Humoral Immunity Flashcards
(33 cards)
Humoral Immunity
B lymphocyte-mediated immunity
Immunity that can be transferred from an immune to a non-immune person by transfer of serum that contains antibody; Intravenous immunoglobulin (IVIG)
The gamma-globulin protein fraction of serum contains the antibody activity
Antibody activity = specific recognition and binding to the inducing antigen
Antibody Function
Ab: ability to recognize AND bind the foreign Ag
Highly specific binding site for foreign materials that promotes Ab protective effects such as inhibition of microbial adherence, phagocytosis, etc.
Humoral Immunity and Extracellular Microbes
Humoral immunity protects against extracellular microbes or immunogenic molecules such as bacterial toxins. This includes extracellular phases of viral infection
Ab are in extracellular spaces only and do not cross the membranes
B cells have surface receptors that interact with extracellular substances to cluster the receptors and induces proliferation of those B cells with those receptors on them
Ab will accumulate and concentration will rise in circulation and prevents reinfection of the same pathogens (provides immediate protection once re-exposed)
B cell Maturation
B cells mature in bone marrow
Each clone expresses a unique antigen receptor (surface antibody or immunoglobulin) generated by random DNA recombination of multiple gene segments encoding immunoglobulin protein chains.
~1011 possible different receptor combinations
Immature B cells with autoreactive receptors are deleted by apoptosis (clonal deletion)
Antigen-activated B cells synthesize and secrete a soluble form of this receptor (plasma antibody) which accumulates in fluids and specifically binds and eliminates the stimulating antigen.
Lab Markers for B cells
surface Ig
CD19
CD21
Clonal Expansion of B cells
B cell with naïve Ig, then see any type of chemical determinant (free or bound unlike T cells that can only see bound) and will undergo initial stages of activation, but to undergo full process must see cytokine and surface to surface from helper T cells (full maturation and proliferation)
Under the influence of cytokines from T cells, they will differentiate along different paths aka T cell dependent maturation
Ag driven: Ab bind and help eliminate Ag, but once Ag drops the stimulus the cells die via apoptosis, but the other B cells will persist as memory cells in case of re-exposure for immediate protection
B cell Affinity
As they are replicating in germinal center, there is a somatic mutational process that mutates the AA sequences in Ag binding site (high rate) to increase Ab for target
B cells can lose affinity altogether, but most of them increase the affinity and continue to bind with highest strength and affinity they continue to proliferate
Ig Class Switching
Ig class switching under T cell control, and regulated in regards to T cell signals to change which Ig’s are expressed
Polyclonal Ab Response
Great diversity of B cells with individual specificities
Large molecules (10000MW), chemically complex, and biologically degradable = foreign molecules; most are large proteins
Ag determinant – only 6 AA in size, so if have protein with 100s of AA long, any of the chemical determinants are multiple stimulators of multiple B cells to cause proliferation and get Ab to each stimulus
Anti-polio for example, do not make just one Ab, you make thousands of different Ab that goes with each different determinant on that virus
Ab has two identical binding sites, but have heterogenous response (many different Ab attack)
Structure of Immunoglobulins
Structural domains have conserved (C) or variable (V) structure between Ig molecules with different antigen specificity
Monomeric Ig has 4 covalently linked polypeptide chains: 2 identical heavy chains (H) and two identical light chains (L)
The sequence is conserved, and at N terminal regions they have variable AA sequence (compare between two Ab, this is where you see the structural differentiation between the two)
Fab Region: for Ab binding
Tail = class and represent Ab differences = Fc region = constant fragment; this region is C1 binds of the classical complement pathway; Fc regions cluster together and C1 binds to Fc region to become activated; also involved in opsonization because phagocytes have an Fc receptors that recognize the tail of the Ig, and phagocytes will bind and forms a bridge between bound substance and promotes phagocytosis
Antigen Binding Sites
VH and VL domains fold to form antigen binding sites that resemble pockets, grooves, open faces, or extrusions. Each monomeric Ig has 2 identical binding sites.
High specificity of Ab and how they work
Bind small chemical determinants, but very specific = lock and key 3D complimentary interaction
Reaction is non-covalent
Ig Class
Ig class (isotype) is based on similarities of H chain structure. Secreted forms of IgA and IgM exist as multimers.
