I&I 2024

Question 1

Sentinel cells in the skin

Answer 1

macrophages
mast cells
dendritic cells (DCs) including epidermal Langerhans cells.
dendritic cell (DC) subsets, including dermal DCs and plasmacytoid DCs (pDCs)
T cell subsets, including CD4+ T helper 1 (TH1), TH2 and TH17 cells, γδ T cells and natural killer T (NKT) cells.

Question 2

TNF-α promotes a coagulable state by

Answer 2

increasing the shedding of the protein C receptor and inhibiting thrombomodulin production, inducing complement activation and stimulating the production of tissue factor by endothelial cells and mononuclear phagocytes.

Question 3

Azurophilic granules contain

Answer 3

MPO (peroxidase-positive granules); proteases such as cathepsins, proteinase-3, and elastase; and antimicrobial proteins such as defensins and the BPI.
MPO, α-defensins, bactericidal/permeability-increasing protein (BPI), elastase, proteinase-3, and cathepsin G.

Question 4

Specific granule neutrophil contain

Answer 4

Alkaline phosphatase
Lactoferrin
Lysozyme
NADPH oxidase
Collagenase
Cathelicidin

Question 5

specific granule eosinophil contain

Answer 5

Cathepsin
Major basic protein
Eosinophil cationic protein
Eosinophil peroxidase
Eosinophil-derived neurotoxin

Question 6

specific granular basophil contain

Answer 6

Heparin
Histamine

Question 7

Citrullination

Answer 7

a post-translational modification (PTM) that involves the hydrolysis of the positively charged guanidium group on arginine to generate a neutral urea (Fig. 1a)1. Citrullination plays crucial roles in many physiological processes, including the epigenetic regulation of gene transcription, neutrophil extracellular trap (NET) formation or NETosis, and maintaining pluripotency

Question 8

Citrullination is catalyzed by

Answer 8

the protein arginine deiminases (PADs) (Fig. 1a), a group of four catalytically active cysteine hydrolases (PAD1–4). PADs are Ca2+-dependent enzymes and the presence of calcium increases PAD activity by >10,000-fold. Calcium-binding leads to dramatic conformational rearrangements, particularly of the nucleophilic cysteine (C645 in PAD1, 4; C647 in PAD2; C646 in PAD3) to form a catalytically competent active site.

Question 9

Aberrant protein citrullination is a hallmark of

Answer 9

multiple autoimmune disorders, including rheumatoid arthritis (RA), multiple sclerosis (MS), ulcerative colitis (UC), and lupus, as well as several neurodegenerative diseases and cancer.

Question 10

BPI protein

Answer 10

Bacterial permeability-increasing protein

Question 11

serous

Answer 11

of, relating to, or resembling serum

Question 12

serous fluid

Answer 12

a clear to pale yellow watery fluid that is found in the body especially in the spaces between organs and the membranes which line or enclose them (such as the heart and pericardium or abdomen and peritoneum) and that when occurring in large quantities is indicative of a pathological condition (such as cirrhosis or heart failure) or surgical complication

Question 13

Identifying the 5 exudate wound drainage types & differences

Answer 13

Serous exudate:
This type appears as a clear or pale yellow, thin, and watery plasma. During the inflammatory stage, serous is a regular part of healing, and small amounts are considered normal. However, if there are moderate to heavy amounts, this may indicate a high bioburden count.

Sanguineous exudate:
When fresh blood leaks from a wound, this is sanguineous drainage. This is most commonly seen in deep partial- and full-thickness wounds. In the inflammatory stage, a small amount is a normal occurrence. But if noted outside of this stage, sanguineous can be a result of trauma to the wound.

Serosanguineous exudate:
The most common type of secretion seen in wounds is serosanguineous. Appearing thin, watery, and pale red to pink in color, this occurs in the inflammatory stage. A small amount of this is considered normal in wound healing.

Seropurulent exudate:
When the secretion is thin, watery, cloudy, and yellow to tan in color, it is considered seropurulent. When this type is present, it is usually the first sign the body is fighting an infection, according to Dashner. She added that if an infection is present, honey with a foam border dressing can be used as a treatment method, although this depends on the size and location of the wound and the amount of exudate.

Purulent exudate:
Drainage that is thick, opaque, and tan, yellow, green, or brown in color is purulent. This is never a normal occurrence in the wound bed and is often associated with infection or high bacterial levels. Dashner stated that this type is considered the most severe because it can indicate an active infectious process and may need to be cultured.

