Immune Response and Cell Functions

Lymphatic System

• The lymphatic system is a network of vessels, tissues, and organs that helps maintain fluid balance in the body and plays a crucial role in immunity.
• It consists of lymph, lymphatic vessels, structures and organs containing lymphatic tissue, and red bone marrow.
• The lymphatic system functions to drain excess interstitial fluid, transport dietary lipid, and carry out immune responses.

Immunity or Resistance

• Immunity is the body's ability to ward off damage or disease.
• Two types are present, innate (non-specific) and adaptive (specific).
• Innate immunity is present at birth and involves no specific recognition of invaders, and no memory component.
• Adaptive immunity is based on specific recognition of invaders with a memory component of previous exposure to a pathogen.

Lymphatic Vessels and Lymph Circulation

• Lymphatic vessels begin as lymphatic capillaries, which are closed at one end.
• These capillaries collect excess interstitial fluid, which becomes lymph.
• Lymphatic vessels unite to form larger vessels similar in structure to veins but with thinner walls and more valves.
• Lymphatic vessels pass through lymph nodes and encapsulated organs containing masses of B and T cells.

Lymphatic Capillaries

• Lymphatic capillaries are slightly larger in diameter than blood capillaries.
• They have a unique one-way structure that permits interstitial fluid to flow into them but not out.
• Anchoring filaments help widen the openings when interstitial fluid accumulates.

Lymph Trunks and Ducts

• Lymphatic vessels unite to form lymph trunks.
• The principal trunks are lumbar, intestinal, bronchomediastinal, subclavian, and jugular.
• Lymph from the trunks flows into two main channels – thoracic and right lymphatic ducts.
• These ducts empty the lymph into the venous blood.

Lymphoid Cells

• Lymphocytes are the main cells involved in the immune response and come in two main varieties: T cells and B cells.
• T cells manage the immune response and destroy foreign cells.
• B cells produce plasma cells, which secrete antibodies that immobilize antigens.
• Other lymphoid cells include macrophages (phagocytize foreign substances and help activate T cells), dendritic cells (spiny-looking cells similar to macrophages that capture antigens and bring them back to lymph nodes), and reticular cells (fibroblast-like cells that produce a stroma supporting other cell types in lymphoid organs).

Lymphatic Tissues and Organs

• Lymphatic tissues and organs are grouped into two categories based on their function.
• Primary lymphatic organs are sites where stem cells divide and become immunocompetent to produce a normal immune response (red bone marrow and thymus).
• Secondary lymphatic organs are sites where most immune responses occur (lymph nodes, spleen, lymphatic nodules).

Lymphoid Organs

• Lymphoid organs include the thymus, lymph nodes, spleen and lymphatic nodules.
• Tonsils are in the pharyngeal region and Thymus is located in the thorax and most active during youth.
• Spleen curves around the left side of the stomach.
• Peyer's patches are in the intestine, and the appendix.
• The thymus is important in T-lymphocyte maturation.

Thymus

• The thymus contains an outer cortex and inner medulla.
• The cortex has densely packed lymphocytes and scattered macrophages.
• The medulla contains fewer lymphocytes and thymic corpuscles.
• The thymus is different from other lymphoid organs.
• It functions strictly in T lymphocyte maturation and does not directly fight antigens.

Lymph Nodes

• Lymph nodes are located along lymphatic vessels, scattered throughout the body.
• The stroma supports the connective tissue.
• The parenchyma is the functional part of the node with an outer cortex containing B cells (lymphatic nodules) where plasma cells and memory B cells form, and an inner cortex comprised of T cells and dendritic cells, and a medulla containing B cells, antibody-producing plasma cells from the cortex, and macrophages.

Spleen

• The spleen is the largest single mass of lymphatic tissue in the body.
• It has stroma consisting of a capsule, trabeculae, reticular fibers, and fibroblasts.
• The spleen contains white pulp, which contains lymphocytes and macrophages, and red pulp, which has blood-filled venous sinuses, splenic cords, red blood cells, macrophages, lymphocytes, plasma cells, and granulocytes.
• Macrophages in the spleen remove ruptured, worn-out, or defective blood cells.