Most Ig are monomeric, but IgA is a dimer (J chain protein that hooks them together) and IgM is a pentamer and so large it is confined to intravascular spaces
Initially all B cells will secrete is IgM, but then class is based on conserved regions on heavy chains and encoded on different genes than the variable regions that determine Ag specificity, so under T cell influence, the B cell can switch IgM to any of the other Ig, and conserves the specificity of the conserved part of the protein
IgA
IgA: monomer, dimer; mucosal immunity
IgD
IgD: naïve B cell antigen receptor
IgE
IgE: monomer; mast cell activation (type I hypersensitivity), defense against helminthic parasites
IgG
IgG: monomer; opsonization, complement activation, Ab dependent cell mediated cytotoxicity, neonatal immunity, feedback inhibition of B cells; long term immunity with longest concentration and half life
IgM
IgM: pentamer; naïve B cell antigen receptor and complement activation
IgM is expressed with a transmembrane domain not secreted, but following activation it ceases to express the transmembrane domain and it becomes the secreted form of protein
B cells have a period where they can have both surface Ig and are secreting at the same time, but once fully mature to plasma cell can only secrete
IgM is a monomer when attached to B cell, but once secreted is a pentamer
Plasma Half Life and Concentration of Ig
Plasma Half Life (days): IgG > IgA > IgM > IgE
Plasma Concentration: IgG > IgA > IgM > IgE > IgD
Effector Functions of Ab
Plasma cells secrete them and stay in plasma
Ab specifically recognize and bind inducing Ag/immunogen
Toxic molecule: Ab binding mediates toxicity, and blocks the toxic activity aka neutralize
Ab binding and coating to viral/bacterial surface can block microbial attachment to tissues
Opsonization: Ab promote phagocytosis via the Fc Ig region by coating the pathogen
Any cell with Fc receptors, especially NKC, which are not phagocytic or specific but can be targeted to specific cell by an Ab
If viral infection in cell, if Ab binds to surface similar to opsonization, NK cells will recognize the Ig through Fc receptors and bind that target and mediate killing = Ab mediated killing
Once you make a specific Ab, the IgG/IgM can activate the classical pathway of complement via C1q of the pathway
All important in extracellular spaces against extracellular microorganisms
Ag Presentation by B cells to CD4 T cells
Antigen binding causes B cells to express MHC II-peptide antigen complexes, B7, CD40, and cytokine receptors on their cell membrane for receipt of T helper co-stimulatory signals (CD40L and cytokines).
Ag uptake, because B cells are not phagocytic, but have a receptor that binds to foreign material and can undergo receptor mediated endocytosis and the B cell expresses MHC II once proteins are processed and then receive help from the CD4 T cell; costimulatory exchanges involving B cell CD28 and CD40, and then CD40 ligand on the T cell and finally release of GFs from T cell that induces B cell growth and differentiation
CD4 T cell Activation of B cells
Antigen-specific CD4+ T helper lymphocytes provide help for B cell activation.
Th cells recognize peptide-MHC II presented by B cells and provide signals for B cell proliferation, isotype switching, and differentiation into plasma cells and memory cells
Required B7-CD28 interaction for Th activation
T cell Dependent B cell Activation
Naive B cells use surface IgM (and IgD) to bind and internalize specific antigen for processing and presentation of foreign peptide determinants with MHC II to TH cells (T helper lymphocytes)
B cell antibody production to most complex protein immunogens is dependent on:
1st: Specific antigen recognition and crosslinking of surface immunoglobulin (B cell receptor complex)
2nd: T helper cell-derived co-stimulatory signals via B cell-T cell contact (CD40L-CD40 ligation, cytokines, etc.)
Lymphatic Tissue Interaction of T and B cells
T cell is being independently activated by seeing peptides on dendritic cell in T cell rich areas
B cells are seeing Ag and processing peptide in follicle
Early activated T and B cells will migrate towards each other and reciprocally upregulate chemokine receptors and get early Ab production and some B cells migrate back into follicle and begin massive proliferation to form the germinal center and some migrating follicular T helper cells maintain this processes by providing ongoing help to continue proliferation and affinity maturation
Ag Exposure in B and T cells
B cell is repeatedly being exposed to peptides via follicular dendritic cell in the germinal centers and can trap Ab-Ag complexes to bind on dendritic cell and hold Ag for long periods of time for repeated exposure for B cells and lead to affinity maturation
T cell can sense many different peptides, and must get infection to get immunity, but you have the ability to respond to different immunogens even before exposed, but develop better response the next time