Question 14

“Negative” acute-phase proteins

Answer 14

decrease in inflammation. Examples include albumin, transferrin, transthyretin, retinol-binding protein, antithrombin, transcortin. The decrease of such proteins may be used as markers of inflammation. The physiological role of decreased synthesis of such proteins is generally to save amino acids for producing “positive” acute-phase proteins more efficiently.

Question 15

Positive acute-phase proteins

Answer 15

serve (as part of the innate immune system) different physiological functions within the immune system. Some act to destroy or inhibit growth of microbes, e.g., C-reactive protein, mannose-binding protein,[3] complement factors, ferritin, ceruloplasmin, serum amyloid A and haptoglobin.
Fibrinogen, prothrombin, factor VIII, von Willebrand factor,
Plasminogen activator inhibitor-1 (PAI-1)

Question 16

Lipopolysaccharide

Answer 16

Endotoxin. a collective term for components of the outermost membrane of cell envelope of Gram-negative bacteria, such as E. coli and Salmonella[2] with a common structural architecture. Lipopolysaccharides (LPS) are large molecules consisting of three parts: an outer core polysaccharide termed the O-antigen, an inner core oligosaccharide and Lipid A (from which toxicity is largely derived), all covalently linked.

Question 17

Endotoxin

Answer 17

Lipopolysaccharide. a collective term for components of the outermost membrane of cell envelope of Gram-negative bacteria, such as E. coli and Salmonella[2] with a common structural architecture. Lipopolysaccharides (LPS) are large molecules consisting of three parts: an outer core polysaccharide termed the O-antigen, an inner core oligosaccharide and Lipid A (from which toxicity is largely derived), all covalently linked.

Question 18

PAMPs

Answer 18

Pathogen-associated molecular patterns.
DAMPs = damage-associated molecular patterns.

Question 19

Bruton disease

Answer 19

X- linked Agammaglobulinemia

Question 20

X- linked Agammaglobulinemia

Answer 20

First described by Bruton
X-linked disorder
Found in male babies expressed around 5 to 6 months of age (maternal IgG disappears)
In boys, pre-B cells did not differentiate into mature B lymphocytes
There is a mutation in the gene that encodes for a tyrosine kinase protein
A low level of all immunoglobulins (IgG, IgA, IgM, IgD, and IgE) is present
Infants with X-linked agammaglobulinemia suffer from recurrent bacterial infections: otitis media, bronchitis, septicemia, pneumonia, and arthritis, and Giardia lamblia causes intestinal malabsorption.
Intermittent injections of large amounts of IgG keep the patient alive, but a patient may die at a younger age if infection with antibiotic-resistant bacteria occurs.
Bone marrow transplantation is critical.

Question 21

Selective Immunoglobulin IgA Deficiencies

Answer 21

IgA deficiency is more common than other deficiencies of immunoglobulins.[4]
These patients are more prone to recurrent sinus and lung infections.
A malfunctioning in heavy-chain gene switching may cause this problem.
Treatment should not include gammaglobulin preparations to prevent hypersensitivity reactions.
In the western world, selective IgA deficiency occurs in about 1 in 600 individuals.
In the rare subset of patients in whom IgE or IgG anti-IgA antibodies have formed, anaphylactic reaction to blood products may occur.

Anti-IgA antibodies have been detected in 76.3% of IgA deficient individuals who had a history of anaphylactic transfusion reaction versus 21.7% of asymptomatic IgA deficient individuals.

Currently, there are no universal guidelines for screening for anti-IgA antibodies.

Question 22

DiGeorge syndrome

Answer 22

Congenital thymic aplasia (DiGeorge syndrome)[5]

Tetany is present.
Fungal and viral infections are common.
A transplant of the fetal thymus is needed to correct this deficiency.

Question 23

Chronic Mucocutaneous Candidasis[6]

Answer 23

Selective defect in the functioning of T-cells.
Patients with this disorder usually have a normal T-cell mediated immunity to microorganisms other than Candida.
B-cell function is normal.
Disorders affect both genders, and it is inherited.
Patients, in addition to the above, will have other disorders like parathyroid deficiencies.
Antifungals are useful.

Question 24

Hyper-IgM syndrome

Answer 24

This disorder is characterized by bacterial infections, including pneumonia, meningitis, otitis, among others that start in early childhood.
High levels of IgM.
Other immunoglobulins are defective.
Lymphocytes are normal in numbers.
The gene encoding the CD40 ligand on T lymphocytes is faulty.
B and T lymphocyte cooperation in the immune response are compromised.
The failure to interact with CD40 results in an inability of the B cell to switch from the production of IgM to the other classes of antibodies.
Immunoglobulin therapy is recommended.

