INMUNO: BOARDS AND BEYOND Flashcards
What is systemic lupus erythematosus (SLE)?
An autoimmune disorder commonly occurring in middle-aged women, characterized by non-specific symptoms like fatigue and fever, and often symmetrical, polyarticular arthritis.
What are common symptoms of SLE?
Fatigue, fever, symmetrical polyarticular arthritis, signs of joint inflammation (warmth, erythema, swelling), and skin manifestations such as a “butterfly rash.”
Describe the classic skin manifestation of SLE.
The “butterfly rash,” which involves a rash on the malar skin (cheeks) and nose.
What is the significance of C3 levels in lupus?
C3 is the most abundant complement protein, and lupus leads to decreased C3 levels due to complement consumption. Low serum complement levels are characteristic of lupus.
Name two other conditions that can cause low serum complement levels (besides from lupus)
Post-streptococcal glomerulonephritis and membranoproliferative glomerulonephritis.
What are interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-α)?
Inflammatory cytokines that act as pyrogens, triggering fever and causing other inflammatory responses, including joint swelling.
What effects does TNF-α have on the body?
It causes vascular leakage, reduces the utilization of fatty acids, and can lead to cachexia.
In a woman with SLE, what would you expect regarding cytokine levels?
Increased serum levels of IL-1 and TNF-α, especially during episodes of inflammation such as fever and joint swelling.
What does recurrent Neisseria meningitidis infections indicate?
A classic presentation of “late complement deficiency,” which involves a deficiency of complement factors C5 to C9.
What is the role of complement factors C5 to C9?
They are required for the formation of the membrane attack complex (MAC), a key defense mechanism against encapsulated bacteria like Neisseria.
How do patients with C5-C9 deficiency typically present outside of Neisseria infections?
They are usually healthy and do not experience severe or life-threatening infections from other causes.
Are recurrent infections with Neisseria meningitidis life-threatening in patients with C5-C9 deficiency?
No, they are common but rarely severe or life-threatening.
What autoimmune disorder is most commonly associated with deficiencies in early complement proteins (C1 through C4)?
Systemic lupus erythematosus (SLE), often developing at an early age.
Why is it paradoxical that complement deficiencies are linked to an inflammatory disorder like SLE?
Complement deposition is a component of inflammatory reactions, yet deficiencies in early complement proteins (C1-C4) are associated with SLE.
How do children with early complement deficiencies present in terms of infections?
They may have recurrent infections, but these infections are not typically limited to Neisseria, as seen in late complement deficiencies.
What specific complement deficiency is associated with infections due to encapsulated bacteria in early childhood?
Complete deficiency of C3, a major opsonin of the complement system, is linked to infections, especially with pneumococcus.
What is factor H?
A glycoprotein found in human plasma, synthesized by the liver and some blood cells, that binds to C3b and inhibits complement activation.
How does factor H affect complement activation?
It binds to C3b and destroys C3b convertase, halting the complement activation process.
In which types of cells has factor H expression been demonstrated?
In cells from several malignancies, including lung carcinomas.
How do tumors utilize factor H to evade the immune system?
By synthesizing factor H, tumors can inhibit complement activation and evade immune detection.
Is produced by the liver and binds mannose found in bacteria. As an activator of the immune system, blocking MBL activity would not increase complement activity as shown in the graph.
Mannose-binding lectin (MBL)
Is a complement protein, and the first protein of the classical pathway. Blocking C1 activity would limit complement activation, not increase complement activity
Complement component 1 (C1)
Is an acute phase reactant produced by the liver in response to inflammation. It can bind bacterial polysaccharides to activate the complement system. Blocking CRP activity would limit complement activation
C-reactive protein (CRP)
What symptoms are consistent with paroxysmal nocturnal hemoglobinuria (PNH)?
Hemolytic anemia (reduced hemoglobin, jaundice, increased reticulocyte count), recurrent abdominal pain, and a history of thrombosis.
What causes PNH?
A lack of glycosylphosphatidylinositol (GPI) anchor proteins that hold CD55 and CD59 on the surface of erythrocytes.
What are CD55 and CD59, and what role do they play in PNH?
