IMMUNOLOGY

1. IMMUNOLOGY

2. Overviewof the immune system

3. Non specific (innate or natural immunity) Response is antigen-independent. There is immediate maximal response. Not antigen-specific. Exposure results in no immunologic memory Specific Immunity (acquired or adaptive) Response is antigen- dependent. There is a lag time between exposure and maximal response. Antigen-specific. Exposure results in immunologic memory Differences between:

4. Host Defenses

5. First line of Defense Mechanical Factors: Physical barriers to pathogens • Skin • Epidermis consists of tightly packed cells with keratin which is a protective protein. • Mucous membranes

6. Lacrimal apparatus: Washes eye • Saliva: Washes microbes off • Urine: Flows out, flushing. • Vaginal secretions: Flow out

7. Chemical Factors • Fungistatic fatty acid in sebum. • Low pH (3-5) of skin. • Lysozyme in perspiration, tears, saliva, and tissue fluids except CSF. • Low pH (1.2-3.0) of gastric juice and vaginal acidity. • Transferrins in blood reduce iron so inhibit microbial growth.

8. Normal Microbiota • Microbial antagonism/competitive exclusion: • Normal microbiota antagonize pathogen: 1-By competing with pathogens for nutrients, for colonization site by producing substances harmful to the pathogen. 2- By altering conditions that affect the survival of the pathogen. e.g. normal microbiota in vagina alters pH to prevent overpopulation of C.albicans which is a pathogenic yeast caused vaginitis.

9. Second line of Defense Phagocytosis Inflammation Fever Antimicrobial substances

10. Nonspecific DefensesNonspecific defenses deny pathogens access to the body or destroy them without distinguishing among specific types.

11. Nonspecific DefensesNonspecific defenses deny pathogens access to the body or destroy them without distinguishing among specific types.

12. Formed Elements In Blood (note functions) • RBC’s • WBC’s • Agranulocytes • 1. Monocytes and • 2. Lymphocytes • Granulocytes • 1. Neutrophils (PMNs) • 2. Basophils and • 3. Eosinophils

13. Cells of the Immune System

14. Organs of the immune system During embryonic life, haemopoeitic stem cells develop in fatal liver and other organs, these stem cells reside in the bone marrow in postnatal life. There is primary lymphoid system which is responsible for the evolution and maturation of immune cells (Bone marrow and thymus). and secondary lymphoid system (tonsils, peyer patches, spleen and other lymph nodes all over the body), responsible for trapping of foreign antigen, residence of immune cells.

15. Phagocytosis .

16. Inflammation • Redness • Pain • Heat • Swelling (oedema) • In acute-phase proteins are activated (complement, cytokine, kinins) - chemical messengers • Vasodilation (histamine, kinins, prostaglandins, leukotrienes) - bring in more help • Margination and immigration of WBCs • Tissue repair

17. Chemicals Released by Damaged Cells

18. The Complement System In serum 30 proteins produced by the liver, activated in a cascade as previous catalyzes the next step. Outcomes of Complement system • Opsonization • Chemotaxic • Cell lysis

19. Effects of Complement Activation • Opsonization or immune adherence: enhanced phagocytosis • Membrane attack complex: cytolysis • Attract phagocytes

20. Classical Pathway

21. Alternative Pathway

22. Interferons (IFNs) Antiviral proteins • Alpha IFN & Beta IFN: Cause cells to produce antiviral proteins that inhibit viral replication • Gamma IFN: Causes neutrophils and macrophages to phagocytize bacteria

23. Interferons (IFNs) New viruses released by the virus-infected host cell infect neighboring host cells. 5 The infecting virus replicates into new viruses. 2 6 AVPs degrade viral m-RNA and inhibit protein synthesis and thus interfere with viral replication. Viral RNA from an infecting virus enters the cell. 1 The infecting virus also induces the host cell to produce interferon on RNA (IFN-mRNA), which is translated into alpha and beta interferons. 3 Interferons released by the virus-infected host cell bind to plasma membrane or nuclear membrane receptors on uninfected neighboring host cells, inducing them to synthesize antiviral proteins (AVPs). These include oligoadenylate synthetase, and protein kinase. 4

24. Specific Defenses of the Host The Immune Response

25. SpecificDefenses of the Host: The Immune Response *Antigen (Ag) : A substances that causes the body to produce specific antibodies or sensitized T ells, also called immunogen. *Antibody (Ab): A proteins produced by the body in response to an antigen, and capable of combining specifically with that antigen. • Serology: Study of reactions between antibodies and antigens. • Antiserum: Generic term for serum because it contains Ab. • Globulins: Serum proteins • Gamma () globulin: Serum fraction containing Ab.

