Innate Immunity

Innate Immunity Innate immunity refers to the natural defense mechanisms that an individual possesses from birth, even before encountering specific pathogens or antigens. Mechanism of innate Immunity 1. Mechanical barriers and surface secretion : ● Intact skin and mucous membranes constitute a barrier that cannot be penetrated by most microorganisms. ● The sticky mucus covering mucous membranes traps any foreign material. ● Cilla of the respiratory tract epithelium sweep foreign material out. ● Blinking, sneezing and coughing reflexes expel foreign particles. ● The flushing action of saliva, tears and urine helps in washing microbes from the body. ● Sweat and sebaceous secretions contain substances. (e.g. lactic acid and ammonia) that inhibit microorganisms. ● Saliva, tears and mucous secretions of respiratory, alimentary and genitourinary tracts contain lysozyme which is bactericidal. ● Gastric and vaginal acidity inhibit growth of microorganisms. 2. Normal bacteria flora : Bacteria of the normal flora produce bacteriocins and acids that destroy microorganisms & They compete with pathogens for essential nutrients. ☆ Notes : Suppression of normal flora pathogens by antibiotics may lead to infection with potential (superinfection). 3. Soluble defense factor : A number of microbicidal substances are present in tissues and body fluids and act in defence against microbes. They include : ● Lysozyme: It is an enzyme that lyses bacteria by destroying the peptidoglycan of their cell wall. ● Complement: It is a group of plasma proteins that act together to attack extracellular pathogens. The ● complement components are present in an inactive form, and can be activated either spontaneously by certain pathogens. ● Acute phase proteins: These are present at very low levels in normal serum, but their concentration rises dramatically, shortly after the onset of an infection. ☆Microbial products, e.g. endotoxins, stimulate macrophages to release cytokines, which stimulate the liver to produce a large number of acute phase proteins. ☆ These proteins limit the spread of the infectious agent or stimulate the host response. Examples include fibrinogen and C-reactive protein (CRP). ● Interferons: There are 2 types of interferons. Type I interferon (a and ẞ) is part of Innate immunity It is secreted by virus-infected cells and prevents viral replication 4. Cellular defense factor Phagocytes: Particles, eg. bacteria, entering the tissue, fluids or blood are rapidly engulfed by phagocytic cells. This process of engulfment (internalization) of particulate matter is termed phagocytosis. Phagocytes contain digestive enzymes capable of degrading ingested material. The main phagocytic cells are: 1. Neutrophils 2. Monocytes/macrophages ( monocytes in the blood and macrophages in the tissues) 3. Dendritic cells The process of phagocytosis occurs in subsequent steps: a. Migration (Chemotaxis) b. Attachment C. Engulfment D. Killing Migration (Chemotaxis): Microorganisms and injured tissues elaborate chemotactic factors that attract phagocytic cells to the site of infection. Some of the complement components and some cytokines may have chemotactic properties. Microorganism + injured tissue = phagocytic attract Cytokines  are signaling proteins that play a crucial role. in your immune system.  Attachment: Phagocytes have receptors on their surface that can recognize non- specific molecules common to many pathogens, allowing attachment to them. Some microorganisms may alter these molecules or cover themselves with a thick capsule that is not recognized by any phagocyte receptor. Attachment may still occur if these microorganisms become coated with molecules which the phagocytes can recognize. These may be an antibody, a complement component or other molecules (e.g. CRP). In this case, the process is called opsonization and the substance which helped phagocytosis is called Bacteria an opsonin Careercells dead Cells Receptors of phagocytes + molecule ( un common ) = attachment to pathogens Opsonization: Is an immune process which uses opsonins to tag foreign pathogens for elimination by phagocytes. ( cancer cells , dead cells ) Engulfment: The cytoplasmic membrane of the phagocyte surrounds the organism and encloses it in a vacuole termed phagosome. Lysosomes, which are bags of enzymes, then fuse with the phagosome forming phagolysosomes, in which the engulfed material is killed and digested. Cytoplasmic membrane + phagocyte = Phagosome , phagosome + lysosome = Phagolysosome ( killing & digesting ) Killing: This occurs by 2 mechanisms: O₂ dependent mechanism: After engulfment, there is a respiratory burst consisting of a steep rise in O₂ consumption. This is accompanied by an increase in the activity of a number of enzymes and leads to the generation of various reactive oxygen intermediates, such as hydrogen peroxide and singlet oxygen, which are lethal to microorganisms. O2 independent mechanism: These are the lysosomal enzymes (lysozyma elastase, hydrolase ... etc) Antigen presentation: Macrophages help to show part of the foreign agents they have eaten to T cells, so that the T cells can start responding to them. Thus, they are among a group of cells called antigen presenting cells (APCs). Secretion: They secrete chemical mediators called cytokines, e.g. Interleukins. Direct cytotoxicity: They may kill targets without engulfing them. Helminthic parasites which are too large to be engulfed can be killed by macrophages releasing their toxic contents onto them, also tumour cells can be killed in a similar way. Eosinophils: They are granulocytes present mainly in tissues. In the blood, they form 1-3 % of TLC (Total Leucocyte Count). Functions: They are mainly of importance in defence against helminthic parasite Infections. Such parasites, which are too large to be phagocytosed, can be killed by eosinophills releasing the toxic contents of their granules onto them. They also play an important role in allergic reactions. Eosinophils also have phagocytic properties. Basophils and mast cells: Basophils are found in the blood in very low concentrations (0-2% of TLC). Mast cells are found in tissue. They are present either around the blood vessels or in the submucosa. Function: Both basophils and mast cells have similar functions. They possess granules containing a number of important mediators such as histamine. Release of these mediators: Contributes to inflammation Plays an important role in allergy Natural killer cells: They are large granular lymphocytes which can be distinguished from B and T lymphocytes. They constitute 10-15% of peripheral blood lymphocytes. Functions: They are capable of non-specific killing of tumor cells and virus-infected cells in a manner similar to cytotoxic T cells; however, they differ from cytotoxic T cells in the. way they recognize their targets. ☆ They secrete cytokines such as interferon Chemical mediators released at the site of Infection trigger an inflammatory response. The events that occur during inflammation are vasodilatation, Increased vascular permeability and migration of leucocytes from the blood stream across the vasculer endothelium into the inflamed tissues to combat the invading microbe. This migration is mediated by certain molecules, termed adhesion molecules, which are expressed on the surface of leucocytes and vascular endothelium. ● They may kill targets without engulfing them. Helminthic parasites which are too large to be engulfed can be killed by macrophages releasing their toxic contents onto them, also tumour cells can be killed in a similar way. ● They are mainly of importance in defence against helminthic parasite Infections. Such parasites, which are too large to be phagocytosed, can be killed by eosinophills releasing the toxic contents of their granules onto them. They also play an important role in allergic reactions. Eosinophils also have phagocytic properties.