Question 25

Interleukin-12 receptor deficiency

Answer 25

Mycobacterial infections are frequent due to the lack of the interleukin-12 receptor. Treatment involves selective antimicrobials.

Question 26

Severe combined immunodeficiency disease (SCID)

Answer 26

There is a failure of early stem cells to differentiate into T and B lymphocytes. Deficiency of the interleukin-2 receptor is the most prevalent. Other problems are due to defective genes encoding ZAP-70, Janus kinase 3, and the genes involved in the DNA recombination of immune cells receptors: RAG1 and RAG2. Clinically characterized by a variety of infections, including those caused by opportunistic pathogens. Selective antibiotics, antivirals, and antifungals are available after the pathogen identification. Immunosuppressive therapy is not needed after allograft transplantation.

Question 27

Severe combined immunodeficiency disease (SCID)

Answer 27

Without HSC transplantation, death occurs in the first year of life. Some patients develop a morbilliform rash shortly after birth due to maternal T cells transferred across the placenta and attack the baby causing GVHD. Affected present with oral candidiasis (thrush), extensive diaper rash and failure to thrive.

Question 28

Wiskott-Aldrich syndrome

Answer 28

X-linked Thrombocytopenia, eczema and marked vulnerability to recurrent infection resulting in early death. This syndrome is associated with normal T-cell numbers with reduced functions, which get progressively worse. IgM concentrations are reduced, but IgG levels are normal. Both IgA and IgE levels are elevated. These patients have a defective WASP, which is involved in actin filament assembly.

Question 29

V(D)J recombination

Answer 29

(variable–diversity–joining rearrangement) is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire of antibodies/immunoglobulins and T cell receptors (TCRs) found in B cells and T cells, respectively. The process is a defining feature of the adaptive immune system.

Question 30

Immunodeficiency with ataxia-telangiectasia

Answer 30

Autosomal recessive Ataxia (abnormal gait) Telangiectasia (vascular malformation) Increased incidence of tumors esp. lymphoma May effect both B and T cells. Thymic hypoplasia Defective isotope-switched antibodies mostly IgA and IgG2. Chromosome 11, encodes a protein kinase called ATM (ataxia telangiectasia mutated) activates p53, important in response to DNA damage (double-strand breaks) important in V(D)J recombination.

Question 31

Immunodeficiency with ataxia-telangiectasia

Answer 31

This is a deficiency of T-cells associated with a lack of coordination of movement (ataxia) and dilation of small blood vessels of the facial area (telangiectasis). T-cells and their functions are diminished to various degrees. B-cell numbers and IgM concentrations are normal to low. IgG is often reduced, and IgA is considerably reduced. There is a high incidence of malignancy, especially leukemias, in these patients.

Question 32

MHC deficiency (Bare leukocyte syndrome)

Answer 32

This subjects have fewer CD4+ or CD8+ T lymphocytes that predispose these individuals to be prone to recurrent infections. Antibody production is affected and predispose to bacteremia.

Question 33

Hereditary angioedema

Answer 33

autosomal dominant genetic pattern. Caused by C1 inhibitor deficiency Clinically characterized by generalized edema including the one leading to acute suffocation Therapy with oxymetholone and danazol can be helpful in correcting the defect.

Question 34

C3 deficiency.

Answer 34

Frequent infections by extracellular bacteria

Question 35

C5 deficiency predisposes to

Answer 35

viral infections.

Question 36

deficiency of the membrane attack complex (MAC) are particularly susceptible to

Answer 36

bacteremia caused by Neisseria species.

Question 37

C2 and C4 deficiencies

Answer 37

Autoimmune diseases caused by C2 and C4 deficiencies and mimics systemic lupus erythematosus.

Question 38

Chronic granulomatous disease (CGD)

Answer 38

mostly an X-linked disorder. It is clinically characterized by a defective NADPH that interferes with the intracellular ability of neutrophils to kill engulfed bacteria species. NADPH oxidase is required for the generation of peroxidase and superoxides that will kill the organisms. The intracellular survival of the organisms leads to the formation of a granuloma, an organized structure consisting of mononuclear cells. These granulomas can become large enough to obstruct the stomach, esophagus, or bladder. Patients with this disease are very susceptible to opportunistic infections by certain bacteria and fungi, especially with Serratia and Burkholderia. Nitroblue tetrazolium (NBT) dye reduction test confirms the diagnosis of CGD and the dichlorofluorescein (DCF) test is also useful. Aggressive therapy with wide-spectrum antibiotics and antifungal agents is required.

