Immune Response

Periodontics Immune Response Important Questions and Answers

The periodontal tissues are constantly exposed to the microflora environment that is comprised of harmful/toxic substances that can initiate the periodontal disease process. The periodontal structures are maintained in health by the presence of an immune mechanism that prevents these bacterial products from causing damage to the tissues.

Question 1. What are the components of the immune system?
Answer:

The Immune response is of two types – the innate and the adaptive immune response. While the former is non-specific and is the first response to occur, the latter is specific to particular microorganisms and takes over in the second phase an orderly sequence of events.

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• Innate Immune responses are provided by the epithelial barrier, acute phase proteins, antimicrobial peptides, complement system, and the immune cells.
• The cells of the innate immune mechanisms are – the neutrophils, monocytes, and macrophages of the leukocyte population.

Question 2. Describe the role of the innate responses.
Answer:

Neutrophils (Polymorphonuclear Leukocytes)

They are the most abundant of the white blood cells, comprising about 60%–70%, and form an important part of the first line of defense.

• They are produced in the bone marrow and the mature form is present in the bloodstream as laminar flow, in health. The neutrophil is of an irregular shape and contains multiple lobes and abundant cytoplasmic granules.
• Their primary function is phagocytosis, a process where they engulf and kill the bacteria.
• The neutrophils leave the bloodstream in response to signals that they receive in the presence of noxious stimuli. The concerted processes of (1) margination, where they align themselves against the vessel wall, (2) diapedesis, where they leave the vessel into the tissues, and (3) chemotaxis, directed movement through a chemical gradient result in the arrival of the cell to the site of injury.
• Here they engulf and phagocytose the bacteria and other foreign particles.
• The mechanism by which the neutrophils bring about phagocytosis can be oxygen-dependent or oxygen-independent.
• The granules in the neutrophils are of primary importance in phagocytosis, which is of two types—primary or the azurophilic granules and the specific granules. The specific granules secrete lysozyme and lactoferrin, which have both bactericidal and static activity.
• The zurophil granules secrete small antimicrobial peptides, enzymes viz. cathepsin G and lysozyme. The secretion from the granules from the non-oxidative arm of phagocytosis is also relevant in the subgingival environment.

Macrophages (Mononuclear Cells)

• The monocytes are agranular leukocytes that originate in the bone marrow and circulate in the peripheral blood before entering tissues to replenish tissue-specific macrophage populations viz.
• osteoclasts (bone), microglia cells (CNS), Langerhans cells (skin), histiocytes (connective tissue), and Kupffr cells (liver).
• They have a longer rate of survival, unlike the neutrophils, and are cells of chronic inflammation. They respond, move, and phagocytose similarly to that of neutrophils. In addition, they take up antigens to be presented to the lymphocytes.
• They are versatile cells as they play multiple roles. They also ingest dead and worn-out cells, act against infection with fungi or parasites, and activate the adaptive immune response by the process of antigen presentation.

Question 3. Describe the role of adaptive immune responses.
Answer:

• The hallmark of this arm of immune response is its specific recognition, i.e. to recognize foreign substances or “non-self’.
• The other feature or function is its ability to mount an immune response against specific bacteria, like the P.gingivalis through clonal expansion and immunologic memory.
• They can also play a regulatory role, i.e. turn of immune responses when the infection has been cleared.
• The two arms of the acquired immune response are Cell-mediated responses and humoral responses. While the former involves the T-lymphocytes, the latter is brought about by the B-cells.

T-Cells (T-Lymphocytes)

They are obtained from the lymphoid lineage of cells in the marrow, which has a round, dense nucleus and less cytoplasm.

• The lymphocytes constitute about 20% of the total WBCs, of which 60%–80% are the T-cells. They are associated with two major immune functions- effector and
  regulatory.
• They are broadly classified into Helper T cells (TH cells), cytotoxic cells (CTLs), and regulatory cells (Treg). They are identified by phenotypic markers {Cluster of Diffrentiation} CD4 for helper T cells and CD8 for cytotoxic T cells.
• They recognize the antigen presented to them with the help of a T cell receptor present on their surface.
• The helper T cells take part in the immune mechanism by the synthesis of soluble factors called cytokines that promote the differentiation of phagocytes and other cells, while the cytotoxic cells act by phagocytosing intracellular pathogens.
• Regulatory T cells prevent tissue damage by controlling excessive immune responses.

B Cells (Lymphocytes)

B cells are also of lymphoid lineage, derived from the bone marrow, which is the major source of stem cells from which the immune cells develop. They undergo
differentiation under the influence of a special microenvironment.

• B cells take part in immune mechanisms through the production of antibodies or immunoglobulins (Igs). The B cell has to transform to become a plasma cell before it secretes the antibodies.
• The various types of immunoglobulins are IgM, IgA, IgG, IgD, and IgE. The functions of the Igs are to aggregate and eliminate the micro-organisms by antigen-antibody binding, opsonization, or activation of the complement cascade.
• IgG is the most important of the serum immunoglobulins which is further subdivided into four classes—IgG1, IgG2, IgG3, and IgG4.

Question 4. What are cytokines and their role in inflammation?
Answer:

• Cytokines are substances (kine) produced by cells (cyto). In the inflammatory environment, these are proteins that are secreted by the immune cells and can act on and influence other immune cells and host cells.
• Cytokines may be classified as proinflammatory when they increase the inflammatory response and anti-inflammatory when they decrease the inflammatory response.

Proinflammatory Cytokines

• The important members of their family are interleukin (IL) 1, 6, and TNF-α. These cytokines increase the inflammatory process, leading to greater infiltration of immune cells to the affected site.
• They also lead to increased synthesis of matrix metalloproteinases (MMPs) and greater osteoclastic activity. They may act synergistically along with eicosanoids such as prostaglandin E2 (PGE2) to increase the inflammatory outcome.
• Taken together, the proinflammatory cytokines may lead to increased soft and hard tissue loss observed in periodontal disease.

Anti-inflammatory Cytokines

• The important members of their family are interleukin (IL) IL-4 and 10. These cytokines reduce the inflammatory process and may promote tissue growth.
• The balance of pro and anti-inflammatory cytokines is required for the maintenance of periodontal health.
• It is thought that the disease process occurs as a result of loss of this balance, either in the form of increased proinflammatory cytokines or decreased anti-inflammatory cytokines in the periodontal tissues.