Innate Immunity: Components & Epithelial Barriers

• Innate immunity refers to defense mechanisms that are always present, ready to combat microbes and other offending agents.
• It results in a rapid response to microbes and reacts in essentially the same way to repeated infections.
• The two major types of protective reactions of the innate immune system are inflammation and antiviral defense.
• Characteristics include existing at birth, acting as the first line of defense, existing naturally, being non-specific, and having no immune memory.

Components of Innate Immunity

• It includes Epithelial Barriers, Phagocytes, Dendritic Cells, Mast Cells, Eosinophils, Basophils, Innate Lymphoid Cells, Natural Killer Cells, and Lymphocytes with Limited Diversity

Epithelial Barriers

• Epithelial Barriers are major interfaces between the body and the external environment.
• They include the skin and mucosal surfaces of the gastrointestinal, respiratory, and genitourinary tracts.
• Epithelial cells provide physical and chemical barriers against infection.

Phagocytes: Neutrophils and Monocytes/Macrophages

• Phagocytes, or Phagocytic cells, circulate looking for potential threats to engulf and destroy.
• Phagocyte means “eating cell”.

Neutrophils

• Neutrophils, also called polymorphonuclear leukocytes (PMNs), have a multilobed nucleus.
• Production of neutrophils from the bone marrow increases rapidly in response to certain bacterial and fungal infections, increasing blood numbers up to 10 times the normal.
• Neutrophils phagocytose (ingest) and destroy microbes in the circulation.
• They are recruited to sites of tissue damage, initiating the clearance of cell debris, even in the absence of infection.
• Neutrophils live for only several hours in tissues, with a lifespan of 1-2 days, and do not provide prolonged defense

Monocytes/Macrophages

• Monocytes are less abundant in the blood than neutrophils.
• They ingest microbes in the blood and tissues.
• During inflammatory reactions, monocytes enter tissues and differentiate into macrophages, surviving in these sites for long periods.
• Macrophages ingest and destroy microbes.
• They clear dead tissues and initiate tissue repair and produce cytokines that induce and regulate inflammation.

Macrophage Activation

• Macrophages may be activated by two different pathways that serve distinct functions.
• Classical macrophage activation (M1) or pro-inflammatory macrophages are involved in destroying microbes and triggering inflammation.
• Alternative macrophage activation (M2) or anti-inflammatory macrophages are more important for tissue repair and to terminate inflammation.
• An example for macrophage activation disorder is impaired wound healing in diabetes

Dendritic Cells

• Dendritic cells function as guards in tissues.
• They respond to microbes by producing numerous cytokines, which initiate inflammation and stimulate adaptive immune responses.
• They capture protein antigens and display fragments of these antigens to T cells, forming a bridge between innate and adaptive immunity.

Mast Cells

• Mast cells are bone marrow-derived cells with abundant cytoplasmic granules present throughout the skin and mucosal barriers.
• They can be activated by microbial products
• Mast cell granules contain histamine that cause vasodilation and increased capillary permeability and proteolytic enzymes that can kill bacteria or inactivate microbial toxins Mast cells also synthesize and secrete cytokines (e.g., tumor necrosis factor [TNF]), which stimulate inflammation
• Mast cell products provide defense against helminths and other pathogens, as well as protection against insect venoms, and they are responsible for symptoms of allergic diseases.
• Mast cells are present in all connective tissues, especially under epithelia, and are usually located adjacent to blood vessels.
• The body’s mast cells are activated by binding of an allergen and depends on the route of entry of the allergen; inhaled allergens activate mast cells in the submucosal tissues of the bronchus, whereas ingested allergens activate mast cells in the wall of the intestine.
• When mast cells exposed to the allergen, they are activated to secrete inflammatory mediators such as histamine.

Clinical Syndromes caused by Mast cells hypersensitivity and Therapy

• Examples include Hay fever, food allergies, and Asthma.
• Anaphylaxis, a systemic reaction characterized by edema in many tissues and a fall in blood pressure (anaphylactic shock), is the most severe form of immediate hypersensitivity.
• Causes include bee stings, injected or ingested penicillin-family antibiotics, and ingested nuts or shellfish.
• The reaction is life threatening because of the sudden fall in blood pressure and airway obstruction.
• Therapy is aimed at inhibiting mast cell and reducing inflammation
• Common drugs include antihistamines for hay fever, inhaled corticosteroids to relax bronchial smooth muscles and reduce airway inflammation in asthma, and epinephrine (adrenaline) in anaphylaxis.

Eosinophils

• Eosinophils are granulocytes that target multicellular parasites.
• They secrete a range of highly toxic proteins and free radicals that kill bacteria and parasites.

Basophils

• Basophils are blood granulocytes with many structural and functional similarities to mast cells.
• Basophils constitute less than 1% of blood leukocytes (white blood cells)

Innate Lymphoid Cells

• Innate lymphoid cells (ILCs) are tissue-resident cells that produce cytokines similar to those secreted by helper T lymphocytes but do not express T cell antigen receptors (TCRs)

Natural Killer Cells

• NK cells recognize infected and stressed cells.
• They respond by killing these cells and by secreting the macrophage-activating cytokine Interferon gamma (IFN-γ).

Lymphocytes with Limited Diversity

• Several types of lymphocytes that have some features of T and B lymphocytes also function in the early defence against microbes and may be considered part of the innate immune system
• These lymphocytes express antigen receptors (as do classical T and B cells), but the receptors have limited diversity.

Explore innate immunity, the body's rapid defense system. Learn about its components, including epithelial barriers, phagocytes, and natural killer cells. Understand how these barriers provide physical and chemical protection against microbes.