Cell and organs of immune system. Chapter 2 Kuby

Transcription

1 Cell and organs of immune system Chapter 2 Kuby

2 Key concepts from last lecture Pathogen Antigen Antibody? B cells (Plasma cells) T cells (Th&Tc) Innate immunity Adaptive immunity Passive immunity Active immunity History Overview of immune response Cell mediated immunity Humoral immunity Phases of immune response Adaptive immunity has memory Primary and secondary response What happens on immunization

3 Today s Objectives 1. What are the main cell types of the immune response? 2. Where are they, where do they come from, what do they look like, what are their major functions? 3. How does this package fit together to give you a circulating immune system? 4. Describe the overall physical organization of the immune system and the different roles played by primary and secondary lymphoid organs.

4 Blood composition 55% Plasma (fluid matrix of water, salts, hormones, proteins, Ab, metabolites, etc.) 45% Cellular elements: Red Blood Cells (RBCs): 5-6 million RBCs/ml of blood. Contain hemoglobin which transport oxygen and CO 2. White Blood Cells (WBCs also called leukocytes): 5,000-10,000 WBCs/ml of blood. Play an essential role in immunity and defense. Include: Lymphocytes: T cells, B cells and NK cells Macrophages (phagocytes) Granulocytes: Neutrophils, basophils, and eosinophils. Platelets/Thrombocytes: Cellular fragments. 250, ,000/ml of blood. Important in blood clotting, release growth factors/cell differentiation/proliferation/blood cells/blood vessel/healing properties.

5 Name two types of fluid that circulate in our body? 1. Blood 2. Lymph: Tissue fluid/interstitial fluid/intercellular fluid Colorless, composition similar to blood serum. Collected from tissue into lymph vessels by diffusion Along with it are collected Antigens (pathogens/toxins) Added to blood in the heart

6 Where are they (immune components)? Blood Serum Proteins White Blood Cells (Leucocytes) Immunoglobulins Complement Clotting factors Growth factors Many others Lymphocytes (T cells, B cells & NK cells) Phagocytic/den dritic cells (macrophages, dendritic cells, NK cells etc)

7 Where are they? Eosinophil Neutrophil Macrophage Lymphocytes 15-40% Basophil

8 Hematopoiesis The process of proliferation differentiation & maturation of blood cell

9 Hematopoiesis Mostly in bone marrow from stem cells Regulated by cytokines & growth factors

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11 Routes for hematopoietic stem cell (HSC) HSC HSC Self renewing Differentiation and Maturation Blood Cell (RBCs and WBCs)

12 Stromal cells Non-hematopoietic cells found in bone marrow Form a meshwork for HSC growth Provide microenvironment consisting of cellular matrix + hematopoietic growth factors (these proteins/growth factors induce differentiation and maturation) Thus stromal cells support HSC differentiation and maturation When infection occurs: Activated T cell and macrophages produce hematopoitic growth factors stimulate hematopoiesis

13 Development of immune cells Dendritic cell HSC Macrophage Myeloid Progenitor Lymphoid Progenitor Natural killer (NK) cell Monocyte Neutrophil Granulocyte monocyte progenitor T cell Progenitor T H cell Eosinophil Basophil Eosinsophil progenitor Basophil progenitor B cell Progenitor T C cell B cell Megakaryocyte Platelets RBC Erythroid progenitor Dendritic cell

14 Where do they come from?

15 Where do they come from?

16 Cytokines and Growth factors IL = Interleukins

17 In Vitro Hematopoiesis Adherent layer of stromal cells Bone marrow cells added (HSCs) Cell culture in semisolid agar Growth of bone marrow cell colonies Used for detection and identification of HGFs Eg. Cytokine called colony stimulating factors (CSFs) Acidic glycoproteins Induce the formation of hematopoitic cell lines Eg. Cytokine Erythropoietin (EPO) Glycoprotein involved in terminal development of RBCs

18 Cells of the Immune System Immune System Bone marrow Myeloid Cells lymph Lymphoid Cells Granulocytic Monocytic T cells B cells NK cells Neutrophils Basophils Eosinophils Macrophages Dendritic cells Helper cells Cytotoxic cells Plasma cells

19 Lymphocytes Group of WBC (20-40%) 99% cells in lymph Three classes of lymphocytes Morphologically similar Each has distinct function Circulate in blood and lymph Migrate to tissue spaces and lymphoid organs

20 Lymphocytes Classes Class B Lymphocytes T lymphocytes a) Helper T cell b) Cytolytic T cell Natural Killer cells Function Antibody production -Stimuli for B-cell growth and activation - Release cytokines for macrophage activation - Phagocytic, Lysis of pathogen infected cells - Lysis of pathogen infected cells, virus infected cells, tumor cells etc