CD55 (decay accelerating factor) and CD59 prevent complement activation on red blood cells. Their absence allows the complement system to attack erythrocytes, leading to hemolysis.
When is hemolysis most evident in PNH patients?
In the morning, when urine is especially concentrated, causing it to turn red due to the presence of heme.
Does hemolysis occur only at night in PNH?
No, hemolysis occurs throughout the day, despite the name “nocturnal.”
Besides erythrocytes, which other blood components can be affected by PNH?
Leukocytes and platelets, potentially leading to pancytopenia.
What are some common features of PNH?
Thrombosis (most common cause of death), abdominal pain, fatigue, jaundice, and erectile dysfunction in men.
Why might PNH be diagnosed late?
It is a rare disorder that can be easily missed for many years before a diagnosis is made.
What causes hereditary angioedema?
Deficiency of the C1 inhibitor protein.
What is the main symptom of hereditary angioedema?
Recurrent episodes of swelling and edema due to excess bradykinin.
What causes hereditary spherocytosis?
Deficiency of spectrin, a red blood cell membrane protein.
What abnormality is observed in the peripheral blood of patients with hereditary spherocytosis?
The presence of spherocytes (abnormally shaped red blood cells).
What complication may arise from hereditary spherocytosis?
Splenomegaly due to splenic destruction of red blood cells.
What is the role of glucose-6-phosphate dehydrogenase (G6PD) in red blood cells?
G6PD helps generate nicotinamide adenine dinucleotide phosphate (NADPH), which protects cells from oxidative damage
How does G6PD deficiency affect red blood cells?
It leaves red blood cells vulnerable to oxidative damage due to insufficient NADPH levels
What triggers hemolysis in patients with G6PD deficiency?
Exposure to oxidative triggers such as fava beans and certain medications.
What is the consequence of hemolysis in G6PD-deficient patients?
It can lead to anemia and related symptoms.
What causes hereditary angioedema (HAE)?
Deficiency of the C1 inhibitor protein.
What are the functions of the C1 inhibitor protein?
It inhibits the activity of complement factor C1 and breaks down the inflammatory protein bradykinin.
Why do patients with HAE experience recurrent episodes of swelling?
Elevated bradykinin levels lead to vascular leakage and edema, especially during physiological events that increase bradykinin.
What are common triggers for swelling in HAE patients?
Dental work, cold exposure, and certain foods.
What are the potential serious consequences of laryngeal swelling in HAE?
It can lead to hypoxemia and death.
Why do standard treatments like epinephrine, antihistamines, and glucocorticoids not work in HAE?
They do not counteract the effects of bradykinin, which is responsible for the swelling.
What is the first-line treatment for HAE?
Infusion of C1 inhibitor concentrate from human plasma.
What is the role of complement factor C1 in the classical pathway?
C1 cleaves C4, leading to the production of a C3 convertase.
What clinical finding is associated with HAE due to the deficiency of C1 inhibitor?
Low C4 levels due to the consumption of C4 in the absence of C1 inhibitor.
In absence of C1 inhibitor, C4 is consumed, leading to low C4 levels, one of the hallmark clinical findings of
HAE
What clinical scenario is indicated by recurrent Neisseria infections in a patient?
Terminal complement deficiencies (deficiencies in complement proteins C5-C9).
Why are Neisseria bacteria particularly problematic in patients with terminal complement deficiencies?
Neisseria are encapsulated bacteria that resist phagocytosis, making them highly reliant on the complement system for defense.
What is the CH50 test?
A screening test for complement deficiencies that assesses the function of the complement system.
How is the CH50 test conducted?
Sheep RBCs with antibodies are mixed with the patient’s serum; normal results indicate all complement components are present and functioning.
What does an abnormal CH50 test result indicate?
One or more factors are deficient in the complement system.
Would the CH50 test be normal or abnormal in the scenario of terminal complement deficiencies?
Abnormal.
Is a component of complement activation via the lectin pathway.
Mannose binding lectin
Is a surface marker that protects cells from complement mediated destruction.
CD59
What autoimmune disorder is commonly associated with deficiencies in early complement proteins (C1-C4)?
