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HAEMOTOLOGY > Red cell Antibodies and their Role in Immune Haemolysis > Flashcards

Red cell Antibodies and their Role in Immune Haemolysis Flashcards

1
Q

an Immunogen is anything that

A

stimulates a specific immune response ie see as ‘foreign’

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2
Q

an Antigen may be comprised of several

A

epitopes

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3
Q

each specific Antibody will bind to a particular epitope on a

A

antigen

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4
Q

Immunogenicity is a measure of the ability of an antigen too

A

to provoke an immune response

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5
Q

degree of polymorphism

determines

A

foreignness

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6
Q

Immunogenicity is dependant on what features of an antigen

A 
degree of polymorphism
molecular shape, charge, size and complexity
accessibility 
number of copies
homozygous versus heterozygous
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7
Q

Primary Immune Response

occurs when antigen is first encountered. Antibody production follows in 4 phases

A

lag phase
log phase
plateau phase
decline phase

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8
Q

Immunoglobulin class switch
from IgM to …..
and is what cell dependant

A

IgG

t cell dependant

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9
Q

class-switch gene recombination occurs during

A

B cell maturation

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10
Q

secondary immune response occurs

A

second exposure to antigen

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11
Q

in secondary immune response is lag time reduced or increased

A

reduced

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12
Q

In secondary immune response antibody titre rises .. . . .. and reaches a ……….

A

more quickly and reach’s a higher plateau of antibody levels

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13
Q

In secondary immune response memory B cells …..

A

Respond in a T cell independant way resulting in an immediate IgG response

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14
Q

in secondary response antibodys produced have improve …. and .,….

A

affinity and avidity

affinity is the strength of the bond between an individual antibody and antigen

avidity is the overall strength of the bond between a multi - epitope antigen and its respective polyclonal antibody

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15
Q

Red cell membrane structures are composed of …. and how immunogenic are they

A

Proteins: very strongly immunogenic

carbohydrates: not always immunogenic

Glycoproteins: carbohydrate chains linked to a protein backbone
often strongly immunogenic

Lipids: Poorly immunogenic

Glycolipids: Carbohydrate chains linked to lipid
moderately immunogenic

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16
Q

What is the immunological response to Protein antigens Rh

A

T cell dependant response

predominately IgG antibodies

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17
Q

What is the immunological response to Carbohydrate antigens ABO

A

Mostly T cell independent response

predominantly IgM antibodies

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18
Q

what is the immunological response to glycoprotein K, Fy

A

mostly t cell dependant response

predominately IgG antibodies

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19
Q

what is the immunological response to glycolipid P1

A

mostly T cell independent response predominantly IgM antibodies

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20
Q

Antibodies are …. found in

A

glycoprotein molecules

found in all body fluids

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21
Q

IgM and IgG function as

A

blood group antibodies

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22
Q

IgM reacts to what antigens and are ….

A

carbohydrate / glycolipid antigens and are mostly t cell dependant

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23
Q

IgG reacts to what antigens and are

A

protein / glycoprotein antigens and mostly T cell dependent response

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24
Q

interchain disulphide bonds link

A

both heavy and light chains together and link the two heavy chains together in the ‘Hinge ‘ region

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25
Q

light and heavy chains have distinct

A

regions characterised by either the similarity (Constant Section) or the heterogeneity (Variable Section) of the amino acid structure

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26
Q

five types of heavy chains which determines the

A

Ig class

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27
Q

each light chain has one variable (VL) and one constant

A

(CL) domain

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28
Q

each heavy chain has one variable (VH) and either

A

3 or 4 constant (CH) domains

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29
Q

each variable domain has three

A

hypervariable regions

30
Q

hypervariable regions

are orientated together to form a

A

3-D shape which is complementary to the specific epitope

31
Q

what is the Antibody binding site

A

(Fab region)

32
Q

heavy chain constant domains are involved in the

A

effector functions of the Ig (Fc region)

33
Q

proteolytic enzymes (at appropriate conc.) cleave the

A

basic Ig structure into distinct regions

34
Q

Papain produces

A

two separate Fab fragments

one Fc fragment

35
Q

Pepsin produces

A 
Fc fragments 
one F(ab´)2 fragment
36
Q

Haemolytic Transfusion Reactions
antibody mediated removal of…….
IgM or IgG alloantibodies may cause significant levels of…..

