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Nonspecific (natural or innate) and cellular immunity in details

Immunology is defined as the study of the molecules, cells, organs, and systems responsible for the recognition and disposal of foreign material. Immunology began as a branch of microbiology. The study of infectious disease and the body’s response to them has a major role for the development of immunology. Moreover, the concept of germ theory of disease has contributed to the field of immunology.


Immunity can be defined as the way in which the body can protect itself from invasion by pathogenic microorganism


It was Edward Jenner who first studied the response of the body to foreign substances. He observed that dairy maids who had naturally contracted a mild infection called cowpox seemed to be protected against smallpox, a horribly disfiguring disease and a major killer.
Immunity can be defined as the way in which the body can protect itself from invasion by pathogenic microorganism and provide a defense against their harmful effect. 




Immunity is classified in to two major groups
• Nonspecific immunity
• Specific immunity

Nonspecific (natural or innate) immunity.

Non-specific immunity, also called natural or innate immunity, is the first line of defense against any infectious agent. Nonspecific host responses provide an effective barrier that prevents the microorganisms from penetrating, inhibit or destroy the invader if it gains access to the tissues, and eliminate or neutralize any toxic substance elaborated by infectious agent. Several mechanisms are available in the immunocompetent host. These include physical or mechanical barrier, biochemical factors, cellular mechanism, role of normal flora and inflammatory reactions.

Physical or mechanical barrier

The unbroken skin and mucus membrane are effective mechanical barriers to infectious agents. The surface of the skin is also inhibitory to the growth of most microorganisms because of low moisture, low pH, and the presence of secreted inhibitory substance. However, it is possible for some microorganisms to enter the skin through hair follicles, sebaceous glands or sweet glands.

Similarly, mucus membranes consist of an epithelial layer and an underlying connective tissue layer. They line the entire digestive, respiratory, urinary, and reproductive tracts. For example, the epithelial surface that lines the nasal cavity and throat are protected by a combination of mucous production and cilliary movement. Because mucous is so viscous, microorganisms adhere to it.
Besides, the action of coughing removes mucus that contains microorganisms. In the urethra rapid flow of urine washes away most microorganisms. Tear that wash the conjunctiva perform a similar defensive function.

Biochemical factors

These are chemical secretions produced by the body that inhibit microbial growth. The following are included as an example, keratin is a skin protein produced by the outer most cells of the skin, since it has very little water, the skin becomes very dry and therefore to most species of microorganism. The growth of microorganisms is inhibited in the gastrointestinal tract by hydrochloric acid and bile salt, which are secreted by the stomach and liver, respectively.

Lysozyme is an enzyme found in many body fluids and secretions such as tears. It can break down the cell wall of Gram-positive bacteria and a few gram-negative bacteria by hydrolyzing the peptidoglycan layer. Complement is a family of more than twenty different proteins in serum that function as a non-specific defense against infection.

Interferons are small proteins produced by eucarytic cells in response to viral infection. The virally infected cell produces interferon for a few hours, even for a day, and it will excrete and used by other cells. When these cells become infected with the same or unrelated virus, the interferons cause the cells to produce molecules that prevent replication of the infecting virus.


Cellular mechanism


Alveolar macrophages like neutrophils and natural killers remove particles and organisms that enter the alveoli. Neutrophils are the first phagocytes in the infected area that can non-specifically phagocytize some microbes. Natural killer cells are large lymphocytes whose function is to kill undesirable cells such as tumor cells and virus infected cells.

Role of normal flora

The human body is inhabited by a large number of microorganisms, mainly bacteria, which together, are called the body’s normal flora or commensals. The term normal flora implies that such microbial inhabitants are harmless For the most part, normal flora microorganisms do not cause disease.
The commensal can stop the growth of potentially pathogenic organisms through different mechanism such as occupying attachment sites and by producing substance against pathogenic organism. They also compete for essential nutrients for their growth.

The inflammatory response is the vascular and cellular reaction to the presence of invading microorganisms or injury. It is one of the most effective defense mechanism in human and other animals. The process of inflammation may be divided in to the following stages:
• Initiation (Damage to tissue)
• Tissue response
• Leukocyte response
• Tissue repair (resolution)
• Cure.

The damaged cells at the site of injury initiate the tissue response by releasing chemical factors such histamine, which in turn trigger vasodilatation and increased permeability of capillaries, permitting influx of fluids and blood cells in to the site. Then, the phagocytic cells accomplish the leukocyte response, by engulfing the microbes and damaged tissue.

In addition to destroying and removing an injurious agent such as a microbe or its products, the inflammatory response also limits the effects of the agent or its products by confining it or walling it off from the surrounding tissues.

The final stage of inflammation is tissue repair, when all harmful agents or substances have been removed or neutralized at the injury site. The ability of a tissue to repair itself depends on the part of the tissue involved. Skin, being a relatively simple tissue has a high capacity for regeneration. But nerve tissue in brain, appears not to regenerate.
 
