Sparsh Gupta acute inflammation,vascular and cellular changes
exogenous chemotactic molecules
Bacterial products
Both antibody dependent and independent complement pathway converge on which complement component? (a) C3 (b) C5 (c) C1q (d) C8
C3
Most important mediator of chemotaxis is:
C5a
endogenous chemotactic molecules
C5a • LTB4 • IL-8
Bleeding time assesses:
Function of platelets
Cytokines that mediate innate immunity
IL-1, TNF, IFN, IL-6. IL-12
In genetic deficiency of MPO the increased susceptibility to infection is due to:
Inability to produce hydroxyl-halide radicals
Partial thromboplastin time correlates with:
Intrinsic and common pathway
Deficiency of integrin
LAD 1
All of the following are mediators of inflammation except: (a) Tumour necrosis factor-a (TNF-a) (b) Interleukin-1 (c) Myeloperoxidase (d) Prostaglandins
Myeloperoxidase
Bradykinin causes:
Pain at the site of inflammation
In inflammatory process, the prostaglandin E1and E2 cause
Vasodilatation
Conversion of prothrombin to thrombin requires:
X; Ca ++
IL-10 and TGF-b
down regulate immune responses.
IL-2
growth factor for T-cells.
C3b
required for opsonisation and favor phagocytosis by neutrophils and macrophages.
IL-12
stimulates differentiation to T H1 pathway.
chemotaxis, leukocyte recruitment and activation
(a) C5a (b) Leukotriene B (c) Chemokines (d) IL-8 (e) Bacterial products (f) TNF
Absolute lymphocytosis is seen in
(b) TB; (c) CLL; (d) Brucellosis
The role of bradykinin in process of inflammation is:
(d) Increased vascular permeability > (c) Pain
relative lymphocytosis
1. All causes of neutropenia. 2. Infective hepatitis 3. Convalescence from acute injection. 4. Infant with infections, malnutrition and avitaminosis.
Absolute lymphocytosis
1. Bacterial infections like tuberculosis, brucellosis, syphilis, pertussis, and toxoplasmosis. 2. Viral infections like mumps, rubella, and infectious mononucleosis. 3. Leukemia (chronic lymphocytic). 4. Thyrotoxicosis
Functions of bradykinin
1. Increases vascular permeability 2. Contraction of smooth muscles 3. Dilation of the blood vessels • 4. Pain when injected into the skin Out of these actions of bradykinin, the increase in vessel permeability is a better answer as it is the hallmark of acute inflammation.
All of the following are a family of selectin except (a) P selectin (b) L selectin (c) A selectin (d) E selectin
A selectin Selectins are a family of proteins that are involved in the cellular process of rolling interactions. The following are the three types of selectins: • E selectin (CD 62E) - Present on cytokine-activated endothelial cells and interacts with sialyl lewis X receptor on the leukocyte. • L selectin (CD 62L) - Present on leukocytes and interacts with glycoprotein adhesion molecules (GlyCAM-1), Mad CAM-1 and CD34 on endothelial cells. • P selectin (CD 62P) - Present on platelets and endothelial cells and interacts with sialyl lewis X receptor on leukocytes.
All of the following are signs of inflammation except (a) Pain (b) Swelling (c) Redness (d) Absence of functional loss
Absence of functional loss
Which of these is not a granulomatous disease (a) Leprosy (b) Tuberculosis (c) Sarcoidosis (d) Amebiasis
Amebiasis
All of the following are mediators of acute inflammation except (a) Angiotensin (b) Prostaglandin E2 (c) Kallikrein (d) C3a
Angiotensin Kallikreins like bradykinin, PGs and complement components are mediators of acute inflammation.
Caseous necrosis in granuloma are not found in (a) Tuberculosis (b) Leprosy (c) Histoplasmosis (d) CMV (e) Wegener's granulomatosis
Ans. (b) Leprosy; (d) CMV; (e) Wegener's granulomatosis Caseous necrosis is characteristic of tubercular granuloma, rare in others type of granulomatous disease. TB granuloma is a prototype of immune granuloma. These are caused by insoluble particles; typically microbes that are capable of inducing a cell mediated immune response. Granulomatous lesions may develop in liver in CMV infection.
Prostaglandins are synthesized from:
Arachidonic acid (Ref: Robbins 9/e p84) Arachidonic acid is an essential fatty acid which is acted on by the enzyme cyclo-oxygenase (COX) leading to the formation of the prostaglandins. Q Also know: • Linoleic, linolenic and arachidonic acid are examples of polyunsaturated essential fatty acids Q (PUFA) which means they cannot be synthesized in the human body. • Docosahexaenoic acid Q is an essential fatty acid present in breast milk which is required for myelination of nerves Q . • Richest source of PUFA is safflower oil Q • Coconut oil Q is the poorest source of PUFA
To which of the following family of chemical mediators of inflammation, the Lipoxins belong?
Arachidonic acid metabolites Lipoxins are a recent addition to the family of bioactive products generated from arachidonic acid. They have anti-inflammatory activity
Chronic granulomatous disease is:
Associated with formation of multiple granulomas It is a congenital and not acquired leucocyte function defect.
An 18-year-old woman, Sheila is being evaluated for recurrent facial edema, especially around her lips. She also has recurrent bouts of intense abdo-minal pain and cramps, sometimes associated with vomiting. Laboratory examination finds decreased C4, while levels of C3, decay-accelerating factor, and IgE are within normal limits. A deficiency of which one of the following substances is most likely to be associated with these clinical findings?
C1 esterase inhibitor • Deficiencies of C1 esterase inhibitor result in recurrent angioedema, which refers to episodic non-pitting edema of soft tissue, such as the face. Severe abdominal pain and cramps, occasionally accompanied by vomiting, may be caused by edema of the gastrointestinal tract (GI). C1 inhibitor not only inactivates C1, but also inhibits other pathways, such as the conversion of prekallikrein to kallikrein. It also leads to excess production of C2, and bradykinin. It is the uncontrolled activation of bradykinin that produces the angioedema, • A deficiency of decay accelerating factor (DAF), which breaks down the C3 convertase complex, is seen in paroxysmal nocturnal hemoglobinuria (PNH).
