Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Case 17 > Theme 1: HIV and Immunology > Flashcards

Theme 1: HIV and Immunology Flashcards

1
Q

what type of virus is HIV?

A

a human retrovirus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

how is HIV transmitted?

A

blood: IVDU, blood transfusion, needles tick injuries
sexual transmission
mother to baby transmission:at birth, breast-feeding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

how does HIV lead to immunodeficiency?

A

through infection and destruction of CD4 T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is AIDS?

A

aquired immune deficiency syndrome. this is the name given to a group of infections and illnesses that happen when your immune system becomes severely damaged by HIV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what affects HIV transmission?

A

biggest impact on transmission is the HIV viral load. if there is an undetectable viral load then HIV will not be passed on.
decreased risk with circumcision
increased risk with concomitant (accompanying) STI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what is seroconversion?

A

HIV infection transitions to detectable presence of HIV antibodies in the blood- becomes HIV positive. happens 2-6 weeks after exposure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what are the symptoms experienced during HIV seroconversion?

A 
rash 
lymphadenopathy
fever
sore throat 
headaches
diarrhoea 
20% asymptomatic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what are the clinical stages of HIV infection?

A

stage I- asymptomatic, can have generalised lymphadenopathy, performance scale 1: asymptomatic, normal activity.
stage II- weight loss (<10% body weight), minor mucocutaneous manifestations (seborrheic dermatitis, fungal nail infections, recurrent oral ulcerations), herpes zoster, recurrent URTI, performance sale 2: symptomatic, normal activity.
stage III- weight loss (>10% body weight), unexplained chronic diarrhoea, unexplained prolonged fever, oral candidiasis, oral hairy leukoplakia, pulmonary TB, severe bacterial infections (pneumonia, pyomyositis), performance level 3: bedridden <50%of last month.
stage IV (AIDS defining events)- HIV wasting syndrome, pneumocystic pneumonia, toxoplasmosis, CMV infection in abnormal organs (reitinits), candidiasis of the oesophagus, trachea, bronchi, extra pulmonary TB, lymphoma, kaposi’s sarcoma, HIV encephalopathy. typically seen when CD4 count drops below 200

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what are the tumours seen in HIV?

A

mostly virally induced and driven
kaposi’s sarcoma- human herpes virus 8
lymphomas- epstein barr virus
cervical and anal carcinoma- HPV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is PCP and how is it treated/ prevented?

A

Pneumocystis carinii pneumonia
most common AIDS defining illness, occurs when CD4<200
usually subacute presentation with dry cough, night sweats, SOB, desaturation on exercise
treatment- cotrimoxazole- 120mg/kg in 3 divided doses
prevention- primary prophylaxis if CD4<250- cotrimoxazole 960mg 3x week, same for secondary prophylaxis after PCP. HAART until sustained undetectable viral load and CD4>200

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

how is HIV diagnosed?

A

blood or saliva testing for antibodies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is reverse transcription?

A

the conversion of the viral RNA genome into a DNA provirus. this provirus is then integrated into the hosts genome causing lifelong infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what are the main receptors that HIV interacts with?

A

primary receptor: CD4

secondary receptors: CCR5 or CXCR4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what is CCR5 and CXCR4?

A

CCR5- chemokine receptor, macrophage tropic- found on macrophages. HIV which interacts with CCR5 is known as M-tropic/ R5 tropic HIV. R5 strains are generally found in early stages of infection.
CXCR4- chemokine receptor, T cell tropic. R4 tropic strains are generally found later infection and associated with faster T cell clearance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

how does the virus enter cells?

A

CD4 and CCR5/CXCR4 are involved in fusion of the viral and cellular membranes. fusion is driven by the viral proteins gp120 and gp41 which exist as a complex on the viral cell membrane. the gp120/gp41 complex interacts with CD4 which results in the exposure of a fusion domain on gp41 which interacts with the host cell membrane and changes occur causing the membranes to fuse.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

how is an immature virion activated after it is released from the cell?

A

viral poly proteins chains are cleaved by viral protease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what are PAMPs and what are they recognised by?

A

pathogen associated molecular patterns are recognised by pattern recognition receptors (PRRs) e.g. a toll like receptor on innate immune cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what are DAMPs?

A

damage associated molecular patterns which are released when host cells are damaged when pathogens enter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

where do B and T cells mature?

A

T cells- thymus

B cells- bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what cells bring the gap between the innate and adaptive immune system?

A

dendritic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

which cells control cell mediated immunity?

