Flashcards in Immunology 8 (Kyle) Deck (69)
What the the primary function of the B cel arm of the adaptive immune response?
Priduction of Ab, they make cytokines to but Ab's are more important.
Do Ab's destruct or destroy pathogens?
No, they tag them for destruction tho. "The Black Spot"
What allows B cell responses to increase in affinity as they develop ?
What allows B cell responses to be tailored to best deal with the particular pathogen
What aspect of B cells allow B cell responses to be retained providing long lived protection to that particular pathogen.
Memory B cells
What is the first signal that activates the b cells? What does it bind to and what does this cause the B cell to do?
The antigen binds BCR [IgM] causing crosslinking and clustering of BCR's which activate the signal transduction unit.
**It takes multiple Antigen-BCR complexes for activation.
What composes the signal transduction unit of the BCR ?
IG-alpha / IG-beta complex - These contain cytoplasmic tails have immunoreceptor tyrosine based tails. When phosphorylated they initiate intracellular signaling.
What is the co-receptor for the BCR and what does it do?
If the co-receptor is activated do you still need co stimulation by a T-cell?
CR2- Complement receptor 2, which binds to the complements that are bound on the surface of a pathogen. This enhances the effect of the BCR: antigen complex.
A second signal is still required for B cell activation.
What do B cells activated by TH2-CD4 differentiate into?
Memory cells and plasma cells.
What is the signal transduction unit for the BCR ?
The Ig-alpha / Ig-beta complex
What happens to a B cell that is activated by a determinant but does not recieve the secondary stimulation from T cells?
They become anergic and die. The absence of T cells means there is no infection.
What type of antigens can activate B cells in the absence of T cell help?
Thymus-independent antigens. (TI-antigens)
Do thymus dependent antigens require co-stimulation via T cells?
Yes but you can get around this in two ways.
What are TI-1 antigens?
Mitogens, they can activate B cells without T cell stimulation. They do this by binding to the BCR and also the Pattern Recognition Receptor.
At high concentrations can TI-1 antigens activate B cells? If so what type of B cell?
At high concentrations TI-1 antigens can activate almost any B cell regardless of the BCR specificity.
What do M cell mitogens do ?
Antigens that cause polyconial activation. An example of this is Lipopolysaccharide (LPS) which is a component of gram negative bacteria.
How to TI-2 antigens work ?
What are TI-2 antigens composed of ?
They work by heavily cross linking BCR's on the surface of the B cell to the point where no additional activation is needed.
They are composed of cell wall polysaccharides (repetitive structures)
What do TI-2 antigens respond to?
What are the limitations of TI-2 antigens ?
1. There is no significant isotype switching
2. No affinity maturation takes place
3. No immunological Memory is provided.
Can infants mount a TI-1 or TI-2 antigen response?
TI-2 antigens will not be present until the child is about age 5
Infants can mount a TI-1 response.
What happens to a b cell in the presence of high concentration of TI antigens ?
What happens to B cells in the presence of low concentration of TI antigens?
1. Polyconial B cell activation will lead to a nonspecific antibody response.
2. TI-1 antigen specific (IgM) Ab response.
Where are germinal centers located?
What are the two main functions in the Germinal center?
Aomatic hypermutation resuts in cells with higher and lower affinity for antigen.
What are the unique cells found in the germinal center?
Follicular dendritic Cells (FDC's) they have lots of Fc receptors and complement recptors to trap antigen. They populate the germinal centers and B cells compete to bind antigen in the germinal centers.
The V chain of the Ig are susceptible to what?
A high rate of mutation.
Do plasma cells have surface Ig ?
What surface receptors do plasma cells have?
None. They have a high rate of Ig secretion tho.
Can plasma cells be induced to grow, dxhibit somatic hypermutation, or take part in isotype switching?
No they are terminately differentiated and their only job is to secrete antibodies.
Why is IgG so important?
IgG is the most abundant Ab for the control of infection.
1. It can fix complement
2. Most Phagocytes and NK cells have Fc receptors that recognize IgG
Tell me about IgM
IgM is the first Ab produced every B cell. It is secreted in its pentameric form and is carried via the blood to sites of tissue damage and infection throughout the body.
Where is IgA found ?
Synthesized by plasma cells that reside primarily in secondary lymphoid tissues that ln the mucosal surfaces of the body (MALT)
What is transcytosis?
The transport of molecules from one side of an epithelium to the other by endocytosis into vesicles on one side of the cell with release from the other side.
What is a Poly Ig Receptor?
A receptor on the basolateral surface of the epithelial cells that binds to polymeric immunoglobulins, especially IgA, and transports them across the epithelium via transcytosis. The receptor can also bind IgM but it is much less efficient.
What is a brambell receptor?
