Question

In innate immune response,

a) How is the virus recognized by the host? Explain and name the cells/receptors involved

b) What signaling pathways are triggered? Name and explain the major pathways needed to mount an antiviral response.

Answer 1

Innate is non specific or natural immunity present from the birth and consists of many factors that are relatively non specific. It provide first line of defense against pathogens. It is not specific to any one pathogen but acts against all foreign molecules and pathogens. It also does not rely on previous exposure to a pathogen and response is functional since birth and has no memory.

a) many molecules involved in innate immunity have the ability to recognize a given class of molecules i.e. recognize pattern. Patterns are conserved structures and invariant among microorganisms. Pattern recognition molecules that recognize Pathogen-Associated Molecular Pattern (PAMP) may be soluble circulating proteins or cell surface receptors.

Many PAMPs are recognized by pattern recognition molecules present on the surface of phagocytic cells. Mannose binding lectin (MBL) and C-reactive protein (CRP) are soluble pattern recognition molecules that bind to microbial surfaces and promote their opsonization. Toll- like receptors (TLR) are a class of pattern recognition molecules that function exclusively as signaling receptors. There are at least 10 distinct proteins in this family of mammalian receptors. For example, TLR-4 signals the presence of bacterial lipopolysaccharide and heat shock proteins. TLR-2 signals the presence of bacterial lipoproteins and peptidoglycans.

B) major pathways for antiviral response in innate immunity are:

Physical barriers: first line of defense against microorga isms. It include skin and mucous membrane. Most organisms and foreign substances cannot penetrate intact skin.secondly the acidic pH of sweat and sebaceous secretions and the presence of various fatty acids and hydrolytic enzymes like lysozyme inhibits the growth of most microorganisms. Similarly resporatory and gastrointestinal tracts are lined by mucous membrane. Mucous membrane entraps foreign microorganisms. Tears contain lysozyme, lactoferein, IgA and thus provide chemical as well as physical protection.

Chemical mediator: include complement, cytokines,acute phase proteins,enzymes like lysozyme and many others.

Complement: complement is a heat labile component of blood plasma that augments phagocytosis. It also bridges innate and adaptive immunity. The complement system is composed of 30 serum proteins. Activation of complements in response ro certain microorganisms results in a controlled enzymatic cascade, which targets the membrane of pathogenic organism and leads to their destruction.

Cytokines: it includes monokines, lymphokines, interleukins, i terferons and others. Interferons are cytokines made by cells in response to virus infection, which essentially induce a generalized antiviral state in surrounding cells. Chemokines are small, positively charged secreted proteins that have a central role in guiding the migrations of various types of white blood cells. They bind to the surface of endothelial cells and to negatively charged proteoglycans of the extracellular matrix in organs. By binding to G- protein linked receptors on the surface of specific blood cells, chemokines attract these cells from the blood stream into an organ, guide them to specific locations within the organ, and then help stop migration.

Cellular defense: many specialized cell types like neutrophils, macrophages, monocytes,natural killer cells participate in innate host defense mechanism. Phagocytosis is a fundamental protective mechanism carroed out by these cell types.

Inflammatory barriers: inflammation is an important non specific defense reaction to cell injury. The inflammatory response is mediated by a variety of signaling molecules. Activated macrophages produce chemokines. Some of these attract neutrophils which are the first cells recruited in large numbers to the site of the new infection.others later attract monocytes and dendritic cells. The dendritic cells pick up antigens from the invading pathogens and carry them to nearby lymph nodes, where they present the antigens to lymphocytes to marshal the forces of the adaptive immune system. Two principal mediators of inflammatory response are histamine and kinins. Both cause vasodilation and increased permeability of capillaries.