5.2 blood and immune - lect 4-6

Question 1

what species have adaptive immunity, and in which was it first seen

Answer 1

jawed vertebrates, was first seen in jawless fish

Question 2

what is the process of changing the position of a gene in a genome called, and what components does it require

Answer 2

• transposition
• requires transposase/recombinase enzyme, and recognition sequences (RS) at the end of genes

Question 3

what is the Ig domain, and what is its structure

Answer 3

a stable protein structure that makes up antibodies.
it consists of two antiparallel beta sheets connected by loops and a central disulphide bond

Question 4

describe the structure of a whole antibody

Answer 4

2 heavy chains and 2 light chains, joined by disulphide bonds in order of: L-H-H-L.
Constant lower Fc ‘effector’ region determines the function of the antibody, and binds to Fc receptors on immune cells, and C1 complement protein.
Upper Fab region provides the specificty/diversity of the antibody, and contain the antigen binding sites.

Question 5

IgM

Answer 5

‘mega’
default form of antibody made by all naive B cells.
has two forms; membrane-bound two armed form, and soluble large pentamer form

Question 6

lgG

Answer 6

‘guardian.’
most abundant type.
neutralises toxins, long-term immunity
produced from IgM after they switch classes.
found in blood and can cross the placenta to provide neonatal immunity.

Question 7

lgD

Answer 7

‘developmental’
like a BCR, fixed to membrane of immature B cells and plays important role in their differentiation.

Question 8

lgA

Answer 8

‘armour’
protects mucosal surfaces
found in blood and mucosal secretions; breast milk, tears, stomach
provides gut immunity to neonates.
has two forms; exists as monomer and dimer secretory forms

Question 9

define affinity and avidity

Answer 9

affinity is the strength of a singular binding site attraction, while avidity is the overall strength of interaction including multiple binding sites

Question 10

IgE

Answer 10

‘emergency’
least abundant
important in atopic allergy and inflammation.
binds to mast cells/basophils and triggers histamine release.

Question 11

what does monovalent mean

Answer 11

refers to a singular binding site

Question 12

describe the structure of antigen-binding site domain in antibodies

Answer 12

consists of the variable domain of each the light and heavy chain at the top of the Fab region.
each V domain contains 3 discrete regions of amino acid variation, called CDR1, 2, and 3 (complementarity determining regions,) which are hypervariable loops connecting beta strands.
therefore each antigen-binding site consists of 6 total hyper variable loops

Question 13

explain how diversity arises in antigen binding sites

Answer 13

in VDJ recombination, junctional diversity arises at the VDJ join as the joining is very imprecise, with lots of base-pair changes occurring, creating lots of variation in central CDR3 loop.
CDR 1 and 2 don’t contain the VDJ join, their variation comes from random selection of one of many unique V segments during recombination.

Question 14

explain how VDJ recombination happens, distinguish between heavy and light chains

Answer 14

RS sequences at the end of DNA segments are recognised by recombinase enzymes unique to lymphocytes, RAG1 and RAG2.
heavy: a D joins to a J, then a V joins to the DJ
light: V joins to J

Question 15

what is a naive B cell

Answer 15

an immature B cell that hasn’t encountered any antigens yet and has low affinity

Question 16

describe clonal selection

Answer 16

when a B cell encounters an antigen that it has sufficient avidity to, it proliferates

Question 17

describe affinity maturation

Answer 17

as B cells proliferate, they undergo random somatic hypermutation, causing some affinity-enhancing mutations which are selected for, ultimately producing mature B cells with high avidity and specificity

Question 18

what is thrombopoietin?

Answer 18

hormone that stimulates platelet production from megakaryocytes

Question 19

what are the two different cells of affinity maturation and their functions?

Answer 19

plasma cells - secrete long-lived antibodies specific to antigens
memory b-cells - reside in lymph nodes and tissue ready to rapidly respond to its antigen

Question 20

explain what a B-cell is doing if it “switches from using the μ (M) to the γ (G) heavy chain”

Answer 20

it is class-switching as it undergoes maturation, from producing IgM (mu) antibodies to IgG (gamma)

Question 21

where are and what is the significance of ‘germinal centres’

Answer 21

they are within follicles of lymph nodes, and are transient (not permanent) structures formed when needed, in order to perform function of being site for B cell clonal selection and affinity maturation

Question 22

what must occur before/in order for clonal selection?

Answer 22

B cell must be activated by antigen, and be helped by a CD4+/helper T cell

Question 23

where exactly is variation located in Igs that creates our repertoire of diverse antibodies?

Answer 23

in the CDR regions of the variable domain of Ig genes

Question 24

in adaptive immunity, a secondary response is ___________ than the primary response (which explains the mechanism of vaccines and boosters)

Answer 24

stronger and faster

Question 25

what is 'lockjaw'

Answer 25

bacterial infection disease caused by tetanus toxin which affects the nervous system and causes muscle spasms

Question 26

why are babies susceptible to whooping cough

Answer 26

they rely completely on maternal IgG antibodies crossing the placenta to neutralise pertussis toxin and prevent them from getting lung damage

Question 27

what is a toxoid

Answer 27

an inactive variant of a toxin which is used in vaccines to 'train' the immune system against the toxin

Question 28

whooping cough: bacteria, toxin, effect

Answer 28

bordetella pertussis secretes pertussis toxin affects cilia in lung, causing coughing and lung irritation

Question 29

what are the primary lymphoid organs and secondary tissues

Answer 29

bone marrow and thymus are primary lymphoid organs, lymph nodes and spleen are secondary tissue

