immuno - antibody structure and function

Zostavax is a vaccine against _________ virus. what is the basis of this vaccine? efficacy against rash and post-herpetic neuralgia (phn)? duration?

varicella-zoster virus

live, weakened form of chicken pox

against rash: 51&

against phn: 67%

duration: after 4 years efficacy against phn decreases to 30%

why would someone need/get zostavax?

if they had chickenpox as a child, it prevents zoster

if you never had chickenpox, you dont need this vaccine

Shingrix is a vaccine against ______. mechanism of action? efficacy against rash and phn? duration?

varicella-zoster

surface sitting protein and 2 adjuvants

against rash: mid to high 90% range

against phn: upper 80's to low/mid 90% range

duration: after 4 years protective effect is still about 80%

which vaccine is preferred for varicella-zoster?

SHINGRIX

shingrix: recommendations for use

can be given once pt is 50 years of age

2-dose vaccine, second dose given after 2-6 months

PREFERRED

even if already had zosvtavax, you should receive the two doses of shingrix

shingrix side effects

fever, myalgia, chills, pain at injection site, use OTC NSAIDs to help with side effections

a reaction to first dose does not predict reaction to second dose

antibodies in general are _____ proteins. they circulate ____ and contribute to ____. they can be membrane bound or _____. their protein class is called _____

soluble

freely

secreted

globulins

____ cells secrete antibodies

plasma cells

antibodies are membrane bound as _____ receptor

B cell

Function of Fab region

hypervariable region: specificity to antigen - where antigen binds

function of Fc region

constant region: biologic function

biologic functions of Fc region

- neutralization of toxins

- immobilization of microorganisms

- precipitation followed by phagocytosis

- activation of complement

- placental crossing

importance of papain?

proteolytic enzyme discovered to split Ig molecule at hinge region --> shows us that Fc cannot bind antigen and must be responsible for biologic activity

importance of pepsin

helped determine structure of antibodies

what did mercaptoethanol teach us?

disulfide bond breaker

2 identical light chains

2 identical heavy chains

ALL immunoglobulins contain

2 identical light chains

2 identical heavy chains

- light chains and heavy chains held together by disulfide bonds

2 Fab fragments and 1 Fc fragment

2 classes of light chains

kappa and gamma

differences in heavy chains allow for division of Ig's into different isotypes or classes:

IgA, IgD, IgE, IgG, IgM

distringuishing features of heavy chains include

- protein sequences

- carbohydrate content

- size

- in the constant regions of heavy chains

disulfide chains can be ____ and ____-chain

intra (within) and inter (between)

disulfide chains can be ___ or ___ and __ or __

V (variable) C (constant

H (heavy) L (light

function of hinge region

permits Ig flexibility

_____ region binds to specific antigen

variable (hypervariable) region on Fab light and heavy chains

isotypes (classes) allow for different _____ _____

biologic responses

what are allotypes

based on genetic differences of members of the same species, differences due to different alleles of same constant region gene

what are idiotypes

differences due to rearrangement of VH and VL encoding genes within a given isotype

2 forms that antibodies exist in

1. as membrane-bound antigen receptors on B cells

2. as secreted proteins

membrane bound antibodies are made by ____ and exist on _____. function?

B cell, B cell

recognize antigens to start B cell activation

secreted antibodies are present in ____ and _______. function?

blood, mucosal secretions

eliminate microbes and their toxins in humoral immunity

IgG characteristics (miss versatility)

most common Ig

lightest Ig

longest 1/2 life (23 days)

best for passive immunization

agglutination and precipitation

passage through placenta

opsonization

antibody-dependent, cell-mediated cytotoxicity

activation of complement

neutralization of toxins

immobilization of bacteria

neutralization of viruses

what is agglutination and precipitation

clumping of INSOLUBLE agents

precipitation of SOLUBLE agents

complexes are easily phagocytized

importance of passage through placenta with IgG

occurs at month 3 or 4

transfer of immunity from mom to fetus

responsible for hemolytic disease of the newborn (Rh- mom, Rh+ fetus, immune system attacks)

Characteristics of IgM (mister big)

heaviest MW

macroglobulin

pentameric molecule - 5 binding sites for antigen

intravascular spaces

5 day half life

antigen-specific B cell receptor

first Ig produced following immunization/infection

the best at activating complement

synthesized by fetus at abt 5 months

efficient agglutinator

isohemagglutinins (blood type)

Characteristics of IgA (dont cry for me IgA)

2 four chained units linked by J chain

extra secretory component (S unit, binds and transmits IgA to mucosal surfaces)

major antibody in external secretions (tears, saliva, mucus, sweat, gastric fluid

component of MALT

bactericidal activity (when lysozyme is present)

antiviral activity

efficient agglutinating antibody

characteristics of IgD (dull, dull, dull)

very low and variable amounts in serum

co-expressed with IgM on surface of mature B cells

role in elimination of B cells with capacity to generate autoantibodies (react to self)

characteristics of IgE (AllergE)

has an extra CH domain that allows binding of mast cells and basophils

very low concentration in serum, more common in extravascular

hypersensitivity type 1!

role in parasitic infection, protection against worms

rank Ig's from heaviest to lightest

1. IgM

2. IgA

3. IgE

4. IgD

5. IgG

which Ig crosses placenta?

IgG

how many binding sites on each Ig?

IgM: 10

IgG: 2

IgA: 4

IgE: 2

IgD: 2

which Ig is most common in serum

IgG

which 2 Ig's fixes complement?

IgM and IgG

IgG Fc portion binds to ____

phagocytes

IgE Fc portion binds to

mast cells and basophils

MAIN function of IgM

main antibody of primary responses, best as fixing complement

MAIN function of IgG

main blood antibody of secondary responses, neutralizes toxins, opsonization

MAIN function of IgA

secreted into mucus, tears, saliva, colostrum

MAIN function of IgE

antibody of allergy and parasitic activity

MAIN function of IgD

B cell receptor

B cell receptors bind to _____

specific, intact antigens

_____ _____ are structurally similar to B cell receptors but arent anchored to a membrane

secreted antibodies

clonal selection of B cells generates a _______ and a _____

clone of short lived activated effector cells

clone of long-lived memory cells

in a primary immune response, binding of antigen to mature lymphocyte induces _____

lymphocyte's proliferation and differentiation

what are monoclonal antibodies?

homogenous populations of antibody molecules

derived from a single antibody-producing cell

all antibodies are identical and of same precise specificity for a given epitope

biologic immunotherapy agents: various drugs or toxins are be combined with monoclonal antibodies to _____

deliver agents to target tissues

example of biologic immunotherapy agents

anti-VEGF

Anti-VEGF treats ____ and ____. there are 3 common injection drugs which are ___, ____, ____.

AMD and DR

avastin, lucentis, eylea

3 other examples of biologic immunotherapy agents

tumor-specific monoclonal antibodies, autoimmune conditions, COVID-19

class II MHC molecules are located mainly on ____, ______, and ______.

dendritic cells

macrophages

B cells

function of class II MHC

display antigens to helper T cells

T cell/thymus independent antigens activate B cell antibody synthesis without significant _________. this is predominant ____ response to these antigens.

T cell help

IgM