A

transfused ‘foreign’ red cells

of red cell destruction

37
Q

Haemolytic Disease of the Foetus and Newborn (HDFN)

IgG alloantibodies may cause

A

foetal/newborn morbidity & mortality

38
Q

Autoimmune Haemolytic Anaemias (AIHA)

IgM or IgG auto-antibodies mediate removal of

A

‘self’ red cells

39
Q

Structure of IgM and held together by

A

pentameric structure consisting of five linked basic Ig units
held together by disulphide bonds and a separate J chain

40
Q

IgM characterises what response

A

primary

41
Q

IGM cannot cross the

A

placenta

42
Q

Igm is optimal at what temp

A

4.c

43
Q

What does IgM activate

A

complement

44
Q

clinically significant IgM is still reactive at/near

A

37oC

45
Q

IgM can cause ….

which involve

A

cause intravascular haemolysis….
‘Immediate-type’ transfusion reactions
cold-type autoimmune haemolytic anaemia

46
Q

IgM very efficient as a ….

and detected in,,,…

A

agglutinating agent due to polyvalent structure

vitro by direct ‘saline’ methods

47
Q

four IgG subclasses

A

(IgG1, IgG2, IgG3, IgG4

48
Q

IgG1 & IgG3 are most significant as

A

Blood Group Antibodies

49
Q

Production of IgG

A

predominant Ig in the secondary immune response
usually seen as Immune Antibodies
result of Pregnancy or Transfusion
usual antibody response to ‘protein antigens’

50
Q

can all IgG classes cross placenta

A

yes

51
Q

macrophages carrying …. bind to cells coated with …. results in …..

A

FcyR

IgG

extravascular haemolysis

this all activates complement

52
Q

What two pathways mediate immune haemolysis

A

classical
- mediated by red cell antibody bound to Antigen

Alternative
- independent of antibody

53
Q

The classical pathway is initiated by

A

Ag/Ab reaction on a cell surface

54
Q

Destruction of antibody coated in red cells by

A

Haemolysis

  • cascade completion results in ‘doughnut-like’ lesions in red cell membrane
  • this haemolysis is Intravascular

Immune adherence (opsonization)

  • sequence stops at intermediate (C3b) stage
  • red cells destroyed phagocytic cells carrying complement and IgG receptors
  • haemolysis is Extravascular haemolysis
55
Q

what are the four stages of classical pathway

A

attachment or complement binding
Activation
Amplification
Membrane Attack phase (this is common for both alternative and common pathway)

56
Q

what is the aim of stage 1 in complement pathway

A

binding of C1 complex

57
Q

What is C1 composed of …. and dependant on ….

A

C1q: C1r2: C1s2 complex

and dependant Ca2+

58
Q

what does C1 require

A

two Fc regions to lie in close proximity so C1q can then bind to the adjacent Fc sections via receptors on globular head regions

59
Q

What happens when C1r is bound to Fc sections on antigen

A

C1r becomes an active enzyme

60
Q

Stage 2 C1r then cleaves to

A

C1s

61
Q

In stage 2 (activation) C1 interacts with C2 but how

A

C4 is first cleaved into the C4b (largest fragment) and C4a

C4b binds covalently to the cell surface

C2 then binds to the C4b

C2 is then cleaved by C1s to produce C2b

the resulting C4b2a complex is the C3 convertase of the classical pathway

62
Q

In stage 3 (amplification phase) C4b2b does what

and what else happens

A

cleaves C3 into C3a and C3b

there is a major amplification as the large fragment C3b binds covalently to the cell surface

C3b is quickly inactivated in the plasma phase

bound C3b has immune adherence properties

the smaller C3a fragment is released into the fluid phase where it acts as an anaphylatoxin

a small amount of C3b binds to form C4b2bc3b complex
which is known as C5 convertase

63
Q

Stage 4 part 1. what does C5 do and then what happens

A

C5 binds to the C3b component of the C5 convertase

the serine protease activity of C2b then cleaves C5 into C5b and C5a

the smaller C5a is released into the fluid phase

this is both has anaphylatoxic and chemotactic properties

C5b then binds C6 and C7

64
Q

membrane attack phase 2 what does C5b67 do and what happens next

A

the trimolecular complex of C5b67 then binds to the cell membrane

C7 inserts into the lipid bilayer

C8 and then 10-16 molecules of C9 bind to create a membrane lesion

this membrane lesion is know as the membrane attack complex (MAC)

65
Q

What are the properties of MAC

A

pore is hydrophobic externally but hydrophilic internally

allows influx of solutes and water across lipid bilayer

results in cell lysis

66
Q

Antibody complement activation

A

Igm > IgG3> IgG1> IgG2: IgG 4 does not bind

67
Q

regulation occurs in what stages of the classical pathway

A

AMPLIFICATION

MAC

ACTIVATION

68
Q

how is the classical pathway regulated

A

by inhibitors that act directly on activated complement components

by rapid disassociation of newly formed complement complexes

by transient binding sites of activated components

69
Q

what inhibitor affects the Activation complex amd regulates it

A

C1 inhibitor; short life span of C2b ; transient binding site of C4b

70
Q

Amplification stage what regulates it

A

action of factor I; short life span of C3b

cell surface inhibitors eg decay accelerating factors (DAF) prevents assembly and promotes dissociation of the C3 convertase components

71
Q

what regulates the membrane attack complex

A

action of plasma and membrane bound inhibitors

HAEMOTOLOGY (6 decks)

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