Question 30

what is the BCR

Answer 30

an membrane bound molecule on B cells that recognises antigens

Question 31

what is the 'beta barrel'

Answer 31

the name for the structure of the Ig fold

Question 32

which Ig classes activate complement

Answer 32

IgM and IgG

Question 33

what compound is the main cause of oedema

Answer 33

histamine

Question 34

what is anaphylaxis

Answer 34

hypersensitivity reaction involving multi-system organ collapse, in which swelling is extreme at multiple sites (most commonly around the face), airways constrict, and blood pressure drops

Question 35

rhesus haemolytic anaemia is an example of what hypersensitivity

Answer 35

type II hypersensitivity: attack on baby by mothers antibodies due to baby being Rh protein positive, while mother is Rh negative

Question 36

explain rhesus haemolytic anaemia

Answer 36

rhesus factor is a blood protein antigen. if mother is Rh negative (has never seen Rh antigen before) and baby inherits Rh positive from father, and baby's blood crosses placenta and mingles with mothers, mother developed antibodies which attack the baby's RBCs, triggering phagocytosis and causing them to lyse

Question 37

what are the 4 types of hypersensitivity? (minus type 3)

Answer 37

1 - atopic allergy 2 - complement mediated hypersensitivity 4 - delayed type hypersensitivity (DTH)

Question 38

how does the mantoux test work

Answer 38

a small amount of PPD (purified protein derivative, an extract from mycobacterium tuberculosis) is injected under the skin. 3 days later, the size of the welt is measured. if it is large and red, patient has been exposed to Mtb as they have PPD specific T cells.

Question 39

how is atopic allergy treated

Answer 39

by desensitisation. small amounts of antigen injected weekly for 3-6 months, causing the body to produce high-affinity IgG antibodies that outcompete IgE to bind the antigen. therefore mast cells are not activated, and allergic response doesn't occur.

Question 40

process of creating mAbs

Answer 40

1. inject mouse with antigen 2. later remove spleen which contains B cells 3. fuse with B cell myeloma cells (immortal cancerous B cells, producing no antibodies) in polyethylene glycol to form a hybridoma 4. grow the hybridomas, and test them for antibody strength

Question 41

what does polyethylene glycol do in mAb production

Answer 41

melts membranes, allowing antibody-producing B cells and immortal myeloma B cells to fuse into a hybridoma

Question 42

what are monoclonal antibodies and their pros

Answer 42

lab-made antibodies that bind to a specific antigen, highly specific and can be made to just the right affinity with minimal off target effects or adverse reaction

Question 43

type 4 hypersensitivity involves what immune cell

Answer 43

T cells

Question 44

what is cellular immunity

Answer 44

the cellular arm of the adaptive immune response, involving T cells and destroying infected cells.

Question 45

what type of organ is the thymus and where is it located

Answer 45

a primary lymphoid organ, located just above the heart

Question 46

explain how T cells are developed

Answer 46

hematopoietic cells migrate from the bone marrow to the thymus where they become T cells and undergo thymic education to learn tolerance and differentiate into either helper or cytotoxic T cells by responding to MHC in the thymus

Question 47

T cells do not recognise antigen unless...

Answer 47

it is presented on an MHC molecule

Question 48

what is MHC

Answer 48

membrane histocompatibility complex, a gene coding for surface proteins that presents fragments of virus like a flag to T cells

Question 49

what is meant by MHC being polymorphic

Answer 49

many different sets of alleles/variants of the gene in the population

Question 50

where is variation located in HLA/MHC molecules

Answer 50

around the peptide binding cleft

Question 51

why do TCRs only bind to MHC

Answer 51

they learn to do so in thyme education

Question 52

HLA are expressed on what cells?

Answer 52

most cells in the body

Question 53

what is codominance and where/how does it have effect in cellular immunity

Answer 53

when genes are equally expressed maternally and paternally, so both alleles are expressed. it occurs in MHC genes, and results in double the variation of the types of HLA expressed.

Question 54

what is MHC restriction

Answer 54

the fact that T cells must at the same time recognise non-self antigen and self MHC antigen, and thus can only recognise antigen that is presented by their own MHC molecules

Question 55

what is the benefit of MHC polymorphism

Answer 55

strengthens the individual's immune system's ability to detect and respond to infection, and increases survival for the population as somebody somewhere probably has the ability to detect a pathogen

Question 56

what is tolerance and why is it important

Answer 56

the immune system's ability to recognise and not attack the body's own cells and tissues, important to avoid autoimmune diseases like diabetes

Question 57

what/when is a T cell a 'double positive'

Answer 57

in the thymus, when they express both CD4 and CD8 antigen

Question 58

what are CD4 and CD8

Answer 58

accessory molecules on T cells that are complementary to and associate with the MHC and peptide

Question 59

how does AIDS arise, why is there no vaccine

Answer 59

HIV virus uses CD4 antigen as receptor to replicate within helper T cells. long term depletion of helper T cells leads to loss of ability to respond to simple infection. no vaccine can be defined as the virus RNA is so variable

Question 60

what is the basis of transplant/graft rejection

Answer 60

MHC is highly polymorphic; there are 100s of versions of each gene, and each person has a total of 12 separate MHC molecules. T cells therefore recognise other peoples MHC as foreign as they were never trained to recognise it, and activate an immune response against the transplant.

Question 61

MHC polymorphism is associated with... pros and cons

Answer 61

pros: diversity in immune capability cons: makes tissue transplant really hard, and is associated with many autoimmune diseases

Question 62

what is keytruda

Answer 62

an immunotherapy cancer drug

Question 63

what are examples of monoclonal antibody drugs

Answer 63

infliximab and pembrolizumab