Test 1: lecture 9 and 10 B cells Flashcards
cell mediated immunity by T cells and NK cells
- Direct elimination or killing of cells bearing foreign antigen
- Production of immuno-regulatory cytokines
humoral response is by ___
B cells and plasma cells
- Production of antigen-specific soluble molecules (antibodies, also called immunoglobulins) that are secreted into the body “humor”.
- Antibodies are effector molecules that eliminate pathogens
- Important for immunological memory
Modulation of immune responses through ___ release
cytokine
3 ways B and T cells talk to each other
- Direct binding of T helper cells to B cells
- T cell cytokines control antibody production by B cells
- B cell cytokines regulate T cell differentiation induced by antigen
The B cell receptor and the secreted antibodies are comprised of immunoglobulin proteins with the same ___
antigen specificity
(react to the same thing)
shape of B cell receptor
similar to how antibodies are designed
light and heavy chain, IgA abd IgB
variable and constant region
The primary “job” of B lymphocytes is to specifically ___(microbes, toxins, and other threats) and generate ____against it
recognize an antigen
effector molecules (antibodies)
B cells can also acts APCs, produce cytokines and eat things
3 steps of B cell development
3 steps of B cell activation
3 primary lymphoid organ
thymus
bone marrow
burse fabricius (birds)
where do B cells develop
humans : bone marrow
birds: Bursa of fabricious
where does proliferation and differentiation of B cells occur
in the periphery → secondary lymphoid organs → spleen, lymph nodes ect.
variable area of the C cell receptor is made from ___
gene segments (V,C,J)
gene segment for constant (C)
these undergo somatic recombination to create new Bcell
allelic exclusion ensures that each B cell only produces antibodies for one antigen
___ brings together single segments of each type of locus to create unique B cells
somatic recombination
___ is used to ensure B cells only produce antibodies for one antigen
allelic exclusion
•Through combination of ___ segments and light/heavy chains, an almost limitless diversity of B cells can be achieved
V/D/J/C
•The main molecule involved in the recombination process is ___, an enzyme that plays a key role in the rearrangement and recombination of the genes of V(D)J gene segments.
RAG (recombination-activating gene)
Two main RAG molecules, RAG 1 and RAG 2
how does negative selection work
immature B cells that react to self antigens in bone marrow are killed, only B cells that do not react to self are allowed to survive and move to blood
4 things will happen to B cells that remain in bone marrow:
- Clonal deletion (apoptosis)
- Anergy (lack of responsiveness, no BCR expressed on B cells)
- Receptor editing (changes specificity of the BCR)
- Ignorance (leads to potential autoimmunity)
4 things will happen to B cells that remain in bone marrow after negative selection
- Clonal deletion (apoptosis)
- Anergy (lack of responsiveness, no BCR expressed on B cells)
- Receptor editing (changes specificity of the BCR)- sequence changed to not react to self any more
- Ignorance (leads to potential autoimmunity) → woops makes it out of bone marrow by accident - autoimmune issues
B cells that make it out of the bone marrow after negative selection are considered
self tolerant
B cells mature into plasma cells in the ___
germinal centers of secondary lymphoid organs such as the lymph nodes and spleen
___ collects antigens from tissues
lymph nodes
___ collects antigens from circulation
spleen
___ provide the infrastructure for lymphocytes to find cognate antigen & become activated
Secondary lymphoid organs
(i.e, lymph nodes, germinal centers)
Secondary lymphoid organs are important for initiating primary (adaptive) response because they bring together ___
antigen bearing DCs
B cells and T cells
B cells will mature into ___
antibody secreting plasma cells
memory B cells
Antigen binds to BCR - induces ___ and antibody production.
proliferation
Costimulation / accessory signals from TH cells that recognize the same antigen enhance Ab production and initiates ___
affinity maturation and isotype switching.
how does B cell activation work in lymph nodes?
antigens brought in by afferent lymphatic vessels,
B cells will recognize the entire antigen, eat it and present it on its surface
T cells will recognize pieces of antigen and will bind to B cell that matches
T cells will produce co-stimulatory molecules to cause B cells to proliferate and isotype switch
B and T that recognize the same antigen will bind together and form primary focus → primary follicle → germinal center where B cells will proliferate and turn into memory cells (IL-4)or antibody producing plasma cells (IL-10)
how are B cells activated
antigen will bind to receptor be eaten, broken up and presented on MHC class II
helper T cell that recognizes that antigen will bind and produce cytokines (co stimulatory molecules) that and activate B cell to induce isotype switch
•T cells upregulate CD40L and produce immunoregulatory cytokines such as IL4.
