Response Also known as effector function. Eliminate or neutralize foreign organisms. Later exposure to same foreign organism memory response heightened immune reactivity.
Immunity “ State of protection from infectious diseases”
Nonspecific Immunity “ Basic resistance to disease that a species possesses”
Anatomic Barriers Skin Sebaceous Glands secrete sebum low pH (3-5) Inhibitory to growth of most microorganisms. Mucous membranes of the respiratory/GI/Urogenital tracts Secrete mucuc traps microorganisms and expels them by movement of celia.
Physiologic Barriers Temperature pH Soluble factors Gastric juice acidic organisms can’t survive. Newborns less acidic gastric juice more susceptible to infections.
Soluble factors Complement = serum proteins that are non active. when pathogen enters activated membrane damaging reactions clear infections
Endocytic and Phagocytic Barriers Endocytosis “Macromolecules in the ECF internalized by cells” Phagocytosis “More specialised and involves plasma membranes expanding around macromolecules Specialized phagocytic cells include: monocytes, macrophages and neutrophils.
Specific Immunity “ Reflecting the presence of a specific and functional immune system ” Properties of self immunity SPECIFICITY MEMORY DIVERSITY SELF/NONSELF RECOGNITION
Cells and Organs of The Immune System WBC or leukocytes development of immune response . Cells of The Immune System LYMPHOCYTES are CORE cells of the immune system. WHY? SPECIFICITY MEMORY DIVERSITY SELF/NONSELF RECOGNITION
Cells of The Immune System <1 Basophil 1-3 Eosinophil 1-6 Monocyte 20-40 Lymphocyte 50-70 Neutrophil 7.3 x 10 6 Leukocytes 2.5 x 10 6 Platelets 5 x 10 6 RBC % Cells/ml Cell Type
Haematopoiesis “ Formation and development of white blood cells and red blood cells from stem cells ” Begins in the yolk sac in the first few weeks of embryonic developments Yolk Sac Spleen/Liver Spleen/Liver/Bone marrow Bone marrow Birth
Stem Cells 1/10 4 bone marrow (BM) cells Pluripotent (Differentiate along a number of pathways). Two main lineages from stem cells: Lymphoid stem cells Myeloid stem cells These further differentiate into committed progenitor cells. Progenitor cells respond to particular growth factors differentiation to mature RBC’s and WBC’s.
Lymphoid Cells Lymphocytes are WBC responsible for immune response. Based on function and cell membrane components Lymphocytes Null B T
Effector cells: B cells: Plasma cells T cells: T helper cells (T H ) and cytotoxic T cells (CTL) Lymphocytes express glycoprotein as membrane cluster of differentiation ( CD )
B Cells Mature in the BM. Mature B cells have antibodies (Ab) on their surface ( 1.5x10 5 molecules/cells). All antibodies on a single B cell have identical binding sites for antigen (Ag). B cells express CD45 B cells also express MHCII functions as antigen presenting cell (APC).
T Cells Produced in BM. Matures in thymus. Recognise Ag ONLY if presented on MHC complex. Possess distinctive membrane molecules.
T Cell Subtypes Express CD4 and are class II restricted. T Helper Cells (T H ) Secrete lymphokines activation of B cells, cytotoxic T cells and other immune cells.
Cytotoxic T Cells (T C ) Express CD8 and are class I restricted. Ratio of T H :T C is 2:1 in normal blood. Altered in autoimmune diseases and immunodeficiency. Suppressor T Cells (T S ) Not isolated yet. May suppress humoral and cell-mediated immunity.
Null Cells Lack CD4 and CD8. Lack specificity and memory. Natural killer cells (NK). 5 - 10 % of lymphocyte population. Display cytotoxicity towards a variety of tumours, in absence of previous immunisation
Macrophages Either fixed or free. Motility by amoeboid movement. Nomenclature depends on location Kidney:Mesangial cells Liver: Kupffer cells Connective tissue: Histiocytes Lung: Alveolar macrophages Brain: microglial cells.
