Body Defenses

The Lymphatic System and Body Defenses

The Lymphatic System

Consists of two semi-independent parts
Lymphatic vessels
Lymphoid tissues and organs

Lymphatic system functions
Transports escaped fluids back to the blood
Plays essential roles in body defense and resistance to disease

Lymphatic Characteristics
Lymph—excess tissue fluid carried by lymphatic vessels

Properties of lymphatic vessels
One way system toward the heart
No pump
Lymph moves toward the heart
Milking action of skeletal muscle
Rhythmic contraction of smooth muscle in vessel walls

Lymphatic Vessels
Lymph capillaries
Walls overlap to form flap-like minivalves
Fluid leaks into lymph capillaries
Capillaries are anchored to connective tissue by filaments
Higher pressure on the inside closes minivalves
Fluid is forced along the vessel
Lymphatic collecting vessels
Collect lymph from lymph capillaries
Carry lymph to and away from lymph nodes
Return fluid to circulatory veins near the heart
Right lymphatic duct
Thoracic duct

Harmful materials that enter lymph vessels
Cancer cells
Cell debris 

Lymph Nodes
Filter lymph before it is returned to the blood
Defense cells within lymph nodes
Macrophages—engulf and destroy foreign substances
Lymphocytes—provide immune response to antigens

Lymph Node Structure
Most are kidney-shaped and less than 1 inch long
Outer part
Contains follicles—collections of lymphocytes
Inner part
Contains phagocytic macrophages

Flow of Lymph Through Nodes
Lymph enters the convex side through afferent lymphatic vessels
Lymph flows through a number of sinuses inside the node
Lymph exits through efferent lymphatic vessels
Fewer efferent than afferent vessels causes flow to be slowed

Other Lymphoid Organs
Several other organs contribute to lymphatic function
Peyer’s patches

Located on the left side of the abdomen
Filters blood
Destroys worn out blood cells
Forms blood cells in the fetus
Acts as a blood reservoir

Thymus Gland
Located low in the throat, overlying the heart
Functions at peak levels only during childhood
Produces hormones (like thymosin) to program lymphocytes

Small masses of lymphoid tissue around the pharynx
Trap and remove bacteria and other foreign materials
Tonsillitis is caused by congestion with bacteria

Peyer’s Patches
Found in the wall of the small intestine
Resemble tonsils in structure
Capture and destroy bacteria in the intestine

Mucosa-Associated Lymphatic Tissue (MALT)
Peyer’s patches
Other small accumulations of lymphoid tissue
Acts as a sentinel to protect respiratory and digestive tracts

Body Defenses
The body is constantly in contact with bacteria, fungi, and viruses
The body has two defense systems for foreign materials
Innate (nonspecific) defense system
Adaptive (specific) defense system
Immunity—specific resistance to disease

Innate (nonspecific) defense system
Mechanisms protect against a variety of invaders
Responds immediately to protect body from foreign materials
Adaptive (specific) defense system
Specific defense is required for each type of invader

Innate (Nonspecific) Body Defenses
Innate body defenses are mechanical barriers to pathogens such as
Body surface coverings
Intact skin
Mucous membranes
Specialized human cells
Chemicals produced by the body 

Surface Membrane Barriers:
First Line of Defense
Skin and mucous membranes
Physical barrier to foreign materials
Also provide protective secretions
pH of the skin is acidic to inhibit bacterial growth
Sebum is toxic to bacteria
Vaginal secretions are very acidic
Stomach mucosa
Secretes hydrochloric acid
Has protein-digesting enzymes
Saliva and lacrimal fluid contain lysozymes, an enzyme that destroy bacteria
Mucus traps microogranisms in digestive and respiratory pathways

Cells and Chemicals:  Second Line of Defense
Natural killer cells
Inflammatory response
Antimicrobial proteins

Natural killer (NK) cells
Can lyse (disintegrate or dissolve) and kill cancer cells
Can destroy virus-infected cells
Release a chemical called perforin to target the cell’s membrane and nucleus, causing disintegration

Inflammatory response
Triggered when body tissues are injured
Four most common indicators of acute inflammation
Results in a chain of events leading to protection and healing

Functions of the inflammatory response 
Prevents spread of damaging agents
Disposes of cell debris and pathogens through phagocytosis
Sets the stage for repair

Process of the inflammatory response:
Neutrophils migrate to the area of inflammation by rolling along the vessel wall
They squeeze through the capillary walls by diapedesis to sites of inflammation
Neutrophils gather in the precise site of tissue injury (positive chemotaxis) and consume any foreign material present.

Cells such as neutrophils and macrophages
Engulf foreign material into a vacuole
Enzymes from lysosomes digest the material

Neutrophils move by diapedesis to clean up damaged tissue and/or pathogens
Monocytes become macrophages and complete disposal of cell debris

Antimicrobial proteins
Attack microorganisms
Hinder reproduction of microorganisms
Most important
Complement proteins

Complement proteins
A group of at least 20 plasma proteins
Activated when they encounter and attach to cells (complement fixation)
Damage foreign cell surfaces
Release vasodilators and chemotaxis chemicals, cause opsonization

Proteins secreted by virus-infected cells
Bind to healthy cell surfaces to interfere with the ability of viruses to multiply

Abnormally high body temperature
Hypothalamus heat regulation can be reset by pyrogens (secreted by white blood cells)
High temperatures inhibit the release of iron and zinc from the liver and spleen needed by bacteria
Fever also increases the speed of tissue repair

Adaptive Defense System: Third Line of Defense
Immune response is the immune system’s response to a threat
Immunology is the study of immunity
Antibodies are proteins that protect from pathogens

Three aspects of adaptive defense
Antigen specific—recognizes and acts against particular foreign substances
Systemic—not restricted to the initial infection site
Memory—recognizes and mounts a stronger attack on previously encountered pathogens

Types of Immunity 
Humoral immunity = antibody-mediated immunity
Provided by antibodies present in body fluids
Cellular immunity = cell-mediated immunity
Targets virus-infected cells, cancer cells, and cells of foreign grafts

Antigens (nonself) 
Any substance capable of exciting the immune system and provoking an immune response
Examples of common antigens
Foreign proteins (strongest)
Nucleic acids
Large carbohydrates
Some lipids
Pollen grains

Human cells have many surface proteins
Our immune cells do not attack our own proteins
Our cells in another person’s body can trigger an immune response because they are foreign
Restricts donors for transplants

Many small molecules (called haptens or incomplete antigens) are not antigenic, but link up with our own proteins
The immune system may recognize and respond to a protein-hapten combination
The immune response is harmful rather than protective because it attacks our own cells

Cells of the adaptive defense system
Lymphocytes respond to specific antigens
B lymphocytes (B cells)
T lymphocytes (T cells)
Macrophages help lymphocytes

Immunocompetent—cell becomes capable of responding to a specific antigen by binding to it
Cells of the adaptive defense system 

Originate from hemocytoblasts in the red bone marrow
B lymphocytes become immunocompetent in the bone marrow (remember B for Bone marrow)
T lymphocytes become immunocompetent in the thymus (remember T for Thymus)

Arise from monocytes
Become widely distributed in lymphoid organs
Secrete cytokines (proteins important in the immune response)
Tend to remain fixed in the lymphoid organs

Humoral (Antibody-Mediated) Immune Response
B lymphocytes with specific receptors bind to a specific antigen
The binding event activates the lymphocyte to undergo clonal selection
A large number of clones are produced (primary humoral response)

Humoral Immune Response
Most B cells become plasma cells
Produce antibodies to destroy antigens
Activity lasts for 4 or 5 days
Some B cells become long-lived memory cells (secondary humoral response)

Secondary humoral responses
Memory cells are long-lived
A second exposure causes a rapid response
The secondary response is stronger and longer lasting

Active Immunity
Occurs when B cells encounter antigens and produce antibodies
Active immunity can be
Naturally acquired during bacterial and viral infections
Artificially acquired from vaccines

Passive Immunity
Occurs when antibodies are obtained from someone else
Conferred naturally from a mother to her fetus (naturally acquired)
Conferred artificially from immune serum or gamma globulin (artificially acquired)
Immunological memory does not occur
Protection provided by “borrowed antibodies”

Monoclonal antibodies 
Antibodies prepared for clinical testing or diagnostic services
Produced from descendents of a single cell line
Examples of uses for monoclonal antibodies
Diagnosis of pregnancy
Treatment after exposure to hepatitis and rabies

Antibodies (Immunoglobulins or Igs)
Soluble proteins secreted by B cells (plasma cells)
Carried in blood plasma
Capable of binding specifically to an antigen

Antibody structure 
Four amino acid chains linked by disulfide bonds
Two identical amino acid chains are linked to form a heavy chain
The other two identical chains are light chains
Specific antigen-binding sites are present

Antibody classes 
Antibodies of each class have slightly different roles
Five major immunoglobulin classes (MADGE)
IgM—can fix complement
IgA—found mainly in mucus
IgD—important in activation of B cell
IgG—can cross the placental barrier and fix complement
IgE—involved in allergies

Antibody function 
Antibodies inactivate antigens in a number of ways
Complement fixation

Cellular (Cell-Mediated) Immune Response
Antigens must be presented by macrophages to an immunocompetent T cell (antigen presentation)
T cells must recognize nonself and self (double recognition)
After antigen binding, clones form as with B cells, but different classes of cells are produced
T cell clones
Cytotoxic (killer) T cells
Specialize in killing infected cells
Insert a toxic chemical (perforin)
Helper T cells
Recruit other cells to fight the invaders
Interact directly with B cells
Regulatory T cells
Release chemicals to suppress the activity of T and B cells
Stop the immune response to prevent uncontrolled activity
A few members of each clone are memory cells

Organ Transplants and Rejection
Major types of grafts
Autografts—tissue transplanted from one site to another on the same person
Isografts—tissue grafts from an identical person (identical twin)
Allografts—tissue taken from an unrelated person
Xenografts—tissue taken from a different animal species

Autografts and isografts are ideal donors
Xenografts are never successful
Allografts are more successful with a closer tissue match

Disorders of Immunity: 
Allergies (Hypersensitivity)

Abnormal, vigorous immune responses

Types of allergies
Immediate hypersensitivity
Triggered by release of histamine from IgE binding to mast cells
Reactions begin within seconds of contact with allergen
Anaphylactic shock—dangerous, systemic response
Delayed hypersensitivity
Triggered by the release of lymphokines from activated helper T cells
Symptoms usually appear 1–3 days after contact with antigen

Disorders of Immunity: Immunodeficiencies
Production or function of immune cells or complement is abnormal
May be congenital or acquired
Includes AIDS (Acquired Immune Deficiency Syndrome)

Disorders of Immunity: 
Autoimmune Diseases
The immune system does not distinguish between self and nonself
The body produces antibodies and sensitized T lymphocytes that attack its own tissues

Examples of autoimmune diseases
Multiple sclerosis—white matter of brain and spinal cord are destroyed
Myasthenia gravis—impairs communication between nerves and skeletal muscles
Type I diabetes mellitus—destroys pancreatic beta cells that produce insulin
Disorders of Immunity: 
Autoimmune Diseases
Examples of autoimmune diseases
Rheumatoid arthritis—destroys joints
Systemic lupus erythematosus (SLE)
Affects kidney, heart, lung, and skin
Glomerulonephritis—impairment of renal function

Self Tolerance Breakdown
Inefficient lymphocyte programming
Appearance of self-proteins in the circulation that have not been exposed to the immune system
Eye lens
Proteins in the thyroid gland
Cross-reaction of antibodies produced against foreign antigens with self-antigens
Rheumatic fever

Developmental Aspects of the Lymphatic System and Body Defenses
Except for thymus and spleen, the lymphoid organs are poorly developed before birth
A newborn has no functioning lymphocytes at birth, only passive immunity from the mother
If lymphatics are removed or lost, severe edema results, but vessels grow back in time