Certain ___ can activate B cells in the absence of T cell help allowing rapid antibody production against many bacterial pathogens. In the absence of T cell help, the antibodies do not undergo affinity maturation or isotype switching.
microbial antigens
Out of the many different mature B cells, only the ones that are activated (___) start proliferating (____) and differentiate into plasma cells, which produces the specific Ab, and memory B cells
clonal selection
clonal expansion
___ produce antibodies
plasma cells
how are plasma cells different from B cells
- They do not express surface immunoglobulin or MHC II and cannot present Ag to T cells.
- Plasma cells migrate to specific sites in lymphoid organs (e.g. red pulp in the spleen) and the bone marrow
- Most plasma cells are short-lived (weeks to months) but a few long-lived plasma cells survive in the bone marrow and produce Ab
have a high-rate Ig secretion
are not inducible
isotype switching
T cells will cause B cells to switch from IgM to other immunoglobulins by changing the genetic recombination of the C segment → changes the constant region. variable and light chains stay the same
how does a immature B cell change the type of Ig it produces?
T cells will cause isotype switching
T cells will cause B cells to switch from IgM to other immunoglobulins by changing the genetic recombination of the C segment → changes the constant region. variable and light chains stay the same
affinity maturation
somatic hypermutation
random change in sequence of the antibody (amino acids change)
AID (activation-induced (cytidine) deaminase) → enzyme that causes the change
this will create B cells with all different levels of binding, any that bind worse are removed creating a class of very specific antibody responses
somatic hypermutation is caused by ___
(Enzyme responsible is the Activation- Induced (Cytidine) Deaminase, or AID)
random change in DNA sequence that creates different levels of affinity of B cells for antigen → affinity maturation
Gene recombination during development, clonal expansion, isotype switching and affinity maturation ensure huge ___yet high ___ of the antibody response
diversity
specifity
B cells that recognize antigen will multiply(clonal expansion), while these cells multiply some genetic recombination occurs (somatic hypermutation) , those that have improved affinity survive and bind to antigen coated DC cells that cause B cells to produce different type of Ig (class switching) and mature into plasma cells or memory cells (differentiation)
___ do not secrete antibodies but can turn into plasma cells upon activation
memory B cells
(can live for many years)
usually come from cells that have undergone affinity maturation and isotype switch
secondary response to re-exposure
primary vs secondary immune response
will have bigger response the second exposure (more IgG B cells→ more antibodies)
regulatory B cells
type of B cell that creates cytokines
responds to CD4 T cells and produce IL10 to create different type of t cells
IL10 → will decrease immune response
antibodies or ___
Ig immunglobulins
make up of antibodies
- They are built of 2 heavy chains and 2 light chains linked through disulfide bridges
- The N-terminal domain of each chain has a variable structure and determines antigen specificity
The other domains form the constant region defining isotype and effector function
light chain and heavy chain are held together by
disulfide bones
(antibodies /Ig)
variable region of the antibodies ___
antigen recognition specificity
constant region of the antibody will ___
effector function
neutralization, complement activation, sensitization, phagocytosis, opsonization
antigen binds to antibody by __
non covalent binding such as H bonding and electrostatic
C3 and C4 will bind covalently
antibody affinity
better fit will bind better
constant K if many antigens binded to antibodies vs free floating antigens and antibodies
variable region + antigen =
Fab region
affinity vs avidity
1 Fab = 1 antigen and 1 variable area = affinity→ intrinsic affinity
2 or more Fab = avidity → functional affinity
valance
repeated or not? in same molecule
interactions between the Ag and Ab depends on :
- The nature of the antigen (Valence(repeated or not) of the antigen)
- Specificity and affinity of the antibody
- Ab type and class (Monoclonal, polyclonal, IgG, IgM)
determinant
also called epitope
region of the antigen recognized by the Fab region of an antibody
true or false a univalent and unideterminant antigen can agglutinate?