Both antibody dependent and independent complement pathway converge on which complement component?
C3
Which of the following complement component can be activated is both common as well as alternative pathways?
C3 The complement proteins can be activated by 3 pathways; classical, lectin and alternate pathways. Terminal pathway is common to the first three pathways and is present at the level of post activation stage of C3. It eventually leads to the membrane attack complex that lyses cells. As can be seen in the text, C3 is the first common complement protein to be activated in both classical and alternate pathway.
Which complement fragments are called 'anaphylatoxins
C3a and C5a Anaphylatoxins are chemicals which increase vascular permeability and cause vasodilation mainly by releasing histamine from mast cells. C3a, C5a and to a small extent C4a are called anaphylatoxins.
Factor present in the final common terminal complement pathway is: (a) C4 (b) C3 (c) C5 (d) Protein B
C5 The terminal pathway that is common to all pathways of the complement system leads to the membrane attack complex and consists of factors C5, C6, C7, C8 and C9 (C 5b6789 ).
Chemotactic complement components are
C5a
Endogenous chemoattractant is:
C5a
A middle aged scientist Sudarshan is working in the laboratory on the mechanisms involved in inflammation. He observes that the leucocytes leave the blood vessels and move towards the site of bacteria. Which of the following is likely to mediate this movement of the bacteria?
C5a The movement of the leucocytes described in the question is known as chemotaxis. It is a unidirectional movement of the cells along a chemical gradient.
Opsonins
Carbohydrate binding proteins
A 45-year-old poor man Teja has a chronic cough, a cavitary lesion of the lung, and is sputum positive for acid-fast bacilli. Which of the following is the principle form of defense by which the patient's body fights against this infection?
Cell-mediated immunity The principle host defense in mycobacterial infections is cell-mediated immunity, which causes formation of granulomas. In many infectious diseases characterized by granuloma formation, the organisms may persist intracellularly for years in the granulomas to be a source of activation of the infection later. While antibody-mediated phagocytosis and neutrophil ingestion of bacteria (options a and d) are a major source of host defense against many bacteria but they are not active against Mycobacteria. IgA-mediated hypersensitivity (option c) is not involved in the body's defense against Mycobacteria.
A 3-year-old boy, Krish presents with recurrent bacterial and fungal infections primarily involving his skin and respiratory tract. Physical examination reveals the presence of oculocutan-eous albinism. Examination of a peripheral blood smear reveals large granules within neutrophils, lymphocytes, and monocytes. The total neutrophil count is found to be decreased. Further workup reveals ineffective bactericidal capabilities of neutrophils due to defective fusion of phagosomes with lysosomes. Which of the following is the most likely diagnosis?
Chediak-Higashi syndrome Chediak-Higashi syndrome is an autosomal recessive disorder characterized by the abnormal fusion of phagosomes with lysosomes, which results in ineffective bactericidal capabilities of neutrophils and monocytes. These abnormal leukocytes develop giant intracytoplasmic lysosomes. Abnormal formation of melanosomes in these individuals results in oculocutaneous albinism. Most of these patients eventually develop an "accelerated phase" in which an aggressive lymphoproliferative disease, possibly the result of an Epstein-Barr viral infection, results in pancytopenia and death.
After extravasation, leukocytes emigrate in the tissue towards the site of injury. It is called as
Chemotaxis
Symptoms of toxoplasmosis
Chorioretinitis Q is the commonest manifestation of this disease when transmitted congenitally. In the acquired disease, there is usually absence of symptoms.
All of the following vascular changes are observed in acute inflammation, except: (a) Vasodilation (b) Stasis of blood (c) Increased vascular permeability (d) Decreased hydrostatic pressure
Decreased hydrostatic pressure With acute inflammation, hydrostatic pressure is increased (due to increased blood flow from vasodilation) and at the same time osmotic pressure is reduced because of protein leakage (due to increased permeability)
PAF causes all except (a) Bronchoconstriction (b) Vasoconstriction (c) Decreased vascular permeability (d) Vasodilation
Decreased vascular permeability (Ref: Robbins 8/e p60, 9/e p73) PAF is another phospholipid-derived mediator having the following inflammatory effects: • Platelet aggregation • Vasoconstriction • Bronchoconstriction • At extremely low concentration, it may cause vasodilation and increased venular permeability • Increases leukocyte adhesion to endothelium (by enhancing integrin-mediated leukocyte binding), chemotaxis, degranulation, and the oxidative burst. • Stimulates the synthesis of other mediators, particularly eicosanoids, by leukocytes and other cells
In acute inflammation endothelial retraction leads to
Delayed prolonged increase in permeability
Which one of the following statements is not correct regarding 'Stem cell'? (DPG 2011) (a) Developmental elasticity (b) Transdifferentiation (c) Can be harvested from embryo (d) "Knockout mice" made possible because of it
Developmental elasticity Stem cells show the property of developmental plasticity (Not developmental elasticity) which is also known as transdifferentiation. A change in stem cell differentiation from one cell type to another is called transdifferentiation, and the multiplicity of stem cell differentiation options is known as developmental plasticity
chief source of vitamin K in the human body.
Diet Q and intestinal bacteria Q
Delayed transient increase in permeability
Direct endothelial injury
Delayed prolonged bleeding is caused by:
Direct injury to endothelial cells
In acute inflammation due to the contraction of endothelial cell cytoskeleton, which of the following results?
Early transient increase The hallmark of acute inflammation is increased vascular permeability.
Delayed permanent increase
Endothelial cell retraction, endothelial cell damage
C-C beta chemokines includes
Eotaxin
most characteristic of granuloma:
Epithelioid cell
Tensile strength of wound after laparoscopic cholecystectomy in a 30 year old woman depends upon: (a) Replacement of type 3 collagen (b) Extensive cross-linking of tropocollagen (c) Macrophage activity (d) Granulation tissue
Extensive cross linking of tropocollagen Fibrillar collagens (mostly type I collagen) form a major portion of the connective tissue in repair sites and are essential for the development of strength in healing wounds. Net collagen accumulation, however, depends not only on increased collagen synthesis but also on decreased degradation. The recovery of tensile strength results from the excess of collagen synthesis over collagen degradation during the first 2 months of healing, and, at later times, from structural modifications of collagen fibers (cross-linking, increased fiber size) after collagen synthesis ceases.
