Im*

Difference between CD45RO and CD45RA?

CD45RO is the isotype expressed on memory CD4 and CD8 cells and on CD4 effector cells lacksA,B and C exons that encode extracellular domains CD45 RA is the isotype expressfed on naive CD4 and CD8 cells. (contains A exon)

Defensins mechanism of action?

Defensins Cysteine-rich cationic peptides produced by epithelial barrier cells in the skin, gut, lung, and other tissues and in neutrophil granules that act as broad-spectrum antibiotics to kill a wide variety of bacteria and fungi. The synthesis of defensins is increased in response to stimulation of innate immune system receptors such as Toll-like receptors and inflammatory cytokines such as IL-1 and TNF. They are short cationic peptides of around 30-40 amino acids that usually have three disulfide bonds stabilizing a common amphipathic structure—a positively charged region separated from a hydrophobic region. Defensins act within minutes to disrupt the cell membranes of bacteria and fungi, as well as the membrane envelopes of some viruses. The mechanism is thought to involve insertion of the hydrophobic region into the membrane bilayer and the formation of a pore that makes the membrane leaky. Beta1-defensin is composed of a short segment of alpha helix resting against three strands of antiparallel Beta sheet (green), generating an amphipathic peptide with charged and hydrophobic residues residing in separate regions. This general feature is shared by defensins from plants and insects and allows the defensins to interact with the charged surface of the cell membrane and become inserted in the lipid bilayer. Although the details are still unclear, a transition in the arrangement of the defensins in the membrane leads to the formation of pores and a loss of membrane integrity (bottom panel). Human Paneth cells make as many as 21 different defensins, many of which are encoded by a cluster of genes on chromosome 8.

Write the disease if we have mutated btk?

X-linked (Bruton) agammaglobulinemia

Antibody- antigen interaction in H20 solution in equimolar concentration, what happens?

You will have a tighter bond due to that the interaction in a van der waals bond. • Hydrophobic interactions occur when two hydrophobic surfaces come together to exclude water. The strength of a hydrophobic interaction is proportional to the surface area that is hidden from water. For some antigens, hydrophobic interactions probably account for most of the binding energy. In some cases, water molecules are trapped in pockets in the interface between antigen and antibody. These trapped water molecules may also contribute to binding, especially between polar amino acid residues. Due to van der waals bond.

Transcription factor of T reg and which cytokines induce it?

natural regulatory Tcells (natural Te, 9 cells} Regulatory CD4 T cells that are specified in the thymus. They express FoxP3 and bear the markers CD25 and CD4 on their surface. Cf. induced regulatory T cells. IL-2 activates the transcription factor STAT5, which may enhance expression of FoxP3

A common thing between II 4 and II 10?

• IL 4 and Il 10 are Both secreted from Th2 and they both inhibit Th1.

MHC restriction for which lymphocytes?

• MHC I binds to CD8 T cytotoxic cells and MHC II binds to CD4 T helper cells.

A gene mutated in an immunodeficiency of the innate immune system?

• Mutation in the gene encoding GATA-2 transcription factor and in the gene encoding the MCM-4 DNA helicase leads to a reduced or absent NK cells. • Phox-91. • Leukocyte adhesion deficiency type 1 which a mutation in gene encoding the β chain (CD18) of β2 integrins. Two genetic causes of NK cell deficiency have been identified including an autosomal recessive CD16 functional defect and an autosomal dominant GATA2 mutation causing classic NK deficiency.

The antiviral state?

• Type I interferons singaling activate transcription of STAT1, STAT2, and IRF9 that confer on the cells a resistance to viral infection called an antiviral state. Plasmacytoid dendritic cells produce type I interferons in response to viral infections.The antiviral action of type I interferon is primarily a paracrine action in that a virally infected cell secretes. Type I interferon induced genes: -protein kinase (PKR), blocks viral transcriptional and translational events -RNase L, promotes viral RNA degradation Type I interferons cause sequestration of lympho- cytes in lymph nodes, thus maximizing the oppor- tunity for encounter with microbial antigens. Type I interferons increase the cytotoxicity of NK cells and CD8+ CTLs + promote the differentiation of naive T cells to the TH1 subset of helper T cells. Type I interferons upregulate expression of class I MHC molecules and thereby increase the probability that virally infected cells will be recognized and killed by CD8+ CTLs.

Mechanism underlying complement activation?

-Activation of the complement system by bacterial surfaces leads to a cascade of proteolytic reactions that coats microbes with complement fragments -Complement-coated microbes are recognized and bound by specific complement receptors on macrophages -taken up by phagocytosis, and destroyed.

Write an autocrine cytokine

-Development as TH17 involves the initial production by the T cell of the cytokine IL-21, which acts in an autocrine manner to activate STAT3, a transcription factor required for development as TH17. -Activated T cells secrete and respond to IL-2. Activation of naive T cells in the presence of co-stimulation through CD28 signaling induces the expression and secretion of IL-2 and the expression of high-affinity IL-2 receptors. IL-2 binds to the high-affinity IL-2 receptors to promote T-cell growth in an autocrine fashion. Il-4 stimulates the development of Th2 effector cells from CD4+T cells and functions as an autocrine growth factor for differentiated Th2 cells.

Alternative pathway of the complement properdin (Factor P)?

-Protein secreted by activated neutrophils in plasma. -Properdin binds and stabilizes c3bBb complex (C3 convertase) -attachment of properdin favoured in microbes. -Properdin is the only known positive regulator of complement -properdin could therefore direct the activity of the alternative complement pathway to pathogen surfaces.

Write 2 synergic cytokines?

-TNF-a and IFN-y released by activated T cells also act synergistically to change the shape of endothelial cells, allowing increased blood flow, increased vascular permeability, and increased emigration of leukocytes, fluid, and protein into the infected tissue -TNF-a and LT-a can synergize with IFN-y in macrophage activation and in killing some target cells through their interaction with TNFR-I, which induces apoptosis -addition of IL-4 or IL-13 to TNF-alpha or IL-5 has synergistic effects on eosinophil activation, suggesting that the combined effects of different cytokines present in BALF following allergen provocation can enhance eosinophil activation in vitro. IL-18 and IL-12 for Th1 differentiation in response to viral infection

Write a cytokine responsible for specific immunity ???

1) IL-2 stimulates growth of Th,TCT, T reg+NK cells 2) IL-4 stimulate differentiation of T cells into Th2+ BCGF+ class switching from IgE and IgG 3) IL-5 promotes growth and differentiation of B cells+ enhances class switching to IgA+ stimulates growth+ differentiation of eosinophils 4) IFN-Y- cytokine for activating macrophages, it also induces the production of MHC-I molecules, MHC-II molecules, and co-stimulatory molecules by APCs in order to promote cell-mediated immunity 5) IL-13 B cell isotype switching to IgE

Write at least two T cells immunodeficiencies?

