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)
