Lec 38: Lymphocytes and Lymphoid Organs, I & II

Question 1

What are the lymph organs:

Answer 1

Lymph nodes, spleen, appendix, tonsils / adenoids, thymus, spleen, bone marrow, peyer’s patches

Question 2

What connective tissue structures are involved in the lymphatic system?

Answer 2

T cells, B cells, bone marrow, natural killer T cells

T cells: play a central role in cell-mediated immunity and have a TCR which senses an MHC class receptor with a peptide.

B Cells: responsible for antibody production. Humoral response to an antigen that results in the secretion of antibodies by plasma cells derived from B-lymphocytes.

Natural killer T cells NKT cells: (not to be confused with natural killer cells of the innate immune system) bridge the adaptive immune system with the innate immune system. Recognize peptide antigens presented by MHC molecules, NKT cells recognize glycolipid antigens (peptides) presented by a molecule called CD1d. Once activated, these cells can perform functions ascribed to both Th and Tc cells

Question 3

What structures are considered diffuse lymphatic tissue?

Answer 3

Peyer’s Patches: (in between temporary and permanent structure) organized lymphoid nodules. Aggregations of lymphoid tissue found in the lowest portion of the small intestine. Provides immune surveillance of the intestinal lumen and facilitates the generation of the immune response within the mucosa.

Adenoids (pharyngeal tonsils)/tonsils: collections of lymphoid tissue roof of the pharynx of the throat, first line of defense against ingested or inhaled foreign pathogens

Question 4

What is the role of lymphatic vessels?

Answer 4

permeates all tissues of the body and has two functions. 1. acts to return extracellular fluids to blood circulatory system. 2. acts as pathway for certain cells of the immune system to move between different parts of body, as well as re-enter the circulatory system. Or move from circulatory system back to lymphatic organs.

Question 5

Describe the humoral immune response:

Answer 5

Humoral immune response: response of activated B-lymphocytes that have been presented with a foreign antigen.

• Mediated by interaction between macrophage, T-lymphocyte and B-lymphocyte
• Causes clonal proliferation of activated B-lymphocytes
• Clonally produced B-lymphocytes differentiate into plasma cells or memory B-lymphocytes
  
  • Plasma cells are short lived and secrete copious amounts of antibody that are specific for an epitope of the antigen
    
    • Antibodies act to identify foreign cells for attack by other components of the immune system such as T-lymphocytes
    • Antibodies can also identify particulates and viruses for phagocytosis and destruction by other leucocytes such as neutrophils and eosinophils.
  • B-lymphocyte memory cells remain dormant and will rapidly respond to future encounters with the same antigen by clonal proliferation resulting in the formation of plasma cells that secrete antibodies specific for that antigen.

Question 6

Describe the cell mediated immune response:

Answer 6

Cell-mediated immune response: antigen activates T-lymphocytes to produce cytotoxic substances that cause the destruction of the antigen containing cell

• Mediated by interaction between macrophage and T-helper (Th) and T-cytotoxic (Tc) lymphocytes
• Causes clonal proliferation of Tc lymphocytes
• Clonally produced Tc lymphocytes differentiate into either Tc memory cells or Tc effector cells
  
  • Tc effector cells - actively kill invading foreign cells
  • Tc memory cells remain dormant and will rapidly respond to future invasions by foreign cells expressing the same antigen

Question 7

What is MALT?

Answer 7

Diffuse lymphatic tissue/MALT (mucosa-associated lymphoid tissue):

small concentrations of lymphoid tissue found in various sites of the body, such as the gastrointestinal tract, thyroid, breast, lung, salivary glands, eye, and skin. MALT is populated by lymphocytes such as T cells and B cells, as well as plasma cells and macrophages, each of which is well situated to encounter antigens passing through the mucosal epithelium. In the case of intestinal MALT, M cells are also present, which sample antigen from the lumen and deliver it to the lymphoid tissue. These tissues comprise the largest (admittedly diffuse) lymphoid organ in the body and contain about 70% of the body’s immune cells.

Question 8

Describe the structure and function of the palatine tonsils:

Answer 8

• On left and right in rear area of oral cavity.
• Dense lymphoid tissue that forms a band of lymphatic nodules that lie just below a non-keratinized, stratified, squamous epithelium lining the oral cavity in this region.
• Overlying epithelium forms invaginations called multiple crypts that penetrate into the band of nodules.
• These crypts act as collecting places for cellular debris and bacteria as well as some living lymphocytes that have migrated into the crypts.
• The band of lymph nodules is separated from underlying tissues by a partial capsule of dense connective tissue.