21 Lymphocyte subsets Naive T cell CLP Common Lymphoid Progenitor Naive B cell Antigen activation Antigen activation T C cell CYTOTOXIC T LYMPHOCYTES Kill pathogen infected cells T H cell T HELPER CELLS Activate B cells and macrophages Secrete cytokines B cell PLASMA CELLS Produce antibodies

22 Adaptive immunity Naive Lymphocyte Antigen activation Effector cells Short life (days to weeks) Eliminate antigen Memory cells Long lived years Give life long immunity against a particular antigen T C cell CYTOTOXIC T LYMPHOCYTES T H cell T HELPER CELLS B cell PLASMA CELLS

23 Name and Maturation B cell mature in bone marrow Called B cell (not true) B cells got their name because B cell differentiation was first demonstrated in the bursa of Fabricius of chicken embryos. T cell mature in thymus therefore called T cell

24 B cell Membrane bound Immunoglobulins (Ig)/Antibodies (Ab) on surface These are receptors for Ag: recognize free Ag ~1.5 x 10 5 Ab on B-cell surface Other molecules on B-cell surface are CD40 (interaction with T H cell), MHCII (APC), (Major histocompatibility complex) CR1 and CR2 (receptor for complement products) B cell Ab binds to Ag and also interacts with T H /macrophages Activation of naïve B-cell B cell divides and differentiate Plasma cells + Memory cells Plasma cells secrete Ab and die in 1-2 weeks

25 T cell Membrane bound T cell receptor (TCR) on surface TCR receptor for Ag Does not recognize free Ag Recognizes Ag bound to MHC molecules on self-cells T H cells express CD4 = CD4 + T-cell T C cells express CD8 = CD8 + T-cell CD4 + T-cell recognize Ag bound to MHC II CD8 + T-cell recognize Ag bound to MHC I CD4 + T-cell: CD8+T-cell/T H :T C = 2:1 T H cells Ag on MHCII Activated Effector cells Secrete cytokines Cytokines activate Bcell, Tcell and macrophages T c cells Ag on MHCI Interaction + Cytokines =Activated Effector cells= cytotoxic Tcell (CTL) Recognize and eliminate infected cells

26 Regulatory T cells (Treg) CD4 + CD25 + Foxp3 + regulatory T cells, or "T regs " Also known suppressor T cells (T s ) The immune system must discriminate between self and non-self. When self/non-self discrimination fails, the immune system destroys cells and tissues of the body and as a result causes autoimmune diseases (AID). Autoimmunity against hematopoietic stem cell causes Aplastic anemia Bone marrow transplant /Stem cell transplant Regulatory T cells actively suppress activation of the immune system and prevent pathological self-reactivity, i.e. autoimmune disease. The critical role regulatory T cells play within the immune system is evidenced by the severe autoimmune syndrome that results from a genetic deficiency in regulatory T cells.

27 Functions of T reg cells 1. Prevention of autoimmune diseases by establishing and maintaining immunologic self-tolerance. 2. Suppression of allergy and asthma. 3. Induction of tolerance against dietary antigens, i.e. oral tolerance. 4. Induction of maternal tolerance to the fetus. Still research is ongoing?

28 A third kind of lymphocytes Release lytic granules that kill Virus infected cells + Tumor cells Granules contain porins and granzyme (serine) proteases Cause lysis or apoptosis of infected/tumor cells

29 Natural Killer cells NK cells recognize potential target cells by the following ways Tumor cells and virus infected cells display Ags on surface Antibodies (produced against these Ags by immune system) bind to theses Ags on the surface of infected cells CD16 receptor on NK cells recognizes antibodies (Fc) Destroys the target cell Process is called Antibody dependent cell mediated cytotoxicity (ADCC) NK cells also recognize abnormalities on infected or tumor cells Reduction in display of MHCI on surface Unusual profile of surface Ags

30 The cells of the immune system White Blood Cells Lymphocytes Other WBCs B, T, NK Phagocytic APC Phagocytic Secretory Dendritic Macrophages Neutrophil Eosinophil Basophil Mast cell

31 Big in size Fix or moving Professional APC Secrete hydrolytic Enz. Innate immunity Professional APC Present to T H cells Most abundant WBCs Migrate to infection sites kill the invader

32 Phagocytic Phago = eating Cyte = cell Read from Kuby

33 Phagocytic Motile Damage parasite memb Non-phagocytic Allergic responses Heparin (stop blood coagulation) +Histmine (allergic reaction) Non-phagocytic MC Precursor in Bone marrow Migrate blood tissue Differentiate in tissue Role in allergic reactions

