Theme 1: HIV and Immunology Flashcards

Question

where are MHC I found and what is their purpose?

Answer 1

MHC I molecules are found on the surface of all nucleated cells. they present peptides made within the cell. if the cell is infected these peptides will be pathogenic. MHC I presents antigens to cytotoxic (CD8+) T cells and if the cell is infected they will induce apoptosis in the cell.

Answer 2

MHC II molecules are found on professional antigen presenting cells (APCs) such as dendritic cells, B cells and macrophages. they present antigens from extracellular pathogens that have been phagocytosed to naive T helper cells (CD4+) causing them to activate.

Answer 3

MHC I has 1 alpha chain with 3 subunits and 1 beta2 microglobulin unit.

Answer 4

MHC II molecules have 1 alpha chain with two subunits and 1 beta chain with 2 subunits. the two chains are of similar sizes

Answer 5

1. the MHC alpha chain binds to calnexin in the ER. the beta2 micro globulin then binds to the alpha chain and the complex is released from calnexin. 2. the MHC I complex then binds to a complex of chaperone proteins (Erp57, calrectulin and tapasin- which help stabilise and position MHC I) and to TAP ( a transporter involve in antigen processing). this forms the peptide loading complex. 3. proteins in the cytosol are degraded by the proteasome into peptide fragments which enter the ER via TAP. 4. the peptide fragment binds to MHC I and this causes the release of the chaperone complex and TAP. the MHCI: antigen complex is then exported to the surface of the cell

Answer 6

1. MHC II molecules are found bound to and invariant chain in the ER. this stopes peptide fragments binding in the ER 2. the invariant chain causes the MHC II to leave the ER in a vesicle which enters the endolytic pathway and becomes more acidic. 3. the drop in pH cleaves the invariant chain leaving CLIP (class II associated invariant chain peptide) still bound to the MHC. endocytose pathogens are degraded into peptide fragments by hydrolytic enzymes but CLIP prevents them from binding to MHC. 4. HLA-DM binds to MHC II and removes CLIP so that an antigen can bing. the MHCII:antigen complex is then expressed on the cell surface?

Answer 7

they consist of one alpha chain and one B chain with CD3 molecules on either side.

Answer 8

1. T cells derived from hfaematopoeic stem cells leave the bone marrow and migrate to the thymus for development and maturation. 2. these T cell progenitors are double negative for CD4 and CD8 and have no TCR or CD3. 3. thymic stroll cells commit the T cell progeintors to the T cell lineage via the NOTCH-1 signalling receptor which imitates TCR gene rearrangement and the T cell beigins to express both CD4 and CD8- it is double positive. 4. genes for the beta chain undergo V(D)J recombination first. unsuccessful rearrangement leads to apoptosis. the cell starts to express CD3 and the alpha chain then also rearranges. 5. positive selection then occurs followed by negative selection. 6. T cell stops expressing either CD4 or CD8 and the mature single positive T cells leave the thymus to be activated in secondary lymphoid organs.

Answer 9

positive selection- T cells are destroyed if the TCR cannot recognise self MHC negative selection- T cells destroyed if they react to self antigen (a small number of self reactive T cells become regulatory T cells)

Answer 10

programmed cell death protein 1 this causes apoptosis in self reactive T cells and reduces apoptosis in regulatory T cells (which suppress the immune system)

Answer 11

1. the MHC II:peptide complex binding to the TCR. this binding is further strengthened by the interaction of CD4 with a region on the MHC. 2. co- stimulatory molecules on both cells interacting. the main signal is provided by CD28 (on the T cell) binding to b 7 (on APC). 3. the release of cytokines from the APC. these cytokines also determine the fate of the cell.

Answer 12

INF-gamma and IL-12

Answer 13

TGF-beta, IL-6 and IL-23

Answer 14

TGF-beta and IL-2

Answer 15

produced by most naive T cells upon activation and acts as a motive feedback mechanism that enhances survival and proliferation of T cells

Answer 16

1. CTLA-4- an inhibitory receptor for B7 which is expressed by activated T cells. it binds to B7 with a higher affinity than CD28 and therefore limits the proliferative response of activated T cells 2. anergy- a state when a T cell cannot respond to its specific antigen.