Cryoprecipitate is rich in which of the following clotting factors?
Factor VIII Cryoprecipitate is a rich source of Factor VIII
Criteria for SIRS (2 or more of the following conditions)
Fever Q (oral temperature >38 o C) or hypothermia Q (<36 o C) • Tachypnea Q (>24 breaths/minute) • Tachycardia Q (>90 beats/minute) • Leukocytosis Q (>12,000/μl), leucopenia Q (<4,000/μl), or >10% Q bands
Function of defensin
Firm adhesion
E cadherin gene deficiency is seen in:
Gastric cancer Cadherin is derived from the "calcium-dependent adherence protein." It participates in interactions between cells of the same type. The linkage of cadherins with the cytoskeleton occurs through the catenins. The cell -to-cell interactions mediated by cadherin and catenins play a major role in regulating cell motility, proliferation, and differentiation and account for the inhibition of cell proliferation that occurs when cultured normal cells contact each other ("contact inhibition"). • Reduced function of E-cadherin is associated with certain types of breast and gastric cancer. • Mutation and altered expression of the Wnt/β-catenin pathway is implicated in in gastrointestinal and liver cancer development.
systemic vasculitis causing granulomas
Giant cell arteritis • Takayasu's disease • Wegener's granulomatosis • Churg-Strauss syndrome
A 45-year-old man, Suveen presents with pain in the mid portion of his chest. The pain is associated with eating and swallowing food. Endoscopic examination reveals an ulcerated area in the lower portion of his esophagus. Histologic sections of tissue taken from this area reveal an ulceration of the esophageal mucosa that is filled with blood, fibrin, proliferating blood vessels, and proliferating fibroblasts. Mitosis is easily found, and most of the cells have prominent nucleoli. Which of the following statements best describes this ulcerated area?
Granulation tissue Tissue repair involves the formation of granulation tissue, which histologically is characterized by a combination of proliferating fibroblasts and proliferating blood vessels. Proliferating cells are cells that are rapidly dividing and usually have prominent nucleoli.
In acute inflammation the tissue response consists of all except (a) Vasodilatation (b) Exudation (c) Neutrophilic response (d) Granuloma formation
Granuloma formation Granuloma formation is associated with chronic inflammation and not with acute inflammation.
The following host tissue responses can be seen in acute infection, except: (a) Exudation (b) Vasodilation (c) Margination (d) Granuloma formation
Granuloma formation Granuloma formation is characteristic of chronic granulomatous inflammation and is not seen in acute inflammation. • Vasodilation, increase in permeability, exudation, margination, rolling etc. are seen in acute inflammation.
Syphilis
Gumma: lesion enclosing wall of histiocytes; plasma cell infiltrate; central cells are necrotic without loss of cellular outline
Epithelioid granuloma is caused by:
Helper T-cell Granuloma is a focus of chronic inflammation consisting of a microscopic aggregation of macrophages that are transformed into epithelium-like cells surrounded by a collar of mononuclear WBC, principally lymphocytes and occasionally plasma cells. CD 4 Helper T-cells are involved in granuloma formation as it secretes IFN-γ, IL-2 and IL-12.
Vitamin K deficiency can cause
Hemorrhagic disease of newborn
Lewis triple response is caused due to:
Histamine Histamine is a vasoactive amine that is located in most body tissues but is highly concentrated in the lungs, skin, and gastrointestinal tract. It is stored in mast cells and basophils. When it is injected intradermally it causes the triple response consisting of: • Red spot: Due to capillary dilatation • Wheal: Due to exudation of fluid from capillaries and venules • Flare: Redness in the surrounding area due to arteriolar dilation mediated by axon reflex.
Increased vascular permeability
Histamine and serotonin C3a and C5a (by liberating vasoactive amines from mast cells, other cells) Bradykinin Leukotrienes C4;D 4 , E 4 PAF Substance P
Caseating granuloma are seen in: (a) Histoplasmosis (b) Sarcoidosis (c) Coccidiodomycosis (d) All
Histoplasmosis
Caseous granuloma is seen in (a) Histoplasmosis (b) Silicosis (c) Sarcoidosis (d) Foreign body
Histoplasmosis
Reed Sternberg cells are seen in
Hodgkin's lymphoma Q
The Eosinophils secrete all except (a) Major basic protein (b) Hydrolytic enzyme (c) Reactive form of O 2 (d) Eosinophilic chemotactic factor
Hydrolytic enzyme
Interleukin secreted macrophages, stimulating lymphocytes is
IL - 1 > (d) IL-6 • Macrophages release IL - 1 which stimulates the T - helper cells. • The T - cells in response proliferate and release IL - 2 which in turn further stimulates T - cell proliferation and B cell proliferation and differentiation into plasma cells. • Please note that even IL-6 (produced by macrophages) acts on late stages of B cell differentiation enhancing antibody formation. Still, IL-1 being the most important cytokine having systemic effects of inflammation has been chosen as the answer here in preference to IL-6.
Which of the following is not a pyrogenic cytokine? (a) IL - 1 (b) TNF (c) IFN - α (d) IL - 18
IL -18 Pyrogens are substances which cause fever. These can be either exogenous or endogenous. The endogenous pyrogens (also called as the pyrogenic cytokines) include: • IL-1 Q • IL-6 Q • Tumor necrosis factor Q (TNF) • Ciliary neurotopic factor Q (CNTF) • IFN-α Q (alpha) Harrison clearly mentions that the IL-18 Q which is a member of IL-1 family does not appear to be a pyrogenic cytokine.
Fever occurs due to:
IL 1 TNF Prostaglandins
Inflammatory mediator of generalized systemic inflammation
IL-1
Endogenous pyrogens -
IL-1, TNF-a, IL-6, Ciliary neurotropic factor and IFN-a.
Cytokines regulating lymphocyte growth, activation and differentiation
IL-2, IL-4, IL-12, IL-15, TGF-b
Eosinophils are activated by:
IL-5 IL-5 is required for the development and maturation of the eosinophil.
Cytokines that activate inflammatory cells:
IL-5 activates eosinophils. • TNF induces acute inflammation by acting on neutrophils and endothelial cells.
