Type IV Immunopathology Flashcards

1
Q

Explain the initiation and elicitation of an immune response in type IV immunopathology (poison ivy example)

A

Initiation: poison ivy contain urushiol, which can penetrate intact skin and become associated w/ MHC dendritic cells. Dendritic cells travel to draining lymph nodes, present MHC+antigen to Th0 precursors -> Th0 precursons differentiate into Th1 and Th17 cells.

No inflammatory reaction because the stimulant is already gone!

Elicitation: actual reaction from first exposure. Memory-T-cell form expanded clones get activated in area of urushiol contact, Th1 cells secrete IFNgamma, which attracts a huge amount of macrophages -> inflammatory response. Delayed hypersensitivity (6-12 hrs after exposure to be visible, 24-48 hrs to peak)

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2
Q

Explain tuberculin skin testing

A

Mantoux skin test - .1 mL of PPD is injected intradermally. Antigen taken up by local macrophages and dendritic cell, presented on MHC Class II. IF subject had expanded # of Tb memory cells, attract macrophages and show inflammatory response. (48 hrs after injection, +15mm=positive)

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3
Q

What is anergy?

A

A complete lack of response of body’s defense mechanisms to foreign substances. Pretty much you need to react to SOMETHING.

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4
Q

What is the QUantiFERON-TB Gold Test

A

Preferred when subject has been BCG immunized
Purified human strain of m. tuberculosis proteins are added to sample of whole blood. After incubation, concentration of INFgamma is measured.

Even after immunization, this stays negative!

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5
Q

Describe contact dermatitis

A

This is NOT ALLERGIES! :D

Has to pass through intact skin to reach antigen presenting cells, associated with MHC Class II. This involved nickel, hair due, latex, topical antibiotics, soaps, etc.

To treat: avoid the thing, topical steroids

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6
Q

Describe HIV patients adverse rxn to abacavir

A

8% of HIV patients given abacavir, a nucleoside reverse transcriptase inhibitor, deveop abacavir hypersensitivity sydrome

Typically have HLA-B*57-1 (Class I, recongnize CTL)

Basically a drug induced autoimmune reaction

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7
Q

What is an HLA association noted for carbamezapine

A

HLA-B*1502, associated w/ Stephens-Johnson Syndrome or Toxic Epidermal Necrolysis

Found in Han Chinese, Thai, Malay and Indian populations

Its no good

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8
Q

Describe the process of graft rejection

A
  1. ) First set rxn - mouse A to M gets rejected in 10-20 days. Recepient has 5-10% of its T-cells able to react w/ foreign MHC b/c they look like self MHC+peptide
  2. ) Second set rxn - mouse A to M gets rejected in 5-10 days. Secondary response form T-cell memory! Specific!!!!
  3. ) Hyperacute “white graft” rxns - if you keep doing the adobe, eventually the graft will be rejected before healing (remains white and bloodless.) Common with xenografts b/c you often already have some kind of immune response against other animals.
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9
Q

Multiple Sclerosis

A

demyelinating disease, T-cell reactivity to auto-antigen (myelin basic protein) responts to therapies targeted at T cells (such as natalizumab) AND B-cell depleting therapies (like rituximab)

Your brain is an antigen, but T-cells won’t go in. UNLESS presented the “proper” way via dendritic cells and THEN make an immune response, T-cells go into the brain!

Molecular mimicry is LIKELY the cause of MS.

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10
Q

Hashimoto Thyroiditis

A

destructive attach by T-cells on thyroid antigens. Most common cause of hypothyroidism.

T-cell and anti-thyroid antibodies used to confirm diagnosis

Obvi 5x more in women

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11
Q

Sjorgen Syndrome

A

second most common autoimmune disease.

Characterized by dry eyes and dry mouth. Autoimmune rxn against exocrine glands (saliva and tears)

Involves CTL -> genetic and environmental predispositions

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12
Q

Juvenile Diabeetuuuus

A

antibodies to insulin secreting beta cells found in over 90% of pts at time of diagnosis

Antibodies are mostly markers -> T-cells are implicated in pathogenesis

Strong HLA association: linkage disequilibrium between HLA-DR3 & HLA-DQ2 or HLA-DR4 & HLA-DQ8

Thought to be a problem b/c allows ready presentation of islet associated peptides.

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13
Q

Graft v. Host Rxns and the 2 subtypes

A

There is a good chance that graft contains T-cells, which will try to reject the host…

  1. ) Acute GvHD -> 2-10 weeks after bone marrow transplant. Symptoms include musculopapular skin rash, diarrhea, hepatic inflammation w/ jaundice and infection. (in bone marrow, removing T-cells may prevent acute GvHD, but may make graft less successful!)
  2. ) Chronic GvHD ->months to years after transplant, even for pts w/ perfect HLA match (minor histocompatibility antigens)
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14
Q

Graft vs. Leukemia Reaction

A

Patients that receive stored, pre-treatment marrow of themselves have fewer GvHD symptoms BUT higher rate of leukemia relapse

Thus, marrow w/ active T-cells may be important in fighting leukemia AND for the success of the transplant

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15
Q

Th2 cells in immunopathology

A

Found in asthma and chronic work infestation

activate macrophages (M2) which produce fibrosis and attract eosinophils.

Mycobacterium leprae - some have strong Th1 response, some have strong Th2!
Th1 response=large skin and nerve legions with infection
Th2 response=controlled infection, widely disseminated in small granulomas

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