In this table are listed the organs, tissues, cells, and soluble factors that we will be studying in this course, noting that they will be first addressed separately as components of the innate immunity, and components of the adaptive immunity.

Soon, you will find that there are a lot of interactions between the two.

Note that red blood cells and platelets are not directly involved in the defense against infection, but they do contribute to the immunological response: Red blood cells help in the removal of antigen-antibody complexes from the blood circulation, while platelets contribute to the inflammatory response beside their well-known essential role in blood coagulation.

The bone marrow is a primary lymphoid tissue, where blood cells, including immune cells, are developed from a common precursor, the hematopoietic stem cell.

Most cells undergo maturation in the bone marrow, except for T cells, which have to migrate to the thymus and undergo maturation there.

The spleen and lymph nodes are classified as secondary lymphoid organs, where immune cells are positioned and ready to respond to foreign agents such as pathogens, which are collectively referred to as “foreign antigens” or simply as “antigens”.

Here you can see the location of the lymphoid organs and tissues in the body.

The bone marrow is the primary lymphoid tissue, whereas the thymus is the primary lymphoid organ, both colored in red in this figure.

Secondary lymphoid organs, including the lymph nodes and spleen, and tissue are highlighted in yellow.

As you can see, lymph nodes are abundant and they’re located at the junction of the lymphatic vessels.

The bone marrow consists of the spongy and pink tissue found in bone cavity.

Bone marrow serves as the site of development and differentiation of stem cells into blood cells, including red blood cells or erythrocytes, white blood cells, and megakaryocytes, which are the precursors to platelets. Blood cells development is also referred to as hematopoiesis.

Most blood cells develop and mature in the bone marrow, except for the precursor of T cells or progenitor T cells, which develop in the bone marrow, but mature in the thymus.

Here you see the pathway of migration of T cells.

T cells develop in the bone marrow into T-cell precursors also called progenitor T cells, which migrate to the thymus, where they undergo maturation.

Mature T cells are released from the thymus into the blood circulatory system, and they travel to the secondary lymphoid organs such as the lymph nodes (colored in green) and the spleen (colored in purple), and in the Gut-Associated Lymphoid tissue or GALT. In the absence of activation by specific antigen, mature T cells continue to recirculate between the blood, secondary lymphoid tissues, and lymph. This phenomenon is referred to as lymphocyte traffic.

Let’s consider the organization of the spleen.

The spleen is the largest secondary lymphoid organ, which serves as the site of trapping of antigens from the blood circulation.

The spleen contains two regions, namely the red pulp and the white pulp, each of which has its own specific function.

The white pulp is composed of periarteriolar lymphoid sheaths or PALS, each containing a T cell zone, a B cell zone that contains both primary follicles and germinal centers, and a marginal zone where macrophages and dendritic cells are located. The Red pulp contains worn-out red blood cells, hence the designation of Red blood cell cemetery.

This is a section of the spleen in which nodules of white pulp are scattered within the more extensive red pulp.

The white pulp is essentially a secondary lymphoid tissue within the spleen, where lymphocytes, macrophages, and dendritic cells are positioned and ready to interact with each other in order to mount an adequate response to blood-borne pathogens.

A transversal section of the spleen shows that the PALS is comprises a sheath of lymphocytes that’s adjacent to the arteriole. The cell zone is colored in blue and next to it is the B cell zone that is colored in yellow.

Lymphoid follicles comprise a germinal center, a B-cell corona, and a marginal zone containing macrophages and differentiating B cells.

Abutting the red pulp, both follicles and PALS are surrounded by a perifollicular zone containing a variety of cells, including erythrocytes, macrophages, T cells, and B cells.

Lymph nodes are located at the junctions of lymphatic vessels, and their function is to trap foreign organisms that are brought in through the blood circulatory system or lymphatic system.

Some of the antigens that enter these organs are met by macrophages upon entering the lymph nodes.

Macrophages in the lymph nodes are located in the subcapsular sinus, medullary sinus, and medullary cord.

