Lymphatic System and Immunity

Introduction to the Lymphatic System and Immunity

• The lymphatic system, also known as the lymphoid system, defends the body from external and internal threats.
• The immune system includes all body cells and tissues involved in immunity.
• Immunity is the ability to resist infection and disease.
• Pathogens are disease-causing organisms, including viruses, bacteria, fungi, and parasites.

Components of the Lymphatic System

• Lymph is fluid similar to plasma, but lacks plasma proteins.
• Lymphatic vessels transport lymph from peripheral tissues to veins.
• Lymphoid tissues are connective tissues dominated by lymphocytes.
• Lymphoid organs are the sites where lymphocytes form, mature, or become activated.

Functions of the Lymphatic System

• Primary lymphoid tissues and organs are where lymphocytes are formed and mature, including the red bone marrow and thymus.
• Secondary lymphoid tissues and organs are where lymphocytes are activated, including the tonsils, lymph nodes, and spleen.
• Lymphocytes and other lymphoid cells are produced, maintained, and distributed by the lymphatic system.
• Excess fluid is returned from tissues to the bloodstream by the lymphatic system.
• The composition of interstitial fluid is regulated by the lymphatic system.

Thymus

• The thymus is a pink, grainy lymphoid organ in the mediastinum, located above the heart.
• This organ atrophies after puberty and becomes inactive.
• The thymus is divided into two thymic lobes.
• It regulates T cell development and maturation.
• T cells divide in the cortex of the thymus.
• Mature T cells migrate into the medulla of the thymus.

Spleen

• The spleen is a large lymphoid organ located lateral to the stomach.
• The spleen filters blood to remove abnormal blood cells
• Iron is recycled from red blood cells in the spleen.
• The spleen mediates immune responses to antigens in the blood involving macrophages, B cells, and T cells.
• The diaphragm and the left kidney are in contact with the spleen.
• Splenic veins, arteries, and lymphatic vessels enter the spleen at the hilum.
• The red pulp contains many red blood cells.
• The white pulp resembles lymphoid nodules.

Immunity Overview

• Immunity is the ability to resist and defend against infectious organisms and other damaging substances.
• Immune response is the body's reaction to infectious agents and other abnormal substances.
• Resistance refers to the body's ability to maintain immunity.

Lymphatic Vessels

• Lymphatic vessels begin as fenestrated capillaries.
• Lymph is transported through vessels and lymph nodes and into the vena cava.
• Larger lymphatic vessels contain one-way valves and smooth muscle.

Lymphocytes

• Lymphocytes contain a single, large nucleus, a small amount of cytoplasm, and a wide range of surface proteins.
• B lymphocytes develop in bone marrow.
• T lymphocytes begin development in bone marrow but complete it in the thymus.
• Lymphocytes are classified by surface proteins referred to as Cluster of Differentiation (CD) markers.

Types of Immunity: Innate

• Innate immunity is a nonspecific defense mechanism
• It includes physical barriers and internal defenses.
• It is present at birth.
• It does not distinguish one threat from another.
• It always works the same way against any type of threat.

Types of Immunity Adaptive

• Adaptive immunity is a specific defense mechanism.
• It protects against specific antigens.
• It depends on the activities of B and T lymphocytes.
• It develops after exposure to an antigen.
• It protects against future attacks by the same pathogen.

Innate Defenses

• Innate defenses are the first line of defense and are non-specific.
• These include physical barriers, phagocytes, immune surveillance, interferons, complement, inflammation, and fever.

Physical Barriers

• Physical barriers prevent pathogens from entering the body.
• Examples include skin, hair, and mucous membranes of internal passageways.
• Mucus and secretions that flush away materials, like sweat and urine, are physical barriers.
• Secretions that kill or inhibit microorganisms, containing enzymes, antibodies, or stomach acid, are also physical barriers.

