PHSC1312 Microbiology/Immunology Lecture 16 B Lymphocyte Effector Response & Antibodies

CXCR5 upregulation

What happens on the primed CD4+ T cell that allows it to migrate into the B cell follicle?

CD40L and IL21

What does the T cell express in the germinal center?

Class switching and somatic hypermutation

What do B cells start to undergo after T cell CD40L and IL21 expression in the germinal center?

Plasma cells

B cells that have rearranged their intracellular organelles, so it's all about protein synthesis and will only synthesize the antibody

Antibody

soluble immunoglobulin produced by B cells and plasma cells

Opsonize same target that triggered activation

What do IgM produced by plasma cells do?

PAMP/PRR ligation

What allows a dendritic cell to know what has been taken in and tell the CD4+ T helper cell?

B cell

Which cell uses the costimulation and cytokine production in the germinal center as confirmation to begin forming antibodies?

Constant region

determines the antibody isotype

Variable region

determines the antigen recognition

AID recombination

process responsible for heavy chain isotype/class switching

Antigen binding site

Where is the emphasis placed for somatic hypermutation?

Activation induced cytidine deaminase

enzyme that introduces nucleotide changes in the variable heavy (VH) and variable light (VL) chains within the hypervariable region

Induce DNA breaks and repairs

What does activation-induced cytidine deaminase (AID) do?

Nucleotide substitutions

occur in the variable heavy and variable light regions through AID and increase diversity of B cell pool

Increase B cell diversity

What do nucleotide substitutions by AID do?

Compete for antigens in B cell zone

What do the expanded pool of B cell clones do?

Mutating variable region for more customized fit at antigen binding site

What is happening in somatic hypermutation?

B cell clones want to receive B cell survival signal from binding antigens

Why do B cell clones begin competing with each other after somatic hypermutation?

Constant region

Where is the emphasis placed for class switching?

Class switching

involves irreversible gene rearrangement of constant region on the VDJ genes to different isotypes with the same antigen specificity

Irreversible

Is the gene rearrangement in class switching reversible or irreversible?

Antibody specificity for antigen

What stays the same or is NOT impacted by class switching?

Germinal center

Where does class switching occur?

Antigen dependent

What type of process is the class switching and hypermutation?

Antibodies

mediators of the humoral immunity in adaptive compartment

Neutralization of microbes or toxic microbial products, activation of the complement system, opsonization of pathogens for enhanced phagocytosis, antibody dependent cell mediated cytotoxicity (ADCC), antibody mediated mast cell activation to expel parasitic worms

five functions of antibodies as mediators of the humoral immunity in adaptive immune compartment

Affinity

strength of the binding between a single site of an antibody and an epitope of an antigen

Epitope

the part of an antigen molecule to which an antibody attaches itself

Strength between antibody and epitope on antigen

What is affinity?

Avidity

overall strength of attachment

Overall strength of attachment

What is avidity?

Valency

the number of antigenic determinants that an antibody is capable of binding

Number of epitopes an antibody can bind

What is valency?

2

How many antigen binding sites does a monomer have?

4

How many antigen binding sites does a dimer have?

10

How many antigen binding sites does a pentamer have?

Higher valency, higher avidity

What is the relationship between valency and avidity?

IgM

first isotype secreted; concentration declines as production accelerates; can oligomerize to pentamer, highest valency and avidity; activates classical complement system

IgD

mostly found on B cell surface as BCR; secretion in small amounts; binds antigens in extracellular fluid; involved in T cell independent sensitization of B cell activation

IgG

largest and most diverse class of antibodies; most abundant in circulation; responsible for resistance to many viruses, bacteria, and toxins; can cross the placenta; driven by IFN gamma and recognized by cells expressing Fc gamma receptor

IFN gamma

Which cytokine drives IgG?

Th1

Which helper cell drives IgG?

IgA

found in secretions such as mucus, tears, saliva, and semen; attack pathogens before inside internal tissues; circulate individually or as dimers; can pass through breast milk; guided by IL-17 and recognized by immune cells expressing the Fc alpha receptor

IL17

Which cytokine drives IgA?

Th17

Which helper cell drives IgA?

IgE

prevalent in individuals with allergies and asthma; binds the Fc epsilon region; stimulates release of histamine and other chemicals that accelerate inflammation; important for helminths; driven by IL-4

IL4

Which cytokine drives IgE?

Th2

Which helper cell drives IgE?

Block receptors, sequester cytokines, shut off T cell activation, conjugate drug to antibody

What are some examples of things antibodies can be used to do therapeutically?

Pepsin and Papain

two enzymes used to form antibody fragments

Pepsin

enzyme that cleaves just below antibody hinge region liberating the top of the molecule

Below hinge region

Where does Pepsin cleave on an antibody?

F(ab')2

part after Pepsin cleavage?

Antigen binding

What function remains when cleavage by Pepsin?

Effector function, complement activation, and Fc receptor recognition

What functions go away when cleavage by Pepsin?

Papain

enzyme that liberates the Fab (antigen recognition) part and the Fc portion remains connected

Fab and Fc

parts after Papain cleavage

Reduce overreaction to therapeutic agent

What can eliminating the Fc region via enzyme do?