Cells and Tissues of Immune System Cadet PDF

BIOM 611G, Medical Microbiology PCOM Georgia CELLS AND TISSUES OF THE IMMUNE RESPONSE Valerie E. Cadet, PhD Assistant Dean of Health Equity Integration Professor of Microbiology and Immunology...

BIOM 611G, Medical Microbiology PCOM Georgia CELLS AND TISSUES OF THE IMMUNE RESPONSE Valerie E. Cadet, PhD Assistant Dean of Health Equity Integration Professor of Microbiology and Immunology BMS1 & BMS2 Department of Biomedical Sciences November 21,  CELLS OF THE 2 IMMUNE SYSTEM Morphology and Functional Characteristics COMPONENTS OF BLOOD Plasma Red blood cells (Erythrocytes) Normal Peripheral Blood Smear White blood cells (Leukocytes ) Platelets BLOOD CELLS AND THEIR APPROXIMATE LIFE SPAN 4  GENERATION OF THE WHITE BLOOD CELLS AKA LEUKOCYTES  Derived from Hematopoietic stem cells (HSCs)  Granulocytes  Neutrophils  Eosinophils  Basophils  Mast cells  Monocytes  Differentiate into macrophages  Dendritic cells  Many dendritic cells are of myeloid linage  Lymphocytes  T cells  B cells  NK cells 5  CELLS OF THE IMMUNE SYSTEM: WHITE BLOOD CELLS Myeloid Progenitor Lymphoid Progenitor All the cellular elements of the blood, including cells of the immune system, arise from pluripotent hematopoietic stem cells (HSCs) in the bone marrow Lymphoid Progenitor 6  CELLS OF THE IMMUNE A. 1. SYSTEM Granulocytes Neutrophils 2. Basophils C. Antigen presenting cells (APCs) 3. Eosinophils 1. Macrophages 4. Mast cells 2. Dendritic cells 3. Follicular dendritic cells (FDC) B. Phagocytes 1. Neutrophils (polymorphonuclear D. Lymphocytes phagocyte/ PMN) 1. T-lymphocytes (T cells) 2. Macrophages (mononuclear phagocytes) 2. B-Lymphocytes (B cells) 3. Dendritic Cells (DC) 3. Natural Killer cells (NK cells) 7 A. GRANULOCYTES 1. Neutrophils (polymorphonuclear phagocyte/ PMN) 2. Mast cells 3. Basophils 4. Eosinophils 8  1. NEUTROPHIL  aka polymorphonuclear leukocytes (PMNs)  Lobulated nucleus  Most important cell in defense against extracellular bacteria  ~60% of WBCs  Production stimulated by G-CSF  Phagocyte: killing and degradation of phagocytosed material  Also kill via neutrophil extracellular traps (NETs)  Express FcR for IgG and CRs  Mediates earliest phase of inflammation  Function for 1-2 days once in tissue  Activated function: phagocytosis and bactericidal hCAP18- human cationic antimicrobial protein mechanisms First  Abundant in pus (typically dead since short lived and when responders they kill, they typically die themselves) Short-lived 9 http://vimeo.com/70326148; http://www.youtube.com/watch?v=fpOxgAU5fFQ Form pus CLINICAL CORRELATION: ABNORMAL NEUTROPHIL COUNT (+/-)  Neutrophilia  Elevated number of neutrophils in blood often indicative of bacterial infection  Neutropenia  Reduction of neutrophils in blood  Gram (-) aerobic bacteria (eg, Escherichia coli, Klebsiella species, Pseudomonas aeruginosa) most common  Gram (+) cocci, Staphylococcus species and Streptococcus viridans most common  Candida species are the most common fungi 10 2 & 3. MAST CELLS AND BASOPHILS  Mast: present in tissue (skin and mucosal epithelia)  Basophil: present in blood (can enter tissue)  High affinity FcR for IgE  Binding of IgE leads to degranuation >> histamine release (inflammation) 11  Important against helminths, allergic diseases, inflammation  4. EOSINOPHILS  Blood granulocytes BM derived  U-shaped nucleus  Low #s in blood; can be present in peripheral tissues  FcR for IgG and IgE  Azurophilic granules = primary granules  Contain acid hydrolases, myeloperoxidase, lysozyme  Activated function: mediates killing of helminths (parasitic worms) & other parasites; allergic responses 12  4. EOSINOPHILS  Blood granulocytes BM derived  Bilobed nucleus  GM-CSF, IL-3 and IL-5 responsible for development  Can be present in peripheral tissues  FcR for IgG and IgE  Activated function: mediates killing of helminths (parasitic worms) & other parasites 13 B. PHAGOCYTES 1. Neutrophils (polymorphonuclear phagocyte/ PMN) 2. Macrophages (mononuclear phagocytes) 3. Dendritic Cells (DC) 14  PHAGOCYTES PERFORM PHAGOCYTOSIS Cells with a primary function to ingest and destroy microbes and get rid of damaged tissues  Imagine stepping outside barefoot and getting a splinter in your foot.  