The estimation of the prothrombin level is useful in the following clotting factor deficiency, except: (UP 2006) (a) II (b) V (c) VII (d) IX
IX
Diapedesis
Immigration of the leukocytes through the vessel wall to the site of inflammation Most important molecule for diapedesis is CD31or PECAM-1 Q (platelet endothelial cell adhesion molecule). occurs predominantly in the venules (except in the lungs, where it also occurs in capillaries).
Which of the following is not true? (a) NADPH oxidase generate superoxide ion (b) MPO kills by OCl - (c) Chediak-Higashi syndrome is due to defective phagolysosome formation (d) In Bruton's disease there is normal opsonization
In Bruton's disease there is normal opsonization bruton's agammaglobulinemia is an X-linked immunodeficiency disorder characterized by the failure of B-cell precursors (pro-B cells and pre-B cells) to mature into B cells due to mutation of B-cell tyrosine kinase (Btk). Btk is required for the maturation of pre-B cell to mature B cell. So, plasma cells derived from B cells are absent and therefore, production of immunoglobulins is impaired. The disease is seen almost entirely in males. It usually does not become apparent until about 6 months, when maternal immunoglobulins are depleted. Opsonisation is a process by which preferential phagocytsosis of the opsonised bacteria is done by neutrophils and macrophages. This process also requires antibodies. In bruton's disease therefore, the opsonisation is defective. Other options have been explained in the review of chapter 2 in detail.
A 5-year-old female Sukanya is hospitalized with fever and hemorrhagic skin lesions on her lower extremities. About five months ago she was successfully treated with penicillin for bacterial meningitis. She likely to be suffering from which of the following immune system disorders?
Inability to form the membrane-attack complex. Patients having deficiency of the complement factors that form the membrane attack complex (MAC i.e. C5b-9 complex) experience recurrent infections by Neisseria species (Choice d). The Neisseria disease in these patients is mild because the remainder of the immune system is intact. MAC is the final end-product of complement activation and it forms a pore in the bacterial cell membrane leading to cell lysis. Choice A) Pure T-cell dysfunction is thymic hypoplasia seen in Di George syndrome. In this condition, there is congenital absence of the thymus and parathyroid glands caused by maldevelopment of the 3rd and 4th pharyngeal pouches. So, patients have pure T-cell lymphopenia (causing recurrent viral and fungal infections) and hypocalcemia. (Choice B) Chronic granulomatous disease (CGD) is an example of deficient intracellular killing due to absent NADPH oxidase. (Choice C) Young adults infected with Neisseria meningitidis may be at increased risk for disseminated infection if they produce too much serum IgA antibody. In these patients IgA attaches to the bacteria and blocks attachment of the IgM and lgG antibodies that induce complement-mediated bacterial lysis. Normally, IgM and lgG activity helps protect against bacterial dissemination.
Cytokines
Includes interleukins; ( c) Are polypeptide (complex protein): Cytokines are peptide mediators or intracellular messengers produced by wide variety of haemopoietic and non- haemopoietic type of cells in response to immuno, inflammatory or infectious disease states. Most of the lymphokines exhibit multiple biological effects and same effect may be caused by different lymphokines.
Function of adhesion molecules Thrombospondins
Inhibit angiogenesis
Cell-matrix adhesions are mediated by?
Integrins The cell adhesion molecules (CAMs) are classified into four main families: • Immunoglobulin family CAMs • Cadherins • Integrins: bind to extracellular matrix (ECM) proteins such as fibronectin, laminin, and osteopontin providing a connection between cells and extracellular matrix (ECM) • Selectins - Cadherins and integrins link the cell surface with the cytoskeleton through binding to actin and intermediate filaments. - Laminin is the most abundant glycoprotein in the basement membrane and has binding domains for both ECM and cell surface receptors.
A 14 month old boy Chunnu is being evaluated for recurrent, indolent skin infections and gingivitis. On taking a detailed history from the mother, she tells very valuable point that he had delayed separation of the umbilical cord which occurred around 9-10 weeks after his birth. Which of the following proteins is most likely under-expressed in this boy?
Integrins The clinical features and history described in the stem of the question are consistent with a diagnosis of leukocyte adhesion deficiency. Clinical findings associated with this syndrome include late separation of the umbilical cord, poor wound healing, recurrent skin infections (without formation of pus), gingivitis and periodontitis. In immune deficiencies, late separation of the umbilical cord alone should raise the question of Leukocyte Adhesion Deficiency type I (LAD I). (Choice a) Deficiency of late complement components (i.e. C5b-9) results in an inability to form the complement membrane attack complex and a greater risk of severe infections caused by Neisseria organism. • (Choice b) Transcobalamin II is a carrier protein for vitamin B12 after it is absorbed in the ileum. Its deficiency is not associated with immunodeficiency. • (Choice d) a 2 -globulins are normal serum proteins (like haptoglobin, ceruloplasmin and a 2 -macroglobulin) produced by the liver and kidneys.
Pro inflammatory Cytokines include all of the following except: (a) Interleukin 1 (b) Interleukin-10 (c) Interleukin 6 (d) TNF- Alpha
Interleukin-10 The following are the anti inflammatory cytokines: • IL-10 • TGF-β • IL-4 • IL-13
Which of the following statements in context of endothelial cell contraction in inflammation is false? (a) Endothelial cell contraction is the commonest mechanism of increased permeability (b) Endothelial cell contraction is responsible for immediate transient response (c) It affects venules, capillaries and arterioles commonly. (d) It is associated with the release of histamine, substance P and bradykinin.
It affects venules, capillaries and arterioles commonly. Direct quote from Robbins.....'Endothelial cell contraction is classically seen in the venules 20 to 60 µm in diameter leaving the capillaries and the arterioles unaffected'.
