(1) angeborene Immunität

D)

The correct answer is D. The enzyme splits starch and is of importance for digestion but not for protection. Intact skin prevents entry of microorganisms. Damage, as in burns, causes vulnerability to infection. Mucus lining the mucosal surfaces of the body tends to inhibit direct attachment of infectious microorganisms to the mucosal surface. Gastric acid provides a hostile environment to many microorganisms. Gut microflora produce antibiotic substances, colicins, which can kill other bacteria.

D)

The correct answer is D. Many PRR are lectin-like in that they recognize exposed microbial sugars. Gram-negative bacteria produce LPS, the biologically active lipid A moiety of which is recognized by LPS-binding protein (LBP); the LBP-LPS complex is captured by the CD14 scavenger molecule on phagocytic cells which then become activated through Toll-like receptor-4 (TLR4). PAMPs are recognized by the pattern recognition receptors. Lipoteichoic acid is produced by Gram-positive bacteria and acts as a PAMP. Unmethylated guanosine-cytosine dinucleotide sequences in bacterial DNA are an example of a PAMP linked to intracellular infection.

E

The correct answer is E. Endothelial cells are not essentially phagocytic although they do contribute by the production of mediators of the inflammatory process, particularly acute inflammation, and were previously lumped together with the mononuclear phagocyte system in what was known as the reticuloendothelial system (RES). Monocytes circulate in the blood, being derived from hematopoietic myeloid stem cells. Monocytes settle to become phagocytic Kupffer cells in the liver. The mononuclear phagocytes that form the mesangium in the glomeruli are part of this system. Macrophages lining the medullary sinuses are part of the mononuclear phagocyte system.

C

The correct answer is C. The granules contain a wide spectrum of microbicidal agents. The bone marrow hematopoietic stem cell is the precursor of the formed elements of the blood which include the PMN. The granular polymorphonuclear cell which stains with basic dyes (i.e., the basophil) is similar to a mast cell. The major professional phagocytic cells are the neutrophils and the macrophages. The word neutrophil implies that the granules stain neither with acid nor basic dyes. The eosinophil has granules that stain with the acid dye eosin and is important in defense against parasitic infections.

D

NO is produced following the induction of nitric oxide synthase. O2− is the superoxide anion obtained by addition of an electron to molecular oxygen by the cytochrome b558oxidase system. Oxygen is utilized as a substrate to which cytochrome b558 transfers an electron from NADPH. Hydrogen peroxide is generated from O2− and, although not as active as the free radicals, is more stable and therefore diffuses further. The hydroxyl radical is one of the most reactive free radicals known and is formed by the reduction of H2O2, for example following its reaction with Fe2+.

E

The correct answer is E. The defensins are peptide antibiotics present in the granules in extremely high concentration. Anti-toxins are usually antibodies. The defensins are part of the oxygen-independent defensive system of the neutrophil. There are enzymes within the neutrophil granules, some of which participate in the production of reactive intermediates and some of which help the digestion of killed microorganisms, but the defensins do not have enzymic activity. Neutrophils possess various cell surface glycolipids, but these are not defensins.

A

TLR9 recognition of these microbial dinucleotide sequences leads to activation of the NFκB transcription factor. It is the TLRI/TLR2 heterodimer that recognizes bacterial lipopeptides. Lipoteichoic acid is recognized by the TLR2/TLR6 heterodimer. Following its ligation by LPS-binding protein, the LPS from Gram-negative bacteria is recognized by TLR4 in a CD14-dependent process. The presence of double-stranded RNA is a marker of viral infection and is detected by TLR3.

B

C3bBb is the C3 convertase enzyme generated in the alternative complement pathway and is responsible for splitting off the small peptide C3a, leaving C3b as a residue. C3b is an opsonizing agent that assists phagocytosis and also contributes to some of the cleavage enzymes. Factor B is cleaved by factor D and then contributes the resulting Bb fragment to the alternative pathway C3 convertase (see learning response B). Factor D splits factor B to form Bb. Factor H combines with C3b making it vulnerable to cleavage by factor I. It displaces factor Bb from the convertase so leading to its destabilization.

D

These terminal components form a complex that inserts into the membrane to form a transmembrane ion channel which leads to lysis of the cell. The hydroxyl radical is a reactive oxygen intermediate. The colicins are antibiotics produced by the gut microflora. C3bBb3b is the convertase that splits component C5 to give C5a and C5b. Properdin is a component of the alternative pathway which stabilizes the C3bBb C3 convertase.