1. DiGeorge syndrome: 22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches, which results in absent thymus and parathyroids, so T cells are not developed, this causes recurrent viral/ fungal infections+ conotruncal abnormalities 2. Il-12 receptor deficiency: Il-12 along with IFN-Y induce Helper T cells to differentiate into Th1 cells. So deficiency in Il-12 results in decrease in Th1 response. It is an autosomal recessive disease. Th1 cells secrete IFN-Y and Il-2 so when there's a deficiency in Th1 there's also a deficiency in IFN-Y and Il2 3. Autosomal dominant hyper-IgE syndrome (Job syndrome) Deficiency of Th17 cells due to STAT3 mutation --> imapaired recruitment of neutrophils to sites of infection Increased levels of IgE, decreased levels of IFN-Y + increased levels of eosinophils 4. Chronic mucocutaneous candidiasis T cell dysfunction

IL-4 (at least 2 functions)?

1. IL-4 stimulates B cells to produce IgE antibodies (isotype switching) also enhances switching to IgG4 and inhibits switching to IgG2a and IgG2c isotypes 2. Induces differentiation of Th2 cells with Il-2 3. Inhibits Th1 cell with Il-10 4. Il-4 acts a B cell growth factor 5. Il-4 and Il-13 stimulate the recruitment of leukocytes, notably eosinophils by promoting the expression of adheson molecules on endothelium and the secretion of chemokines that bind chemokine receptors expressed on eosinophils

3 examples of the use of monoclonal antibodies

1. Identification of phenotypic markers unique to particular cell type (recognition of cell populations, e.g Clusters of Differentiation) 2. Immunodiagnosis (detection of infectious antibodies via urine/blood/tissues) 3. Tumor identification (determine tissue source of tumour via staining) 4. Therapy ( antibodies against TNF used to treat Rheumatoid arthritis+other inflammatory diseases+ CD20 for the treatment of B cell leukemias 5. Functional analysis of cell surface and secreted molecules (purify selected cell populations from complex mixtures to facilitate the studies) Cancer Rheumatoid arthritis Multiple sclerosis Cardiovascular disease Systemic lupus erythematosus Crohn's disease Ulcerative colitis Psoriasis Transplant rejection, and several more conditions In these conditions the monoclonal antibody targets and interferes with the action of a chemical or receptor that is involved in the development of the condition that is being treated. For example, a monoclonal antibody used for treating cancer may block a receptor that cancer cells use for preventing the immune system from the destroying the cancer cell. Blocking this receptor allows the immune system to recognize cancer cells and destroy them.

What signalling pathway activates pyroptosis?

1. NLRP3 signaling leads to the generation of pro-inflammatory cytokines and to cell death through formation of a multiprotein complex known as the inflammasome 2. Activation of the inflammasome proceeds in several stages: The first is the aggregation of LRR domains of several NLRP3 molecules, or other NLRP molecules, by a specific trigger or recognition event. 3. This aggregation induces the pyrin domains of NLRP3 to interact with pyrin domains of another protein named ASC (also called PYCARD). 4.ASC is an adaptor protein composed of an amino-terminal pyrin domain and a carboxy-terminal CARD domain. 5. Pyrin and CARD domains are each able to form polymeric filamentous structures 6. The interaction of NLRP3 with ASC further drives the formation of a polymeric ASC filament, with the pyrin domains in the center and CARD domains facing outward. 7. These CARD domains then interact with CARD domains of the inactive protease pro-caspase 1, initiating CARD-dependent polymerization into discrete caspase 1 filaments. 8. This aggregation seems to trigger the autocleavage of pro-caspase 1, which releases the active caspase 1 fragment from its autoinhibitory domains. 9. Active caspase1 then carries out the ATP-dependent proteolytic processing of pro-inflammatory cytokines, particularly IL-1B and IL-18, into their active forms. Caspase 1 activation also induces pyroptosis through an unknown mechanism that is associated with inflammation because of the release of these pro-inflammatory cytokines upon cell rupture

Production of monoclonal antibodies 3 stages

1. Spleen cells producing antibody from mouse immunized with antigen A 2. Myeloma cells (immortal) lacking antibody secretion and the enzyme HGPRT 3. Mix and fuse cells with PEG to produce a hybrid cell line called a hybridoma 4. Transfer to HAT medium (immortal hybridomas proliferate; mortal spleen cells and unfused HGPRT-myeloma cells die 5. Select hybridoma that makes antibody specific for antigen A 6. Clone selected hybridoma producing anti-A antibody

Advantages of polyclonal antibodies

A mixture of different antibodies produced by many clones of B lymphocytes that may each bind to different portions (epitopes) of an antigen (so-called polyclonal antibodies) Polyclonal antibodies recognize multiple epitopes on any one antigen. 1. They are able to expand on the signal expelled by the target even though it is very low intensity. 2. More tolerant of minor antigen changes (eg polymorphism, heterogeneity of glycosylation or slight denaturation) than monoclonals. 3. Can identify proteins of high homology to the immunogen protein, and can be used to screen for the target protein in species other than that of the immunogen. 4. When dealing with chromatin immunoprecipitation, the polyclonal antibodies work best because they have a broader target area and can pick up even the lowest resonance when it comes to the expression of certain types of protein 5. Often the preferred choice for detecting denatured proteins. 6. They are hardier than other types of antibodies and can withstand more disruptions or alterations in the antigens. They can withstand harsher conditions and more diverse environments. 7. Polyclonals are extremely inexpensive and fast easy to create.

Phenotype of Natural Killer cells? Which markers are expressed?

A subset of innate lymphoid cells that function in innate immune responses to kill microbe-infected cells by direct lytic mechanisms and by secreting IFN-γ. NK cells do not express clonally distributed antigen receptors like Ig receptors or TCRs, and their activation is regulated by a combination of cell surface stimulatory and inhibitory receptors, the latter recognizing self MHC molecules. They can be identified in the blood by expression of CD56 and the absence of the T cell marker CD3. Most human blood NK cells also express CD16, which is involved in recognition of antibody-coated cells. CD16 binds to the Fc regions of certain types of antibodies called IgG1 and IgG3 During an infection, the adaptive immune system produces IgG1 and IgG3 antibodies that bind to microbial antigens expressed on the surface of infected cells, and CD16 on NK cells can bind to the Fc regions of these antibodies. As a result, CD16 generates activating signals, through its associated signalling partners, and the NK cells may kill the infected cells that have been coated with antibody molecules- antibody-dependent cell-mediated cytotoxicity

CD45 where do you find it and whats its enzymatic activity

A transmembrane tyrosine phosphatase found on all leukocytes. It is expressed in different isoforms on different cell types, including the different subtypes of T cells. Tyrosine phosphatase that regulates T and B cell activation Tyrosine phosphatase, augments signaling through antigen receptor of B and T cells, multiple isoforms result from alternative splicing CD45 protein is a receptor tyrosine phosphatase expressed in all hematopoietic cells. CD45RO (lack L-selectin): lsoform of CD45 containing none of the A, B,and C exons (on memory CD4 cell+CD8 +effector CD4) CD45RA: lsoforms of CD45 containing the A exon (on naive CD4 cell+CD8) CD45RB: lsoforms of CD45 containing the B exon CD45RO: memory T cells; subset of B cells, monocytes, macrophages CD45RA: naive T cells, B cells, monocytes CD45RB: B cells, subset of T cells

Enzyme that initiates somatic hypermutation, gene rearrangement, isotope switching?

