Lecture 23: Immune Lymphatic System Part I

Question 1

Define Innate Immunity

Answer 1

• Lacks immune specificity and memory
• Response = inflammation
• Neutrophils are the first responders

Question 2

Define Acquired Immunity

Answer 2

• Develops in response to antigens
• More powerful than innate immunity
• Takes longer to develop
• Displays specificity and memory

Question 3

Define Passive Immunity

Answer 3

• Temporary immunity due to donated antibodies (i.e., transplacental passing of maternal antibodies to fetus)

Question 4

Define Active Immunity

Answer 4

• Long-lasting/permanent immunity due to self exposure to antigen resulting in memory T cells and B cells specific for antigen

Other Immunities:
Cell-mediated immunity, and Humoral immunity
- See Slide 5

Question 5

Describe Lymphoid Tissue

Answer 5

• Appears in body as a gradient from diffuse lymphoid tissue to aggregated lymphoid tissue to lymphoid organs
• Lymphoid organs:
• Primary: Includes Thymus and Bone Marrow
• • Precursor cells mature into immunocompetent cells. Each cell is programmed to recognize a specific antigen.
• Secondary: Includes Lymph nodes, spleen, tonsils
• • Trapped antigens stimulate clonal expansions of mature T and B cells.
• Lymphocytes originate in primary lymphoid organs and then take up residence in secondary lymphoid organs.
• Lymphoid nodule (follicle)
• Primary vs secondary (with germinal center)

Question 6

Describe Lymphoid Follicles

Answer 6

• Lymph follicles (nodules):
• Are not enclosed within a capsule.
• Occur singly or in aggregates.
• Are sites of B cell localization and proliferation.
• Transient.
• Primary follicles (nodules):
• Are spherical, tightly packed accumulations of virgin B cells and dendritic reticular cells that have not been exposed to antigens.
• Secondary follicles (nodules):
• Are derived from primary follicles that have been exposed to nonself antigens.
• Are not present at birth.
• Structure of a secondary lymph follicle:
• Corona (cortex):
• • Darker peripheral region
• • Composed of densely packed B lymphocytes
• Germinal center:
• • Central, lighter stained region.
• • Composed of B lymphocytes, memory B cells, plasma cells, dendritic reticular cells which function as antigen-presenting cells.
• Vascular supply:
• Arteriole and venule supply the cortex
• Another arteriole and venule supply the center
• Lymph capillaries are not present

Question 7

Compare Diffuse Lymphoid Tissue to Aggregated Lymphatic Tissue

Answer 7

• Diffuse lymphoid tissue is made up of scattered clusters of plasma cells, macrophages, and lymphocytes located in the connective tissue stroma and various other sites.
• Subcutaneous-associated lymphoid tissue is found in the papillary layer of the dermis.
• Lamina propria-associated lymphoid tissue includes:
• • MALT = mucosal-associated lymphoid tissue
• • BALT = bronchial-associated lymphoid tissue
• • GALT = gut-associated lymphoid tissue
• Aggregated lymphoid tissue is beneath and in contact with the epithelium:
• Includes various tonsils and Peyer’s patches in the ileum
• See Slide 10

Question 8

Describe Lymphopoesis

Answer 8

• All immune system cells originate in bone marrow.
• Immature T cells travel to thymus.
• B-cells travel to specific regions in lymphoid tissue.
• See Slide 12 & 13

Question 9

Describe B Cells

Answer 9

• Maturation of B cells involves the appearance of certain cell surface receptors:
• IgM and IgD
• MHC class II proteins
• Complement receptors
• IgFc receptors

Question 10

List the 5 antibody classes

Answer 10

IgA, IgD, IgG, Ig M, IgE

Question 11

Describe the structure of an antibody

Answer 11

Antibody structure:

• Light and heavy chains
• Highly variable regions:
• • Fab fragment
• • Recognizes antigen
• Less variable regions:
• • Fc fragment
• • Binds antibody to cells

Question 12

Briefly describe the characteristics of the 5 classes of immunoglobulins

Answer 12

• 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
• IgE: Associated with allergic responses
• IgM: First antibody class expressed by developing B cells

Question 13

Describe the major histocompatibility complex

Answer 13

• Function:
• Main function of MHC gene products is the presentation of antigenic peptides to T cells.
• Classes of MHC gene products:
• MHC I: Expressed on the surface of all cells except trophoblast and red blood cells
• MHC II: Expressed on the surface of B cells and antigen-presenting cells
• CD8+ T cells recognize peptide fragments of foreign proteins bound to MHC class I on the surface of cells.
• CD8 is a member of the Ig superfamily.
• • Both the CD8 and the T cell antigen receptor are required for the binding of MHC class I protein fragments.
• CD4+ T cells recognize peptide fragments of foreign proteins bound to MHC class II proteins on surface of APCs.