C

Bacteria coated with C3b adhere to C3b receptors on professional phagocytic cells. C5a, not C3b, is chemotactic for neutrophils. C3a and C5a, small peptides split off from the parent C3 and C5 molecules, are anaphylatoxins that trigger mast cell degranulation. There is no evidence that C3b directly injures bacteria. The inactive form of C3 is obtained by splitting the C3b to form iC3b, C3d, and C3dg.

E

Neutrophils are chemotactically attracted to the site of inflammation by C5a and mast cell chemotactic factors such as leukotriene B4. The arterioles dilate rather than constrict. The endothelial cells separate and make the basement membrane accessible to the neutrophils. Macrophages are in the minority in acute inflammation. Mast cells, unlike basophils, do not migrate to a significant extent but their degranulation mediates acute inflammatory reactions.

D

Lysozyme splits the peptidoglycan of bacterial cell walls. Lysozyme is a protein present in extracellular fluids and in certain granules of professional phagocytic cells. Although complement activation involves an enzyme cascade, lysozyme has no role in this process. Lysozyme is an enzyme, but its activity is not proteolytic. Lysozyme is not present in mast cells.

B

Chondroitin sulfate is a cell matrix component. Serum amyloid P component is an acute phase reactant whose concentration increases dramatically on infection. C-reactive protein is an acute phase reactant which binds to certain bacterial polysaccharides and activates the first component of complement. Mannose-binding lectin is a major acute phase protein which binds to mannose on bacteria, fixes complement, and facilitates adherence to macrophages. Fibrinogen shows a moderate increase in concentration on infection.

C

Derepression of genes in the target cell result in the synthesis of a protein kinase and an endonuclease. Interferons are present in birds, reptiles, and fishes as well as higher animals. There are three main families of interferons: α, β, and γ. In fact, the interferons render cells unable to support viral replication, thereby establishing a cordon sanitaire around the site of a virus infection so restraining its spread. Interferons were first recognized by the phenomenon of viral interference in which an animal infected with one virus resists superinfection by a second unrelated virus.

D

Perforin inserts into the target cell membrane thereby facilitating entry of TNF and granzymes into the target cell. Their activity is stimulated by interferon. They contain perforin, which is released on contact with a target, inserts itself into the target cell membrane, and creates a pore through which granzymes are transferred into the target cell. TNF produced by NK cells contributes to the killer function. NK cells contain a number of serine proteases of the granzyme family, one of which, granzyme B, can split procaspase 8 and thereby activate apoptosis in the target cell.

A

They do stain with acidic dyes. The secreted basic protein damages helminth membranes. The peroxidase contributes to the generation of reactive oxygen intermediates. There is a respiratory burst involving the concomitant generation of active oxygen metabolites. The C3b receptors bind opsonized pathogens, including microorganisms and larger parasites such as helminths.

C

The ability to ingest bacteria and kill them is a major feature of these professional phagocytic cells. Loss of neutrophils renders the host very susceptible to overwhelming infection. The production of reactive oxygen intermediates is not the only mechanism of attack. The oxygen-independent mechanisms such as lysozyme, defensins, and so on are not the only mechanisms of attack. Macrophages but not neutrophils secrete a number of complement components. Interferon is active against viruses.

B

C5a is a powerful chemotactic agent and also an anaphylatoxin. C9 is the terminal complement component which forms part of the membrane attack complex. C3 has no direct biological action but is split to give C3a and C3b when the complement system is activated. C3b opsonizes microorganisms for adherence to phagocytic cells. C5b initiates formation of the membrane attack complex.

A

Activation of mast cells releases chemotactic factors for neutrophils and also vasoactive mediators such as histamine. The influx of neutrophils represents part of the acute inflammatory response itself. The increase in vascular permeability is an essential feature of the acute inflammatory response itself. C3 has no biological activity before being cleaved. Lysozyme is not a part of the acute inflammatory process although it may be released from neutrophils, and also participate in intracellular killing within the neutrophils following phagocytosis.

B

The NLRP3 inflammasome converts pro-IL-β to active IL-1β. IL-8 leads to the release of IL-18. Although the NLRP3 inflammasome is involved in the generation of pro-inflammatory cytokines, the pro-inflammatory cytokine TNF is not one of them. Interferon-α is not generated by the NLRP3 inflammasome. PAF is not generated by the NLRP3 inflammasome.