Lymphocytes Flashcards
What is adaptive immunity?
An adaptive immune response is initiated when a pathogen overwhelms innate defence mechanisms.
As the pathogen replicates and antigen accumulates, sensor cells of the innate immune system become activated to trigger the adaptive immune response.
Expansion of antigen-specific lymphocytes that target the pathogen specifically and to the formation of memory cells that provide long-lasting specific immunity.
What major event triggers the adaptive immune system activation?
B or T lymphocytes encounter antigens (corresponding to a pathogen) for which their receptors have specific reactivity]
3 hallmarks of adaptive immune response?
Creates immunological memory => more rapid and heightened immune response upon re-exposure to same pathogen
Highly specific; With the ability to recognise “non-self” antigens in the presence of “self”, during the process ofantigen presentation (possible through the highly variable antigen receptors)
Long-lasting protection
What is the problem with specificity of antibodies?
We are exposed to a large amount of different microbes and hence antigens – no predicting which ones.
The adaptive immune system is highly specific but needs to respond to them all.
To do so there must be a very large pool of cells with specific receptors (large repertoire of lymphocytes receptors) that can recognise these huge array of antigens.
How is diversity generated in the adaptive immune response?
Immunoglobulin gene rearrangement -
Each BCR receptor chain (kappa, lambda and heavy chain genes) is encoded by separate multigene families/clusters on different chromosomes
During B cell maturation (in bone marrow) these gene segments are rearranged and brought together
Note that the T-cell receptor gene segments are arranged in a similar pattern to immunoglobulin gene segments and are rearranged by the same enzymes (occurs in the thymus).
Can you think of any problems with this process of gene rearrangement?
With so many different antigen receptors being generated randomly during the lifetime of an individual, there is a possibility that some receptors might react against an individual’s own self antigens.
Which cells are lymphocytes and what process are they produced by?
Lymphopoiesis -
B cells
T cells
Natural killer cells
What are the two primary cells of the immune response and which response are they part of?
T-cells - cell mediated response
B-cells _ humoral/antibody response
What are the differences between T-cells and B-cells?
T-cells mature in thymus and B cells in bone marrow
T-cells inside lymph nodes- peyers patches, B cells are outside
B cells have immunoglobulin receptors, T cells have CD receptors
What are the three types of T cells and what are their functions?
Natural killer/cytotoxic - kills cells infected with viruses or other intracellular pathogens bearing the antigen
Helper T cells - Provide signals often in the form of specific cytokines which activate the function of other cells such as B-cell production/macrophage killing
Regulatory T cells - supress activity of other lymphocytes and help limit possible damage
Which molecule distinguishes T helper and T killer cells?
CD4 – helper
CD8 - killer
What do Th1 cells do?
B cell class switching, macrophages and inflammation
produce cytokines IFN-γ (+ Tumour Necrosis Factor + Interleukin 12)
Extra explanation: Promote B cell class switching that favours production of IgG antibodies Help to eradicate infections by microbes that can survive or replicate within macrophages (evade the intracellular killing mechanisms/fusing with lysosomes recognises antigens on infected macrophages activates the macrophage further through the release of IFN-γ, enabling them to destroy intracellular microorganisms more efficiently
What do T-helper cells produce?
Cytokines
What do Th2 cells do?
allergies and worm
production of IL-4, IL-5, and IL-13.
extra:
control infections by extracellular parasites, particularly helminths, by promoting responses mediated by eosinophils, mast cells, and IgE
required for class switching of B cells to produce IgE, the primary role of which is to fight parasitic infections.
IgE is also the antibody responsible for allergies – so pro-allergic
What does Th17 do?
neutrophils, bacteria and fungi
TH17 cells produce the cytokines IL-17, IL23, IL-6
Induced in response to extracellular bacteria and fungi, and amplify neutrophilic responses that help to clear such pathogens
What do Tfh cells do?
B cell support
Produce IL-21
T follicular helper (TFH) cells interact with B cells to regulate antibody production during the immune response
What do Tr regs do?
