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General Pathology > Exam #3: Immunopathology I > Flashcards

Exam #3: Immunopathology I Flashcards

1
Q

What is a Type I Hypersensitivity reaction? What cells mediate a Type I Hypersensitivity reaction?

A

This is an allergic reaction/ anaphylaxis that is

  • TH2 cells
  • IgE antibodies
  • Mast cell degranulation
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2
Q

What is a Type II Hypersensitivity reaction? What cells mediate Type II Hypersensitivity reactions?

A

This is antibody-mediated hypersensitivity that is caused by:

  • Secreted IgG antibodies
  • Secreted IgM antibodies
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3
Q

What is a Type III Hypersensitivity reaction? What cells mediate Type III Hypersensitivity reactions?

A

This is immune-complex mediated disorder, where antigen-antibody complexes deposit in the blood deposit in tissue & induce inflammation

  • IgG antibodies
  • IgM antibodies
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4
Q

What is a Type IV Hypersensitivity reaction? What cells mediate Type IV Hypersensitivity reactions?

A

This is cell mediated immune disorder; sensitized T-cells are the cause tissue injury

  • Th1
  • Th17
  • CTLs
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5
Q

Describe the general mechanism of Type II Hyersensitivity.

A

Antibodies react with antigens on the patient’s cell surfaces or ECM.

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6
Q

Describe the mechanism of Type I Hypersensitivity.

A

1) Activation of Th2 cells & IgE class switching in B-cells in response to an allergen
2) Production of IgE
3) Binding of IgE to Fc receptor on mast cells
4) Repeat exposure to allergen–>mast cell degranulation

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7
Q

Describe the mechanism of Type III Hypersensitivity.

A

Immune complexes are deposited in tissue & induce complement activation

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8
Q

What is a hallmark example of Type III Hypersensitivity?

A

Lupus

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9
Q

What are the antibodies produced against in SLE?

A

Nuclear antigens

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10
Q

Describe the mechanism of Type IV Hypersensitivity.

A

1) Exposure of naive T-cell to antigen via presentation from dendritic cell
2) Differentiation of antigen-stimulated T-cells to Th1 or Th17
3) Subsequent exposure to antigen–>immune response that causes sx.

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11
Q

What is the hallmark example of Type IV Hypersensitivity reaction?

A

Rheumatoid Arthritis

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12
Q

What is an autograft?

A

Graft of your own tissues

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13
Q

What is an isograft?

A

Graft from an identical twin i.e. same genetic background

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14
Q

What is an allograft?

A

Graft from the same species but a different genetic background

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15
Q

What is a xenograft?

A

Graft from a different species

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16
Q

Generally, what are the two pathways of T-cell mediated transplant rejection?

A

1) Direct pathway= T-cells of the transplant recipient recognize donor MHC molecules on the surface of circulating APCs from the graft
- CD8+ cell recognize MHC I & differentiate into CTLs
- CD4+ cells recognize MHC II & differentiate into Th1 effector cells

2) Indirect pathways= recipient T-cell recognize MHC antigens of the graft donor, after they are presented by the RECIPIENT’S antigen presenting cells

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17
Q

What are the two general mechanisms T-cell mediated transplant rejection?

A

1) Cell-mediated cytotoxicitiy (CD8)= CTLs destroy graft parenchyma & endothelial cells by releasing perforin & granzyme
2) Delayed type hypersenstiivty (CD4)= helper (Th1 & Th17) lymphocytes secrete cytokines that recruit mononuclear cells & release inflammatory mediators, leading to tissue damage

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18
Q

What are the two cell types that are injured in transplant rejection?

A

1) Epithelial cells

2) Vascular cells

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19
Q

What are the humoral mechanisms of transplant rejection?

A

Type II Hypersensitivity
- Antibodies bind HLA antigens in the graft endothelium & activate complement

Type III Hypersensitivity
- Antigen- antibody complexes form in the circulation, deposit, and fix complement

**Both responses are to donor HLA antigens

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20
Q

Generally, what is transplant rejection?

A

Immune damage resulting from recipient response to allograft HLA antigens

21
Q

What is hyperacute rejection? Specifically, what is the timeline & what are the cellular mediators? What is the typical morphology of the affected graft?

A
  • Mins- hours
  • Preformed antidonor antibodies are present in the circulation of the recipient & attack the graft immediately after it is put in

*****Leads to fibrinoid necrosis & thrombosis

22
Q

What is acute rejection? Specifically, what is the timeline & what are the cellular mediators? What is the typical morphology of the affected graft?

