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Questions and Answers
What is the main characteristic of AIDS?
Which of the following infections is considered an opportunistic infection in AIDS patients?
Which neoplasm is most frequently associated with HIV infections?
Which microorganism is associated with cryptococcal infections in AIDS patients?
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What type of therapy is associated with increased risk of opportunistic infections due to immunosuppression?
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What primarily causes graft rejection during transplantation?
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Which type of graft rejection happens immediately after transplantation?
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What is the main cellular component responsible for acute cellular rejection of a transplant?
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What major mechanism is mainly responsible for humoral reactions during graft rejection?
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What is the consequence of hyperacute rejection observed in the kidney?
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Which hypersensitivity reaction types are involved in graft rejection?
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What pathological feature characterizes hyperacute rejection in a kidney transplant?
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What event usually triggers acute rejection to occur after transplantation?
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What primarily causes acute humoral rejection in grafts?
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What is a key microscopic finding in chronic rejection of a transplant?
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Which treatment method can enhance graft survival when donor compatibility is low?
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Which type of T cell primarily mediates Graft Versus Host Disease (GVHD)?
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What condition can occur when immunologically competent donor cells are transplanted into a compromised host?
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What is an effect of high-dose immunosuppression in transplant patients?
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Which organ transplant is most commonly associated with Graft Versus Host Disease?
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What is one of the basic consequences of acute GVHD?
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What is the primary purpose of total body irradiation before transplantation?
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Which of the following strategies can help minimize graft-versus-host disease (GVHD)?
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What defines Severe Combined Immunodeficiency (SCID)?
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What genetic defect is most commonly associated with X-linked SCID?
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What condition is characterized by a lack of or hypoplasia of the thymus?
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Which immunodeficiency syndrome is related to a failure in the maturation of B-cell precursors?
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Which is NOT a consequence of immunodeficiency syndromes?
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What is a common cause of autosomal recessive SCID?
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What condition is characterized by an absent or markedly decreased concentration of all classes of immunoglobulins?
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What type of congenital immunodeficiency is found in approximately 1 in 850 people?
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Which syndrome results from a defect in isotype switching due to a mutation in the X-chromosome gene encoding CD40L?
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What is a common feature of common variable immunodeficiency?
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Which of the following conditions is associated with an increased frequency of malignancies, such as gastric cancer and lymphoma?
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What is a key characteristic of isolated IgA immunodeficiency?
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What condition is associated with reduced intracellular killing and phagosome-lysosome fusion?
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What type of immunodeficiency is typically more common, primary or secondary?
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Study Notes
Tissue Transplantation
- Grafts are divided into four types.
- Grafts contain tissues of the organ (MHC), lymphocytes of the donor and macrophages (APC) of the donor.
Problems of Transplantation
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Graft rejection: Host's immune system attacks the graft.
- Occurs due to MHC (HLA) differences between donor and recipient.
- T lymphocytes and antibodies react against graft antigens, destroying the tissue.
- Types II, III, and IV hypersensitivity reactions are involved.
- Kidneys are the most commonly transplanted organ.
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Graft versus host reaction (GVHD): Donor's immune system attacks the recipient's body.
- Occurs when immune-competent cells from the donor recognize recipient's HLA antigens as foreign and attack them.
- Seen mostly in bone marrow transplantation.
- CD8+ T cells attack host tissues through delayed type hypersensitivity (DTH) and cell-mediated cytotoxicity.
Mechanisms of Graft Rejection
- Cellular reactions: Mediated by T cells, responsible for graft rejection.
- Humoral reactions: Involve preformed circulating antibodies due to previous sensitization by blood transfusions or pregnancies.
Pathology of Graft Rejection (Renal)
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Hyperacute rejection:
- Occurs immediately after transplantation.
- Preformed antidonor antibodies bind to graft endothelium.
- Caused by previous sensitization.
- Characterized by vascular anastomosis, cyanosis, bloody urine, fibrinoid necrosis of arterioles/arteries, and thrombi.
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Acute rejection:
- Occurs within days after transplantation or after stopping immunosuppressive therapy.
- Cellular rejection: T cells destroy graft parenchyma and vessels.
- Humoral rejection: Antibodies damage graft vasculature.
- Cellular rejection manifests as interstitial mononuclear cell infiltrate.
- Humoral rejection manifests as acute necrotizing vasculitis leading to narrowing of arterioles and renal infarction.
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Chronic rejection:
- Occurs months or years after transplantation.
- Cause: T cell reactions and cytokines leading to vascular smooth muscle proliferation and fibrosis.
- Microscopic findings: Vasculitis with intimal fibrosis, obliteration of vessel lumens, renal ischemia, glomerular fibrosis, interstitial fibrosis and tubular atrophy.
Increasing Graft Survival
- HLA-compatible donor: Ideal but rarely available except for identical twins or 1:4 sibling matches.
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Immunosuppression: High-dose prednisolone or cytotoxic therapy.
- Causes non-specific immunosuppression, increasing risk of opportunistic infections.
- Antithymocyte antibodies: Newer treatment option.
- Repeated blood transfusions: From the same donor before transplantation improves success rates.
Graft-Versus-Host Disease (GVHD)
- Definition: Immunologically competent cells from donor attack recipient tissues due to HLA differences.
