6 HYPERSENSITIVITY REACTIONS Flashcards
TYPE I Hypersensitivity reaction, aka:
Anaphylactic type, Allergy
What is there a release of in Type 1?
Vasoactive amines and other mediators derived from the mast cells or basophils and affecting vascular permeability and smooth muscles in various organs
What is the mechanism of the “First Encounter with allergen (antigen or allergy)” in Type 1 reaction?
Most commonly via INHALATION (ex. Pollen) > Blood
What happens after the first encounter with allergen in Type 1 reaction?
There is an immune response (IgE) immunoglobulins (antibodies) > bind to receptors on mast cells, which contain granules filled with histamine
Is there a physiological reaction with the first encounter in Type 1 reaction?
NO, no physiological reaction
What does an “Allergen” cause activation of?
CD4+ T-cells (TH 2 type) > secretion of cytokines IL-4 and IL-5 > IgE production and recruitment of eosinophils
What happens with a “Second Encounter” during a Type 1 reaction?
ANTIBODIES PRODUCED from first encounter, bind to the antigen (allergen) forming the *Antigen-antibody complex
What happens to mast cells during a second encounter with allergen in Type 1 reaction?
Mast cells undergo degranulation > HISTAMINE released
What does the Second encounter with allergen produce during a Type 1 reaction?
Eicosanoids, Leukotriens, and PGD2 are also produced (vasodilation and bronchospastic reactions)
What type of reaction occurs during a Second Encounter with Allergen (Type 1 Reaction)?
Pathophysiological Reaction (due to factors released)
What are the functions of Histamine?
- Vasodilation
- Increased permeability of Blood Vessels
- Bronchospasm
- Increased mucus production (submucosal glands) very important in the bronchioles
What are the 2 types of clinical reactions?
1) Systemic Anaphylaxis
2) Local Reaction
What is Systemic Anaphylaxis due to?
Parental Administration (injection/appearance) of allergen
What does systemic anaphylaxis result in?
Itching
- Hives (aka Urticaria) > changes in the skin
What are hives aka?
Urticaria
What happens to breathing in Systemic Anaphylaxis?
- Bronchospasm: Due to factors released in bronchospastic reactions
What type of Reaction will you see Laryngeal Edema?
Type 1 Systemic Anaphylaxis
What is laryngeal edema?
Can develop within a minute after contact with allergen. Causes swelling of larynx leading to closing of the laryngeal opening > Strangulation > Difficulty Breathing > Death (Immediate treatment: puncture above episternal notch)
What type of reaction would you see abdominal cramps, diarrhea, and vomiting?
Type 1 Systemic Anaphylaxis
What type of Reaction would you see Vascular (anaphylactic) shock?
Type 1 Anaphylactic Type, Allergy
Systemic Anaphylaxis
What is Vascular (anaphylactic) shock?
Sudden systemic vasodilation because blood flows (due to gravity) to where there is more concentration of vessels > no blood to brain causes patient to pass out > DEATH.
- Onset may be immediate or not
What is the #1 cause of death in Type 1 reaction?
Vascular Anaphylactic Shock (Systemic Anaphylaxis)
What does a local reaction depend on?
How allergen is contacted
What symptoms will you see with Local Reaction Type 1 Anaphylactic Type, Allergy
Urticaria (via skin contact) - Same as systemic anaphylaxis = Itch, pain, and swelling (Without inflammatory response)
What Type Hypersensitivity will you see Hay fever?
Type 1 Anaphylactic Type, Allergy
LOCAL
Hay fever aka
Acute allergic conjunctivitis or acute rhinitis (via inhalation)
What type of reaction would you see Atopic aka Extrinsic Bronchial Asthma?
Type 1 Anaphylactic allergy (LOCAL)
What is Atopic aka Extrinsic Bronchial Asthma?
Pathogenic reaction in Type 1 local allergic reaction. Important the familiar predisposition for this. Serious, 2 different pathological mechanisms, only 1 of which is associated with allergy
What are the 2 types of Atopic aka Extrinsic Bronchial Asthma
Extrinsic Bronchial Asthma
Intrinsic Bronchial Asthma
What are the key features of Extrinsic Bronchial Asthma?
- Via Type I allergic Reaction
- Common in KIDS, familial predisposition to localized type I hypersensitivity reactions
- Genetic predisposition
What are the key features of Intrinsic Bronchial Asthma? **
- NOT ASSOCIATED WITH TYPE I HYPERSENSITIVITY **
- AUTOIMMUNE
What minor symptoms will you see with LOCAL REACTION Type 1 Hypersensitivity?
Diarrhea, vomiting, contact allergic dermatitis - blistering
Who has predispositions to Type 1 Anaphylactic Reactions?
More likely in children who are not fed breast milk for at least 3 months
- Family predisposition
Type II Reaction aka
Anti body Dependent (dependent on the presence of Ab)
What is the definition of Type II - Antibody Dependent (dependent on the presence of Ab) ?
Mediated by antibodies directed against target antigens on the surface of cells or other tissue components. Complement system work with humoral activity not cell - mediated
What are the 3 subtypes of Type II Antibody Dependent (dependent on presence of Ab)?
1) Complement Dependent Reactions
2) Antibody-Dependent Cell-Mediated Cytotoxicity
3) Antibody-Mediated Cellular Dysfunction
Complement Dependent Reactions are seen in ______
Glomerulonephritis
What disease would you see Complement Dependent Reactions?
Autoimmune Disease - antibodies for target (self) cells
How does the Complement dependent reaction activate?
Complement activation via Classical Pathway (DIRECT LYSIS)
What is the “Classical Pathway”?
DIRECT LYSIS
Antigen-antibody complex formed (Ab binds to the Ab receptor at the allergen surface) > complement activation (via classical pathway) > MAC (Membrane Attack Complex = makes holes in the target antigen cell) > Releases enzymes and target cell is destroyed
Complement activation via Alternative Pathway =
OPSONIZATION
What is the Alternative Pathway?
After antigen-antibody complex formation > Via C3b (aka opsonin) > complex binds to target tissue making it more easily phagocytized by phagocytic cells
What are the Disorders associated with Alternative Pathway OPSONIZATION?
- Glomerular Pathology
- Hemotransfusin Reactions
- Erythroblastosis Fetalis
What happens during Glomerular Pathology?
Body starts producing Ab against Ag in the basement membrane, this forms the Ab-Ag complex and complement activation
> Disruption of BM, Hydrolytic enzymes and activated oxygen causes attraction of PMN cells (Phagocytosis)
What is Frustrated Phagocytosis associated with?
Glomerular Pathology
What is Frustrated Phagocytosis?
Occurs when the phagocytic cells cannot engulf the large sized antigen
What is Hemotransfusin Reactions?
Associated with blood transfusions between a donor and a recipient where the blood types are not matched (blood types: O, A, B, AB)
> Leads to HEMOLYSIS
What is Erythroblastosis Fetalis?
Associated with the other 2 antigens found on RBC’s Rh factor. 85% of people have Rh antigen on their RBC’s > Rh (+) individuals. The other 15% are Rh (-)
What happens during the First Exposure: First Pregnancy?
Rh (+) dad + a Rh (-) mom > during delivery blood is mixed through the placenta. Mom is exposed to Rh (+) blood type, no pathological reaction occurs.
Mom produces anti-Rh antibodies after the first delivery
Second Pregnancy of the Rhesus Conflict:
With a second Rh (+) fetus > mother plasma goes to the blood circulation of the fetus through the placenta:
What can the Second Pregnancy of the Rhesus Conflict cause?
- RBC lysis & clumping (hemolysis) > Jaundice and Death
- In fetus anti-Rh antibodies into fetus
- Transfusion needed
What are examples of complement - dependent reactions?
- Autoimmune Hemolyitic Anemia
- Certain Drug Reactions
- Pemphigus Vulgaris
What is Autoimmune Hemolytic Anemia?
Agranulocytosis and thrombocytopenia Ex. Hemosiderosis
What are Certain drug reactions associated with Examples of Complement Dependent Reactions?
Can lead to production of anti-neutrophil antibodies > Decreased Neutrophils > DEATH
What is Pemphigus Vulgaris?
Antibodies against Desmosomal proteins > Ab bind to the desmosomal proteins > Interference with complement - dependent reactions > Causes blisters
What is the function of Antibody-Dependent Cell-Mediated Cytotoxicity?
