Lymphoid organs

Innate immunity

Present from birth

Physical barriers (skin, mucous membranes of GI, respiratory, and urogenital tracts) that prevent infection or penetration

Leukocytes, lymphocytes, antimicrobial chemicals

Leukocytes (innate)

Neutrophils and other leukocytes remove bacteria, fungi, and parasites using toll-like receptors for recognition and binding

Natural killer cells (innate)

Primitive lymphocytes that destroy unhealthy host cells

Antimicrobial chemicals (innate)

HCl, defensins, lysozyme, complement proteins, interferons

Produced by leukocytes and barrier cells

Toll-like receptors

Receptors on leukocytes that allow for recognition and binding to invading microorganisms

Adaptive immunity

Develops slowly

Based on antigens being presented to lymphocytes in blood, lymph, ET, and CT

Produces memory cells that permit rapid response upon re-exposure to specific invaders

Cytokines

Peptides and glycoproteins that coordinate cell activities in innate and adaptive immune responses

Involved in chemotaxis, increasing mitotic activity of leukocytes, stimulation/suppression of lymphocytes, and stimulation of phagocytosis/directed cell killing by innate immune cells

Important for pharmaceutical action

Primary lymphoid organs

Thymus, bone marrow

Secondary lymphoid organs

Lymph nodes, spleen, mucosa-associated lymphoid tissue (MALT)

MALT

Lymphoid tissue found in the mucosa (epithelial lining and underlying tissue) of organs

70% of body’s immune cells (most B cells and some CD4+ T cells) found here

Contain lymphocytes, plasma cells (secrete IgA), APCs, and lymphoid nodules (B cells)

Antigen

Molecule recognized by cells of adaptive immune system, typically eliciting a response

Bacteria, protozoa, tumor cells, etc

Cellular response

Lymphocytes eliminate an antigen

Humoral response

Antibodies eliminate an antigen

Antibodies

Glycoproteins that interact with antigen determinants/epitopes

Have variable portions (F_ab) on the heavy and light chains that form an antigen binding site and a constant region (F_c) that can bind to surface receptors of several cell types

Produced by plasma cells (connective tissue)

IgG

Most common antibody

Found in fetal circulation, blood, CT, and lymphoid organs

Activate phagocytosis and neutralize antigens

IgM

Pentamer that makes up 5-10% of antibodies

Found on B lymphocyte surfaces, blood, CT, and lymphoid organs

First antibody produced in initial immune response and activates complement system

IgA

Second most prevalent antibody

Dimer with J chain and secretory component

Found in secretions, blood, CT, and lymphoid organs

Protects mucosa

IgD

Very rare

Found on surface of B lymphocytes, blood, CT, and lymphoid organs

Triggers initial B cell activation

IgE

Very rare

Found on mast cells and basophils, blood, CT, and lymphoid organs

Neutralization

Antibody covers biologically active portion of microbe or toxin

Agglutination

Antibody cross-links cells, forming a clump for easier removal

Precipitation

Antibody cross-links circulating particles (i.e., toxins) forming an insoluble antigen-antibody complex

Complement fixation

Fc region of antibody binds complement proteins and activates complement system

Opsonization

Fc region of antibody binds to receptors of phagocytic cells, triggering phagocytosis

Activation of NK cells

Fc region of antibody binds to an NK cell, triggering release of cytotoxic chemicals

Major histocompatibility complex (MHC)

Protein complex on the surface of antigen-presenting cells

Two classes

MHC Class I

Presented by all nucleated cells

Self-antigens that cause T-cells to ignore a cell

MHC Class II

Present on cell surface of cells of mononuclear phagocyte system

Bind fragments of proteins that the cell has ingested

Antigen presenting cells MHC

All express MHC Class II molecules

Mononuclear phagocyte cells and dendritic cells

T lymphocytes

Comprise ~75% of circulating lymphocytes

Recognize antigenic epitopes and perform various functions

Cell activation requires costimulation by cell surface receptors (TCRs) and CD4/CD8

Helper T cells

CD4 cells

Assist with immune response by producing cytokines to promote B cell differentiation, activate macrophages and cytotoxic lymphocytes

Cytotoxic T lymphocytes

CD8+ cells

Bind antigens on foreign cells or virus-infected cells (cell mediated immunity)

Regulatory T cells

CD4+ and CD25+ cells

Inhibit specific immune cells

B lymphocytes

Surface receptors for antigens are monomers of IgM or IgD (BCRs)

Receptor binds antigen and complex is endocytosed, degraded, and peptides are presented on MHC Class II molecules

Helper T cells bind the cell and activate it with a cytokine to induce recombination of immunoglobulin genes and stimulate cell proliferation

Lymphoid tissue composition

All organs except the thymus supported by a three-dimensional network of reticular fibers (type III collagen), some of which form densely-packed fibrous trabeculae

Lymphocytes and macrophages

Lymphoid nodule (follicle)