- Occurrence: Primarily in HSC/BM transplantation, rarely in solid organ transplants with lymphoid cells (e.g. liver).
- Main cells involved: CD8+ T lymphocytes.
- Consequences: Gastroenteritis, skin rash, jaundice, etc.
- Minimization: Proper HLA typing, donor T cell depletion before transplantation.
Immunodeficiency Syndromes
- Definition: Deficient or absent cellular and/or humoral immune functions.
- Clinical manifestations: Increased susceptibility to infections and certain cancers
Primary Immunodeficiency Classification
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B-cell deficiencies:
- X-linked agammaglobulinemia (Bruton type): Failure of B-cell precursor maturation due to Btk mutation.
- Common variable immunodeficiency: Normal B-cell numbers but inability to differentiate into plasma cells.
- Isolated IgA deficiency: Impaired differentiation of B lymphocytes into IgA-producing plasma cells.
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T-cell deficiencies:
- Hyper-IgM syndrome: Defect in isotype switching, high IgM/IgD, low IgG/IgA/IgE due to CD40L mutation.
- DiGeorge syndrome: T-cell deficiency due to thymus hypoplasia or absence (CATCH 22 syndrome).
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Severe combined immunodeficiency (SCID): Severe combined immunodeficiency (SCID): Impaired lymphocyte development.
- X-linked SCID: Most common form, X-linked mutation affecting cytokine receptors.
- Autosomal Recessive SCID: Deficiency of ADA enzyme.
- Complement system deficiencies: Defects in complement proteins.
- Phagocytic system deficiencies: Defects in phagocyte function.
Severe Combined Immunodeficiency (SCID)
- Clinical features: Prominent susceptibility to fungal, viral, and bacterial infections, reduced humoral and cellular immunity.
- Genetic defects: Varied and often unknown.
- X-linked SCID: Most common form, X-linked mutation affecting cytokine receptors.
- Autosomal Recessive SCID: Deficiency of ADA enzyme.
DiGeorge Syndrome
- Definition: T-cell deficiency due to abnormal thymus development (hypoplasia or absence).
- CATCH 22 syndrome: Cardiac abnormality, abnormal facies, thymic aplasia, cleft palate, hypocalcemia.
- Cause: Chromosome 22q11 deletion.
X-linked Agammaglobulinemia (Bruton)
- Definition: Failure of B-cell precursor maturation due to Btk mutation.
- Features: Absent or decreased B cells and immunoglobulins.
- Clinical presentation: Onset after 6 months of age, increased susceptibility to infections caused by encapsulated bacteria.
Common Variable Immunodeficiency
- Definition: Normal B-cell numbers but inability to differentiate into plasma cells.
- Clinical presentation: Late-childhood onset of hypogammaglobulinemia and recurrent infections.
- Risk factors: Increased frequency of malignancies later in life (gastric cancer, lymphoma).
Isolated IgA Immunodeficiency
- Prevalence: Most common congenital immunodeficiency, 1:850 people.
- Cause: Impaired differentiation of naïve B lymphocytes to IgA-producing plasma cells.
- Clinical presentation: Often asymptomatic.
- Complications: Recurrent infections, respiratory allergies, autoimmune diseases (SLE, rheumatoid arthritis).
X-linked Hyper-IgM Syndrome
- Definition: Defect in isotype switching, leading to high IgM/IgD and low IgG/IgA/IgE antibodies.
- Cause: Mutation of X-chromosome gene encoding CD40L, disrupting B-cell activation.
- Clinical presentation: Pyogenic infections, susceptibility to Pneumocystis jiroveci.
Chediak-Higashi Syndrome
- Definition: Reduced intracellular killing, chemotaxis, and phagosome-lysosome fusion.
- Features: Proteinase deficiency, NK cell defects, platelet and neurological disorders.
Secondary Immunodeficiency
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Causes:
- Malnutrition.
- Diabetes and other metabolic diseases.
- Infections (e.g., HIV/AIDS).
- Cancer.
- Renal diseases.
- Chemotherapy or radiotherapy.
- Immunosuppressive therapy.
AIDS (Acquired Immunodeficiency Syndrome)
- Definition: Infectious disease caused by HIV, characterized by immunosuppression, opportunistic infections, secondary neoplasms, and neurologic manifestations.
-
AIDS-Defining Lesions in HIV-infected patients:
-
Opportunistic infections:
- Pneumocystis jiroveci pneumonia.
- Candida albicans infections.
- Cytomegalovirus enteritis/pneumonitis.
- Atypical mycobacterial infections.
- Cryptococcus neoformans meningitis.
- Cryptosporidium enteritis.
-
Neoplasms:
- Kaposi's sarcoma.
- Non-Hodgkin lymphoma.
- Carcinoma of the uterine cervix.
- Squamous cell carcinoma of the skin.
-
Opportunistic infections:
Kaposi's Sarcoma
- Definition: Atypical spindle cells surrounding slit-like vascular spaces.
- Significance: Frequent finding in patients with AIDS.
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Description
Explore the intricacies of tissue transplantation, including the types of grafts and the mechanisms underlying graft rejection. Learn about graft versus host reactions and the importance of MHC differences between donors and recipients. This quiz covers essential concepts vital for understanding transplant immunology.
