Hypersensitivity Flashcards
Hypersensitivity
defect in regulation or targeting of the usually beneficial immune response
i.e. overreaction of normal immune response triggered by self/microbial/environmental antigens
Triggers of hypersensitivity
3 types of antigens
- “self” antigens -autoimmunity
- microbial antigens - excessive inflammation
- Environmental antigens - allergy/atopy
What are the 4 types of hypersensitivity?
Type I - Immediate hypersensitivity
Type II - Antibody-mediated
Type III - Immune complex-mediated
Type IV - T cell-mediated
Names for Type 1 Hypersensitivity
Immediate, IgE-mediated, allergy/atopy
Timing of Type 1 Hypersensitivity
within minutes (very rapid)
Mechanism of Type 1 Hypersensitivity
cross-linking of IgE triggering mediator release in mast cells
Involve antigen-specific IgE on effector cells
Various mediators in Type 1 Hypersensitivity
vasoactive mediators (e.g. histamine)
lipid mediators
cytokines
Most common type of hypersensitivity
Type 1
Allergy =
histamine
Examples of allergic diseases (Type 1 Hypersensitivity)
- Allergic rhinitis (“hay fever”)
- Atopic asthma
- Anaphylaxis (food allergy, stinging insect allergy, drug allergy)
Potential causes of increase in Type 1 Hypsersensitivity prevalence within the past 50 years
- hygiene hypothesis
- environmental factors
Similarities between Type II and III hypersensitivity
both mediated by antibodies (involve IgG and IgM)
frequently involve auto-antibodies (failure in developing or loss of self-tolerance)
less commonly involve foreign antigens
Type II Hypersensitivity
- Injury related to antibody directly binding to target
- Antigens are specific cells or extracellular matrix
Differences between Type II and III Hypersensitivity
Type II: Local, tissue/cell specific (i.e. “targeted”)
Type III: Systemic
Type III Hypersensitivity
- Injury related to immune complex deposition
- Antigens are present in circulation
Names for Type II Hypersensitivity
antibody-mediated, cytotoxic
Timing for Type II Hypersensitivity
couple days up to a week
Mechanism of Type II Hypersensitivity
3 mechanisms:
- complement/Fc receptor inflammation
- opsonization/phagocytosis
- receptor activation
1st mechanism of Type II Hypersensitivity
“Complement- and Fc receptor-mediated inflammation”
Antibody binds antigens and attract neutrophils and/or complement which lead to inflammation and injury
Goodpasture syndrome
Anti-glomelular basement membrane disease
What are antibodies directed against in Goodpasture syndrome?
Abs against basement membrane in kidney and lung
Activate complement and Fc receptors (of neutrophils), leading to inflammation
Symptoms of Goodpasture syndrome
Blood in urine, Blood in lung, kidney failure and fatigue
2nd Mechanism of Type II hypersensitivity
Opsonization and phagocytosis
Ab coat the outside of cells and then phagocytes come and eat them up
ITP (Idiopathic thrombocytopenic purpura)
Autoantibodies against platelets –> opsonization
Symptoms of ITP
- Recurrent nose bleeds
- Easy bruising
- Petechiae
AIHA (Autoimmune hemolytic anemia)
Autoantibodies against RBC membrane proteins
Pts. have symptoms of anemia
On blood smear, less RBCs; not donut shaped - vary in size; no central pallor
3rd mechanism of Type II Hypersensitivity
Abnormal physiologic responses without cell/tissue injury - Abs turn things on or off
- Antibody stimulates receptor without hormone (e.g. Grave’s disease: Ab against TSH receptor leads to hyper-stimulation of thyroid and production of thyroid hormones)
- Antibody inhibits binding of NT to receptor (e.g.: Myasthenia Gravis: Ab bind ACh receptors, preventing ACh from signaling from nerve to muscle)
Why are Grave’s disease and Myasthenia Gravis examples of Type II Hypersensitivity?
