32 B cells Flashcards
o Originate from a stem cell (lymphocyte precursor, marker CD43)
o B cell (marker CD19)
o After exposure to antigen, mature, naïve, B cell differentiates into memory cells and plasma cell
1) Antigen independent: Generation of diverse repertoire of mature B cells
2) Antigen dependent: Activation
3) Survival
4) Proliferation
5) Differentiation
Stages of the life of B cells
T/F. if a particular antigen activates the membrane bound Ig, antibodies (secreted form Igs) are released that are specific for that unique antigen. As the immune response progresses and additional signals are received from other immune cells, the B cell’s affinity for recognizing this antigen increases (increased expression of the given Ig in the cell membrane)
True
B cells that only express IgM and IgD (~1%) in their plasma membranes
Naive B cells
These cell types have already undergone class switching. Ig isotype in the membrane will be whatever the class switching has set it to.
Experienced & memory B cell types
Location: blood, tissues, and mucosal sites
Function: It can neutralize toxins (antigens), and it can prevent the entry and spread of pathogens, it can also be recognized by its Fc domain by other immune cells that will eventually clear the infection
Anitbodies aka secreted form Immunoglobulins
Functions to bind epitopes and bring in enough Ig-beta and Ig-alpha to transmit the signal to the cell.
BCR
These molecules allow the pathogen (which has already activated the compliment) to cross-link additional BCRs due to the fact that it is coated w/ c3d, bringing together additional Ig-alpha and Ig-beta units
CR2 & CR1
Low levels of circulating antibody. The mutation is in the gene encoding Bruton’s kinase (a tyrosine kinase) that is involved in the signaling of the BCR. Because it is involved in the signaling of the BCR, that BCR is not going to be able to survive, proliferate, or differentiate
• Igs in immature B cells: One of the functions of the heavy chain of the new Ig is signaling for proliferation (of this specific immunoglobulin) in the cytoplasm. For this reason, B cells to not reach maturity. Results in low levels of circulating mature B cells and low levels of Igs. B/c the signal is specific for B cells and excludes T cells, the cell-mediated immunity is relatively unaffected.
• Clinical signs: Clinically, there will be increased susceptibility to extracellular pathogens (specifically bacterial infections), presents w/ recurrent pyogenic bacterial infections (as in any other B cell infection).
• Treatment: pooled gamma globulin is effective against many pathogens, and reduces the number of infections
X-linked hypogammoglobulinemia (Bruton’s Agammaglobunimia)
- Signal 1: The engagement and cross-linking of the BCR (i.e. the BCR recognizing the antigen)
- Signal 2: CD28 (on the helper T cell) must interact w/ B7 (on the B cell), and CD40L (T cell) must interact with CD40 (B cell). This results in a signal being sent to both the helper T cell and the B cell (the B cell is activated mainly by signaling from cytokines that are secreted from the activated T cell)
2 signals for activation of a naive B cell
Molecule found on the surface of Th cells. Must interact with B7 on a B cell in order to activate the B cell
CD28
Molecule found on the surface of B cells. Must interact w/ CD40L on a T cell in order for the B cell to be activated. Note: This interaction is important for class switching and affinity maturation. This response leads to expression of genes whose products are required for functional responses of B cells
CD40
1) First a B cell is activated by binding an antigen
2) The antigen is now internalized (receptor mediated phagocytosis)
3) The phagolysosome digests the antigen
4) Antigen is presented to an experienced CD4+ cell, which releases cytokines that signal for proliferation B cells (mainly IL-2)
5) This B cell is going to mature and differentiate into either a memory cell or a plasma cell (secretes antibody)
Process of B cell activation
Cytokine released by experienced CD4+ cells upon presentation of antigen to the CD4+ cell. This cytokine signals for proliferation of B cells and many other immune cells
IL-2
The type of T helper cell that is able to establish a germinal center
Follicular helper T cell
T/F. The germinal center of the lymph nodes is where clonal expansion occurs as well as the two major processes that establish specificity for the antigen after the antigen has been recognized (class switching & affinity maturation)
True
Very similar to what happened with the T cells, some antigens do not need the help of the T cell to activate a B cell. This case involves a lipid or a carbohydrate that has many repeated units. An antibody is divalent, therefore a repeated unit will cause many antibodies to come together can cause extensive receptor cross-linking, eliminating the need for the help of T helper cells. These agents are known as ___
Mitogens
T/F. The T-cell independent response is specific to the antigen that activated the B cell receptor
False. This response is not specific (the T cell-mediated response is). However, it will allow us to establish antibodies to mount an antibody response a wide variety of pathogens
