Interferon

1. Interferon A nonspecific defense mechanism prevents the spread of viruses within the body by interfering with virus replication. This defense is provided by a group of proteins named interferon. The secretion of two interferon, called interferon-alpha (IFN-α) and interferon-beta (IFN-β) from virus infected cells signals to the surrounding cells the presence of the virus and induce the cell resistance. The viral nucleic acid that accumulates in a virus infected cell during viral replication stimulates the cells to synthesize and secrete interferon.

2. the interferon it secrets binds to nearby healthy cells, initiating in them a series of intracellular changes that cause the cells to become more resistant to the virus. RNA-degrading enzymes and protein synthesis inhibitors in the cytoplasm. Interferon-gamma (IFN-γ) Is secreted not by the virus infected cells, but by active T-cells, and NK cells, and it has a broader range of effects. In addition to inhibiting viral replication, IFN-γ enhances phagocytosis, boosts antibody production in B- cells, and helps to activate NK cells and cytotoxic-T cells to kill cancer cells and viral infected cells

3. Large granular lymphocytes that are derived from the bone marrow, its about 10% of total lymphocytes in blood they circulate in the blood and contain cytolytic granules and surface markers. Natural Killer cell (NK cell)

4. Extracellular killing of virally infected cell by natural killer (NK) cell

5. They possess activating receptors which recognize structures on the surface of virally infected cells or on tumor cells. Many of the ligands for the activating receptors can also be present on non-infected normal cells, and therefore the NK cells also possess inhibitory receptors to prevent killing of normal cells. These inhibitory receptors, which inhibit the signals from the activating receptors, recognize self-molecules such as the major histocompatibility complex (MHC) class I glycoprotein normally found on the surface of all nucleated cells.However, virally infected or tumor cells often lose expression of MHC class I. Thus, only in the absence of MHC class I is the killing of the target cell allowed to proceed.

6. Natural killer cells possess both activating and inhibitory receptors Activation of the NK cell ensues and leads to secrete of granules contents into the space between the two cells. This is followed by target cell death.

7. The most important of these granule contents is a perforin or cytolysin, it can insert itself into the membrane of the target forming a transmembrane pore. In addition to perforin, the granules contain lymphotoxin-α and granzymes, one of which, granzyme B, can function as an NK cytotoxic factor by inducing apoptosis (programmed cell death) in the target cell. An alternative recognition system for NK-cell mediated killing can involve engagement of up regulated Fas receptor molecules on the target cell surface by the FasL (Fas-ligand) on the NK cell, a process that also induces apoptosis.

8. NK cell has a receptor for called (Fc receptor) which can binds with Fc portion of Ab which is bound with infected cell and cause lysis of the infected cell by a process called Antibody dependent cell mediated cytotoxicity (ADCC)

9. cytokines such as interleukin (IL-1) and tumor necrosis factor (TNF), which play an important role in inflammation Not only do NK cells have the ability to lyse virally infected and tumor cells, but they also produce a wide range of cytokines once they are activated. • granulocyte macrophage colony-stimulating factor (GM-CSF), interferon  (IFN) and transforming growth factor-β (TGFβ), which modulate the acquired immune response • Natural killer cells also regulate B-cell function when they are activated.

10. Antigens and immunogenicity Immunogens: Any material inters the body and provokes the immune system to produce a specific Ab which can bind specifically with that Ag. Sometimes Ag is not immunogenic material and in this case we called it Hapten. Epitopes: (also called determinant groups or antigenic determinants): are the sites either on or within the antigen with which antibodies and T-cell receptors react. Size of epitopes: Epitopes are very small (i.e., just four or five AA or monosaccharide residues).

11. The epitopes on the Ag can be linear (i.e., continuous within the AA sequences of the molecule) or conformational (i.e., containing AA that end up in the same area on the surface of the protein but are not adjacent in the peptide chain).

12. Ag in order to be immunogenic should have the following important points. Foreignness Molecularsize Chemical structure Foreignness: means the Ag which inters the body is foreign and this structure is not found inside the body An Ag must be foreign or alien to the host with which it makes contact, the greater the phylogenetic difference, the use of transplant terminology helps to clarify this concept.

13. Autologous Ag are found within the same individual. That is, they are not foreign to that individual. For example, a skin graft from a man’s thigh to his chest is an autograft. It is not foreign and will not be attacked by the immune system. Syngeneic Ag are found in genetically identical individuals (e.g., identical twins). A graft between identical twins is a syngeneic graft or an isograft, and is not foreign. Allogeneic Ag are found in genetically dissimilar members of the same species. For example, a kidney transplant from mother to daughter is called allograft. It is foreign, and therefore can induce an immune response in the recipient.

14. Xenogeneic Ag are found in different species. For example, a transplant of a monkey’s to human is called a heterograft, or xenograft, and it is highly immunogenic. The term heterologous sometimes is used as a synonym for xonogeneic. Forssmann Ag (heterphile Ag) They are present in deferent species of human, and animals, have in common 1 or more shared epitopes. As a result they are cross react with the same Ab because of the presence of this shared epitopes.

15. Molecular size when we got long Ag mean there is many epitopes and it is better immunogenic when such epitope is variable, therefore polymerization of large quantity of sugar is not good immunogenic because they are same epitopes, but when they are variable sugar or amino acid they are good immunogenic. Hapten Haptens are usually unique molecules sometimes called (incomplete or partial) antigens. They usually too small to be immunogenic (less than 5 KD) Some person are sensitive to penicillin in this case this penicillin will bind to albumin and together the size become more than 5KD and the immune system will recognize it.

16. Chemical structure:

17. Adjuvants • Adjuvants can act as depots and prolong the period of exposure to the immunogen • The adjuvant may be irritant that increase the inflammatory response at the site of immunogen administration. • Some adjuvants may amplify the proliferation of immunologically committed cells.

18. Types of antigens T-independent antigens are antigens which can directly stimulate the B cells to produce antibody without the requirement for T cell help (polysaccharides). These antigens are characterized by the same antigenic determinant repeated many times. Many of these antigens can activate B cell clones specific for other antigens (polyclonal activation). T-independent antigens are generally more resistant to degradation and thus they persist for longer periods of time and continue to stimulate the immune system.

19. T-dependent antigens are those that do not directly stimulate the production of antibody without the help of T cells. Proteins are T-dependent antigens. Structurally these antigens are characterized by a few copies of many different antigenic determinants Hapten-carrier conjugates are immunogenic molecules to which haptens have been covalently attached. The immunogenic molecule is called the carrier. Structurally these conjugates are characterized by having native antigenic determinants of the carrier as well as new determinants created by the hapten (haptenic determinants). In such conjugates the type of carrier determines whether the response will be T-independent or T-dependent.

20. Superantigens When the immune system encounters T-dependent antigen, only a small fraction of the T cell population is able to recognize the antigen and become activated. However, there are some antigens which polyclonally activate a large fraction of the T cells (up to 25%). These antigens are called superantigens. Examples : Staphylococcal enterotoxins, Staphylococcal toxic shock toxin, Staphylococcal exfoliating toxins and Streptococcal pyrogenic toxin exotoxins