Activation-induced (cytidine) deaminase (AID) An enzyme expressed in B cells that catalyzes the conversion of cytosine into uracil in DNA, which is a step required for somatic hypermutation and affinity maturation of antibodies and for Ig class switching. Activation induced deaminase Other enzymes involved in class switching: Uracil-DNA-glicosylase, and AP-endonucleas.

What adaptive immunity means?

Adaptive immunity= The form of immunity that is mediated by lymphocytes and stimulated by exposure to infectious agents. In contrast to innate immunity, adaptive immunity is characterized by exquisite specificity for distinct macromolecules and by memory, which is the ability to respond more vigorously to repeated exposure to the same microbe. Adaptive immunity is also called specific immunity or acquired immunity. The adaptive immune system uses three main strategies to combat most microbes. ● Antibodies. Secreted antibodies bind to extracellular microbes, block their ability to infect host cells, and promote their ingestion and subsequent destruction by phagocytes. ● Phagocytosis. Phagocytes ingest microbes and kill them, and antibodies and helper T cells enhance the microbicidal abilities of the phagocytes. ● Cell killing. Cytotoxic T lymphocytes (CTLs) destroy cells infected by microbes that are inaccessible to anti- bodies and phagocytic destruction. The goal of the adaptive response is to activate one or more of these defense mechanisms against diverse microbes that may be in different anatomic locations, such as the intestines or airways, the circulation, or inside cells. All adaptive immune responses develop in sequential steps, each of which corresponds to particular reactions of lymphocytes.

What effector functions are carried by IgG3?

Being a potent pro-inflammatory antibody, its shorter half-life may function to limit the potential of excessive inflammatory responses Opsonization and phagocytosis complement activation neonatal immunitya(placental transfer)

The role of pd1 receptor

Also known as CD279 is expressed on activated T cells and B cells Binds PD-L1 and PD-L2; inhibits T cell activation role in down-regulating the immune system and promoting self tolerance by suppressing T cell inflammatory activity. PD-1 is an immune checkpoint and guards against autoimmunity through a dual mechanism of promoting apoptosis (programmed cell death) in antigen-specific T-cells in lymph nodes while simultaneously reducing apoptosis in regulatory T cells PD- ligand interactions inhibit the activation of effector cells, especially in peripheral tissues.

Interleukins involved in the activation of macrophages (both classical and alternative)?

Alternative activation: Macrophages that differentiate under the influence of the TH2 (humoral) - cell cytokines IL-4 and IL-13. They produce the enzyme arginase, which helps increase the contractility of intestinal smooth muscle in response to parasite infection and promotes tissue remodeling and repair. Also known as M2-type macrophages. Classical activation : pro-inflammatory macrophages (Ml- pe macrophages), which tend to differentiate after interaction with TH1 cells- cell cytokines IFN-Y, IL-10

Epitope is

An individual antigen receptor or antibody recognizes a small portion of the antigen's molecular structure, and the part recognized is known as an antigenic determinant or epitope Typically, proteins and glycoproteins have many different epitopes that can be recognized by different antigen receptors. Macromolecules, such as proteins, polysaccharides, and nucleic acids, are usually much bigger than the antigen- binding region of an antibody molecule (see Fig. 5-6). Therefore, any antibody binds to only a portion of the macromolecule, which is called a determinant

Which factors determine anergy of lymphocyte T

Anergy= absence of the normal immune response to a particular antigen or allergen. TCR-induced signal transduction is blocked in anergic cells. In different experimental models, it is attributable to decreased TCR expression (perhaps because of increased degradation;) and recruitment to the TCR complex of inhibitory molecules such as tyrosine phosphatases. ● Self antigen recognition may activate cellular ubiquitin ligases, which ubiquitinate TCR-associated proteins and target them for proteolytic degradation in proteasomes or lysosomes. The net result is loss of these signaling mol ecules and defective T cell activation. One ubiquitin ligase that is important in T cells is called Cbl-b. This enzyme is involved in maintaining T cell unresponsiveness to self antigens. ● When T cells recognize self antigens, they may engage inhibitory receptors of the CD28 family, whose function is to terminate T cell responses. The functions of the best known inhibitory receptors of T cells are described in the section that follows. outcome of antigen recognition by T cells, particularly CD4+ cells, is determined by a balance between engagement of activating and inhibitory receptors. Although many inhibitory receptors have been described, the two whose physiologic role in self-tolerance is best established are CTLA-4 and PD-1. Studies of these inhibitory receptors have increased our understanding of tolerance mechanisms and led to new therapeutic approaches for manipulating immune responses. . CTLA-4 is a member of the CD28 receptor family it binds to B7 molecules.

Draw excess of antigen

Antigen excess (also known as "prozone" or "hook effect") occurs when antigen is present in such high levels that it limits the antigen-antibody crosslinking, resulting in the formation of smaller immune complexes causing immunoassays to underestimate high concentrations of protein

Difference between antigen and immunogen?

Antigens are substances that bind specific lymphocyte receptors whether or not they stimulate immune responses. e.g hapten antigenic but not immunogenic has one epitope (e.g peptides, metal ions) Immunogens are substances that bind specific lymphocyte receptors and stimulate immune response Hapten (possess immunoreactivity)+ carrier (immunogenecity) =immunogen

Function of the lysozyme? Where functions?

Antimicrobial proteins comprises enzymes that attack chemical features specific to bacterial cell walls. Such antibacterial enzymes include lysozyme and secretory phospholipase A2, which are secreted in tears and saliva and by phagocytes. Lysozyme is a glycosidase that breaks a specific chemical bond in the peptidoglycan component of the bacterial cell wall. Lysozyme selectively cleaves the Beta-(1,4) linkage between these two sugars and is more effective in acting against Gram-positive bacteria, in which the peptidoglycan cell wall is exposed, than against Gram-negative bacteria, which have an outer layer of LPS covering the peptidoglycan layer. Lysozyme is also produced by Paneth cells, specialized epithelial cells in the base of the crypts in the small intestine that secrete many antimicrobial proteins into the gut. ..

Structure and function of BCR?

