Session 7 Flashcards
(50 cards)
Where are the lymphocytes in lymph nodes?
T cells in the parafollicular cortex and B cells in the lymphoid follicle.
Give a little bit of information on B and T lymphocytes
• Produced by the bone marrow
• T cells mature in the thymus
• B cells mature in tissues following contact with Antigen
• Present in the blood
• ∼5-15%B cells, ∼70% of cells
• Accumulate in key lymphoid tissues
o Mucosa-associated lymphoid tissue (MALT)
o Lymph nodes
o Spleen
• Lymphadenopathy
Occurs when B and T cells are activated by the antigen
What are the three clinically important lymph node regions?
Neck (Cervical)
Armpit (Axillary)
Groin (Inguinal)
How are antigens recognised by T lymphocytes?
• Antigen recognition receptor recognises the MHC associated peptide.
o T cell receptor (TCR): αand βchains with a variable and a constant region. Antibody binds in both alpha and beta chain in the variable region. this doesn’t activate the T cell though.
o After binding, there’s signal transduction to CD3 complex which signals lymphocyte to activate.
o Accessory molecules (CD4 or CD8)
• Diversity of antigen receptors
o Combinatorial diversity (>10^16 possible TCR)
• Forms of antigen recognized
o Peptides displayed by MHC molecules
• Different subtypes
o Helper T cells (CD4+) recognise peptide presented by MHC class II molecules
o Cytotoxic T cells (CD8+) recognise peptide presented by MHC class I molecules
What is the limiting factor in T cell recognition?
Not the TCR as variable region has so many different possible configurations to bind with a massive variety of MHC associated peptides/antigens but instead it is the MHC molecule itself which can only bind to a limited number of peptides.
Which cells can present both MHC class I and class II molecules?
Only antigen presenting cells.
How does costimulation work in T cell activation?
1st signal is from MHC associated peptide binding with TCR, second is from B7 protein binding with CD28 and third is cytokines released from APCs.
What are the products of T cell activation?
CD4+ T cells become T helper cells
CD8+ T cells become cytotoxic T cells
How do cytokines help activate CD4+ T cells?
APCs send cytokines to naïve CD4+ t cells and based on the cytokine they differentiate into different subtypes: IL-12 leads to TH1 formation IL-4 leads to TH2 formation IL 1/IL6 leads to TH17 formation IL10/TGFbeta lead to Treg formation
TH1 is the best CD4+ helper response that we have against most intracellular and some extracellular microbes because TH1 response can activate CD8+ cells helping them fully differentiate into cytotoxic T cells, enhance the phagocytic activity of macrophages and make chemokines that draw them in and encourage B cells to produce IgG or IgA which are appropriate to fight the infection. this combined immune response is best against intracellular pathogens and is called cell mediated immunity because its mostly based on the activation of macrophages and CD8+ T cells.
If the pathogen is purely extracellular then IL 4 will be produced causing naïve CD4+ cells to become TH2 and induce humoral immunity which is a antibody based response using primarily B cells. these B cells produce IgE which can opsonise large pathogens like parasites and worms. However they are too large to be phagocytosed so Eosinophils and Mast cells (in allergies) produce cytotoxic chemicals to kill the parasite.
TH17 goes on to recruit and activate neutrophils
Treg is involved in tolerance and immune suppression. these prevent the immune response from being excessive by stopping function of TH1 and TH2.
For intracellular pathogens we recruit TH1 and extracellular we recruit TH1 and TH2.
How are the effector functions of CD8+ T cells carried out?
Naïve CD4+ cells differentiate into TH1 which release cytokines to Effector CD8+ cells which go on to become cytotoxic T lymphocytes which go onto peripheral tissues and kill all of the infected cells (presenting MHC class I)
What is cross presentation?
APCs being able to activate both CD4+ and CD8+ cells
Why does lower CD4+ levels cause lower cytotoxic T lymphocytes?
