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TT DD ex 3 and BL ex 2 > 5 BL Immunopathology Type II > Flashcards

5 BL Immunopathology Type II Flashcards

1
Q

What are the 4 types of immunopathologies?

A

ACID -

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

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2
Q

What is a chronic frustrated response?

A

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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3
Q

Explain the MAJOR mechanism for Type II tissue damage

A

Complement-mediated damage:

Normal cells bound by antibody → Activation of complement → damaged by:

  • lysis (C6-9)
  • Opsonization for phagocytosis (C3b)
  • Release of phagocytic lysosomal enzymes and ROS
  • Release of histamine (C5a, C4a, C3a)
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4
Q

What is stimulatory hypersensitivity?

A

Used to be called Type V

Autoantibody is able to mimic the ligand and work at that particular receptor → constitutive activation of the receptor and the breakdown of normal regulation methods.

Ex: LATS (long acting thyroid stimulator) on the thyroid receptor –> Graves disease

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5
Q

Explain inappropriate tachycardia

A

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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6
Q

What are the 3 main mechanisms for TypeII tissue damage

A
  1. complement mediated damage (major)
  2. Stimulatory Hypersensitivity
  3. Antibody-Dependent Cell mediated cytotoxicity (ADCC)
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7
Q

Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC):

A 
Antibodies (IgG) bind target cells.→Stressed cells express surface molecules → NK recognizes them →
natural killer (NK) cells have Fc receptor → can bind to the Fc portions of bound IgG → release cytokines and iNF gamma→start apoptosiis
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8
Q

Example of Type II mechanism of disease of:

Muscle

A

Myasthenia Gravis

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9
Q

Example of Type II mechanism of disease of:

Lung and Kidney

A

Goodpasture Syndrome

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10
Q

Example of Type II mechanism of disease of:

Heart

A

Rheumatic Heart Disease

& Dressler Syndrome

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11
Q

Example of Type II mechanism of disease of:

Red cells

A

Autoimmune Hemolytic Anemia

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12
Q

Example of Type II mechanism of disease of:

Platelets

A

Thrombocytopenic Purpura (ATP)

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13
Q

Example of Type II mechanism of disease of:

Thyroid

A

Graves’ Disease

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14
Q

Example of Type II mechanism of disease of:

Pancreatic islets

A

Juvenile diabetes

Type 1 diabetes

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15
Q

Myastenia Gravis

A
  • 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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16
Q

AIRE

A

(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.

17
Q

Goodpasture Syndrome

A
  • 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)
18
Q

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

A

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

  • Type II hypersensitivity
19
Q

Rheumatic Heart Disease

A
  • 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)

20
Q

Dressler Syndrome

A

• 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
21
Q

Autoimmune Hemolytic Anemia

due to?

A

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
22
Q

Autoimmune Thrombocytopenic Purpura (ATP)

A
  • Bleeding abnormalities due to platelet destruction by autoAbs
  • Platelets opsonized for destruction in the spleen
23
Q

Graves’ Disease

A

“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 )

24
Q

Juvenile diabetes

Type 1 diabetes

A

• AutoAbs to islet-associated antigens

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

25
Q

Linear immunoflourescent patterns

A

represent Ab that directly attack BM and so they can uniformly distribute along the membrane.

These indicate Type II immunopathology

26
Q

Lumpy-bumpy immunoflourescent patterns

A

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

27
Q

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

A

Anti-IgG to see the IgG that is bound to the BM

  • ie: good pasture’s syndrome
28
Q

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

A
  • 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).
29
Q

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

A

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

30
Q

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

A

• Damage results from Abs binding to self-cells

31
Q

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

A
  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
32
Q

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

A

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

33
Q

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

A

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
34
Q

Examples of type II hypersensitivity

A
  1. Myasthenia gravis
  2. Rheumatic heart disease
  3. Dressler’s syndrome
  4. Goodpasteurs
  5. Graves disease
  6. autoimmune thrombocytopenic purpura
  7. . AIHA

TT DD ex 3 and BL ex 2 (21 decks)

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