The Lymphatic System and Immunity

 

I.                     Lymphatic System

A.      Functions

1.    Return tissue fluid to the bloodstream

2.    Absorb fat from intestinal villi

3.    Defend against disease

 

B.      Lymphatic Vessels

1.    Structure

a.      Capillaries are like blood capillaries but have special valves

(1)   Valves let lots of stuff in but not back out

(2)   Structurally are like one-way flaps between endothelial cells

b.      Larger lymphatics are like veins, with valves

(1)   Valves inside to prevent backflow

2.    Function

a.      Lymph is moved through lymphatics by squeezing of muscles and pressure changes in the thorax

b.      Lymph vessels merge until they join one of two main ducts

3.    Main ducts

a.      Thoracic duct – larger than right lymphatic duct, collects from left side of head and neck, left arm, and everything below

(1)   Empties into left subclavian vein

b.      Right lymphatic duct – collects only from right arm and right side of head

(1)   Empties into right subclavian vein

 

C.     Lymphoid Organs - contain lymphocytes

1.    Spleen

a.      Left upper abdominal cavity

b.      Structure

(1)   Similar to lymph node

(2)   CT capsule

(3)   Outer CT under capsule reaches inward and divides the spleen into lobules

(4)   Lobules contain capillary sinuses, red and white pulp

(5)   Red pulp contains RBCs, lymphocytes, and macrophages

(6)   White pulp contains lymphocytes and macrophages

c.      Functions

(1)   Capillary sinuses can expand to hold a lot of blood – acts as a blood reservoir

(2)   RBC graveyard – RBCs recycled here

(3)   Filters blood, some immune surveillance

(4)   If removed (easily damaged by physical trauma) functions can be taken over by other organs

2.    Lymph Nodes

a.      Structure

(1)   Small round or ovoid structures

(2)   Fibrous CT capsule

(3)   CT divides into nodules (like spleen lobules) which contain lymph sinuses

(4)   Macrophages and lymphocytes hang out on reticular fibers that span the sinuses, filter the lymph

b.      Functions

(1)   Filtration and immune surveillance

(2)   When leukocytes are exposed to antigen they are activated and mount an immune response

c.      Locations

(1)   Lymph nodes located in groups as well as singly

(2)   Groups include inguinal, axillary, cervical

(3)   Nodules may occur in many tissues without being in a lymph node: tonsils, Peyer’s patches in intestinal submucosa, etc.

d.      Lymph Nodes and Illnesses

(1)   Lymphadenitis – inflammation of lymph nodes due to infection

(2)   Lymphangitis – spread of the infection to the lymph vessels

(3)   Edema – accumulation of tissue fluid due to inability of lymph vessels to return lymph to the circulation as fast as it filters out of circulation

a)     Elephantiasis – clogging of lymphatics by roundworms, results in swelling of arms, legs, or external genitals

b)     Congestive heart failure: systemic or pulmonary edema

(4)   Lymphoma – cancer of the lymph nodes (Hodgkin’s disease)

3.    Thymus

a.      Located along trachea from larynx to mediastinum

b.      Largest just after birth, degenerates with age

c.      Divided into lobules by CT

d.      T cell maturation: sorts out self-reactive T cells (which commit suicide) and those that recognize self antigens and don’t attack the body

e.      Secretes thymosin – stimulates T cell maturation

4.    Red Bone Marrow

a.      Structure

(1)   Network of reticular fibers

(2)   Reticular cells and hematopoietic stem cells

b.      Function

(1) Gives rise to all blood cells

c.      Location

(1)   Not present in shafts of long bones in adults

(2)   Present in flat and irregular bones – skull, sternum, ribs, clavicle, pelvis, vertebrae; also some in epiphysis of femur and humerus

d.      Bone Marrow Biopsy and Transplant

(1)   Biopsy at iliac crest, local anesthetic

(2)   Transplants: Leukemias and other blood disorders, some solid tumor after massive treatments, matching issues

 

II.                   Immunity

A.      Definition – the body’s ability to defend itself against infectious organisms, foreign cells, and cancer cells

 

B.      Nonspecific Defenses – work against everything

1.    Barriers

a.      Skin and mucous membrane

b.      Secretions: sweat and sebum contain lysozyme, IgA, and are slightly acidic

c.      Mucous elevator

d.      Stomach: HCL

e.      Normal flora inhibit colonization by other organisms

2.    Inflammatory Reaction

a.      Injury to tissue causes release of histamine from mast cells and activation of a number of chemicals that mediate inflammation, including bradykinin ® potentiates histamine effects and causes pain

b.      Histamine causes vasodilation and increases vascular permeability

c.      Neutrophils and macrophages are “called” to the site of injury by the chemicals released; phagocytize debris and bacteria, release chemicals that destroy invading cells (and innocent bystanders)

d.      Clotting may be activated to wall off the area

e.      Neutrophils eat up and die, make up pus

f.        Four cardinal signs of inflammation:

(1)   Heat

(2)   Swelling

(3)   Redness

(4)   Pain

3.    Protective Proteins

a.      Complement system – a number of plasma proteins activated by antibody binding to antigen and certain bacteria

(1)   The series of proteins is activated in sequential order in a cascade

(2)   Result in release of inflammatory chemicals and formation of MAC

b.      Interferon

 

C.     Specific Defenses – reactions against specific challenges

1.    Antigens – any thing that elicits an immune response

a.      Usually proteins because more structurally complex things are more antigenic

b.      Usually not a protein of your own body (except “self” antigens; HLA)

2.    Cells

a.      T cells

(1)   Mature in the thymus

(2)   Either directly attack other cells, or mediate the immune response

(3)   Clonal selection causes clonal expansion after antigen exposure

b.      B cells

(1)   Mature in the bone marrow

(2)   After stimulation with antigen turn into memory cells and plasma cells, make antibodies

(3)   Clonal selection

3.    Antibody-Mediated Immunity

a.      General structure

(1)   Variable regions – bind to specific antigens

(2)   Constant region

b.      Functions

(1)   Antigen inactivation (toxins)

(2)   Enhance phagocytosis (aggregation, agglutination)

(3)   Fix complement

c.      Types

(1)   IgG – main type in circulation

(2)   IgA - secretory

(3)   IgE – basophils and mast cell, allergic reactions

(4)   IgM – largest (pentamer), initial response

(5)   IgD – antigen receptor on B cells

4.    Cell-Mediated Immunity

a.      T cells interact with HLA (MHC) antigens

(1)   Present on somatic cells (class I) and APCs (class II)

(2)   APCs – macrophages and dendritic cells (Langerhans cells)

b.      Class I

(1)   Cytotoxic

(2)   Attack virus infected cells and cancer cells

c.      Class II

(1)   Helper

(2)   Stimulate B cells and other T cells

 

III.                  Immunotherapy

A.      Active immunity

1.    Naturally acquired

a.      Recovery from disease

2.    Artificially acquired

a. Immunization

 

B.      Passive immunity

1.      Naturally acquired

a.      Across placenta

b.      Mother’s milk

2.      Artificially acquired

a.      RhoGam

b.      Monoclonal antibodies

 

C.     Lymphokines (cytokines)

1.    Immunostimulatory proteins released by leukocytes (T cells, B cells, macrophages and dendritic cells)

2.    Stimulate WBC formation, maturation, and function

3.    Used as therapeutic agents especially against cancer

a.      Interferon (from T cells)

b.      Colony stimulating factors – promote maturation and mobilization of lymphocytes and macrophages

c.      Interleukins – keep cytotoxic T cells and B cells active longer

 

IV.               Immunological Side Effects and Illnesses

A.      Allergies

1.    IgE mediated

a.      Binds to basophils and mast cells, stimulates histamine release

b.      Histamine stimulates mucus production, bronchioconstriction, vasodilation, and increased capillary permeability

2.    Anaphylactic shock – BP drop due to hypovolemia

3.    Allergy shots – stimulate IgG to bind up antigen before IgE gets involved

 

B.      Tissue Rejection

1.    Transplantation issue

2.    Combated by matching and immunosuppression

 

C.     Autoimmune Diseases

1.    Loss of self-tolerance

2.    Exposure to an antigen that activates a T cell population and mimics a self antigen

a.      T cells then recognize certain self proteins as foreign

b.      Attack the body’s own cells

3.    Myasthenia gravis – Ach receptors blocked by antibodies

4.    Multiple sclerosis – myelin sheath attacked

5.    Systemic lupus erythematosus (SLE) – anti-nuclear antibodies, depositon in kidney, kidney failure

6.    Rheumatoid arthritis

a.      Destruction of normal tissue in joints

b.      Replaced with scar tissue

c.      Bones can heal, may fuse across the joint

7.    Type I diabetes

a.      Destruction of b-cells

8.    Rheumatic fever induced cardiomyopathy

a.      Molecular mimicry by streptococcus

b.      Antibodies cross react with heart tissue, damage muscle and valves

 

D.     Immune Deficiency

1.    SCID – Severe Combined Immunodeficiency

a.      Inherited

b.      Complete lack of immune systems

c.      Bone marrow transplant or live in a bubble

2.    AIDS

a.      HIV viruses

b.      Profile: Was initially identified in homosexual men,

c.      Infection of T4 cells

d.      AIDS = <200 T4 cells per cubic millimeter of blood

e.      Death due to opportunistic infections

f.        Treatments: drugs that interfere with replication

(1)   AZT

(2)   ddi

(3)   ddC

g.      Vaccine?? (it’ll be tough)

 

V.                 Effects of Aging

A.      Thymus Degeneration

1.    T cell numbers drop (but not due to thymic degeneration)

a.      Increase chances of cancer (debatable)

 

B.      B cell problems

1.    Clones not produced

2.    Antibodies not as effective

3.    Loss of self-tolerance

a. Autoimmunity