T-Lymphocytes and Immune Response

• Pathogens can invade living tissues through the skin, gut, respiratory tract, and genitourinary tract linings.
• The immune system has two branches: cell-mediated and humoral immunity.
• Lymphatic cells, tissues, and organs form the morphologic basis of the immune system.

Lymphatic Cells

• Lymphocytes are the predominant cells in lymphatic tissues/organs, making up 20-50% of circulating leukocytes.
• Lymphocyte numbers increase in response to viral infections.
• Lymphocytes differentiate into two functional types: T-lymphocytes and B-lymphocytes.

T-Lymphocytes

• Originate in bone marrow, migrate to the thymus to develop into mature T-cells (thymus-dependent).
• Destroy antigens via direct cytotoxic activity or by activating B lymphocytes/macrophages.
• T cell stimulation leads to cell-mediated immune response or cellular immunity.
• T lymphoblasts differentiate into T cell subsets.

T Helper Cells

• Help other lymphocytes using interleukins.
• Activate B cells for antibody production and regulate cytotoxic T cell function.
• Characterized by surface markers: CD4, pan-T cell markers (CD2, CD3, TCR).
• HIV depletes T helper cells, impairing immune response and leading to opportunistic infections in AIDS.

Cytotoxic T Cells

• Mediate cell-mediated immunity by killing infected/malignant cells.
• Carry the CD8 surface marker and pan-T cell markers.
• Require T helper cell interaction for activation and cytotoxic function proliferation.

Suppressor T Cells

• Responsible for turning off immune response by inhibiting cytotoxic/helper T cells when the stimulus is removed.
• Suppress immune responses to self-antigens.
• Also carry CD8 marker and are sometimes referred to as suppressor/cytotoxic cells.

T Memory Cells

• Increase the supply of immunologically competent lymphocytes.
• Provide a quicker immune reaction upon subsequent antigen exposure.

B-Lymphocytes

• Derived from colony-forming cells in bone marrow; mature in bone marrow.
• B cell maturation was first studied in birds in the Bursa of Fabricius.
• Antigen exposure stimulates B lymphocytes to transform into lymphoblasts, then differentiate into plasma cells or B memory cells.

Immune Response

• An immune reaction starts when a B cell encounters an antigen.
• The initial response is the primary immune response.
• Some cells from the clone become memory cells, which are circulating lymphocytes that respond rapidly to subsequent antigen challenges.
• Secondary immune response involves greater antibody production and immunoglobulin production, leading to long-term immunity, as seen with vaccinations.
• Stimulation of B cells results in the humoral immune response.

Plasma Cells

• Appear in peripheral lymphoid tissues, not the circulation, after B cell stimulation.
• They synthesize antibodies, also known as immunoglobulins (IgG, IgA, IgD, IgM, IgE).

Antigen Presenting Cells (APCs)

• Heterogeneous group of cells that ingest, process, and present antigen fragments to lymphocytes.
• Found in peripheral blood and afferent lymph, e.g., Langerhans cells in the epidermis.

Large Granular Lymphocytes (LGL)

• Have more cytoplasm than small lymphocytes.
• Function as natural killer (NK) cells, killing virus-infected and cancer cells.

Macrophages

• Act as tissue macrophages
• Present antigens to T lymphocytes after activation
• Kill bacteria and some cancer cells
• Regulate some T helper functions.

Lymphatic Tissues

• Exist as diffuse deposits or nodules throughout the body and come in two forms, loose and dense.

Loose (Diffuse) Lymphoid Tissue

• Has lymphocytes and related cells in larger quantities than in typical connective tissues.
• No nodular organization and little delineation from surrounding tissue.

Dense Lymphoid Tissue

• Characterized by densely aggregated cells (mostly small lymphocytes).
• Tissue is clearly delineated from surrounding tissues.

Lymphatic Organs

• Tissues and cells assemble into organs, classified as central/formative or peripheral/reactive.

Central/Formative Lymphatic Organs

• Bone marrow and thymus gland
• Sites for initial lymphocyte differentiation, not typically sites of immune reactions.

Peripheral/Reactive Lymphatic Organs

• Lymph nodes, spleen, tonsils, Peyer's patches
• Sites of immune reactions for lymphocyte surveillance of body cavities and fluids.

Histology of Formative Lymphoid Organs

• Bone marrow generates unspecified lymphocytes and is where B lymphocyte differentiation occurs.
• Thymus will be described.

Thymus

• Lobed organ with each lobe divided into lobules.
• Each lobe is covered by a CT capsule with septae dividing the lobules.
• Lobules have a darkly stained outer cortex with densely packed thymocytes/T lymphocytes, without nodules.
• The inner medulla is lightly stained and has fewer thymocytes, plus Hassal's corpuscles (aged epithelial reticular cells).

Histology of Reactive Lymphoid Organs

• Diffuse lymphoid tissue is in tubular organs of digestive, respiratory, urinary, and reproductive systems.
• It is located below the epithelial lining in the CT layer called lamina propria.

Function of Diffuse Lymphoid Tissue

• Surveillance/"screening" of sub-epithelial connective tissue in tubular organs
• Provides quick response to penetrating foreign organisms.

Tonsils

• Palatine, pharyngeal (adenoids), and lingual tonsils form a lymphoid tissue "ring" in connective tissue (lamina propria) below the pharynx's epithelium.
• Partially encapsulated by loose to moderately dense CT.
• Function in surveillance/screening of oral and pharyngeal areas against foreign organisms.

Peyer's Patches

• Located in the ileum wall
• Function in surveillance/"screening" of the small intestine's lumen.
• Characterized by large spherical aggregates (nodules) of dense lymphoid tissue in the submucosa, bulging into the ileum lumen.

Appendix

• Lymphoid nodules are structurally and functionally similar to Peyer's patches.
• They prime the immune system against microorganisms in the colon.
• This ensures the destruction of microorganisms if they penetrate the colon wall or peritoneal cavity.

Lymph Nodes

• Located along lymphatic vessels, covered by a dense CT capsule.
• The cortex has B lymphocyte aggregates.
• Medulla contains lymphoid tissue in dense medullary cords, B lymphocytes, plasma cells, and associated microvasculature.

Lymph Node Functions

• Filter and screen lymph.
• Facilitate lymphocyte movement from blood into lymphoid tissue (via high endothelial post-capillary venules).
• Expose lymphocytes to antigens, stimulating immune responses.
• Serve as a site for final stages of T lymphocyte differentiation and B lymphocyte differentiation into plasma cells.

Spleen

• Covered by a dense CT capsule.
• Contains two types of parenchyma tissue: white pulp and red pulp.

White Pulp

• Mostly made of non-nodular dense lymphoid tissue.

Red Pulp

• Contains small arteries, capillaries, and diffuse lymphoid tissue in cords (splenic cords or cords of Billroth).