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3s2: Infection and Immunity > Week 2 > Flashcards

Week 2 Flashcards

1
Q

What is an overview of immunoglobulins?

A

Antigen binding proteins
Present on B cell membrane confers antigenic specificity
Secreted by plasma cells

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2
Q

What is an overview of the function of antibodies?

A

Effectors of humoral immunity:
Search out and neutralise antigens
Mark antigens for elimination

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3
Q

What is the basic structure of antibodies and their isotypes?

A

Two identical light chains kappa, lambda
Two identical heavy chains mu, gamma, alpha, delta and epsilon
Hinge region though sometimes constant domain

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4
Q

What is an overview of the different types of antibodies?

A

IgM, IgG (g1, g2, g3, g4), IgA alpha1, alpha2), IgD, IgE resp

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5
Q

What is an overview of the size and structure of antibodies?

A

2 identical light chains and 2 identical heavy chains
~25,000 x2
~50,000 x2
total: ~150,000daltons/subunit

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6
Q

What joins the antibiotic chains together?

A

disulphide bonds join Light-Heavy, Heavy-Heavy number and position of S-S bonds varies also non-covalent interactions

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7
Q

What makes up the binding site of antibodies?

A

A group of amino acid residues in both the have and light variable domains

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8
Q

What is an overview of the constant domain?

A

Also known as the Fragment crystallisable
Constant domain of the heavy chain, determines the isotype therefore the different biological functions

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9
Q

What is an overview of immunoglobin domains?

A

“immunoglobulin fold”
b-pleated sheets alternating hydrophobic and hydrophilic amino acids 2 b sheets held together by S-S bond
Domains found in many proteins: immunoglobulin superfamily

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10
Q

What are cells that contain immunoglobulin domains?

A

Ig, TCR, MHC molecules (class I and II), B cell receptor, T cell accessary proteins (CD2, CD4, CD8, CD3), b2 microglobulin, adhesion molecules (VCAM-1), PDGF

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11
Q

How large is the complementary determing regions?

A

~110 amino acids NH3 terminal region of H or L chain varies greatly => V regions (variable) VL and VH
Most differences between antibodies are within complementary determining regions of the V regions (CDRs) = antigen binding site

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12
Q

What is the molecule type for immunoglobulins?

A

Glycoproteins - carbohydrate attachment in constant
region (prevent 2 heavy chains from nestling close to each
other – contributes to ability to bind complement proteins)

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13
Q

What is an overview of variable region?

A

Antigen binding site
Complementary Determining Regions CDRs
CDR1, 2, 3 of VH and VL domains
Complementary structures between CDR (Ab) and Ag
Conformational changes may be induced by Ag binding
More variation in heavy chain but both diverse

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14
Q

What is an overview of the constant region?

A

Biological functions determined by amino acid sequence
CH1 and CL extend Fab arms facilitating Ag interaction

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15
Q

What is an overview of the hinge region?

A

gamma, delta, alpha heavy chains
proline rich
flexible – Fab arms can assume various angles relative to
one another
IgE and IgM: 4th constant domain, no hinge region

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16
Q

What is the function of immunoglobulins?

A

Abs do not kill or remove pathogens just by binding to them must evoke responses
Constant heavy part responsible for interactions with other proteins and cells

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17
Q

What is an overview of antibodies helping with opsonisation?

A

IgG (1,3)
Promotion of phagocytosis by macrophages (mf) and neutrophils FcR (Fc receptors) bind C region of most IgG subclasses
Binding of FcR to Fc-Ag triggers phagocytosis

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18
Q

What is an overview of antibody dependent cell mediated cytotoxicity?

A

Antibodies bound to target cells (virus infected) with Fc receptors of NK cells directs cytotoxic activity
apoptosis not phagocytosis
IgG antibodies

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19
Q

What is an overview of the activation of complements by antibodies?

A

IgM and IgG(3)
IgM and IgG activate series of serum glycoproteins
lysis of bacterial cell by perforation of membranes

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20
Q

What are overview of immune complexes by antibodies?

A

Precipitation (agglutination)
Neutralisation IgA, IgG - blocks toxin binding, bacteria attachment

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21
Q

What is an overview of antibodies for allergic reactions?

A

Mediation of allergic reactions IgE
Mast cell activation

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22
Q

What is an overview of maternal antibodies for baby protection?

A

Trancytosis IgA
Passive immunisation IgG (1,3,4)

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23
Q

What is an overview of IgG?