Why don’thttp://www.cellsalive.com/mac.htm you get sick from the bacteria covering the splinter?  Neutrophil phagocytosing a bacteria (video is sped up)  The immune cell locates the bacteria using chemotaxis. https://www.youtube.com/watch?v=Z_mXDvZQ6dU Mayer-Scholl A, Hurwitz R, Brinkmann V, Schmid M, Jungblut P, et al. (2005) Neutrophil engulfing Bacillus anthracis 15 2. MACROPHAGES  aka mononuclear phagocyte  Phagocyte: killing and degradation of phagocytosed material  Tissue resident cells derived from circulating monocytes which have large horseshoe nucleus  Specialized phenotype depending on tissue/organ  Express many types of receptors: PRRs, FcRs, CRs  Professional APC (pAPC): constitutively expresses MHC Class II  Activated function: phagocytosis, wound healing, killing of tumor cells, cytokine secretion, inflammation (recruit neutrophils), antigen presentation (pAPC), granuloma formation MACROPHAGES ARE DERIVED FROM MONOCYTES  3. DENDRITIC CELLS (DC)  Phagocyte  Professional APC (pAPC): constitutively expresses MHC Class II  Essential for activating naïve T cells  Long-lived, similar to macrophages  Classical DCs  Skin, mucosa, organ parenchyma  Plasmacytoid  early responders to viral infections)  Interstitial DCs  populate organs such as heart, lungs, liver, intestines  Secrete:  Activated function: phagocytosis, killing of tumor cells, cytokine secretion, inflammation, antigen presentation (pAPC) C. ANTIGEN PRESENTING CELLS (APC) 1. *Macrophages 2. *Dendritic cells 3. Follicular DCs 4. *B cells (will discuss in lymphocyte section) *Professional APC (pAPC): constitutively expresses MHC Class II, essential for activating naïve CD4+ T cells 19 3. FOLLICULAR DC (FDC)  Found in lymphoid follicles (B cell areas) of the lymphoid tissue intermingled with activated B cells  APC for B cells  Unrelated to DCs that present to T cells  Do Not Express MHC II Molecules  Express FcR for antibodies and complement receptors  Non-haematopoietic cells (not BM derived) Electron microphotograph of a follicular dendritic cell isolated from a rat lymph node The inset illustrates the in vitro interaction between a dendritic 20 cell and a lymphocyte as seen in phase contrast microscopy D. LYMPHOCYTES 1. Natural Killer cells (NK cells) 2. B-Lymphocytes (B cells) 3. T-lymphocytes (T cells) 21 1. NATURAL KILLER (NK) CELLS  Make up about 10% of lymphocytes in blood and lymphoid tissue  Larger than T and B cells  Cytoplasm contains granules  Bridges innate and adaptive immunity  Receptor: CD16 and CD56  Induced by: IL-12, IL-18, type I IFN  Secrete: IFN-γ, perforin, granzyme  Activated function:  Kill infected, stressed or damaged and tumor cells 22  2. B LYMPHOCYTE AND PLASMA CELL  The job of the B cell is to make and secrete antibodies  It does this by differentiating into a plasma cell following activation by antigen B Cell Plasma cell 23  WHAT’S AN ANTIBODY?  