Immunoglobulins and B cell Effector Functions

the humoral immune response is for ___________ microbes

extracellular microbes

the cell-mediated immune response is for _____________ microbes

intracellular microbes

what are the phases of the humoral immune response?

recognition phase and activation phase (B cell proliferation and differentiation)

what happens in primary lymphoid tissues?

Lymphocyte maturation

what B cells are present in primary lymphoid organs?

B cell residents: Precursor cells and Differentiated cells (Plasma cells, memory cells)

what does thymus dependent mean?

it describes antigens that trigger an immune response requiring the assistance of T-helper cells, which originate from the thymus gland

what happens in the secondary lymphoid organs?

Naïve B cells become activated

what B cells are present in secondary lymphoid organs?

B cell residents: Mature naïve cells and Differentiated cells: Plasma cells, memory B cells

what does the lymphatic system do?

Connects lymph nodes and Drains blood of waste products, damaged cells, pathogens

what are the 4 anatomical parts of a lymph node?

the outer cortex (B cell zone), paracortex (T cell zone), medulla, lymphoid vessels

what are the parts of the outer cortex?

1.) Follicle - Naïve B cells, memory B cells

2.) Germinal center - rapidly dividing B cells, follicular dendritic cells

what is found in the paracortex of a lymph node?

T cells, dendritic cells, macrophages

what is found in the medulla of a lymph node?

Plasma cells, circulating lymphocytes, macrophages

what is found in the lymphoid vessels?

Afferent: Antigen from tissues drains into lymph node

Efferent: B and T cell effectors leave

B cells are defined by their _________

B cell receptor (found on B cell surfaces or secreted by plasma cells)

what processes require thymus-dependent antigens?

Antigen processing, immune response dynamics, isotype switching, affinity maturation, immune memory, activation of B cells (require helper T cells)

what happens in signal 1 with B cells?

B cells become activated when their BCRs are cross-linked by antigen

what happens in crosslinking between antigens and BCRs?

Antigens with multiple repeating epitopes bind to several BCRs at once, the cross-linked BCRs will then cluster on the cell surface, increasing intracellular signal transduction

what does the BCR complex trigger?

intracellular signaling and antigen internalization

what do accessory molecules on the BCR do?

initiate signal transduction which conveys activation signals through the cytoplasm and into the nucleus.

what is ITAM and what does it do?

short molecular sequence that helps to transduce signals from the accessory molecules to inside the B cell

why are BCR-antigen complexes internalized?

for antigen processing and presentation as peptide fragments on MHC class II molecules

what are the changes in phenotype function as a result of signal 1?

entry into cell cycle (mitosis), increased cytokine receptor expression, low -level IgM secretion, migration out of lymphoid follicles

what are the functional consequences of signal 1?

clonal expansion, response to cytokines produced by Tfh cells, Begin Humoral immune response, Interaction with Tfh cells (↓ chemokine receptors, ↑ Ag presentation)

against what types of pathogens in immunity are T follicular helper cells important for?

all types of pathogens

what kinds of cytokines do T follicular helper cells (Tfh) secrete?

IL-21

where do T cells and B cells interact at?

the junction of the Parafollicular cortex and lymphoid follicle

how many signals do b cells require to become activated?

3 distinct signals

what leads to signals 2 and 3?

Antigen-specific T:B interaction

B cells present antigen to helper T cells and the activated helper T cells deliver signals to B cells via CD40L and cytokines

signal 2 in B cells is...

CD40L on T helper cell to CD40 on B cell

signal 3 in B cells is...

cytokines from T helper cell to receptors on the B cell

what is a hapten?

small molecules that are antigenic but not immunogenic

what is a carrier protein?

higher molecular weight molecule that is antigenic and immunogenic

what is the hapten-carrier effect?

small molecules called haptens, which are too small to trigger an immune response alone, can become immunogenic when chemically bonded to a carrier protein

why can the hapten-carrier effect occur?

because cooperating T and B cells recognize different epitopes on the same antigen complex

many common ___________ can function as haptens

allergens (penicillin, etc.)

what does clonal expansion allow for in B cells?

produces daughter B cells that share affinity and specificity with the parent cells

what are the steps to creating B cell diversity?

1.) clonal expansion

2.) somatic hypermutation & affinity maturation

3.) selection (live or die)

4a.) recirculation 4b.) class switch recombination

5.) differentiation

what does somatic hypermutation (SHM) and selection do?

generates antibody diversity and preserves high affinity clones

what initiates SHM?

activation-induced cytidine deaminase (AID), which is only expressed in germinal center B cells

what happens in selection?

B cells that recognize Ag displayed on FDCs with high affinity are selected to survive and mutations that impact BCR folding and BCR:antigen interactions are selected to die

how many subclasses does IgG have? how many subclasses does IgA have?

IgG has 4, IgA has 2

what induces heavy chain isotype switching?

CD40L + cytokine signals

what do AID inactivating mutations lead to in heavy chain isotype switching?

AID inactivating mutations result in Hyper IgM Syndrome Type 2

what does heavy chain isotype switching result in?

Result in new heavy chain class, with same specificity as the original B cell (unchanged V region)

IFN-γ induces switching to which antibody?

IgG (subclasses 1 and 3)

IL-4 induces switching to which antibody?

IgE, IgG4

TGF-β, and BAFF induce switching to which antibody?

IgA

Thymus- independent responses are reduced in:

a.) children

b.) adults

c.) elderly

children

antibodies are produced by

plasma cells

maturation of the humoral response occurs in....

germinal centers

what are the 7 main antibody functions?

neutralization, opsonization, complement activation, ADCC, anti-worm immunity, mucosal immunity, neonatal immunity

what is neutralization?

when an antibody blocks translocation, motility, growth, and colonization

how does neutralization work in viruses vs bacteria?

Viruses: Block membrane fusion and receptor engagement Bacteria: Block virulence factors important for adhesion and invasion

what is opsonization?

it is Fc mediated (IgG1 and IgG3 interactions with Fc-gamma receptors), IgG marks a pathogen for destruction making it easier for phagocytes to find and digest them.

Mast cell degranulation is mediated with what antibodies?

Fc mediated with IgE interactions

the destruction of large helminths is mediated by what antibodies?

Fc mediated (IgE interactions with Fc-epsilon receptors)

what are the pros and cons of eosinophils activating with IgE?

they can release highly toxic granule proteins and free radicals to kill pathogens! but they also can cause significant damage to host tissues in allergic reactions :(

what is Antibody-dependent Cellular Cytotoxicity (ADCC)?

similar to the killing mechanism of cytotoxic T cells, Antibodies bind to a cell with antigens and NK cell releases granules containing perforin and granzymes

ADCC is mediated by what antibodies?

Fc mediated with IgG1, IgG3

what is ADCC important for?

eliminating cancer cells or cells with pathogen-derived components on their surface

activation of complement is mediated by what antibodies?

Fc mediated with IgM, IgG1, and IgG3

Neonatal immunity is mediated by what antibodies?

Fab and Fc mediated with IgG and IgA

what are the practical applications for antibodies?

vaccines, immunotherapeutic tools, immunodiagnostics, research reagents

what allows pathogens to bypass vaccine immunity?

escape mutations