A

most abundant Ig in serum ~80%
4 sub classes - differ in hinge region and different biological activities

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24
Q

What is an overview of IgG subtypes?

A

IgG1,3,4 cross placenta
IgG3 best complement activator
IgG1,3 mediate opsonisation

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25
Q

What is an overview of IgM?

A

~5-10% serum Ig monomeric IgM is membrane bound on B cells
1st class of Ig produced in primary response
Activates complement mucosal secretion

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26
Q

What is an overview of IgM structure?

A

IgM secreted as pentamer - held together by S-S
additional Fc-linked polypeptide: J (joining) chain

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27
Q

What is an overview of IgA?

A

~10-15% serum Ig predominant Ig in secretions: breast milk, saliva, tears, mucous (MALT)

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28
Q

What is an overview of IgA structure?

A

monomer (serum), dimer (secreted) or trimer J chain and secretory component
Cross-link large antigens prevents attachment of pathogens to mucosal cells (neutralisation)

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29
Q

What is an overview of IgE?

A

Binds FcR on blood basophils and tissue mast cells
Cross-linkage of receptor-bound IgE by Ag (allergen)
=> degranulation
=> release of pharmacologically active mediators

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30
Q

What is a overview of IgE targets?

A

anti-parasitic response
mediates immediate hypersensitivity reactions hayfever, asthma, hives, anaphylactic shock

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31
Q

What is an overview of IgD?

A

~0.2% serum Ig
with IgM is major membrane bound Ig expressed by mature B cells
no biological effector function has been found

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32
Q

What are antigens?

A

Substance (typically protein/peptide, but some polysaccharides, lipids and glycolipids) with ability to combine specifically with final products of response

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33
Q

What recognise antigens?

A

Capable of being recognised by B cell receptor, or TCR when complexed with MHC (or CD1 in case of lipids)

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34
Q

What are immunogens?

A

Substance with ability to INDUCE humoral and/or cell-mediated response = immunogens

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35
Q

What is the difference between B cells and T cell interaction with antigen?

A

B cells - binary complex of membrane through antibody to epitope of anitgen
T cells - Involves ternary complex of T-cell receptor, antigen and MHC molecule

36
Q

Do B cells and T cell binding bind to soluble antigens?

A

B cells - Yes
T cells - No

37
Q

Do B cells and T cells require the involvement of MHC molecules?

A

B cells - Not required
T cells - Required to display processed antigen

38
Q

What is the chemical nature of antigens required for B and T cells?

A

B cells - Protein, polysaccharide and lipids
T cells - Mostly proteins, but some lipids and glycolipids presented on MHC-like molecules

39
Q

What is an overview of the epitope properties for B cells and T cells?

A

Accessible, hydrophilic, mobile peptides containing sequential or nonsequential amino acids

40
Q

What is a epitope?

A

A group of amino acids or other chemical groups exposed on the surface of a molecule, frequently a protein, which can generate an antigenic response and bind antibody

41
Q

What properties of immunogen determines immunogenicity?

A

“Foreignness” [nonself] - phylogenetic distance
Molecular size
Chemical composition and heterogeneity - experiments with synthetic polymers
Susceptibility to Ag processing and presentation - large molecules more readily phagocytosed

42
Q

What is an overview of sea urchin antigen: size, complexity and B and T cell response in mice?

A

Large complex molecule
Both B cell and T cell large response

43
Q

What is an overview of rat myosin antigen: size, complexity and B and T cell response in mice?

A

Large complex molecule
B cell and T cell slight response due to phylogentic distance

44
Q

What is an overview of bacteria polysaccharride: size, complexity and B and T cell response in mice?

A

Large and not complex (long repeat sequence of repeating units)
Generates large B cell response
No T cell response as it isnt processbale and presentable

45
Q

What is an overview of sea urchin histone: size, complexity and B and T cell response in mice?

A

Small slightly complex
Slight response for B and T cells due to less complexity reduced complexity

46
Q

What is an overview of sea urchin myosin peptides: size, complexity and B and T cell response in mice?

A

Small slightly complex
No b cell response due to no 3d structure for epitope binding to occur
T cell response occurs due to the molecule still interacting with the MHC molecules

47
Q

How can biological systems impact immunogenicity?