false
there is only 1 place for an antibody to bind = unideterminant→ uni-epitope
anti- bodies can not cross link (agglutinate)
precipitation of antibody and antigen
antigens with many spots for Ab to bind (multi-determinant) will allow for Ab to cross link and bind to each other → creating a large heavy structure that agglutinates and sinks
specificity and cross reactivity of antibody
specificity → all of the Ab react to the different epitope (binding sites) on the antigen
cross reaction → only one type of antibody react to the antigen (light binding)
neutralization by antibodies
toxins = bind to antibody and make inactive
viruses → bind and prevent virus from binding to human cell
bacteria → prevent bacteria from binding to self
opsonization
antibodies will tag an antigen to prepare it to be eaten by other immune cells
___ describes the tagging of antigens by immune effectors such as antibodies or complement
opsonization
___ describes the tagging of antigens by immune effectors such as antibodies or complement
opsonization
antibody binding to antigen can lead to activation of complement system which leads to ___
innate immunity
lysis, release of inflammatory mediators, and facilitate phagocytosis
____ - different individuals may have allelic differences in antibody genes. Typically a few amino acids in heavy chain.
antibody allotype
IgM
- Monomeric membrane-bound form expressed during B cell development
- First antibody produced after immunization
.•Elevated IgM indicates recent infection
- Secreted as large pentameric macroglobulin
- Does not pass through human placenta.
- Only isotype synthesized in appreciable amounts by a fetus.
- IgM include isohemagglutinins, naturally occurring antibodies against ABO blood groups.
- Activates/fixes complement, does not neutralize toxins or viruses.
___ is the first antibody produced after immunization
IgM
___ antibody does not pass through the human placenta
IgM → large amounts are made in a fetus
___ activates or fixes complement system and does not neutralize toxins or viruses
IgM
IgG
- Predominant antibody in blood, lymph, CSF,
- Four subclasses (IgG1-4) with distinct effector profiles
- longest lasting Ig
- Only isotype to pass placenta, also in colostrum.
- Ab-dependent cell-mediated cytotoxicity. Binds target and Fc receptors on NK cells focusing the killer cell to its target.
- Activates the complement system.
- Opsonizes – binds Fc receptors of phagocytic cells- tags to be eaten
- Neutralizes toxins (passive immunization), viruses (blocks attachment sites) and immobilizes bacteria
___ is the only isotype of Ig that can pass through the placenta
IgG
___ trigger the complement system, opsonize and neutralize toxins, viruses and bacteria
IgG
___ is important in secondary immune response
IgG
___ cause ab-dependent cell-mediated cytotoxicity. Binds target and Fc receptors on NK cells focusing the killer cell to its target.
IgG
IgD
- Rare (0.25% of all immunoglobulins).
- IgD is coexpressed on the surface of mature B cells with IgM. Starts to being expressed when the B cells migrate from the bone marrow to peripheral lymphoid tissue.
- Immunological function still not fully understood; possible role in respiratory immune defense, negative selection of autoreactive B cells. Potentially also involved in allergic reactions.
Binds to and activates basophils and mast cells
help with microbiome in GI tract?
__ might help with the microbiome of the GI tract
IgD
IgA
- Two subclasses: IgA1 and IgA2 (in humans)
- Major isotype of external secretions (saliva, tears, mucus, sweat, gastric fluid, colostrum).
- IgA-secreting plasma cells are found in the lymphoid tissues underlying mucosal surfaces.
- Poly-Ig-receptor transfers IgA through epithelial cells and into extracellular fluids.
- Defense against local infections, prevents attachment and penetration by microbes.
- Does not strongly fix or activate complement
- Secretory IgA is antiviral, prevents virus attachment and agglutinates.
- Monomeric form remains systemic
___ helps maintain the microbiome of the gut inside the gut
IgA
IgA transferred to lumen of the GI and binds to antigens in the GI and promote growth (colonization) or breakdown of some pathogens
___ receptor transfer IgA into the gut lumen
pIgR
___is actively transported across epithelial cells, neutralizes pathogens, keeps commensal flora in check, and exports toxins
•Dimeric IgA
IgE
allergies
- Role in parasitic (helminths) infections, hypersensitivity and allergic reactions.
- IgE can attach to mast cells and eosinophils that have a high affinity Fc receptors for the CH chain of IgE, thereby thereby inducing degranulation of these cells, which release histamine and other pro-inflammatory and toxic factors (involved also in allergy).
- No complement fixing.
binds to parasites
___ binds to parasites and cause inflammatory response
IgE
___ antibodies activate complement system
IgM, IgG
polyclonal antibodies
antigen will be reacted to by many different types of antibodies because antigen has many different spots for recognition (multiple epitopes)
___ are uniform, only contain one antibody type against a single antigen/epitope
monoclonal antibodies
FACS
fluorescence activated cell sorter
detects: granularity, size and fluorescence
stain with antibodies bound to a specific color, can sort by that color to find specific type of cell
