Overview of the Lymphatic System and Immunity

Chapter 22

Overview of the Lymphatic System and Immunity

▪Lymphatic System- includes the cells, tissues, and organs responsible for defending the body against both environmental hazards and internal threats.

▫Lymphocytes are the primary cells of the lymphatic system

▫Innate (Nonspecific) defenses-

▫Adaptive (Specific) defenses-

▫Immunity-

▫All cells and tissues involved with the production of immunity are sometimes considered to be part of the immune system.

Organization of the Lymphatic System

▪The lymphatic system consists of:

1) lymph-

2) lymphatic vessels-

3) lymphoid tissues and organs

primary lymphoid tissues-

secondary lymphoid tissues-

4) lymphocytes and phagocytic cells

▪Functions of the lymphatic system-

▪Lymphatic Vessels-

▫Lymphatic capillaries-

▫Small lymphatic vessels-

▫Major lymph collecting vessels-

-Superficial lymphatics-

-Deep lymphatics-

-Deep and superficial lymphatics merge to form larger lymphatic trunks, which drain into larger ducts; the right lymphatic duct and the thoracic duct.

-Right lymphatic duct drains lymph from the right side of the body superior to the diaphragm.

-Thoracic duct drains lymph from the rest of the body

▪Lymphocytes- account for 20-40% of circulating white blood cell population. There are three classes of lymphocytes in blood; T cells, B cells, and NK cells

▫There are many types of T cells, including; cytotoxic T cells, helper T cells, suppressor T cells. They account for about 80% of circulating lymphocytes.

▫B cells account for about 10-15% of circulating lymphocytes.

-When stimulated, B cells differentiate into plasma cells which are responsible for production and secretion of antibodies (immunoglobulins).

▫NK cells, the remaining 5-10% of circulating lymphocytes, are large granular lymphocytes, attack foreign cells, virus infected, and cancer cells.

▫Lymphocytes are not evenly distributed in the blood, bone marrow, and lymph tissues and organs

▫Lymphocytes have relatively long life spans, 80% live up to 4 years, some up to 20 years.

▫Lymphopoiesis (production of lymphocytes) involves the bone marrow, thymus, and peripheral lymphoid tissues.

-Hemocytoblasts in the red bone marrow produce two types of lymphoid stem cells.

-Divisions of T, B, or NK cells can only render daughter cells of the same type.

▪Lymphoid Tissues-

▫Lymphoid nodule- lymphocytes are densely packed in an area of areolar tissue

-MALT- mucosa-associated lymphoid tissue- collection of lymphoid tissues linked with the digestive system.

-Tonsils- large nodules in the walls of the pharynx, usually 5 of them

▪Lymphoid Organs-

▫Lymph Nodes- small oval organs surrounded in a fibrous CT capsule.

-Trabeculae-

-Afferent lymphatics-

-Efferent lymphatics-

-Lymph flow-

▫Thymus-

-Capsule divides the thymus into lobes, septa further divide thymus into lobules.

-Reticular epithelial cells surround clusters of lymphocytes in the cortex. They maintain the blood-thymus barrier and secrete thymus hormones.

-Thymosins- name given to the group of hormones produced in the

thymus that function to development and maintenance of T cells

▫Spleen-

Functions of the spleen include:

-Soft organ that’s shape reflects its association with the structures around it.

-Contains red pulp (large quantities of RBC) and white pulp (similar to lymphoid nodules)

Nonspecific Defenses

▪Physical Barriers-

▪Phagocytes-

▫Microphages-

▫Macrophages-

-Fixed macrophages-

-Free macrophages-

-Both classes of macrophages are derived from monocytes of the blood.

▫Most phagocytes die before they have engulfed more than 25 bacteria (about an hour).

▪Immune surveillance-

▫Abnormal cells contain antigens that are not found on normal cells

▫NK cells respond to a variety of abnormal antigens, and will result in that cell being attacked, much less selective than B or T cells.

