Innate Immune System

                                                               Abel Goa, Sunday, November 18, 2012
                                                               Power Point Presentation: Elective in Immunology
                                                               Topic: Innate Immune System

Innate Immune System

• Prevents entry of microorganism into tissues
• Once they gain entry, eliminates them prior to the occurrence of disease
• Nonspecific
• Fast! Occurs within minutes of pathogen recognition
• Does not generate immunologic memory

Function of Innate Immune System

• Acting as a physical and chemical barrier to infectious agents
• Recruiting immune cells to sites of infection, through the production of chemical factors, including specialized chemical mediators, called cytokines
• Activation of the complement cascade to identify bacteria, activate cells and to promote clearance of dead cells or antibody complexes
• The identification and removal of foreign substances present in organs, tissues, the blood and lymph, by specialized white blood cells
• Activation of the adaptive immune system through a process known as antigen presentation

Relationship of Innate Immune System to Adaptive Immune System

Defensive Barriers

Innate immunity can be seen to comprise of four types of defensive barriers

o Anatomic

o Physiologic

o Phagocytic/Endocytic

o Inflammatory

Anatomical Barrier

The skin consists of two distinct layers: a thinner outer layer—the epidermis—and a thicker inner layer—the dermis

• Epidermis: Epithelial surface impermeable to most infectious agents 
• The dermis: Sebaceous gland produce an oily secretion called sebum. Sebum consists of lactic acid and fatty acids, which maintain the pH of the skin between 3 and 5; this pH inhibits the growth of most microorganisms

Mucous membrane lines the conjunctivae and the alimentary, respiratory, and urogenital tracts.
Although many pathogens enter the body by binding to and penetrating mucous membranes, a number of nonspecific defense mechanisms tend to prevent this entry

• Saliva 
• Tears 
• Mucous secretion

Other properties of mucous membrane in dealing with pathogens

• Cilia: Synchronous movement of cilia propels mucus-entrapped microorganisms out of the lower respiratory tract 
• Peristalsis: Helps to remove infectious agent from the GIT 
• Normal flora: Generally out-compete pathogens for attachment sites and for necessary nutrients

Physiologic Barrier

Physiologic barriers that contribute to innate immunity

• Temperature, e.g. in many species of animals, their normal body temperature can inhibit growth of pathogens 
• pH, e.g. gastric acid-very few organism can survive the low pH of the stomach content 
• Various soluble and cell associate molecule

Various soluble and cell mediated molecule

• Lysozymes: a hydrolytic enzyme found in mucous secretions and in tears, is able to cleave the peptidoglycan layer of the bacterial cell wall 
• Alpha-defensins: anti-fungal peptides (intestinal tract) 
• Beta-defensins: anti-microbial peptides (respiratory, urogenital tract) 
• Surfactant-A and D proteins: opsonize pathogens for enhanced phagocytosis (lung)
• Interferon: a group of proteins produced by virus-infected cells. Inhibits viral replication and activates other cells which kill the pathogen 
• Complement: a group of about 25 serum proteins that circulate in an inactive state. Once activated, they either destroy pathogens directly or facilitating their clearance 
• Transferin and Lactoferin deprive microorganism of iron 
• Fibronectin coats (opsonizes) bacteria and promote their rapid phagocytosis 
• Toll like receptors- recognise microbial molecules, signals cells to secrete immunostimulatory cytokine

Phagocytic Barrier 

Another important innate defense mechanism is the ingestion of extracellular particulate material by phagocytosis

• Internalization of pathogen into phagosome 
• Fusion of phagosome with lysosomes that contain anti-microbial compounds (lysozyme) 
• This may be sufficient to kill the pathogen 
• If not, reactive oxygen and nitrogen species may need to be generated

Source: Image from Kuby Immunology Textbook

Leukocyte Player of the Innate Immune System

Source: Unknown

Inflamatory Response

• Inflammation is one of the first responses of the immune system to infection or irritation 
• Inflammation is stimulated by chemical factors released by injured cells and serves to establish a physical barrier against the spread of infection, and to promote healing of any damaged tissue following the clearance of pathogens 
• The end result of inflammation may be the marshalling of a specific immune response to the invasion or clearance of the invader by components of the innate immune system
• Initiated by cells already present in all tissues, mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells and mastocytes. These cells present on their surfaces certain receptors named pattern recognition receptors(PRRs), which recognise molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs) 
• At the onset of an infection, burn, or other injuries, these cells undergo activation (one of their PRR recognize a PAMP) and release inflammatory mediators responsible for the clinical signs of inflammation
• 5 signs of Inflammation 
o rubor (redness),
o tumor (swelling),
o calor (heat), and
o dolor (pain).
o functio laesa (loss of function)

• The cardinal signs of inflammation reflect the three major events of an inflammatory response

1. Vasodilation—an increase in the diameter of blood vessels—of nearby capillaries occurs as the vessels that carry blood away from the affected area constrict, resulting in engorgement of the capillary network
2. An increase in capillary permeability facilitates an influx of fluid and cells from the engorged capillaries into the tissue. Accumulation of exudate contributes to tissue swelling
3. Influx of phagocytes from the capillaries into the tissues is facilitated by the increased permeability of the capillaries. Their migration through the tissue to the site of the invasion is called chemotaxis

• As phagocytic cells accumulate at the site and begin to phagocytose bacteria, they release lytic enzymes, which can damage nearby healthy cells. The accumulation of dead cells, digested material, and fluid forms pus
• The events in the inflammatory response are initiated by a complex series of events involving a variety of chemical mediators whose interactions are only partly understood

Source: Image from Kuby Immunology Textbook

Among the chemical mediators released in response to tissue damage are various serum proteins called acute-phase proteins

• C-reactive protein is a major acute-phase protein. C-reactive protein binds to the C-polysaccharide cell-wall component found on a variety of bacteria and fungi. This binding activates the complement system, resulting in increased clearance of the pathogen either by complement-mediated lysis or by a complement mediated increase in phagocytosis

Chemical factors produced during inflammation (histamine, bradykinin, serotonin, leukotrienes, and prostaglandins) sensitize pain receptors, cause vasodilatation of the blood vessels at the scene, and attract phagocytes, especially neutrophils. Neutrophils then trigger other parts of the immune system by releasing factors that summon other leukocytes and lymphocytes. Cytokines produced by macrophages and other cells of the innate immune system mediate the inflammatory response. These cytokines include TNF, HMGB1, and IL-1

Enzymes of blood clothing system

• These enzymes activate an enzyme cascade that results in the deposition of insoluble strands of fibrin, which is the main component of a blood clot. The fibrin strands wall off the injured area from the rest of the body and serve to prevent the spread of infection 
• Once the inflammatory response has subsided and most of the debris has been cleared away by phagocytic cells, tissue repair and regeneration of new tissue begins

Reference

Kuby Immunology Textbook

Note: Lost my references. Kuby Immunology Textbook is the only book I can remember (Not sure who the authors or any other details about the book)