Lymphatic & Immune System

Dr. Michael P. Gillespie

Important Terminology

Pathogens – disease producing microbes such as bacteria and viruses.

Resistance – the ability to ward off damage or disease through our defenses.

Susceptibility – our lack of resistance or vulnerability.

Types Of Resistance

Nonspecific resistance – innate defenses. Present at birth. Provides immediate, but general protection

against invaders. Mechanical and chemical barriers of the skin and

mucous membranes (1st line of defense). Acidity of the gastric juice.

Types Of Resistance

Specific resistance – immunity. Develops in response to contact with a particular

invader. Occurs more slowly than nonspecific resistance. Involves activation of specific lymphocytes. The lymphatic and immune system is responsible

for this kind of resistance.

Components

Lymph fluid. Lymphatic vessels. Various structures containing lymphatic

tissue. Red bone marrow – stem cells develop into

lymphocytes (among other types) here.

Lymph Fluid

A clear liquid. Blood plasma filters through the capillaries

into the interstitial fluid. After interstitial fluid passes into lymphatic

vessels it is called lymph.

Lymphocytes In The Immune Response

B cells. T cells.

Functions Of Lymphatic & Immune System

1. Draining excess interstitial fluid. 2. Transporting dietary lipids and lipid

soluble vitamins (A, D, E, and K). 3. Carry out immune responses.

Lymphocytes, aided by macrophages, recognize foreign cells, microbes, toxins, and cancer cells.T cells destroy the intruders.B cells produce antibodies that recognize foreign cells.

Lymphatic Vessels & Circulation

Lymphatic vessels begin as lymphatic capillaries. Lymphatic capillaries unite to form larger

lymphatic vessels. Lymphatic vessels are similar to veins, but have

thinner walls and more veins. Lymph flows through lymph nodes (masses of B

cells and T cells).

Lymphatic Vessels & Circulation

In the skin, lymphatic vessels generally follow veins.

Lymphatic vessels of the viscera generally follow arteries.

Avascular tissues lack lymphatic capillaries (cartilage, epidermis, cornea of the eye).

The CNS, portions of the spleen, and bone marrow also lack lymphatic capillaries.

Lymphatic Capillaries

Slightly larger than blood capillaries. Permit fluid to flow into them, but not out. Lacteals – specialized lymphatic capillaries

in the small intestine that carry dietary lipids. Lymph here appears white due to the lipids and is referred to as chyle.

Lymph Trunks & Ducts

Lymph vessels merge and unite to form trunks.

Principal trunks: Lumbar, intestinal, bronchomediastinal,

subclavian, and jugular trunks. Lymph passes from lymph trunks into two

main channels, the thoracic duct and the right lymphatic duct.

Thoracic (Left Lymphatic) Duct

Begins as a dilation of the cisterna chyli anterior to the 2nd lumbar vertebra.

Receives lymph from the left side of the head, neck and chest, left upper limb, and the entire body inferior to the ribs.

Thoracic (Left Lymphatic) Duct

Drains into the left subclavian vein. Drains the following trunks:

Right and left lumbar trunks. Intestinal trunk. Left jugular trunk. Left subclavian trunk. Left bronchomediatinal trunk.

Right Lymphatic Duct

Drains lymph from the upper right side of the body into venous blood via the right subclavian vein.

Drains lymph from the following trunks: Right jugular trunk. Right subclavian trunk. Right bronchomediastinal trunk.

Formation & Flow Of Lymph

Many components of blood plasma freely flow through the capillaries to form interstitial fluid.

More fluid filters out of blood capillaries than is reabsorbed by them (about 3 liters more).

Formation & Flow Of Lymph

The excess fluid drains into lymphatic capillaries and becomes lymph.

Lymph returns plasma proteins to the blood (they cannot be reabsorbed by the blood capillaries).

Lymphatic vessels have valves to ensure one way flow.

Sequence Of Fluid Flow

Blood capillaries (blood) > interstitial spaces (interstitial fluid) > lymphatic capillaries (lymph) > lymphatic vessels (lymph) > lymphatic ducts (lymph) > subclavian veins (blood).

Pumps To Return Lymph

Skeletal muscle pump. Respiratory pump.

Edema & Lymph Flow

Edema – excessive accumulation of interstitial fluid.

Edema can be caused by obstruction of lymph flow due to an infected lymph node or blocked lymphatic vessel.

Increased capillary blood pressure can cause edema by producing accumulation of interstitial fluid faster than it can flow into the lymphatic vessels.

Elephantiasis

Lymphatic Organs & Tissues

Primary lymphatic organs – sites where stem cells divide and become immunocompetent. Red bone marrow. Thymus.

Lymphatic Organs & Tissues

Secondary lymphatic organs – sites where most immune responses occur. Lymph nodes. Spleen. Lymphatic nodules (follicles) – these are tissues

not organs because they lack a capsule.

Thymus

A bilobed organ located in the mediastinum between the sternum and the aorta.

The cortex consists of T cells.

Thymus

Pre-t cells migrate from the bone marrow and mature into T cells here.

The medulla consists of more mature T cells and macrophages.

The thymus is large in an infant, but begins to atrophy after puberty.

Lymph Nodes

Located along the lymphatic vessels. There are about 600 bean shaped lymph

nodes. They are scattered throughout the body, but

usually occur in groups.

Lymph Nodes

The outer cortex contains aggregates of B cells called lymphatic nodules (follicles).

When B cells encounter a foreign antigen, they develop into antibody producing plasma cells or into memory B cells (which persist to recognize the foreign antigen in the future).

Lymph Nodes

The inner cortex contains primarily T cells, which proliferate when exposed to a foreign antigen. They then migrate to areas of the body with antigenic activity.

The medulla contains B cells, antibody-producing plasma cells, and macrophages.

Lymph Flow

Lymph flows through the node in only one direction.

Afferent (to carry toward) vessels carry lymph to the node.

Efferent (to carry away) vessels carry lymp away from the node.

Lymph Nodes

Lymph nodes serve to filter lymph. Foreign substances are trapped within the

reticular fibers. Macrophages destroy foreign substances by

phagocytosis. Lymphocytes destroy substances via other

immune responses.

Metastasis

Metastasis is the spread of disease from one part of the body to another.

The blood vessels and lymph nodes serve as routes for metastasis.

Metastasis

Cancer cells may travel through the lymphatic vessels and lodge in a lymph node.

Cancerous lymph nodes feel enlarged, firm, non-tender, and fixed to underlying structures.

Lymph nodes enlarged due to infection are soft, movable, and very tender.

Spleen

The spleen is the single largest mass of lymphatic tissue.

It is located in the left hypochondriac region between the stomach and the diaphragm.

Spleen

B cells and T cells carry out immune functions in a similar fashion to lymph nodes.

Macrophages destroy blood born pathogens by phagocytosis.

Blood cell related functions: Removal of worn out or defective RBCs by

macrophages. Storage of platelets (1/3). Hemopoiesis (production of RBCs) during fetal life.

Ruptured Spleen

The spleen is the most often damaged organ in cases of abdominal trauma.

Blows to the left inferior chest can fracture ribs and rupture the spleen.

Intraperitoneal hemmorrhage and shock follow.

Ruptured Spleen

Splenectomy (removal of the spleen) is needed to prevent death due to bleeding.

The red bone marrow and liver take over many of the functions of the spleen; However, immune functions are decreased.

Ruptured Spleen

Sepsis (blood infection) is more likely to occur due to loss of the filtering and phagocytosis of the spleen.

These patient must take antibiotics prior to any invasive procedures to reduce the risk of sepsis.

Lymphatic Nodules

Lymphatic nodules are egg-shaped masses of lymphatic tissue that are not surrounded by a capsule.

The are scattered through mucous membranes of the GI, urinary, reproductive, and respiratory systems.

Lymphatic Nodules

They are referred to as mucosa-associated lymphatic tissue (MALT).

Large aggregations of these nodules are referred to as tonsils (5 of them). A single pharyngeal tonsil (adenoid), 2 palatine

tonsils, 2 lingual tonsils.

Development Of Lymphatic Tissues

Lymphatic vessels develop from lymph sacs that are derived from mesoderm.

The jugular lymph sacs appear first, then the retroperitoneal lymph sac, then the cysterna chyli, and finally the posterior lymph sacs.

Nonspecific Resistance: Innate Defenses

Present at birth. Offer immediate protection against a wide

variety of pathogens and foreign substances.

Nonspecific Resistance: Innate Defenses

First line of defense: skin and mucous membranes. Epidermis. Mucous membranes, mucus, hairs, cilia. Lacrimal apparatus manufactures and drains tears. Saliva washes microbes from the teeth. Flow of urine retards microbial colonization. Vaginal secretions move microbes out of the body. Defecation and vomiting expel microbes. Sebaceous glands secrete sebum which forms a protective film. Perspiration flushes microbes and contains lysozyme. Acid gastric juice destroys microbes.

Nonspecific Resistance: Innate Defenses

Second line of defense: internal defenses. Antimicrobial proteins.

Interferons (IFNs) and transferrins inhibit bacterial growth and replication.

Natural killer cells and phagocytes. Inflammation.

Redness, pain, heat, swelling. Emigration of phagocytes.

Fever. Inhibits the growth of microbes and speeds up body reactions

that aid repair.

Specific Resistance: Immunity

Specific resistance or immunity is the ability of the body to defend itself against specific invading agents such as bacteria, toxins, viruses, and foreign tissues.

Specific Resistance: Immunity

Antigens (Ags) are substances that are recognized as foreign and provoke immune responses.

2 properties distinguish immunity from nonspecific defenses: 1. Specificity. 2. Memory.

Immunocompetence

Immunocompetence is the ability to carry out immune responses.

Lymphocytes called B cells and T cells carry out immune responses.

Immunocompetence

Both of these types of cells develop from the primary lymphatic organs (red bone marrow and thymus).

B cells mature in the bone marrow. Pre-t cells from the bone marrow migrate to

the thymus where they mature.

Types Of Immune Responses

Cell-mediated immune responses. T cells become cytotoxic T cells that attack the

invading antigen directly.

Antibody-mediated immune responses. B cells secrete antibodies (abs) or

immunoglobulins. Antibodies bind to and inactivate specific antigens.

Immune Response & Invader Types

Cell-mediated immunity is effective against: 1. Intracellular pathogens that reside within host cells.

Fungi, parasites, and viruses. 2. Some cancer cells. Foreign tissue transplants.

Antibody-mediated immunity is effective against: 1. Antigens present in body fluids. 2. Extracellular pathogens in body fluids (bacteria).

Most pathogens elicit both responses.

Characteristics Of Antigens

Immunogenicity – the ability to provoke an immune response by stimulating the production of specific antibodies.

Reactivity – the ability of an antigen to react with specific antibodies.

Epitopes – the small parts of antigen molecules that initiate immune responses.

Entire microbes or parts of microbes may act as antigens.

Routes Of Antigens Into Lymphatic Tissue

Most antigens that enter the bloodstream are trapped as they flow through the spleen.

Antigens that penetrate the skin enter lymphatic vessels and lodge in lymph nodes.

Antigens that penetrate mucous membranes are entrapped by mucosa-associated lymphatic tissue.

Hapten

A hapten is a smaller substance that has reactivity, but lacks immunogenicity.

It can only stimulate an immune response if it is attached to a larger carrier molecule.

Poison ivy is an example of a hapten.

Major Histocompatibility Complex (MHC)

The major histocompatibility complex (MHC) antigens are “self antigens”.

The MHC are located in the plasma membrane of body cells.

Unless you have an identical twin, your MHC antigens are unique.

These are responsible for identifying a foreign antigen as not self.

Histocompatibility Testing

The more similar the MHC antigens, the greater the histocompatibility.

Greater histocompatibility leads to a lower likelihood that the organ or tissue will be rejected.

Processing & Presenting An Antigen

B cells recognize and bind to foreign antigens; However, T cells only recognize fragments of antigenic compounds that are “presented” with the MHC.

Processing Of Exogenous Antigens

Exogenous antigens are outside of body cells.

Ingestion of the antigen by the antigen-presenting cells (APCs).

Processing Of Exogenous Antigens

Digestion of the antigen into peptide fragments. Antigen fragments fuse to MHC-II complexes,

which are then inserted into the plasma membrane of the APC.

The APCs then migrate to lymphatic tissue where they “present” the antigen fragment-MHC-ii complex to T cells to inform them to attack.

Processing Of Endogenous Antigens

Endogenous antigens are inside of body cells.

The MHC-I complex binds with the antigen fragments inside infected cells.

The new antigen fragment-MHC-i complex moves to the plasma membrane of the cell for “presentation”.

Cytokines

Cytokines are small protein hormones that stimulate or inhibit many normal cell functions, such as cell growth and differentiation.

Cytokine therapy is the use of cytokines to treat medical conditions.

Interferons were the first cytokines to be effective against human cancer.

Cell-mediated Immunity

A cell-mediated immune response begins with the activation of a small number of T cells by a specific antigen.

Once a T cell has been activated, it undergoes proliferation and differentiation into effector cells.

Effector cells recognize and attack the specific antigen.

Types Of T Cells

Helper T (TH) cells {CD4+} – resting (inactive) TH cells recognize antigen fragments associated with MHC-II molecules. When activated, they secrete a variety of cytokines that attack the invaders.

Types Of T Cells

Cytotoxic T (TC) cells {CD8+} – recognize foreign antigens associated with MHC-I molecules. They are capable of lysing affected cells.

Memory T cells – these cells remain from a proliferated clone after a cell-mediated response. This allows for a swifter response with subsequent infection.

Elimination Of Invaders

Cytotoxic T cells are the soldiers that battle with foreign invaders.

Cytotoxic T cells use 2 killing mechanisms: Perforin forms holes in the plasma membrane of the

target cell, which allows extracellular fluid to flow in causing the cell to burst (cytolysis).

Lymphotoxin is secreted, which activates enzymes within the target cell. These enzymes cause the targets DNA to fragment and the cell dies.

Graft Rejection

Organ transplantation involves the replacement of an injured or diseased organ with an organ donated by another individual..

Usually, the immune system recognizes the proteins of the transplanted organ as foreign and mounts immune responses against them.

This process is known as graft rejection.

Graft Rejection

The more closely matched the histocompatibility, the less likely the organ is to be rejected.

Organ recipients receive immunosuppresive drugs to reduce the risk of rejection.

This increases the risk of infection by some diseases.

Antibody-mediated Immunity

Cytotoxic T cells leave lymphatic tissue to search out and destroy a foreign antigen; However, B cells stay put.

When B cells are exposed to a foreign antigen, they differentiate into plasma cells that secrete specific antibodies, which circulate through lymph and blood to reach the site of invasion.

Activation, Proliferation, & Differentiation Of B Cells

Antigens bind to B cell receptors, which activates them.

B cells enlarge, divide, and differentiate into plasma cells which secrete antibodies.

Some B cells do not differentiate, but remain as B memory cells.

Antibodies enter circulation and form antigen-antibody complexes with the antigen that initiated their production.

Antibodies

Antibodies (Ab) combine specifically with the antigen that initiated their production.

Antibody Actions

Neutralizing antigen – blocks or neutralizing some bacterial toxins and prevents bacterial attachment to cells.

Immobilizing bacteria – some form against cilia or flagella.

Antibody Actions

Agglutinating and precipitating antigen – cause agglutination (clumping together) of pathogens for easier phagocytosis and precipitation.

Activating complement. Enhancing phagocytosis – attracts

phagocytes.

Complement System

The complement system is a defensive system consisting of plasma proteins that attack and destroy microbes.

This system leads to the following events” inflammation, enhancement of phagocytosis, and bursting of microbes.

Complement System

Inflammation increases the permeability of blood capillaries allow WBCs to emigrate into affected tissues.

Opsonization – complement fragment c3b binds to the surface of the microbe and interacts with receptors on phagocytes.

Cytolysis – complement proteins form a membrane attack complex (MAC) that inserts on the membrane and forms large holes.

Immunological Memory

The immune system can remember specific antigens that have triggered immune responses, either through antibodies, or long lasting lymphocytes.

Immune responses are much quicker and more intense after a second exposure.

The antibody titer can be utilized to measure immunological memory.

Memory cells may remain for decades.

Self-recognition & Self-tolerance

To function properly T cells must: Recognize your own major histocompatibility

complex (MHC) proteins (self-recognition). They must lack reactivity to peptide fragments

from your own proteins (self-tolerance).