Innate Immunity PDF

Innate immunity By Reem abdelrahman Lecturer of microbiology and immunology Faculty of medicine Helwan university Objectives: Define immunity and immune system with their two major arms. Recognize first defense line of innate immunity. Recognize second defense line of in...

Innate immunity By Reem abdelrahman Lecturer of microbiology and immunology Faculty of medicine Helwan university Objectives: Define immunity and immune system with their two major arms. Recognize first defense line of innate immunity. Recognize second defense line of innate immunity. Identify phagocytosis and its stages. define opsonization.  IMMUNITY The main function of the immune system is to prevent or limit infections by microorganisms such as bacteria, viruses, fungi and parasites. This defensive function is performed by various cellular and humoral components which interact with each other producing a coordinated immune response that eliminates the pathogen or minimizes the damage it causes.  Immune system acquired innate immune (adaptive) system immune system Innate immunity acts as a first If these innate defenses fail, the line of defense against infectious acquired immune system is called agents which are checked before upon. they cause overt infection.  Immune system Innate immunity Adaptive immunity First defense Second Cell mediated Humoral line defense line  innate and acquired immunity do not operate in total independence of each other. They cooperate in important ways to produce more effective immunity. The communication system through various cytokines and adhesion molecules.  INNATE (NON-SPECIFIC) IMMUNITY Innate immunity is the natural inborn barrier against invasion by microorganisms. Characters of innate immunity: 1. It is non-specific, 2. acting against any foreign invader e.g. microorganisms. 3. It is not acquired through previous exposure to infectious agents. 4. It does not react against self molecules.  Components of innate immunity First line of Second line of natural defense natural defense Mechanical Chemical Normal Circulating Cells of Innate Inflammatory Cytokines barriers barriers microbiota effector proteins Immunity Barriers Intact skin and Sweat , mucous sebaceous Lactobacilli Lysozymes Phagocytes membrane secretions Hair coughing Natural killer Lysozymes Complement and sneezing cells Acidic PH , Tears and Acute phase hydrolytic blinking reflex proteins enzymes Acidic PH Interferons  First line of natural defense Mechanical Chemical Normal barriers barriers microbiota Intact skin and Sweat , mucous sebaceous Lactobacilli membrane secretions Hair coughing Lysozymes and sneezing Acidic PH , Tears and hydrolytic blinking reflex enzymes Acidic PH I- First Line of Natural Defense: 1- Mechanical Barriers hair at the intact skin nares, blinking Mucous and mucous coughing reflex and secretions membranes and tears sneezing I- First Line of Natural Defense: 1- Mechanical Barriers at the portal of entry. I- First Line of Natural Defense: 1- Mechanical Barriers at the portal of entry. These include: The intact skin and mucous membranes are effective barriers against most microorganisms. Epithelia of the skin, GIT, and respiratory tract produce: 1- peptides that have natural antibiotic functions e.g. defensins. 2- Epithelia also secrete cytokines e.g. IL-1. The hair at the nares, coughing and sneezing help to expel foreign particles. Mucous secretions trap many organisms which are pushed outside the body by the continuous movement of cilia in the respiratory tract. The blinking reflex and tears expel foreign particles or bacteria entering the conjunctiva.  Skin Mucociliary escalator Flushing action of saliva, tears, urine I- First Line of Natural Defense: 2- chemical Barriers Sweat and Hydrolytic sebaceous Lysozyme enzymes Acidic pH secretions and HCL  I- First Line of Natural Defense: 2- Chemical Barriers at the portal of entry. These include: Sweat and sebaceous secretions in the skin have antimicrobial actions by acidic pH and high fatty acids content. Lysozyme, an enzyme that dissolves bacterial cell walls (by breaking down peptidoglycan). It is present on the skin, in tears and cervical secretions. Hydrolytic enzymes in the saliva, HCL of the stomach, proteolytic enzymes in the small intestine are bactericidal. Acidic pH in the adult vagina is protective. Antimicrobial HCl in stomach Lysozyme in tears /saliva Peptides in sweat  I- First Line of Natural Defense: 3- Normal microbiota : Site: present at the portal of entry Action: suppress the growth of many pathogenic bacteria and fungi by competition for essential nutrients or by production of inhibitory substances such acids. Example: in the adult vagina an acidic pH is maintained by normal microbiota namely lactobacilli, that interfere with the establishment of pathogenic organisms. Effect of their suppression by antibiotics: leads to superinfection with potential pathogens.  Second line of natural defense Circulating Cells of Innate Inflammatory effector Cytokines Immunity Barriers proteins Lysozymes Phagocytes Natural killer Complement cells Acute phase proteins Interferons II- Second Line of Natural Defense: 1- Circulating effector proteins Acute phase Interferons Lysozyme Complement proteins (IFNs)  II- Second Line of Natural Defense: 1- Circulating effector proteins in serum and body fluids suppress the growth and promote killing of microbes. They include: Lysozyme present in all body fluids. Complement: It is a group of proteins in serum and body fluids. They promote inflammation, phagocytosis (opsonization) and lysis of bacteria. Acute phase proteins: These are substances that increase in response to inflammation as; C-reactive protein (CRP). They are synthesized in the liver in response to certain cytokines, mainly, IL-1, and IL-6; these are produced by macrophages when stimulated by microbial products. Function of acute phase proteins: 1- enhance host resistance. 