Immunology 6 Flashcards
Describe antigen-dependent B cell activation and differentiation
Specific antigen + co-stimulation activates resting B cells
Activated B cells:
Enter cell cycle/mitosis leading to clonal expansion
Cells then differentiate into memory B cells and plasma cells (effector B cells), which produce antibodies
Structure of lymph node interior?
B cell zone - inc. stromal cells with opsonin receptors for opsonins on antigen, like C3b
B cells also have PRRs to recognise PAMPs
B cells produce low affinity, antigen-specific antibodies (no memory cells), like IgM Same mechanism can occur, with stromal cells, with additional T cell help to produce a germinal centre, leading to memory B cell production and antibody production
Difference between production of antibodies by B cells?
B cells alone - produce low affinity, antigen-specific antibodies (no memory cells); in other words, IgM only
B cells + T cell help - high affinity, antigen-specific antibodies (+ memory cells); in other words, IgM initially and then IgG, IgA, IgE and IgD
Describe IgG
Most abundant Ig in PLASMA, and is actively transported across PLACENTA
4 sub-types - IgG1-4
Describe IgA
2nd most abundant Ig type
Monomeric form - blood
Dimeric form - BREAST MILK (passive transfer of pre-formed, protective anitbodies from mother to baby), saliva, tears, mucosal secretions
Describe IgM
As a surface bound monomer is BCR (B cell receptor antigen) and is only antibody produced in response to nucleic acids
PRIMARY RESPONSE:
1st Ig type produce during an immune response (present only in plasma/secretions - pentameric so efficiently binds to antigens on pathogens)
Describe IgD
Extremely low levels in blood
When surface bound act as BCR
Uncertain function
Describe IgE
Extremely low levels normally but are produced in response to PARASITIC infection and ALLERGIC responses
Dual biological function of antibodies?
Have variable and constant regions:
Variable regions have RECOGNITION function - binding to antigen mediated by variable region sites
Constant regions (Fc) have EFFECTOR function - clearance mechanisms mediated interaction by Fc region with effector molecules, like COMPLEMENT and Fc receptors
Function of high affinity, neutralising antibodies binding to antigens?
Protective
Prevent viruses from infecting host cells using AGGLUTINATION (of virus particles by antibodies) - this is IMMUNE COMPLEX FORMATION
Also, to prevent microbial toxins from disrupting normal cell function, like diphtheria toxin and tetanus toxin - the antibody blocks the binding to the toxin to a cellular receptor
Effector functions of antibodies?
Can activate classical complement pathway
Can function as opsonins
Can help stimulate NK cells
Can trigger allergic responses, like asthma, allergy, anaphylaxis
How can antibodies help stimulate NK cells?
Results in Antibody-Dependent Cell-Mediated Cytotoxicity
Antibody binds antigens, on surface of target cell Fc receptors, on NK cell recognise bound antibody
Cross-linking of Fc receptors signals NK cells to kill the target cell
Target cell dies by apoptosis
What are opsonins and how do antibodies function as them?
Coating of micro-organisms by immune proteins (opsonins), like C3b, CRP and antibodies
Phagocytes express Fc receptors that bind to the constant regions of Igs - opsonisation enhances phagocytosis, especially encapsulated bacteria
How can antibodies trigger allergic responses?
IgE binds to allergen and IgE also binds to Fc receptor on mast cell, which degranulates A
Effector functions of different antibody classes?
Functions of antigen activated T cells?
Help activate other immune cells - HELPER T CELLS/Th (CD4+ cells) become activated when presented with peptide antigens, which are presented using MHC Class II on antigen-presenting cells
Kill infected and cancer cells - CYTOTOXIC T CELLS/Tc/CTLs (CD8+ cells) become activated when presented with peptide antigen, which are presented using MHC Class I on all nucleated cells
Types of T cells?
CD4+ is a resting T cell, when activated becomes a helper T cell
CD8+ is a resting T cell, when activated becomes a cytotoxic T cell
Function of effector Th cells?
Key master regulators of immune system - can “help” STIMULATE OTHER IMMUNE CELLS, like CD8+ cells (to become cytotoxic cells), macrophages and B cells, using cytokines and direct cell contact
How do effector Th cells help T cell responses?
CD4+ cell binds to peptide presented by dendritic cell, using T cell receptor (TCR)
CD8+ cell binds to peptide presented by dendritic cell, using TCR CD4+ cell activated a Th cell, which produced IL-2, stimulating production of multiple Th cells
IL-2 also stimulates CD8+ cells to activate into Tc cells
How do effector Th cells help macrophages?
- Effector Th cells migrate from lymph node into sites of infection/inflammation
- Th cells are re-activated by macrophages in an antigen-specific manner
- Th cells express co-stimulatory molecules and hyper-activate macrophages, using IFNγ, enhancing their killing activities and pro-inflammatory responses
How do effector Th cells help B cells?
Help B cells respond effectively to PROTEIN ANTIGENS (provide signal 2)
- Protein antigen bound to BCR is internalised by B cell Antigen is degraded and peptides are presented on the B cell surface complex with MHC-II
- Effector Th cells move into B cell zone, of lymph node, where they are re-stimulated by B cells in an antigen-specific manner and start to express CD40L Re-activated effector Th cells stimulate B cell to proliferate and survive (via CD40L : CD40 interactions)
- Effector Th cells secrete cytokines that further activate B cell and stimulate germinal centre response
What does the germinal centre response involve?
B cell proliferation
Antibody heavy chain switching
Generation of high affinity antibodies
Differentiation into plasma cells and memory B cells
What is antibody heavy chain switching (class switching)?
B cells switch antibody heavy chain constant region gene segment they use
Describe generation of high affinity antibodies
AKA somatic hypermutation
Aim - produce antibodies that recognise the SAME ANTIGEN with INCREASED AFFINITY:
Point mutations made in heavy/light chain gene segments that encode for the variable antigen binding sites of antibodies
Functions of cytotoxic T cells?
Fas ligand mediated killing
Kill infected host cells - effector cytotoxic T cells exit lymph node, migrate to sites of infection, recognise and kill infected tissue cells in an antigen-specific manner:
CTL recognises and binds virus-infected cell peptide, presented by MHC-I
CTL programs target for death, inducing DNA fragmentation
CTL migrates to new target
Target cell dies by apoptosis
Proteins in lytic granules of cytotoxic T cell?
Perforin - polymerises to form a pore in target membrane
Granzymes - serine proteases, which acitvate apoptosis once in the cytoplasm of the target cell
Granulysin - induces apoptosis
Describe immunological memory
Once adaptive immune system has recognised and responded to a specific antigen, it exhibits life-long immunity to this antigen
Cells of immunological memory?
Memory Th cells
Memory Tc cells
Memory B cells
Long-lived plasma cells
What are memory cells?
Memory cells are small, long-lived re-circulating antigen-specific cells that are primed and ready to respond upon re-encounter with same antigen
High numbers and have a lower threshold for activation
Memory B cells have already undergone class switching and somatic hypermutation
