Cells Of Lymphatics Flashcards
What is the function of the lymphatic system?
Function:
- monitor body surfaces and interstitial fluid compartments
- Removal of excessive interstitial fluid
- Provides defense mechanisms
- production of immune cells (lymphocytes, monocytes, plasma cells)
- fatty acid absorption and transport of fat, chyle to general circulation
Basis for this self defense- enable the body to distinguish self from non self
-carried out by-cells, effector molecules, tissues and organs
What are GHRH organs of the lymphatic system?
Primary- bone marrow, thymus
Secondary - spleen, tonsils, lymph nodes, diffuse lymphatic tissue, lymphatic nodules
What are the cells of the lymphatic tissue?
Principal effector cells
Support cells
Specialized epithelial and stromal cells
What are the principal effector cells?
Lymphocytes, B cells, T cells, natural killer
What are the support cells?
Monocytes, macrophages, neutrophils, basophils, eosinophils, dendritic cells, follicular dendritic cells
What are the specialized epithelial and stromal cells?
Reticular cells, langerhans, epithelioreticular cells
Summarize lymphocytes
- non terminally differentiated cells
- responsible for immunologic. Surveillance
- 60-80%, mainly long lived, mature T cells, circulating pool of immunocompetent cells
- 30% short lived, immature, or activated but destined for specific tissue (connective tissue, epithelia)
What are the characteristics of T lymphocytes?
Differentiate in the thymus
Long lived, cell mediated immunity, 60-80% of lymphocytes
Secrete cytokines when activated
-cytokines affect the function of effector cellls (T & B, monocytes, macrophages, APCs)
Express- CD2, CD3, CD5, CD7, CD28, CD40L
T cell receptors (TCR)- recognize antigen attached to identification molecules (MHC molecules)
What are the subclasses of T lymphocytes?
-T helper cells (Th1, Th2)
TH cells recognize antigens presented by antigen presenting cells (APCs)
Express CD4, in addition to those mentioned above
- Cytotoxic lymphocytes (CTL) - “patrols”
- CTLs - recognize antigens presented on cancer or viral infected cells
- CTLs- express CD8, in addition to those mentioned above
How are TH cells activated ?
I) first signal, when they interact with MHC-Ag complex
II) Costimulatory signal, between T cell and APC
Synthesize interleukins (CD4+ cytokines which stimulate differentiation and proliferation of T, B, & NK cells)
What are the functions of TH1 cells?
Recognize Ag presented by APCs
Synthesize- IL2, IFN-y, TNF-a-
Interact with cytotoxic lymphocytes, cells and macrophages to control intracellular pathogens
Whaat are the functions of TH2 cells?
Recognize Ag presented by APCs
Synthesize IL4, IL5, IL10, IL13
interact with B lymphocytes to initiate antibody mediated immune response for extracellular pathogens
Whaat is the function of CD8+ lymphocytes?
Express CD8, Kill target cells - cancer cells, viral infected cells, parasites, transplanted cells, cells infected with intracellular microorganism
What is the cell mediated immune response of CD8 T cells?
Destruction of a transformed or virus infected cell by cytotoxic CD8+ T lymphocyte
Activation: TCR binds the MHC 1-Ag complex on target cell
-Clonal expansion:cell division and differentiation into killer cells
Killer cells: performing (perforate cells), granzymes (activate caspases-cell apoptosis), granulysin
What are the functions of regulator (suppressor) T lymphocytes?
Suppress the immune , response to self and foreign antigens by influencing other cells of
- CD4+ cells that co-express CD25+ and FOXP3 - Secrete IL10, TGF-B - delayed hypersensitivity reaction (type IV)
What is the function of gamma/delta T lymphocytes?
Develop in thymus
Reside and form first line of defense in epithelia
What are MAIT lymphocytes?
Mucosa invariant T lymphocytes
How much of circulating lymphocytes natural Killer cells?
5-10% of circulating lymphocytes
Describe natural killer cells
- Neither B nor T lymphocytes but share same line of development
- Innate immunity
- Programmed to kill target cells similar in fashion to CTL method
- Enzymes released: granzymes and perforins
- CD markers- CD16, CD56, CD94
- Express Fc receptors-recognize the Fc region of antibodies coating target cells
- NK associated lysis of cells coated by antibodies (IgG) or complement (C3)- (antibody dependent cell-mediated cytotoxicity, ADCC)
Describe B lymphocytes
- differentiate in bursa equivalent organs
- participate in humoral immunity
- variable life span
- express antigen binding site, B cell receptor (BCR) and MHC II on their surface
CD markers: CD9, CD19, CD20, CD40
Whaat are the subtypes of B cells?
Plasma cells: production and secretion of antibodies (immunoglobins, Ig)
Memory B cells: respond to second encounter with the same antigen
Explain the activation of B lymphocyte
I) first signal, when they interact antigen- BCR-Ag compl3x
- Antigen is engulfed by B cell - Antigen-antibody(Ag-Ab) complex is eliminated by NK cell destruction, phagocytosis by macrophages or eosinophils
II) Costimulatory signal-, between the B cell and TCR on Th cell.