BCR (B cell receptor) The cell surface antigen receptor on B lymphocytes, which is a membrane bound immunoglobulin molecule. TLRs, the BCR, the TCR, and many cytokine receptors of the TNF and IL-1R family activate NF-κB, The BCR is made up of membrane-bound immunoglobulin and an associated disulfide-linked Igα and Igβ heterodimer, each Igα and Igβ contains ITAM motifs in their cytoplasmic tails. Signaling pathways linked to the BCR are broadly similar to signaling pathways downstream of the TCR Structure of the B Cell Receptor for Antigen Membrane IgM and IgD, the antigen receptors of naive B cells, have short cytoplasmic tails consisting of only three amino acids (lysine, valine, and lysine). These tails are too small to transduce signals generated after the recognition of antigen. Ig-mediated signals are transduced by Igα and Igβ that are disulfide linked to one another and are expressed in B cells non-covalently associated with membrane Ig. ITAM motif in their cytoplasmic tails, are required for the transport of membrane Ig molecules to the cell surface, and together with membrane Ig form the B cell receptor (BCR) complex. B cell receptor complexes in class-switched B cells, including memory B cells, contain membrane immunoglobulins that may be of the IgG, IgA, or IgE classes Function: BCR signaling leads to PIP3 formation, which binds other signaling molecules, leading to activation of B cell High affinity B cells, which are best able to recognize and respond to antigen, may activate endogenous inhibitors of Fas when their BCRs recognize antigen and thus be protected from death, while low affinity B cells are killed. Plasma cells are morphologically distinct, terminally differentiated B cells committed to abundant antibody production . They are generated after the activation of B cells through signals from the BCR, CD40, TLRs, and other receptors including cytokine receptors.

Write the target cells of these two cytokines.

Both cytokines act synergistically on endothelial cells. • IL-4 B cells: isotype switching to IgE T cells: TH2 differentiation, proliferation Macrophages: alternative activation and inhibition of IFN-γ-mediated classical activation Mast cells: proliferation (in vitro) • IL-13 Epithelial cells: increased mucus production Fibroblasts: increased collagen synthesis Macrophages: alternative activation B cells: isotype switching to IgE

Most abundant circulating complement fragment?

C3 because is involved in all pathways:classical, alternative and lectin pathways, and all those pathways result in the generation of enzyme complexes that are able to cleave c3, e.g in classical and lectin pathways c2b and c4b form c3 convertase and in alternative c3b and Bb.

Write the thioester bond in C3B and the ester bond with the surface of the microbe?

C3 in plasma is being continuously cleaved at a low rate to generate C3b in a process that is called C3 tickover. The C3 protein contains a reactive thioester bond that is buried in a region of the protein known as the thioester domain. When C3 is cleaved, the C3b molecule undergoes a dramatic conformational change and the thioester domain flips out (a massive shift of about 85 Å), exposing the previously hidden reactive thioester bond. A small amount of the C3b may become covalently attached to the surfaces of cells, including microbes, through the thioester domain, which reacts with the amino or hydroxyl groups of cell surface proteins or polysaccharides to form amide or ester bonds. If these bonds are not formed, the C3b remains in the fluid phase, and the exposed and reactive thioester bond is quickly hydrolyzed, rendering the protein inactive. As a result, further complement activation cannot proceed.

Why is C3 concentration highest in the plasma?

C3 plays a central role in the activation of complement system. Its activation is required for both classical and alternative complement activation pathways. Normally, C3 in plasma is being continuously cleaved at a low rate to generate C3b in a process that is called C3 tickover. The C3 protein contains a reactive thioester bond that is buried in a region of the protein known as the thioester domain.

3 functions of complement?

C3b and ic3b (product of cleavage from c3b)—opsonization C3a, C4a, C5a— induce acute inflammation via activatyion of mast cells, that start to degranulate realing vasoactive mediators that are called anaphylatoxins = anaphylaxis. C5a—neutrophil chemotaxis. C5b-9—cytolysis by MAC.

Markers of stem cells

CD 34, Cd45

Surface markers on naive and effector?

CD27 expression is a marker for memory B cells. naive T cells express CD45RA most activated and memory T cells CD45RO Memory T cells, like naive but not effector T cells, express high levels of the IL-7 receptor (CD127). Naïve T cells are CD45RA+, CCR7, +CD62L Memory T cells :CD45RO+, CCR7+CD62L+, Effector memory T cells: CD45RO, +CCR7 Effector cells are CD45RA A common thing between II 4 and II 10

B cells markers of differentiation?

CD45R, MHC class II IgM, CD19, CD20, CD40

2 inhibitors of complement cascade

CD59 =inhibits formation of the Membrane Attack complex (MAC). It is exrpresses on many normal cells, but not on microbes it incorporates inself into assembling MACs after the membrane insertion of C5b-8, and inhibits subsequent addition of C9 molecule S protein = binds to soluble c5b, 6, 7 complexes and prevents their insertion into cell membranes near the site where complement cascade was initiated. The proteolytic activity of C1r and C1s is inhibited by a plasma protein called C1 inhibitor. C1 INH is a serine protease inhibitor that mimics the normal substrates of C1r and C1s. If C1q binds to an antibody and begins the process of complement activation, C1 INH becomes a target of the enzymatic activity of the bound C1r2-C1s2. C1 INH is cleaved by and becomes covalently attached to these complement proteins, and, as a result, the C1r2-C1s2 tetramer dissociates from C1q, thus stopping activation by the Both S protein and CD59 inhibit formation of MAC. These inhibitors are significant so complement attacks only microbes and not normal cells.

3. Write prevents complement activation on the host (CD59)?

CD59 is a regulator of complement activation. It incorporates itself into assembling MACs after the membrane insertion of c5b-8 so inhibits the subsequent addition of c9 molecules, present on normal cells. Viruses such as HIV, human cytomegalovirus and vaccinia incorporate host cell CD59 into their own viral envelope to prevent lysis by complement.

Innate immunity receptors

Chemotactic receptors, such as the f-Met-Leu-Phe receptor, which binds the N-formylated peptides produced by bacteria and guides neutrophils to sites of infection. c5a receptor on mast cells TLR-4, signals the presence of LPS by associating with CD14, the macrophage receptor for LPS. TLR-4 is also involved in the immune response to at least one virus, respiratory syncytial virus, although in this case the nature of the stimulating ligand is not known. Another mammalian Toll-like receptor, TLR-2, signals the presence of a different set of microbial constituents, which include the proteoglycans of gram-positive bacteria,

Which chromosome encodes for kappa light chain

Chromosome 2

What happens in all complement pathways after the activation of C3 convertase?

Classical pathway: 1. C3 convertase activates C3, it is cleaved c3a leaves and c3b binds to c3 convertase 2. c4b+c2a+c3b complex forms c5 convertase 3. c5 binds to c5 convertase and becomes cleaved, so c5b binds to the complex subsequently and c5a leaves 4. Late steps of complement activation Alternative pathway: 2. c3b+cBb+c3b complex forms c5 convertase Lectin pathway: 2. c4b+c2a+c3b form c5 convertase

Say three intra-vesicular pathogens?