Question 14

Describe T Cells

Answer 14

• 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
• Bind to an antigen presenting cell
• Undergo mitosis
• Releases: Perforins and Fas ligand
• Recognize antigens bound to MHC class I molecules
• Mediators of cellular immunity

Question 15

Describe CD16+ T Cells

Answer 15

• Natural killer (NK) T cells
• Activated (by tumor cell antigens) T-helper cells release cytokines:
• Interleukin-2: Stimulates proliferation of NK cells
• Interferon-γ Activates NK cells
• Macrophage activating factor (MAF): Activates macrophages
• Chemotactic factor
• Tumor necrosis factor (TNF-β): Kills tumor cells directly
• See Slide 20 & 21

Question 16

Describe T-Cell Mediated Immunity

Answer 16

• Macrophage phagocytizes foreign material.
• Foreign proteins are broken down into fragments, some of which have antigenic properties (epitopes).
• Antigens are expressed on surface of macrophage bound to MHC-II
• MHC-II/antigen complex is presented to activated helper T cell.
• Activated T cell undergoes mitosis:
• Some daughter cells become memory cells
• Some daughter cells secrete interleukins
• T cells attract B cells
• B cells have access to free antigens
• B cells undergo mitosis
• Some daughter cells become plasma cells: Secrete appropriate antibodies
• Some daughter cells become memory cells
• See Slides 24 - 26

Question 17

Describe the Complement System

Answer 17

• The complement system is an array of about 20 serum proteins which are synthesized in the liver and found in the blood.
• Classic pathway: Cascade is activated by antibody binding to a pathogen.
• Alternate pathway: Cascade is directly activated by the pathogen.
• The complement system facilitates inflammatory responses.
• The complement cascade (either pathway) involves coating the pathogen with complement initiating the cascade.

Question 18

Describe the Activation System

Answer 18

• C1 (the first complement factor in the cascade) is made up of three subcomponents: C1q, C1r, C1s)
• Immunoglobulins bind to surface of pathogen.
• C1q binds to Fc region of Ig:
• -Activates C1r:
• –Which Activates C1s
• —Which Initiates complement cascade.
• C1s → C4 → C4a+ C4b
• C4b binds to surface of pathogen
• C1s → C2 → C2a + C2b
• C2b binds to C4b → C4b-2b complex
• (= C3 convertase)
• See Slide 30-34
• C4b-2b complex (C3 convertase) → C3
• → C3a and C3b
• C3b is the most important opsonin
• Multiple C3b bind to C3 convertase →
• C4b-2b-3b complex (= 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.

Question 19

Describe the complement system

Answer 19

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 antigens more palatable to phagocytes.
• Release of chemotactic agents (chemokines) which attract phagocytes (chemotaxis) to the areas of infection or inflammation.

Question 20

Compare parenchyma vs stroma

Answer 20

• 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

Question 21

Describe the basic structure of a lymph node

Answer 21

• 1-25 mm in diameter
• Hilus:
• Entry and exit point for vessels
• • Efferent lymphatic vessels as well as arteries and veins enter/leave through the hilus.
• • Afferent lymphatic vessels enter the convex side of the node.
• Capsule:
• Dense collagen fibers, some elastic fibers and smooth muscle fibers
• Trabeculae: …uhhhhh. Doesn’t really say anything.
• Cortex:
• Outer: Contains lymph follicles (nodules)
• Follicles: Contains: B cells, Follicular dendritic cells, and Migrating dendritic cells
• • Secondary: Mantle, and Germinal center
• • Primary: Lack mantle and germinal center
• Deep (inner): Contains TH cells, macrophages, High endothelial venules (HEVs), and Port of entry for circulating differentiated lymphocytes to seed lymph node

Question 22

Describe the medulla in a lymph node

Answer 22

• Irregular arrangement of loose medullary sinuses and dense medullary cords
• Sinuses are lined with macrophages
• 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.
• See Slides 42 & 43