adaptive immunity Flashcards
what is adaptive immunity?
specific and acquired
what are the two types of responses within adaptive immunity?
- cell-mediated responses
- antibody (humoral responses)
what drives cell-mediated immunity?
T cells
what does cell-mediated immunity involve?
the activation of macrophages, natural killer cells and antigen-specific helper and cytotoxic T-lymphocytes
what do B cells produce and what is their function?
antibodies and drive humoral immunity
what is immunological memory?
each pathogen is remembered by a signature T cell and or B cell
when does adaptive immunity kick in?
4-7 days
why do you feel unwell for several days following infection with a microbe?
your body doesn’t recognise – e.g., until the adaptive immune response produces antibodies and T cells to mediate pathogen clearance.
why is the threshold level of antigen important?
the immune system does not need to mediate adaptive immunity if only a small amount of antigen present – e.g., innate immunity can clear the threat without help of adaptive immunity
what are the three main receptors of adaptive immunity?
- T cell receptors
- B cell receptors (immunoglobulins)
- major histocompatibility complex
what is the difference between innate and adaptive receptors?
Innate receptors (e.g., TLRs) don’t have potential to rearrange and change shape to recognize different antigens
Adaptive receptors (e.g., these three) can rearrange structure depending to gene expression of each protein subunit.
where are T cells derived?
bone marrow
where do T cells mature?
thymus
what do T cells give rise to?
cellular immunity
what is thymic education?
checkpoints in place however to ensure T cells only respond to foreign pathogens and not ‘self peptides’
what does CD8 co-receptor bind to?
MHC 1
what does CD4 co-receptor bind to?
MHC 2
what does CD3 co-receptor do?
involved in activation of both CD4+ and CD8+ T cells
what are the two different classes of T cell receptors?
alpha, beta chains
gamma, delta chains (around 5%)
what are alpha chains encoded by?
variable and joining
what are beta chains encoded by?
variable, joining and diversity
how are genes rearranged?
somatic recombination
what is somatic recombination driven by?
RAG (recombinase) enzymes
what are the two types of T cell selection in the thymus?
positive and negative
what do T cells interact with in the thymus?
thymic cortical epithelial cells
What occurs when there’s no recognition during positive selection?
apoptosis
what does too strong binding in negative selection of T cells result in?
recognition of self antigen- apoptosis
what % of T cell progenitors pass the checkpoints of thymic education?
less than 5%
what is required in thymic education for the T cell survival?
moderate affinity
what happens to positively and negatively selected CD4/CD8+ T cells with rearranged T cell receptors after they leave the thymus?
circulate in the blood/lymphatics
some residue in lymph nodes
what is the function of Th1 cells?
support cellular immunity
support macrophage function
source of interferon-y
what is the function of Th2 cells?
support humoral responses and allergic reactions
source of interleukin-5,5,6 (which instruct B cells to produce antibodies)
what is the function of Th17 cells?
suport innate immune responses
enhances clearance of extracellular bacteria and fungi
produces interleukin-17 and 22
what is the function of interleukin-17?
stimulates epithelial cells to produce antimicrobial peptides
what is the function of Tfh cells?
(T follicular helper cells)
found in secondary lymphoid organs in B cell zone
work with B cells for antibody production
what is the function of interleukin-21?
drives B cell proliferation – loss of T follicular helper cells in animal models leads to dysfunctional antibody production in germinal centre of lymph nodes
what is the function of Treg cells?
function in immune response
release inhibitory cytokines eg IL-10
inhibit T cell activation and dendritic cell activation
what is the function on CD8+ T cells?
Activation arises from interactions between MHCI and TCR
Induce host cells to undergo apoptosis (programmed cell death)
Produces enzymes such as granzyme/perforin
Perforin targets apoptotic signalling pathways
what are the five different types of immunoglobiulns produced by B cells?
IgG, IgE, IgD, IgM and IgA
what is the most prominent antibody in the human body?
IgG
how many subsets does IgG have?
four
what do both T and B cell receptors have?
constant and variable regions
what type of chains do B cell receptors have?
light and heavy
what is each B cell development stage defined by?
rearrangements of the immunoglobulin heavy and light chain genes
what do B cells do once in periphery?
migrate to secondary lymphoid organs
what rearrangements are involved in the heavy chain?
variable, diversity and joining
what rearrangements are involved in the light chain?
variable and joining
what do immunoglobulins IgM and IgD have in common?
receptors found on surfaces
what do B cells undergo in the bone marrow?
negative selection (no positive selection)
what happens if there is no reaction of a B cell with a self antigen?
leaves bone marrow into blood
what happens to B cells which react with self antigens?
retained in the bone marrow and removed (doesn’t enter blood)
what are the three main functions of antibodies in the human body?
Neutralisation
Opsonisation
Initiation of complement
what is opsonisation?
refers to coating of pathogens by antibodies or complement proteins
what are the antibody B cell receptors?
IgD and IgM (IgD is the main one)
classical pathway
what are the two ways in which B cells can be activated?
- with T cells
- wihtout T cells
what are antigens which require T cell help called?
Thymus- dependent antigens
what are antigens which dont require T cell help called?
Thymus- independent antigens
what does activation of naive B cells result in?
the rise of plasma cells
what are plasma cells?
antibody factories
T cel independent describes
isotype switching
a biological mechanism that changes a B cell’s production of immunoglobulin from one type to another
what is affinity?
strength of binding of single antibody to antigen
what is avidity?
ability of antibodies to form complexes
affinity and avitidy of antibodies
IgM higher avidity than IgE
IgG and IgA higher affinity than IgM
in lymphoid organs, what does cross talk between B and T cells lead to?
generation of both humoral and cellular immunity
what are germinal centres?
- hubs for T cell and b cell cross talking
- proliferation and differentiation
- somatic hypermutation
vaccination
what is immune tolerance?
Sometimes the immune system can become dysfunctional and in a state of immune unresponsiveness to a particular antigen or set of antigens
- an active response to a particular antigen – can happen in B cells and T cells
- when the immune system is dysfunctional and loses tolerance it can attack it’s own cells leading to autoimmune diseases
what are the two main types of tolerance?
Central – in the primary lymphoid organs (the thymus and bone-marrow)
Peripheral – occurs out with thymus and bone marrow
what prevents the activation of non eliminated self-reactive T cells?
peripheral tolerance
peripheral tolerance T cells
When self-reactive T cells escape into the periphery, peripheral tolerance ensures that they are deleted or become anergic (functionally unresponsive to antigen).
where does peripheral tolerance in B cells occur?
secondar lymphoid organs
anergic
what does a breach of tolerance to self antigens or commensal organisms do?
drives many autoimmune diseases
