1. Type II Hypersensitivity: Antibody-mediated cytotoxicity
Results when Ig or IgM bind to cell surface Ag’s
Activating Complement
Binding Fc receptors on Tc cells promoting ADCC
Both processes result in lysis of the Ab-coated cell
Clinical examples of Type II responses include:
Certain autoimmune diseases where Ab’s produced vs membrane Ag’s
Grave’s Disease – Ab’s produced vs thyroid hormone receptor
Myasthenia Gravis – Ab’s produced vs acetylcholine recpetors
Autoimmune hemolytic anemia – Ab’s produced vs RBC membrane Ag’s
Hemolytic Disease of the Newborn
Hyperacute graft rejection
Blood Transfusion rxns
Graft rejection

2. Type II Hypersensitivity: Transfusion reactions
Produced by mismatched blood types
Destroys foreign RBC by complement-mediated lysis triggered by IgG
Produces fever, intravascular clots, lower back pain, Hgb in urine
Free Hgb produced has 2 fates:
passes to the kidneys – hemoglobinuria
Breaks down to bilirubin..can be toxic

3. Type II Hypersensitivity: Hemolytic Disease of the Newborn
Occurs via maternal IgG Ab’s crossing the placenta
In severe cases causes erythroblastosis fetalis
Most commonly develops in Rh- mother with Rh+ fetus
Exposure to Rh+ fetal RBC’s stimualtes prod of memory/plasma
Activation of memory cells in subsequent pregnancy stim IgG Ab’s which can cross the placenta
mild-severe hemolytic anemia ensues along with bilirubin which affects the brain/CNS
Treatment centers on anti-Rh antibodies (Rhogam)
Mothers can be tested for anti-Rh antibodies to check for a rise in titre
Isolated fetal RBC’s can be checked for anti-Rh IgG w/ Coombs test

4. Hemolytic Disease of the Newborn

5. Type II Hypersensitivity: Drug-induced hemolytic anemia
Drugs such as aspirin and antibiotics can bind to the surfaces of RBC’s
These interactions act similar to hapten-carrier conj.
Such complexes can trigger Ab-mediated cell lysis by complement activation

6. Type III Hypersensitivity: Immune Complex-mediated cytotoxicity
Caused by immune complex deposition in tissues
Small amts cleared by phagocytic cells
Activates complement which attracts neutrophils and stim Mast cell degranulation
Depending on location, rxn can be localized or systemic
Most damage stems from activity of Neutrophils
Immune complexes can adhere to tissue making it difficult for Neutrophils to phagocytize
Neutrophils continue releasing lytic enzymes, etc.

7. Type III Hypersensitivity: Localized reactions
Arthus rxns:
Exposure to an Ag for which there already is a high [c] of Ab
Produces edema/erythema from damage to bv and tiss
Insect bites
Inhalation of bacteria, fungi, dried fecal matter

8. Type III Hypersensitivity: Systemic (generalized) reactions
Produced when large amounts of Ag enter the bloodstream
The sites of deposition vary; usually in tissues where plasma is filtered
Esp. in kidneys, blood vessels, and joints
Can cause tissue damaging rxns:
Serum sickness
Autoimmune diseases
Drug reactions
Infectious diseases

9. Type IV Hypersensitivity: Delayed-Type Hypersensitivity
Occurs hrs after Ag contact and is mediated by Ag-specific TH1 cells and activated MØ
TH1 cells secrete:
IFN-γ activates MØ
TNF-α and β upregulate CAM’s on local b.v’s
Il-3 and GM-CSF stim bone marrow monocyte output
Initial contact with Ag (sensitization) may induce memory TH1 cells without symptoms

10. Phases of the DTH Response
Sensitization – TH1 cells triggered by contact with APC
Effector response – produces huge influx of activated MØ
Activated MØ is more efficient at antigen-presentation
Release of lytic enzymes lead to non-specific destruction of cells
Works well vs intra-cellular pathogens
If pathogen/particle lingers -> can lead to granuloma formation
Ex: Mycobacterial pathogens in TB and Leprosy

11. DTH Response
Cytokines released include: TNF-β, GM-CSF, and IFN – γ

12. DTH Response
Type IV rxns marked by time delay and recruitment of MØ instead of Neut’s and Eosino’s

13. Contact Dermatitis Produced by a variety of substances
Mostly small molecules attach to a protein in the skin
The Ag-protein complex is processed and presented  sensitize TH1 cells
Subsequent exposure activates TH1 cells  hrs later MØ infiltrate
Activation of MØ causes the inflammation that characterizes the disorder