Lymphocytes Flashcards
What is Adaptive Immunity?
An immune response which is tailored to a specific pathogen - involves the expansion of antigen -specific lymphocytes which target the pathogen specifically and involve the formation of memory cells which provide longer lasting immunity
When is an adaptive immune response generated?
Once the pathogen overwhelms innate defense mechanisms
What major event occurs in the peripheral lymphoid organs/tissues to initiate the adaptive immune response
B or T lymphocytes encounter antigens for which their receptors have specific reactivity to
What is an antigen?
A molecules which is recognized by the highly specialized lymphocyte receptors, which act to induce an adaptive immune response
What are the two hallmarks of the adaptive immune response?
Highly specific and provide lasting immunity
How is diversity generated in the adaptive immune response?
Immunoglobulin gene rearrangement - each BCR chain is encoded by separate multi gene clusters on different chromosome, and during B cell maturation, these gene segments are rearranged and brought together
What are the chains of the BCR receptor?
Kappa, lambda and heavy chain
Where does B cell Maturation occur?
In the bone marrow
What are some problems with the random process of gene reassortment to generate the high number of BCRs we need.
Autoimmunity - producing BCRs and TCRs that complement your own self antigens
What is immunological memory?
Where memory lymphocytes exist in the blood that are able to recognize and bind to the same antigen upon subsequent infections and therefore induce an immune response
What are characteristics of a a secondary immune response?
Faster and must larger response
What are the two primary cells involved in the adaptive immune response and which response are they involved in?
T cells = Cell Mediated Reponse
B cells = Humoral / Antibody Reponse
What are the differences between B cells and T cells?
T cells mature in thymus, B cells in bone marrow
T cells have CD4 and CD8 receptors, B cells have different one
T cells do not produce antibodies, B cells do
B cells need to be activated by T cells to function
B cells tend to stay outside of lymph nodes eg in Peyers Patches, T cells inside lymph nodes
What are the three kinds of T cells?
Regulatory, helper, killer
What happens when an antigen binds to a TCR?
The cell proliferates and differentiates into one of three functional types of effector T cells: Cytotoxic (killer), helper or regulatory
What are cytotoxic T cells?
The kill other cells that are infected with viruses or intracellular pathogens that bear the specific antigen
What do helper T cells do?
They provide signals, normally in the forms of cytokines which activate the functions of other cells, like B cells to produce antibodies w
What do regulatory T cells do?
They suppress the activity of other Lymphocytes and help to limit the possible damage due to immune response
Which CD do T helper cells have?
CD 4
Which CD do T Killer Cells have?
CD 8
What are T Helper Cell 1 (Th1) classified by?
Production of Interferon-gamma, Tumour Necrosis Factor, Interleukin 12
What are Th1 involves in?
B cell class switching, macrophages and inflammation
What are T Help Cell 2 characterized by?
Production of Interleukin 4, 5 and 13
What do Th2 do?
are involved in the B cell class switching to produce IgE for allergic reactions and parasitic infections (ALLERGY AND WORMS)
What are Th17 involved in?
Neutrophil responses which help to clear bacteria and fungi
What do TfH do? t follicular helper cell
B cell support
What do Tregs produce?
IL-10
What are Tregs for?
Anti-inflammatory to limit the immune Reponse
In what way do T helper cells help B cells?
They have surface proteins and secrete cytokines which help the B cells proliferate into antibody- secreting plasma cells and memory B cells
Help finetune the antibody response to increase the affinity of the antibody to the antigen through immunoglobulin class switching
How do CD 8 cytotoxic T cells kill pathogens / cells infected with pathogens?
Infected cell will present viral antigen on MHC1
CD 8 t killer cell detects these non self MHC1 molecules and attacks
Release chemicals like perforin and granzymes
These polymerase the cell membrane, creating pores which allows molecules in and out the cell, disturbing the osmolarity and therefore killing the cell
What do cytotoxic T cells release when they want to kill an infected cell?
Performing and granzymes
What does granzymes cause and how to they enter cells following Cytotoxic T cell recognizing an MHC1
Granzymes causes apoptosis and enter into the infected cell through pore / channels created by perforin
What two regions is the TCR made up of?
Variable region (top part) and constant region (bottom region)
What is an epitope
The part of the antigen which the antibody binds to
What makes up the epitope which the T cell receptors recognize?
The MHC
What are MHC molecules?
Glycoproteins which display peptide fragments of the pathogens proteins (antigens) on their surface
What is the difference between MHC 1 and MHC 2?
MHC 1 is present in every cell and presents to CD 8 cells, MHC 2 only present in APC’s and presents to CD 4
What is the structure of MHC 1?
Has a single variable alpha chain and a common beta-microglobulin
What is the structure of MHC 2?
Has two chains, alpha and beta
What are the “professional” antigen presenting cells which have MHC 2?
Dendritic cells, B lymphocytes and macrophages
Which MHC will interact with TCR?
MHC 2
How is MHC expressed?
Co-dominant
What is meant by the fact that MHC is polygenic?
Contains several different MHC Class 1 and MHC class 2 genes so that every individual possesses a set of MHC molecules with different ranges of peptide binding specificities
What is meant by the fact that MHC is highly polymorphic?
There are multiple variants or alleles of each gene within the population
What is a BCR?
A surface bound Antibody
What does the BCR do?
It encodes the antibody which the B cell will eventually make
What do B cell produce?
Antibody
What two pathways activate B cells?
Thymus defendant (T cells) and thymus independent (antigens)
Explain the thymus dependent pathway of B cell activation?
BCR recognizes antigen
The antigen is then internalized and degraded
Peptides bind to MHC 2 which are expressed at the cell surface
This complex is recognized by CD4 T helper cells
B cells are activated
What can an activated B cell go and do?
Mature into a plasma cell which secretes antibodies, or class switch
Describe the activation of B cells via the thymus independent pathway?
Some microbial constituents can induce antibody production without T helper cells
What are thymus independent antigens and how do they work to induce antibody production?
They are antigens which cross link the BCR on B cells
Only leads to IgM and non memory
What type of molecules are thymus independent antigens?
Highly repetitive molecules eg polysaccharides
What happens after B cells are activated?
Clonal expansion and clonal selection
What is clonal expansion of lymphocytes?
Once a B cell has been activated, it is triggered to divide, giving rise to a clone of identical progeny (also has same MHC). This allows antigen specificity to be maintained as the progeny differentiate into effector cells
What are the five classes of antibody?
IgG, IgA, IgM, IgE, IgD
Which antibody type has the highest affinity?
IgG
Which antibody type is produced first?
IgM
Which antibody type is produced in allergic disease?
IgE
Describe the structure of IgG antibodies?
Made up of two heavy chains and two light chains
The V part at the top is the Fab region, the bottom part is the Fc region
The heavy chains are linked together by disulfide bridges
Has two identical antigen-binding sites
What part of the antibody determines its antigen-binding specificity?
The variable domains of the heavy and light chains
What are the three core functions of antibodies?
- Neutralization
- Opsonization
- Complement activation
Describe the process of antibody neutralization?
Antibodies bind to viruses/bacterial toxins, so they cannot go and damage other cells
Describe the process of opsonization?
Antibodies coat a bacterium to better enable a phagocytic cell to ingest and destroy it
How do antibody opsonised bacterium bind to phagocytic cells?
Fc receptors on ohagocytic cell binds to Fc region of antibody
Describe the process of complement activation?
Complement proteins on bacterium can be recognized by complement receptors on phagocytes which allows for stimulated phagocytosis and the bacterium to be destroyed
Increasing the numbers of what T helper cell will help with an autoimmune disorder?
Treg cells
What is VDJ rearrangement ?
When the many copies of thr V D AND J genes are randomly rearranged so that a variety of TCRs and BCRs can be generated - allows for a large immune cell repertoire
