*Immunology 3 (lectures 5 and 6) Flashcards
What is an antigen?
An substance which can cause an adaptive immune response by activating B cells and T cells
Where are T cells and B cells found?
Constantly circulate through the blood, lymph and secondary lymphoid tissues
Inactive until meet an antigen
What is the purpose of B cells?
Key role in defence against intracellular pathogens via production of antibodies
Purpose of T cells?
Key role in defence against intracellular pathogens (viruses, mycobacteria)
What are the 2 different types of T cells?
Helper T cells
Cytotoxic T cells
What is the role of helper T cells?
Key regulators of the entire immune system
What is the role of cytotoxic T cells?
kill virally infected body cells
How do T cells recognise antigens?
Through their T cell antigen receptor
What is the T cel antigen in terms of proteins?
What chains does it have?
Membrane-Bound protein heterodimer
1 X Alpha chain
1 X beta chain
How does B cells recognise antigens?
Through their b cell antigen receptor
What are B cell antigen receptors?
What chains does this have?
Membrane bound antibody (IgM or IgD)
2 X light chains
2 X heavy chains
What is another name for antibodies?
Immunoglobulins
What are antibodies?
proteins that are produced by B cells in response to an antigen and which bind specifically to that particular antigen
What are the 2 different forms of antibodies?
Those expressed on the surface of B cells
Those secreted as soluble proteins in extracellular fluids
What type of pathogens do antibodies provide defence against?
Extracellular pathogens (most bacteria, viruses and toxins)
What type of regions do both the heavy and light chains have on immunoglobulins?
Constant regions
Variable regions
Does the constant region or the variable region form the antigen binding site?
Variable region
What are the 5 different types of antibodies that exist?
What makes them different?
IgM IgG IgA IgE IgD Different heavy chain constant regions
Heavy chain constant region of IgM?
μ heavy chain
Heavy chain constant region of IgG?
γ heavy chain
Heavy chain constant region of IgA?
α heavy chain
Heavy chain constant region of IgE?
ε heavy chain
Heavy chain constant region of IgD?
δ heavy chain
What is the epitope?
the part of an antigen molecule to which an antibody attaches itself
What are antibody heavy and light chain proteins encoded for by?
Segmented genes in the germ-line genome of haematopoietic stem cells
What happens to gene segments as individual B cells develop?
They randomly rearrange (this also happens in TCR alpha and beta chains in developing T cells)
How is there more antibodies in the human body that there are entire genes in the human genome?
There is radom rearrangement of the segments of genes that code for antibody heavy and light chain proteins in individual developing B cells (a similar process also occurs in developing T cells)
What type of lymphoid tissues do adaptive immune responses occur in?
Secondary lymphoid tissues
What do mature antigen-specific T cells and B cells constantly re-circulate between?
Different primary lymphoid tissues, the blood and lymphatic vessels
Where are mature dendritic cells, pathogens, antigens, debris, etc. trapped?
In secondary lymphoid tissues (lymph in lymph nodes, blood in spleen)
What are the 2 different zones within lymph nodes?
T cell zone
B cell zone (around the edges)
What happens if after several days of being in the lymph node, T cells and B cells don’t encounter their specific antigen?
They return to the blood system
How do antigens from a pathogen enter a lymph node?
Particles and antigens derived from pathogens are release by phagocytes
The pathogen also releases inflammatory TNF alpha that stimulates immature tissue-resident dendritic cells to express B7
Dendritic cells phagocytose these (by joining via PPR and PAMP)
Dendritic cells digests pathogen-derived protein and display small peptides on surface in complex with MHC proteins
Pathogen derived particles, antigens and mature dendritic cells travel to local draining lymph nodes
What do stromal cells do to opsonised antigens in the B cell zone?
Trap them
How many signals does B cell activation require?
2
What are the 2 signals that B cells must receive to be activated by a protein antigen?
BCR + antigen
T cell help
What are the 2 signals that B cells must receive to be activated by any antigen?
BCR + antigen
PRR + PAMP
What are the 2 signals that B cells must receive to be activated by antigens with repetitive antigenic epitopes?
Multiple
BCRs + antigens engaged
What are the only peptide antigens that T cells can recognise?
Those presented by MHC
What do MHC proteins do?
Display peptide antigens to T cells
What are MHC proteins also referred to as?
Human Leucocyte antigens (Human leucocyte antigens)
What are the 2 classes of MHC proteins?
