Fundamentals of

Anatomy & Physiology

Lecture 22: The Lymphatic System and Immunity

Lecturer: Dr. Barjis Room P307 Phone: (718) 260-5285 E-Mail: [email protected]

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

Learning Objectives

• • • Describe the structure and function of lymphatic cells, tissues and organs List the body’s nonspecific defenses and describe the components and mechanisms of each Define specific resistance and distinguish between cell-mediated immunity and antibody mediated immunity

Learning Objectives

• • • Discuss the role of the T cell, B cell and antibodies in specific immunity Describe the origin, development, activation and regulation of normal resistance to disease Discuss the effects of stress and aging on the immune system

lymphatic system

• • The lymphatic system • Contains cells, tissues, and organs responsible for defending the body Lymphocytes resist infection and disease by responding to • Invading pathogens such as bacteria or viruses • Abnormal body cells such as cancer cells • Foreign proteins such as toxins

The Components of the Lymphatic System

The lymphatic system consists of

• • • • Lymph Lymphatic vessels Lymphoid tissues and organs Lymphocytes and supporting phagocytic cells

Functions of lymphatic system

• • • Primary function is production, maintenance, and distribution of lymphocytes • Lymphocytes must: • Detect where problems exist • Be able to reach the site of injury or infection Return of fluid and solutes from peripheral tissue to blood Distribution of hormones, nutrients, and waste product from their tissue of origin to general circulation.

Lymphatic vessels include

• • • Lymphatic capillaries Small lymphatic vessels Major lymph-collecting vessels

Lymphatic Capillaries

Major lymph-collecting vessels

• • • • Superficial and deep lymphatics Thoracic duct Cisterna chyli Right lymphatic duct

The Relationship between the Lymphatic Ducts and the Venous System

• Most of the lymph returns to the venous circulation by Thoracic duct

The Relationship between the Lymphatic Ducts and the Venous System

Lymphocytes

• • Account for 20-30 % of circulating WBC, but body contain 10 to the power of 12 lymphocytes There are tree classes of lymphocytes • T (thymus dependent) cells • B (bone marrow-derived) cells • NK (natural killer) cells

Lymphocytes

• • • •

Major types of T cells

Cytotoxic T cells (T C ) – attack foreign cells Helper T cells (T H ) – activate other T cells and B cells Suppressor T cells (T S ) – inhibit the activation of T and B cells T H and T S cells regulates immune response

Lymphocytes Major types of B cells

• Active B cell differentiates into • Memory B Cell or • Plasma B cell • Plasma B cells synthesize and release antibody

Lymphocyte production (lymphopoiesis)

• • • Lymphocyte production and maturation involves bone marrow, thymus, and peripheral lymphoid tissue B cells and NK cells mature in bone marrow T cells mature in the thymus

The Derivation and Distribution of Lymphocytes

Lymphoid tissue

• • • Connective tissue dominated by lymphocytes Lymphoid nodules • Lymphocytes are packed densely • Found in the respiratory, digestive, and urinary tracts MALT (mucosa-associated lymphoid tissue) • Collection of lymphoid tissues linked with the digestive system

Lymphoid Nodules

Lymphoid organs Lymphoid organs include: lymphoid nodes, thymus and spleen

• Lymph nodes – function in the purification of lymph

The Thymus

• • • • Located behind sternum in anterior mediastinum Reaches its maximum size just before puberty Consists two lobes • Divided into of lobules, each with a cortex and medulla • Lymphocytes in cortex are dividing, when mature migrate to modula and after 3 weeks enter the blood Secretes thymic hormones: thymosins, thymopoietins, and thymulin • stimulate stem cell division and T-cell differentiation

The Thymus

The Spleen

• • Largest mass of lymphoid tissue • Cellular components form pulp • Red pulp contains RBC • White pulp similar to lymphoid nodules Spleen functions include • Removal of abnormal blood cells and other blood components • Storage of iron • Initiation of the specific immune response

The Spleen

Lymphatic system and body defenses

• • Nonspecific defenses • Do not distinguish one type of pathogen (e.g. bacteria) from another type • There are 7 types of non specific defenses Specific defenses • • Protect against one particular threats Specific defense depend upon the activation of lymphocytes

Nonspecific Defenses Physical barriers

• • Keep hazardous organisms outside the body Includes hair, epithelia, secretions of integumentary and digestive systems

Nonspecific Defenses

•

Phagocytes

Remove cellular debris and respond to invasion by foreign pathogens

Nonspecific Defenses Immunological surveillance

• Constant monitoring of normal tissue by NK cells • NK cells • Recognize cell surface markers on foreign cells • Destroy cells with foreign antigens • Activation of NK cells: • • • • Recognition of unusual surface proteins Rotation of the Golgi toward the target cell and production of perforins Release of perforins by exocytosis Interaction of perforins causing cell lysis

Nonspecific Defenses Immunological Surveillance)

How Natural Killer Cells Kill Cellular Targets

Nonspecific Defenses

• • •

Interferons (cytokines)

Interferons are small proteins that act as chemical messengers that coordinate defense Interferons are released by virally infected cells and activated lymphocyytes Interferons bind to the surface of abnormal cells and trigger the production of antiviral proteins that prevents virus proliferation.

