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Hypersensitivity

Any immune response against a foreign antigen exaggerated beyond the norm

Four Types of Hypersensitivity

1. Type I (immediate)
2. Type II (cytotoxic)
3. Type III (immune complex-mediated)
4. Type IV (delayed or cell-mediated)

Type I (Immediate) Hypersensitivity

1. Localized or Systemic reaction that results IMMEDIAYELY from the release of inflammatory molecules in response to antigen.
2. Commonly called allergy; antigens that stimulate it are called allergens
3. Degranulation occurs after cells sensitization of mast cells, basophils and eosinophils

Type I (Immediate) Hypersensitivity - CON'T

4. Site of reaction depends on portal of entry
5. inhaled allergens > asthma
6. Food allergens > diarrhea & other gastrointestinal problems
7. Dermatitis > hives

Mechanisms of a type I hypersensitivity reaction - ESSAY

1. APC PRESENTS ANTIGEN
2. B CELLS ACTIVATED
3. ANTIBODIES PRODUCED
4. ANTIBODIES SENSITIZED
5. HISTAMINES RELEASED

Some common allergens

1. Fungal spore
2. Ragweed
3. Dust mite

Type I Clinical signs of local/acute allergic reactions

Asthma, hives, inflammation, redness

TYPE I Clinical signs of SYSTEMIC allergic reactions

1. Many mast cells may degranulate at once, releasing large amounts of histamine & inflammatory mediators
2. Acute anaphylaxis, anaphylactic shock, suffocation
3. Must be treated with epinephrine

TYPE 1 Diagnosis based on

detection of high levels of IgE against specific allergen

Prevention of TYPE 1 Hypersensitivity

1. Identification & avoidance of allergens
2. Food allergens identified using an elimination diet
3. Immunotherapy ("allergy shots") can help prevent allergic reactions

Treatment of TYPE 1 Hypersensitivity

1. Administer drugs that counteract inflammatory mediators.
2. Antihistamines neutralize histamine
3. Treat asthma with a corticosteroid and a bronchodilator
4. Epinephrine neutralizes many mechanisms of anaphylaxis.
- IT Relaxes smooth muscle
- IT Reduces vascular permeability
- Used in emergency treatment of severe asthma & anaphylactic shock

Type II (Cytotoxic) Hypersensitivity

1. Results when cells are destroyed by an immune response of complement and antibodies
2. A component of many autoimmune diseases

Type II CYTOTOXIC 2 examples

1. Destruction of blood cells following an incompatible blood transfusion.
>CAN result if an individual receives different blood type
2. Development of hemolytic disease in newborns
> Rh- versus Rh+

Events leading to hemolysis

1. TRANSFUSION
2. AGGLUTINATION & COMPLEMENT BINDING
3. HEMOLYSIS

TRUE OR FALSE?
If recipient DOES HAVE preexisting antibodies to foreign blood group, transfused blood cells will work at first until immune system mounts response & kills them.

FALSE!
DOESN'T HAVE PRE-EXISTING

TRUE OR FALSE
If recipient HAS preexisting antibodies to foreign blood group, the transfused blood cells will immediately be destroyed.

TRUE!

The Rh system and hemolytic disease of the newborn

1. Rh antigen
> Common to RBC'S of humans & rhesus monkeys
2. If Rh- woman is carrying an Rh+ fetus, the fetus may be at risk for hemolytic disease
3. To prevent hemolytic disease of newborn, administer ANTI-Rh immunoglobulin

DRUG -induced TYPE II Cytotoxic reactions - ESSAY

1. Drug molecules bind to platelets forming Drug-Platelet Complex.
2. Complexes are antigenic, triggering humoral immune response.
3. Antibodies bind to drug molecules; complement binds to antibodies.
4. Membrane attack complexes of complement, lyse platelet.

Type III (Immune Complex-Mediated) Hypersensitivity

1. Caused by formation of immune complexes
2. Can cause localized reactions
> Hypersensitivity pneumonitis
> Glomerulonephritis
3. Can cause systemic reactions
> Systemic lupus erythematosus
> Rhematoid arthritis

The mechanism of Type III Hypersensitivity - ESSAY

1. Antigen combine w/antib forming antigen-antibody complexes.
2. Most complexes removed by phagocytes, but some lodge in walls of blood vessels.
3. Complexes activate complement.
4. Antigen-antibody complexes & activated complement attract & activate neutrophils, releasing inflammatory chemicals.
5. Inflammatory chemicals damage underlying blood vessel wall.

Type III LOCALIZED Reaction- Hypersensitivity pneumonitis

1. Antigens in lungs stimulates production of antibodies
2. Subsequent inhalation of the same antigen stimulates the formation of immune complexes
3. Activates complement
4. # 1 ACQUIRED

Type III LOCALIZED Reaction -
Glomerulonephritis (Con't)

1. Immune complexes circulating in the bloodstream are deposited on the walls of glomeruli
2. Damage to the glomerular cells impedes blood filtration
3. Kidney failure and ultimately death result

Type III SYSTEMIC Reaction - Rheumatoid arthritis

1. Immune complexes deposited in the joint
> Results in release of inflammatory chemicals
> The joints begin to break down & become distorted
2. Treated with anti-inflammatory drugs

Type III SYSTEMIC reaction - Systemic lupus erythematosus (Con't)

