Immunology
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The document summarizes the innate and adaptive immune system. It describes the lymphocytes (T and B cells) that are key cells of the adaptive immune system. It then focuses on T cells, describing their identification by CD molecules including CD3, CD4, and CD8. It explains the roles of CD4+ T helper cells and CD8+ cytotoxic T cells. It also briefly discusses natural killer cells and their role in killing infected and tumor cells.
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Immunology
- 3. 1. Complement System INNATE IMMUNE SYSTEM 2. Phagocytes (neutrophils, macrophages, mast cells) ADAPTIVE IMMUNE SYSTEM Lymphocytes: T and B Cells
- 4. cells of innate immunity Cells of adaptive immunity.
- 8. Lymphocytes are usually defined by where they undergo their “ basic training” --- Thymus- derived. Bone marrow derived. T – lymphocytes/ T cells B – lymphocytes/ B cells Natural killer T/ NKT cells.
- 9. Lymphocytes can also be defined by the type of receptor they display on their cell surfaces TCR BCR / Ig neither - T cells - B cells - Natural killer cells - NKT cells
- 18. The T cell can be identified by the presence of the CD-3(cluster of differentiation ) molecule which is associated with TCR on the T cell surface. Two other CD molecules are used to identify CD3+ T cell subsets , CD 4 + and CD 8 +
- 19. CD 4 + T CELLS It accounts for approx. 2/3rd of mature CD3 + cells. Also known as Helper T ( Th) cells. CD 4 molecules displayed on the surface of these cells recognize a non peptide binding portion of MHC class II molecules, thus are restricted to the recognition of p MHC class II complexes.
- 21. T helper 1(TH1)- regulation of cellular immunity. -Interferon – y, IL- 2. T helper 2 (TH 2)- helps B cell in isotype switching. - Production of antibodies. - IL- 4, IL-5,IL-6,IL-10. Interferon – y inhibits TH 2. IL-4 & IL-10 inhibits TH 1.
- 22. CD 8 + T cells Comprises approx. 1/3rd of all mature CD3 + T cells. These are ‘restricted’ to the recognition of p MHC I complexes. Also known as – A) Cytotoxic T ( Tc) – identification of cells infected with intracellular organisms, viruses and bacteria and eliminate such cells. B) Suppressor T ( Ts ) – Down regulation of immune
- 23. NATURAL KILLER CELLS Large lymphocytes ( 5 – 10% of peripheral blood lymphocytes ) which develop in the bone marrow. They have an ability to kill virally infected cells and tumor cells without prior sensitization ( no need for antigen recognition) Receptors - KARs and KIRs
- 25. THYMOCYTE DEVELOPMENT: +VE/-VE SELECTION
- 26. T CELL ACTIVATION APC = e.g., Macrophage CD 4+ T cell CD4 MHC Class II Peptide Antigen TCR 1 1st signal. Formation of pMHC: TCR: CD + 2ND signal. Costimulatory Molecules. 2
- 27. CD 4 + CELL MATURATION. TH 1 TH 2
- 28. CD 8 + T CELL MATURATION p MHC CLASS I: TCR: CD8 +( 1st signal) expression of IL – 2 receptors IL – 2 secretion by primed CD4+ ( 2nd signal) cytotoxic T Lymphocytes cell lysis
Editor's Notes
- A wide variety of organisms and their associated molecules like the bacteria, fungi, protozoa, parasites,toxins, cancer pose constant threat to human body. The human immune system is able to identify and neutralize these threats. It is also able to distinguish ‘nonself’ organisms from the molecules which are ‘self’ ie which belongs to the body. The immune system consists of three layers of denfense. The first line of defense is the set of mechanical, chemical and biologic barriers. When this barrier is breached, the second and third line of defense ie the innate and adaptive immunity comes to play.
- On 1st exposure the pathogen is engulfed by the macrophage. Macrophage then becomes an antigen presenting cell. It stimulates the helper T cell to either both stimulate the cytotoxic T cell or the B cell. It also forms the memory T helper cell. The cytotoxic T cells causes the direct killing of the pathogens. The memory T helper cell on subsequent exposure to the same antigen cause the stimulation of memory T cell,cytotoxic T cell and the memory B cell thus ensuing rapid response. Also to be kept in mind that T cell plays a role in defense against the intracellular pathogens and cancer cells
- The complement system and phagocytes make up the innate immune system. Unlike the innate immune system which consists of morphologically distinct cells, the lymphocytes of adaptive immune system consists of cells which are generally look alike except of variation in the sizes.
- The cells of innate immunity includes basophils, eosinophils, neutrophils, monocytes belonging to the myeloid stem cells. The cells of adaptive immunity includes the T cells and the B cells belonging to the lymphoid stem cells.
- T Cells arises from the hematopoeietic stem cell in the bome marrow. The immature T cells are known as prothymocytes. The prothymocytes migrates to the thymus where they develop TCRs and are screened for their ability to distinguish self from nonself. Though must of the thymocytes fail the screening process those that pass able to further differentiate and mature and enter into the circulation as a NAÏVE T CELL.
- MHC class I is found in phagocytes
- The CD 4+ lymphocytes are the work horses of the immune system. This figure shows typical CD 4+ cell with TCR, CD 3 signalling complex molecule and the CD 4 molecule on the cell surface.
- Killer activation receptors and killer inhibition receptors
- NK T CELLS share functional characteristics with the NK CELLS. IT DEVELPOS IN THYMUS AND EXPRESS A TCR OF EXTREMLY LIMITED REPERTOIRE. UNLIKE CONVENTIONAL T CELLS , NKT CELLS RESPOND TO LIPIDS, GLYCOLIPIDS, HYDROPHOBIC PEPTIDES PRESENTED BY MHC class I , CD 1 d and secrete a large amount of IL- 4.
- Epitope specific TCR/ BCR are randomly generated within individual thymus and bone marrow derived lymphocytes by gene rearrangement. Not surprisingly ,some lymphocytes develop receptors that reat with epitopes. However a selection mechanism is in place that removes these cells before they become fully functional and attack the body’s own tissues or organs.
- Figure of an immunologic synapse. The weak interaction beween the TCR an the p MHC is strengthened by binding of the CD 4/ CD 8 WITH THE constant region of p MHC . The complex formation provides the 1st signal. The second signal is provided by the costimulatory molecules. In absence of the secon signal, the naïve T CELL cannot be activated. It either becomes unresponsive- ANERGY OR UNDERGOES APOPTOSIS.
- After the interaction of CD 4+ cell with antigen known as priming, the cells are known as t helper cells. Upon activation the naïve CD 4+ CELL SECRETE various cytokines and express cell surface receptors known as pathway uncommitted T HELPER CELLS. Also some CD 4+ cells also form the MEMORY T HELPER CELLS
- Cytotoxic T LYMPHOCYTES contain perforins and granzymes( serine proteases) to deliver fatal blow to the cell.