1	CLSC320 Principles of Immunology Fundamental Concepts in Immunology Program for Clinical Laboratory Science Unit - 03 Cellular Components of The Immune System
2	Unit – 03 Guidelines Reading assignment: Pages 54 - 77 of textbook Learning objectives: Those listed on page 55 of textbook Key terms: Those listed on pages 55 & 56 of textbook
3	Primary Lymphoid Tissue Primary Lymphoid Tissue: 1.Definition: tissue in which maturation and differentiation of lymphocytes occurs. 2.Bone Marrow ˜all cells of immune system are derived from an undifferentiated stem cell ˜process is called hematopoiesis ˜B lymphocytes mature and differentiate in the bone marrow 3.Thymus gland The T lymphocytes are formed in bone marrow but mature and differentiate in the thymus gland
4	Secondary Lymphoid Tissue Secondary Lymphoid Tissue: 1.Definition: tissue in which humoral and cell-mediated responses to foreign antigens occurs. 2.Encapsulated tissue ˜lymph nodes ˜spleen 3.Non-encapsulated tissue ˜cutaneous lymphoid tissue ˜mucosal lymphoid tissue
5	Lymphoid Nodes cortex paracortex medulla Secondary Lymphoid Tissue: continued afferent lymphatic vessel efferent lymphatic vessel lymphatic artery & vein primary lymphoid follicles germinal centers B lymphs T lymphs Macrophages & Dentritic cells plasma cells B lymphs B lymphs
6	Spleen Secondary Lymphoid Tissue: continued renal surface gastric surface hilum splenic artery splenic vein capsule splenic artery vascular sinosoids splenic vein red pulp Macrophages & red blood cells white pulp follicle marginal zone periarterial lymphatic sheath B lymphs T lymphs
7	Lymph Node Function Secondary Lymphoid Tissue: continued 2.Lymph Nodes Function ˜Primary response: erecognition of lymph-borne antigen by T and B cells eproduction of soluble factors (cytokines) eproliferation of lymphocytes eproduction of effector cells - CD4+ and CD8+ eproduction of effector molecules - antibodies eproduction of memory T and B cells ˜Secondary response ememory cells remain in lymphoid tissue egreater response and more efficient response
8	Function of Spleen Secondary Lymphoid Tissue: continued 3.Spleen Function ˜Primary response: erecognition of blood-borne antigen by T and B cells esimilar to lymph nodes function ˜Secondary response eremoval of aged red cells by the macrophages
9	Hematopoiesis Pluripotential stem cell myeloid cell lymphoid cell pre-T cell pre-B cell B cell plasma cell T cell BFU-E CFU-E RBC=s CFU-Eo Eosino=s CFU-B Baso=s CFU-Meg Plt=s CFU-GM CFU-M Neut=s CFU-Mo Mono=s
10	Sites of Hematopoiesis Site of hematopoiesis: 1.During fetal life ˜blood islands of yolk sac ˜then liver ˜then spleen 2.Birth to puberty ˜bone marrow of long bones 3.Adulthood ˜bone marrow of: ~sternum and ribs ~vertebrae ~iliac crest
11	Growth Stimulating Factors Growth Stimulating Factors: 1.Colony Stimulating Factors (CSF) are cytokines from: ˜stromal cells of bone marrow ˜macrophages in bone marrow ˜kidney - erythropoietin that stimulates CFU-E 2.Interleukin 6 (IL6) ˜works with IL3 to stimulate myeloid stem cell
12	Proliferation & Differentiation Proliferation and Differentiation: 1.All cells of immune system originate in: ˜bone marrow 2.All cells proliferate and differentiate in the bone marrow except: ˜T lymphocytes 3.The T lymphocytes migrate to the: ˜Thymus gland 4.The T lymphocytes differentiate in the: ˜Thymus gland
13	Agents That Induce Proliferation Agents that can induce immune cells to proliferate in vitro: 1.Phytohemagglutinin: ˜T lymphocytes 2.Concanavalin A: ˜T lymphocytes 3.Lipopolysaccharides ˜B lymphocytes ¼ plasma cells 4.Pokeweed mitogen ˜T lymphocytes and B lymphocytes
14	OSF - #5 On pages 64 - 65AOne Step Further@ presents a more in-depth discussion of the Major Histocomaptibility Complex molecules. This presentation is contained on a separate slide presentation called A One Step Further #5" The student may call up the slide program OSF-5 later or click on the arrow below to view slides now.