NO IMMUNE RESPONSE
Produce IL-10, TGF-ß
T regs are anti-inflammatory
Limit the immune response/supress T cell responses
What are the 5 types of CD4 T-cells?
Th1 - B cell class switching, macrophages and inflammation
Th2- Parasitic/allergic
Th17 - bacteria, virus and fungi
Tfh - B cell support
Tregs - no immune response
How do T helper cells contribute to B cell activation?
Effector T cells express surface molecules and cytokines that help the B cell to proliferate and to differentiate into antibody-secreting cells (plasma cells) and into memory B cells
Fine tuning of antibody responses to increase the affinity of the antibody for the antigen and the switching to most immunoglobulin classes other than IgM depend on the interaction of antigen-stimulated B cells with helper T cells.
How do T helper cells contribute to B cell activation?
Effector T cells express surface molecules and cytokines that help the B cell to proliferate and to differentiate into antibody-secreting cells (plasma cells) and into memory B cells
Fine tuning of antibody responses to increase the affinity of the antibody for the antigen and the switching to most immunoglobulin classes other than IgM depend on the interaction of antigen-stimulated B cells with helper T cells.
What is an epitope?
Region of antigen that the receptor binds to
Describe clonal expansion.
Each lymphocyte bears a single, unique receptor
Interaction between a foreign molecules and that receptor leads to activation and expansion of the same cell
Differentiated effector cells of that lineage will bear the same receptor
How to cytotoxic T cells cause cell death?
programmed cell death = apoptosis
Apoptosis is characterized by fragmentation of nuclear DNA
CD8s store perforin, granzymes, granulysin in cytotoxic granules released after target recognition
Perforin molecules polymerise, form pores
How do T cells recognize pathogens?
An individual antigen receptor or antibody recognizes a small portion of the antigen’s molecular structure, and the part recognized is known as an antigenic determinant or epitope.
Epitope = region of pathogenic protein the T cell is specialized for
What makes up the epitope recognized by T cell receptors?
Combination of part of antigenic protein and MHCII
What role does the MHC play in activation of T cells?
T cells detect the presence of an intracellular pathogen because the infected cells/professional APC antigen presenting cells display peptide fragments of the pathogen’s proteins on their surface.
These foreign peptides are delivered to the cell surface by specialized host-cell glycoproteins - the Major Histocompatibility Complex (MHC) molecules.
What is the role of the major histocompatibility complex?
- major role in defining self and non-self antigens
- Presents antigens to T cells
- Critical in surgery and donor matching
What are the two types of MHC molecules?
MHC1 - All nucleated cells, screening mechanism
MHC2 - Professional antigen presenting cell
How does antigen presenting work?
MHCI glycoproteins detect foreign peptides and tell dendritic cells which express more MHCII - professional APCs
T cells then detect the presence of an intracellular pathogen because the infected cells/professional APC display peptide fragments of the pathogen’s proteins on their surface
What is the difference between MHCI and MHCII?
MHCI binds to CD8 T-cells and are present on all nucleated cells
MHCII bind to CD4 T-cells and are only found on professional antigen presenting cells - dendritic cells, B lymphocytes and macrophages
How does MHC interact with T cell receptors?
MHCI presented by the target cell (Intracellular pathogen or antigen) and is presented to CD8 cells
MHCII presented by the antigen presenting cell to the CD4 cells
How do CD8 cytotoxic T lymphocyte scan and effect cells?
Nearly all somatic cells (except red blood cells) express MHC class I molecules.
CD8 cytotoxic T cell is primarily responsible for pathogen surveillance and cytolysis of somatic cells.
Antigens derived from viruses/bacteria multiplying inside the cytosol of an infected cell are displayed on the cell’s surface by MHC I, where they are recognized by the antigen receptors of cytotoxic T cells.
The CD8 cell scans cells, looking for MHC showing non-self; normally, in uninfected cells, MHC I molecules show self peptides.
How do CD4 T cells recognise and affect pathogens?
