Exam #3: Immunopathology I Flashcards by Jonathan Kallevang

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

This is an allergic reaction/ anaphylaxis that is

TH2 cells
IgE antibodies
Mast cell degranulation

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

This is antibody-mediated hypersensitivity that is caused by:

Secreted IgG antibodies
Secreted IgM antibodies

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

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

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

Th1
Th17
CTLs

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Describe the general mechanism of Type II Hyersensitivity.

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

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Describe the mechanism of Type I Hypersensitivity.

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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Describe the mechanism of Type III Hypersensitivity.

Immune complexes are deposited in tissue & induce complement activation

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What is a hallmark example of Type III Hypersensitivity?

Lupus

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What are the antibodies produced against in SLE?

Nuclear antigens

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Describe the mechanism of Type IV Hypersensitivity.

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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What is the hallmark example of Type IV Hypersensitivity reaction?

Rheumatoid Arthritis

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What is an autograft?

Graft of your own tissues

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What is an isograft?

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

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What is an allograft?

Graft from the same species but a different genetic background

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What is a xenograft?

Graft from a different species

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

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

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

1) Epithelial cells

2) Vascular cells

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What are the humoral mechanisms of transplant rejection?

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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Generally, what is transplant rejection?

Immune damage resulting from recipient response to allograft HLA antigens

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

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

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

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

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

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

Months to years
Combined chronic cellular & humoral rejection

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

Where do the preformed antibodies in hyperacute rejection come from?

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

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

``` Adults= Hepatitis C Children= Biliary atresia ```

What is the timeline for acute liver rejection?

Cellular rejection occurs 3 months after transplant

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

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

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

BUN & Creatinine AST & ALT

Describe the microsopic appearance of chronic liver transplant rejection.

- Arterial lesion with foam cells - Myointimal hyperplasia - Luminal obliteration

How is hyperacute rejection prevented?

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

What happens in acute rejection of the heart transplant?

Cell mediated (lymphocyte) destruction of cardiac myocytes.

What are the complications of cardiac transplant?

Graft arteriopathy= silent MI leading to CHF or sudden death Malignancy that happens in the setting of immunosuppression - EBV - B-cell lymphoma

What is graft ateriopathy?

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

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

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

What are the major complications of hematopoietic cell transplant?

- GVHD - Infection - Immunodeficiency

What is graft vs. host disease?

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

Describe the appearance of hyperacute rejection in tissue.

Immune complex fomration leads to: - Fibrinoid necrosis - Vasculitis - Thrombosis & ischemia

What mechansisms of hypersensitivity mediate acute rejection?

II III IV

What is the tissue hallmark in acute rejection?

Inflammation with lymphocytic infiltrates & tubular necrosis

What is the predominant cell types in acute rejection?

Lymphocyte

What kind of vascular injury is seen in acute rejection?

1) Necrotizing vasculitis | 2) Intimal thickening due to accumulation of fibroblasts, foamy macrophages, & myocytes

What are the mechanisms that mediate chronic rejection?

Type II, III, & IV

What are the morphological characteristics of chronic rejection?

Vascular changes, intersisital fibrosis, tubular atrophy, chronic inflammation

What is the triad of acute liver rejection?

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

What is heart transplant indicated for?

Advanced, irreversible myocardial disease with intractable CHF

What are the mechanisms of heart transplant rejection?

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

What happens in acute rejection of the heart transplant?

Cell mediated destruction of cardiac myocytes.

What are the complications of cardiac transplant?

- Graft arteriopathy | - Malignancy that happens in the setting of immunosuppression

What is a hematopoietic transplant?

Bone marrow transplant for: 1) Hematologic disorder 2) Non-hematologic malignancy 3) Immunodeficiency