Cell mediated immunity
     
Cell mediated immunity consists of immune activities that differ from antibody- mediated immunity. It is moderated by the link between T-lymphocytes and phagocytic cells. T-lymphocytes do not directly recognize the antigens of microorganisms or other living cells, but rather when the antigen is present on the surface of an antigen- presenting cell, the macrophages. Lymphocytes are immunologically active through various types of direct cell-to-cell contact and by the production of soluble factors.
It is moderated by the link between T-lymphocytes and phagocytic cells


Cell mediated immunity is responsible for the following immunologic events:

• Immunity to intracellular organisms
• Rejection of foreign tissue grafts
• Immunity to viral and fungal antigens
• Delayed hypersensitivity

Cell- Mediated Response

Sixty to eighty percent of the total circulating lymphocytes are T cells derived from progenitor cells that mature in the thymus gland under the influence of thymic hormones. These cells are responsible for cellular immune responses and are involved in the regulation of antibody reactions either by helping or suppressing the activation of B-lymphocytes.



There are at least three functionally distinct types of T cells: cytotoxic or effector T cells, helper or regulatory T cells, suppressor T cells

Cytotoxic T cells: are effectors cells, found in the peripheral blood that have the capacity to kill other cells. These cells can destroy virally infected cells.

Helper T cells: secret a variety of substances that help B cells make antibody response, stimulate activated T cells to proliferate, and activate macrophages. T helper cells control many B cell functions, including proliferation and differentiation.

Suppressor T cells: are thought mainly to inhibit the response of helper T cells. T suppressor cells are capable of suppressing a variety of T cell functions such as cytotoxic response, and B cell responses such as suppression or T helper cells or antibody synthesis by plasma cells.
All T-cells have antigen receptor protein (T cell receptor) with which they bind foreign antigens. In order to recognize a foreign antigen, T- cells must simultaneously recognize particular types of self-antigens, which are structural components of the surface of human cells. These antigens don’t normally stimulate a destructive immune response.

The antigen-binding site of a T-cell must simultaneously recognize and bind both a foreign and a self-antigen. The self-antigen is known as major histocompatibility complex (MHC), it has two major classes:
Class I major histocompatibility complex antigen present on all nucleated cells of the body, it is recognized by only T cytotoxic cells. Class II major histocompatibility complex antigen, present only on macrophages, it recognized by only T-helper cells.

The first cell to be activated in any immune response is the T helper cell. Activation of T helper cell is enhanced by some factors produced by macrophages. The stimulated T helper cell stimulates itself and proliferate in increased amount. This activated T helper cell also helps to stimulate T cytotoxic cells.

When these cells recognize antigen presented in combination with the class I major histocompatibility antigen. Activated T cells respond with direct cytotoxic killing (T cytotoxic cells) or with immune regulation either by intensifying the immune response (T helper cells) or by lowering the immune response (T suppresser cells).

Helper and suppressor T cells are the principal regulators of immune responses. Sensitized T cells protect the human body against infection by mediating intracellular pathogens that are viral, bacterial, fungal, or protozoal. In addition, T cells are responsible for chronic rejection in organ transplantation.

Delayed Type of Hypersensitivity

Cell- mediated immunity consists of immune activates that differ from antibody mediated immunity. Cell-mediated immunity is moderated by the link between T lymphocytes and macrophages. T cells do not recognize the antigen of microorganisms or other living cells but are immunologically active through various types of direct cell-to-cell contact and by the production of soluble factors.

The delayed type reaction is cells mediated and involves antigen sensitized T cells, which respond directly or by the release of lymphokines to exhibit contact dermatitis and allergies of infection. Delayed hypersensitivity reaction is one of cell mediated immunity immunologic events e.g. Tuberculin test.



Reference
https://www.healio.com/hematology-oncology/learn-immuno-oncology/the-immune-system/adaptive-immunity-humoral-and-cellular-immunity
https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/cellular-immunity
https://www.nature.com/subjects/cellular-immunity
https://courses.lumenlearning.com/boundless-microbiology/chapter/t-cells-and-cellular-immunity/
https://bio.libretexts.org/Bookshelves/Microbiology/Book%3A_Microbiology_(Kaiser)/Unit_6%3A_Adaptive_Immunity/14%3A_Cell-Mediated_Immunity/14.1%3A_Cell-Mediated_Immunity_-_An_Overview
https://courses.lumenlearning.com/boundless-microbiology/chapter/classifying-immunities/
https://www.medicinenet.com/script/main/art.asp?articlekey=26307
https://www.rxlist.com/script/main/art.asp?articlekey=26307
https://medical-dictionary.thefreedictionary.com/natural+immunity
https://www.dictionary.com/browse/natural-immunity
https://bio.libretexts.org/Bookshelves/Microbiology/Book%3A_Microbiology_(Boundless)/11%3A_Immunology/11.12%3A_Classifying_Immunities/11.12A%3A_Natural_Active_Immunity
https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm
https://www.chop.edu/centers-programs/vaccine-education-center/vaccine-safety/immune-system-and-health

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