▫NK cells respond immediately on contact, unlike B and T cells which activation takes a complex, time consuming sequence of events.

▫Activated NK cells react in a predictable way:

▪Interferons-

▫Once an interferon has contacted the surface of a normal cell, it triggers a second messenger pathway that leads to the production of antiviral proteins.

▫Antiviral proteins interfere with the viral replication that takes place inside a cell.

▫There are at least three types of interferons:

-Alpha (a) interferons-

-Beta (b) interferons-

-Gamma (g) interferons-

▪Complement System-

▫Complement proteins interact with one another in chain reactions, two types; classical and alternate pathways.

-Classical pathway-

-Alternate pathway-

-Both end with the conversion of C3 to C3b, stimulation of phagocytosis, and formation of the membrane attack complex (MAC)

▪Inflammation-

▫Inflammation produces local sensations of swelling, redness, heat, and pain.

▫Almost any tissue subjected to physical damage or infection will result in inflammation.

▫The damage to the tissue changes the chemical make-up in the interstitial tissue, which initiates the inflammation response.

▫Inflammation has a number of effects:

▫Inflammation occurs in a series of integrated steps

▪Fever-

▫Circulating proteins called pyrogens can reset the hypothalamic thermostat and raise body temperature.

▫Pyrogens can be stimulated by many things; pathogens, bacterial toxins, antigen-antibody complexes.

▫Within limits, fever can be beneficial.

Specific Defenses: An overview of the Immune Response

▪The basic functional relationship between B and T cells is:

▫T cells are responsible for cell-mediated immunity

▫B cells are responsible for antibody-mediated immunity

▪Both play important roles, but under different circumstances:

▫T cells cannot respond to antigenic materials in solution and activated B cells cannot cross cell membranes

▪Forms of immunity- immunity is either innate or acquired

▫Innate immunity-

▫Adaptive immunity-

-Active immunity:

-Naturally Acquired:

-Artificially Induced:

-Passive immunity:

-Naturally Acquired:

-Artificially Induced:

▪Properties of Immunity- regardless of form, immunity has 4 general properties

1) specificity-

2) versatility-

3) memory-

4) tolerance-

T Cells and Cell-mediated Immunity

▪Key cells in this immunity are cytotoxic T cells, helper T cells, memory T cells, and suppressor T cells.

▪Before an immune response can begin, T cells must be activated by exposure to an antigen, does not occur with direct antigen-lymphocyte contact.

▪Antigen Presentation- T cells recognize antigens only when the antigens are bound to glycoproteins in cell membranes.

▫Glycoproteins are genetically determined, genes are found on a region of chromosome 6 called the major histocompatibility complex (MHC), these proteins are called MHC proteins.

▫There are two major classes of MHC proteins; class I and class II.

-Class I MHC proteins are in the membranes of all nucleated cells, they are continually be added to the cell membrane

-Class II MHC proteins are present only in the membranes of antigen-presenting cells (APC) and lymphocytes.

-Antigen-presenting cells include all the phagocytic cells, Langerhans cells of the skin and dendritic cells of the lymph nodes and spleen.

▪Antigen Recognition- T cell recognition of a specific antigen presented in an MHC protein.

▫Inactive T cells have receptors that recognize class I or class II MHC proteins. These receptors also have binding sites for specific antigens

▫Some T cells respond to antigens bound to class I MHC proteins and others respond to antigens bound to class II MHC proteins.

-This recognition depends on the structure of the T cell membrane.

-Membrane proteins involved in this structure are called CD markers

▫Costimulation-

-CD8 or CD4 markers are bound to the CD3 receptor complex, this complex ultimately activates the T cells.

-Appropriate costimulation proteins appear in the presenting cell only if that cell has engulfed antigens or is infected by viruses

▪Activation of CD8 T Cells- two classes of CD8 T cells are activated by exposure to antigens bound to class I MHC proteins, quick responding cells that give rise to cytotoxic T cells and memory Tc cells, and slower responding cells that give rise to suppressor T cells.