T cell secrete cytokines to stimulate B cell differentiation and proliferation
What is the mononuclear phagocytic system?
- perisinusoidal macrophages (kupfer cells)
- Langerhans cells (skin)
- dendritic cells (spleen, lymph nodes)
- macrophages)
What is non-mononuclear phagocytic system?
B lymphocytes
Epitheliorecticular cells (thymus)
Epitheliorecticular cells (II, III)
What are the mechanisms of macrophages?
Presented antigens to B and T cells
Partially degrade both proteins and polysaccharides
Digest pathogenic microorganism through lysosomal action in combination with CD4+ T lymphocytes
- secrete multiple cytokines (lymphokines, complement components, interleukins) and enzymes (proteases, hydrolases, lipases)
- sequestration and removal of foreign materials and organisms that remain undigested or have not provoked an immune response
What is special about macrophage 1- M1?
Activated by IFN-y
- avidly phagocytic- lyse ingested pathogens and fireign antibodies
- promote inflammatio, ECM damage and apoptosis
-
What is special about macrophage 2(M2)?
Activated by interleukins
Downregulate inflammation
Promotes rebuilding of ECM and cellular proliferation
Stimulates angiogenesis
What is antigen presentation?
Antigen processing and presentation on its surface of APC
- endocytosis of antigen and binding to MHV II molecules in endosomes
- Translocation to the plasma me,Braine
Interaction with CD4+ cells
How do T cells interact with endogenous antigens?
- Antigen proteosome degradation
- Formation of Ag-MHC complex (rER)
- Translocation of complex via Golgi
- Presentation of Ag-MHC-1 on plasma membrane followed by CD8 recognition (CTL)
How do T cells interact with exogenous antigens?
- MHC-II assembly in rER
- Translocation of MHC-II to membrane
- MHC-II displayed on cell surface
- Endosomal endocytosis of MHC-II
- Exogenous Ag endocytosis
- Proteolytic degradation of Ag
- Formation of Ag- MHC-II complex
- Display of Ag.-MHCII complex on cell surface followed by CD4+ T helper recognition
- Lysosomal degradation of failed of Ag-MHC-II recognition
What is an innate response?
Nonspecific immunity
Occurs through action of neutrophils, macrophages, mast cells and NK cells
Fast and nonspecific
Does not produce memory cells
What are adaptive immune responses?
Specific immunity
Depends on initial recognition of antigens by B and T cells
Slower and specific
Produces memory cells
- primary response
- secondary response
What is antibody mediated immunity?
Helper T cells, B-cells and plasma cells
-cause a release of antibodies that act on invading antigen
What is cell mediated immunity?
- Specific T cells that specialize in cytotoxicity
- Granzymes and perforins
What are the types of lymphoid tissue?
-Diffuse lymphoid tissue
- Nodular lymphoid tissue
- solitary nodules
- aggregate nodules
What are the lymphoid organs?
Primary lymphoid organs
- bone marrow
- thymus
- GALT
Secondary lymphoid organs
- lymph nodes
- spleen
- tonsils
Describe diffuse lymphoid tissue
- non encapsulated accumulations of lymphocytes and other free cells (plasma cells, eosinophils, fibroblasts)
- protects the body from antigens
- initial immune response
- located in the Lamina propria (subepithelial tissue)
- Mucosa Associated Lymphatic Tissye (MALT)
What are the cells in a lymphatic nodule?
- Lymphocytes
- Reticular cells
- Dendritic follicular cells
- Macrophages
- Follicular dendritic cells
Whaat is the purpose of lymphocytes in lymphatic nodules?
B lymphocytes
Activated > proliferate> plasma cells & memory cells
What do reticular cells do in lymphatic nodules?
Produce reticular fibers (stroma)
What do dendritic follicular cells do in lymphatic nodules?
Most efficient APCs
PResent antigens on MHC I & MHC II molecules
What are the functions of macrophages in the lymphatic nodules?
Phagocytic & APC (contain MHC I & II molecules)
What are the purposes of follicular dendritic cells?
Dendritic in nature: lack MHC-II molecules: harbors Ag-Ab complexes
What are the characteristics of lymphatic nodules?
-localized concentrations of lymphatics and other free radicals (plasma cells, eosinophils, fibroblasts)
Located in the wall, of the GI ttact (tonsils, ileum), respiratory, genitourinary
- Nonencapsulated, solitary(duodenum) or aggregated (tonsils, peyers patches)
- protects the body from antigens
- Mucosa associated lymph tissue (BALT, GALT)
What are the classifications of lymph nodules/follicles?
Primary
Secondary
What are primary lymph nodules/follicles?
Mainly small lymphocytes
Dense heterochromatin
What are secondary lymph nodules/follicles?
After exposure to antigen
What is the germinal center of the lymphoid nodule/follicle?
Center of lymphocyte activation proliferation and differentiation
- pale staining central region
- large immature lymphocytes with dispersed heterochromatin
- follicular dendritic cells and macrophages
What is the mantle zone or corona of the lymphoid nodule/follicle?
Outer dark staining region, with smaller cells
Where is the thymus located?
Superior mediastinum
What are the characteristics of the thymus?
Primary lymphoid organ
No afferent lymphatics
Origin- mainly 3rd pharyngeal pouch
Mulyipotent lymphoid stem cells invade epithelial rudiment to differentiate as T lymphocytes
Therefore- lymph Ophelia lymph organ
Epithelial component- ERCs(epithelial reticular cells)
Describe the structural integrity of the thymus
Covered by a thin CT capsule
Trabeculae run within to divide tissue as lobules
Each lobule has a cortical cap over portions of highly convoluted but continuous inner medullary tissue
Describe the parenchyma of the thymus
Cortex of parenchyma :
-mainly immature T lymphocytes (thymocytes ) & ERCs (epithelial reticular cells)
Medulla of parenchyma:
-mature T lymphocytes & ERCs
Explain the significance of epithelial reticular cells (ERC’s)
Thymic epithelial reticular cells(ERC’s)- primary support cells in the cortex
Form a cytoreticulum-held together by Desmosomes
Blood vessels in cortex ensheathed by ERC’s
Sequester the developing T cells from blood borne antigens
Where is the blood supply of the thymus?
Enter through trabeculae into cortex and medulla
Characterized by continuous capillaries
What are the components of the blood thymus barrier?
A. Capillary endothelium
B. Capillary basal lamina
C. Perivasculaar connective tissue
D. Epitheliorecticular tissue
E. Epitheliorecticular cell
Blood thymus barrier found only in cortex
Describe the cortex of the thymus
Cortex of tightly packed lymphocytes and support cells epithelial recticular cells (epithelial reticular cells)
Inner medulla- lymphocytes less concentrated
More of ERCs giving eosinophilic appearance
Describe the medulla of the thymus
Blood vessels in medulla lose ERC covering
Lymphocyte differentiate and enlarge
Mature T cells migrate into medullary blood vessels and efferent lymphatics
- ERC’s contract into spherical, degenerative masses- Hassall’s corpuscle
- Hassal’s Corpuscle are found only in the thymic medulla and consist of rings of degenerating epithelial recticular cells
What are lymph nodes?
Kidney or bean shaped organs of variable size
Distributed along the course of lymphatic vessels
Function- filters lymphatic fluid as it passes through them
Mounts immune response by recirculating of lymphocytes
What are the parts of a lymph node?
Capsule- dense connective tissue
-pierced by afferent lymphatics
Outer cortex- collection of lymphocytes- prominent nodules
-abundance of B lymphocytes
Inner cortex/ para cortex - area between outer cortex and medulla
- collection of lymphocytes - abundance of T lymphocytes - no nodules
Medulla- cords and sinuses
Hilum- blood vessels and nerves (enter and leave): lymphatics exit
What are the parts of a lymph node?
Capsule- dense connective tissue
-pierced by afferent lymphatics
Outer cortex- collection of lymphocytes- prominent nodules
-abundance of B lymphocytes
Inner cortex/ para cortex - area between outer cortex and medulla
- collection of lymphocytes - abundance of T lymphocytes - no nodules
Medulla- cords and sinuses
Hilum- blood vessels and nerves (enter and leave): lymphatics exit
Outline the flow of lymph?
Afferent lymph vessels—> subscapular (cortical) sinus—> trabecular sinus—> medullary sinus —> efferent lymph vessel
What are the features of the stroma of the lymph node?
- Reticular cells (modified fibroblasts)- cytoplasmic extensions cover reticular fibers (collagen type III )
- Framework for myeloid organs: bone marrow, lymph node & spleen
Describe the outer cortex of the thymus
Area between capsule and medulla
Characterized by the presence of lymphatic nodules
Primary and secondary nodules
Mainly consisting of B lymphocytes
Presence of few T lymphocytes, macrophages, reticular cells and APCs
Describe the para cortex /deep/inner cortex of the thymus
- Area between outer cortex and medulla
- primarily comprises T lymphocytes
- Characterized by the presence of high endothelial venules
- HEVs- allow for the transition of lymphocytes from the blood stream to lymph tissue within lymph node
- Excess lymph fluid circulating within a lymph node (average 35%) is reabsorbed into these vessels
Discuss the medulla of the thymus
Cords:
-branched cordlike extension of dense lymphoid tissue
-contain primarily B lymphocytes, plasma cells, reticular cells and macrophages
Sinuses:
- Dilated spaces separating medullary cords
- Contain lymph, few wandering macrophages
- Granulocytes maybe present when lymph node is draining an infected region
