Understanding Immunity

• Immunity refers to protection against infectious pathogens but also reactions to noninfectious substances like environmental molecules, tumors, and even one's own molecules, including allergy, tumor immunity, and autoimmunity.
• The immune system is the collection of cells, tissues, and molecules that mediate these reactions.
• An immune response is the coordinated response of immune system cells and molecules to pathogens and other substances.
• Immunology studies the immune system and its functions, garnering attention from scientists, physicians, and the public because it defends against infections and cancer.
• Pandemics such as COVID-19 highlight the significance of immune responses.
• Cancer immunotherapy has transformed cancer treatment.
• Abnormal immune responses can cause inflammatory diseases, allergies, and autoimmune disorders.
• Immune responses can damage transplanted tissues and are a major barrier to organ transplantation success.

Role of the Immune System

• Defense against infections: Deficient immunity increases susceptibility to infections, as seen in AIDS, and vaccinations boost immune defenses.
• Defense against tumors: Potential for immunotherapy of cancer.
• Control of tissue regeneration and scarring: Repair of damaged tissues.
• Cell injury and pathologic inflammation: Immune responses can cause allergic, autoimmune, and other inflammatory diseases, also having harmful infection consequences.
• Recognition of and injury to tissue grafts and newly introduced proteins: Immune responses are barriers to transplantation and gene therapy.
• The importance of the immune deficiencies was tragically emphasized by the influenza pandemic of 1918, the emergence of AIDS in the 1980s, and COVID-19 in 2019 for individuals.
• Pandemics typically subside as a large portion of the population develops herd immunity through vaccination or natural infection.

Immunologic Disorders

• The immune system reacts against potentially harmful infectious pathogens and cancers but does not typically respond to self-molecules or harmless foreign antigens.
• In genetically predisposed individuals, the immune system may mount damaging reactions against self-structures, causing autoimmune diseases, or against common environmental substances, which can cause allergies.
• Inflammation characterizes these disorders and can become chronic, resulting in tissue damage.
• Treatments for chronic inflammatory diseases target components of the immune response, like therapeutic blockade of molecules called cytokines.
• Protective immune responses to infections can lead to tissue damage and organ dysfunction and for instance, in COVID-19, a significant part of the morbidity results from inflammatory responses.

Stages of Host Defense: Innate and Adaptive Immunity

• Infections are defended against through the reactions of innate immunity initially, then later through adaptive immunity.
• Innate immunity, also called natural or native immunity, is always present in healthy individuals to block microbes' entry.
• Adaptive immunity, also called specific or acquired immunity, requires lymphocyte proliferation/differentiation in response to microbes.
• The potency of adaptive immune responses results from the increase in the number of microbe-specific lymphocytes and their specialized functions, together with enhanced responses upon repeated exposures.
• Adaptive immune response takes longer to develop, innate immunity provides defense in the short term.
• Epithelial barriers of the skin and mucosal tissues serve as the first line of defense in innate immunity, alongside antimicrobial substances made by epithelial barrier cells, and other cells located within or under the epithelium.
• Phagocytes and plasma proteins such as the complement system defend against microbes that breach epithelia and enter the tissues or circulation.

Division of Labor: Types of Adaptive Immunity

• Adaptive immunity includes humoral immunity and cell-mediated immunity to defend against microbes in different locations,
• Extracellular microbes are combated by antibodies.
• Intracellular microbes are eradicated by T lymphocytes.
• Humoral immunity is mediated by antibodies, which are produced by B lymphocytes.
• Antibodies enter the circulation, tissue fluids, and mucosal organ lumens like the gastrointestinal and respiratory tracts and defend against microbes by preventing them from infecting tissue cells.
• Antibodies enhance the uptake of extracellular microbes into phagocytes and are transported through the placenta to protect the fetus and newborn.
• Cell-mediated immunity defends against microbes that have entered host cells, like phagocytes, and is mediated by T lymphocytes.
• Cytokine-producing helper T lymphocytes activate phagocytes to destroy microbes, Cytotoxic T lymphocytes kill any type of host cell harboring infectious microbes.
• T lymphocytes recognize protein antigen fragments presented on cell surfaces, while B cells and antibodies can recognize various molecules.
• Active immunity and passive immunity induce defense differently.
• Active immunity is induced by infection or vaccination, where individuals mount a response to eradicate the antigen and develop resistance.
• Passive immunity involves the transfer of antibodies from an immune individual to a naive individual, and provides the recipient with the ability to combat infection temporarily.
• An example of passive immunity: newborns acquire antibodies from their mothers via the placenta and breast milk.