Question 9

Describe the structure and function of pharyngeal tonsils:

Answer 9

• Diffuse lymphoid tissue containing nodules, but no crypts.
• Mostly lie beneath a typical pseudostratified ciliated columnar respiratory epithelium in rear roof of pharynx. Some areas of the covering epithelium may be stratified squamous.
• A thin partial capsule of dense connective tissue separates the lymphoid tissue from underlying tissue.

Question 10

Describe the structure and function of lingual tonsils:

Answer 10

• Situated in the root of tongue.
• Each lingual tonsil consists of numerous. lymphoid nodules surrounding a single crypt
• The crypt is lined by a non-keratinized, stratified, squamous epithelium.
• A thin partial capsule of dense connective tissue separates the lymphoid tissue from underlying tissue

Question 11

What is GALT?

Answer 11

GALT (Gut Associated Lymphoid Tissue): ie Peyer’s patches

Question 12

Describe the structure and function of lymph nodes:

Answer 12

• Present along the course of lymphatic vessels. Multiple lymph vessels may connect to a lymph node.
• Oval or bean shaped bodies surrounded by a dense connective tissue capsule
• Septa or trabeculae extend from capsule into lymph node.
• Filled with stroma consisting of reticular fibers and cells.
• Stroma provides a support network for large numbers of lymphocytes.
• Node consists of:
  
  • A dense outer cortex that consists of numerous lymphatic nodules. Many lymphocytes, macrophages, other antigen presenting cells (APCs), plasma cells and reticulocytes are present. Follicular dendritic cells are found in the germinal centers of lymph nodules that are in the cortex.
  • A less dense medulla consisting of lymphocytes arranged in strands called medullary cords.
    
    • sinuses are present in the medulla
    • Cords and sinuses extend toward a central hilus that is essentially a large trabecula projecting into the lymph node from the connective tissue capsule.
      
      • Arteries enter and veins and lymph vessels exit through the hilus
      • Blood vessels branch from the hilus into the cortical region where they give rise to “bulbs” of capillaries within the germinal centers of the cortical lymph nodules
• Between the cortex and medulla is the paracortical region or thymic dependent zone of the node that contains densely packed cells that are mainly T-lymphocytes.
• This region lacks lymphocytes in animals that have had the thymus removed at birth.
• Cells outside the paracortical region are mostly B-lymphocytes.

Question 13

Describe the structure and function of the spleen:

Answer 13

Spleen: Largest piece of lymphatic tissue in body. Site of formation of activated lymphocytes that enter the circulatory system. Also important in recycling of components of worn-out blood cells. Can be said to act as filter of blood both in an immunologic sense (that is it mediates components of immune response), but also in the sense of removing worn out erythrocytes from circulation.

• Structure
  
  • Surrounded by a dense connective tissue capsule that extends processes (trabeculae) into lymphatic tissue of this organ.
  • Connective tissue contains nerves, blood vessels,lymph vessels, and smooth muscle.
  • A hilus of connective tissue is present medially.
  • Blood vessels and nerves run through the hilum and enter the spleenic pulp via the trabeculae. There are no lymph vessels in the pulp.
  • Pulp is divided into lymphatic nodules of white pulp, surrounded by a spongy lymphatic tissue called red pulp. Color designations have to do with appearance in freshly cut open organ.

Question 14

Describe the structure and function of the thymus:

Answer 14

The thymus consists of multiple lobes each containing characteristic cortical and medullary structure; however, these are not lymphatic nodules (i.e., not a spherical structure that is distinct from surrounding cells). A connective tissue capsule surrounds the thymus.

Question 15

Describe a T_CTL / CD8⁺

Answer 15

Cytotoxic T lymphocyte: (TCTL) = CD8+ T cells

Destroy virally infected cells and tumor cells, and are also implicated in transplant rejection. Known as CD8+ T cells = they express CD8 glycoprotein at their surface. Recognize targets by binding to antigen associated with MHC class I molecules,

* memory tip: 2x4 = 8 for CD4 vs 1x8 = 8 for CD8

Question 16

Describe a helper cell (T_H) = CD4⁺ T cells

Answer 16

Helper cell (T_H) = CD4⁺ T cells: look for phagocytized material being presented by a MHC class II receptor

Assist other white blood cells in immunologic processes, including maturation of B cells into plasma cells and memory B cells, and activation of cytotoxic T cells and macrophages. CD4+ T cells express the CD4 glycoprotein on their surface. Helper T cells become activated when they are presented with peptide antigens by MHC class II molecules, which are expressed on the surface of antigen-presenting cells (APCs). Secrete cytokines to facilitate immune response

* memory tip: 2x4 = 8 for CD4 vs 1x8 = 8 for CD8

Question 17

Describe the role a T regulatory cells (T_REG):

Answer 17

Regulatory cells (T_REG):

Crucial for the maintenance of immunological tolerance. Major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus.