Systemic lupus erythematosus (SLE), often developing at an early age.
Why is it paradoxical for complement deficiencies to be linked to an inflammatory disorder like SLE?
Because complement deposition is a component of inflammatory reactions, and deficiencies would generally be expected to reduce inflammation.
What is still unclear regarding early complement deficiencies and the development of SLE?
The exact mechanism by which deficiencies in early complement proteins lead to the development of SLE is not well understood.
How do early complement deficiencies affect infection susceptibility in children?
Children may have recurrent infections, but these infections are not typically limited to Neisseria, unlike late complement deficiencies.
What is the significance of complete deficiency of C3 in early complement deficiencies?
It is a major opsonin of the complement system and is associated with increased susceptibility to infections, particularly from encapsulated bacteria like pneumococcus.
What is the most common cause of community-acquired bacterial pneumonia?
Streptococcus pneumoniae.
What are pathogen-associated molecular patterns (PAMPs)?
Molecular sequences recognized as foreign by innate immune cells, capable of triggering an immune response.
How do bacterial PAMPs interact with immune cells?
They bind to toll-like receptors (TLRs) on macrophages and other cells, initiating an immune response.
What happens after PAMPs bind to toll-like receptors?
Cytokine release occurs, leading to an acute inflammatory response.
What role does Prostaglandin E2 play in inflammation?
It is an important mediator of inflammation, but it is not produced by bacteria and does not initiate the immune response.
What are alpha and beta receptors?
Adrenergic receptors activated by epinephrine and norepinephrine, important for the sympathetic nervous system response.
Do adrenergic receptors (alpha and beta) initiate the inflammatory response?
No, they do not initiate the inflammatory response, even though they can be activated during infection.
What is cellulitis and what commonly causes it?
Cellulitis is a skin infection of the dermis caused by Group A Streptococcus (S. pyogenes).
How does cellulitis typically develop?
It often develops after damage to the skin, allowing bacterial entry.
What do inflammatory cells like macrophages release during inflammation?
Cytokines into the circulation, leading to systemic features like fever, chills, and sweats.
What are two key cytokines that cause systemic effects of infection?
Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-α).
What is the role of IL-1 in the body?
IL-1 is an “endogenous pyrogen” that acts on the hypothalamus to raise body temperature, causing fever.
What was TNF-α originally described as, and what are its systemic effects?
Originally described as a factor causing necrosis of tumor cells; it causes fever, cachexia, and vascular leak during inflammation.
What cytokines are associated with chronic inflammation?
IFN-gamma and IL-12.
What type of inflammation is cellulitis of 24 hours duration an example of?
Acute inflammation.
What is the role of Prostaglandin E2 in the context of fever?
It is produced in the hypothalamus in response to pyrogens and works locally to alter the temperature set point to cause fever; it does not circulate systemically.
The mechanism of fever involves a pyrogen like TNF-alpha that circulates systemically leading to increased production of
PGE2 which works locally in the hypothalamus.
What is acute endocarditis?
A bacterial infection of the cardiac valves, typically presenting with nonspecific symptoms like fever, chills, and sweats.
What is a classic physical examination finding in acute endocarditis?
A new cardiac murmur.
What are the most common bacteria that cause endocarditis?
Staphylococcus aureus and Viridans group streptococci.
What are acute phase reactants?
Proteins whose serum levels rise in response to inflammation, including C-reactive protein and clotting factors like fibrinogen.
How is the erythrocyte sedimentation rate (ESR) related to inflammation?
The ESR increases in parallel with acute phase reactants, reflecting the speed at which red blood cells settle due to inflammation.
What causes the increase in ESR during inflammation?
Increased levels of fibrinogen, which causes red blood cells to aggregate and settle more quickly.
Where do most acute phase reactants originate?
Most come from the liver.
What major trigger stimulates the release of acute phase reactants?
Interleukin-6 (IL-6).
Besides stimulating liver release of acute phase reactants, what else does IL-6 do?
It can cause fever by acting on the hypothalamus, making it a pyrogen.
What is bronchiolitis and what is its most common viral cause in children under 2 years old?