2- minimize tissue injury. 3- promote the resolution and repair of the inflammatory lesion. Interferons (IFNs): These are a family of proteins which are important in the non- specific defense mechanisms against viral infections. II- Second Line of Natural Defense: 2-Cells of Innate Immunity natural killer phagocytes (NK) cells  II- Second Line of Natural Defense: 2-Cells of Innate Immunity are phagocytes and natural killer (NK) cells Phagocytes are body cells specialized for capture, ingestion and destruction of invading microorganisms i.e. phagocytosis. phagocytic cells include: 1- poly morphonuclear leucocytes (neutrophils). 2- mononuclear phagocytes a) monocytes in the blood b) macrophages in the tissues (big eaters).  The process of phagocytosis includes the following stages: A- Chemotaxis and Migration:  The process of phagocytosis includes the following stages: A- Chemotaxis and Migration: If an infectious microbe breaches an epithelium and enters the sub-epithelial tissues, the resident macrophages are attracted to the site of inflammation by chemotactic substances liberated from microbes and damaged tissues. These include bacterial endotoxins (LPS), IL-8 (chemokine) ………etc. The macrophages respond by producing soluble proteins (cytokines) e.g.IL1. These activate the endothelial cells of the nearby venules to produce adhesion molecules and chemokines, which mediate the migration of leucocytes and monocytes from the blood through the endothelial wall of blood vessels to the tissues (i.e. diapedesis).  B- Attachment PRR- PAMPS attachment: The phagocytes have many receptors on their surface e.g. Toll-like, Fc receptors and Complement receptors; these are called pathogen recognition receptors (PRR). These attach to molecular structures widely expressed on microbes but not on the host cells and are called pathogen associated molecular patterns (PAMPs). These may be sugars, proteins, lipids, nucleic acids or a combination of these molecules. PRRs on phagocytic cells recognize PAMPs directly or indirectly. Opsonization: Attachment and ingestion is greatly enhanced if the organism is coated by its specific antibody, by activated complement C3b or by antibody and C3b (opsonins) and the process is called opsonization. C -Ingestion: The phagocytes proceed to engulf the organism by extending pseudopods around it. These fuse and the organism is included into a vacuole called phagosome. Lysosomal granules then fuse with the phagosome, forming the phagolysosome followed by digestion of organisms. D- Intracellular killing or digestion: A number of antimicrobial and cytotoxic substances produced by activated macrophages can destroy phagocytosed microorganisms. This can occur through: The oxygen-dependent killing system in which oxygen is converted to oxygen radicals which are powerful microbicidal agents. The oxygen-independent killing which is the result of lysosomal granules' content which include; lysozyme and a variety of hydrolytic and proteolytic enzymes.  Natural killer (NK) cells: These are large granular lymphocytes. They have a non-specific cytotoxic activity on tumor cells, virus infected cells and graft cells and are important in innate immunity.  II- Second Line of Natural Defense: 3- Inflammatory Barriers: "inflammatory response”: This includes; vasodilatation of nearby capillaries leading to redness of tissues and increase of tissue temperature, increased capillary permeability and influx of fluids and cells (exudates) into the tissues causing edema, and influx of phagocytes from the capillaries into the site of tissue damage, these engulf bacteria and release lytic enzymes that can damage nearby healthy cells forming the pus. A variety of chemical mediators are responsible for initiation of the inflammatory response. Some of these mediators are released from damaged tissues or invading microbes, some are generated by several plasma enzyme systems, and some are products of leucocytes. Among these chemical mediators are the acute phase proteins, histamine and cytokines. These participate in destroying and removing the invaders and in healing of tissues. II- Second Line of Natural Defense: 4- Cytokines of Innate Immunity: Several pro-inflammatory cytokines play a key role in inflammation i.e. IL-1, IL-6, IL-8 and TNF-𝛼.  Constitutional Factors that Modify Innate and Acquired Immunity: Species factors: Some organisms are pathogenic only to certain species of animals, e.g. M.leprae affects man but not monkey. Certain races are more susceptible than others to certain microbes, e.g. negros and native Americans are more susceptible than the Caucasians to M. tuberculosis. Individuals in the same race may vary in their susceptibility to some organisms depending on their genetic make up, e.g. individuals who have genetic deficiency in G6PD enzyme are resistant to malaria. Age differences in susceptibility are met with, e.g. extremes of age are more susceptible to disease, due to immaturity of the immune system in children and aging of this system in the elderly. Nutritional status; under-nutrition increases susceptibility to disease. Hormones and corticosteroids increase susceptibility to infection. Diabetics are more susceptible to infection. Thank you