Monocytes/Macrophages, neutrophils, eosinophils, and natural killer cells (NK) cells are known as non-T and non-B lymphocytes > Don’t have specific receptors
- These cells have receptors for Fc fragment of IgE (IgG & IgM, rarely IgE)
What is the mechanism of Antibody-Dependent Cell-Mediated Cytotoxicity ?
Antigen-Antibody complex formed (F AB fragment of IgE binds to target cell)
- Non T/ non B cells bind to the free Fc portion > cell death WITHOUT PHAGOCYTOSIS OR COMPLEMENT SYSTEM ACTIVATION**
Why is the mechanism in Antibody-Dependent Cell-Mediated Cytotoxicity important?
Important in parasites, virus-infected cells, tumor cells (antiviral and anti-tumerous activity). But this is not the primary action against viruses because it involves time due to Ab production
What is distinct about Antibody Mediated Cellular Dysfunction?
No phagocytosis nor complement activation
What are the diseases associated with Antibody Mediated Cellular Dysfunction?
1) Myasthenia Gravis
2) Hashimoto’s Thyroiditis
3) Grave’s Disease
4) Pernicious Anemia
What is Myasthenia Gravis characterized as?
Progressive Muscle Weakness. As the day continues muscle becomes very fatigued.
What is the normal function of Ach?
Motor end plate: Neuron Synaptic terminal contains vesicles containing Ach, when impulse is transmitted, degranulation occurs, releasing Ach into synaptic cleft. Ach binds to its receptor on the muscle to induce contraction
What happens in Myasthenia Gravis?
Antibodies against Ach receptors on the muscle prevent muscle contraction (blocking of receptors)
What are the symptoms of Myasthenia Gravis?
Symptoms of muscle weakness progresses through the day especially in muscles most used: Eye lids, pharyngeal, laryngeal muscles…accumulation of antibodies through the day > increasing weakness, leads to death if untreated as it will affect the diaphragm and pharyngeal muscles > CANT BREATHE
What is Hashimoto’s Thyroiditis?
Most common cause of Hypothyroidism in USA (Where iodine levels in the diet are normal - non deficient areas)
What is the 1st described autoimmune disease, 1912 by Hashimoto
Hashimoto’s Thyroiditis
What is the mechanism of The thyroid/TRH?
Hypothalamus releases TRH (thyroid releasing
hormone) —> simulates the anterior pituitary to release
TSH (thyroid stimulating hormone) —> stimulates the
thyroid to release thyroid hormones (T3, T4) —> increased
thyroid hormones in blood cases negative feedback onto
anterior pituitary and hypothalamus (normal regulation)
What happens in Hashimoto’s Thyroiditis?
there is an overproduction of auto-
antibodies against TSH receptors on thyroid gland —>
antibodies bind to the receptors, preventing TSH from
binding to thyroid gland (blocking antibody) Lack of
stimulation (TSH)—> the thyroid gland atrophies->
hypothyroidism
What is an autoimmune diseases more common in females 8:1?
Graves Disease
What is the Mechanism of Grave’s Disease?
same as Hashiomoto´s but Ab do not block the
TSH receptors. Instead, overproduction of auto-antibodies
bind and stimulate TSH receptors (mimic TSH) —>
overproduction of thyroid hormones —> hyperthyroidism
What is “Bulging eyes” associated with Grave’s Disease?
Exopthalmus (bulging eyes)
What is Pernicious Anemia?
Autonomic binding antibody against the intrinsic factor receptors
What is Type III Hypersensitivity reaction?
Immune Complex Mediated Type: Binding of Ab to a fixed tissue (Type I and II binding is to the free target)
How is Type III - Immune Complex Mediated Type actually mediated?
Hypersensitivity is Mediated by deposition of antigen-antibody (immune) complexes, followed by complement activation and accumulation of polymorphonuclear leukocytes.
What is the major characteristic of Type III - Immune Complex Mediated Type?
Antibody/Antigen are usually NOT fixed in the tissue, they are in the blood circulation
What is Phase I of Type III - Immune Complex Mediated Type?
Immune Complex formation
- Antigen is present in blood
- Production of antibodies
- Antigen and antibody bind to form immune complex
What is Phase II of Type III - Immune Complex Mediated Type?
Immune Complex DEPOSITION
- Immune complex attaches to the vessel wall
