Allergy & Hypersensitivity vs Autoimmune Disease Flashcards
What causes Type IV Hypersensitivity
Antigen Specific Effector T-Cells release products that results in an inflammatory reaction
- CD4 TH1 cause the majority of reactions (Insect bite)
- Cytotoxic CD8 can cause some reactions (Poison Ivy-Pentadecacatechol)
Also involved in Chronic Transplant Rejection and Autoimmune Diseases
Type I Hypersensitivity Reaction
Anaphylaxis (Allergy Response)
Soluble antigens trigger release of IgE which triggers mast cell activation
Different methods to treat Allergic Reactions
- Prevention
- Pharmacological
- Immunological (Prevent production of allergen-specific IgE)
Type IV Hypersensitivity Reaction
- TH2
Delayed Type and Contract Type
Soluble antigens trigger TH2 cells to activate Eosinophils
What is Serum Sickness
After administering an IV of therapeutic proteins/Antibodies from another species the body may recognize it as foreign
- Leads to formation of immune Ag:Aby complexes causing symptoms like fever, arthritis, nephritis
Type II Hypersensitivity Reaction
Cytotoxic
Cell Surface Receptors or Cell/Matrix associated antigens trigger release of IgG which attract complements to harm those cells or mark Fc receptors on cells
Inhaled Allergen Process
- Allergen enters the airways and is picked up by APC (Like a B-Cell)
- APC (Like a B-Cell) presents antigen to T-Cell
- TH2 secretes IL-4
- B-Cell develops into Plasma cell and produces IgE
- IgE binds to Fc epsilon receptors on mast cells
- When allergen antigen binds to IgE on mast cell it triggers degranulation
- Mast cell releases inflammatory mediators
How are Hypersensitivity Reactions grouped?
Based on the effector mechanisms that produce the reaction
What reactants are synthesized after Eosinophil cell activation (Chemokine)
- What are their biological effects
CXCL8
- Promotes influx of leukocytes
Autoimmune Disease and Genetic Factor
Susceptibility to an autoimmune disease depends on ones genes (Differs between ethnic groups)
Every autoimmune disease has an HLA gene association
- Between the Polymorphic Class I (A, B, C) and Class II (DQ, DR)
Where are Eosinophils located
Found in loose connective tissue under epithelial and mucosal surfaces
- Respiratory, Gastrointestinal, Urogenital
- Small amount found in peripheral blood
Autoimmune Hemolytic Anemia Mechanism
- IgG and IgM bind to antigens on RBC
- Activates complement through the classical pathway
- RBC coated with antibody and Opsonins (C3b) are cleared from circulation
- Done by Fc/Complement receptors on phagocytic cells in spleen
- Or RBC undergoes lysis after formation of MAC
What are the common sources of allergens?
- Inhaled Materials
- Injected Materials
- Ingested Materials
- Contacted Materials
Mast Cells and Eosinophils what class of molecules are Pre-Packaged. What classes are Synthesized
Enzymes, Toxic Proteins, Cytokines
Cytokines, Chemokines, Lipid Mediators (Eosinophils do not contain pre-packaged cytokines)
What pre-packaged reactants are released by Mast Cells (Enzymes)
- What are their biological effects
Tryptase, Chymase, Cathepsin G
- Remodeling of connective tissue matrix
Systemic Lupus Erythematosus
- Type of Disease
- Autoantigen
- Consequence
- Immune-Complex Disease (Type III)
- DNA, histones, ribosomes, snRNP, snRNP
- Glomerulonephritis, Vasculitis, arthritis
What reactants are synthesized after Eosinophil cell activation (Cytokine)
- What are their biological effects
IL-3, IL-5, GM-CSF
- Amplify eosinophil production by bone marrow
- Cause eosinophil activation
Autoimmune Disease and Lyme Disease
- Tick transmits Borrelia Bacteria through a bite
- Can cause Lyme Arthritis
What reactants are synthesized after mast cell activation (Cytokines)
- What are their biological effects
IL-4,13