All of the following are true in respect of angioneurotic edema except? (AI 2012) (a) It is caused by deficiency of complement proteins (b) It is more common in females (c) It manifests as pitting edema (d) It is an autosomal dominant disorder
It manifests as pitting edema (Ref: Harrison 17th/2066, 18th/2711-3) • Angioneurotic edema is a localised non pitting edema Q involving deeper layers of the skin and subcutaneous tissue. It is an autosomal dominant Q clinical condition caused by deficiency of C1 inhibitor protein (a complement regulatory protein) and associated with elevated levels of bradykinin. It is more common in females • Diagnosis of hereditary angioedema is suggested by the presence of lack of pruritus and urticarial lesions, prominence of recurrent gastrointestinal attacks of colic and episodes of laryngeal edema. The levels of complement proteins C1is normal but levels of C2 and C4 are depleted. • Danazol is the drug which can be used for hereditary angioedema.
Vitamin used for post translational modification of glutamic acid to gamma carboxy glutamate is
K
Deficiency of selectin
LAD 2
Which of the following is found in secondary granules of neutrophils?
Lactoferrin
Birbeck's granules in the cytoplasm are seen in:
Langerhans cells Birbeck granules are rod shaped/Tennis-racket shaped cytoplasmic organelles with a central linear density and a striated appearance. They are diagnostic microscopic feature in Langerhans cell histiocytosis (Histiocytosis X)
Necrotizing epithelioid cell granulomas are seen in all, except: (a) Tuberculosis (b) Wegener's granulomatosis (c) Cat Scratch disease (d) Leprosy
Leprosy
All are true about exudate except (a) More protein (b) Less protein (c) More specific gravity (d) All
Less protein
Which of the following is secondary mediator of the anaphylaxis is: (a) Histamine (b) Proteases (c) Eosinophilic chemotactic factor (d) Leukotriene B 4
Leukotriene B 4
main organ for storage of vitamin K Q .
Liver
Tissue damage
Lysosomal enzymes of leukocytes Reactive oxygen species Nitric oxide
The most important source of histamine:
Mast cells The richest sources of histamine are the mast cells that are normally present in the connective tissue adjacent to blood vessels. It is also found in blood basophils and platelets.
Basement membrane degeneration is mediated by:
Metalloproteinases Extracellular Matrix (ECM) comprises of interstitial matrix and basement membrane. The degradation of collagen and other ECM proteins is achieved by a family of matrix metalloproteinases (MMPs) which are dependent on zinc ions for their activity. • MMP8 and MMP2 are collagenases which cleave type IV collagen of basement membranes. • MMPs also have a role in tumour cell invasion.
Non-caseating granulomas are following except (a) Byssinosis (b) Hodgkin's lymphoma (c) Metastatic carcinoma of lung (d) Tuberculosis
Metastatic carcinoma of the lung (see below) Friends, remember that fungal and mycobacterial granulomas are usually associated with central necrosis but all large caseating granulomas come from small non-caseating granulomas. Granuloma can be seen in both Byssinosis and Hodgkin's lymphomas. • Granulomas are also seen in Hodgkin's disease • So, metastatic carcinoma of lung is the answer of exclusion.
Granuloma is pathological feature of all, except (a) Giant cell arteritis (b) Microscopic polyangiitis (c) Wegener's granulomatosis (d) Churg Strauss disease
Microscopic polyangiitis (Ref: Robbins Illustrated 7th/540) • Microscopic polyangiitis is a small vessel vasculitis showing the presence of necrotizing inflammation of the affected vessels without the presence of granuloma.
All are cytokines except Monoclonal antibody Interleukin Chemokine TNF
Monoclonal antibody
In a granuloma, epithelioid cells and giant cells and derived from
Monocyte - macrophages Monocytes and macrophages fuse together resulting in the formation of epithelioid cells giant cells.
The epithelioid cell and multinucleated giant cells of Granulomatous inflammation are derived from:
Monocyte macrophages Delayed type hypersensitivity (as seen in TB) results from accumulation of mononuclear cells around small veins and venules, producing a perivascular cuffing. Monocytes transform into macrophages which undergo morphological changes to produce epithelioid cells.
A 36-year-old man, Avnish presents with a cough, fever, night sweats, and weight loss. A chest X-ray reveals irregular densities in the upper lobe of his right lung. Histologic sections from this area reveal groups of epithelioid cells with rare acid-fast bacilli and a few scattered giant cells. At the centre of these groups of epithelioid cells are granular areas of necrosis. What is the source of these epithelioid cells?
Monocytes Granulomatous inflammation is characterized by the presence of granulomas, which by definition are aggregates of activated macrophages (epithelioid cells, not epithelial cells). These cells may be surrounded by mononuclear cells. The source of macrophages (histiocytes) is monocytes from the peripheral blood.
Function of adhesion molecules Tenascin family
Morphogenesis Cell adhesion
Granulomatous inflammatory reaction is caused by all, except: (a) M. tuberculosis (b) M. leprae (c) Yersinia pestis (d) Mycoplasma
Mycoplasma (Ref: Robbins 8th/802 9/e p97) • Granulomatous inflammation is a distinctive pattern of chronic inflammatory reaction characterized by focal accumulations of activated macrophages, which often develop an epithelial-like (epithelioid) appearance. • Tuberculosis is the prototype of the granulomatous diseases, but sarcoidosis, Crohn's disease, cat-scratch disease, lymphogranuloma inguinale, leprosy, brucellosis, syphilis, some mycotic infections, berylliosis, and reactions of irritant lipids are also included. • In Robbins (8 th ed, page 802), Yersinia has also been mentioned to be associated with granulomatous inflammation. So, the answer of exclusion is Mycoplasma.
Which of the following mediator? (a) Tumor Necrosis Factor (b) Myeloperoxidase (c) Interferons (d) Interleukin
Myeloperoxidase Myeloperoxidase (MPO) is an enzyme present in primary (or azurophilic) granules of the neutrophils. In the presence of a halide such as Cl-, MPO converts H 2 O 2 to HOCl• (hypochlorous radical) during the process of respiratory burst.
Wound contraction is mediated by:
Myofibroblasts
Oxygen dependent killing is done through (a) NADPH oxidase (b) Superoxide dismutase (c) Catalase (d) Glutathione peroxidase
NADPH oxidase The generation of reactive oxygen intermediates is due to the rapid activation of an enzyme; NADPH oxidase which is involved in oxygen dependent killing. • Catalase, superoxide dismutase and glutathione peroxidase are free radical scavengers that prevent oxygen mediated injury
Which of the following helps in generating reactive O 2 intermediates in the neutrophils?
NADPH oxidase Within the phagocytes, the following reaction takes place: The initiating enzyme for this process is NADPH oxidase (also called respiratory burst oxidase). Glutathione peroxidase, glutathione reductase and superoxide dismutase are examples of anti-oxidants. They reduce free radical formation.
Earliest transient change following tissue injury will be:
Neutrophilia Neutrophils predominate during the first 6 to 24 hours (Neutrophilia). These are replaced by monocytes/macrophages in 24 to 48 hours.
Cytokines are secreted in sepsis and Systemic Inflammatory Response Syndrome (SIRS) by:
Neutrophils Platelets Cytokines are peptide mediators or intercellular messengers which regulate immunological, inflammatory and reparative host responses. They are produced by widely distributed cells like macrophage, monocytes, lymphocytes, platelets, fibroblast, endothelium, stromal cells etc.
Tuberculosis
Noncaseating tubercle (granuloma prototype): focus of epithelioid cells, rimmed by fibroblasts, lymphocytes, histiocytes and langhans giant cell. Caseating tubercle: central amorphous granular debris, loss of all cellular detail; acid-fast bacilli
All are mediators of neutrophils except: (a) Elastase (b) Cathepsin (c) Nitric oxide (d) Leukotrienes
None Cathepsin G is a serine protease secreted by activated neutrophils that play a role in the inflammatory response.
Vitamin K is the other vitamin apart from vitamin D whose deficiency can cause
Osteoporosis
Nephrocalcinosis in a systemic granulomatous disease is due to
Over production of 1, 25 dihydroxy vitamin D Nephrocalcinosis is defined as calcification of the renal interstitium and tubules. It is associated with hypercalcemia. In chronic granulomatous inflammation, the important cells involved are macrophages and lymphocytes. Direct quote Heptinstall's ... 'Sarcoidosis and other granulomatous diseases can be cause of hypercalcemia and hypercalciuria owing to exces vitamin D from extra renal conversion of 1,25 (OH)2D3. Nephrocalcinosis was found to be associated with 22% patients with chronic sarcoidosis'. In other granulomatous conditions (like Sarcoidosis), there is presence of metastatic calcification due to activation of vitamin D precursor by macrophages....... 'Hypercalciuria is seen in almost a third of patients with sarcoidosis. Serum calcium levels in sarcoidosis rise with serum vitamin D levels. This dysregulation of calcium metabolism appears to be modulated through abnormal synthesis of vitamin D by activated pulmonary macrophages and granulomatous tissue that leads to excessive hydroxylation of 25- monohydroxylated vitamin D precursors. This could be an adaptive response to the antigen in sarcoidosis.'
All are granulomatous diseases except (a) Syphilis (b) Sarcoidosis (c) Schistosomiasis (d) P. carinii
P. carinii
Most important for diapedesis?
PECAM The process of leukocyte recruitment is migration of the leukocytes through the endothelium, called transmigration or diapedesis. • Transmigration of leukocytes occurs mainly in post-capillary venules. • Several adhesion molecules present in the intercellular junctions between endothelial cells are involved in the migration of leukocytes. These molecules include a member of the immunoglobulin superfamily called PECAM-1 (platelet endothelial cell adhesion molecule) or CD31 and several junctional adhesion molecules.
Which chemical mediator is an arachidonic acid metabolite produced by cyclo-oxygenase pathway?
PGH2
Bradykinin is for:
Pain Vasodilation Increase vascular permeability Friends, in our opinion the question should have been asked with an "except" because bradykinin has the following effects: • Increases vascular permeability • Arteriolar dilation • Bronchial smooth muscle contraction • Pain at the site of injections/inflammation Since increased vascular permeability is the most characteristic feature of acute inflammation, some people were of the opinion that this could be single best option to be marked presuming the stem of question was correct.
Nitroblue tetrazolium test is used for?
Phagocytes The nitroblue-tetrazolium (NBT) test is the original and most widely known test for chronic granulomatous disease. It is negative in chronic granulomatous disease and positive in normal individuals. It is used for detecting the production of reactive oxygen species in the phagocytes
The complex process of leukocyte movements through the blood vessels are all except (a) Rolling (b) Adhesion (c) Migration (d) Phagocytosis
Phagocytosis
The most important function of epithelioid cells in tuberculosis is: (a) Phagocytosis (b) Secretory (c) Antigenic (d) Healing
Phagocytosis Epithelioid cells and giant cells are apposed to the surface and encompass the foreign body.
The function common to neutrophils, monocytes, and macrophages is
Phagocytosis Friends, the first option actually confused lot of people when the question was asked because of the word 'immune'. Read the complete option carefully before answering the questions in the exam.
Epithelioid granulomatous lesions are found in all of the following diseases, except: (a) Tuberculosis (b) Sarcoidosis (c) Berylliosis (d) Pneumocystis carinii
Pneumocystis carinii
Systemic vasculitis causing necrotizing inflammation
Polyarteritis nodosa (PAN) • Microscopic polyangiitis • Wegener's granulomatosis • Churg-Strauss syndrome
Procalcitonin is used as marker of
Procalcitonin Procalcitonin is an acute phase reactant which is now useful for being a marker of sepsis. It is in fact utilized for differentiating the bacterial and aseptic meningitis.
Vasodilation
Prostaglandins Nitric oxide Histamine
Pain
Prostaglandins Bradykinin
After binding of complement and antibody on the surface of encapsulated bacteria, the process of phagocytosis by polymorphonuclear leukocytes involves which of the following? (a) Fc and C3b (b) receptor mediated endocytosis (c) respiratory burst (d) pseudopod extension
Pseudopod extension Typically the phagocytosis of microbes and dead cells is initiated by recognition of the particles by receptors expressed on the leukocyte surface. Mannose receptors and scavenger receptors are two important receptors that function to bind and ingest microbes. The efficiency of phagocytosis is greatly enhanced when microbes are opsonized by specific proteins (opsonins) for which the phagocytes express high-affinity receptors. Binding of a particle to phagocytic leukocyte receptors initiates the process of active phagocytosis of the particle. During engulfment, extensions of the cytoplasm (pseudopods) flow around the particle to be engulfed, eventually resulting in complete enclosure of the particle within a phagosome created by the plasma membrane of the cell Direct concept quote from Robbins to clarify the answer; How is phagocytosis different from pinocytosis and receptor mediated endocytosis In contrast to phagocytosis, fluid phase pinocytosis and receptor-mediated endocytosis of small particles involve internalization into clathrin Q coated pits and vesicles and are not dependent on the actin cytoskeleton. Option 'a' Both Fc fragment of IgG and C3b are required in opsonisation. It takes place before phagocytosis. • Option 'c' respiratory burst occurs after the formation of the phagolysosome.
