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Chapter 2 Kuby
Todays 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.
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 CO2. 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. 250,000400,000/ml of blood. Important in blood clotting, release growth factors/cell differentiation/proliferation/blood cells/blood vessel/healing properties.
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
Blood
Serum Proteins
Neutrophil
Macrophage Lymphocytes
15-40%
Basophil
Hematopoiesis
The process of
proliferation differentiation & maturation of blood cell
Hematopoiesis
Mostly in bone marrow from stem cells Regulated by cytokines & growth factors
HSC
Self renewing
Stromal cells
Non-hematopoietic cells found in bone marrow
Lymphoid Progenitor
Neutrophil
T cell Progenitor
TH cell
Eosinsophil progenitor
Eosinophil
Basophil progenitor
B cell
Basophil
Megakaryocyte
Platelets
RBC
Erythroid progenitor
Dendritic cell
IL = Interleukins
In Vitro Hematopoiesis
Adherent layer of stromal cells Bone marrow cells added (HSCs)
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
Myeloid Cells
Lymphoid Cells
Granulocytic
Monocytic
T cells
B cells
NK cells
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
Lymphocytes Classes
Class B Lymphocytes T lymphocytes a) Helper T cell Function Antibody production
b)
-Stimuli for B-cell growth and activation - Release cytokines for macrophage activation Cytolytic T cell - Phagocytic, Lysis of pathogen infected cells - Lysis of pathogen infected cells, virus infected cells, tumor cells etc
Lymphocyte subsets
CLP Common Lymphoid Progenitor
Naive T cell Naive B cell
Antigen activation
Antigen activation
TH cell
Adaptive immunity
Naive Lymphocyte
Antigen activation
Memory cells Long lived years Give life long immunity against a particular antigen
B cell
Membrane bound Immunoglobulins (Ig)/Antibodies (Ab) on surface These are receptors for Ag: recognize free Ag ~1.5 x 105 Ab on B-cell surface Other molecules on B-cell surface are CD40 (interaction with TH cell), MHCII (APC), (Major histocompatibility complex) CR1 and CR2 (receptor for complement products) B cell Ab binds to Ag and also interacts with TH/macrophages Activation of nave B-cell B cell divides and differentiate Plasma cells + Memory cells Plasma cells secrete Ab and die in 1-2 weeks
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 TH cells express CD4 = CD4+T-cell TC 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/TH:TC = 2:1 TH cells Ag on MHCII Activated Effector cells Secrete cytokines Cytokines activate Bcell, Tcell and macrophages Tc cells Ag on MHCI Interaction + Cytokines =Activated Effector cells= cytotoxic Tcell (CTL) Recognize and eliminate infected cells
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
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
Lymphocytes
Other WBCs
B, T, NK
Phagocytic APC
Phagocytic
Secretory
Dendritic Macrophages
Neutrophil Eosinophil
Big in size Fix or moving Professional APC Secrete hydrolytic Enz. Innate immunity
Phagocytic
Non-phagocytic MC Precursor in Bone marrow Migrate blood tissue Differentiate in tissue Role in allergic reactions
Lymphocytes
Other WBCs
B, T, NK
Phagocytic APC
Phagocytic
Secretory
Dendritic Macrophages
Neutrophil Eosinophil
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
Based on Function:
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
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.
With age cell content of thymus decreases Size decreases Fat content increases Decline in thymic function Leads to decline in immune function
Birds (Bursa), primates+ rodents (primary lymphiod organ), cattle+sheep (spleen) different site of B cell maturation
Largest lymphatic vessel in the body. Collects most of the lymph in the body Empties it into left subclavian vein
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
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
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
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
Self-reading
Loose clusters: B cells, Plasma cells Th cells Macrophages Ab are secreted in the lumen
M cells
Self-reading
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
Break