Question 18

Describe the role of B cells:

Answer 18

responsible for antibody production. Humoral response to an antigen that results in the secretion of antibodies by plasma cells derived from B-lymphocytes.

Question 19

Describe the role of natural killer T cells:

Answer 19

Natural killer T cells

NKT cells: (not to be confused with natural killer cells of the innate immune system) bridge the adaptive immune system with the innate immune system. Recognize peptide antigens presented by MHC molecules, NKT cells recognize glycolipid antigens (peptides) presented by a molecule called CD1d. Once activated, these cells can perform functions ascribed to both Th and Tc cells

Question 20

Describe T lymphocyte development

Answer 20

• All T cells originate from haematopoietic stem cells in the bone marrow.
• Haematopoietic progenitors (Lymphoid progenitor cells) from haematopoietic stem cells populate the thymus and expand by cell division to generate a large population of immature thymocytes.
• The earliest thymocytes express neither CD4 nor CD8, and are therefore classed as double-negative (CD4-CD8-) cells. As they progress through their development they become double-positive thymocytes (CD4+CD8+), and finally mature to single-positive (CD4+CD8- or CD4-CD8+) thymocytes that are then released from the thymus to peripheral tissues.
• Only 2% survive and leave the thymus to become mature immunocompetent T cells (via selection process)

Question 21

Describe B cell development:

Answer 21

B cells development:

• continuously produced in the bone marrow.
• Once a B cell can express both H and L chains on its membrane, it is officially a B cell. However, it is still immature and can be easily killed by contact with self antigen until it also expressed membrane IgD. The mature B cell that moves into the periphery can be activated by antigen and become an antibody-secreting plasma cell or a memory B cell which will respond more quickly to a second exposure to antigen. B cells which fail to successfully complete B cell development undergo apoptosis

Question 22

Describe clonal selection theory:

Answer 22

Clonal selection theory: explains the functions of lymphocytes response to specific antigens invading the body. Pre-existing group of lymphocytes (specifically B cells), a specific antigen only activates (i.e. selection) its counter-specific cell so that particular cell is induced to multiply (producing its clones) for antibody production. = diversity of antibody specificity

Question 23

Describe peripheral tolerance

Answer 23

Peripheral tolerance is immunological tolerance developed after T and B cells mature and enter the periphery. These include the suppression of autoreactive cells by ‘regulatory’ T cells (Tregs) and the generation of hyporesponsiveness (anergy) in lymphocytes which encounter antigen in the absence of the co-stimulatory signals that accompany inflammation, or in the presence of co-inhibitory signals.

Question 24

Describe the role that antigen-processing cells play in shaping the immune response.

Answer 24

Antigen Presenting Cells include macrophages and dendritic cells in lymphoid organs. There are “professional” APCs that include the B-lymphocytes as well as the epithelial reticular cells of the thymus. They have an active endocytotic system and expression MHC class II molecules.

APCs endocytose/or phagocytose and process antigens (molecule that is recognized by the adaptive immune system– pathogenic). The APCs then present the antigen in conjunction with a MHC class II molecules.

Question 25

Describe what is meant by an MHC-restricted response and what molecules are responsible for this activity:

Answer 25

T-cell receptors (TCRs) only recognize antigenic peptides when presented as part of MHC molecules (interacting with both the MHC and the peptide it presents). This means the T-lymphocytes are MHC-restricted.

Question 26

Compare the mechanisms that T and B lymphocytes use to fight pathogens and contrast the targets that the two cell types address.

Answer 26

T-lymphocytes:

• Pathogen-fighting Mechanisms
  
  • recognize antigenic epitopes via surface protein complexes (TCRs) and MHC classes (I & II)
• Targets
  
  • Helper T Cells: activated helper T lymphocyte → releases IL-2, which serves as the 2d stimulation for CTL; IL-4 stimulates B cells
  • Cytotoxic T Cells: release granzymes and perforins to trigger pathogen apoptosis; activated & memory CTL
  • Regulatory T Cells: inhibit specific immune responses, allow immune tolerance, maintaining unresponsiveness to self-antigens and suppressing excessive immune responses: control TCTL & TH; produce peripheral tolerance that develops in the thymus
  • gamma/delta T cells: (TCR contains gamma and delta chains instead of alpha and beta chains) migrate to the epidermis and mucosal epithelia (do not recirculate); FRONT-LINE cells

B-lymphocytes:

• Pathogen-fighting Mechanisms: Free antigen binds to BCR; B cell engulfs, processes, and presents antigen to activated T_H cell
• Targets: stimulated by Activated TH, the activated B cell proliferates and differentiates to form memory B cells and plasma cells (which produce antibodies)