Lecture 23 - Hypersensitivity Disorders Flashcards
What are the different types of hypersensitivity?
L23 S2-3
Type I:
-caused by mast cells product
Type II:
-caused by Abs against tissue Ag
Type III:
-caused by immune complexes formed by Ab binding circulating Ag resulting in vasculitis
Type IV:
-caused by CD4+ Th1/Th17 cytokines or effector mechanisms of CD8+
Describe the activating mechanism of hypersensitivity type I.
L23 S6-7
No clinical symptoms:
- Th2 cells respond to allergen for first time and stimulate IgE production
- IgE bind FcεRI of mast cells with HIGH affinity
Clinical symptoms:
- upon secondary exposure, FcεRI bound IgE are cross linked by binding allergen
- mast cell effector mechanisms are activated
What are the effector mechanisms of hypersensitivity type I and where do they come from?
L23 S8
Preformed mast cell granule mediators (immediate-phase reaction):
- vasoactive amines (histamine; vessel dilation and permeability)
- proteases (local tissue damage)
Lipid mast cell mediators (immediate-phase reaction):
- prostaglandins (vessel dilation)
- leukotrienes (smooth muscle contraction)
Mast cell cytokines (late-phase reactions):
-e.g. TNF
Differentiate between the immediate and late-phase reactions of hypersensitivity type I.
L23 S8-9
Immediate:
- occurs within minutes
- due to preformed, granule mediators or lipid derived mediators
- causes in vascular dilation and smooth muscle dilation which results in edema and congestion
Late:
- occurs 2-24 hours later
- due to cytokine production
- causes inflammatory infiltrate of eosinophils, neutrophils, and T cells
What are examples of type I hypersensitivity diseases?
L23 S10-12
- anaphylaxis (systemic)
- asthma (local)
- food allergies
- airborne allergies
- contact allergies
Describe the mechanism of type II hypersensitivity activation and its mechanisms.
L23 S14
IgG or IgM bind cell surface Ags
Responses:
- activation of Mφ and neutrophils via Fc receptors (release of ROS)
- classical complement activation (MAC activation and anaphylatoxin production)
What are examples of type II hypersensitivity diseases?
L23 S16
- autoimmune hemolytic anemia
- autoimmune thrombocytopenia
- Grave’s disease (Ab against TSH receptor)
- myasthenia gravis (Ab against ATCH receptor)
- transfusions ABO reactions
- rheumatic fever
What are examples of type III hypersensitivity diseases?
L23 S20
- systemic lupus erythematosus
- serum sickness (i.e. reaction to second dose of anti-venom)
Describe the mechanism of type III hypersensitivity activation and its mechanisms.
L23 S17-19
IgG or IgM binds circulating Ag and is deposited in blood vessels
Mechanisms:
- complexes activate complement pathway releasing anaphylatoxins
- complexes bind Fc receptors of basophils, neutrophils, and mast cells activating them
- cells are destroyed and internal self-Ags are recognized (most common is DNA)
Results in damage to blood vessel -> vasculitis
Describe the mechanism of type IV hypersensitivity activation and its mechanisms.
L23 S21-23
Recognition of (typically) self-Ags by Th1, Th17, or CD8+ cells
Mechanism:
- release of Th1 or Th17 cytokines resulting in macrophage and neutrophils activation
- activation of CD8+ cytotoxic functions
What are examples of type IV hypersensitivity diseases?
L23 S25
- MS (myelin protein)
- rheumatoid arthritis
- IDDM (pancreatic islet Ags)
- Crohn’s disease
- chronic infections (TB)
- contact sensitivity (conjugation of skin proteins with poison ivy protein)
What is delayed-type hypersensitivity?
L23 S26
Type IV hypersensitivity specifically due to CD4+ cells
Delayed because memory CD4+ cell population takes time to expand after Ag challenge
Examples are TB tests, poison ivy reaction, and tetanus/diphtheria immunization reaction
What are granulomas?
L23 S27-28
Dense area of activated Mφ, giant cells, and lymphocytes around area of infection/infected cells
Dense layer of Mφ prevent T-cells and B-cells from accessing bacteria, allowing for prolonged survival
Seen in diseases such as tuberculosis
What is SLE and its characteristics?
L23 S31
Systemic lupus erythematosus
Type III hypersensitity (Immune complex-mediated)
Clinical manifestation:
- rash (specifically butterfly rash on face)
- arthritis
- glomerulonephritis
Diagnostics:
-presence of anti-nuclear Abs
What is RA and its characteristics?
L23 S34
Rheumatoid arthritis
Type II/IV hypersensitivity (Ab-mediated/T cell mediated)
Clinical manifestation:
-inflammation of synovium resulting in destruction of cartilage and bone
Diagnostics:
-presence of Abs that are reactive to Fc region of own IgG (called rheumatoid factors)
What is an Arthus reaction?
L23 S20
Reaction to an administered protein Ag that the individual has previously been immunized to.