aka Immunoglobulin (Ig)  Blood protein molecules secreted by plasma cells (activated B cells)  Bind to antigen to facilitate its removal and/or inactivation  Antigen binding site is exquisitely specific binding optimally to only one antigen  Made up of 4 polypeptide chains 24 Fig. 5-8 ANTIBODIES: THE ARTILLERY OF THE B CELL Fab  Parts of the antibody molecule:  Heavy chains  Determines class of antibody molecule  IgA, IgG, IgD, IgM, IgE  chains designated as a, g, d, m, e  Light chains  kappa and lamda (k) (l)  Antigen-binding site Fc  Hypervariable regions  Fc  Fab 2. CD4 T LYMPHOCYTES + Th cell T reg cell 26  CD4+ CELLS: GENERALS OF THE IMMUNE SYSTEM  Activated function: secrete cytokines  Cytokines direct other immune system cells in battle against microbes  CD4+ cells aka T helper cells  Th1, Th2, Th17, Treg, others 27  Here, let CD4+ T CELLS me help you! Helper T Cells , that’s OK gh. enou more oth ing e. N d o her to ybo dy r Eve off! Regulatory back T cells 28 3. CD8+ T LYMPHOCYTES (CTL) 29 CYTOTOXIC T LYMPHOCYTES (CTL): SPECIAL FORCES  Activated by antigen plus CD4+ cell cytokines  Activated function: Enter tissues as CTL to kill infected host cells and tumor cells T cells (white) attacking 30 a cancer cell B CELL VERSUS T CELL 31 CHARACTERISTICS OF IMMUNE RESPONSES OF T AND B CELLS  Specificity antigen Clonal expansion Antigen receptor  Memory 32  SPECIFICITY AND DIVERSITY OF ANTIGEN RECEPTORS  Specificity  Refers to the ability of the antigen receptors of T and B cells, and of free antibody, to bind to a unique antigen to which no other receptor can bind with same strength.  All antigen receptors on each individual T and B cell bind to the same epitope  All antibody secreted by a plasma cell binds to the same epitope  When a T or B cell proliferates, all daughter cells have receptors that bind to the same epitope as parent cell  Diversity  Refers to the fact that every T or B cell produced by the body has an antigen receptor with a unique specificity  Due to a process of gene recombination- genes from gene families with several to over 100 alleles recombine to form the receptor binding site- gives us the ability to bind to virtually any antigen we encounter 33 MEMORY CELLS CARRY OUT IMMUNE SURVEILLANCE  Memory T and B cells are more easily activated than naïve cells  Memory T cells acquire the ability to enter tissues to hunt for the antigen  Mediated by expression of different homing receptors on memory cells that interact with various addressins on vascular endothelium 34  BRAIN BREAK 35 36 TISSUES OF THE IMMUNE SYSTEM Primary and Secondary Lymphoid Organs How the cells are organized in lymphoid tissues  TISSUES OF THE IMMUNE SYSTEM  Primary Lymphoid Organs  Bone Marrow and Thymus  Maturation Site  Lymphatics  Secondary Lymphoid Organs  Spleen, lymph nodes  MALT (mucosal associated lymph tissue)  GALT (gut associated lymph tissue)  Trap antigen, APC, lymphocyte proliferation 37  PRIMARY LYMPHOID ORGAN: BONE MARROW  Generative lymphoid organ  Site for differentiation of all blood cells  Provides cell-cell interactions and cytokines for the development of all immune cells (hematopoietic cells)  Also contains stromal stem cells for other organs/tissues  B cells differentiate from stem cells in the bone marrow 38  PRIMARY LYMPHOID ORGAN: THYMUS  Generative lymphoid organ  Bilobed Organ on Top of Heart  Reaches Max. Size During Puberty  70g infants, 3 g in adults  Site of T cell differentiation from thymocytes into mature CD4+ and CD8+ T cells  Lymphoid stem cells from bone marrow enter blood, travel to thymus enter and become thymocytes  Early thymocytes express antigen receptors (TCR)  Self/Non-self discrimination  Elimination of self-reacting thymocytes 39 T CELL DEVELOPMENT IN THE THYMUS 40 41 LYMPHATIC SYSTEM  An accessory route by which fluid and protein can flow from interstitial spaces to the blood  Important in preventing edema  Lymph is derived from interstitial fluid that flows into the lymphatics  Major route for absorption of nutrients from the GI tract  Plays important role in the