Nonspecific Defenses

• • •

Complement system

There are 11 plasma complement proteins (C) They are activated by: • • Classical pathway • In Classical pathway compliment binds to Ab molecule, Alternative pathway • In alternative pathway compliment binds to bacterial cell Both pathways trigger: • • • • Chain of reaction and result attraction of phagocytes, Stimulation of phagocitic activity, Promotion of inflammation and Result puncture of bacterial cell

Nonspecific Defenses Inflammation

• • Localized tissue response to injury producing • Swelling • Redness • Heat • Pain Effects of inflammation include • • Temporary repair of injury Slowing the spread of pathogens

Nonspecific Defenses Inflammatory Response

Nonspecific Defenses Fever

• • • • Maintenance of a body temperature above 37.2

o C (99 o F) High temperature may inhibit some viruses and bacterial activities. It increases metabolism (1°C increase in temperature would increase metabolism by 10%) Pyrogens reset the hypothalamic thermostat and raise body temperature • Pyrogen secretion is stimulated by Ag, macrophages

Specific Defenses

• • • Act on specific Ag only T-Cells are responsible for cell mediated immunity (cellular immunity) – defense against abnormal cells and pathogens inside cells B-cells provide Ab-mediated immunity (also called humoral immunity) – defense against Ags and pathogens in body fluid

Specific Defenses Forms of immunity

• Innate immunity • • Genetically determined • Present at birth Acquired immunity • Not present at birth • Achieved by exposure to antigen • Acquired immunity can be • Active immunity • Passive immunity

Types of Immunity

Properties/characteristics of immunity

• • • • Specificity – activated by and responds to a specific antigen Versatility – is ready to confront any antigen at any time Memory – “remembers” any antigen it has encountered Tolerance – responds to foreign substances but ignores normal tissues

The immune system response

• • • • • Antigen triggers an immune response Activates T cells and B cells • T cells are activated after phagocytes exposed to antigen T cells attack the antigen and stimulate B cells Activated B cells mature and produce antibody Antibody attacks antigen

T cell activation

• • • • T cells recognize Ag-glycoprotein complex in cell membrane Glycoproteins are synthesized in the region called Major Histocompatibility Complex (MHC)- so they are known as MHC proteins Each individual have different MHC proteins There are 2 classes of MHC proteins: • MHC class I • MHC class II

MHC classes

• Class I – found on all nucleated cells • • • • They are synthesized, and transported to membrane by vesicles of golgi apparatus As they are formed, they pick up small peptides from the cytoplasm and take them to membrane If the peptides that are picked up by MHC proteins are self (belong to the body), T-cells will ignore them, If the peptides that are picked up by the MHC proteins are none self (do not belong to the body i.e. if they are antigens) then T-cell becomes activated anddestroy the abnormal cell.

Antigens and MHC Proteins

MHC classes

• Class II – found on antigen presenting cells and lymphocytes • • • • • Phagocitic cells engulf pathogen Once the pathogen is inside the phagocitic cell, lysosome action breaks down the pathogen into fragments (Ag) Endoplasmic reticulum produces MHC II proteins Ag fragments will bound to MHC ll proteins and will be presented on the cell membrane MHC II and Antigen complex on the surface of membrane will activate T cells

Antigens and MHC Proteins

B cells and Antibody Mediated Response

• • • B cells produce specific Ab There are millions of B-cells - each with specific Ab on its membrane When B- cells are activated they can produce up to 100 million Ab per hour

Antibodies structure

• Antibodies are Y-shaped proteins consisting of: • Two parallel polypeptide chains • Heavy chains and light chains • Constant region and variable region • Antigen binding site

Antibody Structure

Antibody Structure

Actions of antibodies include:

• • • • • • • Neutralization Agglutination and precipitation Activation of complement Attraction of phagocytes Opsinization Stimulation of inflammation Prevention of adhesion

Classes of Antibodies (immunoglobins)

• • • • • IgG – resistance against many viruses, bacteria and bacterial toxins IgE – accelerates local inflammation and responsible for allergic reaction IgD – found on the surface of B cells IgM – first type secreted after antigen arrives IgA – primarily found in glandular sec

Primary and secondary antibody response

• • Primary response • Takes about two weeks to develop • Produced by plasma cells Secondary response • Rapid increase in IgG • Maximum antibody titer app

Aging and the Immune Response With age

• • • Immune system becomes less effective Increased susceptibility to infection Immune surveillance declines

You should now be familiar with:

• • • • • • The structure and function of lymphatic cells, tissues and organs The body’s nonspecific defenses and the components and mechanisms of each Specific resistance, cell-mediated immunity and antibody mediated immunity The role of the T cell, B cell and antibodies in specific immunity The origin, development, activation and regulation of normal resistance to disease The effects of stress and aging on the immune system