Other immune cells that are present in the lymph nodes include B cells in the cortex, and T cells in the paracortex.

On the right side of the slide is a picture and on the left a schematic diagram of a section of the lymph node.

Note that the lymph node is irrigated by both the blood circulatory system and the lymphatic system. Blood is coming in through the artery and out through the vein. The lymph is coming in through the afferent ducts and out through the efferent duct. Thus, antigens can be brought into the lymph node via both circulatory systems.

The marginal sinus and medullary sinus are the locations at which bacteria that enter through the afferent lymphatic vessels encounter macrophages.

T cell zone in the paracortex is colored in blue. This is where APCs interact with T cells and activate them.

Next to the T cell zone is the B cell zone in the cortex, with resting B cells in the primary follicles, and activated B cells in the germinal centers (colored in yellow).

B cells and T cells enter the lymph node via the artery and they exit the blood circulation via the high endothelial venules or HEV, followed by their migration to their respective zone.

This schematic diagram shows the traffic and fate of pathogens through an abrasion of the epithelium.

1) Bacteria are engulfed by local macrophages and killed by phagocytosis.

2) Dendritic cells bind the pathogen in the infected tissue then begin to process them into antigen peptides on the way to the lymph node. It should be noted that bacteria also enter the lymphatic vessels and travel with the dendritic cells to the lymph node.

3) A Macrophage in the lymph node is shown engulfing bacteria in the process of phagocytosis.

4) Dendritic cells that have entered into the lymph node through the afferent lymphatic vessels attract and interact with T cells (seen in green and blue), activating them.

5) Cytotoxic T cells (seen in green) entering the lymph node through the artery.

6) T helper cells (seen in blue) activate B cells which differentiate into Plasma cells (seen in yellow). Plasma cells produce antibodies (shown as yellow Y shapes) in the lymph node

7) T helper cells and antibodies exit the tissue via the afferent lymphatic vessel to the site of the infection.

Lymphoid tissues at different location in the body share some common characteristics in organization and functions

Secondary lymphoid tissues are the sites of trapping of antigens that come from the mucosal surface via transcytosis by specialized M cells.

M cells act by grabbing and bringing in substances found in the lumen and transport them into the abluminal lymphoid tissue, where B and T cells, DCs and macrophages are positioned.

Lymphoid tissues are differentiated into:

1) GALT which is a well-organized Gut-associated lymphoid tissue, which includes the tonsils and adenoids found along the nasopharynx ,as well as the appendix and the Peyer’s patches lining the small intestine

2) BALT is a less well organized aggregates of Bronchial-associated lymphoid tissue found near the lungs.

3) MALT is the mucosa-associated lymphoid tissue that is more diffuse and found throughout the body

4) VALT or vaginal-associated lymphoid tissue

5) NALT or nasal-associated lymphoid tissue

6) LALT or larynx-associated lymphoid tissues.

Despite being found in different areas all lymphoid tissues have similar functions.

In this slide you can see a diagram of the gut-associated lymphoid tissue (GALT).

Note the position of the lumen, the epithelium and M cell in relation to the lymphoid tissue (colored in blue), which hosts immune cells such as dendritic cells, B cells and T cells.

The function of the M cell is to transport antigens, by a process called transcytosis, from the mucosal surface to the internal lymphoid tissue, where immune cells are located.

The adaptive immune response by B and T cells to the antigens generates effector cells and memory cells, which are ready to mount a strong response should these antigens invade the body due to a breach through the mucosal barrier.

All blood cells are derived from a common precursor: the hematopoietic stem cell in the bone marrow, by a process called hematopoiesis

There are three lineages or pathways of development of blood cells, including the Erythroid / Megakaryocyte lineage, the myeloid lineage and the lymphoid lineage.

The site of human hematopoiesis changes during development.

Following fertilization blood cells are first made in the yolk sac of the embryo, and then it switches to the fetal liver and spleen at around the fourth month during gestation.