A

Genotype of recipient animal - type of response, degree of response, MHC gene products play central role

Immunogen dosage and routes of administration
single dose -> weak response
repeated administration -> strong response

Adjuvants - substances that when mixed with Ag and injected with it, enhance immunogenicity of Ag often used to boost immune response not known how they work

48
Q

What is an overview of TI-1 antigens?

A

TI-1 antigens characterized by the same antigenic determinant repeated many times; can act as polyclonal stimulators (bacterial cell wall components e.g. LPS)

49
Q

What is an overview of TI-2 antigens?

A

~ TI-2 antigens are polymers that activate by cross-linking the B cell receptor; large polysaccharides (e.g. polymeric bacterial flagellin, and poliomyelitis virus)

50
Q

What are the steps for T-independent antigen?

A

Step 1: recognition/cross linking
Step 2: antibody secretion
Step 3: killing/neutralization
Step 4: they induce a weak memory

51
Q

What are T-independant antigens?

A

T-independent (TI) antigens activate B cells without T cell help

52
Q

What is an overview of B cell activation?

A

IgM binds to antigen eg compliment bound C3d
Coreceptors - IGalpha = CD79a and IGbeta = CD79b
Ligand binding to receptor brings about adaptve proteins and phosphorylations, signalling pathway

53
Q

What are the opening steps of T-dependant antigens?

A

Antigen binds to B cell, but B cell isnt fully acitvated unless T helper cells secrete various cytokines
The same antigen will be processed by an antigen processing cell and presented to T cells turning them into T helper cells doing whats said above

54
Q

What happens to acivated B cells by T helper cells?

A

Undergo divison and differentiation to form either Antigen producing cells or memory B cells

55
Q

How do T cells regonise antigens?

A

MHC on antigen presenting cells

56
Q

What is an overview of Epitopes?

A

Part of molecule that is antigenic determinant (part that
Ab or Ag-specific receptor binds to)
B and T cells will recognise different epitopes on same
antigenic molecule

57
Q

What is an overview of the structure of epitopes?

A

1˚, 2˚, 3˚ and 4˚ structure of protein involved
Side chain branching of glycosidic bonds affects epitopes in polysaccharides
Ag-Ab interactions are non-covalent

58
Q

What is an overview of B cell epitopes?

A

B cells recognise soluble antigen
Epitopes tend to be highly accessible sites on exposed
surfaces of antigen
Ab and Ag epitope must have complementary shapes Generally hydrophilic amino acids
Sequential or non-sequential residues
Located in flexible regions of immunogen, display motility

59
Q

What is an overview of T cell epitopes?

A

T cells recognise antigenic peptides (processed) presented in combination with MHC molecules
Trimeric complex: TCR, MHC, antigenic peptide
Antigen processing is required: APCs
Often internal sequences

60
Q

What are the two major pathways for antigen processing and presentation?

A

Endogenous Antigen Pathway
Exogenous / Endocytic processing pathway

61
Q

What sort of target undergo endogenous antigen processing?

A

Viruses and tumours

62
Q

What is the mechanism for endogenous antigen processing?

A

Synthesis of protein Ag in the cytosol
Proteolytic degradation of cytosolic proteins to constituent amino acids and recycled, but some persist as peptides
Transport of sampled peptides into endoplasmic reticulum
Assembly of peptide-class I complex within ER
Expression of complex on the cell surface

63
Q

What is an overview of endogenous antigen presenting?

A

Class 1 histocompatibility molecule, present pepetide eg from virus, CD8 receptor on cytotoxic T cell binds to the Class 1 compatibility molecule

64
Q

How are the proteins either for degradation or presentation selected?

A

How some proteins are selected for degradation to peptides and sampled for presentation remains unclear

65
Q

How do MHC class 1 process peptides?

A

Proteolytic degradation of ubiquinated proteins in proteasome
Transport of peptides into ER by TAP, binding to class 1 MHC molecules
Assembly of alpha chain-Beta2m heterodimers
Transport of peptide-class 1 MHC complex to cell surface
Presentation of peptie-class 1 MHC complex to CD8+ cytolytic T cell

66
Q

What is the function of immunoproteasomes?

A

In APCs and infected cells: immunoproteasome (in addition to normal proteasome) = produces peptides with increased binding to MHCI

67
Q

What is TAP?

A

Transporter associated with antigen processing
Two types, TAP1 and TAP2 forming a functional dimer

68
Q

What is on overview of TAP function?