Question 39

Leukocyte adhesion deficiency syndrome

Answer 39

characterized by pyogenic infections, including pneumonia and otitis. It is an autosomal recessive disease, and the faulty gene encodes for an integrin. There is an impaired adhesion and defective phagocytosis of bacteria. Treatment involves the use of selective antibiotics.

Question 40

DiGeorge anomaly defect

Answer 40

defect in the third and fourth pharyngeal pouches

Question 41

DiGeorge anomaly chromosome

Answer 41

have partial monosomy of 22q11-pter or 10p.

Question 42

In the bare leukocyte syndrome, there is a mutation in the gene that encodes

Answer 42

for the MHC class II transactivator (CIITA), resulting in the absence of class-II MHC molecule on antigen-presenting cells including macrophages and dendritic cells. A mutation in the gene that encodes for a transport-associated protein (TAP) results in the lack of class-I MHC molecule expression, which is manifested by a deficiency of CD8+ T lymphocytes.

Question 43

Isohemagglutinin

Answer 43

The strict definition of this term is an antibody that agglutinates red blood cells from others of the same species. So, technically, we could call any alloantibody identified in human plasma an “isohemagglutinin.” However, blood bankers use the term only in reference to the naturally occurring antibodies in the ABO blood group system: Anti-A in a group B person Anti-B in a group A person Anti-A, anti-B, and anti-A,B in a group O person

Question 44

A negative Mantoux test shows

Answer 44

A negative Mantoux test shows the T-cell deficiency.

Question 45

Enlarged spleen will produce dullness in

Answer 45

Enlarged spleen will produce dullness in Traube's space and the clinical features suggest infectious mononucleosis.

Question 46

cause a widespread erythematous rash in patients with infectious mononucleosis

Answer 46

Amoxicillin is known to cause a widespread erythematous rash in patients with infectious mononucleosis. Therefore, it should not be prescribed to patients with sore throats.

Question 47

The classical triad for mononucleosis

Answer 47

fever, pharyngitis, and lymphadenopathy. Additional complaints include a headache, general malaise, and poor oral intake. Unfortunately for some, fatigue can be persistent for months. Lymphadenopathy is more common in the posterior cervical region.

Question 48

Heterophile antibodies false-negative rate for mononucleosis

Answer 48

The test has a 25% false-negative rate and heterophile antibodies might be undetectable up to the second or third week of infection. Heterophile antibodies are antibodies induced by external antigens that cross-react with self-antigens.

Question 49

Among the most important transcription factors activated by TLR signals are members of the

Answer 49

nuclear factor κB (NF-κB) family

Question 50

Paul Ralph Ehrlich (born May 29, 1932) is an American biologist known for his predictions and warnings about the consequences of population growth, including famine and resource depletion.

Answer 50

Ehrlich became well known for the controversial 1968 book The Population Bomb, which he co-authored with his wife Anne H. Ehrlich, in which they famously stated that "[i]n the 1970s hundreds of millions of people will starve to death in spite of any crash programs embarked upon now."

Question 51

Paul Ehrlich (German; 14 March 1854 – 20 August 1915) was a Nobel Prize-winning German physician and scientist who worked in the fields of hematology, immunology and antimicrobial chemotherapy. Among his foremost achievements were finding a cure for syphilis in 1909 and inventing the precursor technique to Gram staining bacteria.

Answer 51

Magic bullet Ehrlich reasoned that if a compound could be made that selectively targeted a disease-causing organism, then a toxin for that organism could be delivered along with the agent of selectivity. Hence, a "magic bullet"

Question 52

the immunological functions of lymphocytes were unknown before the

Answer 52

1960's

Question 53

bursa of Fabricius

Answer 53

Bruce Glick removed the bursa of Fabricius, a hindgut lymphoid organ, from newly hatched chicks to test its role in behavioural development. The bursectomized birds developed normally but, when birds left over from his experiment were used in a classroom demonstration of antibody production, some of them failed to make antibodies. In follow-up studies, early bursectomy was consistently shown to prevent the development of normal antibody responses. The report of these findings was rejected by a mainstream journal because it was not considered to be of general interest and its publication in Poultry Science in 1956 (Ref. 13) was unnoticed at the time by immunologists.

Question 54

Max Cooper and Robert Good suggested a functional division of labor between cells in the chicken bursa of Fabricius responsible for antibody production and cells that required an intact thymus for manifestation of delayed-type hypersensitivity (Cooper et al11,12 ).

Question 55

Paroxysmal nocturnal hemoglobinuria (PNH)

Answer 55

rare disease that presents clinically with a variety of symptoms, the most prevalent of which are hemolytic anemia, hemoglobinuria, and somatic symptoms including fatigue and shortness of breath. Other findings associated with PNH include thrombosis, renal insufficiency, and in the later course of the disease, even bone marrow failure. The condition is genetic, with the mutations occurring on the X linked gene.

Question 56

first diagnostic test for PNH

Answer 56

Ham test (acidified serum test) in 1937, Ham was able to discover that erythrocytes of individuals with PNH hemolyzed when incubated with normal acidified urine. This resulted in the first diagnostic test for PNH

Question 57

Paroxysmal nocturnal hemoglobinuria occurs due to

Answer 57

loss of complement inhibition specifically CD55 and CD59, the development of a genetic mutation in hematopoietic stem cells. This mutation of the X-linked gene phosphatidylinositol glycan class A (PIGA), produces a deficiency in the glycosylphosphatidylinositol (GPI) protein, which is responsible for anchoring other protein moieties to the surface of erythrocytes.

Question 58

Paroxysmal nocturnal hemoglobinuria occurs due to

Answer 58

The resultant loss of complement inhibition produces chronic complement-mediated hemolysis of PNH cells. This chronic state of hemolysis can be exacerbated if the complement system is activated by stress due to surgery, trauma, or other triggers for inflammation

Question 59

Are men or women affected more with paroxysmal nocturnal hemoglobinuria (PNH)?

Answer 59

Although the condition is due to an X-linked chromosome mutation, women are affected at a slightly higher rate than men. This is because the acquired defect occurs in somatic, or clone, hematopoietic stem cells, rather than germ cells. The phenotype can be created due to a single somatic mutation. Men only have one X chromosome, and women only express a single X chromosome due to lyonization, or inactivation of the duplicate X chromosome. Therefore, once the mutation occurs, the cell line perpetuates the abnormality until clonal superiority is achieved, and the phenotype is expressed.

Question 60

lyonization

Answer 60

inactivation of the duplicate X chromosome in women.

Question 61

Paroxysmal nocturnal hemoglobinuria occurs due to the development of a genetic mutation in hematopoietic stem cells.

Answer 61

the X-linked gene phosphatidylinositol glycan class A (PIGA), produces a deficiency in the glycosylphosphatidylinositol (GPI) protein, which is responsible for anchoring other protein moieties to the surface of erythrocytes. Proteins responsible for the regulation of complement activity, specifically CD55 and CD59, are thereby prevented from attaching to PNH affected cells. The resultant loss of complement inhibition produces chronic complement-mediated hemolysis of PNH cells. This chronic state of hemolysis can be exacerbated if the complement system is activated by stress due to surgery, trauma, or other triggers for inflammation.

Question 62

The PIGA mutation that is responsible for

Answer 62

Paroxysmal nocturnal hemoglobinuria the X-linked gene phosphatidylinositol glycan class A (PIGA),

Question 63

In PNH, what is gets depleted?

Answer 63

Nitric oxide in PNH, these cleaning mechanism pathways are overburdened resulting in free hemoglobin in the intravascular system. The body tries to compensate by irreversibly binding nitric oxide to produce methemoglobin and nitrate, but this ends up depleting the nitric oxide supply.[11] Nitric oxide has multiple essential functions, including vasodilation and relaxation of smooth muscle. When nitric oxide is depleted, smooth muscle dystonia can occur. In PNH, dystonia of the gastrointestinal tract is most common. This is why, in PNH, many patients will present with complaints of dysphagia, esophageal spasm, and abdominal pain. Another consequence of depleted nitric oxide is the inability to vasodilate. For instance, nitric oxide plays a role in the vascular dilatation of the corpora cavernosa. As a result, many male patients present with erectile dysfunction.

Question 64

In PNH, most symptoms that the patients experience results due to

Answer 64

intravascular hemolysis.

Question 65

In PHH, free heme released during periods of hemolysis has a toxic effect on what organ?

Answer 65

Free heme released during periods of hemolysis has a toxic effect on the kidney and can produce an acute kidney injury. Another side effect of chronic hemolysis is iron deposition in the kidney that leads to scarring, cortical infarcts, and proximal tubule dysfunction. This is why hemosiderosis is often seen in patients with hemoglobinuria.

Question 66

leading cause of significant morbidity and the most common cause of death in PNH.

Answer 66

Thrombosis Cerebral and intraabdominal venous thrombosis is commonly seen. The hepatic vein is the most common site for thrombosis in PNH patients.

Question 67

What factors play a role in thrombosis in PNH?

Answer 67

The GPI anchor protein defect created by a PIGA gene mutation enhances platelet activation and aggregation in addition to causing hemolysis of red cells. Nitric oxide depletion and complement activation also promote thrombosis by enhancing platelet aggregation and inflammatory cytokine release, respectively. Finally, the thrombophilia found in PNH is enhanced by defective fibrinolysis. Deficiency or absence of a GPI anchored protein responsible for plasminogen activation is suspected.