15	Cellular Characteristics - Lymphs General Characteristics: 1.Lymphocytic cells ˜Primary function is surveillance ˜Three distinct classes of lymphocytes: eB lymphocytes - have $ antigen eT lymphocytes - have 2 antigen eNull lymphocytes - lack $ and 2 antigens (NK cells) ˜Unique features of lymphocytes: eB lymphocytes - Urecognizes native antigen configuration Urequires T_helper cell interaction eT lymphocytes - Urecognizes processed antigen Urequires MHC interaction
16	Cellular Characteristics - Accessory General Characteristics: 2.Accessory cells ˜Characteristics: edo not have antigen specific receptors edo participate in the initiation of immune responses ˜Cell lines: eMacrophages eDendritic cells eGranulocytes Uneutrophils Ubasophils Ueosinophils
17	T-Lymphocytes - 1 Specific Cell Characteristics: 1.Lymphocytes ˜T- lymphocyte Characteristics: eoriginate in bone marrow emigrate to thymus gland eAT@ stands for thymus-derived lymphocytes eFunctions: Uspecificity of immune response Urecognition of foreign antigen Uself-tolerance erecognition of foreign antigen is MHC- restricted etwo sub-populations: UT_helper - UT_{cytotoxic/suppressor} - CD4+ CD8+
18	CD4-Lymphocytes - 1 Specific Cell Characteristics: cont=d 1.Lymphocytes - continued ˜T_helper - lymphocyte Characteristics: epossess CD4 Atransmembrane@ receptors eCD4 receptor is related to antibody molecules eTwo groups of T_helper cells: UTH1 UTH2 - secrete IL-2 & IFN( - secrete IL-4, IL-5, IL-6, IL-10 -mediate cytotoxicity & local inflammatory reactions -stimulate B-cells to proliferate and secrete immunoglobulins
19	CD4-Lymphocytes - 2 Specific Cell Characteristics: cont=d 1.Lymphocytes - continued ˜T_helper - lymphocyte functions: eonly recognize antigen that is: Ubound to MHC class II molecules on surface of APC=s Uin association with TCR/CD3 and CD4 receptors on T_helper - lymphocyte e secrete cytokines that: Ustimulate activation, proliferation, & differentiation of: -T-cells, B-cells, Macrophages, & granulocytes e secrete cytokines that: Urecruit and activate inflammatory leukocytes
20	CD8-Lymphocytes - 1 Specific Cell Characteristics: cont=d 1.Lymphocytes - continued ˜T_cytotoxic - lymphocyte functions: eonly recognize antigen that is: Ubound to MHC class I molecules on surface of infected (target) cells Uin association with TCR/CD3 and CD8 receptors on T_cytotoxic - lymphocyte e lysis of target cell (infected cell) is done by: Usecretion of toxins from granules that block ions and H₂O from leaving cell resulting in swelling Uactivation of target cell intracellular enzymes resulting in degradation of DNA and cell lysis eT_cytotoxic cells are not destroyed in process of lysing target cells
21	CD8-Lymphocytes - 2 Specific Cell Characteristics: cont=d 1.Lymphocytes - continued ˜T_cytotoxic - lymphocyte functions: - continued emay also participate as effector cells in: Uallograft rejections Utumor rejections ˜T_suppressor - lymphocyte characteristics: ehave CD8 receptor enow believed not to be a distinct type of cell but rather a different function of the T-cell ˜T_suppressor - lymphocyte functions: eblock various immune responses by secreting inhibitory cytokines
22	B-Lymphocytes - 1 Specific Cell Characteristics: cont=d 1.Lymphocytes - continued ˜ B - lymphocyte characteristics: ematuration occurs in the bone marrow esecrete immunoglobulins onto surface membranes ematuration stages: UPre-B lymphocyte -lacks ability to recognize or respond to antigen UImmature-B lymphocyte -has IgM on surface -lacks ability to proliferate or differentiate in response to antigen -stage in which self-tolerance develops
23	B-Lymphocytes - 2 Specific Cell Characteristics: cont=d 1.Lymphocytes - continued ˜ B - lymphocyte characteristics: continued ematuration stages: cont=d UMature-B lymphocyte -has both IgM and IgD -has specificity for antigen -able to respond to antigen UActivated-B lymphocyte (blast) -has both IgM and IgD -transforms in response to antigen UPlasma cell -stage in which immunoglobulins are secreted and released from cell
