Describe Type II immunopathology
- Ab attacks self
- IgG, IgM, or IgA involved
What are the two types of immunologic mechanisms of tissue damage?
1) Complement-mediated damage
2) Stimulatory hypersensitivity
Describe complement-mediated damage
Tissues targeted by the autoAbs damaged by:
1) Lysis
2) Phagocytosis
3) Release of phagocytes’ lysosomal enzymes and ROSs
Describe stimulatory hypersensitivity. Give 2 examples.
When an autoAb is directed against a cell-surface receptor and then behaves as an … AGONIST (ohhhh hellll nah!)
Examples:
1) Graves Disease
2) “Inappropriate” tachycardia
Describe Graves disease
- When IgG targets the TSH receptor on thyroid cells
- Mimics TSH and stimulates T3/T4 (thyroid) hormone production
- There’s a constant (-)ve feedback to the anterior pituitary (that normally releases TSH)
Leads to: HYPERTHYROIDISM
Describe inappropriate tachycardia
- Half of cases have autoAbs target the Beta-adrenergic receptor
- Stimulatory —» fast heart rate w/o cardiac abnormalities
- Primarily women
What is an example of a type II mechanism disease of muscle?
Myasthenia gravis
What is an example of a type II mechanism disease of the kidney?
Goodpasture disease
What is an example of a type II mechanism disease of the heart?
1) Rheumatic heart disease
2) Dressler syndrome
What is an example of a type II mechanism disease of red cells?
Autoimmune hemolytic anemia
What is an example of a type II mechanism disease of platelets?
Autoimmune thrombocytopenia purpura
What is an example of a type II mechanism disease of the thyroid?
1) Hashimoto thyroiditis
2) Graves disease
What is an example of a type II mechanism disease of pancreatic islets?
Type 1 diabetes
What is an example of a type II mechanism disease of the lungs?
Goodpasture syndrome
Describe myasthenia gravis
- Progressive muscle weakness
- Ab made to alpha subunit of AChR
- Normally: Aire drives expression of CHRNA1 which has a gene for AChR-alpha
- Some cases: there are genes that don’t interact w/ Aire —» protein not expressed in thymus —» pre-T cells never see this as self in the thymus
What Cohen said in class:
1) Complement eats neutrophils that respond to autoAb on AChR — can’t eat muscle cells
2) All neutrophil digestive juices released —» damaged neuromuscular end plate
Describe rheumatic heart disease
- Acquired shortly after streptococcal infection (e.g. strep throat)
- B/c of a cross-rxn btwn a Group-A Streptococccus Ag and structure of heart’s endothelial lining —»> neutrophil-mediated tissue destruction
- Thought to be related to genetics
- Though still not sure when and who it will affect
- More common in areas that do not have rapid treatment for strep throat
Describe Dressler syndrome
- After MI, damaged heart muscle cells release proteins not seen by immune system previously —-»> aka “sequestered” Ag
- Ab attacks these Ag (technically an autoAb)
Symptoms:
1) Persistent cardiac pain
2) Fever
3) Malaise
4) Pericardial effusion
When tx includes anti-inflam agents, gets better as heart heals
Describe Goodpasture syndrome
- Uncommon
- AutoAbs target lung and kidney basement membranes (common Ag in both = Type 4 collagen)
Symptoms:
1) Persistent glomerulonephritis
2) Pneumonitis w/ pulm hemorrhages
How would you diagnose Goodpasture syndrome in the kidney indirectly?
- Take normal kidney tissue
- Add pt’s serum
- Add labeled anti-IgG
- Visualize where IgG is near the glomeruli
Will be linear if GPS
How would you diagnose Goodpasture syndrome in the kidney directly?
- Add labeled anti-IgG to pt’s kidney tissue
- Visualize where IgG is near the glomeruli
Will be linear if GPS
Describe “linear” immunofluorescent patterns. What type of immunopathology does it show? Why is that?
In GPS: Anti-IgG goat sera attaches to IgG along basement membrane in glumeruli —> that’s why the fluorescence is linear
Type II
Describe “lumpy, bumpy” immunofluorescent patterns. What type of immunopathology does it show? Why is that?
Anti-IgG binds to IgG which are in clumps throughout glumeruli
Type III
IMPORTANT: Seen in systemic lupus erythematosus
Describe autoimmune thrombocytopenia purpura
- Bleeding abnormalities b/c of platelet destruction (autoAb targets them)
- Platelets are opsonized — destruction is rapid (mainly in spleen)
- May follow viral infection
Requires immunosuppression and splenectomy for TX
Describe autoimmune hemolytic anemia
- May follow a viral infection
- Can be associated w/ another autoimmune syndrome or cancer
- Many drugs can induce this
Cold version: when exposed to cold —»> red cell hemolysis b/c of autoAb which only binds at 15 Celcius
Describe systemic lupus erythematosus
- AutoAb targets dsDNA
- Cell membrane normally protects cell from this autoAb
- But cells die all the time and release dsDNA
Describe rheumatoid arthritis
- Most common autoimmune disease (1 in 100 Americans)
- Rheumatoid factor (RF) detected in pts
- It is IgM anti-IgG’s Fc
- IgG beads mixed w/ pt serum cause beads to agglutinate)
Overall: anti-IgG attacks joints
Describe Hashimoto thyroiditis
- Inflammatory disease of the thyroid
- Thought to be T and B cell immunity to thyroid Ags
Causes: hypothyroidism
What is the innocent bystander effect?
Damage to normal tissue which is infected with truly foreign antigen
You see this in TB a lot —» macros go crazy and eat everything including normal lung tissue
Describe the foreign + self hybrid Ag and its mechanism
- anti-self B cell binds to self plus foreign epitope
- Ingest and digest time
- Foreign epitope presented to Tfh on Class II MHC
- Then activated and makes more Ab that is anti-self
- Also instructed to class-switch by Tfh —» more problems
BE SURE THAT YOU KNOW THIS
Describe the emergence of the forbidden clone
When a clone escapes normal clonal deletion mechanisms and mature —» seen as an Ag
Ex: myasthenia gravis
What is the function of the Aire gene?
- Drives thymic exposure of self-Ags —» negative selection process of pre-T cells
- Encodes a transcription factor that drives transciption of genes for these self-Ag
Remember myasthenia gravis? Aire can’t interact with CHRNA promotor —» no AChR alpha subunit shown to pre-T cells
What role do Treg cells play in Type II immunopathology?
Treg cells may not ensure appropriate immune responses
Allows self-non-self discriminatory process to break down somehow