Bronchiolitis is a respiratory infection commonly caused by respiratory syncytial virus (RSV).
What are typical symptoms of bronchiolitis?
Wheezing, intercostal retractions, and nasal flaring.
How is bronchiolitis typically diagnosed?
Diagnosis is usually made clinically based on symptoms.
What is the primary treatment for bronchiolitis?
Treatment is primarily supportive, although antiviral medications can be used in some cases.
What type of virus is RSV?
Single-stranded RNA virus.
How does RSV infect the body?
It invades nasopharyngeal and lower respiratory epithelial cells.
How is RSV cleared from the body?
Virally-infected cells present viral antigens in the context of MHC Class I, which are recognized by CD8+ T-cells.
What is the role of CD8+ T-cells in clearing RSV infection?
CD8+ T-cells trigger apoptosis of the infected cells to help clear the virus.
Are found in smooth muscle of the lungs. Their activation with beta agonists like albuterol can be used to dilate the bronchioles and relieve wheezing in RSV infection. These receptors are not, however, important for clearing the virus.
Beta-2 receptors
RSV replication occurs within respiratory epithelial cells where the virus is protected from
Macrophages
Produce mucous which protects the airways from pathogens. These cells do not play a direct role in clearance of virally-infected cells.
Goblet cells
What is the most common childhood malignancy?
Acute lymphoblastic leukemia (ALL).
What type of cells does ALL result from the abnormal proliferation of?
Lymphoblasts, most commonly B-cell precursors.
What are common presenting symptoms of ALL?
Fatigue, splenomegaly, and symptoms related to anemia or thrombocytopenia (e.g., pallor, easy bruising, petechiae).
What is the primary treatment for ALL?
Chemotherapy targeting rapidly-dividing cancer cells.
What are common side effects of chemotherapy in ALL?
Mucositis due to GI epithelial cell damage and bone marrow suppression.
How does bone marrow suppression from chemotherapy affect the risk of infection?
It impairs the production of white blood cells, increasing the risk of infections.
What is the absolute neutrophil count (ANC) used to measure?
The risk of infection in patients undergoing chemotherapy.
Why are neutrophils significant in the context of chemotherapy?
They have a short lifespan (1-5 days) and are the first cells to decline with bone marrow suppression; they make up about 50% of white blood cells and are key to innate immunity.
What does neutropenia indicate?
Impairment of innate immunity and a significant risk of infection.
How are patients with neutropenia monitored during chemotherapy?
They are carefully monitored for signs of infection, and chemotherapy may be temporarily discontinued until neutropenia resolves.
What growth factor may be administered to boost neutrophil counts?
Granulocyte colony-stimulating factor (GCSF).
Granulocytes include neutrophils, eosinophils, and basophils. Since the majority of circulating granulocytes are neutrophils, the terms neutropenia and granulocytopenia are often used
Interchangeably.
Antibodies like IgG derive from B-cells and plasma cells. These cells can live for years, and do not decline as rapidly as neutrophils in patients on chemotherapy.
Complement proteins are synthesized in the liver and are not significantly affected by chemotherapy.
CD4+ T-cells and natural killer cells are lymphocytes that can live for years. They do not decline as rapidly as neutrophils in patients on chemotherapy.
What is the primary goal of vaccination?
To generate antigen-specific circulating antibodies and memory lymphocytes.
What type of immune response is generated after the first dose of vaccination?
A relatively weak immune response with production of IgM antibodies, some IgG antibodies, and memory B-cells.
Why is the initial peak production of IgG antibodies after the first vaccination relatively slow?
There are no memory cells present prior to the first exposure.
What happens after the second vaccination in terms of immune response?
Antigens are recognized by memory B-cells, which rapidly differentiate into IgG-secreting plasma cells.
How does the second vaccination affect the quantity of circulating IgG antibodies?
It leads to an increased quantity of circulating IgG antibodies.
What is the impact of memory B-cells on the time required to reach peak antibody production during subsequent vaccinations?
The time required to reach peak antibody production is decreased.
What are common clinical features at presentation for a child with ALL?
Nonspecific symptoms such as fatigue, malaise, fever, and often hepatosplenomegaly.