Lymphatic Nodules

• Lymphatic nodules are scattered throughout the lamina propria of mucous membranes lining various parts of the body, such as the gastrointestinal, urinary, and reproductive tracts.
• They are also part of the mucosa-associated lymphatic tissue (MALT) of the respiratory tract.
• Some are small and solitary, while others are larger, such as tonsils, Peyer's patches, and the appendix.

Antigen Processing

• B cells can recognize and bind to antigens in lymph, interstitial fluid, or blood plasma, whereas T cells only recognize processed antigen fragments presented in a specific way.
• Antigenic proteins are broken into peptide fragments, and are associated with MHC molecules.
• This antigen-MHC complex is inserted into the plasma membrane for T cell binding.

Antigen Presenting Cells (APCs)

• Antigen presenting cells (APCs) include macrophages, dendritic cells, and B cells.
• APCs process and present the antigen, which can penetrate various tissues—skin (Langerhans cells), mucous membranes of various tracts such as respiratory, gastrointestinal, urinary, and reproductive, and lymph nodes.

Exogenous and Endogenous Antigens

• Exogenous antigens are present in fluids outside the body cells (e.g., bacteria, toxins, viruses).
• APCs ingest, process, and place the processed antigen next to MHC-II molecules in their plasma membranes, presenting the antigen to T cells.
• Endogenous antigens are found inside the cell (e.g., infected body cells; cancer cells).
• Infected cells display the antigen fragments next to MHC-I molecules for T cell recognition.

Cell-mediated Immunity

• Cytotoxic T cells attack and destroy invading antigens.
• These cells are particularly effective against intracellular pathogens like viruses, some cancer cells, and foreign tissue transplants.
• T cells are activated by a combination of signaling and costimulation. Anergy (lack of response) can also occur.

Helper T Cell Activation and Clonal Selection

• Helper T cells (CD4+ T cells) recognize and bind to antigen fragments associated with MHC-II molecules.
• Activation leads to clonal selection of helper T cells, producing both active helper T cells and memory helper T cells.
• Activation and clonal selection involve costimulation with interleukin-2 (IL-2).

Cytotoxic T Cell Activation and Clonal Selection

• Cytotoxic T cells (CD8+ T cells) recognize antigen presented with MHC-I molecules.
• Activation leads to clonal selection and the creation of active cytotoxic T cells and memory cytotoxic T cells.

Elimination of Invaders

• Cytotoxic T cells migrate and destroy infected target cells through granzymes inducing apoptosis (cell death) or using perforins, and granulysin for direct cell lysis (cell bursting).
• Macrophages and natural killer (NK) cells also contribute to the eradication of infected cells.
• Tumour antigens, displayed on cancerous cells, may also be targeted for destruction by cytotoxic T cells.

Antibody-Mediated Immunity

• B-cell activation requires antigen binding to BCRs.
• Antigen processing and costimulation by helper T cells result in the development of plasma cells and memory B cells, which produce and release antibodies targeting and neutralizing extracellular pathogens.

Antibodies

• Antibodies are glycoproteins that bind to specific epitopes of antigens that triggered their production. They belong to a group of glycoproteins called antibodies, or immunoglobulins (Igs).
• Antibodies consist of four polypeptide chains—two heavy and two light chains. The variable regions (at the tips of the "Y" shape) of the chains allow for antigen-specific binding, while the constant region (remainder of the chains) determines the type of antibody response.

Immunological Memory

• The body develops memory cells after the first encounter with an antigen. This allows for a faster and more intense response to subsequent exposure to the same antigen. The amount of antibodies (antibody titer) in serum can be measured as a measure of immunological memory.

Self-Recognition and Self-Tolerance

• T cells must be capable of recognizing self-MHC proteins.
• T cells that cannot recognize self-MHC molecules undergo apoptosis.
• Self-tolerance develops through negative selection, eliminating T and B cells that recognize self-peptide fragments. Anergy occurs when cells don't respond to self antigens, becoming unresponsive.