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Questions and Answers
Which types of hypersensitivity reactions are primarily involved in graft rejection?
Which types of hypersensitivity reactions are primarily involved in graft rejection?
What is the primary mechanism responsible for cellular reactions in graft rejection?
What is the primary mechanism responsible for cellular reactions in graft rejection?
Which transplant-related event leads to hyperacute rejection directly after vascular anastomosis?
Which transplant-related event leads to hyperacute rejection directly after vascular anastomosis?
In acute rejection, which of the following typically happens?
In acute rejection, which of the following typically happens?
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What is often observed microscopically during hyperacute rejection?
What is often observed microscopically during hyperacute rejection?
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Which type of graft rejection is most commonly associated with renal transplants?
Which type of graft rejection is most commonly associated with renal transplants?
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What organ is most commonly transplanted, as noted in transplant studies?
What organ is most commonly transplanted, as noted in transplant studies?
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Which factor primarily influences the immune response against a graft?
Which factor primarily influences the immune response against a graft?
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Which opportunistic infection is most commonly associated with patients diagnosed with AIDS?
Which opportunistic infection is most commonly associated with patients diagnosed with AIDS?
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What is a characteristic feature of Kaposi sarcoma in patients with AIDS?
What is a characteristic feature of Kaposi sarcoma in patients with AIDS?
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Which of the following neoplasms is NOT commonly associated with HIV infections?
Which of the following neoplasms is NOT commonly associated with HIV infections?
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In patients with AIDS, which infection generally does NOT contribute to opportunistic infections?
In patients with AIDS, which infection generally does NOT contribute to opportunistic infections?
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What is the primary cause of immunosuppression in AIDS?
What is the primary cause of immunosuppression in AIDS?
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What primary immunodeficiency is characterized by the absence or significant decrease of B cells due to a mutation in B-cell tyrosine kinase?
What primary immunodeficiency is characterized by the absence or significant decrease of B cells due to a mutation in B-cell tyrosine kinase?
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Which of the following is a common feature of Severe Combined Immunodeficiency (SCID)?
Which of the following is a common feature of Severe Combined Immunodeficiency (SCID)?
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What genetic anomaly is associated with DiGeorge syndrome?
What genetic anomaly is associated with DiGeorge syndrome?
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What is typically the most common underlying cause of Autosomal Recessive SCID?
What is typically the most common underlying cause of Autosomal Recessive SCID?
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What procedure is essential before bone marrow transplantation to achieve immunodeficiency in the recipient?
What procedure is essential before bone marrow transplantation to achieve immunodeficiency in the recipient?
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Which immunodeficiency syndrome involves an increased susceptibility to infections and certain cancers due to absent or deficient immune functions?
Which immunodeficiency syndrome involves an increased susceptibility to infections and certain cancers due to absent or deficient immune functions?
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What method can reduce the risk of graft versus host disease (GVHD) following bone marrow transplantation?
What method can reduce the risk of graft versus host disease (GVHD) following bone marrow transplantation?
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Which condition is NOT classified under T-cell deficiencies?
Which condition is NOT classified under T-cell deficiencies?
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What characterizes agammaglobulinemia?
What characterizes agammaglobulinemia?
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Which condition is most likely associated with isolated IgA immunodeficiency?
Which condition is most likely associated with isolated IgA immunodeficiency?
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What is the primary defect in X-linked hyper-IgM syndrome?
What is the primary defect in X-linked hyper-IgM syndrome?
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Which infection is X-linked hyper-IgM syndrome patients particularly susceptible to?
Which infection is X-linked hyper-IgM syndrome patients particularly susceptible to?
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What is a common feature of common variable immunodeficiency?
What is a common feature of common variable immunodeficiency?
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What condition is characterized by reduced intracellular killing and impaired phagosome-lysosome fusion?
What condition is characterized by reduced intracellular killing and impaired phagosome-lysosome fusion?
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Which age group is primarily affected by the symptoms of agammaglobulinemia?
Which age group is primarily affected by the symptoms of agammaglobulinemia?
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Which of the following is NOT a cause of secondary immunodeficiency?
Which of the following is NOT a cause of secondary immunodeficiency?
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Which mechanism is primarily responsible for graft versus host disease (GVHD) following transplantation?
Which mechanism is primarily responsible for graft versus host disease (GVHD) following transplantation?
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In acute humoral rejection, which of the following histopathological changes is typically observed?
In acute humoral rejection, which of the following histopathological changes is typically observed?
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What is one significant consequence of chronic rejection seen microscopically?
What is one significant consequence of chronic rejection seen microscopically?
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Which condition is most likely associated with repeated blood transfusions prior to kidney transplantation?
Which condition is most likely associated with repeated blood transfusions prior to kidney transplantation?
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Which cell type is primarily responsible for inducing tissue damage in the recipient during GVHD?
Which cell type is primarily responsible for inducing tissue damage in the recipient during GVHD?
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What is a common outcome of administering high doses of prednisolone as a form of immunosuppression?
What is a common outcome of administering high doses of prednisolone as a form of immunosuppression?
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Chronic rejection mechanisms are typically associated with which pathological process?
Chronic rejection mechanisms are typically associated with which pathological process?
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Which of these conditions primarily occurs in the setting of hematopoietic stem cell transplantation?
Which of these conditions primarily occurs in the setting of hematopoietic stem cell transplantation?
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Study Notes
Tissue Transplantation
- Grafts are divided into four types:
- Tissues of the organ (MHC)
- Some lymphocytes of the donor
- Some macrophage (APC) of the donor
Problems of Transplantation
-
Graft Rejection (Host versus graft): Occurs when the host's immune system attacks the transplanted tissue.
- The rejection is due to the difference in the MHC (HLA) system of the donor and the recipient.
- Both cell-mediated immunity and antibody responses are mounted against the transplanted tissue.
- Types II, III, and IV hypersensitivity reactions are involved.
- Kidney is the most common transplanted organ.
-
Graft Versus Host Reaction (GVH): Occurs when the donor's immune cells attack the recipient's tissues.
- Most commonly seen after hematopoietic stem cell (HSC) transplantation but can also occur after transplantation of solid organs rich in lymphoid cells (e.g., the liver).
- The donor's T cells recognize the recipient's HLA antigens as foreign and attack them.
- Both CD4+ and CD8+ T cells generate DTH and cell-mediated cytotoxicity.
Mechanisms of Graft Rejection
- Cellular Reactions: Mainly responsible for graft rejection and mediated by T cells.
- Humoral Reactions: May be due to preformed circulating antibodies from previous sensitization by blood transfusions or pregnancies.
Types of Graft Rejection (Renal)
-
Hyperacute Rejection: Occurs immediately after transplantation due to preformed antidonor antibodies binding to graft endothelium.
- The kidney becomes cyanosed and secretes only a few drops of bloody urine.
- Microscopically, arterioles and arteries exhibit acute fibrinoid necrosis of their walls (vasculitis) and narrowing or complete occlusion of their lumens by thrombi.
- The kidney is nonfunctional and has to be removed.
-
Acute Rejection: Occurs a few days after transplantation or after stopping immunosuppressive therapy.
- Acute Cellular Rejection: T cells destroy graft parenchyma and vessels through cytotoxicity and inflammatory reactions.
- Acute Humoral Rejection: Antibodies damage graft vasculature.
- Microscopically:
- Cellular Rejection: Extensive interstitial mononuclear cell infiltrate.
- Humoral Rejection: Acute necrotizing vasculitis leading to narrowing of renal arterioles and infarction of renal cortex.
-
Chronic Rejection:
- Occurs months to years after transplantation.
- Probably caused by T cell reaction and secretion of cytokines that induce proliferation of vascular smooth muscle cells, associated with parenchymal fibrosis.
- Microscopically:
- Vasculitis with marked thickening of intima (intimal fibrosis) leading to obliteration of vessel lumen and renal ischemia.
- Fibrosis of glomeruli, interstitial fibrosis, and atrophy of tubules.
Methods of Increasing Graft Survival
- Finding an HLA-compatible donor, which is only possible in identical twins or 1:4 of brothers or sisters.
- Immunosuppression with high doses of prednisolone or cytotoxic therapy.
- Causes non-specific immunosuppression and can lead to opportunistic infections.
- Antithymocytes antibodies
- Repeated blood transfusions from the same donor before transplantation can increase success.
Graft Versus Host Disease (GVHD)
- Occurs when immunologically competent cells or their precursors are transplanted into immunologically compromised recipients.
- The transferred cells recognize alloantigens in the host and attack host tissues.
- Can be acute or chronic.
- Most commonly seen in the setting of HSC transplantation but can occur following transplantation of solid organs rich in lymphoid cells (e.g., the liver).
- The main cells involved in GVHD are CD8+ T-lymphocytes.
- The donor cells attack the actively proliferating cells of the recipient resulting in gastroenteritis, skin rash, jaundice, etc.
- Minimized by:
- Proper HLA typing.