Question 68

gold standard test for PNH diagnosis.

Answer 68

Diagnostic flow cytometry. It utilizes various monoclonal antibodies, and special reagent called fluorescent aerolysin reagent (FLAER) that binds directly to glycosylphosphatidylinositol (GPI) anchored protein, specifically their glycan portion. This test is capable of evaluating a variety of GPI-anchored proteins, most notably as CD55 and CD59, with high sensitivity and specificity.

Question 69

PNH can be categorized into three types

Answer 69

1. Classic PNH. 2. PNH with another bone marrow (BM) disorder 3. Subclinical PNH.

Question 70

The most common BM disorders that occur with PNH

Answer 70

aplastic anemia (AA) myelodysplastic syndrome (MDS) primary myelofibrosis (PMF).

Question 71

Budd Chiari syndrome.

Answer 71

caused by occlusion of the hepatic veins (usually due to a blood clot) that drain the liver. The symptoms are non-specific and vary widely, but it may present with the classical triad of : abdominal pain, ascites, and liver enlargement. It is usually seen in younger adults, with the median age at diagnosis between the ages of 35 and 40, and it has a similar incidence in males and females. The syndrome can be fulminant, acute, chronic, or asymptomatic. Subacute presentation is the most common form.

Question 72

Most common cause of Budd Chiari syndrome.

Answer 72

The most common cause is due to acquired hypercoagulability associated with myeloproliferative disorders (accounting for 40–50% of cases)

Question 73

Eculizumab works by

Answer 73

inhibition of factor C5. All complement pathways cause the formation of membrane attack complex (MAC). MAC is formed by C3b, C5b, and other complement factors. Eculizumab prevents C5 to convert into C5a and C5b factors; thus, effectively inhibiting MAC formation and complement-mediated lysis.

Question 74

Eculizumab vs Ravulizumab

Answer 74

inhibition of factor C5. Ravulizumab has 3 to 4 times longer half-life and requires dosing every eight weeks. It is shown to be more cost-effective compared to eculizumab. It has fewer breakthrough hemolysis episodes, and it is non-inferior to eculizumab in terms of efficacy and safety profile. However, since the drug is new, there are no long term data available. In the future, ravulizumab will likely replace eculizumab as the first-line treatment for PNH.

Question 75

The membrane attack complex usually works against what

Answer 75

encapsulated bacteria such as Neisseria

Question 76

Functions of C5a

Answer 76

C5a increases the dilation of blood vessels and attracts inflammatory cells especially neutrophils.

Question 77

all Eculizumab and Ravulizumab patients must be vaccinated against what

Answer 77

Neisseria

Question 78

Anemia, cytopenias, and thrombosis make a classic triad that characterizes what

Answer 78

PNH

Question 79

protein S deficiency,

Answer 79

Although venous thrombosis in this patient raises the possibility of protein S deficiency, patients with protein S deficiency usually have deep vein thrombosis in the lower extremities, and hepatic vein thrombosis is uncommon. In contrast, the hepatic vein is one of the most common sites for venous thrombosis in PNH patients.

Question 80

What must be checked before starting a patient on certain biologic medications for immune-mediated rheumatological or gastrointestinal conditions (eg, adalimumab, infliximab).

Answer 80

HBV, HCV, and TB.

Question 81

Flow cytometry detects PNH using the following method.

Answer 81

Aerolysin binds to GPI-linked molecules and causes lysis of normal cells, but in GPI-deficient patients, such as those with PNH, it does not cause cell lysis. FLAER uses an inert form of aerolysin, which is proaerolysin. Proaerolysin selectively binds to GPI anchor protein with high affinity but does not cause cell lysis. All the normal cells will show binding with proaerolysin, but all the PNH cells will not bind with proaerolysin.

Question 82

Hageman factor

Answer 82

Factor XII. Factor twelve

Question 83

Atopy

Answer 83

an increased propensity to develop immediate hypersensitivity reactions.

Question 84

Atopic triad

Answer 84

atopic dermatitis allergic rhinitis asthma

Question 85

Atopic march

Answer 85

Infants develop atopic dermatitis Later develop allergic rhinitis and later develop asthma.

Question 86

Uric acid

Answer 86

a byproduct of purine metabolism. generated from endogenous as well as exogenous sources. The human body makes about 300 - 400 mg of uric acid per day, with most of it being produced in the liver.