CD4+ T cells can differentiate into TH1 cells which release cytokines to help CD8+ T cells fully mature into cytotoxic T lymphocytes so if CD4+ cells are low then there is less maturation of CD8+ cells.
How do cytotoxic T lymphocytes kill infected cells?
It recognises infected by cell by MHC class I presenting viral antigen. it then uses perforin to make a channel into the cytoplasm of the infected cell and then it sends granzyme into the cell which triggers apoptosis.
How do B cells recognise antigens?
• Antigen recognition receptor
o B Cell Receptor or BCR: Membrane bound antibodies
o Unique specificity for each cell
o Antigen binds to variable region called CDR.
o Has constant region made of 2 heavy chains and variable region made of 2 light chains
• Diversity of antigen receptors
o Combinatorial diversity (>10^11 type of BCR due to multiple genes coding for it with different possible combinations.)
• Forms of antigen recognized
o Macromolecules (proteins, polysaccharides, lipids, nucleic acids)
o Small chemicals
How is BCR different from TCR?
BCR can recognise native microbe (macromolecules (proteins, polysaccharides, lipids, nucleic acids) and small chemicals are possible antigens) whereas TCR can only recognise MHC class associated peptide.
How are B lymphocytes activated?
BCRs are crossed over so binding of one antigen activates 2 BCRs . This is the first signal. Signal is transduced and this causes increased B7 costimulators. Antigen is cleaved and taken into the B lymphocyte by endocytosis and the microbial peptide is taken in an endosomal vesicle and presented on MHC class II molecules to CD4+ T cells where the second signal comes from TCR engagement. Simultaneously B7 protein signals CD28 receptor in T helper cell. 3rd signal comes from CD40 ligand upregulation in the T helper cell and then this leads to proliferation and differentiation, antibody production and heavy chain isotype switching. First the CD4+ cells produce IgM but then after this they can switch to IgG, IgA or IgE
What is the outcome of B lymphocyte activation?
• Antibody production (soluble not membrane bound)
o IgM production is T helper independent and produced first
o IgG, IgA, IgE production is T helper dependent(isotype switch)
• Higher affinity as a result of maturation in antibody response so microbe can be detected in low concentration as a result of prolonged or repeated exposure
• Memory B cells can reactivated without the need for T cells.
o Upon re-challenge can give a faster, stronger and longer antibody response
Which area of antibody determines isotype?
Heavy chain
Explain antibody heavy chain isotype switching
initially B cells produce IgM which are Thymus-independent antigens but if activated by effect T helper cells (CD4+ T cells) they can switch isotype with the help of different cytokines to produce different IgG, IgE or IgA. IgG is arguably best as it can enter the peripheral tissues.
How does serum antibody concentration change over time?
Primary response first antibody to be produced is IgM with small amount of IgG but then with second exposure, due to B memory cells there are far more IgG antibodies and less IgM. the response is faster, stronger, with longer duration, higher affinity and with the isotype switch.
How can we see if an infection is chronic or acute?
If acute IgM will be much higher as its first exposure but if chronic, infection will have already been present before so, memory cells will produce IgG so IgG will be much higher than IgM.
What are the effector functions of different antibodies?
IgG Fc-dependent phagocytosis (opsonisation) Complement activation Neonatal Immunity Toxin/virus neutralization
IgE
Immunity against helminths
Mast cell degranulation (allergies)
IgA
Mucosal Immunity
Present in breast
IgM
Complement activation
What are the medical achievements derived from the study of the adaptive immune response?
• Disease prevention o Vaccination (or active immunization) • Immunoglobulin therapies o Immune deficiencies • Immediate protection o Passive immunization (antibody transfer) • Diagnostic tests (antibody-based) o Infectious diseases o Autoimmune diseases o Blood type and HLA types
DiGeorgesyndrome is an immune deficiency resulting from an impaired thymic development. Which of the following immune components will be affected in these patients?
T and B cell function
