Final: Lecture 18 Flashcards
Acquired Immunity
- Develops in response to antigens
- More powerful than innate immunity
- Takes longer to develop
- Displays specificity and memory
Innate Immunity
- Lacks immune specificty and memory, what you’re born with
- Response = Inflammation
- Neutrophils are the first responders
Lymphoid tissue
•Appears in body as a gradient from diffuse lymphoid tissue to aggregated lymphoid tissue to lymphoid organs
Passive immunity
•Temporary immunity due to dontated antibodies (i.e. transplacental passing of maternal antibodies to fetus)
Active immunity
•Long-lasting/permanent immunity due to self exposure to antigen resulting in memory T cells and B cells specific for antigen
Lymphoid organs
- Primary: thymus and bone marrow
* Secondary: lymph nodes, spleen, tonsils
__________ originate in primary lymphoid organs and then take up residence in secondary lymphoid organs.
•Lymphocytes
Lyphopoiesis
- All immune system cells originate in bone marrow
- Immature T cells travel to thymus
- B-cells travel to specific regions in lymphoid tissue
Antibodies (Immunoglobulins)
- 5 classes: IgA, D, G, M, and E
- Light and heavy chains
- Highly variable regions: fab fragment, recognizes antigen
- Less variable regions: Fc fragment, binds antibody to cells
IgA
•Found in saliva, milk, GU and respiratory tracts
IgD
•Found on surface of B cells traveling to lymphoid organs
IgG
- Major Ig in blood
* Responsible for most antibody activity, only one capable of crossing the placenta
IgE
•Associated with allergic responses
IgM
•First antibody class expressed by developing B cells
B cells
- Maturation involves the appearance of certain cell surface receptors
- IgM and IgD, MHC class II proteins, complement receptors, Ig Fc receptors
Major Histocompatibility Complex
- Function: Main function of MHC gene products is the presentation of antigenic peptides to T cells
- MHC 1: Expressed on the surface of all cells except trophoblasts and RBC
- MHC II: Expressed on the surface of B cells and antigen-presenting cells
CD8+ T cells recognize _____ _____ of foreign proteins bound to MHC class I on the surface of cells.
- Peptide fragments
- CD8 member of the Ig superfamily
- Both the CD8 and T cell antigen receptor are required for the binding of MHC class I protein fragments
CD4+ T cells also recognize ____ ______ of foreign proteins bound to MHC class proteins on surface of ___.
- Peptide fragments
* APCs
T cells
- Pre-T cells develop in bone marrow
- Travel to thymus and complete maturation
- CD4+ T cells: recognize antigens bound to MHC class II molecules
- Helper cells: assist CD8+ cell differentiation, assist B cell differentiation
CD8+ T cells
- Cytolytic T cells (kills cells)
- Bind to an antigen presenting cell, undergo mitosis
- Release perforins and Fas ligand
- Recognize antigens bound to MHC class I molecules
- Mediators of cellular immunity
CD16+ T cells
- Natural killer (NK) T cells
- Activated (by tumor cell antigens) T-helper cells release cytokines: Interleukin-2, Interferon-gamma, Macrophage activating factor (MAF), chemotactic factor, tumor necrosis factor
Interleukin-2
•Stimulates proliferation of NK cells
Interferon-y
•Activates NK cells
MAF
•Activates macrophages
Tumor necrosis factor (TNF-ß)
•Kills tumor cells directly
T cells recognize _____ _____ only when they are presented bound to MHC.
•peptide antigens
MHC restriction
- Cytolytic T cells recognize an antigen presented by class I MHC molecules
- Helper T cells recognize an antigen is association with class II MHC
Foreign proteins are broken down into fragments, some of which have antigenic properties called ______.
•Epitopes
Activated T cells undergo mitosis, some daughter cells become ______ cells, while others secrete _______.
- Memory cells
* Interleukins
B cells undergo mitosis, some daughter cells become ______ cells, while others become _______ cells.
- Plasma, secrete appropriate antibodies
* Memory
What is the role of Perforin?
•Pokes holes in cell membranes to kill the infected target cell
The cytolytic T cells protects itself from perforin with _______.
•Protectin, binds to perforin
___ _____, released by the cytolytic T cell and bound to the ___ receptor, together with granzye destroy by apoptosis the target cell.
- Fas ligand
* Fas
Complement system
- Is an array of about 20 serum proteins which are synthesized in the liver and found in the blood
- Facilitates inflammatory response
- Either pathway involves coating the pathogen with complement initiating cascade
Classic pathway
•Cascade is activated by antibody binding to a pathogen
Alternate pathway
•Cascade is directly activated by the pathogen
Activation Sequence
- C1(the first complement factor in the cascade) is made up of three subcomponents.
- Immunoglobulins bind to surface of pathogen
- C1q binds to Fc region of Ig–>activates C1r–>activates C1s—>initiates complement cascade
Activation Sequence after C1s
- C1s–> C4–>C4a + C4b (binds to surface of pathogen)
- C1s–>C2–>C2a + C2b
- C2b binds to C4b–>C4b - 2b complex (=C3 convertase)
Activation Sequence after formation of C3 convertase
- C3 convertase–>C3–>C3a + C3b (most important opsonin)
* Multiple C3b bind to C3 convertase–>C4b - C2b - C3b complex (= C5 convertase) ** really attracts macrophages
Activation Sequence after formation of C5 convertase
- C5 binds to C3b–>C5a + C5b
* When C6, C7, and C8 are added to the complex, they form pores in the membrane of the pathogen. (KILL IT)
The complement cascade results in the following:
- activation of the membrane attack complex (MAC) on the pathogen leading to perforations and lysis
- Production of opsonins, which are coatings that make the antigen more palatable to phagocytes
- Release of chemotactic agents (chemokines) which attract phagocytes (chemotaxis) to the areas of infection or inflammation
Parenchyma
- Consists of the cells that typically pack areas of the lymphoid organ
- Mostly lymphocytes
Stroma
•Consists mostly of reticular fibers and cells, including undifferentiated cells and fixed and free macrophages
Lymph follicles (nodules)
- Gross structure: not encapsulated, cortex of dense, small lymphocytes, germinal center (only present if immune response is going on) of proliferative lymphocytes
- Transient
- Vascular supply: arteriole and venule supply the cortex, another supplies the center, lymph capillaries are not present
Lymph node Hilus
- Entry and exit point for vessels
- Efferent lymphatic vessels as well as arteries and veins enter, carrying away from node
- Afferent enter the convex side of the node
Lymph node Capsule
•Dense collagen fibers, some elastic fibers and smooth muscle fibers
Lymph node Cortex
- Outer: contains lymph follicles (nodules)
- Follicles: contain B cells, follicular/migrating dendritic cells, secondary (mantle and germinal center), and primary (lack mantle and germinal center)
- Deep (inner): Contains Th cells, macrophages, high endothelial venuels (HEVs, port of entry for circulating differentiated lymphocytes to see lymph nodes)
Lymph node Medulla
- Irregular arrangement of loose medullary sinuses (lined with macrophages) and dense medullary cords (consist of blood vessels, lymphoblasts and plasma cells)
- Site of lymphocyte reentry into lymph stream
- Thymic-dependent areas in subcortical and deeper medullary regions, have primary T cells
Thymus Histology
- Capsule: blood vessels, no lymphatics
- Septa: delicate CT
- Most developed at puberty: 10-15 grams at birth, 30-40 at puberty
- Involutes during adolescence, no lymph follicles, afferent lymph vessels, or lymph sinuses
Thymus Cortex
- Cortex (dark staining): small lymphocytes and immunoblasts
- thymocytes migrate from cortical areas to medually
- blood vessels surrounded by continuous epithelial barrier (allows to maintain lymphopoiesis while segregated from antigens)
Thymus Medulla
- Light staining, specialized to allow entry channel into blood stream of differentiating lymphocytes
- Capillary beds are not sheathed by epithelial cells
- Hassall’s corpuscles: whorls of highly keratinized medullary epithelial cells, produce cytokine thymic stomal lymphopoietin
- Stimulates thymic dendritic cells needed for the maturation of single positive T cells
Differentiation of T cells**
- Double negative
- Double positive T cells move to outer cortex
- Single positive move to inner cortex: express TCR receptors and either CD4 or CD8 coreceptors
Double negative T cells
- Lack cell surface molecules typical of mature T cells
- Enter cortex from blood vessels
- Proliferate in subcapsular area*
Double positive T cells
- Move to outer cortex
- Confronted with epithelial cells with cell surface MHC classes I and II for clonal selection (if you aren’t good enough, they will kill you!!!)
- Express both CD4 and CD* coreceptors and TCR receptors
Spleen Morphology
- 5.6 x 4 inches, no lymph sinuses or afferent lymph vessels
- Covered by peritoneum except at hilus
- Blood vessels enter and leave hilus
Spleen Functions
- Only lymphatic organ specialized to filter blood
- Stores and removes worn-out RBCs
- Recycles iron
- Converts hemoglobin to bilirubin
- blood formation in the fetus
Spleen Immunologic functions
- Sreens foreign material in the blood
- Produces lymphocytes and plasma cells (produced in bone marrow, activated by spleen)
- Removal leads to overwhelming bacterial infections in infants, children, and young adults
Spleen Histology
- Capsule: thin, dense fibrous CT with elastic fiber and some smooth muscle
- Trabeculae: extend inward from capsule, covered by mesothelium
Spleen Parenchyma
- B cells located in the peripheral white pulp, often have germinal centers
- T cells found in the areas surrounding the central artery near the center of white pulp
- Reticular fibers are associated with fixed macrophages and support splenic pulp
Spleen White Pulp
- Elongated, branched strands always associated with arteries
- Zones of diffuse lymphoid tissue and germinal centers (contain B cells)
- Lymph follicles, chief site of lymphocyte production
- T-cell areas surround follicles and periarteriolar sheaths (PALS)
Spleen Red Pulp
- Surrounds white, contains large number of RBCs
* Cords of lymphoblasts and plasma cells = Billroth cords
Spleen Vascularization
- Arteries: splenic enters at hilus, trabecular arteries branch off
- Central arteries: adventitia (CT) loosens and becomes mesh-like reticulum infiltrated with lymphocytes
- After capillaries form, supplying white pulp, central arteries lose their white pulp investment and enter red pulp to form penicillus
Penicillus
- composed of pulp arteriole, sheathed arteriole, and terminal capillary
- Terminal cap. drains into intercellular spaces (open system) or venous sinuses lined with reticuloendothelial cells (closed system)