Most important bactericidal agent is: (a) Cationic basic protein (b) Lactoferrin (c) Lysozyme (d) Reactive O 2 species
Reactive oxygen species H 2 O 2 - MPO- halide system is the most efficient bactericidal system of neutrophils.
Function of adhesion molecules Osteopontin
Regulates calcification Mediator of leukocyte migration in inflammation, Vascular remodeling Fibrosis in various organs
An adult old man gets burn injury to his hands. Over few weeks, the burned skin heals without the need for skin grafting. The most critical factor responsible for the rapid healing in this case is:
Remnant skin appendages Skin consists of two layers. Epidermis which is the most superficial layer of the skin constantly replaced from the basal layer and the dermis which is thicker than epidermis and contains adnexal structures. The importance of these adnexal structures is that they contain epithelial cells can proliferate and can heal a partial thickness wound by epithelialization.
In regeneration (a) Granulation tissue (b) Repairing by same type of tissue (c) Repairing by different type of tissue (d) Cellular proliferation is largely biochemical factors
Repairing by same type of tissue
Function of selectin
Rolling and loose adhesion
Diagnosis of toxoplasmosis
Sabin Feldman dye test
Non-caseating granuloma is characteristically seen in
Sarcoidosis
Endothelium leukocyte interaction during inflammation is mediated by/due to
Selectins; Integrins Endothelium and WBC interact through the molecules like Immunoglobulins (family molecules e.g. ICAM-I, VCAM-I), Integrins, Mucin-like glycoprotein and selectins.
A 28-year-old woman, Vimla is being evaluated to find the cause of her urine turning a dark brown color after a recent upper respiratory tract infection. She has been otherwise symptomatic, and her blood pressure has been within normal limits. Urinalysis finds moderate blood present with red cells and red cell casts. Immunofluorescence examination of a renal biopsy reveals deposits of IgA within the mesangium. These clinical findings suggest that her disorder is associated with activation of the alternate complement system. Which of the following serum laboratory findings is the most suggestive of activation of the alternate complement system rather than the classic complement system?
Serum C2 normal, C3 decreased, C4 normal Activation of the complement cascade can produce local deposition of C3, which can be seen with special histologic techniques. If a patient has widespread activation of the complement system, then serum assays of C3 levels might be decreased. • In particular, activation of the classic complement pathway decreases levels of the early complement components, namely, C1, C4, and C2. In contrast, activation of the alternate complement pathway, decreases levels of C3, but the levels of the early factors (C2 and C4) are normal. • An example of a disorder associated with the activation of the alternate complement system is IgA nephropathy (Berger's disease), which is characterized by the deposition of IgA in the mesangium of the glomeruli.
One of the following statements about hematopoietic stem cell is false? (a) Stem cells have self renewal property (b) Subset of stem cells normally circulate in peripheral blood (c) Marrow derived stem cells can seed other tissues and develop into non hematopoietic cells as well (d) Stem cells resemble lymphoblasts morphologically
Subset of stem cells normally circulate in peripheral blood Hematopoietic stem cells have two essential properties that are required for the maintenance of hematopoiesis: pluripotency and the capacity for self-renewal. Pluripotency refers to the ability of a single HSC to generate all mature blood cells. When an HSC divides, at least one daughter cell must self renew to avoid stem cell depletion. Self-renewing divisions occur within a specialized marrow niche, in which stromal cells and secreted factors nurture and protect the HSCs. During stress, HSCs are mobilized from the bone marrow and appear in the peripheral blood.
Free radicals are generated by all except Superoxide dismutase NADPH Oxidase Myeloperoxidase NO synthase
Superoxide dismutase Superoxide dismutase (SOD) is an anti oxidant enzyme Some clarification regarding option 'd'.... 'Nitric oxide (NO), an important chemical mediator generated by endothelial cells, macrophages, neurons, and other cell types can act as a free radical and can also be converted to highly reactive peroxynitrite anion (ONOO-) as well as NO 2 and NO 3- .
Chemotaxis, leukocyte recruitment and activation
TNF, IL-1 Chemokines C3a, C5a Leukotriene B4 (Bacterial products, e.g., N-formyl methyl peptides)
Which of the following adhesion molecules is involved in morphogenesis? (a) Osteopontin (b) Osteonectin SPARC (c) Tenascin (d) Thrombospondins
Tenascin SPARC is secreted protein acidic and rich in cysteine.
A 14-year-old girl Radha has high grade fever. She goes to a physician Dr. Jeeva Roy who orders for some blood investigations. A complete blood count with differential implies the presence of a viral infection. Which of the following best describes the cells that indicate a viral etiology to her illness?
They are basophilic with spherical dark-stained nuclei Lymphocytosis is associated with viral infection. These cells are generally small and are basophilic with spherical dark-stained nuclei normally constituting nearly 30% of leukocytes. There are two types of lymphocytes: T cells (involved in cell-mediated immunity) and B cells (involved in humoral immunity). Monocytes are precursors of osteoclasts and liver Kupffer cells (option b) and also give rise to tissue macrophages and alveolar macrophages. Platelets contain a peripheral hyalomere and central granulomere (option c). Neutrophils have azurophilic granules and multilobed nuclei (option d). They increase in number in response to bacterial infection.
In Lipooxygenase pathway of the arachidonic acid metabolism, which of the following products helps to promote the platelet aggregation and vasoconstriction?
Thromboxane A 2
Function of adhesion molecules Osteonectin (SPARC)
Tissue remodeling in response to injury , Angiogenesis inhibitor
Definite and intermediate host of toxoplasmosis
Toxoplasmosis is transmitted by cat Q (definitive host). Man is the intermediate host
In a lymph node showing non necrotizing and non-caseating granuloma which of the following is suspected?
