Hypersensitivity Flashcards
what is hypersensitivity?
over-reactions to foreign agents: benign or harmful
what is Type I hypersensitivity and what does it cause?
- immediate hypersensitive mediated by IgE, mast cells and eosinophils
- atopy: allergic reaction due to inhaling allergens
- anaphylaxis: system reaction
what is the mechanism of Type I hypersensitivity?
triggered when allergens (pollen, dust, foods etc) bind to IgE on the surface of mast cells and eosinophils that leads to the release of histamines and inflammatory mediators
what are examples of Type I hypersenstivity?
- respiratory tract allergies: hay fever, asthma
- skin reactions: urticaria (hives from insect bites)
- gastrointestinal tract allergies: vomiting, diarrhea
- anaphylaxis
what are the 4 phases of Type I hypersensitivity?
- sensitization phase
- activation phase
- immediate effector phase (mast cells)
- late effector phase (eosinophils)
what happens during the Sensitization Phase of Type I hypersensitivity?
- the allergen is captured by APCs and presented to naive T helper cells
- naive T helper cell differentiate into Th2 cells and becomes active
- Th2 cells release IL-4 which activates B cells
- B cells begin producing large amounts of IgE
- generation of memory responses
what happens during the Activation Phase of Type I hypersensitivity?
- IgE antibodies bind to high affinity (FcεRI) receptors on mast cells and basophils
- re-exposure to the allergen
- cross-linking of IgE: at least two IgE molecules must bind to the allergens simultaneously to become active
- basophils and mast cells are now triggered to begin the process of degranulation
what happens during the Immediate Effector Phase of Type I hypersensitivity?
Mast cells and basophils are activating by
- Calcium influx occurs after signaling pathways are activated inside the mast cell
- A drop in cAMP enhances mast cell degranulation and Increased cGMP supports mast cell activation
- Mast cell activation leads to the activation of enzymes called phospholipases which metabolize arachidonic acid into prostaglandins and leukotrienes
- tyrosine kinases are activated which leads to cytokine production and chemotactic factors that attract neutrophils
- degranulation of the mast calls releases histamine which increases the infiltration of eosinophils
what are the main mediators released, what are their functions and what clinical syndromes can they produce?
- Prostaglandins: vasodilation
- Cytokines: inflammation
- Leukotrienes: smooth muscle cells contraction
- Proteases: tissue damage
- vasoactive amines: vascular dilation, smooth muscle contraction
- modulate adaptive immunity
- allergic rhinitis (hay fever), food allergies, bronchial asthma, anaphylaxis
what are the clinical and pathological manifestations of Allergic Rhinitis, Sinusitis (hay fever)?
- increased mucus secretions
- inflammation of upper airways and sinuses
what are the clinical and pathological manifestations of food allergies?
increased peristalsis due to contraction of intestinal muscles
what are the clinical and pathological manifestations of Bronchial Asthma?
- airway obstruction caused by bronchial smooth muscle hyperactivity
- inflammation and tissue injury caused by late phase reaction
what are the clinical and pathological manifestations of Anaphylaxis?
- fall in blood pressure (shock) caused by vascular dilation
- airway obstruction due to laryngeal edema
what happens during the Late Effector Phase of Type I hypersensitivity?
- production of cytokines continues
- mast cells continue to produce eosinophil chemotactic factors
- recruitment of eosinophils and neutrophils prolongs the late phase
how is an eosinophil activated and what does it release?
- IgE binds to the FcεRII receptors on mast cells allowing them to release eosinophil chemoattractants
- cytokines, chemokines and ribonucleases with antiviral activity
what do eosinophils contain that gives them their anti- parasitic activity?
- major basic protein (MBP): destroys parasites and activates mast cells
- eosinophilic cationic protein (ECP): form ROS- neurotoxins that destroy worms
- leukotrienes (from mast cells): causes smooth muscle contraction to expel parasites
what is the therapy and its mechanism of action for Anaphylaxis syndrom?
- epinephrine: causes vascular smooth muscle contractions and increases cardiac output; relaxes airway muscles and inhibits mast cell degranulation
what is the therapy and its mechanism of action for Bronchial Asthma ?
- corticosteroids: reduce inflammation
- leukotriene antagonists: relax bronchial smooth muscle and reduce inflammation
- phosphodiesterase inhibitors: relax bronchial smooth muscle
what is the therapy and its mechanism of action for various allergic diseases?
- desensitization: repeat administration of low dose of allergens maybe cause T cell tolerance or inhibit IgE production
- Anti-IgE antibody: neutralize and eliminate IgE
- antihistamines: block actions of histamines on vessels and smooth muscles
- cromolyn: inhibits mast cell degranulation
what is Type II hypersensitivity and what causes it?