Properties of Adaptive Immune Responses

• Specificity : ensures responses combat the encountered pathogens or tumors.
• Diversity: enables the immune system to respond to a large variety of antigens.
• Memory: can be enhanced through repeated exposures to the same antigens
• Nonreactivity to self: prevents injury to the host from foreign antigens from the responses to foreign antigens.
• Each lymphocyte expresses a single antigen receptor to respond to only one antigen.
• In adults, there are about 0.5 to 1 × 1012 B and T lymphocytes, consisting of millions of clones, and clones are made up of cells derived from one lymphocyte.
• Before exposure to any one antigen, about 1 in 100,000 or 1 in 1,000,000 lymphocytes are specific for that antigen.
• Lymphocytes will need to give rise to a large number of cells to eliminate the microbes.
• Clonal expansion- the marked proliferative expansion of the clone of lymphocytes specific for any antigen upon exposure to that antigen.
• Immunologic memory optimizes the immune system's ability to combat persistent and recurrent infections.
• Primary immune response the response to the first exposure to antigen is initiated by naive lymphocytes that are seeing antigen for the first time, Immunologically inexperienced.
• Immunological tolerance the unresponsiveness to self and the immune systems ability to coexist with-tolerate- potentially anti-genetic self molecules, cells and tissues.
• Self-tolerance failure is an abnormality in autoimmune diseases

Cells of the Adaptive Immune System

• Cells of the immune system derive from progenitors in the bone marrow and are broadly classified into myeloid cells and lymphoid cells.
• Myeloid cells: consist mainly of phagocytes, antigen presenting cells, and mast cells.
• Lymphocytes: are the only cells that produce clonally distributed receptors specific for diverse antigens and are the key mediators of adaptive immunity.
• Effector lymphocytes: differenciated progeny of naive cells produce molecules that eliminate antigens.
• Memory cells generated from the progeny of antigen-stimulated lymphocytes can survive for long periods in the absence of antigen.

Tissues of the Immune System

• Immune system tissues are: generative lymphoid organs, which are where T and B lymphocytes mature and are activated by antigens, and secondary lymphoid organs, where adaptive immune responses to microbes are initiated Lymph Nodes:
• Encapsulated nodular aggregates of lymphoid tissue
• Located along lymphatic channels throughout the body
• Antigens entering through epithelia or colonizing tissues concentrate in draining lymph nodes Spleen:
• Highly vascularized abdominal organ.
• Blood-borne antigens are captured and concentrated by dendritic cells and macrophages
• Contains abundant phagocytes that ingest and destroy microbes in the lood

Summary

• The immune system defends agains infections and cancers.
• Innate and adaptive are two different types of immunities that eliminate microbes.
• Lymphocytes are the cells of adaptive immunity with receptors specific for different antigens.
• Sequential phases of immune response- antigen recognition by lympohcytes, proliferation/Differentiation, long lived memory.
• B lymphocytes express membrane and recognize antigens, T lympohcytes produce cytokins and recognize peptide fragments on other cells.
• APC's are organized in secondary lymph organs.
• Naive lymphocytes circulate through secondary lymphoid organs, Effector T circulate to sites of infection.

Explore the contrasting roles of innate and adaptive immunity. Learn about the functions of epithelial barriers, antibodies, T lymphocytes, and cytotoxic T lymphocytes. Understand lymphocyte development, antigen recognition, and immune responses.