24	B-Lymphocytes - 3 Specific Cell Characteristics: cont=d 1.Lymphocytes - continued ˜ B - lymphocyte characteristics: continued ematuration stages: cont=d UMemory-B lymphocyte -has both IgM and IgD -has specificity for antigen -able to respond to antigen more rapidly ˜ B - lymphocyte function: efollowing antigenic stimulation they differentiate into plasma cells which produce antibodies emay act as antigen-presenting-cells by presenting antigen with MHC II molecules
25	Null Lymphocytes - 1 Specific Cell Characteristics: cont=d 1.Lymphocytes - continued ˜ Null - lymphocyte characteristics: ealso called natural killer (NK) cells elack sIg=s and TCR=s eexpress CD2 marker on surface eexpress CD16 marker on surface Ureceptor for Fc portion of IgG antibody eexpress receptor for Il-2 on surface esecrete tissue necrosis factor (TNF)
26	Null Lymphocytes - 2 Specific Cell Characteristics: cont=d 1.Lymphocytes - continued ˜ Null - lymphocyte functions: esimilar cytotoxic function as T_cytotoxic lymphs eactivated by T_helper lymphs edifferentiate in response to IL-2 stimulation edestroy target cells by antibody-dependent- cell-mediated cytotoxicity (ADCC) eaction is not MHC restricted eaction does not require previous exposure to antigen
27	Accessory Cells - 1 Specific Cell Characteristics: cont=d 2.Accessory cells ˜ Cell lines involved: emononuclear phagocytes Umonocytes/macrophages Udentritic cells egranulocytic cells Uneutrophils Ueosinophils Ubasophils ˜ Characteristics of all accessory cells: edo not have antigen specific receptors eparticipate in the initiation of immune responses
28	Accessory Cells - 2 Specific Cell Characteristics: cont=d 2.Accessory cells - continued ˜ Characteristics and functions of each cell line: emonocyte/macrophage characterisitics: Uoriginate in bone marrow Uimmature form called monocyte Uin tissue surface receptors for antibodies (FcR) and complement (CR) acquired Uin tissue they are called macrophages or may be called something different based on tissue found in: -liver -lungs -bones -kidneys =Kupffer cells =alveolar macrophages =osteoclasts =mesangial cells
29	Accessory Cells - 3 Specific Cell Characteristics: cont=d 2.Accessory cells - continued ˜ Characteristics and functions of each cell line: emonocyte/macrophage functions: Natural immunity Specific immunity lphagocytosis of antigen * ldegradation of antigen * lsecretion of enzymes lsecretion of cytokines lsecretion of growth hormones lamplify immune response lact as antigen-presenting cell lsecretion of soluble membrane molecules for T- cell activation lphagocytosis of opsonized antigen (antibodies attached to antigen) *see next series of slides for the steps involved in the phagocytosis and degradation of antigen
30	Phagocytosis - 1 lysosomes nucleus antigen antigen adheres to cell via receptor or just contact pseudopodia formed as cell wall begins to surround antigen
31	Phagocytosis - 2 antigen enclosed in a phagosome lysosomes fuse with membrane of phagosome and release contents into phagosome lysosomes contain hydrogen peroxide, peroxidase, lysozyme, hydrolytic enzymes that begin breaking down the antigen
32	Killing Mechanism once antigen is degraded the process of exocytosis takes place where the antigen fragments are expelled from cell Oxygen-Dependent Killing Mechanism 2O₂ + NADPH # NADP⁺ + H⁺ + 2O₂ # H₂O₂ + Cl^- MYELOPEROXIDASE H₂O + OCl^- (CHLORINE)
33	Accessory Cells - Neutrophils Specific Cell Characteristics: cont=d 2.Accessory cells - continued ˜ Characteristics and functions of each cell line: eneutrophil characteristics: Uexpress surface receptors for Fc portion of antibody (FcR). Uexpress surface receptors for complement components (CR) eneutrophil functions: Uact as Aeffector cells@ for humoral immunity by phagocytosis and activation of complement. Urespond to chemotactic stimuli Ureact to cytokines from macrophages Umajor cell involved in the inflammatory response.
