Lymphoid Organs Overview

Primary and Secondary Lymphoid Organs

• The bone marrow and thymus are primary lymphoid organs where lymphocytes mature and express antigen receptors.
• B lymphocytes partially mature in the bone marrow, enter the circulation, and finish maturing in the spleen.
• T lymphocytes mature in the thymus and then enter the circulation.
• Bone marrow is the site where B lymphocytes mature.
• Thymus is where T lymphocytes mature.

Secondary Lymphoid Organs

• Secondary lymphoid organs include lymph nodes, spleen, and mucosal immune system components.
• They initiate and develop lymphocyte responses to foreign antigens.
• Lymph nodes are scattered throughout the body, filter microbes, and are responsible for the acquired immune response against antigens.
• Spleen is an encapsulated organ in the abdominal cavity where opsonized blood cells are removed and lymphocytes respond to blood-borne antigens.
• Mucosal-associated lymphoid tissue (MALT) is a collection of lymphoid tissues lining the respiratory, gastrointestinal, and genitourinary tracts, responsible for immune responses against pathogens invading the mucosa.

The Thymus

• The thymus is a bilobed organ in the anterior mediastinum.
• It grows until puberty and undergoes involution, becoming largely adipose tissue with little remaining lymphoid tissue.
• Its primary role is to select T cells able to recognize self major histocompatibility complex (MHC) (positive selection) and destroy T cells that recognize self-antigen.
• Three main areas are the subcapsular zone (earliest progenitor T cells), the cortex (densely packed developing T cells undergoing selection), and the medulla (fewer, more mature T lymphocytes ready to be released).

DiGeorge Syndrome

• A genetic disorder caused by failure of the thymus to develop, resulting in T cell deficiency due to a chromosomal deletion.

Lymph Nodes

• Afferent lymphatics deliver fluid containing cells encountering pathogens (antigen source) to the lymph node's subcapsular sinus.
• This fluid drains into the cortex, where B cell follicles interact with T cell-rich regions, facilitating antibody production.
• Some follicles contain germinal centers – areas where B cells proliferate and differentiate after encountering antigen.
• Activated B cells mature into plasma cells that secrete antibodies in the lymph node medulla.
• Lymphoid fluid travels out of the lymph node through efferent lymphatics.
• Activated B and T cells, along with antibodies, leave the lymph nodes and enter the bloodstream.

Spleen

• The spleen contains red pulp (degradation of old red blood cells) and white pulp (acquired immune response initiation).
• The white pulp is organized around central arterioles, delivering blood containing lymphocytes and antigens.
• Both the white pulp of the spleen and lymph nodes are organized into T cell-rich regions (periarteriolar lymphoid sheath) and B cell-rich areas (follicles).
• Antigenic stimulation causes B cell proliferation and the formation of germinal centers.

MALT

• MALT is a diffuse collection of lymphoid tissues lining various tracts, including the respiratory, gastrointestinal, and genitourinary systems.
• MALT produces immune responses against pathogens invading the lining of these tracts.
• Like spleen and lymph nodes, MALT contains B cell follicles and distinct T cell-rich regions.
• MALT is not surrounded by a fibrous capsule like the spleen and lymph nodes.
• IgA is the main immunoglobulin produced in MALT.
• MALT is densely populated with commensal microbes, which are essential for normal physiology.
• Subtypes of MALT include BALT (bronchial-associated lymphoid tissue), GALT (gut-associated lymphoid tissue), and CALT (conjunctiva-associated lymphoid tissue).

Cells of the Immune System

• Neutrophils are the most prevalent circulating white blood cells, crucial for acute inflammatory reactions.
• Mononuclear phagocytes comprise circulating monocytes (which become macrophages in tissues) and tissue-resident macrophages (initial origin from yolk sac or hematopoietic precursors during fetal life).

Macrophage Functions

• A primary function of macrophages is to ingest microbes through phagocytosis and then kill them.
• Mechanisms of phagocytosis and killing include: binding to microbes and internalization within a phagosome, phagosome-lysosome fusion, enzymatic degradation of the microbe, and antigen presentation to T lymphocytes.

Mast Cells

• Mast cells reside in connective tissues and are activated by cross-linking of IgE antibodies on their surfaces.
• They release granules containing histamine and other mediators, contributing to allergic reactions and inflammation.
• They also contribute to innate immune responses by recognizing microbial products independently of IgE.

Basophils

• Basophils are blood granulocytes with similarities to mast cells.
• Derived from hematopoietic precursors, they mature in the bone marrow and circulate in the blood.
• They are rarely found in tissues but can be recruited to inflammatory sites.

Eosinophils

• Eosinophils are bone marrow-derived and circulate in the blood, migrating to tissues.
• They contain granules with enzymes harmful to parasite cell walls but which can also damage host tissues.
• Various receptors on eosinophils, including Fc receptors for IgA and IgG, activate them to release their granules.

Natural Killer Cells (NK)

• NK cells are cytotoxic cells that play important roles in innate immune responses, primarily against viruses and intracellular bacteria.
• They kill target cells by releasing perforin (facilitating the entry of granzymes) and granzymes (proteolytic enzymes leading to apoptosis).
• NK cell recognition of infected cells is regulated by activating and inhibitory receptors.

Cytotoxic T lymphocytes (CTLs)

• CD8+ T cells differentiate into CTLs, expressing cytotoxic granules that can kill infected cells.
• The differentiation process requires antigen recognition from dendritic cells, signals from CD4+ helper T cells in some cases, costimulation, and cytokines.

Mechanisms of CTL-Mediated Killing

• CTLs kill target cells by two main mechanisms:
  • Granule exocytosis: releasing perforin/granzyme complexes, leading to apoptosis of target cells.
  • FasL-Fas interaction: Engagement of Fas on target cells by FasL on CTLs triggers apoptosis.

Roles of CD8+ CTLs in Host Defense

• CTLs play a critical role in eradicating intracellular microbial infections by eliminating the reservoir of infection.
• CTL (and NK cell) activity can cause tissue injury during some infectious diseases (e.g., hepatitis B and C viruses).

Helper T Cells

• Naive CD4+ T lymphocytes differentiate into specialized effector T cells:
  • Th1 cells: secrete interferon-gamma (IFN-γ), mediating defense against intracellular microbes.
  • Th2 cells: secrete interleukin-4 (IL-4) and IL-5, promoting IgE- and eosinophil/mast cell-mediated responses against helminths.
  • Th17 cells: promote inflammation and defense against extracellular fungi and bacteria.
  • CD4+ regulatory T cells (Treg): inhibit immune responses.

Role of CD4+ Helper T Cells in Eradicating Infections

• CD4+ T cells recognize antigens of phagocytosed and extracellular microbes.
• They produce cytokines (e.g., IFN-γ) and cell surface molecules that recruit and activate phagocytes to kill microbes.

This quiz covers the functions and roles of primary and secondary lymphoid organs in the immune system. It specifically focuses on the maturation of lymphocytes in the bone marrow, thymus, and their responses in the spleen and lymph nodes. Test your knowledge of these crucial components of immunity.