Classically, Th1 cells are targeted towards intravesicular pathogens such as bacteria and parasites via the activation of infected macrophages, whilst Th2 cells invoke antibody production in B-cells, which neutralise extracellular pathogens and toxins. Mycobacteria -Macrophage activation resulting in granulomatous inflammation and tissue destruction Lysteria monocytogenes- Listeriolysin damages cell membranes Legionella pneumophila- Cytotoxin lyses cells and causes lung injury and inflammation

again Th1 differentiation (transcription factor)?

Differentiation induced by IFN-γ and IL-12 transcription t bet, stat 1 and stat 4

name 3 bacteria's that survive in the lysosomes

Disruption of phagosome membrane, escape into cytoplasm- Listeria monocytogenes Inhibition of phagolysosome formation- Mycobacterium tuberculosis, Legionella pneumophila Inactivation of reactive oxygen and nitrogen species-Mycobacterium leprae (phenolic glycolipid)

Which bond keep together Ig antigen?

Disulfide bonds-4 bonds 2 on the hinge regions of heavy chains and 1 between each Ch1 and Cl

Auto inflammatory disease?

Dysregulated activation of the inflammasome due to autosomal gain-of-function mutations in one or another of its component proteins leads to inappropriately triggered and excess IL-1 production. The result is recurrent attacks of fever and localized inflammation, most commonly in joints and intestines. These disorders are called Cryopyrin Associated Periodic Syndromes (CAPS) and are a subset of a larger group of periodic fever syndromes with similar symptoms caused by excessive production of or responses to inflammatory cytokines. These disorders are also called autoinflammatory syndromes, because they are characterized by spontaneous inflammation without an overt inciting trigger. Inappropriate inflammasome activation has been associated with various diseases. Gout causes inflammation in the cartilaginous tissues by the deposition of monosodium urate crystals which cause inflammation because those crystals activate the NLRP3 inflammasome, which induces the inflammatory cytokines associated with the symptoms of gout. Mutations in the NOD domain of NLRP2 and NLRP3 can activate inflammasomes inappropriately, and they are the cause of some inherited autoinflammatory diseases, in which inflammation occurs in the absence of infection. Mutations in NLRP3 in humans are associated with hereditary periodic fever syndromes, such as familial cold inflammatory syndrome and Muckle-Wells syndrome.Macrophages from patients with these conditions show spontaneous production of inflammatory cytokines such as IL-1Beta. -Familial Mediterranean fever (FMF), which its clinical features are periodic fever, serositis (inflammation of the pleural and/or peritoneal cavity), arthritis, acute-phase response. Its mode of inheritance is autosomal recessive. -Hyper-IgD syndrome (HIDS), which its clinical features are periodic fever, elevated IgD levels and lymphadenopathy. Its mode of inheritance is autosomal recessive. -Blau syndrome NLRP2 mutation, which its clinical features include granulomatous inflammation of skin, eye and joints. Its mode of inheritance is autosomal dominant

Which epitopes are lost during cooking of the food?

Epitopes formed by several adjacent amino acid residues are called linear determinants. conformational determinants are formed by amino acid residues that are not in a sequence but become spatially juxtaposed in the folded protein Both T-cell and B-cell epitopes are important for inducing an immune response to a food allergen, on every single allergen these epitopes are different. B-cell epitopes are the antigenic determinants on the surface of the allergen that are recognized in their natural state by BCR, those epitopes are conformational. 10% of the B-cell epitopes can be linear. This might be the result of several food allergens losing their conformational integrity during cooking and digestion. Linear B-cell epitopes have been identified in various food allergens, incl. allergens from milk, egg, peanut, wheat, soybean, shrimp antibodies that recognise linear epitopes instead of conformational epitopes are chosen for immunodetection.

What are the surface markers of naive lymphocytes in the periphery?

The mature naive B cell surface markers: CD45R MHC class II, IgM, IgD CD19, CD20, CD21 CD40 The mature naive CD4 T cell surface markers: CD4 CD62L CD45RA CD5 The mature naive CD8 T cell surface markers include: CD8 CD45RA.

Clonal exhaustion?

Exhausted CD8+ T cells show numerous functional and phenotypic changes, including reduced production of IFN-γ and increased expression of multiple inhibitory receptors, notable PD-1 and CTLA-4 which lead to programmed cell death In some chronic viral infections, CTL effector responses are generated, but they are then gradually extinguished, a phenomenon that is called exhaustion

Fab fragment composition

Fab portions of the antibody bind to the target protein. 2 pieces Identical to each other and consist of the complete light chain (VL and CL) associated with a VH- CH1 fragment of the heavy chain. These fragments retain the ability to bind antigen because each contains paired VL and VH domains/

How many Fc receptors there are?

Fcγ receptors have been classified into three groups, I, II and III, based on their affinities for heavy chains of different IgG subclasses. 6 Fc receptors/ 9

Write the activation mechanism of that oncogene.

Generally: The activation of oncogenes involves genetic changes to cellular protooncogenes. The consequence of these genetic alterations is to confer a growth advantage to the cell. Three genetic mechanisms activate oncogenes in human neoplasms: (1) mutation, (2) gene amplification, and (3) chromosome rearrangements. These mechanisms result in either an alteration of protooncogene structure or an increase in protooncogene expression. Because neoplasia is a multistep process, more than one of these mechanisms often contribute to the genesis of human tumors by altering a number of cancer-associated genes. Full expression of the neoplastic phenotype, including the capacity for metastasis, usually involves a combination of protooncogene activation and tumor suppressor gene loss or inactivation. RAS Cell activation with growth factors such as epidermal growth factor (EGF) induces Ras to move from an inactive GDP-bound state to an active GTP-bound state. Encodes for a small GTPase which hydrolyzes GTP into GDP and phosphate. Is activated by growth factor signaling and function like a binary switch and growth signalling pathways. Downstream effectors of Ras includes the protein MAPK -regulates genes that mediate cell proliferation RAS oncogene mutation: thyroid tumors, certain leukemias and cancer of pancreas and colon

Which cells from donor in transplantation determine rejection?

Graft rejection is mediated by T cells, including CTLs that kill graft cells and helper T cells that cause cytokine-mediated inflammation resem- bling DTH reactions, and by antibodies

Which is the hypervariable region in the HLA-DR?

HLA-DR is an MHC class II cell surface receptor encoded by HLA complex on chromosome 6 region. Comprise 2 chains alpha and beta and each has 2 domains Hypervariable region is in Beta chain, Beta 1 domain

Which immunoglobulin domains come into contact with an antigenic determinant?