Question 87

The organs responsible for the elimination and excretion of uric acid are the

Answer 87

kidneys and intestines. In the intestinal tract, uric acid is transformed into ammonia and carbon dioxide. Bacteria utilize the intestinal ammonia for metabolism. In the kidneys, almost 100% of uric acid is filtered by glomerulus. Uric acid is further reabsorbed, secreted, and reabsorbed in the proximal convoluted tubule (PCT), ultimately resulting in only 10% fractional elimination in the urine.

Question 88

Hyperuricosuria can be defined as

Answer 88

the daily urinary uric acid excretion of more than 800 mg in men and more than 750 mg in women.

Question 89

Classical macrophage activation

Answer 89

induced by microbial products such as endotoxin, which engage TLRs and other sensors, and by T cell–derived mediators, especially the cytokine IFN-γ.

Question 90

Classically activated (also called M1) macrophages produce

Answer 90

NO and ROS and upregulate lysosomal enzymes, all of which enhance their ability to kill ingested organisms, and they secrete cytokines that stimulate inflammation.

Question 91

alternatively activated (also called M2) macrophages

Answer 91

are not actively microbicidal; instead, their principal function is tissue repair. They secrete growth factors that promote angiogenesis, activate fibroblasts, and stimulate collagen synthesis. They also inhibit inflammation.

Question 92

High endothelial venules

Answer 92

High endothelial venules (HEVs) are modified, postcapillary venules lined by a simple cuboidal, rather than the simple squamous epithelium lining other venules. This modification allows lymphocytes to leave the blood through the HEVs and enter the lymphoid tissue. HEVs are located in the appendix, Peyer’s patch, tonsil and lymph node. HEVs are present in all secondary lymphoid organs with the exception of spleen Evidence accumulated over the past 40 years indicates that blood vessels with HEV features develop in non-lymphoid tissues in many human chronic inflammatory diseases. The expression of high levels of the L-selectin-binding HEV-specific glycoforms of HEV sialomucins is undoubtedly one of the most important features of the HEV endothelium.

Question 93

one of the most important features of the HEV endothelium.

Answer 93

The expression of high levels of the L-selectin-binding HEV-specific glycoforms of HEV sialomucins

Question 94

Most of the inflammasomes that have been described to date contain

Answer 94

a NOD-like receptor (NLR) sensor molecule, namely NLRP1 (NOD-, LRR- and pyrin domain-containing 1), NLRP3, NLRP6, NLRP7, NLRP12 or NLRC4 (NOD-, LRR- and CARD-containing 4; also known as IPAF).

Question 95

Diaphragm muscle from beef cow

Answer 95

Skirt steak (UK). Hanger steak (US) Onglet

Question 96

Etiology of Berylliosis, also known as chronic beryllium disease (CBD)

Answer 96

Exposure to beryllium is the underlying causative factor. Heavy beryllium-using industries include metal machine shops, electronics, defense industries, and beryllium extraction companies. Other industries include ceramic, automotive, aerospace, jewelry making, dental/alloy appliance, and computer. It appears that some people may have a genetic predisposition towards developing severe CBD.[5] Beryllium exposure tends to occur via inhalation of beryllium fumes or dust, but it can also be absorbed following skin exposure. The organic forms of beryllium are rapidly excreted, but the insoluble inorganic particles can remain in the body for many years.

Question 97

The key feature on histopathology of Berylliosis, also known as chronic beryllium disease (CBD)

Answer 97

The key feature on histopathology is the nonnecrotizing granulomas in the lung; which mimic those seen in sarcoidosis.

Question 98

the first lines of treatment for Tuberculosis (TB)

Answer 98

Current first-line treatment for tuberculosis is a quadruple therapy of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) for 2 months, followed by a 4-month continuation of isoniazid and rifampicin and/or ethambutol.

Question 99

The mechanism of action of the other first-line treatment for pulmonary tuberculosis

Answer 99

isoniazid inhibits the DNA synthesis of mycolic acids, rifampicin inhibits the bacterial DNA dependent RNA polymerase and blocks protein synthesis, and the exact mechanism of action of pyrazinamide is unknown. Ethambutol is considered a bacteriostatic drug, interfering with the biosynthesis of arabinogalactan in the cell wall, halting multiplying bacilli.

Question 100

Scotoma

Answer 100

an area of partial alteration in the field of vision consisting of a partially diminished or entirely degenerated visual acuity that is surrounded by a field of normal – or relatively well-preserved – vision.

Question 101

Ethambutol side effects

Answer 101

It chelates copper that inhibits mitochondrial metabolism in the optic nerve, decreasing visual acuity. Serious side effects of ethambutol include confusion, optic neuritis, and liver function abnormalities.

