented in combination
with a "self" receptor called a major histocompatibility complex (MHC)
molecule. There are two major subtypes of T-cells: the killer T-cells and the
helper T-cells. The killer T-cells only recognize antigens coupled to Class I
MHC molecules while the helper T-cells only recognize antigens coupled to Class
II MHC molecules. The killer T-cells are activated when their T-cell receptors (TCR)
bind to specific antigens complexed with the MHC Class I receptors of another
cell. Recognition of this MHC-antigen complex is aided by a co-receptor on the
T-cell, called CD8. The T-cell then travels throughout the body in search of
cells where the MHC I receptors bear this antigen. The helper T-cells regulate
both the innate and adaptive immune responses and help determine which types of
immune responses the body will initiate to respond to a particular pathogen.
These helper T-cells have no cytotoxic activity and do not kill infected cells
or clear pathogens directly, they instead control the immune response by
directing other cells (B-cells, macrophages and killer T-cells) to perform these
tasks. The MHC-antigen complex is recognized by the helper T-cell's CD4
co-receptor. Depending on the size, cytokine signals received, these cells
differentiate into Th1, Th2, Th3, Th17, or other subsets, which secrete
different cytokines.
Regulatory T-cells (Treg-cells) are crucial for the maintenance of immunological
tolerance. Their major role is to shut down T-cell mediated immunity toward the
end of an immune reaction and to suppress auto-reactive T-cells that have
escaped the process of negative selection in the thymus since the thymus is the
principal organ responsible for the T-cell maturation. Two major classes of CD4+
regulatory T-cells have been described, including the naturally occurring Treg-cells
and the adaptive Treg-cells. Naturally occurring Treg-cells (also known as
CD4+CD25+FoxP3+ Treg-cells) arise in the thymus, whereas the adaptive Treg-cells
(also known as Tr1 cells or Th3 cells) originate during a normal immune
response. Naturally occurring Treg-cells can be distinguished from other T cells
by the presence of an intracellular molecule called FoxP3.
The immune system is a remarkably effective structure with specificity,
inducibility, and adaptation. Deregulation of an immune system falls into three
broad categories: immunodeficiency, autoimmunity, and hypersensitivity.
Immunodeficiency occurs when one or more of the components of the immune system
are inactive. Obesity, alcoholism, and drug abuse are common causes of poor
immune function. Acquired immunodeficiency largely contributes to AIDS (Acquired
Immune Deficiency Syndrome), which is caused by the Human Immunodeficiency Virus
(HIV).
Overactive immune response is the other end of immune dysfunction.
Hypersensitivity is a form of an overactive immune response. Allergies are the
most common type of hypersensitivity. Symptoms can range from mild discomfort to
death. Anti-inflammatory drugs are often used to control the symptoms.
Glucocorticoids are the most powerful of these drugs. When the immune system
fails to properly distinguish between self-antigens and non-self antigens and
attacks part of the body, autoimmunity occurs. Autoimmune diseases include
Crohn's disease, diabetes mellitus type 1, lupus, psoriasis, and rheumatoid
arthritis.
T-Cell & B-Cell Activation, T-Cell Anergy and Immune Tolerance, Th1-Th2-Th3,
or Th17 for Autoimmunity and Inflammation PCR arrays can be used to investigate
gene expression changes associated with inflammatory response. To profile the
expressions of various cytokines, one can use QIAGEN's Inflammatory
Cytokines and Receptors, Common Cytokines, Chemokines and Receptors, Interferon
Alpha, Beta Response, and Interferons and Receptors PCR arrays. NFkB or JAK/STAT
PCR arrays can also be used to study the respective signaling pathways.
Complete Array List