CD4 T cells recognise antigen presented by MHC class II proteins, which are expressed by the predominant antigen-presenting cells of the immune system: dendritic cells, macrophages, and B cells.
Thus CD4 T cells tend to recognize antigens taken up by phagocytosis from the extracellular environment (exogenous antigens)
CD4 T cells differentiate into several subsets of effector T cells that orchestrate different immune functions.
How is MHC expressed?
Co-dominant (maternla and paternal genes are both expressed)
therefore each person can have up to 6 of each gene if completely heterozygous
More than 17,000 MHC variants
How is MHC expressed?
Co-dominant (maternla and paternal genes are both expressed)
therefore each person can have up to 6 of each gene if completely heterozygous
More than 17,000 MHC variants
What are two properties of the MHC which makes it difficult for pathogens to evade the response?
MHC is polygenic = it contains several different MHC class I and MHC class II genes, so that every individual possesses a set of MHC molecules with different ranges of peptide-binding specificities.
MHC is highly polymorphic = that is, there are multiple variants, or alleles, of each gene within the population as a whole.
What are B cell receptors?
BCR - surface bound antibody
This encodes the antibody that the b-cell will make
What are the three core protective roles of antibodies?
Neutralisation
Opsonisation
Complement activation
Name the 2 pathways that activate B cells?
Antigen - thymus independent
T cells - thymus dependent
How does the thymus dependent pathway work?
The membrane bound BCR recognises (thymus-dependent) antigen
The receptor-bound antigen is internalised and degraded into peptides
Peptides associate with “self” molecules (MHC class II) and is expressed at the cell surface
This complex is recognised by matched CD4 T helper cell
B cell activated -
T cell will secrete cytokines which may switch the BCR AB class (in proliferating activated B cells) depending on the response needed.(class switched, mature plasma/memory cell)
How does the thymus independent pathway work?
Some microbial constituents can induce antibody production in the absence of helper T cells
These microbial antigens are known as thymus-independent antigens
Such antigens are typically highly repetitive molecules, such as the polysaccharides of bacterial cell walls, and can cross-link the BCR on B cells.
A second signal triggered from direct recognition of a common microbial constituent such as LPS (activating TLR signalling in the B cell)
Only IgM; no memory
What happens once B cells are activated?
Clonal selection - selection of specific B-cell which will produce the correct antibody
Clonal expansion - foreign antigen interacts with the receptor on a B-cell, activated and starts to divide.
It gives rise to a clone of identical progeny, all of whose receptors bind the same antigen
Name the five types of antibodies.
IgG IgM IgA IgD IgE
What is IgG?
Best kind of antibody
highest opsonisation and neutralisation activities
Four subclasses 1-4
What is IgM?
First produced, upon antigen invasion
Not as specific and low affinity
What is IgA?
What is IgD?
A- Expressed in mucosal tissues
D- unknown function
What is IgE involved in?
Allergy
Where do B cells come from?
Derived from stem cells in bone marrow - generation and maturation occurs in the bone marrow in the absence of antigen
Migrate into the circulation and into lymphoid tissues
Describe the structure of the IgG antibody
Consists of two heavy chains and two light chains
The two heavy chains are linked to each other by disulfide bonds, and each heavy chain is linked to a light chain by a disulfide bond.
Two identical antigen-binding sites (bind simultaneously to two identical antigens on a surface)
Two types of light chains, lambda (λ) and kappa (κ), are found in antibodies (never one of each in an antibody)
What is complement activation?
antibodies coat a bacterial cell; C regions form a platform that more efficiently activate complement proteins (covalent deposition on bacterial surface) => complement proteins on the bacterium can be recognized by complement receptors on phagocytes; this stimulates the phagocytes to ingest and destroy the bacterium.
What is opnsonisation?
antibodies coat bacterium to better enable a phagocytic cell such as a macrophage or a neutrophil to ingest and destroy it (Fc receptors on phagocytic cell binds to C region)
What is neutralisation?
antibodies bind to viruses/bacterial toxins and thereby block their access to cells that they might infect or destroy