Question 102

the four-drug combination commonly used to treat tuberculosis.

Answer 102

Rifampin, isoniazid, pyrazinamide, and ethambutol

Question 103

Rifampin acts by

Answer 103

inhibiting bacterial DNA-dependent RNA polymerase, and it commonly causes harmless reddish discoloration of body fluids.

Question 104

Streptomycin is one of the antituberculosis drugs and works by

Answer 104

disruption of protein synthesis. Streptomycin typically does not cause visual disturbances.

Question 105

Azithromycin has potent immunomodulatory activity,

Answer 105

reducing transcription of the gene coding for the inflammatory cytokine interleukin-8 (IL-8). Bronchiolitis obliterans is a form of chronic lung transplant rejection in which persistent inflammation at the level of the bronchiolar epithelium leads to the occlusion of small airways throughout the lung and consequent respiratory insufficiency. Azithromycin acts as an immunomodulator and reduces cellular immunopathologic activity.

Question 106

Mechanism of Actionof azithromycin

Answer 106

Like other macrolide antimicrobials, azithromycin binds to the 23S portion of the 50S bacterial ribosomal subunit. It inhibits bacterial protein synthesis by preventing the transit of aminoacyl-tRNA and the growing protein through the ribosome. Azithromycin is less prone to disassociation from the gram-negative ribosome than erythromycin, conferring its greater efficacy against gram-negative pathogens.[20] Like other macrolides and protein-synthesis inhibitors, azithromycin primarily acts as a bacteriostatic agent, inhibiting bacterial growth rather than directly killing organisms. However, especially at higher doses, azithromycin has been shown to have a bactericidal effect against certain bacteria, such as streptococci and H. influenzae.

Question 107

apicoplast

Answer 107

The apicoplast is a parasitic organelle that performs critical metabolic functions in organisms such as Babesia microti (the etiologic agent of babesiosis in the Northeastern United States). It is believed that the apicoplast derives from endosymbiosis and, hence, has bacteria-like protein synthesis machinery such as a 50S ribosomal subunit. With its ability to readily cross cellular and intracellular membranes, azithromycin inhibits the 50S ribosomal subunit within the apicoplast.

Question 108

Azithromycin has demonstrated efficacy against several parasitic organisms

Answer 108

babesia, plasmodium, and toxoplasma. These organisms have an apicoplast within which azithromycin exerts a protein synthesis-inhibiting effect. Babesiosis is the only parasitic disorder for which azithromycin is considered a first-line agent; however, it may be considered an alternative treatment for malaria or toxoplasmosis in certain circumstances.

Question 109

Eukaryotic parasites, such as babesia, do not have what?

Answer 109

cytoplasmic 50S ribosomal subunits; rather, they have an 80S ribosome consisting of a 60S and 40S subunit. Azithromycin is a specific inhibitor of the bacterial 50S subunit and has no known ability to bind to elements of the eukaryotic ribosome. While eukaryotes do not have cytoplasmic 50S ribosomal subunits, they can have intracytoplasmic organelles that do, likely as a result of endosymbiosis. Therefore, the antiparasitic effect desired by administering azithromycin in this patient with babesiosis is due to the inhibition of the 50S ribosomal subunit within the apicoplast organelle and not due to the inhibition of a cytoplasmic ribosomal subunit.

Question 110

babesiosis

Answer 110

a tick-borne parasitic infection endemic to areas of the Northeastern United States, such as upstate New York (where the Adirondack Mountains are located). The CDC's recommended treatment for babesiosis is azithromycin and the antiparasitic drug atovaquone. In parasites, such as babesia, azithromycin inhibits an organelle called the apicoplast.

Question 111

Mycoplasma pneumonia empiric therapy

Answer 111

community-acquired pneumonia caused by Mycoplasma pneumonia. The empiric therapy generally includes a macrolide (e.g., azithromycin), a respiratory fluoroquinolone (e.g., levofloxacin or moxifloxacin), or doxycycline.

Question 112

Efferocytosis

Answer 112

a physiological process where phagocytic cells remove and digest dying cells, or apoptotic cells (ACs). The term comes from the Latin word efferre, which means "to carry the dead to the grave".

Question 113

The clearance of apoptotic cells by professional and non-professional phagocytes — a process termed

Answer 113

Efferocytosis

Question 114

Efferocytosis

Answer 114

(from the latin word 'efferre', which means 'to take to the grave') effectively means 'burial of dead cells', referring to the engulfment of apoptotic cell bodies by efferocytes that leads to the degradation (via effero-metabolism) of apoptotic content without causing an inflammatory response