Red cell Antibodies and their Role in Immune Haemolysis

Question 1

an Immunogen is anything that

Answer 1

stimulates a specific immune response ie see as ‘foreign’

Question 2

an Antigen may be comprised of several

Answer 2

epitopes

Question 3

each specific Antibody will bind to a particular epitope on a

Answer 3

antigen

Question 4

Immunogenicity is a measure of the ability of an antigen too

Answer 4

to provoke an immune response

Question 5

degree of polymorphism

determines

Answer 5

foreignness

Question 6

Immunogenicity is dependant on what features of an antigen

Answer 6

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

Question 7

Primary Immune Response

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

Answer 7

lag phase
log phase
plateau phase
decline phase

Question 8

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

Answer 8

IgG

t cell dependant

Question 9

class-switch gene recombination occurs during

Answer 9

B cell maturation

Question 10

secondary immune response occurs

Answer 10

second exposure to antigen

Question 11

in secondary immune response is lag time reduced or increased

Answer 11

reduced

Question 12

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

Answer 12

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

Question 13

In secondary immune response memory B cells …..

Answer 13

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

Question 14

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

Answer 14

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

Question 15

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

Answer 15

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

Question 16

What is the immunological response to Protein antigens Rh

Answer 16

T cell dependant response

predominately IgG antibodies

Question 17

What is the immunological response to Carbohydrate antigens ABO

Answer 17

Mostly T cell independent response

predominantly IgM antibodies

Question 18

what is the immunological response to glycoprotein K, Fy

Answer 18

mostly t cell dependant response

predominately IgG antibodies

Question 19

what is the immunological response to glycolipid P1

Answer 19

mostly T cell independent response predominantly IgM antibodies

Question 20

Antibodies are …. found in

Answer 20

glycoprotein molecules

found in all body fluids

Question 21

IgM and IgG function as

Answer 21

blood group antibodies

Question 22

IgM reacts to what antigens and are ….

Answer 22

carbohydrate / glycolipid antigens and are mostly t cell dependant

Question 23

IgG reacts to what antigens and are

Answer 23

protein / glycoprotein antigens and mostly T cell dependent response

Question 24

interchain disulphide bonds link

Answer 24

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

Question 25

light and heavy chains have distinct

Answer 25

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

Question 26

five types of heavy chains which determines the

Answer 26

Ig class

Question 27

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

Answer 27

(CL) domain

Question 28

each heavy chain has one variable (VH) and either

Answer 28

3 or 4 constant (CH) domains

Question 29

each variable domain has three

Answer 29

hypervariable regions

Question 30

hypervariable regions | are orientated together to form a

Answer 30

3-D shape which is complementary to the specific epitope

Question 31

what is the Antibody binding site

Answer 31

(Fab region)

Question 32

heavy chain constant domains are involved in the

Answer 32

effector functions of the Ig (Fc region)

Question 33

proteolytic enzymes (at appropriate conc.) cleave the

Answer 33

basic Ig structure into distinct regions

Question 34

Papain produces

Answer 34

two separate Fab fragments | one Fc fragment

Question 35

Pepsin produces

Answer 35

``` Fc fragments one F(ab´)2 fragment ```

Question 36

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

Answer 36

transfused ‘foreign’ red cells of red cell destruction

Question 37

Haemolytic Disease of the Foetus and Newborn (HDFN) IgG alloantibodies may cause

Answer 37

foetal/newborn morbidity & mortality

Question 38

Autoimmune Haemolytic Anaemias (AIHA) | IgM or IgG auto-antibodies mediate removal of

Answer 38

‘self’ red cells

Question 39

Structure of IgM and held together by

Answer 39

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

Question 40

IgM characterises what response

Answer 40

primary

Question 41

IGM cannot cross the

Answer 41

placenta

Question 42

Igm is optimal at what temp

Answer 42

4.c

Question 43

What does IgM activate

Answer 43

complement

Question 44

clinically significant IgM is still reactive at/near

Answer 44

37oC

Question 45

IgM can cause .... | which involve

Answer 45

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

Question 46

IgM very efficient as a .... | and detected in,,,...

Answer 46

agglutinating agent due to polyvalent structure vitro by direct ‘saline’ methods

Question 47

four IgG subclasses

Answer 47

(IgG1, IgG2, IgG3, IgG4

Question 48

IgG1 & IgG3 are most significant as

Answer 48

Blood Group Antibodies

Question 49

Production of IgG

Answer 49

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

Question 50

can all IgG classes cross placenta

Answer 50

yes

Question 51

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

Answer 51

FcyR IgG extravascular haemolysis this all activates complement

Question 52

What two pathways mediate immune haemolysis

Answer 52

classical - mediated by red cell antibody bound to Antigen Alternative - independent of antibody

Question 53

The classical pathway is initiated by

Answer 53

Ag/Ab reaction on a cell surface

Question 54

Destruction of antibody coated in red cells by

Answer 54

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

Question 55

what are the four stages of classical pathway

Answer 55

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

Question 56

what is the aim of stage 1 in complement pathway

Answer 56

binding of C1 complex

Question 57

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

Answer 57

C1q: C1r2: C1s2 complex | and dependant Ca2+

Question 58

what does C1 require

Answer 58

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

Question 59

What happens when C1r is bound to Fc sections on antigen

Answer 59

C1r becomes an active enzyme

Question 60

Stage 2 C1r then cleaves to

Answer 60

C1s

Question 61

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

Answer 61

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

Question 62

In stage 3 (amplification phase) C4b2b does what and what else happens

Answer 62

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

Question 63

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

Answer 63

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

Question 64

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

Answer 64

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)

Question 65

What are the properties of MAC

Answer 65

pore is hydrophobic externally but hydrophilic internally allows influx of solutes and water across lipid bilayer results in cell lysis

Question 66

Antibody complement activation

Answer 66

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

Question 67

regulation occurs in what stages of the classical pathway

Answer 67

AMPLIFICATION MAC ACTIVATION

Question 68

how is the classical pathway regulated

Answer 68

by inhibitors that act directly on activated complement components by rapid disassociation of newly formed complement complexes by transient binding sites of activated components

Question 69

what inhibitor affects the Activation complex amd regulates it

Answer 69

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

Question 70

Amplification stage what regulates it

Answer 70

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

Question 71

what regulates the membrane attack complex

Answer 71

action of plasma and membrane bound inhibitors