Answer 17

1. a specific CD8 TCR binds to a MHCI:antigen complex; strengthened by CD8 interaction. in some cases this along with the production of IL-2 is enough to activate a T cell to become a cytotoxic T cell 2. in most cases more stimulation is required. in this case the CD8 cell will bind to an MHC I on an activated APC and a T helper cell which recognises a similar antigen will bind to an MHC II on the same APC. this CD4 T helper cell becomes activated and increases the level of co-stimulation provided to the CD8 T cell, as well as producing IL-2. these both promote differentiation of the CD8 T cell into a cytotoxic T cell

Answer 18

cytokines- INF-gamma | function- activate macrophages, enabling intracellular pathogens to be destroyed more efficiently

Answer 19

cytokines- IL-4, IL-5 and IL-13 function- cause degranulation of mast cells and eosinophils and cause secretion of antibodies from plasma cells. target- parasites such as helminths

Answer 20

cytokines- IL-17 and IL-22 function- act on stroll epithelial cells to recruit leukocytes such as neutrophils, to sites of infection and therefore increase inflammation target- extracellular bacteria and fungi

Answer 21

cytokines- IL-21 function- found in follicles of secondary lymphoid tissues, activate and induce class switching allowing them to produce and secrete antibodies target- extracellular pathogens

Answer 22

cytokines- TGF- beta, IL-10 function- down regular differentiation and proliferation of other T cells, maintain tolerance to self reactive T cells to prevent autoimmunity

Answer 23

when a cytotoxic T cell recognises a non-self antigen presented on MHC II it induces apoptosis by releasing cytotoxic molecules: perforin- forms pores in the membrane of infected cells allowing granzymes to enter granzymes- serene protease enzymes that induce apoptosis. when activated cytotoxic T cells express Fas ligand which binds to Fas on target cells causing the infected cell to undergo apoptosis.

Answer 24

a ,e, brane bound antibody found on B lymphocytes which recognises and binds to an antigen on an extracellular pathogen

Answer 25

1. neutralisation- antibodies inhibit the toxic affects of the pathogen or its toxins 2. opsonisation- an antibody bound to a pathogen has a unbound Fc region which can bind to Fc receptors on phagocytic cells helping them to ingest and kill the pathogen 3. complement activation- antibodies can bind to pathogens and trigger complement by activating C1 (classical pathway). deposition of complement proteins enhances opsonisation and can kill bacteria by activating the membrane attack complex

Answer 26

roughly Y shaped, composed of 2 identical light chains and 2 identical heavy chains. the light chains consist of one variable domain and one constant domain. the heavy chains have one variable domain and 3 or 4 constant domains.

Answer 27

the fab fragments

Answer 28

the stem of the Y which consists of the constant domains, binds to effector molecules

Answer 29

kappa or lambda | both light chain constant regions will be the same in one immunoglobulin

Answer 30

the heavy chain

Answer 31

each variable domain contains 3 hypervariable regions. the hyperveriable regions of the light and heavy chains are closely related and together form the antigen binding site

Answer 32

IgM, IgD, IgA, IgG, IgE IgG, IgA, and IgD have 3 constant regions IgM and IgE have 4 constant regions and no hinge region IgG, IgA and IgD are monomeric IgA is usually a dimer but can be secreted as a monomer IgM is secreted as a pentamer

Answer 33

found as 4 subclasses 1,2,3 and 4 found in the blood stream and extracellular space. they are the main circulating ig in the secondary immune response

Answer 34

exists as 2 subclasses 1 and 2 can be found in bloodstream but is mainly found in secretions which act in defence of mucosal surfaces- gut, respiratory tract. it is also secreted into the respiratory tract

