CD8 +

2. CD8+ CD4+

3. Natural Killer (NK) Cells •A group of cells that are classified neither as B- or T-cells, are considered "null cells". NK cells are the biggest of this group: --they lack receptors for antigen recognition; --they can not participate in acquired immunity •Large granular lymphocytes, but since they lack many of the receptors of B- and T-cells, they can not function directly in the acquired immune response. •More closely related to innate immune response.

4. Natural Killer (NK) Cells (cont’d)  •What makes NK a cell unique is their spontaneous ability to kill tumor cells and virus-infected cells, which produce large quantities of -interferon (IFN-).

5. Acquired Immunity Protection by the crude mechanism of innate immunity is augmented by "acquired" or "adaptive" immunity: •Prior exposure- acquired immunity requires prior exposure to the inducing agent for full expression; contact with the immunogen is immunization. •Specificity- the mechanisms of acquired immunity are always highly specific to the immunogen.

6. Acquired Immunity (cont’d) •Memory- primary response to immunization is short-lived with generation of specific memory lymphocytes. Secondary exposure leads to a rapid substantial response. --memory is the rationale for the practice of vaccination. •Discrimination between 'self' and 'non-self'- most important feature of acquired immunity is the ability to distinguish between host and foreign molecules.

7. Binding Antigens by B- and T-Lymphocytes •Bind antigens by means of specialized antigen receptors, and they do collaborate in the immune response. •B-cell antigen receptor is an immunoglobulin (Ig) molecule. •T-cell antigen receptoris a related molecule of different structure called the T-cell receptor (TcR). •B-cells can use their Ig receptors to recognize native antigenic molecules. •T-cells recognize only peptide fragments of antigens prepared by antigen-presenting cells (macrophage-monocyte lineages and the B-cells themselves).

8. Binding Antigens by B- and T-Lymphocytes (cont’d) Common features that characterize mode of antigen recognition: •Cell surface receptors (thousands of them per cell) expressed by an individual T- or B-cell are identical; --confers specificity to respond to a single antigen, and to have limited cross-reactivity. •Antigen receptors are synthesized and expressedprior to encounters with antigens. --immune systems pre-arms itself with a vast array of antigen receptor specificity's.

9. Binding Antigens by B- and T-Lymphocytes (cont’d) •On encounter with an antigen, a T- or B-cellproliferates and differentiates into mature effector cells. --leads to expansion of clones and an effective immune response. •Alternatively, antigen encounter can lead to cell inactivation or immune cell death. --result is specific immune tolerance (that is, "self"). --formulated on theoretical grounds as the clonal selection theory, now supported by experimental evidence.

10. The Antigen-Presenting Cell (APC) •Many short fragments (peptides, carbohydrates) from these antigens are then bound to major histocompatibility complex (MHC) molecules and incorporated into the cell membrane. •If the antigen is of exogenous origin, that is, it came from outside the body, it will bind to class II MHC molecules: --MHC class II are found in APC's. •If the antigen is of endogenous origin, that is, it was produced from inside the infected cell, it will bind readily to class I MHC molecules and move to the cell membrane of the infected cell. --MHC class I are found in virtually all nucleated cells.

13. Antigen Recognition by T-Cells •T-cells do not recognize intact proteins as antigens. --T-cell receptor on T-cells recognizes foreign particle in the groove of MHC class I and II molecules. •Class I MHC molecules are expressed by virtually all cells. --T-cells that express CD8 interact with class I MHC.

14. Antigen Recognition by T-Cells (cont’d) • •In contrast, class II MHC molecules are constitutively expressed on a limited number of cell types. •   --T-cells that express CD4 interact with class II MHC. • •Class II MHC-containing cells have a well-developed lysosomal apparatus, and cause phagocytosis of antigens: • -macrophage-monocytes; -Langerhans cells; • -dendritic cells; and -B-cells are also antigen- • presenting cells.

15. Presentation of Antigen in Class I MHC There are several differences in the mode of antigen presentation by MHC class I restricted CD8+ T-cells: •Class I molecules are expressed by virtually all cell types(therefore, any nucleated cell is a potential APC). •Class I restricted CD8+ T-cells exert primarily a cytotoxic function against virally infected or neoplastic cells. •Antigenic peptide associated with the class I molecule is produced by the antigen presenting cell itself.

16. Presentation of Antigen in Class I MHC (cont’d) •The cell that serves the function of antigen-presenting cell, cytoplasmic proteins are degraded by proteosomes: --multimeric proteases of which are encoded in the MHC complex of genes. --these peptides are then transported to the ER lumen, bind class I molecules and transported to the cell surface.

17. T-Lymphocyte Subsets (cont’d) •CD4 bind MHC Class II-peptides on target APC cells. ("CD" stands for Cluster of Differentiation)  Two subsets of CD4+ T-lymphocytes (~65% of peripheral blood T-cells are CD4+)  T-helper lymphocytes (TH) T-delayed-type hyper- sensitivity (TDTH)  help and induce activation secrete chemotactic of B-lymphocytes factors for macrophages  secrete IL-2, interferon-gamma act as growth factors

18. T-Lymphocyte Subsets (cont’d) •CD8 bind MHC Class I-peptides on target cells. Two subsets of CD8+ T-lymphocytes  suppressor T-lymphocytescytotoxic T-lymphocytes (TS) (TC)  act as a brake on TH release cytolytic lymphocytes substances such a perforin directly onto target cells

19. Need for T- and B-cells for the Humoral Response •An efficient humoral response does not occur in the absence of T-cell because they provide the help needed to promote B-cell proliferation and differentiation into plasma cells. •B-cell growth factors from T-cells: interferon-g, IL-2, IL-4.