T/F. Class-switching occurs in the T cell independent antigen response
False. The problem is that b/c they do not require the T helper cell, they will not be able to perform class switching. Consequences include that only IgM will be produced, also affinity maturation will be impossible (affinity of the antibody will be low)
T/F. Mitogens generate a polyclonal response in B cells. This is not necessarily useful in real life, as it could lead to over-activation of lymphocytes
True
T/F. For most antigens, the T helper cell provides help to the b cell to differentiate into a memory cell or a plasma cell (produces antibody). This differentiation includes two elements: includes somatic hypermutation and class switching. This occurs in the germinal center
True
the process by which the genes undergo mutation and selection that can increase the affinity for the specific region. This allows B cells to bind more effectively to antigens, allowing the B cells to proliferate at an accelerated rate
Affinity maturation
introduces mutations into the genes of the variable region. This is important for increasing the affinity of an Ig and for class switching
Activation-induced cytidine deaminase (AICD)
In the variable region of the antibody molecule, the first antibody made is IgM. As more is made, more T helper cells are activated. These T cells release cytokines that induce mutations in the variable regions. Three outcomes are possible: increase in affinity, decrease in affinity, or no change in affinity (variable region binds to antibody). This process is known as ___
Somatic hypermutation
The process by which the B cell can change the class of antibody that it produces
Class switching
This cytokine causes cross switching to the IgE subtype
IL-4
Once the ILs have been secreted by the T helper cell, along with the CD40-CD40L interaction, ___ occurs
Cross switching
occurs if we have mutations in the CD40 or CD40L (T helper cell deficiency) structures. Cross switching cannot occur. Therefore IgM is the only Ab that is secreted. Also, no affinity maturation. High IgM levels in blood. Low affinity of Igs.
Presents with severe pyrogenic (puss-forming) infections and opportunistic infections
Hyper IgM syndrome
perform neutralization of microbes and toxins. This binds to an epitope and prevents it from performing its functions (ex: entering a cell, entering into the mucosa). Mediated by the Fad (variable) regions. This is mediated by IgG (actually, all Abs can do this). An IgG is better than an IgM at opsonization b/c the IgG has gone through affinity maturation. The IgG has a higher affinity for this antigen
Antibodies
Opsonization is mediated by the ___ region of the Ig. The macrophage (or neutrophil) must recognize this region in order to receive the signal. Opsonization increases the phagocytic capacity of macrophages.
Fc region
o When the microbe is covered w/ antibodies, macrophages can recognize the Fc region of the Ab, leading to opsonization, and macrophages phagocytosis of this antigen is enhanced. This is ___ mediated (Ig isotype)
IgG
the NK cell has a balance of positive and negative signals. This helps the NK cells to recognize another infected cell. It recognizes the infected cell b/c it is coated w the antibody. Ab is recognized by the Fc receptor (these are generally IgG receptors) and apoptosis is induced by the NK cell
Antibody-dependent cellular cytotoxicity (ADCC)
Antibody-dependent cellular cytotoxicity is mediated by which isotype of Igs?
IgG molecules
T/F. Mast cells & eosinophils recognize the Fc receptor of IgEs
True
The most effective Ig at activating complement
IgM. This is b/c it is pentameric
Antibodies can also activate the ___ coplement pathway. Once we activate this complement pathway, phagocytosis of microbes is increased through opsonization (due to complement)
Classical complement pathway
Recruits phagocytic (and inflammatory) cells to assist in inflammation
c5a
Antibodies also activate the classical complement pathway. IgM is most effective at activating complement (b/c it is pentameric. Whereas an IgG molecule contains only a single Fc region, the IgM molecule contains five. This means more binding sites. Once we activate the complement, we can increase phagocytosis of microbes opsonized w/ complement (ex: C3b)
Recruit phagocytic (and inflammatory) cells to assist in inflammation. Mediated by C5a
Promotes the lysis of the microbes through creation of the membrane attack complex
Effector functions of the complement system
1) expansion, 2) contraction, and 3) memory
Three phases of the B cell response
leads to the development of memory cells (longer half-life, do not proliferate to the infected tissues, also they are stimulated very quickly b/c they have a lower threshold for stimulation)
Contraction phase (of B cell response)
. If antigen-antibody complexes are created, they may bind many antigens and end up depositing in the tissue if they remain in the blood for too long. If the complex is deposited into the tissue, a macrophage will attack the tissue, leading to tissue injury. B/c of this, antigen-antibody complex is recognized by the complement. The complement (C3b) is then recognized by phagocytic cells (to digest complement). This also sends a signal to the liver to clear these complexes.
