IMMUNOLOGY Ms. Lucky Juneja Lecturer, School of Biotechnology, DAVV

 Immunity—the state of protection from infectious disease  Via both a non-specific and specific component.  The less specific component, innate immunity, provides the first line of defense against infection, that are not specific to a particular pathogen.  Phagocytic cells, such as macrophages and neutrophils, barriers such as skin, and a variety of antimicrobial compounds synthesized by the host all play important roles in innate immunity.  Adaptive immunity, does not come into play until there is an antigenic challenge to the organism.  Adaptive immunity responds to the challenge with a high degree of specificity as well as the remarkable property of “memory.”

Anatomoic Barriers  Tend to prevent the entry of Pathogen.  Mucous membranes lined at the alimentary, respiratory and urogenital tracts.  Many pathogens enter the body by binding to and penetrating mucous membranes.*ex-saliva, tears, and mucous secretions act to wash away potential invaders, contain antibacterial or antiviral substances  In the lower respiratory tract,it is covered by Cilia,hair like protrusions of epithelial cell membrane.  The movement of cilia propel mucus caused the entrapped micro from these tracts.

 Some organism escaping these defense mechanisms and are able to invade the body through mucous membranes.e.g Infuenza Virus.  Normal flora compete with microbes for attachment sites and nutrients.  Adherence of bacteria to the mucous membrane due to the interaction b/w hair like protusion on bacteria that is Fimbriae/Pili.  Certain Glycoprotein or Glycolipid that experessed only by epithelial cell of mucuos membrane of particular tissue.*

Physiologic Barrier  It include Temperature,Low pH,Chemical mediators.  Normal body temperature inhibits growth of some pathogens.  E.g. Chicken have innate immunity to Antrax due to high body temp.  Acidity of stomach contents kills most ingested microorganisms.  Therefore newborns are susceptible to some diseases their stomach contents are less acid than those of adults.  Lysozyme,Interferon,Complement are Soluble factor that contribute to innate immunity.  Lysozyme are found in mucous secretion,tears.*  Interferon induces antiviral state in uninfected cells.*  Complement lyses microorganisms or facilitates phagocytosis.*

Phagocytic/Endocytic Barrier

Inflammatory Barrier

Adaptive Immunity  Unlike innate immune responses.  The adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogenic challenges.  The adaptive or "specific" immune system is activated by the “non-specific” and evolutionarily older innate immune system.  Adaptive immune responses are not the same in all members of a species but are reactions to specific antigenic challenges.  Adaptive immune responses exhibit four immunologic attributes:specificity, diversity, memory, and self/nonself recognition.

 The antigenic specificity of the immune system permits it to distinguish subtle differences among antigens.  Antibodies can distinguish between two protein molecules that differ in only a single amino acid.  The immune system is capable of generating tremendous diversity in its recognition molecules,allowing it to recognize billions of unique structures on foreign antigens.*

Cells of immune system  An effective immune response involves two major groups of cells: lymphocytes and antigen-presenting cells.  Lymphocytes are types of white blood cells produced in the bone marrow by the process of hematopoiesis.*  It display antigen binding cell-surface receptors, therefore lymphocytes mediate the defining immunologic attributes of specificity, diversity, memory, and self/nonself recognition.  B-Lymphocytes (B-cells), T- Lymphocytes (T-cells).

ANTIGEN-PRESENTING CELLS  Activation of both the humoral and cell-mediated branches of the immune system requires cytokines produced by TH cells.

Antigen Selection of Lymphocytes Causes Clonal Expansion  Clonal selection provides a framework for understanding the specificity and self/nonself recognition that is characteristic of adaptive immunity.

Antigens Antigen.* Immunogenicity/Antigenicity.* Factors that influence immunogenicity.*

Contribution of the immunogen to immunogenicity Foreignness. Molecular size. * Chemical composition. Complexity.