- Stimulate and amplify T-Helper 2 Cell Response
IL-3, IL-5, GM-CSF
- Promote eosinophil production and activation
What do Mast Cells synthesize through oxidation of fatty acids
Produces Prostaglandins and Leukocytes from Arachidonic Acid
Multiple Sclerosis
- Type of Disease
- Autoantigen
- Consequence
- T Cell-mediated Disease (Type IV)
- Myelin basic protein, Proteolipid protein
- Brain degeneration, Paralysis
Subacute Bacterial Endocarditis
- Type of Disease
- Autoantigen
- Consequence
- Immune-Complex Disease (Type III)
- Bacterial Antigen
- Glomerulonephritis
What kind of Type III diseases can a Subcutaneous injection cause
Immune-Complex Deposition in Perivascular area
- Arthus Reaction
What pre-packaged reactants are released by Eosinophils (Toxic Proteins)
- What are their biological effects
Major Basic Protein
- Toxic to parasites and mammalian cells
- Triggers histamine release from mast cells
Eosinophilcationic Protein
- Toxic to parasites
- Neurotoxin
Eosinophil-derived neurotoxin
- Neurotoxin
Kinds of Type I Reactions
Allergic Rhinitis, Asthma, Systemic Anaphylaxis
Acute Allergic Asthma vs Chronic Allergic Asthma
Acute
- Mast Cell Mediated
Chronic
- Eosinophil and Cytokine mediated
Kinds of Type III Reactions
Serum Sickness, Arthus Reaction
What is Autoimmune Hemolytic Anemia
A type II autoimmune disease that targets Erythrocytes
Tissue Specific Effects of Degranulation
- Blood Vessels
- Increased blood flow
- Increased permeability
–> Edema, Inflammation, Increased lymph flow of antigen to lymph nodes
Penicillin Allergy Process
- Penicillin modifies proteins of RBC creating foreign epitopes
- B-Cells activated by antigen and present it to TH2 Cells
- TH2 Cells activate B-Cells and they differentiate into Plasma Cells
- Plasma Cells secrete penicillin- specific IgG
- IgG binds to penicillin modified RBC
- Activation of complement components C1-C9 and formation of membrane attack complex lyses RBC
OR - Activation of complement components C1-C3 leads to covalent bonding of C3b and phagocytosis of antibody and complement coated RBC
What pre-packaged reactants are released by Mast Cells (Toxic Proteins)
- What are their biological effects
Histamine, Heparin
- Toxic to parasites
- Increase vascular permeability
- Causes smooth muscle contraction
Rheumatoid Arthritis
- Type of Disease
- Autoantigen
- Consequence
- T Cell-mediated Disease (Type IV)
- Unknown synovial joint antigen
- Joint inflammation and destruction
Delayed-Type Hypersensitivity
- Antigens and Consequences
Proteins
- Insect Venom
- Mycobacterial Proteins (Tuberculin, lepromin)
Results in Local Skin Swelling
- Erythema
- Induration
- Cellular infiltrate
- Contact Dermatitis
Treatment for Type IV Hypersensitivity
- Avoid contact with agent that cases hypersensitivity
- Monitor for local infection risk
- Corticosteroids, Cyclosporins, and Immunotherapy
What commonly triggers Type I Hypersensitivity
Inhaled particulate Antigen causing Anaphylaxis
Relation between infections and autoimmune disease
Autoimmune can be an adverse side-effect of an immune response to infection
- Antibodies interact with and are specific to infection. However, cells elsewhere in the body may be similar to the infection causing the antibody to attack the body
1. Streptococcal cell wall stimulates antibody response
2. Some antibodies cross-react with heart tissue
3. Rheumatic fever
Symptoms of Serum Sickness
- Fever
- Lymphadenopathy
- Arthralgia
- Cutaneous Eruptions (Urticarial Rash)
- GI Disturbances (Vomiting, Diarrhea)
- Proteinuria
- Decrease serum complement levels
Type IV Hypersensitivity Reaction
- CTL
Delayed Type and Contract Type
Cell-Associated Antigens trigger Cytotoxic T-Cells to induces Cytotoxicity of target cells
What are the different classes of Autoimmune Disease
