Chapter 16

Disorders in Immunity

 Immunopathology

•         Overactivity:

–        Allergies, autoimmunity

•         Underactivity:

–        Immune function suppressed or destroyed

 Allergies

•         Sometimes human body responds to antigens other than pathogenic microorganisms –hypersensitivity – allergy

•         Antigens causing allergies are called allergens

–        Exogenous: Pollen, mold, dust mites, cat and dog antigens, insect venom, etc.

–        Endogenous: Self tissue (autoimmunities)

•         Allergies occur in persons who have been sensitized (previously exposed) to some allergen

Different types of allergic reactions

•         Type I anaphylactic reactions (IgE)

•         Type II antibody-mediated cell damage (IgG; IgM)

•         Type III    immune complex-mediated

•         Type IV   T-cell-mediated or delayed hypersensitivity

 Type I Allergic Reaction

•         Two levels of severity

–        Atopy – local allergy (hay fever, skin rash)

–        Anaphylaxis – systemic reaction (airway obstruction, sometimes fatal)

 Mechanism of Type I Allergy

•         Initial encounter with an allergen (sensitizing dose)

•         Allergen is carried with lymphatics to lymph nodes – B cells are activated and proliferate into plasma cells

•         IgE is produced – binds to the mast cells

–        Mast cells are located in the connective tissue throughout the body

•         No symptoms

•         During the subsequent contact with an allergen,  the allergen attaches to two adjacent antibody molecules already attached to the mast cell

•         This will trigger the mast cell to degranulate - release mediators –(histamine, serotonin, leukotrien…)

•         Symptoms in various organs

•         Chemical mediators target: Skin, upper respiratory tract, gastrointestinal tract, and conjuctiva

•         Histamine is the fastest acting mediator

•         Effects of histamine:

–        Constrict smooth muscle of bronchi – labored breathing

–        Dilates blood vessels – hypotension, tachycardia, shock

–        Increases the permeability of blood vessels (swelling and redness), and mucus secretion (runny nose)

 Diseases Associated with Type I Hypersensitivity

•         Hay fever – allergic rhinitis

–        Reaction to inhaled pollen, mold spores

–        Symptoms: nasal congestion, sneezing, coughing

•         Eczema – atopic dermatitis

–        Sensitization occurs through ingestion, inhalation, skin contact

–        Symptoms: thickened skin, lesion 

Other Allergies

Food Allergy

–        Mode of entry is intestinal

–        Affected: skin, respiratory tract, gastrointestinal system

–        Symptoms: eczema, rhinitis, asthma, anaphylaxis

–        Food allergens: peanuts, fish, milk, shellfish…

 Drug Allergy

–        Some drugs can cause allergic reactions in some individuals (5-10% of patients)

–        The drug allergens: antibiotics (penicillin) sulfa drugs, aspirin

 Anaphylactic Reactions can be:

•         Systemic (antigen is injected)

–         Dilation of peripheral blood vessels – drop of blood pressure – shock

–        Can be fatal within a few minutes

–        Allergy to penicillin

•         Localized reaction (antigen is inhaled or ingested)

–        Itchy, watery eyes, sneezing, coughing.

–        Allergy to pollen, dust mites, mold spores, some food.

 Diagnosis of Allergy

•         Diagnostic tests include:

•         Measuring the blood levels of tryptase (an enzyme released by mast cells)

•         Differential blood cell count (increased levels of basophils and eosinophils – indicate allergy)

•         Measuring the quantity of IgE immunoglobulin in blood

•         Skin test – skin is injected with the pure allergen

Dealing with anaphylactic reaction

•         Avoid contact with sensitizing agent

•         Desensitization therapy (series of increasing doses)

•         Carry at  all times Epinephrine (adrenalin) - reverses the constriction of the airways

•         Treatment:

–        Drugs that block the action of lymphocytes

–        Corticosteroids – prevent synthesis of IgE

–        Antihistamines - Bind to histamine receptors on target organs

 Desensitization

How does it work?

•         The allergen is injected

•         This causes IgG antibodies to be produced (instead of IgE)

•         They bind to allergens

•         Allergens is removed before they react with IgE

Type II Hypersensitivity

•         Involves complement assisted destruction of cells

•         Includes:

–        Transfusion reactions

–        Some types of autoimmunity

 Blood Groups

•         There are four blood types: A, B, AB, O based on the antigens present on the surface of the red blood cells

•         Blood contains antibodies against “non-self” blood type

•         Example: Type A contains antibody against type B

Concerns in Transfusion

•         Which transfusion is safe?

•         Red blood cells of the donor should not be agglutinated with antibodies of the recipient’s blood

•         The perfect match should be used (A     A)

•         Exceptionally

–        O can be used as universal donor

–        AB type is universal recipient

•         Transfusion of the wrong blood type results in destruction of red blood cells – systemic shock and failure of kidneys

 The Rh Factor

•         Rh factor is another antigen found on red blood cells

•         Present in 85% and absent in 15% of humans

•         Blood typing contains information on presence/absence of Rh factor (A⁺, B^-)

 Rh Incompatibility

•         Hypersensitivity can occur when Rh- mother is sensitized with Rh+ red blood cells of her unborn baby

•         In the case of 2^nd pregnancy this can cause hemolysis of red blood cells of the newborn – hemolytic disease

•         Can be prevented by passive immunization of a mother - antibodies against Rh factor injected right after delivery

Type III Hypersensitivity

•         A soluble antigen reacts with antibody (not with the cells as in type II hypersensitivity)

•         Large quantities of Allergen-Antibodies complex is formed

•         This is deposited on basement membrane of epithelial tissue (kidney, lungs, joints, skin)

•         In response – neutrophils release lysozyme that digest the tissue – destructive inflammatory condition

•         Causes severe damage of organs involved

 Type IV Hypersensitivity

•         Also known as delayed hypersensitivity (one to several days following the 2^nd contact)

•         Involves T-cells

•         Include

–        Delayed allergic reactions to infectious agent

–        Contact dermatitis

–        Graft rejection

Infectious Allergy

•         Tuberculin reaction – diagnostic technique for detection of tuberculosis

•         Tuberculin (extract of Mycobacterium tuberculosis) is injected intradermally 

•         A person sensitized to tuberculosis will respond with a raised red bump

 Autoimmune diseases

•         Response of immune system against one’s own organs – involves autoantibodies and T cells

•         Can target several major organs (systemic) or only one organ

•         80 recognized autoimmune diseases

 Some autoimmune diseases

•         Rheumatoid arthritis – IgM, IgG and complement are deposited in the joints

•         Damage to the cartilage in the joints - loss of functioning and mobility

 Lupus

•         One of the most sever autoimmune diseases

•         Production of antibodies against different organs (kidneys, bone marrow, skin, nervous system, joints…)

•         The etiology is unknown

–        Role of hormones – 90% of cases in women

–        Viral infection not excluded

 Multiple sclerosis

•         Neurological disease

•         T cells and macrophages attack myelin sheath of nerves

•         Progression slow

•         The most severe symptoms - paralysis

•         Etiology – may involve an infective agent

 Immunodeficiency Diseases

Components of the immune response are absent

•         Can be caused

–        By inherited abnormalities

•         Congenital absence of thymus (DiGeorge Syndrome)

–        Lack of B and T-cell lines

•         Lack of antibody production

–        Infections (AIDS)

–        Chemotherapy

–        Radiation

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