Found in secondary lymphoid tissues

B cells attach to receptors of dendritic cells, become activated, and aggregate (sometimes along with adjacent T cells in larger nodules)

Have a germinal center where large lymphoblasts undergo proliferation and gene recombination

Nonproliferating B cells form a more darkly stained mantle

Thymus

Bilobed (cortex and medulla) structure in the mediastinum that develops from embryonic endoderm

Induces central tolerance, preventing autoimmunity

Fully formed at birth and actively producing T cells, and undergoes involution at puberty, where it also becomes more fatty

Thymic cells

T lymphoblasts (thymocytes)

Thymic epithelial cells/epithelial reticular cells

Thymic epithelial cells (TECs)

Reticular antigen presenting cells with keratin-containing processes that form barriers

Macrophages and lymphoblasts attach to these cells and interact with MHC class I/II and cytokines

Blood-thymus barrier

Formed by thymic epithelial cells (cytoreticulum) that are joined by desmosomes an occluding junctions

Lining of CT capsule and septa

Along with pericytes, prevent exposure of thymocytes to antigens

Corticomedullary barrier

Thymic epithelial and squamous cells that express MHC class II molecules

Barrier between cortex and medulla of thymus

Hassall corpuscles

Cells found in medulla of thymus that secrete cytokines to control the activity of local dendritic cells

Medulla of thymus

Contains fewer lymphocytes than the cortex and has epithelial cells that have different morphology and function

Contain Hassall corpuscles and supported by TECs that secrete cytokines

Cortex of thymus

Densely packed area with small, highly basophilic lymphocytes that are proliferating and being selected for/against

Supported by cytoreticulum of antigen-presenting TECs

Peyer’s patches

Large clusters of lymphoid nodules located in the wall of the ileum (MALT) that allow for close monitoring of gut microfauna

Contain M (microfold) cells, which are cells with no brush border or glycocalyx that fold over and allow antigens to cross from the lumen to underlying immune cells

Tonsils

Masses of lymphoid nodules that are collected in the walls of the pharynx

Pharyngeal tonsil

Covered by respiratory epithelium with a thin underlying capsule and no crypts

Located in the posterior wall of the nasopharynx

Palatine tonsils

Covered by stratified squamous epithelium with 10-20 tonsillar crypts and a partial CT capsule

Located in the posterior walls of the oral cavity

Lingual tonsils

Covered by stratified squamous epithelium with crypts and no capsule

Found on the surface of the posterior third of the tongue

Lymph nodes

Series of lymph filters that defend against spread of microorganisms and tumor cells

Enclosed environment for antigen presentation and non-IgA plasma cell antibody secretion

Have a reticular stroma to support

Cortex of lymph node

B cells in lymphoid nodules that are organized around dendritic cells

Covered by a CT capsule, with a subcapsular sinus separating nodules from the outer tissue

Paracortex of lymph node

Rich in T cells and contain high endothelial venules with endothelium that express glycoproteins which mediate movement of B/T cells from blood into this region of lymph node

Medulla of lymph nodes

Contain medullary cords (B and T lymphocytes and plasma cells) and medullary sinuses (make up most)

Sinuses have discontinuous endothelium and sometimes contain macrophages and neutrophils

Subcapsular sinus of lymph node

Receives lymph from afferent lymphatics and branches internally among cortical lymphoid nodules, allowing lymph to percolate

Underneath connective tissue capsule of lymph node

Spleen

Largest single accumulation of lymphoid tissue in the body

Involved in blood filtration, fighting blood-borne antigens, and destruction of old erythrocytes

Contains red and white pulp and surrounded by a connective tissue capsule that infiltrates the pulp in the form of trabeculae

Has a hilum where lymphatics enter and leave

Red pulp (spleen)

Filled with blood cells of all types that fill cords and sinuses

White pulp (spleen)

Lymphoid nodules form from periarteriolar lymphoid sheaths (PALS) that are made up of T cells, plasma cells, macrophages, and dendritic cells surrounded a central arteriole

Nodule forms when germinal center of B lymphoblasts displaces the central arteriole to the periphery

Surrounded by red pulp

Red pulp

Composed of sinusoids and splenic cords containing blood cells of all types

Cords are rich in macrophages and lymphocytes

Sinusoids are lined by endothelial cells with large nuclei called stave cells that help separate heathy from unhealthy red blood cells

Blood flow in spleen

Arterioles in the white pulp carry blood into the spleen, where it flows into progressively smaller vessels until it passes into closed or open circulation

Closed circulation

Blood passes directly into splenic sinuses

Open circulation

Blood flows from the vasculature into the lymphoid tissue of the splenic cords (red pulp), where viable blood cells migrate through and reenter the vasculature through the sinus walls

Stave cells

Endothelial cells with bulging nuclei that line splenic sinusoids length-wise

Blood cells move between them to re-enter the vasculature or are removed by macrophages

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