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The Lymphatic System and Immunity

 

An Overview of the Lymphatic System and Immunity

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


Organization 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

 

Lymphatic vessels include

•Lymphatic capillaries

•Small lymphatic vessels

•Major lymph-collecting vessels

 

Major lymph-collecting vessels

•Superficial and deep lymphatics

•Thoracic duct

•Cisterna chyli

•Right lymphatic duct

 

Lymphocytes

•Three classes of lymphocytes

•T (thymus dependent) cells

•B (bone marrow-derived) cells

•NK (natural killer) cells

 

Lymphocyte production (lymphopoiesis)

•Involves bone marrow, thymus, and peripheral lymphoid tissue

•B cells and NK cells mature in bone marrow

•T cells mature in the thymus

 

Lymphoid tissue

•Connective tissue dominated by lymphocytes

•Lymphoid nodules

•Lymphocytes densely packed in areolar tissue

•Found in the respiratory, digestive, and urinary tracts

•MALT  (mucosa-associated lymphoid tissue)

•Collection of lymphoid tissues linked with the digestive system

 

Lymphoid organs

•Lymph nodes – function in the purification of lymph

•Afferent lymphatics – carry lymph to nodes

•Efferent lymphatics – carry lymph from nodes

•Deep cortex dominated by T cells

•Outer cortex and medulla contains B cells

 

The Lymphatic System and Immunity

The Thymus

•Located behind sternum in anterior mediastinum

•Capsule

•Two lobes

•Divided into lobules, each with a cortex and medulla

•Cortical lymphocytes surrounded by reticular endothelial cells

•Maintain blood–thymus barrier

•Secretes thymic hormones: thymosins, thymopoietins, and thymulin

 

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

 

Lymphatic system and body defenses

•Nonspecific defenses

•Do not distinguish one type of threat from another

•7 types

•Specific defenses

•Protect against particular threats

•Depend upon the activation of lymphocytes


Nonspecific Defenses

Nonspecific Defenses, Physical barriers

•Keep hazardous organisms outside the body

•Includes hair, epithelia, secretions of integumentary and digestive systems


(Part 1 - Physical Barriers)

Nonspecific Defenses, Phagocytes

•Remove cellular debris and respond to invasion by foreign pathogens

•Monocyte-macrophage system - Fixed and free

•Microphages – Neutrophils and eosinophils

•Move by diapedesis

•Exhibit chemotaxis


(Part 2 - Phagocytes)

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

 

NK cell activation

•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


(Part 3 - Immunological Surveillance)

Nonspecific Defenses, Interferons (cytokines)

•Small proteins released by virally infected cells

•Trigger the production of antiviral proteins

•Three major types of interferons are:

•Alpha– produced by leukocytes and attract/stimulate NK cells

•Beta– secreted by fibroblasts causing slow inflammation

•Gamma – secreted by T cells and NK cells stimulate macrophage activity


(Part 4 - Interferons)

Nonspecific Defenses, Complement system

•Cascade of ~11 plasma complement proteins (C)

•Destroy target cell membranes

•Stimulate inflammation

•Attract phagocytes

•Enhance phagocytosis

 

Complement proteins interact with on another via two pathways

•Classical

•Alternative


(Part 5 - Complement System)

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

•Mobilization of local, regional, and systemic defenses


(Part 6 - Inflammatory Response)

Nonspecific Defenses, Fever

•Maintenance of a body temperature above 37.2oC (99oF)

•Pyrogens reset the hypothalamic thermostat and raise body temperature

•Pathogens, toxins, antigen-antibody complexes can act as pyrogens

 

 (Part 7 - Fever)


Specific Defenses

Forms of immunity

•Innate immunity

•Genetically determined

•Present at birth

•Acquired immunity

•Not present at birth

•Achieved by exposure to antigen

•Active immunity

•Passive immunity

 

Properties 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 cells and Cell-mediated Immunity

Major types of T cells

•Cytotoxic T cells (TC) – attack foreign cells

•Helper T cells (TH) – activate other T cells and B cells

•Suppressor T cells (TS) – inhibit the activation of T and B cells

 

Antigen presentation

•Antigen-glycoprotein combination appears on a cell membrane

•Called MHC proteins (Major Histocompatibility Complex)

•Coded for by genes of the MHC

•T-cells sensitive to the antigen are activated upon contact

 

MHC classes

•Class I – found on all nucleated cells

•Class II – found on antigen presenting cells and lymphocytes

 

Lymphocytes respond to antigens bound to either class I or class II MHC proteins

•Antigen recognition

•T cell membranes contain CD markers

•CD3 markers present on all T cells

•CD8 markers on cytotoxic and suppressor T cells

•CD4 markers on helper T cells

 

Activation of CD8 cells

•Responds quickly giving rise to other T cells

•Cytotoxic T cells – seek out and destroy abnormal cells

•lymphotoxin

•Memory TC cells – function during a second exposure to antigen

•Suppressor T cells – suppress the immune response

 

Activation of CD4 T cells by antigens presented on class II MHC proteins

•Produces helper T cells and memory T cells

•Activated helper T cells

•Secrete lymphokines that coordinate specific and nonspecific defenses

•Enhance nonspecific defenses

•Stimulate the activity of NK cells

•Promote activation of B cells


B Cells and Antibody-mediated Immunity

B cell sensitization of activation

•Sensitization – the binding of antigens to the B cell membrane antibodies

•Antigens then displayed on B cell Class II MHC

•TH cells activated by same antigen stimulate B cell

•Active B cell differentiates into Memory B Cell or Plasma cell

•Plasma cells synthesize and release antibody

 

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

 

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

•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

 

Focus on Hormones of the Immune System

•Interleukins

•Increase T cell sensitivity

•Stimulate B cell activity, plasma formation, and antibody production

•Enhance nonspecific defenses

•Moderate the immune system

•Interferons

•Tumor Necrosis Factors (TNFs) slow tumor growth

•Colony Stimulating Factors (CSFs)

 

Normal and Abnormal Resistance

Development of the Immune Response

•Immunological competence

•The ability to demonstrate an immune response after exposure to an antigen

•Fetuses receive immunity from the maternal bloodstream

•Infants acquire immunity following exposure

 

Immune disorders

•Autoimmune disorders

•Immune response mistakenly targets normal cells

•Immunodeficiency diseases

•Immune system does not develop properly or is blocked

 

Allergies

•Inappropriate or excessive immune response to allergens

•Immediate hypersensitivity (type I)

•Cytotoxic reactions (type II)

•Immune complex disorders (type III)

•Delayed hypersensitivity (type IV)

•Anaphylaxis

•Circulating allergen affects mast cells throughout body

 

Stress and the immune response

•Interleukin-1 released by active macrophages

•Triggers release of ACTH resulting in glucocorticoid release

•Moderates the immune response

•Lowers resistance to disease

 

Stress can cause the following:

•Depression of the inflammatory response

•Phagocytic reduction

•Inhibition of interleukin secretion


Aging and the Immune Response

With age

•Immune system becomes less effective

•Increased susceptibility to infection

•Immune surveillance declines