Immunoglobulin domain = A three-dimensional globular structural motif found in many proteins in the immune system, including Igs, TCRs, and MHC molecules. Ig domains are about 110 amino acid residues in length, include an internal disulfide bond, and contain two layers of β-pleated sheets, each layer composed of three to five strands of antiparallel polypeptide chain. Ig domains are classified as V-like or C-like on the basis of closest homology to either the Ig V or C domains Variable domain Vl and Vh

Write an hypothetical sequence of the PNP junction?

Hematopoietic stem cells give rise to progenitor that is common lymphoid progenitor which form here gives mainly Pro-B and Pro-T cells with a purine nucleoside phosphorylase deficiency the maturation of B and T cells is unable to happen. an enzyme that is also involved in purine catabolism. PNP catalyzes the conversion of: inosine to hypoxanthine guanosine to guanine Deficiency of PNP leads to the accumulation of deoxyguanosine and deoxyguanosine triphosphate, with toxic effects on immature lymphocytes, mainly T cells. Autoimmune hemolytic anemia and progressive neurologic deterioration are also features of this disorder.

Cytokines and chemokines directing gut homing?

Homing is the phenomenon whereby cells migrate to the organ of their origin. Naive T cell homing to mesenteric lymph nodes and Peyer's patches is the contribution of the Ig superfamily molecule MadCAM-1 (mucosal addressin cell adhesion molecule 1), which is expressed on HEVs in these sites but not typically elsewhere in the body. Naive T cells express two ligands that bind to MadCAM-1, L-selectin and the integrin α4β7, and both contribute to the rolling step of naive T cell homing into gut-associated lymphoid tissues. High endothelial venules (HEV) are specialized post-capillary venous swellings characterized by plump endothelial cells as opposed to the usual thinner endothelial cells found in regular venules. The major integrin on gut-homing B and T lymphocytes is α4β7, which binds to the MadCAM-1 protein expressed on post-capillary venular endothelial cells in the gut lamina propria. Gut homing also requires the chemokine receptor CCR9 on the B and T lymphocytes and its chemokine ligand CCL25, which is produced by intestinal epithelial cells. The combined expression of MadCAM-1 and CCL25 is restricted to the gut. Homing of IgA-producing cells to the colon also requires CCR10 expression and the chemokine CCL28, but this is not a gut-specific pathway because CCL28 is expressed by epithelial cells in other mucosal

Which molecules inhibit TH2?

IFN-Y which is secreted from Th1 cells GATA-3 transcription factor blocks Th1 differentiation by inhibiting expression of signalling chain of the IL-12R Induced by Il-2, Il-4

Structure of molecules that activate IFN type I

IFN-γ is produced by NK cells and acts on macrophages together with Toll-like receptor (TLR) signals delivered by microbes to trigger macrophage activation.

Activators and inhibitors of NK cells

IL-12, IL-15, IL-18, and type I interferons. Each of these cytokines enhances the cytotoxic activity of NK cells, and they can stimulate IFN-γ secretion by the NK cell independent of activating receptors. Activated Receptors= on infected and injured cells (KIR2Ds; CD16; NKG2D) Inhibitory Receptors= on healthy cells LIRs (CD94, ILT-2, KIRs Activators: HLA-C; IgG coated cells; MIC-A MICB Inhibitors: HLA-E; HLA-A, B, C; HLA-C

What immunoglobulins lack the hinge region?

IgE and IgM

What Ig molecules are expressed on memory B cell?

IgG and under certain situation IgA and IgE. The tails of Igα and Igβ are physically associated with Src family tyrosine kinases, including Lyn, Fyn, and Blk. BCR complexes in class-switched B cells, including memory B cells, contain membrane Igs that may be of the IgG, IgA, or IgE classes

Igg2 function

IgG2 recognizes polysaccharides, it acts above all against pneumococcus, meningococcus ... that have the capsule rich in polysaccharides. Furthermore, IgG3, besides opsonizing and stimulating phagocytosis, is also able to activate the classic complement pathway IgG2 = respiratory infections ---> saccharide antigens IgG3 ---> protein antigens of the same infections (both intervene but for different types of epitopes)

What IgG subclass pass through the placenta?

IgG3, IgG1 and IgG4.

Which molecules inhibit TH1?

Il-4 and Il-10 which are released from Th2 cellsc Induced by IFN-Y, Il-12

Which chains of the Ig is found in the urine of a patient affected by myeloma?

Light chains κ /λ

LAK cells (killer cells activated from lymphokine)

Lymphokine-activated killer (LAK) cells NK cells with enhanced cytolytic activity for tumor cells as a result of exposure to high doses of IL-2. LAK cells generated in vitro have been adoptively transferred back into patients with cancer to treat their tumours Generate LAK cells by culturing peripheral blood leukocytes from patients with the tumor in high concentrations of IL-2, and injecting the LAK cells back into the patients

Say why an individual MHC haplotype can bind different peptides compared to a different MHC haplotype?

MHC haplotype is the set of MHC alleles present on each chromosome. The MHC is a large genetic region coding for highly polymorphic, codominantly expressed class I and class II MHC molecules. MHC class 1 and class 2 are molecular fingerprints, different ppl have different sets of those molecules. There are many different types of A genes A1-A50. A genes are slightly different from person to person. MHC I = A C B -genes related to the class 1 formation A, C, B in each of those genes one sequence nucleotide undergoes constant rearrangement, each time of different rearrangement mRNA is made. Each of those mRNAs are different and making proteins with different areas corresponding to the areas of mRNA-those areas are called hypervariable areas-determine antigenic binding. Different antigens fit into those hypervariable areas. Between adjacent parts of alpha 1 and alpha 2 domains of alpha chain are hypervariable regions. For instance, HLA haplotype of an individual could be HLA-A2, c27, B5, DR3 and et.c for each individual there are 12 types of MHC molecules-6 for Class I and 6 for class II Class II molecules expressed only on APCs. MHC class II also 3 loci: DR DQ DP D region subtypes These are present at both maternal and paternal chromosomes. In tissues 6 types of DR, DQ, DP. The person has 12 MHC molecules in total. Maternal and paternal alleles in MHC class I are co-dominant. Every human expresses 6 types (ACB maternal+paternal) of class I molecule on every nucleated cell and platelets.

PI3K signalling?

Membrane PIP3, generated by PI3-kinase (PI3K), activates PDK1, which phosphorylates and activates the Akt kinase, which in turn phosphorylates downstream targets that are involved in cell survival. Biochemical events of mast cell activation.

What is multiple myeloma?

Multiple myeloma= is a form of blood cancer in which a malignant tumor of antibody- producing B cells (plasma cells) often secretes Igs or parts of Ig molecules. Multiple myeloma can produce monoclonal antibodies In multiple myeloma, normal plasma cells transform into malignant myeloma cells and produce large quantities of an abnormal immunoglobulin called monoclonal protein or M protein.