- Depleting donor T cells before marrow transplantation.
Immunodeficiency Syndromes
- Characterized by deficient or absent cellular and/or humoral immune functions.
- Patients with immune deficiency present with increased susceptibility to infections and certain forms of cancer.
Classification of Primary Immunodeficiency
-
B-cell Deficiencies:
- X-linked Agammaglobulinemia (Bruton type): Failure of B-cell precursors to mature into B cells due to mutation of B-cell tyrosine kinase (Btk).
- Affects boys (X-linked).
- Symptoms appear after 6 months of age.
- Increased incidence of otitis media, skin, and respiratory infections caused by Streptococcus pneumoniae or Staphylococcus aureus.
- Common Variable Immunodeficiency (CVID): Most patients have normal or near-normal numbers of B cells in the blood and lymphoid tissues which are not able to differentiate into plasma cells.
- Late-childhood onset of hypogammaglobulinemia and recurrent infections.
- Affects boys and girls equally.
- High frequency of malignancies (gastric cancer and lymphoma) later in life.
- Isolated IgA Deficiency: The most common congenital immunodeficiency, caused by impaired differentiation of naïve B lymphocytes to IgA-producing plasma cells.
- Many are asymptomatic.
- Recurrent sinusitis, pulmonary and urinary infections, as well as recurrent diarrhea.
- High frequency of respiratory tract allergy and a variety of autoimmune diseases.
- X-linked Agammaglobulinemia (Bruton type): Failure of B-cell precursors to mature into B cells due to mutation of B-cell tyrosine kinase (Btk).
-
T-cell Deficiencies:
- Hyper-IgM Syndrome: Affected people have high titers of IgM and IgD antibodies but low titers of IgG, IgA, and IgE antibodies.
- The primary defect is in CD4 T cells.
- The cause is a mutation of X-chromosome gene encoding CD40L.
- Suffer from pyogenic infections and are susceptible to infection with Pneumocystis jiroveci.
- DiGeorge Syndrome: T-cell deficiency due to the abnormal development of the thymus.
- Part of CATCH 22 syndrome: cardiac abnormality, abnormal facies, thymic aplasia, cleft palate, hypocalcemia.
- Caused by a chromosome 22q11 deletion.
- Severe Combined Immunodeficiency (SCID): Prominent susceptibility to severe, recurrent fungal, viral, and bacterial infections.
- Both humoral and cellular immune responses are severely reduced.
- The genetic defects are varied.
- X-linked SCID: The most common form.
- Autosomal Recessive SCID: The most common cause is a deficiency of the enzyme adenosine deaminase (ADA).
- Hyper-IgM Syndrome: Affected people have high titers of IgM and IgD antibodies but low titers of IgG, IgA, and IgE antibodies.
- Complement System Deficiencies
- Phagocytic System Deficiencies
Secondary Immunodeficiency
- More common than primary.
- Main causes:
- Malnutrition
- Diabetes and other metabolic diseases
- Infection (e.g., HIV/AIDS)
- Cancer
- Renal diseases
- Patients receiving chemotherapy or radiotherapy for treatment of cancer.
- Use of immunosuppressive therapy to prevent graft rejection.
AIDS
- Infectious disease caused by human immunodeficiency viruses (HIV).
- Characterized by immunosuppression associated with opportunistic infections, secondary neoplasms, and neurologic manifestations.
- Most common opportunistic infections in AIDS patients:
- Pneumocystis jiroveci pneumonia
- Candida albicans infections of the mouth, esophagus, vagina, and lungs
- Cytomegalovirus enteritis and pneumonitis
- Atypical mycobacterial infection of the gastrointestinal tract
- Cryptococcus neoformans meningitis
- Cryptosporidium enteritis
- Most common neoplasms associated with HIV infections:
- Kaposi sarcoma
- Non-Hodgkin lymphoma
- Carcinoma of the uterine cervix
- Squamous cell carcinoma of the skin
- Kaposi sarcoma: Atypical spindle cells enclosing slit-like vascular spaces. This rare tumor is a frequent finding in patients with AIDS.
Chediak-Higashi Syndrome
- Reduced rate of intracellular killing and chemotactic movement.
- Inability of phagosome-lysosome fusion and proteinase deficiency.
- Associated with NK cell defect, platelet, and neurological disorders.
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Description
Test your knowledge on the types of tissue grafts and the complications associated with transplantation, particularly graft rejection and graft versus host reactions. This quiz covers essential concepts related to the immune response in transplantation, including MHC differences and hypersensitivity reactions.