Role of complement system in contraction phase (of B cell response)
What is the primary Ig isotype produced during the first B cells response to an antigen?
IgM
What is the primary Ig isotype produced during the secondary B cell response to an antigen?
IgG
What type of B cells secrete IgGs?
Memory B cells. These cells have already undergone class switching. Therefore they are able to secrete high-affinity antibodies and also perform numerous other functions
Generally B cells illicit a humoral response which begins w/ an extracellular antigen (mainly bacteria and some fungi). b/c of this the patient presents w/ pyogenic and anteric bacterial infections.
In the lab, depending on the subtype, reduced serum Ig levels will be observed
Histopathology: generally, because we have a defect in this response, we will not form lymphoid organs w/ follicles and germinal centers (b/c this corresponds w/ B cell proliferation). However, in the T cell response, b /c B cells need the T cells for activation, they may present w/ overlapping symptoms
Primary B cell deficiency
Increased susceptibility to viral and intracellular infections (atypical mycobacteria, pneumocystitis jirovaci fungi). If it affects a B cell, T cell deficiency can lead to increased susceptibility to bacterial infections.
Lab: Add a mitogen, and there will be defective T cell proliferation in response to addition of the mitogen in vitro
Histopathology: Reduced T cell zones in secondary lymphoid organs
Primary T cell deficiency
• How are antibodies related to tissue injury? Antibodies can either:
o Bind to receptors and either inhibit or activate the receptor (ex: myestenia gravis)
o Bind to tissue-antigen and deposit into tissues (type 2 hypersensitivity)
o Bind to soluble antigens and form immune complexes that can deposit in the vascular basement membrane (type 3 hypersensitivity)
o One this happens, the same functions are activated (the effector functions and thus, tissue injury, is mediated by the Fc portion of the Ab):
Phagocytosis
Activate complement
ADCC (antibody dependent cytotoxicity)
Just for info
Opsonization
Activate complement
ADCC (antibody dependent cytotoxicity)
Effector functions of antibodies
A set of antigen-binding sites that characterizes the antibodies produced by a particular clone of antibody-producing cells. The ___ is thus the distinctive sequence and region that makes any Ig or TCR unique from others of the same type. Located in the variable region. Corresponds to B & D in the image
Idiotype
IgG, IgM, IgE, IgD are examples of different ___?
Isotypes
This site of cleavage cleaves the antibody into two pieces, giving the Fab and Fc fragments
Pepain cleavage site
An enzyme that cleaves the antibody into the Fab and Fc fragments
Pepain enzyme
Region of an Ab to which complement molecules bind
Fc region
This region determines the effector function of the Ab
Fc region
This region determines the specificity of the Ab
Fab region
is assembled in a pentomer (five Ig molecules). It is the first Ab of the primary response. Used in the lab for agglutination (b/c of pentomeric structure)
IgM
the most prevalent antibody in the blood. Not as good as IgM at fixation of complement, but in can do it. The only Ab that can cross the placenta (this is passive immunity)
IgG
o forms dimers. Most abundant Ab in the body (everything included) b/c it is mainly found in the mucosa (digestive tract, respiratory, reproductive tract, etc). This Ig is not good at fixing complement. The only Ab found in milk
IgA
The only Ab found in milk
IgA
The only Ab that can cross the placenta
IgG
a major Ab for defense against parasite/worms (too big to be phagocytosed by macrophages & neutrophils). Mast cells, eosinophils, basophils all have receptors that recognize this Ig isotype. Once this Fc receptor has recognized the antigen, the mast cell (for example) will degranulate, sending cytotoxic granules to the parasite. A disadvantage is that this mediates hypersensitivity reactions (esp. type 1)
IgE
not much is known. A co-receptor in the naïve B cell. Very little is secreted into the blood
IgD
Patient’s blood is mixed w/ antiserum against either type A or type B blood cells. Slide(s) on which the agglutination reaction occurs indicate the blood type of the patient’s blood
ABO blood type test
To detect the presence of Abs against RBCs (immune mediated hemolysis). Antiserum against human immunoglobulin is used
Direct: Agglutinate the patient’s red blood cells (if Ab binds)
Indirect: Patient’s serum is mixed w/ normal cells prior to agglutination test
Coombs test
Pass cells through an apparatus, then the cells can be shined and divided, separating cell types depending on their characteristics
Flow cytometry
Review the hybridoma image and other diagrams
Do it
