Lymphoid System

Question 1

What does the immune system do?

Answer 1

The immune system is responsible for the defense of the body against the limitless array of potential pathogens and other foreign material (macromolecules, microorganisms, viruses, transformed cells, etc.) that we encounter on a daily basis.

Question 2

What are the components of the innate immune system?

Answer 2

The innate (native, natural) immune system is provided by epithelial barriers and their secretions, and by a host of cells (macrophages, granulocytes, natural killer (NK) cells, etc) that can destroy or remove foreign elements by means of non-specific, stereotypical mechanisms.

Question 3

What is the specific immune system?

Answer 3

The specific (adaptive, acquired) immune system is provided by B-lymphocytes (B-cells) and T lymphocytes (T-cells), which mediate a very specific humoral (antibody-mediated) or cell-mediated immune response respectively. Cooperation between the innate and the specific immune system is the rule, and both humoral and cell-mediated responses may work together in the defense of the organism.

Question 4

What provides the specificity of the adaptive immune system?

Answer 4

The specificity of the adaptive immune system is provided by immunoglobulins (antibody) or by T-cell receptors (TCRs), each of which has the ability to recognize one of potentially billions of different foreign molecules.

Question 5

What molecules mark the cell as “self”?

Answer 5

The recognition of ‘self’ is mediated by the human leukocyte antigen (HLA) complex (major histocompatability complex; MHC).

Question 6

Where would you find MHC I?

Answer 6

MHC I is a receptor molecule that is a transmembrane protein found on virtually all nucleated cells. MHC I displays antigens (normal or abnormal) produced inside those cells.

Question 7

Where would you find MHC II?

Answer 7

MHC II is a transmembrane receptor found on antigen presenting cells (APCs) that is specifically designed for displaying exogenous foreign antigens and “presenting” them to the lymphocytes.

Question 8

How do B-cells recognize antigens?

Answer 8

B-cells recognize antigen by means of surface-bound immunoglobulins (Igs).

Question 9

What are the types of antibodies?

Answer 9

Several types of immunoglobulins (antibodies) exist (IgM, IgD, IgG, IgE, IgA).

Question 10

What are the fundamental units of all antibodies?

Answer 10

All antibodies share a common basic structure, which includes two heavy chains and two light chains (which come together to form an Fc [constant] region) and an antigen-binding region, the Fab domain.

Question 11

During maturation, what are the initial antibodies on a B-cell?

Answer 11

IgM and IgD represent the initial B-cell surface immunoglobulins.

Question 12

What are the first antibodies secreted by a recently formed plasma cell?

Answer 12

The first soluble antibodies secreted by a plasma cell are low affinity IgMs.

Question 13

What is isotype switching?

Answer 13

Cells resulting from the clonal expansion of the original B-cell will undergo affinity maturation and isotype switching resulting in the secretion of higher affinity antibodies (IgG, IgE or IgA). IgG is the predominant Ig found in blood; IgA is, overall, the most abundantly produced of the Igs and is found in many bodily secretions (saliva, mucous, breast milk); IgE is associated with molecules typically considered allergens.

Question 14

What provides the specificity of the T-cell response?

Answer 14

The T-cell receptor provides the antigen specificity for the T-cell response.

Question 15

What are the MHC-I restricted T-cells?

Answer 15

MHC I restricted T-cells are CD8+ cytotoxic lymphocytes (CTLs).

Question 16

What are the MHC II restricted T-cells?

Answer 16

MHC II-restricted T-cells are CD4+ TH cells

Question 17

What is the usual process of a humoral immune response?

Answer 17

A humoral immune response is usually initiated by the binding of antigen to the membrane-bound immunoglobulins on the surface of a B-cell. That antigen will be processed by the B-lymphocyte and then presented in association with MHC II to a TH cell. The release of cytokines by the T-cell will then trigger a clonal expansion of that B-cell into plasma cells and memory B cells.

Question 18

How are NK cells involved in the humor response?

Answer 18

Antibodies may be used for opsonization of foreign cells and their subsequent destruction by phagocytosis or NK cell-mediated lysis.

Question 19

How are macrophages involved in the immune response?

Answer 19

Exogenous antigens can be phagocytosed and processed by macrophages (or other APCs), which then present that antigen in the company of MHC II to TH cells. This triggers proliferation of that particular TH cell (to yield additional TH cells including memory cells) as well as the secretion of cytokines to stimulate increased macrophage activity. This may also activate appropriate B-cells, which is why we now recognize the mutual interactions of humoral and cell-mediated immunity.

Question 20

How are abnormal cells (including those infected by viruses) recognized?

Answer 20

Endogenously produced antigens (e.g. produced by virus-infected cells or tumor cells) will be expressed on the cell surface in association with the MHC I complex. These antigens are recognized by the CD8+ CTLs, which are then activated, resulting in proliferation, memory cell production and cytokine secretion.

Question 21

How do cytotoxic lymphocytes kill target cells?

Answer 21

Cytotoxic lymphocytes kill target cells by the secretion of lytic agents (e.g. perforins, granzymes).

Question 22

Inside the capsule of the thymus, what are the portions of the thymic parenchyma?

Answer 22

There is a cortex and a medulla of the thymus.

Question 23

What makes up the stroma of the thymus?

Answer 23

The epithelioreticular cells (ERC) are the stroma of the thymus. There is no connective tissue within the thymus.

Question 24

What happens to the thymus in adulthood.

Answer 24

It becomes a fatty, involuted structure in the adult.

Question 25

What is the function of the thymic cortex?