Following bone development during gestation, blood cell generation switches from the fetal liver to the bone marrow at around the 4th month.

Thereafter, bone marrow is the primary site for blood cell development throughout the remainder of an individual’s life.

In this slide you can see the three lineages of blood cell development from a common hematopoietic stem cell precursor (colored in brown): the lymphoid lineage, myeloid lineage and erythrocyte/megakaryocyte lineage.

Cells from each lineage will be shown in the next slides.

From the lymphoid lineage, three types of cells are obtained, including the B cells, T cells and NK cells

B and T cells are cells of the adaptive immunity. These cells are not active initially, and they undergo proliferation, and differentiation into effector cells and memory cells upon encountering the respective antigens.

Effector B cells are plasma cells that produce antibodies, whereas effector T cells include T cell helpers that activate and regulate the immunological response of other immune cells, and cytotoxic T cells with the ability to recognize and kill abnormal and infected cells.

NK cells are cells of the innate immunity, and they are specialized in the immune response to viruses.

The myeloid progenitor cell divides and differentiates into seven cell types, including:

Monocytes in circulation, and monocyte-derived tissue macrophages and dendritic cells

There are three types of granulocytes, including neutrophils, eosinophils and basophils in circulation

Tissue mast cells are of unknown precursor cells.

This table provides a list of cells in the immune system that are derived from the three lineages of differentiation of the hemapoietic stem cells.

For now, you just need to get acquainted with their names. More information on these cells will be presented in the next couple of slides.

This table shows the diagrams and pictures of each of the cells types involved in the immune response.

Differences in morphology, nucleus shape and coloration of cytoplasmic granules by hematology stain can be readily observed.

Resting B and T cells can be recognized as small cells with round nucleus and thin cytoplasm.

Effector B cells or plasma cells show an enlarged cytoplasm due to the active production of antibodies.

NK cells are distinguished by the presence of large cytoplasmic granules, and hence they are also referred to as large granular lymphocytes.

Neutrophils are characterized by the multi-lobed nucleus and light blue cytoplasmic granules.

Dendritic cells are recognizable by the presence of dendrites. They play an important role in bridging the innate immunity with the adaptive immunity. They’re often represented as star-shaped cells, and they play a role in T cell activation.

Eosinophils, basophils and mast cells belong to the group of polymorphonuclear granulocytes abbreviated as “polymorphs” or “granulocytes”. These cells have characteristic granules, such as red granules in eosinophils and purple granules in basophils and mast cells.

Monocytes are found in the blood circulatory system, and they are precursors to dendritic cells (DCs) and macrophages.

Also shown are the megakaryocytes, which do not play a role in the immune system, but they are precursors to platelets, and they contribute to wound healing.

Also included are erythrocytes, which play a role in oxygen transport and immune complex removal.

Macrophages are major phagocytic cells and they play a central role in the innate immunity as well as, in the adaptive immunity. Besides performing phagocytosis, macrophages also serve as APCs.

In this section, you will be introduced to the soluble components of the immune system.

Soluble factors of the innate immunity include the complement system, the antimicrobial factors, and the acute phase proteins.

Soluble factors of the adaptive immunity consist of antibodies.

Other soluble factors play a role in both the innate and adaptive immune system, and they include cytokines which can act on a multitude of different cell types including those of the immune system and non-immune associated cells, as well as Chemotactic factors which play a role in attracting cells from the blood circulation to tissues.

It is important to know about the existence of these factors at this time. More details will be provided in subsequent lectures.

Foreign antigens are also attacked by soluble factors of the immune system.

Activation of the complement system causes foreign cells to undergo lysis.

Antimicrobial factors act as natural antibiotics

Antibodies produced by plasma cells bind specifically to pathogens and/or their products, inhibiting their pathogenic effect, facilitating their phagocytosis by phagocytes, enhancing their lysis by the complement system, etc.

Other factors, such as cytokines, chemokines, and chemotactic factors, play a role in intercellular communication and interaction, regulation of immune cell functions, and cell migration.