Progressive muscle weakness because of Ab to AChR Complement- and neutrophil-mediated Becomes harder to stimulate the jxn because of what the neutrophils have barfed up on the end-plate

Immunopathology1 Flashcards by A B

What are the 4 types of immunopathologies?

ACID -

Anaphylactic and Atopic - Type I
Cytotoxic - Type II (Autoimmune)
Immune complex - Type III
Delayed (cell-mediated) - Type IV

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What is a chronic frustrated response?

Immune system can’t get control of a foreign substance so it keeps going on and on trying to defeat it. A chronic response with no resolution

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Explain the major mechanism for Type II tissue damage

Complement-mediated damage: 
Activation of complement leads to 
1. lysis (C6-9) 
2. Opsonization for phagocytosis (C3b) 
3. Release of phagocytic lysosomal enzymes and ROS 
4. Release of histamine (C5a, C4a, C3a)

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What is stimulatory hypersensitivity?

Used to be called Type V

In this case, antibody that is made is able to mimic the ligand for a particular receptor. This leads to constitutive activation of the receptor and the breakdown of normal regulation methods.

Ex: LAST on the thyroid receptor –> Graves disease

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Explain inappropriate tachycardia

Autoantibody is made to the beta-andrenergic receptor, which is stimulatory. Serves as a form of stimulatory hypersensitivity.

Seen mostly in women
Treat with beta-blockers

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What are the 3 main mechanisms for TypeII tissue damage

complement mediated damage (major)
Stimulatory Hypersensitivity
Antibody-Dependent Cell mediated cytotoxicity (ADCC)

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Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC):

Stressed cells express surface molecules → NK recognizes them → 
natural killer (NK) cells have Fc receptor → can bind to the Fc portions of bound IgG → start apoptosiis

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Example of Type II mechanism of disease of:

Muscle

Myasthenia Gravis

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Example of Type II mechanism of disease of:

Lung and Kidney

Goodpasture Syndrome

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Autoimmune Hemolytic Anemia

Rheumatic Heart Disease

& Dressler Syndrome

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Example of Type II mechanism of disease of:

Red cells

Autoimmune Hemolytic Anemia

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Example of Type II mechanism of disease of:

Platelets

Thrombocytopenic Purpura (ATP)

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Example of Type II mechanism of disease of:

Thyroid

Graves’ Disease

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Example of Type II mechanism of disease of:

Pancreatic islets

Juvenile diabetes

Type 1 diabetes

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Myastenia Gravis

Progressive muscle weakness because of Ab to AChR
Complement- and neutrophil-mediated
Becomes harder to stimulate the jxn because of what the neutrophils have barfed up on the end-plate

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AIRE

(Auto-immune regulator) gene:
thymal transcription factor → Drives thymic expression of CHRNA1 gene for AChR alpha subunit→ ensures that maturing T-cells are exposed to lots of different cells → have negative selection against super clingy T-cells.

Goodpasture Syndrome

• Formation of AutoAb to the lung and kidney basement membranes (form of vasculitis)

Type IV collagen (antigen) shared between these two organs
People can cough blood (hemoptosis)

Does Goodpasture syndrome demonstrate immunoflourescence as “linear” or “lumpy bumpy”?

Since autoAb are directed against BM and not trapped as clumps (too big to be filtered), the immunofluorescence is “linear”

Rheumatic Heart Disease

• Occurs shortly after streptococcal infection
• Cross rxn between Group A streptococcus M-protein antigen and laminin on the heart’s endothelial lining
(DIFFERENT FROM ENDOCARDITIS)

Dressler Syndrome

Immune response to pericardial or myocardial antigens
People who have heart attack (sometimes surgery) have some autoantibody which reacts w/ heart
Persistent cardiac pain, fever, malaise
Gets better as heart gets better

Autoimmune Hemolytic Anemia due to?

the patient experiences hemolysis after exposure to cold
- due to an autoantibody which only binds to red cells at about 15 C.
• May follow viral infection, other autoimmune syndromes, or cancer
• Many drugs can induce AIHA

Autoimmune Thrombocytopenic Purpura (ATP)

Bleeding abnormalities due to platelet destruction by autoAbs
Platelets opsonized for destruction in the spleen

Graves’ Disease

“Long-acting thyroid stimulator” LATS
IgG antibody to TSH receptor (LATS) → mimics TSH → thyroid cell secrete thyroid hormones → get Graves disease
(Normal feedback doesn’t work because it isn’t TSH doing the stimulating )

Juvenile diabetes

Type 1 diabetes

• AutoAbs to islet-associated antigens

technically considered Type IV immunopathology, since the antigens are not pathogenic

Linear immunoflourescent patterns

represent Ab that directly attack BM and so they can uniformly distribute along the membrane. These indicate Type II immunopathology

Lumpy-bumpy immunoflourescent patterns

represents clusters of antigen-Ab complexes stuck in the BM b/c they are too big to be filtered. They are non-uniform and are representative of Type III immunopathology

What antibody would you use to see type II immunopathology was involved?

Anti-IgG to see the IgG that is bound to the BM - ie: good pasture's syndrome

How can you tell if the patient's glomerulonephritis was due to Goodpasture's Disease or SLE

* Goodpasture's Disease: Type II immunopathology and is specifically autoAbs directed against the glomerular capillaries. You see linear fluorescence. * SLE: Type III. "serum sickness" type of accumulation in glomerular basolateral membranes. Looks lumpy (Type III).

Describe how antibody-mediated tissue damage could result from: The innocent bystander phenomenon:

Damage occurs because the normal tissue happens to be in proximity to or infected by the REAL foreign antigen

Describe how antibody-mediated tissue damage could result from: Cross-reaction of a foreign antigen with self

• Damage results from Abs binding to self-cells

***Describe how antibody-mediated tissue damage could result from: Coupling self antigen with a foreign antigenic “carrier”

1. B cell binds self plus foreign epitope 2. B cell ingests and digests 3. Foreign epitope is presented to Th2 on Class II MHC 4. Tfh → cytokines→ engages corereceptors 5. B cell is activated → secretes antibody to self → damage

Describe how antibody-mediated tissue damage could result from: Exposure of a sequestered antigen:

If normally sequestered self-antigens (not normally immunogenic) are released into blood stream → trigger immune response bc body hasnt negatively selected against self-antigens

Describe how antibody-mediated tissue damage could result from: Inadequacy of regulatory T cells:

Need a proper balance between all 5 types of T-helper cells (Th1, Th17, Th2, Tfh, Treg) for appropriate immune response - If balance perturbed → failure of regulatory mechanism

Rheumatoid Factor

"the autoantibody" RF: an antibody (predominantly IgM) against the Fc portion of IgG (an antibody against an antibody) - anti IgG -• Marker of disease , not part of pathogenesis