Answer 25

The thymic cortex has positive selection. Thymocytes that bind strongly to MHC I are selected and allowed to proceed to mature in the medulla. Those that don’t recognize self are signaled to undergo apoptosis.

Question 26

What is the function of the thymic medulla?

Answer 26

Thymocytes that recognize and react against self MHC I are selected against and triggered to undergo apoptosis. If they are not adequately screen out, these thymocytes may result in autoimmune disease.

Question 27

What is the function of the epithelial reticular cells?

Answer 27

These are associated with thymocyte differentiation and selection. They secrete a large number of thymic hormones. They provide selection barriers that prevent all but certain cells from entering the thymus. ERC I are the blood-thymic barrier. ERC II express MHC I and II and are the cells that positively select thymocytes. ERC III cells are the barrier between cortex and medulla. ERC IV are on the medullary side of the cortico-medullary junction and ERC V have both MHC I and II and are the negative selecting cells. Finally ERC VI are the cells that make Hassall’s corpuscles.

Question 28

What are Hassall’s corpuscles?

Answer 28

In the thymic medulla, Hassall’s corpuscles, comprised of keratinized type VI epithelial reticular cells, are a common morphological entity (especially in aged thymus) and aid in the histological identification of thymus.

Question 29

What are the functions of lymph nodes?

Answer 29

Lymph nodes are an encapsulated secondary lymphoid organ that serves as a ‘filter’ for antigens traveling within the lymphatic circulation.

Question 30

How do afferent lymphatics enter the lymph node and how does lymph traverse the node?

Answer 30

Afferent lymphatics pierce the capsule of the node and deliver lymph first into a subcapsular sinus. Lymph then follows a series of leaky lymphatic sinusoids that allow for the percolation of the lymph down through the cortex, the subjacent paracortex, and finally into the medulla of the node where medullary cords of lymphoid cells are surrounded by a network of medullary sinuses. The sinuses then coalesce to form the efferent lymphatic vessels that leave the node at its hilum.

Question 31

Where in the node would you expect to find metastatic cells if they are metastasizing via the lymph?

Answer 31

Metastatic cells would tend to lodge in the subcapsular sinus.

Question 32

Where do you find lymphoid follicles in the lymph node?

Answer 32

The B-cell-dependent lymphoid follicles (nodules) are found in the cortex.

Question 33

What are the characteristics of secondary lymphoid follicles?

Answer 33

Primary follicles contain naïve lymphocytes, which, upon encountering their specific antigen, will become activated (i.e. proliferate, convert into plasma cells, etc). This activation can be seen by a clearing of the central portion of the follicle to form a germinal center, the hallmark of a secondary follicle.

Question 34

What is the function of follicular dendritic cells?

Answer 34

A population of follicular dendritic cells serves to sequester antigen and optimize the potential for lymphocyte-antigen interaction. These are a type of antigen presenting cell.

Question 35

What is the paracortex of the lymph node?

Answer 35

The paracortex is a T-cell dependent area immediately below the cortical follicles.

Question 36

What is unusual about blood vessels in the paracortical region of the lymph node?

Answer 36

The high-endothelial venules are found within the paracortical region. Lymphocytes leave the blood stream and enter the lymphatic circulation via these HEVs.

Question 37

What would you expect to find in the medullary cords?

Answer 37

The medullary cords consist of a loose arrangement of lymphocytes, plasma cells, macrophages and supportive reticular cells.

Question 38

What is the function of the spleen?

Answer 38

The spleen acts as an immunological filter for the blood.

Question 39

What are the histologic parts of the splenic parenchyma?

Answer 39

The spleen is surrounded by a capsule and is organized into regions of red pulp and white pulp.

Question 40

What would you find in red pulp?

Answer 40

You would find splenic sinuses and diffuse lymphoid tissue containing macrophages, and reticular connective tissue in the red pulp. There would be large number of red blood cells.

Question 41

What is white pulp?

Answer 41

White pulp consists of aggregates of lymphocytes. These are organized into lymphoid follicles and the PALS (periarteriolar lymphoid sheaths).

Question 42

Describe the circulation of the spleen.

Answer 42

Large blood vessels enter the substance of the spleen via connective tissue trabeculae. Upon leaving the trabeculae, central arteries (arterioles) become ensheathed in a layer of T-cells (the periarteriolar lymphatic sheath - PALS). Lymphoid follicles (B-cells) may be seen associated with (and distorting) the PALS. Branches from the central arteries, called penicillar arteries distribute to the splenic parenchyma. Many of these end by opening into the red pulp. The splenic sinuses have a unique architecture (barrel-stave endothelium with surrounding reticular fibers) that serve as a cellular sieve to filter out aged blood cells.

Question 43

What is meant by “open circulation”?

Answer 43

This means that the penicillar arterioles open into the splenic parenchyma, pouring blood into the red pulp. However, some of these arterioles may have direct continuity with the venous sinuses (closed circulation

Question 44

How do blood cells get into the veins?

Answer 44

Red blood cells, for example, must pass between discontinuous endothelium (stave cells) that form slits along the wall of the splenic sinuses. These cells also must pass a discontinuous basement membrane that surrounds the sinus like hoops around a barrel. Those that cannot pass are broken down.

Question 45

What is “mucosal-associated lymphoid tissue” and where do you find it?

Answer 45

Mucosal-associated lymphoid tissue (MALT) is typically found beneath epithelial surfaces that are common sites of antigen entry (e.g. GI tract, respiratory tract, etc). This may consist of diffuse lymphoid tissue, occasional lymphoid nodules, or aggregates of nodules such as is seen in the Peyer’s patches of the ileum or in the tonsils.