How does infiltration of the bone marrow by malignant cells affect blood counts in ALL?
It can lead to anemia and thrombocytopenia, predisposing to bleeding, bruising, or petechiae.
What type of cells are primarily involved in most cases of ALL?
Immature B-cells (pre-B lymphocytes or B-cell lymphoblasts).
How are leukemic B-cells typically described morphologically?
They have a “large nucleus with scant cytoplasm.”
What cell surface markers are typically expressed by leukemic B-cells in ALL?
CD19 and CD22, both classic B-cell markers.
What is the significance of CD10 in ALL?
It is also called the “common acute lymphoblastic leukemia antigen” (CALLA) and is often expressed by leukemic B-cells.
What immunoglobulin characteristics are present in leukemic B-cells compared to mature B-cells?
Immunoglobulins or light chains may be present but are usually not found on the cell surface as they would be in mature B-cells.
What T-cell marker will not be expressed in leukemic B-cells?
CD3.
What is the most common congenital infection in humans?
Congenital cytomegalovirus (CMV) infection.
What percentage of children born with CMV infection have symptoms at birth?
About 10%.
What are some common symptoms of symptomatic congenital CMV infection?
Petechiae, jaundice, hepatosplenomegaly, small size, and microcephaly.
What is the most serious long-term consequence of congenital CMV infection?
Sensorineural hearing loss.
What type of virus is CMV, and what is a characteristic feature of herpes viruses?
CMV is a herpes virus, and it can lead to a permanent, dormant state of infection (latent infection) after primary infection.
During latent infection with CMV, where does low-level replication occur?
Within peripheral and bone marrow white cells.
What type of antibodies indicate active CMV infection?
IgM antibodies.
What type of antibodies can be found during both active and latent CMV infection?
IgG antibodies.
How does the presence of anti-CMV IgG antibodies in the mother relate to her infection status?
It indicates that she had a CMV infection at some point during her pregnancy, either as a primary infection or reactivation, but does not indicate an active infection currently.
How can we determine that the baby has an active CMV infection?
By the presence of both IgM and IgG antibodies in the baby, with IgM indicating that the antibodies were produced by the baby.
At what gestational age can the fetus start producing its own antibodies?
Around 20 weeks gestation.
Why do newborns rely on maternal antibodies for protection?
The newborn antibody response is relatively weak, and most antibodies in the newborn come from the mother.
Why can’t IgM antibodies cross the placenta?
IgM antibodies are too large to cross the placental barrier.
What does the presence of IgM antibodies in a newborn indicate?
It indicates that the antibodies were produced by the baby, suggesting a congenital infection.
Which type of infection can lead to the presence of IgM antibodies in a baby?
Congenital infection.
If a baby has IgM antibodies, what can we infer about the mother’s infection status?
The mother does not have IgM antibodies, indicating she does not have an active infection; the baby’s IgM is from the baby itself.
All herpes viruses can enter a latent state and reactivate.
CMV, Epstein Barr, Herpes Simplex
Why don’t maternal IgM antibodies provide protection to the fetus?
IgM antibodies are large pentamers that cannot cross the placenta.
What type of immune response is typically associated with polysaccharide vaccines?
A relatively weak and short-lived B-cell response primarily consisting of IgM antibodies
How do polysaccharide vaccines activate B-cells?
They activate B-cells in a T-cell-independent manner, without the support of T-cell-helper activity.
Why are polysaccharide antigens often combined with carrier proteins in vaccines?
The carrier protein activates T-cells, leading to a more robust B-cell antibody response than if the polysaccharide were used alone.
What is a common carrier protein used in polysaccharide vaccine formulations?
Tetanus toxoid.
How can Group B strep (GBS) infections be transmitted from mother to baby?
GBS frequently colonizes the genital tract and can be passed to newborns during vaginal delivery.
What interventions are commonly taken for mothers colonized with GBS during delivery?
They receive antibiotics at the time of delivery to reduce the risk of transmitting the infection to the baby.
What serious conditions can babies develop if infected with GBS during childbirth?
Sepsis, pneumonia, or meningitis.