34 The cells of the immune system White Blood Cells Lymphocytes Other WBCs B, T, NK Phagocytic APC Phagocytic Secretory Dendritic Macrophages Neutrophil Eosinophil Basophil Mast cell

35 Organs of the immune system

36 Lymphatic system: It is a network of lymph vessels that collects the fluid and lymphocytes that escape into the tissues from blood capillaries and returns these back to the circulating system. Lymph organs + lymph

37 Based on Function:

38 MALT: Mucosal associated lymphoid tissue: (less organized compared to lymph nodes, includes: small Intestine Peyer s Patches, tonsil, appendix,)

39 The tertiary lymphoid tissue Far fewer lymphocytes Assumes an immune role only when challenged with antigens Generally result in inflammation. It achieves this by importing the lymphocytes from blood and lymph CALT (Cutaneous Associated Lymphoid Tissues)

40 Thymus Thymus: Site for Tcell dev and maturation Flat Bilobed organ Situated above the heart Each lobe has two compartments Cortex: outer Medulla: inner Cortex: densely packed with immature T cells called thymocytes Medulla: few thymocytes

41 Thymus Cortex+Medulla has stromal cell network Stromal cell network help in differentiation and maturation of T cells Composed of epithelial cells, dendritic and macrophages Thymic epithelial cells called Nurse cells Nurse cells form membrane extensions surround many thymocytes form multicellular complexes Selection process in thymus Only 5% of T cells recognize Ag on MHC complex of APC Rest 95% die (these cannot recognize Ag/or recognize self Ag) Thymus does not work, No T cells, no cell mediated immunity, infectious diseases inc.

42 Age and Thymus With age cell content of thymus decreases Size decreases Fat content increases Decline in thymic function Leads to decline in immune function

43 Birds (Bursa), primates+ rodents (primary lymphiod organ), cattle+sheep (spleen) different site of B cell maturation

44 Largest lymphatic vessel in the body. Collects most of the lymph in the body Empties it into left subclavian vein

45 Blood flowing with pressure Plasma seeps through the walls of capillaries This fluid is called interstitial fluid Most of it returns back to blood Rest of this interstitial fluid is called lymph Lymph collected by lymphatic capillaries network Flows to large lymph vessels Largest lymph vessel called Thoracic duct empties it in heart vein Flow in the lymph achieved by muscles in the body Ag is picked by lymph syst and carries to secondary lymphoid organs: lymph nodes and traped there Lymph system also transports immune components to various sites

46 Bean shaped structure divided into three regions Outer most: Cortex Contains lymphocytes ( B-cells mostly), Mac + dendritic cells = Primary follicle (PF) Ag challange PFs enlarges to Secondary follicles (SFs) Each SF has a germinal centre (GC) GC where B cell proliferate Paracortex Contains ( T-cells mostly + dendritic cells APC:MHCII) to Th cells Medulla Few cells mostly Plasma cells secreting Ab

47 Afferent vessel carries lymph containing pathogens to lymph nodes into Cortex, paracortex medulla. Macrophages/dendritic cells of lymph attack and present Ag by MHC molecules. Activate B cells and T cells Efferent vessel carries lymph away from the lymph nodes Lymph leaving the lymph node is rich in Abs secreted by Plasma cells in medulla and other activaed lyphocytes

48 Spleen Mounts immune response in blood Large ovoid secondary lymphoid organ traps blood born Ag not connected with lymphatic vessles Ag supplied by splenic artery It has a capsule Projection from capsule goes to the interior of spleen compartments are formed Two compartments Red pulp (old RBCs removed here) White pulp Red pulp: Mac+RBCs White pulp: mostly T cells, DC and few B cells, forms PALS Marginal zone Primary follicles + GC

49 Self-reading

50 MALT intestine Mucosal membrane of gastrointestinal tract (stomach+intestine) Loose clusters: B cells, Plasma cells Th cells Macrophages Ab are secreted in the lumen

51 M-cells Epithelial cells specialized for Ag transport

52 M cells lie above Inductive site: M cells

53 Self-reading

54 Evolution and lymphoid cells and organs Innate immunity found in invert. + plants Addaptive immunity mediated by Ab+Tcells found in vertebrates All lyphoid tissues are not present in all vert. With evolution new lymphid organs were added Retains the old ones Eg B and T cells not present in jaw less fish (Lamprey = GALT gut associated) Shark is has jaws and it also has B and T cells

55 Break

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57 Clotting factors in serum