Are these on the placental barrier?
Present in the vascular endothelium, IgG is actively transported from the blood into extracellular spaces by an brambell receptor
What is passive immunization?
Passive immunization is the injection of specific Ab's or T cells to provide protection against a pathogen or toxin. The administration of Ab's may derive from human blood donors, immunized animals or hybridoma cell lines.
What is passive transfer of immunity?
Is the transfer of immunity to a non-immune individual by either natural means (Ig crossing the placental barrier) or by injection of a specific Ab immune serum or T cells.
Where do NK cells come from?
Lymphoid progenitor in the bone marrow but are functionally very different from lymphocytes.
What are mast cells and do they make antigen-specific receptor molecules?
Large granular cells found in large numbers in vascularized connective tissues. They arise from common myleoid precursor in the bone marrow and are innate cells of the immune system.
**They do not make any antigen specific receptor molecules.
What are the only cells that can produce Ab in the absence of T cell help?
TI-1 and TI-2
What antibody will elicit an immune response in congenital athymic individuals ?
Think, If you dont have a thymus, you dont have mature T cells. So the only activation of B cells are going to be through T-Independent antigens.
Do TI antigens ( 1 & 2 ) result in immunological memory ?
No Only T dependent activation can cause differentiation into Memory cells.
Do TI-1 and TI-2 activate T cells ?
Can TD antigen activate T cells ?
No they can only activate B cells.
Can TD antigen induce immunological memory?
Can TI-1 antigen activate non-specific B cells ?
What about TD and TI-2
Do TD and TI-1 require repeated epitopes ?
No but TI-2 does.
Where does the bulk of pathogen specific antibody come from during an immune response?
B cells stimulated by T-dependent antigen
What are the two roles of the BCR ?
1. Binding the cognate antigen
2. Internalizing the antigen so it can be processed and presented on a MHC-2 molecule.
What is a centroblast?
Lymphocytes from the primary focus that travel migrate to the primary follicles as conjugates with their effector helper T cells, Their replication rate increases exponentially and these areas of rapid proliferation are called centroblasts.
Where does affinity maturation take place?
In the centrocytes during the germinal center reaction.
What is isotype switching and where does it take place?
Takes place in B cells in the germinal center, The signals that drive isotype switching are provided by effector T cells that are also proliferating within the germinal center.
What are the three main processes that take place in a germinal center
1. Affinity maturation
2. Isotype Switching
3. Expansion and differentiation of positively selected high-affinity isotype switched B cells.
What is a follicular Dendritic Cell? how does it differ from normal dendritic cells?
These cells pick up antigen but do not internalize it. They display it on their cell surfaces for a long period of time. They allow B cells to compete for binding to that antigen. They also provide survival signals to centrocytes that have high affinity for antigen
What does the antigen bind to on the surface of the FDC ?
The antigen binds to Fc receptors instead of MHC-2 molecules.
What drives isotype switching ?
Cytokines from Th1 cells induce class switching to isotypes of Ab that are what?
Cytokines from Th2 molecules induce the cells to switch to waht type of Ab?
Ab's that are weakly opsonized as well as IgA and IgE
What happens to cells that survive the positive selection (affinity maturation) and isotype switching in the germinal center?
They continue to proliferate and begin to differentiate into plasma cells that then leave the 2degree lymph tissue, they then migrate to peyers patches and the bone marrow.
In a nut shell what the hell is isotype switching and why do we care?
Isotype switching mantains the antigen specificity of the antibody while altering the constant region of the heavy chain (FC region)
*This allows the immune system to diversify the effector mechanism of B cells derived from the original antigen-specific B cell alone.
What are the functions of the Fc regions of the Ab? ( name 3 )
1. Delivery of the Ab to the effector sites
2. Initiation of the classical complement cascade.
3. Recrutement of non-specific effector cells.
What is the first Ab every B cell produces?
IgM which can neutralize pathogens and activate the complement cascade. Its large size makes it inefficent at leaving the endothelial cells to migrate to the site of infection.
What does cytokine IL-5 promote class switching to?
What about IL-4
Can plasma cells be activated to proliferate?
No, literally all they do is secrete antibodies.
What two Ab's are most important for passive immunity?
IgA and IgG
How do Ab's neutralize toxins ?
They bind to the toxin and get phagocytosed before the toxin can injure the cell.
How do Ab's neutralize viruses?
They bind to surface antigens of the virus and cause it to be phagocytosed.
How do Ab's neutralize bacteria ?
Bind to antigens and cause phagocytosis.
What does FC epsilon I do ?
Binds IgE receptor on esoinophils and basophils and causes secretion of granules.
What does FC epsilon RIII do ?
On Nk cells and allows them to detect Fc receptors on NK cells.