Have any GBS vaccine candidates become widely used?
No, despite research efforts, none of the vaccine candidates have become widely used.
Are found on mucosal surfaces like those of the GI tract and nasopharynx. They are rarely produced in response to vaccination except when oral vaccines are used (e.g.: some polio vaccines).
IgA antibodies
Are monomeric antibodies like IgG whose function is poorly understood. Like IgA, they are more commonly associated with mucosal sites. These would not be produced in response to a polysaccharide vaccine.
IgD antibodies
Bind to mast cells and eosinophils for defense against parasites and are often associated with allergy. These would not be produced in response to a polysaccharide vaccine.
IgE antibodies
Can cross the placenta and would provide protection for the baby. If this woman had produced IgG antibodies, the baby would have had protection against GBS.
IgG antibodies
What do killed vaccines contain?
Virus particles but not live viruses.
How do killed vaccines activate B-cells?
The virus particles are recognized by B-cells and engulfed by antigen-presenting cells, which present vaccine proteins to CD4+ T-cells in the context of MHC class II.
What type of antibodies are generated in response to killed vaccines?
Systemic IgM and IgG antibodies.
What is a key limitation of killed vaccines regarding T-cell response?
They do not generate a robust CD8+ T-cell response.
What do live attenuated vaccines contain?
A virus that has been weakened (attenuated) but can replicate in human cells.
How do live attenuated vaccines activate CD8+ T-cells?
Virally-infected cells present viral antigens in the context of MHC class I.
What are the effects of live attenuated vaccines compared to killed vaccines?
Live attenuated vaccines generate both systemic IgG antibodies and a robust CD8+ T-cell response, while killed vaccines primarily activate B-cells.
What are the two types of polio vaccines mentioned, and how do they differ?
The injected killed polio vaccine (Salk vaccine) and the live attenuated oral vaccine (Sabin vaccine); both generate systemic IgG antibodies, but the Sabin vaccine also activates CD8+ T-cells.
No CD8 T-cell response occurs with the injected, killed vaccine because CD8+ T-cell activation requires virally-infected cells
To present antigens in the context of MHC class I.
What is the typical age range for patients with precursor T-cell acute lymphoblastic leukemia/lymphoma?
Teens or early twenties.
What are common symptoms at presentation for this malignancy, precursor T-cell acute lymphoblastic leukemia/lymphoma?
Pallor and weakness from anemia, bleeding and petechiae from thrombocytopenia, and a large mediastinal mass.
What complications can arise from a large mediastinal mass in T-cell acute lymphoblastic leukemia/lymphoma?
Tracheal obstruction and superior vena cava syndrome.
What indicates that malignant cells are of T-cell lineage?
The presence of T-cell receptor gene rearrangement on diagnostic testing.
What does it mean if cancer cells are described as “double negative”?
They do not express CD4 or CD8, indicating they are immature T-cells.
Where are double negative T-cells normally found?
In the subcapsular zone of the thymus.
What surface markers are associated with B-cells?
CD19, CD20, and surface immunoglobulin.
What is the general CD marker classification for T-cells and B-cells?
CD markers with numbers less than 10 are mostly T-cell markers; CD numbers 19 to 23 are mostly B-cell markers.
What is the most common form of renal cancer?
Renal cell carcinoma (RCC).
What is the classic triad of clinical findings for RCC?
Flank pain, hematuria, and a palpable abdominal mass.
What percentage of RCC patients present with the classic triad?
Less than 10%.
How does renal cell carcinoma typically spread?
Via the bloodstream, often through the renal vein.
What is the most common site of metastases for RCC?
The lungs.
What is the prognosis for stage 4 RCC with distant metastases?
Very poor, with a 5-year survival rate of less than 10%.
What types of immune cells does IL-2 activate?
CD4+ T-cells, CD8+ T-cells, and natural killer (NK) cells.
Why is IL-2 significant in cancer therapy?
It was discovered as a T-cell growth factor, leading to advancements in immunotherapy. IL-2 is a T-cell activator.
How is hepatitis B transmitted?
Through sexual contact, sharing dirty needles, accidental needle sticks, or from pregnant women to their child.