1. An autoimmune disease
2. Autoantibodies against DNA result in immune complex formation.
3. Many other autoantibodies can also occur
> Against RBC'S, platelets, lymphocytes, muscle cells
4. Trigger unknown
5. Treatment - immunosuppressive drugs reduces autoantibody formation
6. Treatment - corticosteroids reduces inflammation

Type IV (Delayed or Cell-Mediated) Hypersensitivity

1. Inflammation 12 to 24 h AFTER contact with certain antigens
2. Results from the actions of antigen, antigen-presenting cells, and T cells
3. Delay reflects the time it takes for macrophages & T cells to migrate to and proliferate at site of antigen

Example 1 of Type IV - Tuberculin response

1. Skin exposed to tuberculosis or tuberculosis vaccine reacts an injection of tuberculin beneath skin
2. Used to diagnose contact with antigens of M. tuberculosis
> Red hard swelling develops in individuals previously infected or immunized

Example 2 of Type IV - Allergic contact dermatitis

1. Cell-mediated immune response resulting in an intensely irritating skin rash
2. Triggered by chemically modified skin proteins the body regards as foreign
3. Severe cases acellular, fluid-filled blisters develop
4. Haptens include the oil of poision ivy, formaldehyde, cosmetics, & chemicals used to produce latex
5. Can be treated with corticosteroids

Example 3 of Type IV - Graft rejection

1. Rejection of tissues or organs that's been transplanted
2. Grafts perceived as foreign by a recipient undergo rejection
3. Normal immune response against foreign MHC proteins present on graft cells
4. Likelihood of rejection depends on degree to which graft is foreign to recipient

Type IV - Autograft

Self

Type IV - Isograft

1.Twin brother
2. Genetically identifical sibling or clone

Type IV - Allograft

1. Genetically different member of same species

Type IV - Xenograft

Most intense therapy

An Rh- mother has an Rh- baby. What is the risk of her next baby developing hemolytic disease of the newborn?
1. 50% chance
2. 100% chance
3. 85% chance
4. 0% chance

0% chance

Patients with which of the following types of grafts would require the most intensive therapy with immunosuppressive drugs?
1. autograft
2. xenograft
3. allograft
4. isograft

Xenograft

Type IV - Graft-versus-host disease

1. Donated bone marrow cells regard patient's cells as foreign
2. Donor and recipient differ in MCH I and II molecules
> Grafted T cells attack the recipient's tissues
> Grafted T cells attack the host's antigen-presenting cells
3. Immunosuppressive drugs can stop graft-versus-host disease

TYPE IV - Donor-recipient matching and tissue typing

1. MHC compatibility between donor and recipient difficult due to a high degree of variability
> The more closely the donor and recipient are related, the smaller the difference in their MHC

Autoimmune Diseases

More common in men and elderly

Autoimmune Hypothetical Causes

1. Estrogen may stimulate destruction of tissue by cytotoxic T cells
2. Some maternal cells may cross the placenta, colonize the fetus, and trigger autoimmune disease later in life
3. Environmental factors such as viral infections
4. Genetic factors such as certain MHC genes
5. T cells may encounter self-antigens that are normally "hidden"
6. Microorganisms may trigger autoimmunity due to molecular mimicry
7. Failure of the normal control mechanisms of the immune system
6. May result when an individual begins to make autoantibodies or cytotoxic T cells against normal body components

Autoimmune Diseases - Hypothetical Causes
May be an ESSAY - 4 of the 6

1. Environmental factors such as viral infections
2. Genetic factors such as certain MHC genes
3. T cells may encounter self-antigens that are normally "hidden"
4. Estrogen may stimulate destruction of tissue by cytotoxic T cells

Examples of Autoimmune Diseases - 2 Major categories

1. Systemic autoimmune diseases
2. Single-organ autoimmune diseases

Single-organ autoimmune diseases

1. Autoimmunity affecting blood cells
> Autoimmune hemolytic anemia
2. Autoimmunity affecting endocrine organs
> Type I diabetes mellitus
> Graves' disease
3. Autoimmunity affecting nervous tissue
> Multiple sclerosis
4. Autoimmunity affecting connective tissue
> Rheumatoid arthritis

Conditions resulting from defective immune mechanisms - Two general types

1. Primary
2. Acquired

Primary - BORN WITH

1. Result from some genetic or developmental defect
2. Develop in infants and young children

Acquired - NOT BORN WITH

1. Develop as a direct consequence of some other recognized cause
2. Develop in later life

Primary Immunodeficiency Diseases

1. Many inherited defects in all the body's lines of defenses
> Chronic granulomatous disease
> Severe combined immunodeficiency disease (SCID)
> DiGeorge syndrome
> Bruton-type agammaglobulinemia

Acquired Immunodeficiency Diseases -
Result from a number of causes

1. Severe stress
> Suppression of cell-mediated immunity results from an excess production of corticosteroids
2. Malnutrition and environmental factors
> Inhibit production of B cells and T cells
3. Acquired immunodeficiency syndrome (AIDS)
> Opportunistic infections, low CD4 cells, presence of HIV

Which of the following allergic reactions is the result of type IV (delayed) hypersensitivity?
1. skin irritation after wearing wool
2. sensitivity to pet dander
3. breathing difficulties after exposure to mold spores
4. runny nose triggered by pollen
5. dermatitis in response to latex gloves

5. dermatitis in response to latex gloves

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