B cells and Antibodies (Test 2)

Antibodies (Ab) or Immunoglobulins (Ig)

Glycoproteins that appear in circulation after immunization and the have the ability to react specifically with the antigen used to immunize

Antigen

Substance—protein from a vaccine component, pathogen, tumor cell, allergen that causes an antibody response

Epitope

The part of the antigen that interacts with antibody—usually a small peptide sequence

Hapten

is a small molecule that can elicit an immune response only when it reacts with an endogenous self-protein; Examples (antibiotic drugs)

Monoclonal Antibody (mAB)

are identical immunoglobulins, generated from a single B-cell clone. These antibodies recognize unique epitopes, or binding sites, on a single antigen. The are produced by recombinant biotechnology protocols and are used as therapeutics.

Clonal expansion

the process of rapid cell division resulting in the multiplication of genetically identical cell clones from a single parent cell

Humoral

relating to the body fluids, especially with regard to immune responses involving antibodies in body fluids as distinct from cells

IgM

primary response involves (first antibody to appear on B-cells)

IgG

secondary antibody-response

Measles virus

is especially dangerous because it has the ability to destroy what's been earned: immune memory from previous infections

phagocytic APCs such as macrophages and dendritic cells (DCs)

When a patient is given a vaccine the components of the vaccine are taken up by what?

lymph nodes

Where is the antigen processed and presented to T and B cells during vaccination?

memory

When the antigen specific B and T cells are formed in vaccine administration they continue to produce ____________ B and T cells that provide long term protection against infection with the pathogen.

bone marrow and lymphoid organs (spleen and lymph nodes)

Where does B cell development occur?

BCR

is a fully functional antibody (IgM) bound to a B-cell that is capable of binding antigen

Fc

Antibodies are bound to the surface of B-cells via their _________ receptor.

MCH-II (3 signal model)

How do B cells talk to CD4+ helper T cells?

same

No 2 B cells will secrete antibodies with the _________ variable region.

2 Fab and 1 Fc

What are the antibody structural regions?

2 identical heavy chains and 2 identical light chains

What are the chains of the antibody structure?

variable and constant

What are the domains of the antibody structure?

heavy cain constant Fc region

What determines the the Ig isotype?

disulfide

What type of bonds hold constant chains together on antibodies?

10^18

What is the antibody repertoire (total number is unique Ig's available to a human)?

lock and key epitope specificity

is determined by strength of interaction between epitope and Fab portion of antibody

Tx with enzyme Pepsin

Produces 1 F(ab')2 piece (the Fc portion is hydrolyzed into tiny peptides)

Tx with enzyme Papain

Produces 2 x Fab pieces and an Fc piece

precipitation

reaction of soluble antigen with soluble Ig

agglutination

reaction of antigen expressed on cell-surface with Ig (visible clumps)

neutralization

reaction of Ig with viruses and soluble toxins released by bacteria (result in loss of infectivity)

opsonization

coating of pathogens and foreign particles, prior to recognition by phagocytic cells

complement activation

the complement is composed of approx. 20 serum proteins which promote ingestion of microorganisms by phagocytic cells or by coating bacteria

monoclonal antibodies

single clones of an antibody specific to an antigen

human mab

-umab

mouse mab

-omab

chimeric mab

-ximab

humanized mab

-zumab

target class

Substem A

source (species) sequence

Substem B

bacterial

-b(a)-

cardiovascular

-c(i)-

fungal

-f(u)-

interleukin

-K(i)-

immunomodulating

-L(i)-

neural

-n(e)-

bone

-s(o)-

toxin

-tox(a)-

tumor

t(u)

viral

-v(i)-

chimeric/humanized

xizu

Ustekinumab (STELARA)

-IL-12 and IL-23 blocker indicated for RA/PP/PA

-uses the Fab portion to bind to a shared epitope on IL-12 and IL-23

-prevents these cytokines from acting on their cell receptors block signaling

work outside of cell

Vedolizumab (ENTYVIO)

an integrin receptor antagonist indicated for the treatment of UC and CD

Rimsozumab

I just discovered a new humanized Mab that works on a bone osteoclast protein target. In keeping with the rules, I should name it:

A.Rimtumumab

B.Rimsozumab

C.Rimvizumab

D.Rimciximab

A and C

Which of the following biologics is classified as an immunomodulating human Mab according to nomenclature rules?

A.Certolizumab (CIMZIA)

B.Golimumab (SIMPONI)

C.Vedolizumab (ENTYVIO)

D.Secukinumab (COSENTYX)

4-letter random extension

is mandated by the US Food and Drug Administration (FDA) for new biologic medications including originator and biosimilar biologics

VYEPTI (eptinezumab-jjmr)

indicated for the preventative treatment of migraine in adults

bones and tumors

Most mab are for what?

Alhemo (concizumab-mtci)

For routine prophylaxis of bleeding in hemophilia A and B

Bizengri (zenocutuzumab-zbco)

To treat non-small cell lung cancer and pancreatic adenocarcinoma

Ebglyss (lebrikizumab-Ibkz)

To treat moderate-to-severe atopic dermatitis

Kisunla (donanemab-azbt)

to treat Alzheimer's disease

germinal center

Center- a specialized structure within secondary lymphoid organs in which responding B cells undergo somatic hypermutation and selection for increased antigen affinity (affinity maturation)

somatic hypermutation

process that allows B cells to mutate the genes that they use to produce antibodies. This enables the B cells to produce antibodies that are better able to bind to antigens. These mutations occur in the Fab portion of the antibody

affinity maturation

process by which antibodies gain increased affinity and anti-pathogen activity and is the result of somatic hypermutation (SHM) of immunoglobulin genes in B cells, coupled to selection for antigen binding

class switch recombination

process by which proliferating B cells rearrange the constant region genes (Fc) in the heavy chain to switch from expressing one class of immunoglobulin (such as IgM) to another (such as IgG)

higher-affinity B cell antigen receptors (BCRs)

Affinity maturation drives B cells to evolve toward expression of _____________

GC-B cells

produce high-affinity antibodies via affinity maturation are selected to differentiate into plasma cells and memory B cells through specific gene expression changes that regulate proliferation and differentiation

germinal center (GC) of lymphoid organs

¡are specialized compartments within peripheral lymphoid tissues (e.g., lymph nodes, spleen) and the main structure where antigen-activated B cells diversify by somatic hypermutation (SHM) to generate high-affinity antibodies

light zone and dark zone

What are the 2 anatomical compartments that the GC is divided into?

light zone (LZ)

site of antigen-driven selection and affinity maturation

dark zone (DZ)

is site of B cell proliferation and somatic hypermutation (SMH)