Types of lymphoid organs

• Primary- Sites where lymphocytes develop from progenitor cells into functional and mature lymphocytes. They include bone marrow and thymus.
• Secondary- Sites where lymphocytes interact with each other and non-lymphoid cells to generate immune responses to antigens. They include spleen, lymph node and mucosa associated lymphoid tissue.

Thymus

• Located in superior mediastinum
• Extends from upper limit of pericardial sac into the neck beneath the upper anterior ribs.
• Receives blood supply from internal mammary artery.
• Venous blood drains into brachiocephalic and internal thoracic veins.
• Arises from 3^rd and 4^th brachial pouches, as an epithelial organ, which later gets populated with lymphoid cells.
• Size constantly increases from fetal life till puberty, then progressively decreases in size with ageing.
• Longitudinal fissure divides it into two asymmetric lobes.
• Each lobe is divided into multiple lobules by fibrous septae.
• Each lobule consists of outer cortex and inner medulla. Medulla contains whorls of squamous epithelial cells (Hassal corpuscles)

Spleen

• Located within the peritoneum in the left upper quadrant of abdomen, between the fundus of the stomach and the diaphragm.
• Splenic artery is a branch of the celiac trunk.
• Returning blood drains into portal circulation.
• 10% of individuals have accessory spleens.
• Weight- 100-250gm
• White pulp consists of periarteriolar lymphoid sheath (PALS) - Composed of lymphocytes which surround the arterioles branching off the splenic artery. They contain germinal centers.
• Marginal zone which surrounds the PALS, consists of fine network of filtration bed
• Red pulp consists of splenic sinuses and reticular meshwork (splenic cords of Billroth). The latter is composed of macrophages and dendritic cells.
• Functions of spleen include
  • Clearance of old RBCs
  • Regulation of blood volume
  • Immune function- Removal of bacteria and tumor cells
  • Sequestration of platelets

Lymph nodes

• They are round/ kidney shaped and measure <1cm in size
• Surrounded by collagenous capsule
• Hilum is the region from where blood vessels enter and leave
• Afferent lymphatics perforate the capsule and drain into subcapsular sinus
• Cortex of the lymph node consists of follicles with germinal centers.
• Medulla contains B cells, dendrtitic cells and macrophages.
• Medullary sinuses drain into efferent lymphatic channel.
• Function- Immune response to antigens which are carried in the lymph.

Types of immunity

• Innate/ natural/ native
  • This immunity exists even before any infection.
  • It has evolved to specifically recognize the microbes
  • Cytokines such as TNF alpha, IL1, IL6 and IL12 play an important role
  • There is no memory nor clonal response
  • Recognition of pathogens occurs through receptors such as mannose/ toll like receptors, which are present on macrophages. After binding, pathogen is phagocytosed and killed within the cytoplasm of macrophage.
  • Several plasma proteins such as hemopexin also impart this type of immunity.
• Adoptive:
  • This type of immunity is stimulated by microbes or antigens.
  • It consists of- Cell mediated immunity (T cells) and humoral immunity (B cells)
  • Cell mediated immunity
    • Antigen presenting cell presents processed antigen along with MHC molecules to T helper cells.
    • T helper cell secretes cytokines which stimulate the proliferation of cytotoxic T cells and macrophages.
    • T cells cause lysis of infected cell
    • Macrophages destroy the microbes within their cytoplasm.
  • Humoral immunity
    • B cells recognize antigens via B cell antigen receptor complex.
    • After binding, B cells mature to form plasma cells and secrete specific antibodies, which bind to extracellular microbes (Opsonization).
    • Antibody bound antigens/ microbes are engulfed by macrophages and later killed.
    • CD 4 cells also activate B cells via CD-40 receptor.
  • Types of immunoglobulins
    • IgG-
      • Account for 80% of immunoglobulins in adult plasma
      • Predominant immunoglobulin produced during secondary immune response
      • Half-life- 21 days
      • Useful in opsonization, complement fixation and direct antibody mediated cytotoxicity.
      • Only class of immunoglobulin that crosses placenta
    • IgA
      • 13% of plasma immunoglobulin
      • Primarily produced in mucosa, hence important in mucosal immunity
      • Secreted complexed with a secretory protein, which protects the immunoglobin against proteolytic digestion.
    • IgM
      • 6% of total plasma immunoglobulin
      • Contains 5 immunoglobulin molecules, linked by “J” chain
      • Predominant immunoglobulin formed during primary immune response.
      • Fix the complement more efficiently
    • IgD
      • <1% of plasma immunoglobulins
      • Act as B cell membrane receptors for antigens
    • IgE
      • Associated with immediate hypersensitivity
      • Normally 0.004% of total immunoglobulins
      • Levels are raised in case of atopy and parasitic infestations.
      • Bind via Fc portion to receptors on basophils and mast cells. Binding leads to release of vasoactive amines from mast cells.

Natural Killer cells

• In peripheral smear they appear as large granular lymphocytes
• Account for 5-15% of all lymphocytes
• They cause lysis of tumor cells and virus infected cells, through secretion of perforin and granzyme.
• They can act even in absence of MHC class I and II molecules on target cells.
• Interferon enhances their activity.
• They produce several cytokines such as interferon gamma, TNF- alpha and GM-CSF.
• KIR receptors have inhibitory effect, and they prevent autoimmunity.