The result of an excessive or inadequate immune response is called an immunological disorder.

Hypersensitivity - Hypersensitivity is an "overreaction" of the immune system. There are four types:

-Type I: immediate hypersensitivity (also called anaphylaxis) results from a prior exposure to an
    antigen that evokes a hypersensitive response such as pollen, foods, and insect stings, these
    antigens are called allergens.

-Type II: cytotoxic hypersensitivity is elicited by antigens on cells that the immune system recognizes
    as foreign, for example the wrong blood type.

-Type III: immune complex hypersensitivity is elicited by soluble antigens in vaccines, on
    microorganisms, or on a person's own cells.

-Type IV: cell-mediated or delayed hypersensitivity is induced by exposure to foreign substances
    from the environment, infectious disease agents, and so on.

These reactions depend on which components of the immune system are involved, and how quickly the response occurs.

Autoimmune disorders are also a form of hypersensitivity; the body's immune system does not recognize its own cells or tissues as self and so attacks them.

Summary of the four types
 

IMMEDIATE (TYPE I) HYPERSENSITIVITY - This is also called anaphylactic hypersensitivity, and it is an immediate response to exposure to the allergen.

Mechanism of Immediate Hypersensitivity
    1. Sensitization through first exposure to allergen.
    2. Attachment of IgE to mast cells and basophils.
    3. Second exposure induces cross-linking of IgE causing degranulation (release of preformed
        mediators - primarily histamine but prostaglandins and leukotrienes also participate): capillary
        dilation, contraction of bronchial smooth muscle, increased mucus secretion, stimulation of nerve
        endings (pain, itching).
 
* Localized Anaphylaxis- This immune response occurs first at the site where the allergen enters the
    body.

* Generalized Anaphylaxis- When the response is more widespread and severe it is generalized
    anaphylaxis (think about bee stings!!!).

-In respiratory anaphyalxis the airways become constricted and filled with mucus secretions.

-In anaphylactic shock, blood vessels rapidly dilate and become more permeable, resulting in a
    drastic decrease in blood pressure.

Treatment must be rapid; adrenaline relaxes the smooth muscle of the respiratory passageways and constricting blood vessels.
 

Genetic Factors in Allergy
The numbers suggest there is a genetic component to allergy.

-One difference can be in the membranes, with allergic individuals permitting the passage of larger
    particles than those that are not.
-A second difference may be that phagocytic cells of allergic individuals are not as effective in engulfing
    antigens.

Treatment of Allergies
The only known treatment currently available is desensitization:

1. Inject denatured allergen which may prevent activation of IgE-secreting B cells.
2. Inject small amounts of allergen which causes the production of IgG (blocking antibodies) that would
    combine with the allergen before it has a chance to interact with the IgE on the mast cells.

Antihistamines act only on the histamine-mediated responses, leaving the more potent reaction mediators still active.
 

CYTOTOXIC (TYPE II) HYPERSENSITIVITY
-This type of hypersensitivity is an antigenic response that results in phagocytic action, killer cell activity,
    or complement-mediated lysis. The attachment of antigens to cells leads to these responses which also
    act on neighboring cells and tissues, causing an inflammatory response.
-This is also responsible for autoimmune diseases, transfusion reactions, and hemolytic disease of the
    newborn

Mechanisms of Cytotoxic Reactions
The mechanisms of cytotoxic reactions are not different from the normal immune response to foreign antigens; the difference is that they are large responses that cause, in a sense, secondary damage.

Examples of Cytotoxic Reactions
Transfusion Reactions: -Red blood cells have antigens on their surface that can elicit antibodies; either
    A or B, or both A and B.

-Transfusion of the wrong blood type into a sensitized person elicits the production of IgM
    antibodies.  The IgM can cause clumping because it can bind to several red blood cells at the same
    time (10 antigen binding sites). It also strongly activates complement, and the red blood cells lyse
    within the blood vessels.
- You must remember that blood group AB is known as the "universal recipient" and blood group O is
    known as the "universal donor"
- Hemolytic Disease of the Newborn:  -Besides A and B, a second antigen is present on red blood
    cells, called Rh. Rh negative mothers can be sensitized when giving birth to Rh positive children,
    and so exposure to a second Rh positive child will elicit production of IgG antibodies that can
    cross the placenta and cause a Type II reaction in the fetus; red blood cells are clumped, and
    complement is activated with destruction of the red blood cells. The spleen and liver are damaged
    in their efforts to eliminate the damaged cells.
- Remember, this can be prevented by injecting anti-Rh antibody soon asfter delivery of first baby. This
    will cause destruction of baby cells that gained entry into th mother and no immune response against
    the Rh will be generated.
 

IMMUNE COMPLEX (TYPE III) HYPERSENSITIVITY
Type III hypersensitivity results from formation of antigen-antibody complexes that are not
    appropriately removed from the body through phagocytosis.

- Reacting body components are soluble molecules in the circulation

Mechanism of Immune Complex Disorders
- The immune complexes formed between antigens and antibodies activate complement and are removed
    by phagocytosis. Some small complexes may persist by escaping elimination, and become deposited in
    organs, tissues or joints.
- If complement is activated there, causing the release of histamine and other mediators of allergic
    reactions, phagocytic action can result in tissue damage.

Examples of Immune Complex Disorders
Serum sickness occurred when people were given repeated doses of foreign serum; horse serum
    against diphtheria toxin was used to treat diphtheria as an antitoxin and so many other antigens
    were also present. The immune complexes would lodge in the kidneys, be deposited in joints and
    skin blood vessels.

The Arthus reaction is a local reaction at the point of introduction of an antigen to which individuals
    already have large quantities of antibodies so that large amounts of complex are quickly formed.
    The subsequent action of complement causes cell damage and platelet aggregation that may even
    lead to obstruction of blood vessels.
 

CELL-MEDIATED (TYPE IV) HYPERSENSITIVITY
This type of hypersensitivity is also called delayed hypersensitivity, because the reactions take more than 12 hours to develop. They are mediated by a type of T cell not discussed previously, called delayed hypersensitivity T cells. Antibodies are not involved.

Mechanism of Cell-Mediated Reactions
1. From a first exposure, antigens bound to antigen-presenting cells interact with T cells (CD8) that are
    now sensitized.
2. When the same antigen is presented during a second exposure, the sensitized T cells release
    chemical factors that include gamma-interferon and migration inhibiting factor (MIF). Phagocytosis is
    localized through the action of MIF.

Examples of Cell-Mediated Disorders
Contact dermatitis:
-This is caused by second exposures to substances that include poison ivy, rubber, and so on. These
    act as haptens; they become antigenic by binding to normal host proteins.

Tuberculin hypersensitivity:
-The agent here is an antigenic lipoprotein from the bacterium Mycobacterium tuberculosis. When
    tested subcutaneously for previous exposure using a purified protein derivative of the bacterium,
    the cell-mediated hypersensitivity response of positive individuals results in a raised red region on
    the skin.

Granulomatous hypersensitivity: (TB, leprosy, schistosomiasis)
-This usually occurs when phagocytes have ingested pathogens but failed to kill them. The delayed
    hypersensitivity T cells mediate a continuous reaction that attract cells to the site and leads to the
    formation of a granuloma.