Immunodeficiency diseases of innate immunity

NK cell deficiencies- NK cell deficiencies- Mutations in the gene encoding the GATA-2 transcription factor and in the gene encoding the MCM-4 DNA helicase Toll-like receptor signaling defects

NK method of killing markers of superficial autoimmunity.

NK cells express high levels of NOD2 NOD2. Polymorphisms in this gene are associated with Crohn's disease, one type of inflammatory bowel disease. NOD2 is a cytoplasmic sensor of bacterial peptidoglycans and is expressed in multiple cell types, including intestinal epithelial cells. It is thought that the disease-associated polymorphism reduces the function of NOD2, which cannot provide effective defense against certain intestinal microbes. As a result, these microbes are able to traverse the epithelium and initiate a chronic inflammatory reaction in the intestinal wall, which is a hallmark of inflammatory bowel disease. NK cells may be directly involved in these diseases through their potential autoreactivity or through their interaction with dendritic cells, macrophages or T lymphocytes, thereby inducing excessive inflammation or favouring the adaptive autoimmune response. Thus, NK cells may be implicated in the onset, the maintenance or the progression of autoimmune diseases. In rheumatoid arthritis (RA), an autoimmune disease characterized by joint inflammation, synovium-infiltrating NK cells have been documented.28 These NK cells are CD56bright and produce more interferon (IFN)-γ than blood NK cells from the same patients.13 Moreover, these NK cells can induce the differentiation of monocytes into dendritic cells (DCs). Thus, in RA tissue, NK cells are characterized by disease-promoting functions, which is in contradiction to findings that circulating NK cells in patients with RA are reduced in number and have reduced functions.

Which bonds keep immunoglobulins (Ig's) and antigens (Ag's)?

Non-covalent interactions, including electrostatic forces, hydrogen bonds, van der Waals forces, and hydrophobic interactions

how to obtain Fc which enzyme?

Papain enzyme can breakdown antibody at hinge region, the antibody is broken down into 3 fragments. Add papain to the solution of antibodies Add antigen Some fragments will bind with the antigen The antigen fragments that do not bind with antigens go to the bottom of solution and get crystallized. Out of 3 fragments only 2 could bind to the antigen and the other went down and got crystallized. Ab+ papain → 2 Fab+1 Fc

Lymphocytes in peripheral blood?

Peripheral blood lymphocytes (PBL) are mature lymphocytes that circulate in the blood, rather than localising to organs (such as the spleen or lymph nodes).[1][non-tertiary source needed] They comprise T cells, NK cells and B cells.

What is pyroptosis (apoptotic death by inflammation)?

Pyroptosis is a form of programmed cell death associated with antimicrobial responses during in- flammation. Immune cells that recognise certain danger signals within themselves produce cytokines, swell, burst and die. This releases the cytokines, attracts other immune cells to fight the infection and contributes to inflammation. Some examples of pyroptosis include salmonella-infected macrophages and abortively HIV- infected T helper cells. The initiation of pyroptosis is caused by the recognition of flagellin components of Salmonella and Shigella species (and similar pathogen-associated molecular patterns (PAMPs) in other microbial pathogens) by NOD-like receptors (NLRs). These receptors function like plasma membrane Toll-like receptors (TLRs), but recognise antigens located within the cell rather than outside of it. Inflammasome activation of caspase-1 may also cause a form of programmed cell death called pyroptosis, characterized by swelling of cells, loss of plasma membrane integrity, and release of inflammatory mediators. Pyroptosis results in the death of certain microbes that gain access to the cytosol and enhances the release of inflammasome-generated IL-1β, which lacks a hydrophobic leader sequence that is required for conventional secretion of proteins from cells. In addition to caspase-1- dependent pyroptosis, a caspase-11-dependent pathway of pyroptosis is required for protection against certain bacteria that readily gain access to the cytosol of host cells, but the innate stimuli that activate this pathway are not yet known.

In which stage of maturation does receptor editing occur?

Receptor editing is a process that occurs during the maturation of B cells, self-reactive immature B cell. Immature B lymphocytes that recognize self antigens in the bone marrow with high affinity either change their specificity or are deleted. Self antigen recognition by immature B cells induces reactivation of RAG genes and the rearrangement and production of a new Ig light chain, allowing the cell to express a different (edited) B cell receptor that is not self-reactive. The original VJκ exon encoding the variable domain of an autoreactive light chain gene is typically deleted and replaced by a new rearrangement involving an upstream Vκ and a downstream Jκ gene segment. If the editing process fails to generate an in-frame productive κ light chain rearrangement on either chromosome, the activated immature B cell may then go on to rearrange the λ light chain locus that is located on a different chromosome. Almost all B cells bearing λ light chains are therefore cells that were once self-reactive and have undergone receptor editing.

What prevents complement activation on the host?

Regulators of complement activity. -C1 estrase inhibitor: stops the activation by classical pathway -Factor I: cleaves c3b and c4b by using factor H, MCP C4BP or CR1 as cofactors -Factor H: for alternative pathway binds to c3b and displaces Bb -c4 binding protein (c4bp): binds c4b and displaces c2 -DAF: displaces 2a from c4b and Bb from C3b (dissociation of C3 convertase) -CD59: blocks C9 binding and pvents formation of the MAC (membrane attack complex_)

Function of s1pr1 s1p

S1P is a lipid chemoattractant which controls the exit of Naive T cell from lymph nodes it binds to a G-coupled receptor-S1PR1 on T cells.Signals generated by S1P binding to S1PR1 on naive T cells stimulate directed movement of the cells along the S1P concentration gradient out of the lymph node parenchyma to circulation via conc. gradient maintained by S1P-degrading enzyme, S1P lyase (are located in tissues) .So lipid is catabolized in tissues more than in lymph and blood. Naive T cell enters lymph node, where S1P conc. low, S1PR1 is reexpressed over a period of several hours. This time lag allows a naive T cell to interact with antigen-presenting cells. Once the S1PR1 receptor is expressed, the T cell leaves the lymph node and is directed down the S1P concentration gradient into the efferent. If a naive T cell is activated by antigen in the lymph node, the reexpression of S1PR1 is suppressed by IFN type I for several days, and therefore the ability of the cells to leave the lymphoid tissue in response to an S1P gradient is delayed. Antigenic stimulation +IFNs--> increase expression of CD69 on T cell which binds to S1PR1 and reduces its expression, so T cell is insensitive to S1P gradient allowing T cell to remain in the lymphoid organ and undergo clonal expansion+ differentiation into effecor T cells. When this is complete, the cells lose CD69, reexpress S1PR.

Conformation assumes by IgM in the absence or presence of the antigen?

Soluble IgM is in planar form Antigen bound IgM is in staple form

Unique immune cells of nervous system

Some monocytes shift to CNS during early phase of development, they become permanent residents= microglia

To which region of the TCR does the superantigen bind?

Superantigen is a polyclonal stimulus , Superantigens are rrecognized by T cells without being processed into peptides that are captured by MHC molecules Bacterial superantigens bind mainly to the V beta CDR2 loop and to a smaller extent to the V beta CDR1 loop and and an additional loop hypervariable 4 or HV4 loop Superantigen binds to specific variable region on the Beta chain of the T-cell Receptor and to the alpha chain of MHC clsass II molecules.

List the cytokines involved in septic shock?

Systemic shock reaction that can follow infection of the bloodstream with endotoxin-producing Gram-negative bacteria. It is caused by the systemic release of TN F-a and other cytokines. Also called endotoxic shock. TNF-a released in septic shock also triggers blood clotting in small vessels throughout the body IL-6, and IL-1 are the principal cytokine mediators of septic shock, but IFN-γ and IL-12 may also contribute TNF and IL-1 act on leukocytes and endothelium to induce acute inflammation, and both cytokines induce the expression of IL-6 from leukocytes and other cell types. TNF, IL-1, and IL-6 mediate protective systemic effects of inflammation, including induction of fever, acute-phase protein synthesis by the liver, and increased production of leukocytes by the bone marrow. Systemic TNF can cause the pathologic abnormalities that lead to septic shock, including decreased cardiac function, thrombosis, capillary leak, and metabolic abnormalities due to insulin resistance.

Structure and function of TCR?

TCR antigen receptor consists of heterodimer--> 2 transmembrane poplypeptide chains. On N terminal variable regions of each chain and on C terminal Constant regions. Disulfide bridges between extracellular cysteine residues and between alpha and beta chain in the hinge region. They have a 5-12 amino acid residues (too small to transduce signal) Beta chain of Variable domain contains 4th hypervariable region where superantigen binds. The TCR complex is made up of the TCR α and β chains that contribute to antigen recognition and the ITAM-containing signaling chains CD3 γ, δ, and ε as well as the ζ homodimer. The CD3 chains each contain one ITAM, whereas each ζ chain contains three ITAMs TCR ligation results in tyrosine phosphorylation of CD3 and ζ ITAMs by Src family kinases and the re- cruitment of ZAP-70 to the phospho-ITAMs, each SH2 domain of ZAP-70 binding to one phosphorylated tyrosine of the ITAM. Activated ZAP-70 phosphorylates tyrosine resi- dues on adaptors, and downstream enzymes are recruited to the signalosome. To activate T cell

Function of Th1 cells

TH1 cells secrete IFN- γ, which acts on macrophages to increase phagocytosis and killing of microbes in phagolysosomes and on B lymphocytes to stimulate production of IgG antibodies that opsonize microbes for phagocytosis. Help for antibody production may be provided not by classical TH1 cells, most of which migrate out of lymphoid organs to sites of infection and inflammation, but by follicular helper T (TFH) cells that remain in lymphoid organs and produce IFN-γ. The role of IFN-γ in antibody production is established in mice but not in humans. TH1 cells also produce TNF, which activates neutrophils and promotes inflammation.

Write the effects of these cytokines.

TNFα and IFNγ act synergistically to change the shape of endothelial cells, allowing increased blood flow, increased vascular permeability, and increased emigration of leukocytes, fluid, and protein into the infected tissue.

Through which cells does the Salmonella pass to cross the barrier of the gastrointestinal tract?

The gut-associated lymphoid tissues (GALT) include the tonsils, adenoids, appendix, and specialized structures in the small intestine called Peyer's patches antigen is collected by specialized epithelial cells called microfold or M cells The lymphocytes form a follicle consisting of a large central dome of B lymphocytes surrounded by smaller numbers of T lymphocytes. Dendritic cells resident within the Peyer's patch present the antigen to T lymphocytes. Lymphocytes enter Peyer's patches from the blood and leave through efferent lymphatics. Effector lymphocytes generated in Peyer's patches travel through the lymphatic system and into the bloodstream, from where they are disseminated back into mucosal tissues to carry out their effector actions

In how long the levels of tryptase fall?

The measurement of blood tryptase level is now widely used as a marker of mast cell degranulation for in vitro confirmation of anaphylaxis. Beta-tryptase is released from mast cells but not from basophils and diffuses more slowly than histamine. The concentration of tryptase peaks 1-2 hours after the onset of reaction and remains elevated with a half-life of 1.5-2.5 hours. The samples for tryptase testing should be collected within 6 hours of anaphylaxis onset and again after 24 hours to check that the value has returned to normal. Tryptase can also be detected in postmortem specimens after death from suspected anaphylaxis.31

enzyme that converts the inactive precursor in the active form?

The proteases of the complement system are synthesized as inactive pro-enzymes (or zymogens) , which become enzymatically active only after proteolytic cleavage, usually by another complement protein. The complement pathways are triggered by proteins that act as pattern recognition receptors to detect the presence of pathogens. This detection activates an initial zymogen, triggering a cascade of proteolysis in which complement zymogens are activated sequentially, each becoming an active protease that cleaves and activates many molecules of the next zymogen in the pathway, amplifying the signal as the cascade proceeds. This results in activation of three distinct effector pathways—inflammation, phagocytosis, and membrane attack—that help eliminate the pathogen.

The unit of measure of affinity and which one is found between Ig and antigen?

The strength of the binding between a single combining site of an antibody and an epitope of an antigen is called the affinity of the antibody. The affinity is commonly represented by a dissociation constant (Kd), which indicates how easy it is to separate an antigen-antibody complex into its constituents. A smaller Kd indicates a stronger or higher affinity interaction because a lower concentration of antigen and of antibody is required for complex formation.

How many types of activation of lymphocyte B there are? ++

There are: Helper T cells, which are usually CD4+, express surface molecules such as CD40 ligand (CD154) and secrete cytokines that bind to receptors on macrophages and B lymphocytes, leading to their activation. Susceptibility genes may disrupt self-tolerance mechanisms, and infection or necrosis in tissues promotes the influx of autoreactive lymphocytes and activation of these cells, resulting in tissue injury. Adaptor molecule called SAP (SLAM-associated protein) that binds to a family of cell surface molecules involved in the activation of NK cells and T and B lymphocytes, including the signaling lymphocyte activation molecule (SLAM).

Function of the cationic protein of eosinophils?

To destroy tough integuments of helminths. Is a neurotoxin

Write an oncogene?

a gene having the potential to cause a normal cell to become cancerous Src Ras Myc RTK CTK

Give an example of three intravesicular pathogens.

extra boost of activation to kill the pathogen: this is one of the roles of theTH1 subset of CD4T cells.

What is contained in the secondary granules of eosinophils?

lysosomal hydrolyses , major basic protein and eosinophil cationic protein and eosinophil peroxidase and lipid mediators, cathepsin