Lecture 8: Adaptive Immunity and Immune Recognition Flashcards
What are the general features of adaptive immunity?
evolutionarily relatively new
slow, but highly specific response directed against antigen
forms immunological memory = results in a rapid 2˚ response
What are the soluble factors of adaptive immunity?
antibodies
What are the cell-associated factors of adaptive immunity?
B cell receptors, T cell receptors and MHC molecules
What are the specialised cells of adaptive immunity?
B cells (B1/B2) T cells (Th1, Th2, Th17, Tfh, Th17, Treg and cytotoxic T cells) semi-invariant T cells (NKT, MAIT), ɣσ T cells
What is the priming phase of adaptive immunity?
first time the adaptive immune system encounters an antigen
What is the effector phase of adaptive immunity?
activated adaptive cells differentiate into effector cells to fight infection and eliminate pathogen
What is the contraction phase of adaptive immunity?
most effector cells die following clearance of the pathogen
What is the memory phase of adaptive immunity?
some long lived memory cells remain to ensure that the immune system can respond faster and stronger upon re- encountering that pathogen
What makes adaptive immunity highly specific?
highly diverse antigenic receptors formed by random gene rearrangement
What makes adaptive immunity respond slower?
this is because major effector functions include antibody production, cytokine secretion and cytotoxicity, some of which take days
What is the outcome of the adaptive immune response?
removal/neutralisation of the pathogen and resolution of infection and memory
What ability does memory grant the adaptive immune system?
the ability to respond stronger and faster on second encounter of the same pathogen
Which lineage comprises cells of the adaptive immune system?
the lymphoid lineage
What are B cells derived from and where do they mature?
from lymphoid progenitor
mature in bone marrow
How many BCRs does each B cell have?
around 100,000 each with the same specificity
What does BCR engagement lead to?
proliferation and transition into plasma cells (‘effector B cells’)
What do plasma cells secrete?
soluble BCR (= antibodies) that have same specificity as surface receptor
What is humoral immunity?
B cell-mediated
What are T cells derived from and where do they mature?
from lymphoid progenitor in bone marrow
develop and become educated in the thymus
What co-receptors do T cells express?
either CD4 (MHC class II restricted) or CD8 (MHC class I restricted)
How do T cells recognise antigens?
via distinct cell surface receptors (α/β T cell receptor) with high degree of specificity
requires processing of antigen by the APC and presentation on MHC
What happens after T cells are activated?
they can leave the blood and survey the periphery: accumulating where they are needed
What is the role of CD4+ Helper T cells?
regulators of immune responses
What is the role of CD8+ Cytotoxic T cells?
cytotoxic (perforin, granzymes)
What is cell-mediated immunity?
T cell-mediated
What determines whether a naive CD4+ T cell will become a Tfh, Th2, Th1, Th17 or iTreg?
the cytokines released during activation
What does each lymphocyte carry?
a single and unique specificity for antigen
What does diversity in lymphocyte specificity provide us with?
the greatest opportunity to fight infections throughout our lifetime - therefore it is important to remember that these cells are present (in low numbers) prior to an infection
How does clonal expansion occur?
at first there are multiple lymphocytes clones with different specificities -> deletion of self-reactive clones (clonal deletion) -> clonal selection -> clonal expansion
When it’s a one in a million chance, how does one lonely antigen-specific lymphocyte meet its perfect antigenic match?
‘speed dating’ in specialised
areas/hubs in secondary lymphoid organs
anatomical structure makes the impossible a reality
What are the rules of lymphocyte engagement?
naïve lymphocytes recirculate through lymph node/spleen via blood
antigens/pathogens are funnelled from the periphery into the local lymph nodes
How do naïve lymphocytes recirculate through lymph node/spleen via blood?
enter lymph node via blood vessels: lymphocytes squeeze through the walls of specialised blood vessels
How are antigens/pathogens funnelled from the periphery into the local lymph nodes?
extracellular fluid (lymph) flows from peripheral tissue and is collected by lymphatic vessels and delivered to the draining lymph node activated dendritic cells migrate to lymph node and presents antigen to T cells
What are the features of antigens?
can be simple or complex
any substance that may be specifically bound by immunoglobulin or T cell receptor
What is an epitope?
an antigenic determinant
part of the antigen that is recognised
each lymphocyte is specific for one epitope
What is an immunogen?
substance that induces a specific immune response
all immunogens are antigens
Which factors affect immunogenicity?
foreignness, high MW, chemical complexity, degradability and also genetic variation of individual, dosage of immunogen, route of administration
Are most proteins strongly immunogenic?
yes and protein carriers can increase immunogenicity of other molecules
What are haptens?
small organic moiety attachable to larger structure
target of antibody response (contains Ab determinant)
non-immunogenic
What are carriers?
usually protein or polypeptide (e.g. ovalbumin)
required for adaptive immune response
minimum size required to cross-link surface BCRs
contains T cell determinants
In order to generate an antibody response to the hapten, what must hapten? lol
hapten must be covalently linked to the carrier
How many molecules does the innate immune system recognise vs the adaptive immune system?
innate: ~1000
adaptive: >10^7
How many types of receptors are there in the innate immune system vs the adaptive immune system?
innate: <100 types, each invariant
adaptive: 2 types (Ig, TCR)
How are receptors distributed in the innate immune system vs the adaptive immune system?
innate: non-clonal
adaptive: clonal
How would receptors be expressed within a population of lymphocytes before encountering an antigen?
single unique receptors would be expressed on each lymphocyte
How do T cell receptors recognise antigen?
in the form of a complex of a foreign peptide bound to an MHC molecule
What must happen in order for peptides to be presented?
must be processed
What is required to make an effective response to the peptide antigen?
the CD4 and CD8 cell-surface proteins of T cells must directly contact MHC molecules
What can immunoglobulins recognise?
all manner of shapes and chemical compositions because they are highly specific, discriminating between small differences in protein sequences and chemical compositions
The majority (~90%) of B-cell receptor epitopes are what?
conformational (discontinuous)
How do immunoglobulins bind to antigens?
bind to conformational shapes on the surfaces of antigens using a variety of non-covalent forces
also influenced by steric constraints
