IMMUNITY is a biological
phenomenon, which consists in a long-term autosupport of the genetic "self" and "not-self"
balance in the body under foreign surroundings.
IMMUNE SYSTEM develops and releases certain
mechanisms to exert the phenomenon. Understanding the basis of IMMUNOLOGY is achieved by the
study both of the protective mechanisms challenged by "not-self" and of regulatory processes, which form
internal homeostasis of "self" in the body.
Immunity may be
innate (or nonspecific) and adaptive
(acquired or specific).
Paralysis of one component either some components of immunity may
lead to immunodeficiencies and loss of
host defense against infections, or tumours.
Dysregulation of the immune system may result in
allergies (based on hypersensitivity of four types) and
tumours. The importance of the immune system is illustrated
by appearance about twenty years ago of a new disease -
AIDS (acquired immunodeficiency syndrome) in which all the immune disorders
is a macromolecule, which contains a foreign or autologous information to
launch immune responses. On the other hand, any antigen can be often used by
explorers as an immunobiological marker. An appreciable account of various
antigens is about 1018.
IMMUNOGLOBULIN (Ig) is a molecule of the immune system. Antibodies
as well as receptors can be bound to appropriate antigens.
are major cells of the immune system. In fact, the immune system is a hierarchic
totality of lymphoid cells (1013). There are
T cells and
B cells. Other cells (e.g. macrophages, dendritic cells, neutrophils,
mast cells, etc) also attend many immune reactions.
Let us take functions of the immune system. The strategical
function of the system is to switch genetic programme of ontogenesis, which
goes ahead since birth till death under alien surroundings.
Tactical functions of the immune system:
1. Defense from "not-self" by nonspecific and specific mechanisms.
2. Elimination of modified "self".
3. Regulation of cell/tissue growth and maturation.
The immune system functions as a partner of the central
nervous system, the endocrine system and the liver
very close to regulate the homeostasis.
There are two groups of mechanisms by which the immune system exerts its
I. INNATE MECHANISMS, including NONSPECIFIC RESISTANCE:
- Resisting barriers: the skin, ciliated epithelium, sebaceous and sudoriferous
glands, digestive enzymes, etc.
- Normal microbial cover of the body.
- Liver (cytochrome P450 system).
- Interferons (IFNs), NK cells, NKT cells and gdT cells.
- Acute-phase reaction.
- Proinflammatory cytokines.
- Natural antibodies.
- Toll-like receptors (TLR).
- Antimicrobial peptides (defensins and cathelicidins).
II. ADAPTIVE MECHANISMS, or SPECIFIC IMMUNE RESPONSES:
- HUMORAL, or B-cell-mediated immune responses lead to production of
plasma cells, which release the immunoglobulins (IgM, IgG, IgA, IgE, IgD).
- CELLULAR or T-cell-mediated immune responses
result in formation of the effector T cells:
- 1. Cytotoxic T cells (or killer T cells).
- 2. Effector T cells of the immune inflammation.
In innate immunity the immune system can recognize native "not-self" whereas in adaptive cases it always recognizes the processed "not-self" only that takes some time. Innate immunity is completed in non-clonal form.
As contrasted to the immune responses, immunological tolerance
is the state of specific unresponsiveness to an antigen.
Functional organization of the immune system may be considered
at organic, cellular and molecular levels.
There are two types of the immune system organs,
central (or primary) and
peripheral (or secondary). BONE MARROW is a central
organ where all the immune cells are born and only B cells mature (process termed as B
lymphopoiesis). THYMUS is the
other central organ in which T cells mature (T lymphopoiesis). This organ also masters the whole
In the peripheral organs lymphocytes may be definitively matured after
the interaction to antigens as a result of specific immune responses. The peripheral organs are:
- Lymph nodes, lymphatics and spleen.
- Mucous associated lymphoid tissue (MALT) including tonsils, Peyer's patches, isolated
follicles, appendix, etc. In total, MALT may be divided in some levels:
Eusthachian tube - TALT, nasal - NALT, bronchus (including mammary glands in females) - BALT,
gut - GALT (small and large intestines).
- Skin associated lymphoid tissue (SALT).
Cells of the immune system may be divided into four functional groups:
- ANTIGEN-PRESENTING CELLS:
- Macrophages, type 1 and type 2 dendritic cells, B cells.
- REGULATORY CELLS:
- Native regulatory T cells (Treg), inducer T cells, type 1 helper T cells, type 2 helper T cells, type 3 helper T
type 1 regulatory T cells.
- EFFECTOR CELLS:
- MEMORY CELLS:
- Memory CD4+T cells, memory CD8+T cells.
- Long-lived plasma cells, memory B cells.
There are some peculiarities of lymphocytes:
in blood/lymph flow,
intertissue spaces and secretions.
2. Capacity of recognizing
, i.e. the interaction with
"not-self" and "self" on principle "antigen (ligand) - receptor"
3. Clonal cell differentiation
(McF. Burnet) and
ability to form net elements
4. Ability to continuous re-arrangement
in their genome
concerning need to form specific response to any
5. Capacity of memorizing
fact of antigen encounter to provide the body with highly efficient fast immune
responses to the antigen in future.
CLONE is a
lymphocyte population committed to a certain antigen. It is considered there are dozens
million B-cell clones and T-cell clones in each human organism. A committed lymphocyte involved
in immune response becomes primed lymphocyte.
CD nomenclature ("cluster of differentiation") based on
monoclonal technology allows specifying the cells concerning
their origin, differentiation stage, activated state, etc.
MAJOR CD MARKERS
Lymphoid stem cell
Helper/inducer T cell
Cytotoxic T cell
CD19, CD72, CD79, etc
There are lots of molecules, which are engaged in immune
processes. All the molecules of the immune system must be classified.
SPECIFIC IMMUNE RESPONSE'S MOLECULES are unique
substances characteristic for each clone and each specific process:
- Antigen-recognizing immunoglobulin receptors of B cells (BCR).
- Soluble immunoglobulins: IgM, IgG, IgA, IgE, IgD.
- Antigen-recognizing T-cell receptors (
- Soluble fragments of TCR (Transfer Factors).
- Antigen-presenting molecules: human leukocyte antigens of histocompatibility
and CD1 (a, b, c, d and e).
PATTERN REGOGNITION RECEPTORS
take part in innate immunity:
- Secreted molecules.
- Phagocytosis receptors.
- Toll-like receptors (TLR1-TLR11).
ADHESION MOLECULES provide interactions
between immune cells and ligands by means of direct contact:
- Immunoglobulin superfamily.
- Mucin-like molecules, or vascular addressins.
- TNF/NGF superfamily.
- Link family.
IMMUNOCYTOKINES are immune system's
hormones, which can regulate the relationships between the cells nearby and a long way off:
- Interleukins (ILs).
- Colony-stimulating factors (CSFs).
- Interferons (IFNs).
- Tumour necrosis factors (TNFs).
- TGF superfamily.
VARIOUS MEDIATORS OF THE IMMUNE INFLAMMATION: