Immunologic Disorders

Components of the Immune System:

• Lymph, bone marrow, thymus, spleen, leukocytes, antibodies, complement, tonsils and adenoids are among the major components of the immune system.

Antibodies-1:

• IgG is the most abundant antibody in blood.  Only antibody to cross the placenta.


• IgA is the second most abundant antibody in blood. Is the main antibody found in bodily secretions: tears, saliva, mucous, respiratory, intestinal and others.


• IgM third most abundant antibody in the blood and the largest.

Cytokines:

• Interleukins are modifiers of a body�s immune response and modulate inflammation.  They are produced by cells such as lymphocytes, macrophages and monocytes. 


• Growth factors are proteins that are able to stimulate cellular proliferation and differentiation.  They typically act as signaling molecules between cells promoting cell differentiation and maturation. 


• Interferons are a group of proteins which inhibit viral replication in the host�s body.



Hypersensitivity � Type 1:  (Also known as Immediate Hypersensitivity)

• An allergic response due to re-exposure to a specific antigen.


• Is an inflammatory response e.g. asthma, rhinitis.


• Exposure can be a result: ingestion, inhalation, injections or direct contact.


• Mediated by IgE antibodies.


• Results in an immediate release of histamine, tryptase, arachidonate and derivatives by basophils and mast cells.



Hypersensitivity � Type 2: (Also known as Cytotoxic Hypersensitivity)

• Antibody mediated generally by IgG and to a lesser extent IgM.


• Process typically involves K-cells rather than mast cells.


• May involve complement that binds to cell-bound antibodies.


• Antibodies react with �self� antigens.


• Tissue damage may result.


• Antibodies bind to antigens forming complexes that activate the complement for eliminating cells presenting foreign antigens.


• Acute inflammation created at the site were Ag-Ab complexes causing cell lysis and death.


• Example is Erythroblastosis Fetalis the mother produces antibodies that attack the red blood cells of the fetus.  This can occur when the mother and baby have different blood types.



Hypersensitivity � Type 3: (Also known as Immune complex Hypersensitivity)

• Circulating antibodies react with free antigen.


• The complexes can be deposited on tissue which may trigger complement reaction resulting in tissue damage. 


• Aggregations of antigens and IgG and IgM form in the blood.


• The reaction can take hours to days to develop.


• Systemic Lupus Erythematosus is an example of this.  Antinuclear antibodies generate circulating immune complexes that activate complement.  Results in systemic inflammation of body tissues. 



Hypersensitivity � Type 4: (Also known as Delayed Hypersensitivity)

• Cell mediated immune response.


• CD8 cytotoxic T cells and CD4 helper T cells are key molecules involved.


• Antigen presenting cell are macrophages and they release Interleukin 1 stimulating CD4 cell proliferation.


• Activated CD8 cells and macrophages destroy target cells.


• Memory TH1 cells release cytokines that recruit and activate macrophages.


• Examples of this is contact dermatitis i.e. Poison Ivy.



Immunodeficiency Disorders - 1

• Immunodeficiency disorders are a malfunction of the immune system that result in the development and frequent reoccurrence of disease that are also more severe and longer lasting then typical.


• One or more components is defective or missing from the immune system.


• Immunodeficiency disorders can be inherited.


• Temporary immune deficiencies can develop as a function of disease.



Immunodeficiency Disorders - 2

• Depressed immune response due to smoking, stress, surgery transfusions etc.


• Inherited poorly functioning immune system.


• B-cell system not functioning correctly so unable to make antibodies.



Immunodeficiency Disorders - 3

• Thymus missing, small or defective, lacking T-cells.


• Severe Combined Immunodeficiency Disease: birth defect of several immune system organs or defenses.



Autoimmune Diseases: 

• The immune system looses the ability to discriminate between self and other. 


• T-cells and antibodies (called auto-antibodies) are made and directed against �self� cells.  Rheumatoid factor is an auto-antibody. 


• Causes of auto immune diseases include: heredity, infections, certain drugs, sunlight and hormones.


• Type 1 diabetes is caused by the immune system attacking the pancreas cell. 


• AIDS:  The HIV virus attacks and destroys T-cells.  Can also be a latent infection.


• Rheumatoid arthritis:  The body does not distinguish correctly between self and non-self.  The body produces an antibody known as Rheumatoid Factor which is directed against the body�s own immune system.



Definitions:

• Hypersensitivity:  an exaggerated immune response to a foreign agent.


• Inflammation: the first response of the immune system it involves leukocytes entering a site of injury or infection.


• Anaphylaxis:  is a rapid and severe allergic response.


• Auto-immune disease: the failure of the immune system to recognize �self� from other cells.  This results in an immune response against its own cells and tissues.


• Asthma:  is a disease of the respiratory system often resulting from an immune response resulting in inflammation.


• Rheumatoid arthritis is a chronic inflammatory autoimmune disease in which the joints are attacked.


• Mast cells:  contain histamine and heparin and are involve in allergy and anaphylaxis.  They are similar to basophils and granulocytes.


• Cytokines:  peptides and proteins that are used as cell to cell signals. 


• Macrophages