Autoantibodies are involved, and the Abs bind particular cells and disease is tissue specific
Clinical examples of Type II Hypersensitivity
- Acute rheumatic fever - Abs against myocardial Ags ( cross-reactive anti-strep Abs)
- Pemphigus vulgaris - Abs against desmosomes
- Pernicious anemia - Abs against intrinsic factor
Names for Type III Hypersensitivity
Immune-complex mediated
Timing for Type III Hypersensitivity
several days up to a couple weeks
Mechanism of Type III Hypersensitivity
- Abs bind Ags forming complexes
- Complexes not efficiently cleared
- Deposit in vessels or tissue
- Trigger complement/Fc receptor inflammation
(e.g.: vasculitis)
Type III Hypersensitivity and diphtheria treatment from horse serum
- Horse injected w diphtheria toxin –> induce Abs
- Anti-diphtheria horse serum injected into humans to treat diphtheria
- Some patients receiving the anti-diphtheria horse serum developed (1) fever, (2) hives and (3) joint pain
note: symptoms occured with anti-diphtheria horse serum AND with horse serum alone
repeated exposure to horse serum led to quicker and quicker rxns because already had developed antibodies
Type III Hypersensitivity and SLE (systemic lupus erythematosus)
Multiple nuclear autoantibodies: dsDNA, ribo-nucleopreotins, histones
SLE also has examples of Type II Hypersensitivity with the blood issues
but joint pain, nephritis and vasculitis are classic of Type III
Clinical examples of Type III Hypersensitivity
Poststreptococcal glomerulonephritis - group A strep Ag
Polyarteritis nodosa - Hep B surface Ag
Slowest Hypersensitivity type
Type IV
Names for Type IV Hypersensitivity
delayed type, cell-mediated
Timing for Type IV Hypersensitivity
1-3 days
Mechanism of Type IV Hypersensitivity
2 mechanisms: (both T cell mediated)
- CD4 T-cell cytokine-mediated inflammation
- CD8 T-cell direct cytotoxic killing
Type IV Hypersensitivity and antibodies
T-cell mediated rather than antibodies - not transferrable by serum
1st mechanism of Type IV Hypersensitivity (Cytokine-mediated inflammation)
CD4 indirectly causes injury by releasing inflammatory cytokines (e.g. IFNgamma)
What is FoxP3
TF associated with regulatory T cells
Suppressive cytokines secreted by Tregs
IL-10 and TGFbeta
Cytokine associated with allergy
IL-4
TB test is example of what type of hypersensitivity
Delayed-type hypersensitivity (DTH)
Type IV Hypersensitivity since CD4+ T cells are involved
Clinical examples of Type IV Hypersensitivity (cytokine-mediated inflammation)
MS
Type 1 diabetes
IBD
Rheumatoid arthritis
2nd mechanism of Type IV Hypersensitivity
T cell-mediated killing of host cells; direct tissue injury by CD8+ cytotoxic T cells
Examples of CTL mediated Type IV Hypersensitivity
poison ivy (contact dermatitis)
Poison ivy (contact dermatitis)
Urushiol - colorless oil
- low molecular weight, lipid soluble so crosses cell membrane
- modifies intracellular ksin proteins; presented on MHC Class I –> cells appear FOREIGN
- CTLs trigger cell destruction by apoptosis
delayed, develops over 12-48 hours
Poison ivy (contact dermatitis) onset
delayed, develops over 12-48 hours
note: this is Type IV Hypersensitivity (not Type I so not immediate)
Treatment options for Types I-IV Hypersensitivity
- Antihistamines, epinephrine
- Plasmapheresis, immune biologics (target specific cytokine)
- IVIG (high doses lead to immune suppression)
- Corticosteroids (reduce inflammatory cytokines produced)
Diseases involving Type II Hypersensitivity
Goodpasture, AIHA, ITP, Graves, Myasthenia gravis
Diseases involving Type I Hypersensitivity
Allergic diseases and anaphylaxis
Diseases involving Type III Hypersensitivity
Lupus, serum sickness, post-strep glomerulonephritis, polyarteritis nodosa
Diseases involving Type IV Hypersensitivity
TB, contact dermatitis