What are common symptoms of acute hepatitis B?
Malaise, nausea, right upper quadrant pain, jaundice, and dark urine.
What laboratory findings are typical in acute hepatitis B?
Marked elevations of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), usually over 1000 U/L.
Which serological markers are present in the acute phase of hepatitis B?
Hepatitis B surface antigen (HBsAg) and IgM to hepatitis core antibody (anti-HBc).
What percentage of patients fully recover from acute hepatitis B?
Most patients fully recover, but some may develop chronic hepatitis B.
What is the primary role of cytotoxic CD8+ T-cells in viral infections?
To recognize virally-infected cells and induce apoptosis, thereby eliminating the cellular machinery needed for viral replication.
How do hepatocytes present viral antigens to CD8+ T-cells?
Hepatocytes present viral antigens on their surface in the context of MHC class I molecules.
What type of infections are children with interferon-gamma (IFN-γ) receptor deficiency prone to?
Atypical (non-tuberculosis) mycobacterial infections.
What is the role of CD4+ Th1 cells in the immune response to mycobacteria?
Th1 cells secrete IFN-γ to stimulate macrophages, enhancing their ability to fight infections.
What cytokine do macrophages release to stimulate Th1 cells?
Interleukin-12 (IL-12).
What genetic deficiencies can impair the immune response to mycobacteria?
Deficiencies in either the IL-12 receptor or the IFN-γ receptor.
What rare disorder is associated with deficiencies in the IFN-γ receptor or IL-12 receptor?
Mendelian susceptibility to mycobacterial disease (MSMD).
What is Bacillus Calmette-Guerin (BCG)?
A live, attenuated form of Mycobacterium bovis used as a vaccine against tuberculosis.
Why can the BCG vaccine cause infection in children with MSMD?
Because BCG is a live vaccine, it can lead to infection in individuals with impaired immune responses to mycobacteria.
What should be considered in a child with recurrent atypical mycobacterial infections?
What should be considered in a child with recurrent atypical mycobacterial infections?
What is the common name for infectious mononucleosis?
“Mono” or “the kissing disease.”
How is Epstein-Barr virus (EBV) primarily transmitted?
Through direct contact, often via saliva.
What age group is most commonly affected by EBV-related infectious mononucleosis?
Young patients, especially college students.
List some common symptoms of infectious mononucleosis.
Fatigue, headache, malaise, hepatosplenomegaly, pharyngitis, and cervical lymphadenopathy.
What type of virus is EBV?
A herpes DNA virus.
Which type of cells does EBV infect and transform?
B-cells.
Name some B-cell malignancies associated with EBV.
Burkitt’s lymphoma and Hodgkin’s lymphoma.
What are atypical lymphocytes, and how do they appear in EBV infection?
Atypical lymphocytes are larger than normal lymphocytes with nucleoli in the nucleus and indented cytoplasm.
What laboratory criteria can help diagnose EBV infection?
At least 50% lymphocytes and at least 10% atypical lymphocytes in the white blood cell count.
What type of T-cells increase in number during an EBV infection, and what is their role?
CD8+ (cytotoxic) T-cells, which help eliminate EBV-infected B-cells.
What happens to EBV after the acute infection resolves?
It enters a dormant (latent) state and can remain lifelong in the host.
When does reactivation of EBV typically occur?
It can reactivate later in life, especially in immunocompromised individuals.
What can reactivation of EBV in immunocompromised patients lead to?
It can lead to B-cell malignancies, similar to those associated with HIV infection
What is a common condition that can trigger EBV reactivation?
Immunocompromised states, such as HIV infection.
What organism causes pneumocystis pneumonia (PCP)?
Pneumocystis jirovecii, a fungus.
In which patients does PCP typically cause disease?
It primarily affects immunocompromised patients, such as those with HIV/AIDS or those undergoing cytotoxic chemotherapy.
How is PCP diagnosed?
Through silver staining of respiratory specimens, which reveals small, round fungi.
What is the role of alveolar macrophages in defending against Pneumocystis?
They recognize the fungus and activate, releasing cytokines that lead to the activation of CD4+ T-cells.