- antibody- mediated cytotoxicity
- it is a targeted immune response where antibodies mistakenly attack specific cells or tissues
what antibodies is Type II hypersensitivity mediated by and what do they cause?
- IgG: hemolytic diseases of new borns
- IgM: blood transfusion reactions
what is the general mechanism of Type II hypersenstivity?
- Antibodies (IgG or IgM) recognize and bind to specific antigens leading to the activation of complement, opsonization and antibody dependent cellular toxicity pathways which results in the destruction of the targeted cells or disruption of their function
what is the mechanism of destruction for a blood transfusion reaction?
- production of IgM antibodies in response to the carbohydrate antigens (A, B, H) on the surface of the transfused RBCs in a T independent manner
- IgM then binds to the blood group antigens on donated blood and cause massive agglutination and destruction
what are the symptoms of a blood transfusion reaction?
- fever
- hypotension
- nausea
- vomiting
- back and chest pain
- RBC debris damaging the kidneys
explain Erythroblastosis Fetalis (hemolytic disease of newborns)
- mother is RH- and father is Rh+ and they have a Rh+ child
- mother is exposed to Rh+ child and creates memory cells
- second child is Rh+ and due to the memory cells mother makes IgG that will cross placenta and destroy fetuses Rh+ blood cells
- leads to enlargement of the liver and spleen, hemorrhages and elevated bilirubin
what is the test to determine if a mother’s serum contains anti-Rh antibody?
- indirect coombs test
what is Type III hypersensitivity and what can it cause?
immune reaction caused by the formation of immune complexes that can cause arthus reaction and serum sickness
what is the mechanism of Type III hypersensitivity ?
- Immune complexes are formed when antibodies (usually IgG or IgM) bind to soluble antigens in the blood or extracellular fluid
- Immune complexes deposit in blood vessel walls, kidneys, joints, lungs, and other tissues due to failure in being cleared
- complement cascade is activated
- The activated immune cells release enzymes and reactive oxygen species (ROS), which cause tissue damage in response to inflammation
what is Arthus Reaction?
A localized reaction to a vaccine or antigen injection, in which immune complexes form at the site of injection and cause localized vasculitis (inflammation of blood vessels).
what is serum sickness?
Occurs after exposure to foreign proteins, often from animal serum or monoclonal antibodies where the body produces antibodies against these foreign proteins, forming immune complexes that deposit in tissues
what can serum sickness cause and how?
- nephritis and arteritis.
- Antigen and antibody react and form immune complexes that activate complement that get bigger and are deposited on basement membranes
what is Type IV hypersensitivity and what can it cause?
- delayed hypersensitivity: T cell mediated diseases
- can cause contact dermatitis, tuberculin reactions and granulomatous reactions
what is the mechanism of Type IV hypersensitivity ?
- Antigen-presenting cells (APCs) pick up the antigen and present the antigen to naive CD4+ T cells (T helper cells)
- T cells are activated and differentiate into Th1 cells
- Th1 cells produce cytokines, IFNγ, TNF-beta, IL-3/GM-CSF and chemokines
- cytokines act on vascular endothelium and recruit more T cells and phagocytes
- Th1 cells activate CD-8 CTL
- phagocytes, CTL and inflammation lead to development of lesion
what can cause contact dermatisis?
- poison ivy binding to host protein
- metals like nickel in jewelry
- chemicals like detergents used in laundry
- infections with viruses like chickenpox blisters
how is poison ivy dermatitis caused?
- pentadecacatechol comes in contact with the dermis of the skin activating a cutaneous reaction
- the antigen binds to host proteins
- the molecule is presented by langerhans cells and keratinocytes to the Th1 cells
- activated Th1 cells produce cytokines (INFγ that activate macrophages and MIF and MCP-1 that recruit macrophages )
- macrophages produce tissue destructive enzymes and activate Th1 cells causing blisters
what are tuberculin reactions and what are they used for ?
- the injection of soluble antigens under the dermis
- used as a skin test for determining previous exposure to mycobacterium tuberculosis
what is the mechanism of tuberculin skin reactions?
- Antigen presented by dendritic cells and macrophages
- Activation of Th1 cells
- Activation of endothelium
- Infiltration and activation of phagocytes and CTL
- Production of cytokines, chemokine and enzymes
what are granulomatous reactions and what are some examples?
- an immune mechanism to confine what it finds hard to eliminate by walling them off in a granuloma which consists of macrophages, Th1 cells and fibroblast in layers
- ex: tuberculosis, visceral leishmaniasis and hansen disease
what is leishmania?
parasite that lives inside macrophages
what is hansen disease?
leprosy caused by myobacteria lepra
what are the novel therapies for hypersensitivity?
- block co-stimulatory molecules (CD28:CD80/86)
- block signal transduction
- block cytokine and cytokine receptors
- block adhesion molecules
