Question

2. Identify the ligand, microorganism recognized and cell carrying receptor for TLR3, 4, 5, 7
3. Describe the role of NFkB, IL-6, TNF-a, and IL-1B _
4. List the major components of the complement system
5. Describe how the Membrane Attack Complex (MAC) kills cells

Answer 1

C.Interleukin 1 beta. Interleukin 1 beta , also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor , is a cytokine protein that in humans is encoded by the IL1B gene.

The fever-producing property of human leukocytic pyrogen (interleukin 1)was found and named lymphocyte-activating factor (LAF) because it was a lymphocyte mitogen.

IL-1β is a member of the interleukin 1 family of cytokines. This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1 . This cytokine is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. The induction of cyclooxygenase-2-COX2..by this cytokine in the central nervous system (CNS) is found to contribute to inflammatory pain hypersensitivity.

.Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the IL6 gene.

Functions.-

• IL-6 is an important mediator of fever and of the acute phase response.
• It is capable of crossing the blood-brain barrier and initiating synthesis of PGE2 in the hypothalamus, thereby changing the body's temperature set point.
• In muscle and fatty tissue, IL-6 stimulates energy mobilization that leads to increased body temperature.
• IL-6 can be secreted by macrophages in response to specific microbial molecules, referred to as pathogen-associated molecular patterns (PAMPs). These PAMPs bind to an important group of detection molecules of the innate immune system, called pattern recognition receptors (PRRs), including Toll-like receptors (TLRs). These are present on the cell surface and intracellular compartments and induce intracellular signaling cascades that give rise to inflammatory cytokine production.
• IL-6 is found in many supplemental cloning media such as briclone.
• Inhibitors of IL-6 (including estrogen) are used to treat postmenopausal osteoporosis.
• IL-6 is also produced by adipocytes and is thought to be a reason why obese individuals have higher endogeneous levels of CRP.
• Intranasally administered IL-6 has been shown to improve sleep-associated consolidation of emotional memories.
• IL-6 is responsible for stimulating acute phase protein synthesis, as well as the production of neutrophils in the bone marrow. It supports the growth of B cells and is antagonistic to regulatory T cells.
• When psychologically stressed, the human body produces stress hormones like cortisol, which are able to trigger interleukin-6 release into the circulation.

D.COMPONENTS. The complement system consists of atleast 30 chemically and immunologically distinct serum protiens which make up the complement components,the properdin system and the control protiens.The biological activities of this system affect both innate and acquired immunity far beyond the earlier concept of antibody-mediated lysis of bacteria and erythrocytes.Initially,the structual protiens were thought to be involved in complement pathways in innate immunity but interactions of cellular receptors with C protiens which control B cell activation play a crucial role in the highly developed acquired immune system.FRACTIONS- Complement is a complex of nine different fractions C1 TO C9 .The fraction C1 occurs in serum as a calcium ion dependent complex,which on chelation with EDTA yields three protien subunits called C1q,r,s.Thus C is madeup of a total of 11 different protiens.C fractions are named C1 to C9 in the sequence of the cascading reaction,except that C4 comes after C1 before C2.The model traditionally used to explain C activity in immune cytolysis is the lysis of erythrocyte sensitised by its antibody.The erythrocyte[E] antibody[A] complex is called EA and when C components are attached to EA ,the product is called EAC ,followed by the components that have reacted.When a C component acquires enzymatic or other demonstrable biological activity,it is indicated by a bar over the component number,for example,enzymatically activated C1 showed as C1-[bar],fragments cleaved from C components during the cascade are indicated by small letters C3a,C3b.Inactivated forms of C components are indicated by the prefix 'i' [iC3b].

E.Membrane attack complex: An abnormal activation of the complement (protein) portion of the blood that forms a cascade reaction and brings blood proteins together, binds them to the cell wall, and then inserts them through the cellmembrane.Bacterial infections can result in severe diseases. The complement system resides in all body fluids, and when activated can form pores in the surface of the bacteria by the formation of the membrane attack complex. As a result, crucialbacterial functions are deregulated and the bacteria is killed.