Class I MHC
Class II MHC
What is class I MHC expressed on? What does it do?
All nucleated cells
Presents peptide antigens to cyctotoxic T cells
What is Class II MHC expressed on?
What does it do?
Only expressed on professional antigen presenting cells (dendritic cells, macrophages and B cells)
Present peptide antigens to helper T cells
How many signals does T cell activation require?
2
What are the 2 signals required for B cell activation?
Signal 1 = MHC peptide and TCR
Signal 2 = B7 and CD28
What happens once B cells are activated?
They undergo clinical expansion and differentiate into memory B cells and plasma effector B cells
What type of antibody is produced by B cells which are activated by protein antigen: BCR and PRR:PAMP?
Are memory cells produced
Low affinity, antigen-specific IgM
No memory cells
What type of antibody is produced by B cells which are activated by protein antigen: BCR and T helper cells?
Are memory cells produced
High affinity, antigen-specific antibodies (IgM initially and then all types)
Memory cells are produced
What is the most abundant Ig in plasma?
IgG
How amen subtypes of IgG are there?
4
What type of Ig is actively transported across the placenta?
IgG
What is the second most abundant Ig type?
IgA
Where is IgA found? (4)
Monomeric form = blood
Dimeric form = breast milk, saliva, tears, mucosal secretions
How do mothers provide protective antibodies to their young?
IgG through the placenta (levels decrease when the baby is born = transiently low IgG between 3 months and a year when the baby is still making own)
Dimeric IgA through breast milk
What is the first Ig to be produced during an immune response?
IgM (present only in plasma/ secretion)
Where is IgD found?
Extremely low levels in blood
Where is IgE found?
What is it produced in response to?
Extremely low levels normally
Produced in response to parasitic infections and allergic responses
What is the constant region of the heavy chains of an antibody called?
Fc
What are the 2 purposes of antibodies?
Binding to antigens
Clearance mechanisms mediated by interaction of Fc region with effector molecules (complement, Fc receptors)
What does the binding of high affinity neutralising antibodies to viruses prevent?
The virus infecting host cells
Microbial toxins from disrupting normal cell function
What complement pathway can antibodies activate?
The classical complement pathway
What 3 molecules can act as opsonins?
C3b
CRP
Antibodies
How do bacteria opsonised by antibodies bind to phagocytes?
Through Fc receptors that bind to the constant region of the Ig
How can antibody binding cause NK cells to kill target cells
Antibody-dependent Cell-mediated Cytotoxicity
How can IgE lead to allergic responses?
IgE binds an allergen and then binds to a mast cell via an Fc receptor
This causes degranulation
What is the name of helper T cells when they are resting and not effector cells?
CD4+ cells
What is the name of cytotoxic T cells when they are resting and not effector cells?
CD8+ cells
What 2 things cause CD4+ to become Th?
Peptide
MHC II
What 2 things cause CD8+ cells to become Tc?
Peptide
MHC I
What is the purpose of T helper cells?
To help stimulate other immune cells (CD8+, macrophages, B cells through cytokines and direct cell contact)
How do Th cells stimulate CD8+?
Through IL-2
How do effector Th cells help macrophages?
Th cells migrate from lymph node into sites of infection/ inflammation
The cells are re-activated by macrophages in an antigen-specific manner
The cells express co-stimulatory molecules and hyper-activate macrophages enhancing their killing activities and pro-inflammatory responses (through IFNgamma)
How do effector Th cells help B cells?
Protein antigen bound to BCR is internalised by the B cell
Antigen is degraded and peptides are presented on the B cell surface in complex with MHC-IIEffector Th cells move into B cell zone of the 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 the B cell to proliferate and survive (via CD40L : CD40 interactions)
Effector Th cells secrete cytokines that further activate the B cell and stimulate the Germinal Centre response
What is the germinal centre response?
B cell proliferation
Antibody heavy chain switching
Generation of high affinity antibodies
Differentiation into Plasma cells and Memory B cells
What happens to effector cytotoxic T cells?
they exit lymph nodes, migrate to sites of infection, recognise and kill infected tissue cells in an antigen specific manner (target cells die by apoptosis)
What is immunological memory?
What type of memory cells are produced?
Once the adaptive immune system has recognised and responded to a specific antigen, it exhibits life-long immunity to this antigen Memory Th cells Memory Tc cells Memory B cells Long-lived plasma cells
