B lymphocytes and antibodies

how do immunoglobulins mediate humeral immunity

binding to antigens

What is the difference between cell and humoral immunity?

- Humoral immunity produces antigen-specific antibodies and is primarily driven by B cells
- Cell-mediated immunity on the other hand does not depend on antibodies for its adaptive immune functions and is primarily driven by mature T cells, macrophages and the release of cytokines in response to an antigen.

What is X-linked agammaglobulinemia? (XLA)

immunodeficiency in which patients are deficient in B lymphocytes and immunoglobulin production.

how do immunoglobulins combat pathogens

1. neutralisation
2. opsinisation
3. complement activation

how do antibodies neutralise antigens?

- bind bacterial toxins to prevent interacting with their targets
- prevent viruses and bacteria attaching to the surface of host cells

how do immunoglobulins opsonise antigens for uptake by phagocytes

- Fc receptors bind to Fc regions of immunoglobulins
- phagocytosis of immunoglobulin-antigen complexes via Fc receptors leads to the degradation of the antigen

what can immunoglobulins activate?

what three things are activated

the classical complement pathway

1. complement mediated neutralisation
2. complement mediated lysis
3. phagocytosis via complement receptors

what is the Fc regions bound by

Fc receptors expresses by phagocytes and other immune cells

how many domains do the light chains have?

- 2 immunoglobulin domains , one variable and one constant

how many domains to the heavy chains have?

- 4 domains, one variable and three constant

what domains join together to form the antigen binding site?

variable domain of the light chain and the variable domain of the heavy chain

do constant domains differ?

no, not between immunoglobulins of the same class

do variable domains differ?

yes, gives antigenic specificity

what are the loops known as

complementary dertiming regions (CDR) and hypervariable loops

do immunologlobulons use covalent bonds to bind antigens or react or catabolise antigens?

no

what bonds to they use to bind antigenic epitopes?

non- covalent :

electrostatic interactions, hydrogen bonds, hydrophobic intnteraction, van-de-waals

this is all reversible

where are immunoglobulins present?

extracellular fluids including, the blood, tissue fluids and mucous secretions

where is sequence variation most concentrated?

the CDR

where are epitopes exposed?

on the surface of the antigen molecule

what can epitopes be?

continuous or discontinuous

how are discontinuous epitopes lost?

by unfolding or denaturing protein antigens

how many amino acids or sugar residue are epitopes?

not that epitopes fro T cell are 8-12 proteins

12- 16 amino acids
5-6 sugar residues

how many classes of immunoglobulin is there?

5

what are they five classes of immunoglobulin:

IgM - (mu) heavy chain
IgG- (gamma) heavy chain
IgA- (alpha) heavy chain
IgE- (epsilon) heavy chain
IgD- (delta) heavy chain

what do heavy chain determine?

the functional specialisation of immunoglobulins

Structure of IgM

- has four CH domains
-pentameric: 10 antigen binding binding sites
- the J chain promotes IgM polymerisation

facts of IgM

- first antibody secreted in response to foreign antigen
- confined to vascular system due to its size
-low affinity, despite having 10 binding sites
- these 10 binding sites enable it to bind to polyvalent antigens such as bacterial surfaces

functions of IgM

- neutralise antigens
- agglutinates
-activates classical complement pathway
-IgM is effective in limiting the spread of microorganisms via th blood stream

what is the largest immunoglobulin

IgM

structure of IgG

there are four distinct isotypes: IgG1, IgG2, IgG3, IgG4

monomeric

each gamma heavy chain has 3 CH domains

two antigen binding sites

IgG facts

- produced in the secondary response to antigen by B-cells, in the lymph nodes and spleen
-small size enables it to diffuse from the bloodstream into the extra-vascular sites

IgG functions

- neutralises antigens
-opsinises antigens for uptake by Fc receptors on phagocytes
-activates the classical complement pathway
- during pregnancy it is activist transported across placenta into the foetus to protect newborn babies for the first 3-6 months

IgA structure

- alpha heavy chain has 3 CH domains
- exists in both monomer and a dimer
- j chain is required to link two monomers together

where is IgA produced?

produced by B -cells in the mucosal associated lymphoid tissues during secondary immune response

where is the majority of IgA secreted?

mucousal epithelial surfaces

how does IgA neutralise antigens (this is its predominant function)

- prevents bacterial toxins binding to their cellular targets
-inhibitits microbial adhesions to epithelia
-inhibits viral infectivity

what is IgA poor at

- opsonisation
-complement activation

IgE structure

monomeric, heavy chain has 4CH domains

functions of IgE

- produced in response to some antigens , usually B-cells in MALT
- importnat in the immune response against worms and other parasites
- involved in type I hypersensitivity responses

where is the vast majority of IgE bound?

to Fc epsilon receptors on mast cells, basophils and eosinophils

- binding of IgE molecules to polyvalent antigens cross-links Fc epsilon receptors and triggers release of inflammatory mediators

structure and function of IgD

- monomer, 3CH domains
- acts as antigen receptor on immature B cells and is present in the blood at very low concentrations

what does recognitions an capture of an antigen by BCR drive?

proliferation of that B-lymphocyte and generation of:
- long lived memory cells
-short lived immunoglobulin secreting plasma cells that secrete large quantities of immunoglobulin specific for the antigen

what b cells are allowed to proliferate?

the ones that are specific to the antigen

plasma cells

- in secondary lymphoid tissues
- secrete large amounts of antibody
-24-48 hour life
- antibody meter blood within the lymphoid tissue and are able to circulate throughout the vascular system

memory B -lymhocytes

- long lived
-express membrane immunoglobulin but do not secrete significant quantities
- if same antigen found again, they are stimulated ti divide

how to T lymphocytes regulate the B-lymphocyte response to antigen?

- signals from T cells promote proliferation of B memory and plasma cells
- B cell must capture and present there antigen to a T cell that is specific for the same antigen
-antgen is endocytosis, process and these peptides are presented by MHC II molecules to CD4+ T lymphocytes
- t lymphocytes will give signals to B lymphocyte that will actfacte proliferation of B lymphocyte

where do b cells mirgrate

b cells migrate into secondary lymphoid tissues

where do b cells proliferate

germinal centres

once antigen is cleared , germinal centres shrink

b -cells have to be in proximity to interact

how does antigen delivery to the lymph nodes differ from antigen delivery to thes spleen

lymph nodes: lymphatic vessels that drain fluid from the tissues
spleen: bloodstream