A

Peptides move from the proteasome to TAP dimer
Peptide is moved through endoplasmic reticulum by passage through a tube in the TAP
The peptide emerges on the lumen side of the ER and is ready to be attached to MHC class 1

69
Q

What is an overview of MHC class 1 alpha chain?

A

It is synthesied on the rough endoplasmic reticulum
It associates with the chaperone protein calnexin that assists in proper folding
Class 1 alpha chain then becomes associated with the Beta2 microglobulin chain, releasing calnexin

70
Q

What is ERp57?

A

ERp57 - endoplasmic reticulum protein 57

71
Q

What happens with ERp57?

A

Tapasin (TAP associated protein) bring the Class 1 complex close to TAP transporter
Calreticulum (chaperon protein)
ERp57, tapasin and calreticulum assocociate with the class 1 complex

72
Q

What happens to the calreticulin-tapasin-associated class 1 MHC molecule?

A

The antigenic peptide is added, releasing the other factors
Insertion of the antigenic peptide into class 1, groove is a signal transit the class 1 molecule to the outer surface of the cell membrane

73
Q

What is an overview for cytotoxic t cells and relationship with intracellular pathogens?

A

CTLs activated by endogenous or intracellular antigens are the main effectors for intracellular pathogens

74
Q

What is immune evasion in relationship to MHC class 1?

A

Pathogens can interfere with Class I MHC expression to escape killing by CTLs by various mechanisms

75
Q

What are examples of pathogens escape death by cytotoxic T cells?

A

Adenovirus protein keeps MHC class I in the ER
Toxoplasma gondii induces inability to upregulate MHC class I
Mycoplasma tuberculosis downregulates CD1 presents glycolipid antigens to TCR]
HIV Nef protein downregulates MHC class I

76
Q

What are methods for virus to inhibit TAP?

A

Herpes simplex virus - ICP47 binds with nanomolar affinity to TAP and blocks peptide binding
Human herpesvirus 5 - U56 inhibits ATP binding to TAP via its ER-luminal domain
Bovine herpes virus - UL49.5 induces proteasomal degradation of TAP complex

77
Q

What is the base of exogenuous antigen processing and presentation?

A

MHC class II
Using exogenous antigens

78
Q

What is an overview of the mechanism of APC of MHC class II?

A

Endocytosis of Ag from the extracellular environment into APCs
Processing (time and metabolism dependent) of the Ag in acidic lysosomes with cellular proteases (cathepsin, leupeptin) needed, leading to the generation of peptides
Binding of peptides to MHC molecules within specialized vesicles
Surface expression of peptide-class II MHC molecule complex
Recognition of the complex by T cells (CD4) specific for the complex

79
Q

What are the steps for MHC class II presenting?

A

Internalisation of protein by endocytosis into endosome
Proteolytic processing of protein in endosome or lysosome generating peptides
Class II MHC polypeptide synthesis inside rough endoplasmic reticulum

80
Q

How is the MHC class II proteins prevented from binding to endogenously derived peptides?

A

LI protein binds to alpha-beta hetrodimer of the MHC class II to prevent endogenously derived peptides to MHC class II

81
Q

What happens after the production of MHC class II?

A

Fusion of endosomal derived CIIV/MIIC vesicle with exocytic vesicles containing class II MHC
Degredation of Li and DM mediated release of CLIP (class II
invariant chain peptide) and binding of peptide antigen to class II MHC molecule
Fusion of vesicle with plasma membrane: expression of peptide class II MHC complexes on cell surface
Presentation of peptide class II MHC complex to CD4+ helper T cell

82
Q

What is an overview of HLA-DM?

A

HLA-DM acts like a catalyst to influence binding of peptides for CLIP

83
Q

How does HLA-DM function?

A

li (invariant chain) binds to MHC class II in ER it assembles – prevents binding of peptides from endogenous pathway.

Proteolytic cleavage to CLIP and then HLA-DM mediated exchange of CLIP for exogenous peptide allows correct peptides to bind

84
Q

What is an overview of class II MHC on antigen presenting cell?

A

In normal APCs peptides are loaded onto class II molecules
In the absence of HLA-DM, the CLIP fragment isn’t removed and the blocked MHC molecule is unable to activate T cells

85
Q

What is a brief overview of the cross presentation pathway of exogenous and endogenous MHC pathways?

A

APCs can divert Ags obtained by exogenous to a pathways that leads to MHC I presentation

86
Q
A

3s2: Infection and Immunity (12 decks)

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