Type II
- Antibody reacting with cell surface/matrix antigen
Type III
- Immune complexes
Type IV
- T-Cell Mediated Cytotoxicity
No Type I as no autoimmune disease is mediated by IgE
Tissue Specific Effects of Degranulation
- Gastrointestinal
- Increased Fluid Secretion
- Increased Peristalsis
–> Expulsion of GI tract contents (diarrhea, vomiting)
Immune Complex Stoichiometry
Early
- Too little antibody, lots of antigens
–> Small immune complexes are formed however, complement is not activated, and are not cleared from circulation
Intermediate
- Amount of antigens is comparable to antibody
–> Immune complexes are formed that can fix complement and are cleared from circulation
Late
- Large amounts of antibody, little antigen
–> Immune complexes of intermediate size can fix complement are cleared from circulation
What kind of Type III diseases can a inhaled dose cause
Immune-Complex Deposition in Alveolar Capillary interface
- Farmer’s lung
Arthus Reaction Process
- Antigen introduced into subcutaneous tissue
- Local AGC process the antigen and present it to T-Cells
- TH1 Cells recognize antigen and release cytokines which act on vascular endothelium
- Recruitment of T cells, phagocytes, fluid, and proteins to the site of antigen injection
- Visible legions form
Mechanism of Type I Hypersensitivity
- IgE binds to Fc Epsilon receptors on granulocyte cells. (Mast Cells, Eosinophils, Basophils)
- Antigen binds to IgE triggering granulocyte cell
- Degranulation of cell releasing pre-packaged inflammatory mediators
- Later stage mediators are also synthesized by the cells after activation
What is an Arthus Reaction
Occurs after injection of sub-cutaneous Ag
- Results in localized area of erythema and hard swelling caused by immune complex formation
Kinds of Type IV TH1 Reactions
Contact Dermatitis, Tuberculin Reaction
Tissue Specific Effects of Degranulation
- Airways
- Decreased diameter
- Mucus secretion
–> Expulsion of airway contents (phlegm, coughing)
What pre-packaged reactants are released by Eosinophils (Enzymes)
- What are their biological effects
Eosinophil Peroxidase
- Toxic to target by catalyzing halogenation
- Triggers histamine release in mast cells
Eosinophil Collagenase
- Remodels connective tissue matrix
What causes Type III Hypersensitization
Small, insoluble immune complexes of Antigen and Specific Antibody are deposited on walls of blood vessels (kidneys) or lung alveoli
- Activates complement on tissue surface leading to inflammatory response and tissue damage
What causes a bullseye rash
Lyme Disease
What reactants are synthesized after mast cell activation (Lipid Mediator)
- What are their biological effects
Leukotriene C4, D4, and E4
- Causes smooth muscle contraction
- Increases vascular permeability
- Causes mucus secretion
Platelet-activating factor
- Chemotactic for leukocytes
- Amplifies production of lipid mediators
- Activates neutrophils, eosinophils, and platelets
What causes Type II Hypersensitivity
- Small molecules that covalently bind to surface of human cells
- Produce modified structure that is recognized as foreign by immune system
- Cell destruction through IgG antibody formation, complement protein, and phagocytosis
Kinds of Type II Reactions
Drug Allergies (Penicillin)
Type 1 diabetes (insulin-dependent diabetes mellitus)
- Type of Disease
- Autoantigen
- Consequence
- T Cell-mediated Disease (Type IV)
- Pancreatic Beta-Cell antigen
- Beta-Cell Destruction
Mixed Essential Cryoglobulinemia
- Type of Disease
- Autoantigen
- Consequence
- Immune-Complex Disease (Type III)
- Rheumatoid factor IgG complexes (With or without hepatitis C antigens)
- Systemic Vasculitis
What are the difference in the granules of Basophils vs Mast Cells
Similar
- Both have same stem-cell precursor
