Lesson 66: B lymphocyte and antibody production

B lymphocyte

Semi pro APC

Become plasma cell and make antibody

If they become infected, they can present antigen to CTL just like any other nucleated infected host cell

Antibody

Bind microbial antigen and help destroy extracellular pathogen

• activate complement cascade

  • Generate complement opsonin

  • MAC generated

• Target microbes for phagocytosis: Opsonins

• Help NK cells target and kill host infected and tumor cells

ADCC

Antibody dependent cell cytotoxicity

Presence of antibody in serum indicates what?

Adaptive humoral immune response

Why do we want to detect a humoral immune response

Determine of the animal was exposed to a particular pathogen

Determine if animals immune response was able to respond to vaccine

Help with diagnosis

B cell respond to non protein antigen

• Some b cells have BCR that recognize non protein antigen such as carbohydrates and lipid molecules

• B cells that respond to non protein antigens do not receive cytokine help from T helper cells

  • response is limited

  • no memory cells so no memory response

  • No antibody switch

  • Only IgM

  • Plasma cells short lived

B cells respond to protein antigen

Th cell activated by APC

b cell presents peptide to activated Th cell

Th cell cytokines help B cell

• Memory b cell

• class switching

• antibody affinity maturation

• plasma cells long lived

How b cells get cytokine help from th cell

• BCR binds protein epitope it recognizes

• b cell process and presents peptide to th cell

• b cell receives cytokine help from th cell

• b cell clonally expands and differentiates

  • Plasma cells: antibody

  • memory cells

Clonal expansion of antigen specific b cell

there are multiple different epitopes on single protein antigen. Multiple b cell clones activated and expand resulting in a polyclonal antibody response

Class of antibody depends on type of cytokine help

Cytokines from T1 helper cell promote antibody that help other immune cell

• opsonizing antibody: helps phagocytic cell target microbe

Cytokines from t2 helper cells promote neutralizing antibody

Cytokines from t heper cells allow for antibody class switching

Fab part doesnt change but Fc part does

Fc region determines the class of antibody and what it can do

As b cells are activated, first antibodies are always IgM

With more cytokine signals, the dominant class of antibody made will change

B cell memory response

Feature of adaptive immune response

Memory B and T cells are long lived and are activated more quickly

Primary response: 7-10 days

Memory response: 1-3 days

Antibody affinity maturation

Progressive increase in affinity of antibody

affinity = strength of antibody binding to antigen

Ability of b cells to become plasma cells that make higher and higher affinity antibody require cytokine help

Polyclonal antibody

Animal exposed to a pathogen that expresses many epitopes

Antibody made to all different epitope with varying degree of affinity

Polyclonal: many b cell clones are present, each specific to particular epitope of the antigen

Monoclonal antibody

From a single B cell clone

designer antibody

Made in lab by fusing plasma cell to cancer cell allowing it to live forever and make antibodies forever

Serum protein electrophoresis

Immunoglobulins or glycoproteins in serum

Positive charge: electrophoresis separates out proteins in serum based on charge; Ig migrates towards negative cathode

Most antibodies in Gamma globulin

Structure if antibody molecule

Fab region: binds antigen

Fc region:

• Consists if H chains

• responsible for biological activity

• links bund antigen to molecules or cells causing destruction of antigen

• Fc molecules specific to a particular class of antibody

Classes of antibody

Refers to Fc part

IgG, IgM, IgE, IgA

class(Fc region) of antibody determines what it does

fab part determines what antigen it can bind to

Fc region of antibody

Determines class of antibodies

Determines biological activity

Constant regions of H chain differ and result in antibody adapted to perform different functions

IgG

Most IgG in blood

Made later in immune response

main antibody of memory response

Small so can easily leave blood and enter tissue and body surfaces

Binds pathogen and toxins to neutralize

binds phagocytes via fc region: opsonizes

complement activation and destruction of microbe

• C1 binding

Antibody dependent cell cytotoxicity

paces through placenta to fetus

Antibody with highest concentration in colostrum

and breast milk. IgG provides passive immunity to the fetus.

IgM

Pentameric nature allows it to bind strongly to microbes and large,complex antigens (good at neutralizing viruses)

▪ Good at aggregating/agglutinating

▪ Size limits its ability to penetrate tissues. Confined to blood and lymph

▪ First Ig class made in a primary immune response, but usually has short half-life,

• Thus, if present at high level, MAY be an indication of a recent, primary exposure to antigen

▪ Complement can bind IgM–

▪ No Fc receptor on phagocytes for IgM–

IgA

• IgA – monomeric in serum

• Dimeric form involved in mucosal transport and protection at the

mucosal surfaces

▪ Dimeric has secretory piece that prevents it from being degraded by proteases in the intestine

▪ Passes from mammary tissue into milk

▪ Protective of gut of newborn

▪ Crosses mucosal surfaces (gut, respiratory and UG tracts)

mucosal protection!!!

▪ Found in tears, saliva, & bile

IgE

• One “Y” shaped molecule (similar to

IgG)

• Largely responsible for adaptive immunity to parasitic worms

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• Mediates Type-I hypersensitivities (allergies)

▪ B-cells make IgE to an allergen

▪ IgE binds mast cells via the Fc region, as mast cells have FcR

for IgE. (FcεR)

▪ If allergen shows up again and binds the IgE bound to the mast

cell, the mast cell degranulate

Antibody to other antibody

Antibodies can be made against other antibodies

Ex. goat anti gog IgG

• means an IgG antibody from a dog was injected into a goat and the goats plasma cells made antibody against the dog IgG

Why would we ever want to make an antibody against an antibody?

Use as a reagent in immunodiagnostic test