▫Cytotoxic T cells seek out and destroy abnormal and infected cells.

-Highly mobile cells that roam throughout injured tissue

-Once bound to its target antigen presented on a class I MHC protein, it will immediately destroy that cell, by one of 3 different ways:

-Takes about 2 days or more from the presence of an antigen to high enough concentrations of cytotoxic T cells to be effective.

▫Memory Tc cells ensure there will be no delay in the response if that specific antigen reappears.

-If the antigen appears again, the memory cells will immediately differentiate into cytotoxic T cells.

▫Suppressor T cells suppress the responses of other T cells and B cells by secreting suppression factors.

▪Activation of CD4 T Cells- Upon activation, CD4 T cells undergo a series of divisions that produce helper T cells and memory TH cells.

▫The memory TH cells remain in reserve

▫Helper T cells secrete a variety of cytokines that coordinate specific and nonspecific defenses and stimulate cell-mediated and antibody-mediated immunities:

B Cells and Antibody-Mediated Immunity

▪B cells are responsible for launching a chemical attack on antigens by producing appropriate antibodies

▪B Cell Sensitization and Activation

▫Each kind of B cell carries its own particular antibody molecules in its cell membrane

▫Sensitization-

▫B cells have class II MCH proteins, integrating antigens onto the surface, this activates the B cell, but needs to be “O.K’d” by a helper T cell.

▫Once a sensitized B cell makes contact with a helper T cell, it binds to the MCH complex, recognizes the antigen, then begins secreting cytokines that promote B cell activation.

▫When B cells have been activated, they begin dividing, producing plasma cells and memory B cells.

*see fig. 22-22 to visualize this process*

▪Antibody Structure

▫An antibody consists of two parallel pairs of polypeptide chains: one pair of heavy chains and one pair of light chains, both containing constant segments and variable segments

▫There are five types of constant segments:

▫The antigen binding site-

▫When an antibody binds to its corresponding antigen molecule, an

antigen-antibody complex is formed.

▫Antigenic determinant sites-

▫Complete antigen-

▫There are 7 ways in which the antigen may be eliminated:

*look over table 22-1 for descriptions of the classes of antibodies*

▪Primary and Secondary Responses to Antigen Exposure

▫Primary responses-

▫Antibody titer-

▫If the exposure ends, the antibody concentration declines because:

▫Two types of antibodies are involved in the primary response, IgM, IgG

▫Secondary responses-

▫If a second exposure takes place, the memory cells immediately start dividing into plasma cells, which secrete massive quantities of antibodies

▫The antibody titer of a secondary response rises quicker and higher than in the primary response

Normal Resistance and Abnormal Resistance

▪Immunological competence-

▪Immune Disorders-

▫Autoimmune disorders-

-Autoantibodies- antibodies released from B cells that target normal

body cells and tissues.

-For unknown reasons, the risk of autoimmune problems increases if an individual has an unusual type of MHC proteins.

▫Immunodeficiency diseases- can result from:

1) problems with the embryological development of lymphoid organs and tissues

2) an infection with a virus that depresses the immune function

3) treatment with, or exposure to, immunosuppressive agents

SCID- severe combined immunodeficiency disease- genetic disorder where individual fails to develop either cellular or anti-body mediated immunity.

-AIDS is an immunodeficiency disease that targets helper T cells

▫Allergies-

-Immediate hypersensitivity-

- anaphylaxis-

▪Stress and the Immune Response

▫Long-term secretion of glucocorticoids, GAS, can inhibit the immune response and lower resistance to disease. Glucocorticoids have the following effects on tissues which can alter the effectiveness of specific and nonspecific defenses:

1) depress the inflammatory response

2) reduce the activities and numbers of phagocytes in peripheral tissues

3) inhibition of interleukin secretion.

Aging and the Immune System

▪With age, T cells become less responsive to antigens

▪B cells are less active due to the decrease in helper T cells, antibodies are not produced as quickly

▪Increases an individual’s susceptibility to viral and bacterial infection.