Answer 35

found in blood but not in tissues | main Ig in the primary immune response

Answer 36

the monomeric forms of IgM and IgD. these are the first antibodies to react to a new antigen before class switching

Answer 37

1. combinatorial diversity (genetic rearrangement) 2. junctional diversity 3. affinity maturation 4. class switching

Answer 38

each variable domain is encoded by a random combination of each of the V (variable), D (diversity- only in heavy chains) and J (joining) exons from each gene complex. heavy chain reaarangement occurs first: 1. a random D gene segment is joined to a random J gene segment by 'looping out' of the excess DNA. this process is catalysed by RAG1 and RAG2 proteins. 2. RAG proteins then join a random V gene segment to the DJ gene segment producing one continuous segment which codes the variable region. 3. C exons encode the constant region. a c segment is joined to the VDJ exon by differential splicing. the mRNA can then be translated into a functional heavy chain. light chain rearrangement occurs in a similar way but there are only the V and J segments.

Answer 39

increasing diversity via the formation of junctions between gene segments. 3 processes: 1. junctional flexibility- slight variations in the positions of segmental joining when exons are spliced. 2. nucleotide addition- nucleotides can be added between the gene segments by the enzyme TdT (terminal deoxynucleotide transferase) 3. nucleotide deletion

Answer 40

in naive B cells | process can lead to non-functional rearrangements which cause the B cell to not mature

Answer 41

a process which makes an antibody a better for its antigen. when activated B cells are replicating they express an enzyme called activation induced cytidine deaminase (AID) which creates mutations in the variable region (somatic hypermutation). antibody mutations that result in higher affinity for the specific antigen are positively selected for. those which reduce affinity are destroyed. therefor antibodies produced later in the primary immune response and in the secondary immune response will therefore have increased affinity for the antigen

Answer 42

``` the first immunoglobulin expressed by the B cell is IgM (or IgD). however later in the immune response the same variable region can be expressed with a different constant region (class switching): before each heavy chain C segment there is a DNA segment called a switch site (except delta). when a B cell is activated AID initiates class switching. two switch sites are joined together and the other C segments are looped out and deleted. ```

Answer 43

class switch to IgE and IgG1

Answer 44

class switch to IgG3 and IgG2a

Answer 45

switch to IgG2b and IgA

Answer 46

switch to IgG1, IgG3, IgA

Answer 47

B cell activation requires signalling from the BCR and from one other signal either thymus- dependant antigen activation or thymus independent antigen activation.

Answer 48

1. B cell presents an antigen on MHC II which is recognised by a TCR on a Tfh cell. once activated the Tfh cell expresses CD40L and secretes cytokines 2. CD40L interacts with CD40 on the B cell. IL-21 and IL-4 secreted by the Tfh cell interact with their specific receptors on the B cell to provide survival signals 3. the B cell becomes activated, undergoes proliferation and differentiates into plasma cells

Answer 49

sites where mature B cells undergo proliferation, differentiation, affinity maturation and class switching, leading to plasma cells being produced.

Answer 50

cause migration of B and T cells to areas of lymphoid tissue where they can interact.

Answer 51

B cells are activated without help from Tfh cells. instead other surface receptors (toll-like receptors) recognise ligands to provide the second signal. to strengthen this signal cross linking of the BCR with the toll-like receptor occurs which induces pro-survival signals. however this produces low affinity antibodies (no affinity maturation) and there is no class switching. so thymus dependant antigen activation produces a stronger immune response.

Answer 52

the memory B cell present s the antigen to memory Tfh cells. this activates the memory Tfh cell to reactivate and it can then help to activate the memory B cells. these then rapidly differentiate into plasma cells and secondary germinal centres form. high levels of highly specific IgG antibodies are produced.

Answer 53

the follicles

Answer 54

the paracortex

Answer 55

T cell dependant B cells- found in follicles T cell independent B cells- found in marginal zone T cells- peri-arteriolar lymphatic sheath

Theme 1: HIV and Immunology Flashcards

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