Macrophages Activation by IFN from T H cells. Activated Macrophages: a) Secrete more inflammatory mediators. b) Increased microbicidal activity c) Increased activation of T cells d) Increased expression of MHCII better as APC.
Neutrophils Stain with both acidic and basic dyes. Increased number indicated infection. First arrival at site of inflammation. Possess phagocytic properties
Eosinophils Stain with Eosin Y (acidic dye). Less phagocytic than neutrophils Important in fighting parasitic infections.
Basophils Stain with methylene blue (basic dye). Non phagocytic Major role in allergic reactions
Mast Cells Skin and connective tissues of organs. Granules containing histamine development of allergies. Dendritic Cells Express high levels of MHCII good APC. Capture Ag in tissue then travel to lymphoid organs where they present it to T cells.
Organs Of The Immune System Sites of maturation of lymphocytes. Primary Organs Thymus: T cell maturation Bone marrow: B cell maturation Lymphocytes then become IMMUNOCOMPETENT
Trap antigens Secondary Organs Sites of interaction between immunocompetent cells and the antigen. Lymph nodes : Trap antigen from intracellular fluids Spleen : Trap antigens from blood M ucosal- A ssociated L ymphoid T issue ( MALT ): Trap antigens entering from several mucous membrane surfaces.
Cortex : Densely packed with thymocytes maturation begins. Thymus Medulla : Sparsely populated with thymocytes fully mature. Exit thymus via postcapillary venules. T cell receptor diversity generated by a series of random gene rearrangements.
T cells recognizing self MHC molecules are released from thymus. Positive Selection Negative Selection Self-reactive thymocytes (i.e. recognise MHC + self antigen) are eliminated.
Lymph is produced from plasma seeping through thin capillary walls. Secondary Lymphoid Organs Lymph Nodes Contain Lymphocytes, macrophages and dendritic cells. Cortex, paracortex and inner medulla.
Cortex = B lymphocytes and macrophages B cells differentiate into plasma and memory cells. Paracortex = T lymphocytes and dendritic cells. Medulla = Plasma cells secreting antibody.
Humoral and Cell-Mediated Immunity “ Immunity conferred on a nonimmune individual by administration of serum antibodies from an immune individual” Humoral Immunity Antibodies produced interact with antigens and the antigen is then eliminated.
Cell-Mediated Immunity “ Immunity only transferred on by T cells” Cytokines secreted by T H cells activate phagocytic cells + B cells.
Recognition Of Antigen by B and T Lymphocytes Lymphocytes recognise DISCRETE sites on the antigen called EPITOPES. B cells recognise epitopes alone. T cells recognise epitopes in association with MHC molecule on the surface of a self cell. Humoral branch : Recognise enormous variety of epitopes on bacteria, viruses and soluble proteins from invading pathogens.
Cell-Mediated branch : Recognise altered self cells such as a virus-infected self cell and a cancerous cells. Generation of Lymphocyte Specificity and Diversity Mature immunocompetent humans contain large numbers of antigen-reactive clones of B and T cells. Specificity of each clone is determined by random rearrangements in the bone marrow during maturation of the lymphocytes.
Antigen processing and Presentation Processing “Conversion of proteins into MHC-associated peptide fragments” Presentation of antigen with MHCI or MHCII molecules is determined by route of entry of antigen into the cell.
Exogenous Antigens Produced outside host cell. Enters cell by endocytosis or phagocytosis. Associated with MHCII on APC.
Endogenous Antigens Produced within the host cell. Degraded endogenously into peptide fragments. Associated with class MHCI molecule. Examples are viral proteins within cells and unique proteins synthesized by cancerous cells.
Clonal Selection Role of antigen is to SELECT for and EXPAND population of lymphocytes with a given genetic specificity. Humoral and Cell-Mediated Responses
Reading Immunology. Janis Kuby. W.H.Freeman and Company Chapters 1 and 3