Toxoplaxmosis This is a characteristic feature of toxoplasmosis.
When a cell transforms itself into different lineage the ability us know as:
Trans-differentiation Tissue stem cells which are thought to be lineage-committed multipotent cells, possess the capacity to differentiate into cell types outside their lineage restrictions (called trans-differentiation). For example, hematopoietic stem cells may be converted into neurons as well as germ cells.
A 72 year-old man Kishori Lal presented to surgery OPD with a history of difficulty in micturition, increased frequency of urine and lower backache for the past 8 months. Digital rectal examination reveals an enlarged prostate with irregular surface. The surgeon orders for the serum PSA levels which are found to be increased and X ray spine shows osteoblastic lesions. A diagnosis of metastatic prostate cancer is made. Mr Lal also complaints of significant weight loss, loss of appetite and loss of energy over the past 45 days. His current complaints can be attributed to which of the following?
Tumor necrosis factor-a Cachexia, or wasting due to cancer, manifests with weakness, weight loss, anorexia, anemia, and infection. The principal cytokine responsible for such manifestations is tumor necrosis-a (TNF-a). Fibroblast growth factor is involved in wound healing. Interleukin-2 (IL-2) is an immune-stimulant produced by activated T cells. Vascular endothelial growth factor is important in the proliferation of blood vessels in a growing tumor.
Main feature of chemotaxis is
Unidirectional locomotion of the neutrophils Chemotaxis is defined as locomotion oriented along a chemical gradient.
Cryoprecipitate is rich in which of the following clotting factors:
VIII Cryoprecipitate is a source of Fibrinogen (factor I), Factor VIII and Von-Willebrand factor Q • Treatment of choice for Hemophilia A Q , von Willebrand disease Q and hypofibrinogenemic states Q . • If factor VIII is unavailable, cryoprecipitate may be an alternative, since each unit contains about 80 IU of factor VIII.
Following injury to a blood vessel, immediate haemostasis is achieved by which of the following?
Vasoconstriction After initial injury there is a brief period of arteriolar vasoconstriction mediated by reflex neurogenic mechanisms and augmented by the local secretion of factors such as endothelin(a potent endothelium-derived vasoconstrictor.
Histamine causes
Vasodilation
Which among the following is the hallmark of acute inflammation?
Vasodilation and increase in permeability Direct quote "a hallmark of acute inflammation is increased vascular permeability leading to the escape of protein-rich exudate into the extravascular tissue, causing edema".
Characteristic of acute inflammation is:
Vasodilation and increased vascular permeability
Which of the following is absolutely essential for wound healing? (a) Vitamin D (b) Carbohydrates (c) Vitamin C (d) Balanced diet
Vitamin C Healing is modified by a number of influences (including both systemic and local host factors) frequently impairing the quality and adequacy of both inflammation and repair. Ascorbic acid deficiency causes reduced cross linking of tropocollagen to collagen So, the patient has increased bleeding tendencies and poor wound healing.
Vitamin K is required for the activation of
Vitamin K is required for the activation of factors 2,7,9,10 The reason why vitamin K is required for these factors is the gamma carboxylation of glutamate Q .
Ultra-structurally, endothelial cells contain
Weibel-Palade bodies
Neutrophils
Wound healing, umbilical cord detachment, and the fighting against cutaneous infections all depend on the ability of neutrophils to exit the intravascular space and initiate inflammation in the skin.
Febrile response in CNS is mediated by
a) Bacterial toxin; (b) IL-1; (d) Interferon; (e) TNF Fever is produced in response to substances called pyrogens that act by stimulating prostaglandin synthesis in the vascular and perivascular cells of hypothalamus.
Leprosy
acid-fast bacilli in macrophages; non-caseating granulomas
LAD I
an autosomal recessive condition caused by absence of the CD18 antigen that is necessary for the formation of integrins (Choice c). Integrins are essential for the migration of leukocytes from the blood vessels to the tissues to exert their effect. A leukocyte circulating in the blood vessel undergoes a well-characterized multistep process of reaching the site of infection. • One of the initial steps is rolling mediated by selectins. • The subsequent step is firm adhesion which is mediated by integrins. • Then transmigration takes place followed by chemotaxis.
Integrins
bind to extracellular matrix (ECM) proteins such as fibronectin, laminin, and osteopontin providing a connection between cells and extracellular matrix (ECM)
Defensin
cationic arginine rich peptides having broad antimicrobial activity found in Azurophil granules of neutrophils.
Drug of choice for toxoplasmosis
combination of pyrimethamine and sulfadiazine
Exogenous pyrogens
endotoxin of gram '-' bacteria, superantigens (gram '+' bacteria)
PGE2
final mediator responsible for causing elevation of the thermoregulatory set point by increasing the concentration of cAMP.
exogenous pyrogens
include microbial products and toxins; classical example is endotoxin Q produced by gram negative bacteria. Body temperature is regulated at the level of the hypothalamus. Most individuals with hypothalamic damage have subnormal and not supranormal body temperature.
Earliest indicator for vitamin K deficiency is
increased PT Q value.
Langhans giant cell
is seen in tuberculosis. They have horse shoe shaped nucleus.
Cadherins and integrins
link the cell surface with the cytoskeleton through binding to actin and intermediate filaments.
Laminin
most abundant glycoprotein in the basement membrane and has binding domains for both ECM and cell surface receptors.
PGe 2
most important chemical responsible for elevation of hypothalamic set point in the body. So, NSAIDs reduce fever by inhibiting cyclooxygenase and reducing prostaglandin concentration.
Endothelin
potent endothelial derived vasoconstrictor
C5a
powerful chemotactic agent for neutrophils, monocytes, eosinophils and basophils.
Cat scratch disease
rounded or stellate granuloma containing central granular debris and recognizable neutrophils; giant cells uncommon
Drug of choice for toxoplasmosis in pregnancy
spiramycin
IL-4
stimulates differentiation to TH2 pathway.
IL-15
stimulates the growth and activity of NK cells.
Touton giant cells are seen
xanthoma