Foreignness  When an antigen is introduced into an organism, the degree of its immunogenicity depends on the degree of its foreignness.  The greater the phylogenetic distance between two species, the greater the structural difference between them.  Ex- BSA is not immunogenic when injected into a cow but is strongly immunogenic when injected into a rabbit.  BSA would be expected to exhibit greater immunogenicity in a chicken than in a goat, which is more closely related to bovines.

Chemical composition Size and foreignness are not, by themselves, sufficient to make a molecule immunogenic. Synthetic homopolymers (polymers composed of a single amino acid or sugar) tend to lack immunogenicity regardless of their size. Copolymers composed of different amino acids or sugars are usually more immunogenic than homopolymers of their constituents. These show that chemical complexity contributes to immunogenicity. Therefore, it is clear that all four levels of protein organization contribute to the structural complexity of a protein and hence affect its immunogenicity

SUSCEPTIBILITY TO ANTIGEN PROCESSING AND PRESENTATION  Large, insoluble macromolecules are more immunogenic than small, soluble ones because the larger molecules are more readily phagocytosed and processed.  Macromolecules that cannot be degraded and presented with MHC molecules are poor immunogens.  Ex-polymer of D-amino acids, which are stereoisomers of the naturally occurring L-amino acids.*

GENOTYPE OF THE RECIPIENT ANIMAL  The genetic constitution (genotype) of an immunized animal influences the type of immune response the animal manifests, as well as the degree of the response.*

ADJUVANTS  Adjuvant are substances, when mixed with an antigen and injected with it, enhance the immunogenicity of that antigen.  The antibody response of mice to immunization with BSA can be increased fivefold or more if the BSA is administered with an adjuvant. They appear to exert one or more of the effects:- 1.Antigen persistence is prolonged. 2.Co-stimulatory signals are enhanced. 3.Local inflammation is increased. 4.The nonspecific proliferation of lymphocytes is stimulated.

 Aluminum potassium sulfate (alum) prolongs the persistence of antigen.  When an antigen is mixed with alum, the salt precipitates the antigen.  Injection of this alum precipitate results in a slower release of antigen from the injection site, so that the effective time of exposure to the antigen increases from a few days without adjuvant to several weeks with the adjuvant.

Epitopes  Epitopes are the immunologically active regions of an immunogen that bind to antigen-specific membrane receptors on lymphocytes or to secreted antibodies.  Paratope.  B cells recognize soluble antigen.*  T cells recognize only peptides combined with MHC molecules on the surface of antigen-presenting cells.

Properties of B-Cell Epitopes Are Determined by the Nature of the Antigen-Binding Site  The B-cell epitopes on native proteins are composed of hydrophilic amino acids on the protein surface that are topographically accessible to free antibody.  Amino acid sequences that are hidden within the interior of a protein often consist of hydrophobic amino acids, and cannot function as B-cell epitopes unless the protein is first denatured.

 Antibody binds to an epitope by weak noncovalent interactions.  The antibody’s binding site and the epitope must have complementary shapes that place the interacting groups near each other.  The size of the epitope recognized by a B cell can be no larger than the size of the antibody’s binding site.

 Complex proteins contain multiple overlapping B-cell epitopes, some of which are immunodominant.  Immunodominant epitope*.

Properties of T-cell epitopes Gell and Benacerraf compared the humoral (B-cell) and cell- mediated (T-cell) responses to a series of native and denatured protein antigens.

Antigenic peptides recognized by T cells form trimolecular complexes with a T-cell receptor and an MHC molecule.*

Hapten and Antigenicity  Karl Landsteiner in the 1920s and 1930s created a simple, chemically defined system for studying the binding of an individual antibody to a unique epitope on a complex protein antigen.

 When multiple molecules of a single hapten are coupled to a carrier protein, the hapten becomes accessible to the immune system and can function as an immunogen.

 Landsteiner found that the overall configuration of a hapten plays a major role in determining whether it can react with a given antibody.  For example, antiserum from rabbits immunized with aminobenzene or one of its carboxyl derivatives (o-aminobenzoic acid, m- aminobenzoic acid, or p-aminobenzoic acid) coupled to a carrier protein reacted only with the original immunizing hapten and did not cross-react with any of the other haptens