Phagocytes

• Phagocytes are cells that attack and engulf microorganisms and debris.
• Microphages include neutrophils and eosinophils that enter peripheral tissues to fight infections by phagocytosis.
• Macrophages are large phagocytic cells derived from monocytes.
• Phagocytes move through capillary walls (emigration).
• Phagocytes are attracted or repelled by chemicals in surrounding fluids (chemotaxis).

Macrophage Phagocytosis

• Macrophages are drawn to a site by chemotaxis.
• Physical interaction occurs between the macrophage and the foreign threat.
• Macrophages produce pseudopodia that extend around the foreign threat.
• Pseudopodia fuse, enclosing the foreign threat within a vesicle, forming a phagosome.
• The phagosome internalizes and fuses with a lysosome.
• Proteases and toxic chemicals in the lysosome kill the foreign threat.
• Parts of the foreign threat are then exposed on the cell surface for antigen presentation.

Natural Killer Cells

• Natural killer cells perform immune surveillance.
• They look for abnormal cells, such as cancer cells or cells infected by viruses.
• Natural killer cells induce apoptosis in virus-infected and cancer cells.
• They release granules containing powerful proteases and perforin.
• Natural killer cells secrete alpha-defensins which are anti-microbial peptides.
• Impairments in natural killer cell development display a heightened incidence of blood cancer.

Interferon

• Interferons (IFNs) are small proteins released by tissue cells infected with viruses.
• Interferons are cytokines, which are chemical messengers released by tissue cells and important to the immune response.
• These trigger the production of antiviral proteins in healthy cells.
• They're released by virally infected cells and bind to receptors on neighboring cells.
• Interferons activate enzymes that inhibit protein synthesis and break down viral mRNA.

Complement System

• The complement system consists of more than 30 special complement proteins.
• It assists antibodies in destroying pathogens.
• Complement proteins work in cascades.
• The complement system integrates innate and adaptive immune responses.

Complement System Functions

• The complement system promotes bacterial lysis, capillary permeability, opsonization, and chemotaxis.

Inflammation

• Inflammation is a localized tissue response to injury triggered by any stimulus that kills cells or injures tissue.
• Cardinal signs and symptoms of inflammation include redness (due to increased blood flow), swelling (due to increased capillary permeability), heat (due to increased blood flow), and pain (due to chemicals released by injured cells).

Inflammation Mechanisms

• Inflammation isolates injured/infected tissue.
• It initiates defense mechanisms, including phagocytosis, chemotaxis, pyrogens, interferon, and complement.

Inflammatory Steps

• Mast cells are activated by chemical changes in tissue due to injury.
• Mast cells release histamine, heparin, and other chemicals.
• Increased capillary permeability and blood flow in the affected area result from histamine release.
• Clot formation occurs around the injured area for temporary repair.
• Complement activation and complement proteins attacks pathogens within the blood
• Neutrophils are activated.

Neutrophil Activation

• Neutrophils secrete cytokines to attract other neutrophils and macrophages through chemotaxis.
• Margination occurs when leukocytes stick to the blood vessel wall.
• Diapedesis is the movement of leukocytes squeezing through blood vessel walls into the tissue.

Symptoms of Inflammation

• Redness and warmth result from histamine-stimulated vasodilation.
• Swelling is due to vasodilation.
• Pain is caused by the release of PGE2.
• Necrosis involves local tissue destruction and death in the area of injury.
• Pus is a mixture of debris, fluid, dead tissue cells, and neutrophils.
• An abscess is an accumulation of pus in an enclosed space.

Fever

• Pyrogens are fever-inducing agents that cause the hypothalamus to raise body temperature.
• Pyrogens cause the hypothalamus to release prostaglandins, resulting in a resetting of the thermostat and a fever.
• When activated phagocytes are released they induce the release of prostaglandins in the hypothalamus.
• Prostaglandin synthesis is inhibited by aspirin and glucocorticoids.

Adaptive Defenses

• Adaptive defenses result from the activities of B and T cells.

Adaptive Immunity

• Adaptive immunity is achieved through cell-mediated immunity, antibody-mediated immunity, and the interaction between the two.
• Cell-mediated immunity involves direct physical and chemical attacks by activated T cells on pathogens.
• Antibody-mediated immunity involves B cells giving rise to cells that produce circulating antibodies.

Adaptive Defenses: Antigens

• Antigens are chemical targets that stimulate an immune response.
• These can be pathogens, parts of pathogens, products of pathogens, or other foreign substances.
• Lymphocyte activation occurs when a lymphocyte comes in contact with an appropriate antigen.
• Clonal selection occurs when an activated lymphocyte divides to produce a clone: all identical cells that are sensitive to the same antigen.

Adaptive Immunity: Antigens

• An antigen is anything that triggers an adaptive immune response.
• The immune system recognizes epitopes, which are antigenic sites on macromolecules.
• Common antigens include components of bacteria, viruses, pollen, animal dander, food, and drugs.

Antigen Presentation

• T cells recognize antigens that are presented.
• MHC proteins are membrane protein "signatures" that identify the cell as "self."
• Antigen presentation occurs when an antigen-MHC complex appears in the membrane.

Major Histocompatibility Complex (MHC)

• Individuals inherit one copy of each MHC gene from each parent, making each individual unique.
• MHC is critical for cells to communicate what is self versus non-self.
• MHC I molecules are expressed on the surface of all cells except erythrocytes and docks with CD8 on Tc cells.
• MHC II molecules are only expressed on macrophages and B cells and docks with CD4 on TH cells.

Antigen Recognition

• T cells have receptors that bind to Class I or II MHC molecules.
• CD (cluster of differentiation) markers are proteins that allow for antigen recognition.
• CD8 markers are found on cytotoxic T cells and interact with Class I MHC.
• CD4 markers are found on helper T cells and interact with Class II MHC.

Cytotoxic T Cells

• A cytotoxic T cell recognizes and binds to its target
• Once a cytotoxic T cell is activated and goes through cell division, the clones produces go out to tissues and release perforins to destroy target cell's plasma membrane

Helper T Cells

• Helper T cells accelerate cytotoxic T cell maturation.
• macrophages are attracted and stimulated by Helper T cells.
• Cytotoxic T cells are supported by Helper T cells.
• B cells are stimulated by Helper T cells

B Lymphocytes

• B Lymphocytes exposure to the specific antigen activates a B lymphocyte.
• B Lymphocytes undergo multiple cell divisions which is the process of cloning.
• B Lymphocytes can become memory cells which can be used in later infection of the same pathogen.
• B Lymphocytes can become plasma cells which produce 2,000 antibodies per second.

Primary vs Secondary Responses

• The difference in the response is due to memory B cells in the Secondary response.
• Antibodies are produced faster in a secondary response.

Antibodies

• Antibodies are composed of two pairs of polypeptide chains: one pair of heavy chains and one pair of light chains.
• Antigen-binding sites on antibodies bind to epitopes.

Antibody Functions

• Lymphocytes such as T and B cells rely antibodies for specific immunity responses.
• Antibodies are known as immunoglobulins and are separated into five classes: IgG, IgA, IgM, IgE, IgD
• Immunoglobulin IgG antibodies are circulating, Immunoglobulin IgA antibodies are secretory, Immunoglobulin IgM antibodies are antigen receptors, Immunoglobulin IgE antibodies exhibit hyersensitivity, Immunoglobulin IgD antibodies are antigen receptors.

Antibody-Antigen Complex

• In the antibody-antigen complex different molecules are involved such as B cells, B-Cell antibody receptors, surface antigen, VH VL CH.

Antibody Functions

• The functions of antibodies in adaptive immunity include triggering antigen neutralization through covering and blocking the surface of the antigen, antigen agglutination through clumping larger complexes and making them more easily recognized by macrophages, antigen precipitation of antigens out of solution to be easily recognized by macrophages, complement activation to cause cell lysis, lymphocyte recruitment and activation.