immune system 42  LYMPHATIC SYSTEM  Lymphatic vessels pick up fluid in tissues & return it to blood vessels near heart  Not a complete circuit  Rather a 1-way system Lymph derived from interstitial fluid that feeds into the lymphatic system first enters terminal lymphatics thus has a similar composition as interstitial fluid 43 http://encyclopedia.lubopitko-bg.com/The_Lymphatic_System.html  LYMPHATICS: A SUMMARY  Highly permeable, collect interstitial fluid and return it to circulatory system  The remaining fluid, called lymph, is collected by the lymphatic capillaries  Through series of larger lymphatic vessels.  Also carried in lymph are antigens and/or microbes from infected tissues, tissue dendritic cells  Lymph nodes are scattered along the lymphatic vessels  Filters lymph by removing antigens 44 SECONDARY LYMPHOID ORGANS  Lymph nodes  Spleen  MALT  mucosal-associated lymphoid tissue  GALT  gut-associated lymphoid tissue  BALT  Bronchial-associated lymphoid tissue 45  SECONDARY LYMPHOID ORGANS: DRAINING LNS  Simple definition:  Small, bean-shaped glands in the lymphatic system where lymph is filtered, and lymphocytes are formed.  Working definition:  Highly organized centers of immune cells that filter antigen from the extracellular fluid.  Subcapsular sinus: allows lymph to traverse from the afferent lymph vessels, through the sinuses, and out the efferent vessels.  The sinuses are studded with macrophages, which remove 99% of all delivered antigens. 46 SEGREGATION OF T AND B LYMPHOCYTES IN DIFFERENT REGIONS OF PERIPHERAL LYMPH NODES 47 LYMPH NODES AS SITES OF ANTIGEN ENCOUNTER FOR LYMPHOCYTES 48  SECONDARY LYMPHOID ORGANS: SPLEEN  The site of immune responses to blood Ags  Removes antigens from blood for interaction with T and B lymphocytes in white pulp  T cell zone  Periarteriolar lymphoid sheaths (PALS)  B cell zone  Follicle  Marginal zone Clinical context: What is a potential consequence of splenectomy? 49 SECONDARY LYMPHOID ORGANS: MUCOSAL-ASSOCIATED LYMPHOID TISSUE  MALT is scattered along mucosal linings in the human body  The most extensive component of human lymphoid tissue  Functions: protect the body from an enormous quantity and variety of antigens  MALT nomenclature incorporates location  Gut-associated lymphoid tissue (GALT)  Bronchial/tracheal-associated lymphoid tissue (BALT)  Nose-associated lymphoid tissue (NALT)  Vulvovaginal-associated lymphoid tissue (VALT)  Additional MALT exists within the accessory organs of the digestive tract, predominantly the parotid gland. 50  EXAMPLES OF MALT Peyer’s patch Tonsils Intestinal villi Intestinal villi contain contain intraepithelial lymphatics (lacteals) lymphocytes (IELs) 51 MALTGALT: A FOCUS ON PEYER’S PATCHES 52  LYMPHOCYTE RECIRCULATION  Naïve lymphocytes  those which have not yet encountered the antigen to which they are specific  circulate between the secondary lymphoid tissues via the lymphatics and blood  Memory cells  acquire the ability to enter tissues 53 LYMPHOCYTE RECIRCULATION: A SECOND LOOK 54 PUTTING IT ALL TOGETHER… 55  CATEGORIZING AND 56 RECOGNIZING THE CELLS OF THE IMMUNE SYSTEM ANTIGEN PRESENTING CELLS Antigen presenting cells pAPC 1. X 1. X 2. X 2. X 3. X 3. X 4. xx 57 GRANULOCYTES PHAGOCYTES 1. x 1. x 2. x cells 2. x cells 3. x 3. x 4. x 58 MYELOID-DERIVED LYMPHOID-DERIVED CE x CELLS 1.x 1. 2.x cells 2. x cells 3. x 3. x 4. x 5. x 6. x 59 INNATE IMMUNE CELLS ADAPTIVE IMMUNE CELLS 1. x 1. x 2. x cells 2. x 3. x 3. x 4. x 5. x 6. x 7. x 60 EXAMPLE QUESTION A child fell and sustained a skin wound which became infected with extracellular bacteria. Phagocytes recruited to the injured skin included which of the following: A. Opsonins B. Mast cells C. Neutrophils D. T cells E. NK cells 61