A
  • Days- months
  • Cellular rejection i.e. CD4 & CD8 T-cell mechanisms

*****Leads to lymphocytic infiltrates & tubular necrosis

23
Q

What is chronic rejection? Specifically, what is the timeline & what are the cellular mediators? What is the typical morphology of the affected graft?

A
  • Months to years
  • Combined chronic cellular & humoral rejection

*****Vascular changes, interstitial fibrosis, tubular atrophy, chronic inflammation

24
Q

Where do the preformed antibodies in hyperacute rejection come from?

A

1) Prior transplant
2) Blood transfusions
3) Multiparous women

25
Q

What is the most common indication for liver transplant in adults? Children?

A 
Adults= Hepatitis C 
Children= Biliary atresia
26
Q

What is the timeline for acute liver rejection?

A

Cellular rejection occurs 3 months after transplant

27
Q

What is chronic liver transplant rejection? Describe the presentation of chronic liver rejection.

A

In chronic rejection, there is a disappearance of bile ducts due to direct immunologic destruction or loss of blood supply

  • End result is portal & hepatic fibrosis
  • Jaundice is the common presenting symptom
28
Q

What labs are elevated in in kidney rejection vs. liver rejection?

A

BUN & Creatinine

AST & ALT

29
Q

Describe the microsopic appearance of chronic liver transplant rejection.

A
  • Arterial lesion with foam cells
  • Myointimal hyperplasia
  • Luminal obliteration
30
Q

How is hyperacute rejection prevented?

A

Cross-matching recipient serum with donor lymphocytes to determine the presence of cytotoxic Ab to donor MHC Class I & II antigens

31
Q

What happens in acute rejection of the heart transplant?

A

Cell mediated (lymphocyte) destruction of cardiac myocytes.

32
Q

What are the complications of cardiac transplant?

A

Graft arteriopathy= silent MI leading to CHF or sudden death

Malignancy that happens in the setting of immunosuppression

  • EBV
  • B-cell lymphoma
33
Q

What is graft ateriopathy?

A

Narrowing of a lenghty stretch of coronary vessel caused by intimal hyperplasia, which can lead to silent MI, CHF, & sudden death

34
Q

What are the major drugs that are used for immunosuppressive therapy?

A

1) Cycloporine= blocks “NFAT”–a transcription factor necessary for IL-2
2) Steroids= suppress macrophage activity & inflammation
3) Drug inhibitors of lymphocyte proliferation

35
Q

What are the major complications of hematopoietic cell transplant?

A
  • GVHD
  • Infection
  • Immunodeficiency
36
Q

What is graft vs. host disease?

A

Generally, competent cells transplanted into the crippled host recognize host cell antigens & attack. Common targets inlude the epithelial of:

  • Skin
  • GIT
  • Liver

*****Specifically, donor T-cells recognize host HLA antigens & mount a Type IV reaction

37
Q

Describe the appearance of hyperacute rejection in tissue.

A

Immune complex fomration leads to:

  • Fibrinoid necrosis
  • Vasculitis
  • Thrombosis & ischemia
38
Q

What mechansisms of hypersensitivity mediate acute rejection?

A

II
III
IV

39
Q

What is the tissue hallmark in acute rejection?

A

Inflammation with lymphocytic infiltrates & tubular necrosis

40
Q

What is the predominant cell types in acute rejection?

A

Lymphocyte

41
Q

What kind of vascular injury is seen in acute rejection?

A

1) Necrotizing vasculitis

2) Intimal thickening due to accumulation of fibroblasts, foamy macrophages, & myocytes

42
Q

What are the mechanisms that mediate chronic rejection?

A

Type II, III, & IV

43
Q

What are the morphological characteristics of chronic rejection?

A

Vascular changes, intersisital fibrosis, tubular atrophy, chronic inflammation

44
Q

What is the triad of acute liver rejection?

A

1) Portal tract inflammation
2) Bile duct epithelial damage
3) Endothelitis of portal vein & hepatic artery branches

45
Q

What is heart transplant indicated for?

A

Advanced, irreversible myocardial disease with intractable CHF

46
Q

What are the mechanisms of heart transplant rejection?

A

Classic cellular rejection with interstitial & perivascular T-cell infiltrates that cause MYOCYTE necrosis
- Don’t grow back

47
Q

What happens in acute rejection of the heart transplant?

A

Cell mediated destruction of cardiac myocytes.

48
Q

What are the complications of cardiac transplant?

A
  • Graft arteriopathy

- Malignancy that happens in the setting of immunosuppression

49
Q

What is a hematopoietic transplant?

A

Bone marrow transplant for:

1) Hematologic disorder
2) Non-hematologic malignancy
3) Immunodeficiency

General Pathology (33 decks)

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