Difference
- Mast Cells secrete IL-4 and IL-13 to initiate TH2 lymphocyte activation
What pre-packaged reactants are released by Mast Cells (Cytokines)
- What are their biological effects
TNF-alpha
- Promote inflammation
- Activates leaky endothelium
- Stimulates cytokine production
Allergic Reaction Treatment
(Pharmacological)
- Block effector pathways (Histamine receptor blocker)
- Suppress leukocyte function (Corticosteroids)
- Prevent degranulation (Cromolyn Sodium)
- Treat anaphylactic reaction (Epinephrine –> Produces a vasoconstriction effect)
What is an Autoimmune Response
Antibody and T-Cells attack healthy cells and tissues as though they were infected with a pathogen
- Remains throughout lifetime of patient
- Increases in severity and can contribute to cause of death
What are Urticarial Rashes
Type III Hypersensitivity reaction
- Oral edema without mucosal involvement resulting in red wheal-like swellings that overlap each other
Treatment Strategies for Type II and Type III Hypersensitivity Reactions
- Discontinue any drug that elicits hypersensitivity
- For blood products be careful of cross matching ABO and Rhesus antigens
- For mild cases (Urticaria) use antihistamines
- For Anaphylaxis use epinephrine, oxygen supplementation, airway management, ECG monitoring, IV fluids/dialysis
What reactants are synthesized after Eosinophil cell activation (Lipid Mediators)
- What are their biological effects
Leukotrienes C4, D4, E4
- Cause smooth muscle contraction
- Increase vascular permeability
- Cause mucus secretions
Platelet-Activating Factor
- Chemotactic to leukocytes
- Amplifies production of lipid mediators
- Activates neutrophil, eosinophils, and platelets
What are the different types of Type IV Hypersensitivity Reactions
Delayed-type Hypersensitivity
Contact Hypersensitivity
Type III Hypersensitivity Reaction
Immune Complex
Soluble antigens trigger release of IgG which acts on complement phagocytes triggering immune complex and downstream inflammatory effects
Allergic Reaction Treatment
(Immunological)
- Desensitization Procedure
- Shift away from IgE towards IgG4 isotype - Series of allergen injections
- Small initial dose and gradual increase - Vaccination wit discrete allergen-derived peptides
- Promotes TH1 response, or anti idiotype antibody vaccine
Serum sickness process
- Body sees antigens from a IV Ag injection as foreign
- Leads to formation of immune complexes between IgG and antigen
- Activation of complement releases inflammatory mediators like C5a, C3a, and C4a.
- C5a induces mast cell degranulation
- Local inflammation, movement of fluid and protein into tissues
What kind of Type III diseases can an IV High Dose injection cause
Immune-Complex Deposition in Blood Vessel Walls
- Vasculitis
Immune-Complex Deposition in Renal Glomeruli
- Nephritis
Immune-Complex Deposition in Joint Spaces
- Arthritis
What reactants are synthesized after mast cell activation (Chemokines)
- What are their biological effects
CCL3
- Chemotactic for monocytes, macrophages, and neutrophils
What do Eosinophils do
- Regulates expression of Fc epsilon and Complement receptors after simulation by inflammation environment
- Releases highly toxic molecules after degranulation
What is linkage disequilibrium
Particular alleles of polymorphic HLA genes are combine in HLA haplotypes at higher frequency for a particular disease
- More likely for alleles to combine and form the phenotype for a disease
What is autoimmune disease
Adaptive immune responses that become misdirected at healthy cells and tissues developing into chronic diseases
Type IV Hypersensitivity Reaction
- TH1
Delayed Type and Contract Type
Soluble antigens trigger TH1 cells to activate macrophages
Kinds of Type IV Reactions
Chronic Asthma, Chronic Allergic Rhinitis