26. Serum Proteins

27. The Immune Response Two arms • Acquired immunity:The ability obtained and developed during an individual's lifetime, to produce specific antibodies or T-cell. The factors involved in this immunity known as: 1. Humoral immunity: from humors, because they were found in the body fluid, it Involves Ab produced by B cells(B lymphocytes). 2. Cell-mediated immunity: Involves specialized lymphocytes T cells or T lymphocytes

28. Acquired Immunity • Natural Acquired:( Active and passive). • Artificially Acquired:( Active and passive). *Naturally acquired active immunity • Resulting from Antigen enter the body naturally (infection). *Naturally acquired passive immunity • Antibodies via transplacental or via colostrum *Artificially acquired active immunity • Injection of Antigen (vaccination) *Artificially acquired passive immunity • Injection of performed Antibody.

29. Antigenic Determinants • A specific region on the surface of an antigen to which antibodies recognize and react with, it is called epitopes.

30. Haptensit is a molecule too small to stimulate the antibody formation by itself but only when combine with a carrier molecule. e. g. penicillin antibiotic.

31. Factors Influencing ImmunogenicityA. The Immunogen 1- Foreignness The immune system normally discriminates between self and non-self such that only foreign molecules are immunogenic. 2- Size: the larger the molecule the more immunogenic it is likely to be.( generally substances with mol.wt.> 100,000 dalton are potent immunogenic). • 3- Chemical Composition: The more chemical complexity of the substance is the more immunogenic it will be.

32. 4- Physical form - In general particulate antigens are more immunogenic than soluble ones and denatured antigens more immunogenic than the native form. 5. Degradability - Antigens that are easily phagocytosed are generally more immunogenic. This is because for most antigens (T-dependant antigens) the development of an immune response requires that the antigen be phagocytosed, processed and presented to helper T cells by an antigen presenting cell (APC).

33. CHEMICAL NATURE OF IMMUNOGENS: A. Proteins -The vast majority of immunogens are proteins. These may be pure proteins or they may be glycoproteins or lipoproteins. In general, proteins are usually very good immunogens. B. Polysaccharides - Pure polysaccharides and lipopolysaccharides are good immunogens. C. Nucleic Acids - Nucleic acids are usually poorly immunogenic. However, they may become immunogenic when single stranded or when complexed with proteins .D. Lipids - In general lipids are non-immunogenic, although they may be haptens. In an antigen, the same antigenic determinant repeated many times .

34. TYPES OF ANTIGENS T-independent Antigens- T-independent antigens are antigens which can directly stimulate the B cells to produce antibody without the requirement for T cell help . In general, polysaccharides are T-independent antigens. T-dependent Antigens - 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.

35. LYMPHOCYTES Both B cells and Tcells originate from stem cells in adult red bone marrow or in the fetal liver. (RBCs, macrophages, neutrophiles, and other WBCs also originate from these same stem cell). Some cells pass through the THYMUS and emerge as mature T-cells. Other cells probably remain in the Bone marrow and become B-cells.

36. Both types of cells then migrate to lymphoid tissues, such as lymph nodes or spleen. Once in these organs, B cells recognize antigens by means of antigen receptors which are antibody molecules on their surface (IgD).

37. After antigen exposure, B-cells changed to memory cells and antibody-secreting plasma cells. Once re-exposure to antigen, memory cells quickly proliferate to produce more plasma cells. Further differentiation of the activated B-cell into clone occurs, resulting in the formation of large antibody-secreting cells called plasma cells.

38. Plasma cells are relatively short-lived (less than 1 week) but excrete large amounts of antibody during this period. Memory cells, in contrast, are very long-lived cells, and on re-exposure to the initial stimulating antigen, they quickly transform into plasma cells and begin secreting antibody.

39. Antibody Structure

40. IgG antibodies • Monomer • 80% of serum antibodies • Fix complement • In blood, lymph, intestine • Cross placenta • Enhance phagocytosis; neutralize toxins & viruses; protects fetus & newborn • Half-life = 23 days

41. J Chain C4 IgM antibodies • Pentamer • 5-10% of serum antibodies • Fix complement • In blood, lymph, on B cells • Agglutinates microbes; first Ab produced in response to infection • Half-life = 5 days

42. Secretory Piece J Chain IgA antibodies • Dimer • 10-15% of serum antibodies • In secretions • Mucosal protection • Half-life = 6 days

43. IgD antibodies • Monomer • 0.2% of serum antibodies • In blood, lymph, on B cells • On B cells, initiate immune response • Half-life = 3 days

44. IgE antibodies • Monomer • 0.002% of serum antibodies • On mast cells and basophils, in blood • Allergic reactions; lysis of parasitic worms • Half-life = 2 days

45. Clonal Selection • Bone marrow gives rise to B cells. • Mature B cells migrate to lymphoid organs. • A mature B cells recognizes epitopes.

46. Clonal Selection

47. Self-tolerance • Body doesn't make Ab against self • Clonal deletion • The process of destroying B and T cells that react to self antigens

48. The Results of Ag-Ab Binding

49. Antibody titer • Is the amount of Ab in serum

50. Monoclonal Antibodies • Hybridomas are produced by fusing a cancer cell with an Ab-secreting plasma cells • Ideally, if an antibody-producing B cell could be grown by standard cell-culture method , it would produce the Highly specific,only desired antibody in unlimited amounts.