Lecture Outline

CHAPTER OVERVIEW: This chapter introduces the lymphatic system including diffuse lymphatic tissues. Inflammation, non-specific immunity and specific immunity are described and contrasted. The cells of the immune system and their functions as well as the structure and function of antibodies are discussed.

OUTLINE (two to four fifty-minute lectures):

 Chapt. Object.

Topic Outline, Chapter 22

 

Figures & Tables

Trnspcy. Acetates

Trnspcy.

Masters

 

I. Lymphatic System

Clinical Focus, p.704; Systemic Interactions, p.728; Fig. 22.1, p.699

TA-281

 

1

      A. Functions of the Lymphatic System

     
 

          1. Fluid Balance

     
 

              a. Drains Excess Interstitial Fluid

     
 

              b. Carries Solutes and Returns them to Blood

     
 

          2. Fat Absorption and the Lacteals

     
 

          3. Defense

     
 

              a. Filtration of Foreign Materials by Spleen and Lymph Nodes

     
 

              b. Specialized Functions of Lymphocytes

     

3

      B. Lymphatic Organs

     
 

          1. Lymphatic Tissue Characterized by

     
 

              a. Lymphocytes

     

4

              b. Macrophages

     
 

              c. Dendritic Cells

     
 

              d. Reticular Cells and Associated Reticular Fibers

     

2

          2. Diffuse Lymphatic Tissue and Lymph Nodules

Fig. 22.2, p. 699

   
 

          3. Tonsils

Fig. 22.3, p.699

 

TM-82

 

              a. Palatine Tonsils

                  1). "The Tonsils"

     
 

                  2). Between Oral Cavity and Pharynx

     
 

              b. Pharnygeal Tonsil

     
 

                  1). "The Adenoid" When Enlarged

     
 

                  2). In Wall at Junction of Nasal Cavity and Oral Cavity

     
 

              c. Lingual Tonsil on Posterior Surface of Tongue

     
 

              d. Chronic Infection May Lead to Surgical Removal of Tonsils or Adenoids

     

2

          4. Lymph Nodes

Fig.22.4, p.700

TA-282

 
 

              a. Size 1-25 mm Length

     
 

              b. Distributed Along Lymph Vessels

     
 

              c. Paired Aggergations

     
 

                  1). Inguinal - Groin Region

     
 

                  2). Axillary - Armpit Region

     
 

                  3). Cervical - Neck Region

     
 

              d. Internal Structure

     
 

                  1). Capsule

     
 

                  2). Trabeculae

     
 

                  3). Collections of Lymphatic Cells and Lymph Sinuses

     
 

                      a). Cortex

     
 

                      b). Medulla with Medullary Cords

     
 

              e. Function to Filter Lymph

Clinical Note, p.701

   
 

                  1). Afferent and Efferent Lymphatic Vessels

     
 

                  2). Sinuses Lined by Phagocytic Cells

     

4

              f. Lymphocyte Proliferation can be Stimulated - Forming Germinal Centers, esp. in Cortex

     

2

5. Spleen

     
 
            1. Size of a Clenched Fist - Located in Extreme Upper Left of Abdominal Cavity

 

 

   
 

              b. Internal Structure - Fibrous Capsule and Trabeculae - Blood Vessels Enter/Leave at Hilum

Fig. 22.5, p.702

TA-283

 
 

              c. Red Pulp - Lymphatic Tissue Associated with the Venous Sinuses and Veins

     
 

              d. White Pulp - Lymphatic Tissue Associated with the Arterial Supply; Periarterial Sheath

     
 

              e. Functions -Detects and Responds to Foreign Substances - Mechanisms Similar to Lymph Nodes

     
 

              f. Destroys/Removes Worn-out Red Blood Cells - Macrophages in Red Pulp

     
 

              g. Acts as a Blood Reservoir

Clinical Note, p. 701

   
 

                  1). Contraction of Smooth Muscle in Splenic Blood Vessels and Capsule Move Blood Into Gen. Circulation

     
 

                  2). Under Sympathetic control

     

2

      6. Thymus Gland

     
 
            1. Location - Superior Mediastinum, Deep to Manubrium of Sternum
            2. Size Varies Throughout Lifespan- Greatest Size Before Puberty

Fig. 22.6, p.703

TA-284

 
 

              c. Internally - Capsule with Trabeculae Forming Lobules

     
 

                  1). Lymphocytes in Cortex of Each Lobule

     
 

                  2). Medullary Thymic Corpuscles (Hassall's Corpuscles)

     
 

                      a). Epithelial Origin

     
 

                      b). Unknown Function

     
 

              d. Reticular Cells Form Blood-Thymic Barrier

     
 

              e. Functions to Produce Lymphocytes

     
 

              1). Thymic Lymphocytes Move to Other Locations by Transport in the Blood

     
 

              f. Blood-Thymic Barrier Prevents Direct Response to Foreign Substances at Thymus

     
         
 

II. Immunity

     
 

      A. Ability to Resist Damage From Foreign Substances

     
 

          1. Specificity

     
 

          2. Memory

     
 

      B. Immunity = Ability to Destroy/Remove Pathogen Before Symptoms of Disease Develop

     
         

3

III. Innate (Nonspecific) Immunity

     
 

      A. Mechanical Barriers - Prevent Entry Into Body

     
 

          1. Physical Barriers

     
 

          2. Washing Substances

     
 

              a. Simple Fluid Movement - Tears, Saliva, Urine

     
 

              b. Complex Movement - Mucus

     
 

                  1). Upper Resp. Tract - Swallowing and Sneezing

     
 

                  2). Lower Resp. Tract - Coughing

     
 

      B. Chemical Mediators

Table 22.1, p.704

   
 

          1. Complement

Fig. 22.7. p.706

TA-285

 

 

              a. 20 Proteins in Complement Cascade

     
 

              b. Alternate Pathway Activation

     
 

                  1). Part of Innate Immunity

     
 

                  2). Stabilization of Spontaneously Activated C3 by Foreign Substance

     
 

              c. Classical Pathway is Part of Adaptive Immunity

     
 

              d. Funcitons of Complement System and its Components

     
 

                  1). Form Holes in Cell Membranes

Fig. 22.7, p.706

TA-285

 
 

                  2). Enhance Phagocytosis of Foreign Substances

     
 

                  3). Attract Immune System Cells to Site of Infection

     
 

                  4). Promote Inflammation

     
 

          2. Interferons

Clinical Note, p.705

   
 

              a. Protein Substance Produced by Cells Infected by a Virus

     
 

              b. Promote Production of Anti-viral Proteins by Neighboring Cells

     
 

                  1). These Anti-viral Compounds Prevent Viral Replication

     
 

                  2). Not Specific - Protect Against Many Different Viruses

     

4

      C. Cells = Primarily Leukocytes

Table 22.2, p.707

   
 

          1. Attracted by Chemotactic Factors

     
 

              a. Complement, Leukotrienes, Kinins and Histamine

     
 

              b. Cells Move Along Concentration Gradient to Site of Injury/Infection = Process of Chemotaxis

     
 

              2. Neutrophils

     
 

                  a. Lysosomal Enzymes

     
 

                  b. Accumulation = Pus

     
 

              3. Macrophages (and Mononuclear Phagocytic System)

     
 

                  a. Monocytes that Have Reached the Tissues; Esp. Near Points of Microbe Entry

     
 

                  b. Also Secrete Interferon, Prostaglandins, and Complement

     
 

                  c. Line Sinuses of Spleen & Lymph Nodes

     
 

          4. Basophils, Mast Cells and Eosinophils

     
 

              a. Basophils and Mast Cells Release Chemicals that Promote Inflammation

     
 

              b. Eosinophils Release Chemicals that Limit Inflammation and Kill Some Parasites

     
 

          5. Natural Killer Cells

     
 

              a. Type of Lymphocyte (up to 15%)

     
 

              b. Destroys Infected and Tumor Cells - Nonspecific

     

5

      D. Inflammatory Response

Fig.22.8, p.708

 

TM-83

 

          1. Complex Sequence Coordinated by Chemical Mediators

     
 

          2. General Effects

     
 

              a. Vasodilation and Increased Local Blood Flow

     
 

              b. Chemotactic Attraction of Phagocytic Cells

     
 

              c. Increased Vascular Permeability - Fibrinogen and Complement Enter Tissue Fluid from Blood

     
 

          3. Local Inflammation

     
 

              a. Effects Confined to Specific and Limited Area

     
 

              b. Symptoms:

     
 

                  1). Redness

     
 

                  2). Heat

     
 

                  3). Swelling

     
 

                  4). Pain

     
 

                  5). Loss of Function

     
 

          4. Systemic Inflammation

     
 

              a. Occurs in Many Parts of the Body at the Same Time

     
 

              b. Symptoms Additional to Local Syptoms at Sites of Inflammation

     
 

                  1). Increased Production of Neutrophils by Bone Marrow

     
 

                  2). Pyrogens Stimulate Fever Produciton

     
 

                  3). If Severe Enough, Shock due to Increased Vascular Permeability and Plasma Volume Loss

     
         
 

IV. Adaptive Immunity

Table 22.3, p.710

   
 

      A. Ability to Recognize, Respond to and Remember a Specific Substance

     

6

          1. Substances Capable of Stimulating Active Immunity = Antigens

     
 

              a. Usually Large Molecules; MW > 10,000

     
 

              b. Haptens are Smaller, Combine with Other Molecules to Promote Adaptive Immune Response

Clinical Note, p.709

   
 

          2. Foreign Antigens - Originate Outside the Body

     
 

          3. Self-Antigens - Found as Components of the Body's Own Cells

     
 

          4. Two Mechanisms of Immunity

     
 

              a. Humoral Immunity

     
 

              b. Cell-Mediated Immunity

     

7

      B. Origin and Development of Lymphocytes

Fig. 22.9, p.710

TA-286

 
 

          1. Stem Cells in Red Bone Marrow

     
 

          2. Positive Selection Process for Survival of Cells Capable of Immune Response

     
 

          3. Lines of B and T Cell Clones

     
 

              a. T Cells Mature in Thymus

     
 

              b. B Cells Mature in Red Bone Marrow

     
 

          4. Negative Selection for Removal of Clones Against Self-Antigens

     
 

          5. Lymphocytes Circulate Between Blood and Lymphatic Tissues

     
 

              a. Five Times as Many T Cells as B Cells in Blood

     
 

              b. Movement Allows

     
 

                  1). Increased Encounter with Antigens

     
 

                  2). Migration to Sites of Infection

     

7, 8

      C. Activation of Lymphocytes

     
 

          1. Antigenic Determinants and Antigen Receptors

Fig. 22.10, p.711

   
 

              a. Epitopes = Specific Regions of a Given Antigen that Active Lymphocytes

     
 

              b. Several Epitopes per Antigen

     
 

              c. Antigen Receptors Same on all Cells of a Clone

     
 

              d. Different Sturcture on B Cells and T Cells

Fig. 22.11, p.711

TA-287

 

9

          2. Major Histocompatibility Complex (MHC) Antigens

     
 

              a. Glycoproteins on Cell Surfaces

     
 

              b. Function in Lymphocyte Activation

     
 

              c. MHC Class I Antigens on Nucleated Cells

Fig. 22.12a, p.712

TA-288

 
 

                  1). Normally Display Self-Antigens

     
 

                  2). Display Foreign Antigens in Infected/Altered Cells

     
 

                  3). MHC Restricted Activation of T Cells

Predict Quest. 1

   
 

              d. MHC Class II/Antigen Complexes on Antigen-Processing Cells

Fig. 22.12b, p.712

TA-289

 
 

                  1). B Cells, Macrophages, Monocytes, and Dendritic Cells

     
 

                  2). Display End-Products of Processing of Foreign Antigens

     
 

                  3). Stimulates Increase in Immune System Activity

     
 

                      a). Cell Division

     
 

                      b). Antibody Production

Predict Quest. 2

   

9

              3. Costimulation = Requirement for Second Signal in Addition to MCH II/Antigen Complex

Fig. 22.13a, p.713

TA-290

 
 

                  a. Chemical Signal -Cytokines, Lymphokines

Table 22.4, p.714

   
 

                  b. Other Surface Proteins

Fig. 22.13b, p.713

TA-290

 
 

                      1). B7 to CD28 Connection

     
 

                      2). CD4 (Helper T Cells) to MHC II Connection

     
 

              4. Lymphocyte Proliferation Requires Increased Numbers of Helper T Cells

Fig. 22.14, p.715; Fig. 22.15, p.716

TA-291 TA-292

 
 

      D. Inhibition of Lymphocytes

Clinical Focus, pp.723-724

   
 

          1. Tolerance = Unresponsiveness to Antigen Resulting from Exposure

     
 

          2. Induced Several Ways

     
 

              a. Deletion of Self-Reactive Lymphocyte Clones

     
 

              b. Preventing Activation of Lymphocytes - Anergy - Usu. by Blocking Costimulation

Clinical Note, p.714

   
 

              c. Activity of Supressor T Cells

     

10

      E. Antibody - Mediated (Humoral) Immunity

Clinical Focus, pp. 725-726

   

11

          1. Antibodies - Specialized Proteins Produced in Response to an Antigen

Fig. 22.16, p.717 Table 22.5, p.717

TA-293

 
 

              a. Gamma Globulins and Immunoglobulins

     
 

              b. Five Classes - IgG, IgM, IgA, IgE, and IgD

     
 

              c. General Structure

     
 

                  1). Variable Region - Combines w/ Epitope of Antigen

     
 

                  2). Constant Region - Responsible for Other Activities

     
 

                      a). Activates Complement

     
 

                      b). Attaches Antibody to Cells

     
 

                      c). All Antibodies of the Same Class Have Same Constant Region

     

11

          2. Effects of Antibodies

Fig. 22.17, p.718

TA-294

 
 

              a. Two General Ways of Directly Affecting Antigens

     
 

                  1). Inactivates Antigen Function

     
 

                  2). Binds Several Antigen Particles Together

     
 

              b. Opsonins - Increases Phagocytosis of Antigens

     
 

              c. After Antigen Bound

Clinical Note, p.718

   
 

                  1). Activates Complement Cascade (IgG, IgM)

     
 

                  2). Initiates Inflammatory Response Through Degranulation of Mast Cells or Basophils (IgE)

     

12

          3. Antibody Production

Fig. 22.18, p.719

TA-295

 
 

              a. Primary Response Following First Exposure of B Cell to Antigen

     
 

                  1). Activation of B Cells

     
 

                  2). Series of Cell Divisions

     
 

                      a). Plasma Cells -Secrete Antibodies

     
 

                      b). Memory B Cells

     
 

                  3). IgM First Class of Antibody Secreted

     
 

                  4). Primary Response Takes 3 to 14 Days

     
 

              b. Secondary (Memory) Response After Subsequent Exposure Activates Memory B Cells

Fig. 22.18, p.719

TA-295

 
 

                  1). Faster - Hours to Days

     
 

                  2). Greater Amount of Antibody Produced

     
 

                  3). New Memory Cells Produced

Predict Quest. 3

   

10, 13

      F. Cell-Mediated Immunity (T lymphocytes)

     
 

          1. Most Effective Against Intracellular Pathogens

     
 

          2. T Cell Activation

Fig. 22.19, p.720

TA-296

 
 

              a. Regulated by Antigen-Presenteing Cells and Helper T Cells

     
 

              b. Effector T Cells and Memory T Cells Produced

     
 

          3. Cytotoxic T Cells

Predict Quest. 4

   
 

              a. Lyse Cells with Foreign Antigens

     
 

              b. Release of Cytokines, esp. for Recruitment of Phagocytic Cells

     
 

          4. Delayed-Hypersensitivity T Cells

     
 

              a. Respond to Antigens by Releasing Cytokines

     
 

              b. Involved in Allergic Reactions

Clinical Focus, pp.725-726

   

14

V. Immune Interactions

        1. Immune System Responses Involve Several Components Acting Together

 

Fig. 22.20, p.721

TA-297

 

15

VI. Immunotherapy - Treat Diseases by Altering the Immune System Response

Clinical Note, p.722

   
 
        1. Vaccinations Stimulate Acquired Immunity
        2. Monoclonal Antibodies

      a. Humanization

     

16

VII. Acquired Immunity - Four Ways to Acquire Active Immunity

Fig. 22.21, p.722

 

TM-84

 

      A. Active Natural Immunity

     
 

          1. Natural Exposure to Antigen

     
 

          2. May be Symptomatic or Asymptomatic First Exposure

     
 

      B. Active Artificial Immunity

     
 

          1. Vaccination

     
 

              a. Vaccine Contains Epitope of Pathogen

     
 

              b. Altered Antigen Stimulates Immune System Without Producing Symptoms

     
 

          2. Produces Long-Lasting Immunity Without Suffering Disease Symptoms

     
 

      C. Passive Natural Immunity

     
 

          1. Transfer of Antibodies from Mother to Child

     
 

              a. IgG Across Placenta

     
 

              b. IgA in Mother's Milk

     
 

          2. Protection Lasts only as Long as the Antibody Molecules Themselves

     
 

      D. Passive Artificial Immunity

     
 

          1. Transfer of Antibodies Produced by Immune Response of Another Animal

     
 

          2. Immediate Protection of Short Duration

     
 

VIII. Systems Pathology: Systemic Lupus Erythematous

Predict Quest. 5

   

IMPORTANT CONSIDERATIONS: Much of the detail of the control of specific antibody production is as yet poorly understood. It is up to the instructor to decide how detailed a knowledge of the types and mechanisms of antibody production for which the students will be responsible. If this material is to be covered in two lectures, the detail of the mechanisms of immunity will most likely be sacrificed. One lecture will be spent on the general structure and function of the lymphatic tissues and organs and the second lecture on immunity, with brief review of the various mechanisms responsible for the development of immunity. The complexity of the complement system deserves class time so students can be helped to sort through the steps and make sense of it. If there are four lectures possible then one lecture covers the general structure and organization of the lymphatic system, one on non-specific immunity and inflammation, one on B-cells and antibody-mediated immunity, leaving T-cells, cell- mediated immunity and a review of the types of acquired immunity for the last lecture. The organization of the lymphatic system and the relation of the lymphatic organs to the cardiovascular system are important topics for students to understand if they are ever to appreciate the coordination of immune system function.

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