A

T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

which cells control humoral immunity?

A

B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what are major histocompatibility complexes?

A

they are cell surface molecules that present peptide fragments to naive T cells in order to activate them and turn them into effector T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what is HLA?

A

human leukocyte antigen- the complex of genes that encode the production of MHC molecules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

where are MHC I found and what is their purpose?

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

where are MHC II molecules found and what are their purpose?

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what is the structure of MHC I?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

what is the structure of MHC II?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

how are antigens presented on MHC I?

A
  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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

how are antigens presented on MHC II?

A
  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?
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

what is the structure of the TCR?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

describe the process of T cell developmet

A
  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.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

what is positive and negative selection?

A

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)

34
Q

what is the function of pd-1?

A

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)

35
Q

what are the 3 signals needed for CD4 T cell activation?

A
  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.
36
Q

which cytokines induce CD4 T cells to become Th1 cells?

A

INF-gamma and IL-12

37
Q

which cytokine induces formation of Th2 cells?

A

IL-4

38
Q

which cytokines induce formation of Th17 cells?

A

TGF-beta, IL-6 and IL-23

39
Q

which cytokines induce formation of Tfh cells

A

IL-6

40
Q

which cytokines induce the formation of iTreg cells?

A

TGF-beta and IL-2

41
Q

what is the role of IL-2?

A

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

42
Q

how is clonal expansion regulated?

A
  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.
43
Q

what are the 2 mechanisms in which CD8 T cells are activated?

A
  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
44
Q

what cytokines do Th1 cells produce and what is their function?

A

cytokines- INF-gamma

function- activate macrophages, enabling intracellular pathogens to be destroyed more efficiently

45
Q

what cytokines do Th2 cells produce and what is their function?

A

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

46
Q

what cytokines do Th17 cells produce and what is their function?

A

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

47
Q

what cytokines fo Tfh cells produce and what is their function?

A

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

48
Q

what cytokines to regulatory T cells produce and what is their function?

A

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

49
Q

how do cytotoxic T cells kill cells infected with intracellular pathogens?

A

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.

50
Q

what is a BCR?

A

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

51
Q

what are the 3 ways in which antibodies protect extracellular spaces from pathogens?

A
  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
52
Q

what is the structure of antibody molecules?

A

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.

53
Q

what are the variable arms of an antibody called?

A

the fab fragments

54
Q

what is the Fc fragment of the antibody?

A

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

55
Q

what are the different subgroups of light chain constant region?

A

kappa or lambda

both light chain constant regions will be the same in one immunoglobulin

56
Q

what determines the immunoglobulin class?

A

the heavy chain

57
Q

what is the antigen binding site made up of?

A

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

58
Q

what are the 5 immunoglobulin classes and their structure?

A

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

59
Q

what is the function of IgG?

A

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

60
Q

what is the function of IgA?

A

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

61
Q

what is the function of IgM?

A

found in blood but not in tissues

main Ig in the primary immune response

62
Q

what antibody exists on the surface of B cells as the BCR?

A

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

63
Q

what are the processes which generate antibody diversity?

A
  1. combinatorial diversity (genetic rearrangement)
  2. junctional diversity
  3. affinity maturation
  4. class switching
64
Q

what is the process of combinatorial diversity?

A

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.

65
Q

what is junctional diversity?

A

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
66
Q

when does combinational and junctional diversity occur?

A

in naive B cells

process can lead to non-functional rearrangements which cause the B cell to not mature

67
Q

what is affinity maturation?

A

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

68
Q

what is the process of class switching?

A 
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.
69
Q

which class switch does IL-4 induce?

A

class switch to IgE and IgG1

70
Q

which class switch does IFN-gamma induce?

A

class switch to IgG3 and IgG2a

71
Q

which class switch does TGF-beta induce?

A

switch to IgG2b and IgA

72
Q

which class switch does IL-21 induce?

A

switch to IgG1, IgG3, IgA

73
Q

how are B cells activated?

A

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

74
Q

what is thymus-dependant antigen activation?

A
  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
75
Q

what are germinal centres?

A

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

76
Q

what is the function of chemokine secreted by stroll and follicular dendritic cells?

A

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

77
Q

what is thymus independent antigen activation?

A

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.

78
Q

how are memory B cells reactivated during the secondary immune response?

A

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.

79
Q

where are B cells found in lymph nodes?

A

the follicles

80
Q

where are T cells found in the lymph nodes?

A

the paracortex

81
Q

where are T and B cells found in the spleen?

A

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

Case 17 (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions