4.5 Lymphocytes Flashcards
What does adaptive immunity involve?
Expansion of antigen-specific lymphocytes and production of memory cells for long 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 molecule which is recognized by the specialised lymphocyte receptors, which acts to induce an adaptive immune response
State 3 characteristics of the adaptive immune response
Has memory
Needs time to develop
Improves efficacy of innate immune response
How is antigen receptor diversity generated in the adaptive immune response?
Each BCR chain is coded for by multigene clusters on different chromosomes
During B cell maturation, these genes are brought together and rearranged in VDJ recombination
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 VDJ recombination to generate the high number of BCRs we need?
Autoimmunity – producing BCRs and TCRs that react with self-peptides
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 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
B cells – humoral
What are the differences between B cells and T cells? LAMAR
Location – B cells outside lymph nodes, T cells inside
Antibodies – B cells only
Maturation – B cells in bone marrow, T cells in thymus
Activation – T cells activate B cells
Receptors – T cells CD4 and CD8, B cells different
What are the three kinds of T cells?
Regulatory, helper, killer
What happens when an antigen binds to a TCR?
T cell proliferates and differentiates into T effector cells
Either killer, helper or regulatory
What are cytotoxic T cells?
They kill virus infected cells or intracellular pathogens that bear the specific antigen
What do helper T cells do?
Produce cytokines which activate functions of other cells
E.g. signals to B cells to produce antibodies
What do regulatory T cells do?
Suppress lymphocyte activity and limit immune response to reduce damage
Which CD do T helper cells have?
CD4
Which CD do T killer cells have?
CD8
What is the Th1 class of CD4 T helper cell?
Pro-inflammatory, boosts immune response
What is the Th2 class of CD4 T helper cell?
Pro-allergic, boosts multicellular response
What is the Th17 class of CD4 T helper cell?
Pro-inflammatory, controls bacterial or fungal infection
What is the Treg (Th0) class of CD4 T helper cell?
Anti-inflammatory, limits immune response
What is the Tfh class of CD4 T helper cell?
Pro-antibody
What does Th2 do specifically?
Involved in B cell class switching to IgE
For allergic reactions and parasitic infection
What does Th1 produce?
IL-1, 2, 3, 12
IFN-gamma
TNF-alpha
Which CD4 T helper cell class includes interleukins 4, 5 and 13?
Th2
Which class of CD4 T cells includes interleukins 6, 17 and 23?
Th17
Which class of CD4 T cells includes interleukin 21?
Tfh
In what way do T helper cells help B cells?
Surface proteins secrete cytokines so B cells proliferate into plasma and memory cells
Trigger immunoglobulin class switching to increase the antibody’s affinity to the antigen
How do CD8 cytotoxic T cells kill pathogens or infected cells?
Infected cells display viral peptides on MHC I
CD8 recognises non-self MHC, releases contents of granules
Perforin creates pores in membrane, granzymes trigger cascade leading to cell death
What do cytotoxic T cells release when they want to kill an infected cell?
Perforin, granzymes, granulysin
What does granzymes cause and how do they enter cells?
Cause apoptosis
Enter through pores created by perforin
What two regions is the TCR made up of?
Variable region (top part)
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 bind and display pathogen peptide fragments on APCs for T cell recognition
How do MHC I and MHC II differ?
MHC I processes extracellular pathogens in the cytosol and present to CD8
MHC II processes intracellular pathogens in endosomes and present to CD4
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 cells are MHC I and MHC II present on?
MHC I – all nucleated cells
MHC II – dendritic cells, B cells, macrophages
Which MHC will interact with TCR?
MHC II
What gene codes for MHC?
HLA gene
How is MHC expressed?
Co-dominant
What is meant by the fact that MHC is polygenic?
MHC contains 3 class I and 3 class II loci
Thus everyone has MHC molecules with different 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 two pathways activate B cells?
Thymus dependent – T cells
Thymus independent – antigens
Explain the thymus dependent pathway of B cell activation?
BCR recognises antigen
Antigen internalised and degraded into peptides
Peptides displayed on MHC II, complex recognised by CD4 T cells
Tfh produces cytokines and co-stimulatory markers, activating B cells
Describe the activation of B cells via the thymus independent pathway?
Thymus independent antigens directly activate B cells
Second signal is sent by PAMPs (e.g. LPS)
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 IgM antibodies are produced and no memory cells
What type of molecules are thymus independent antigens?
Highly repetitive molecules e.g. polysaccharides
What happens after B cells are activated?
Clonal expansion and clonal selection
What is clonal expansion of lymphocytes?
Activated B cells divide and give rise to clones with identical progeny and MHC
This maintains antigen specificity as the progeny differentiate into effector cells
Which antibody type has the highest affinity and is most abundant?
IgG
Which antibody type is produced first?
IgM
Which antibody type is produced in allergic disease?
IgE
Describe the structure and function of IgG antibodies
Monomer
Neutralisation, opsonisation, precipitation
Pass through placenta to give baby passive immunity
Describe the structure of IgA antibodies and where they are found
Dimer
Saliva, skin, GI mucosa, breast milk
Describe the structure and function of IgM antibodies
Pentamer and monomer (exists as BCR)
Monomer activates complement for MAC formation and opsonisation
Pentamer binds multiple antigens (e.g. mismatched transfusion reaction)
How many epitopes does the IgM pentamer have?
10
Describe the structure and function of IgE antibodies
Monomer
Anaphylaxis (type I hypersensitivity)
Tags parasites for eosinophils to destroy
Describe the structure and function of IgD antibodies
Monomer
Acts as BCR
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 phagocytic 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
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 somatic hypermutation?
Switching from IgM to IgG production
Producing antibodies of higher affinity
What can lipopolysaccharides provide for B cell activation?
Primary and secondary stimuli
List the functions of interleukins 1-6
HOT T-BO IS A CUTIE
1 – hot, fever
2 – T cell stimulation
3 – bone marrow stimulation
4 – IgE class switching from IgM
5 – IgA, eosinophils
6 – acute phase protein production
What does IL-8 stimulate?
Chemotaxis
What is IL-10 involved in and what class of CD4 T cell produces it?
Anti-inflammatory response
Produced by Treg
What does IFN-gamma do?
Activates macrophages
What does TNF-alpha do?
Cytotoxic to tumor cells