34	Accessory Cells - Eosinophils Specific Cell Characteristics: cont=d 2.Accessory cells - continued ˜ Characteristics and functions of each cell line: eEosinophil characteristics: Uexpress surface receptors for Fc portion of IgE antibody. eEosinophil functions: Uact as Aeffector cells@ for immune response to parasites. Uact as Aeffector cells@ in allergic reactions Umost effective in destroying large antigens such as helminthes (worms). Ugrowth & differentiation is stimulated by T-cell cytokines.
35	Accessory Cells – Basophils - 1 Specific Cell Characteristics: cont=d 2.Accessory cells - continued ˜ Characteristics and functions of each cell line: eBasophil characteristics: Usmallest number of circulating white cells Uin tissue these may become the mast cell Umembrane enclosed granules contain: ~histamine ~heparin ~serotonin ~ECF-A ~NCF-A ~Proteases increased vascular permeability smooth muscle contractor anticoagulant smooth muscle contractor eosinophil chemotactic factor neutrophil chemotactic factor destroy blood-vessel membrane destroy complement split factors induce bronchial mucus secretions
36	Accessory Cells – Basophils - 2 Specific Cell Characteristics: cont=d 2.Accessory cells - continued ˜ Characteristics and functions of each cell line: eBasophil functions: Uact as Aeffector cell@ in IgE mediated hypersensitivity reactions Ubind free circulating IgE Ucross-linking of bound IgE on mast cell surface causes degranulation to occur. Ureleased substances are inflammatory and vasoactive (see list under characteristics).
37	Cellular Components Press the ESC key to end program
38	One Step Further Cell Markers & Receptors OSF - 5 Pages 63 - 65 click to return to main program
39	Markers & Receptors - 2 Definition: Cell markers are molecules expressed on the surface of normal cells that may act as receptors (attachment sites) for other molecules or be unique markers that help identify a lineage of cells Receptors for antigens: eAll immune cells except natural killer cells (NK) have molecular receptors for the recognition of specific antigens eExamples of these molecular receptors include: ŽT-cell receptors (TCR=s) ŽB-cell receptors (BCR=s) all are surface immunoglobulins (sIgs) ŽCD3 proteins work in conjunction with TCR=s ŽMajor Histocompatibility Complex molecules
40	Markers & Receptors - 3 Phenotypic markers: ethese markers serve to identify and differentiate lymphocytic cells eExamples include: ŽCD4+ ŽCD8+ on T_Helper or T4 cells on T_Cytotoxic or T8 cells antigen + MHC class II antigen + MHC class I Fc receptors: ethese receptors located on surface of some cells serve as attachment sites for the Fc portion of immunoglobulins eExamples include: ŽFc(R I ŽFc(R II ŽFc(R III also called CD64 also called CDW32 also called CD16
41	Markers & Receptors - 4 Biological responses to Immunoglobulins binding to Fc receptors include: ephagocytosis eendocytosis erelease of inflammatory mediators eenhanced antigen presentation eremoval of stimulating antigen from immune system
42	Markers & Receptors - 5 Complement receptors: emolecules located on the surface of some cells act as attachment sites for various components of the complement system eCategories of receptors: Žfragments of C3 ŽC3a and C5a Žregulatory receptors
43	Tumor Markers - 6 click to return to main program