L13: Adaptive immune response: Effector phase Flashcards
(31 cards)
Which area of the lymphoid tissue do you find CD4+/ CD8+ T cells? Where do you find B cells?
CD4+/CD8+ T cells–> parafollicular cortex
B cells–> lymphoid follicle
Where a B and T lymphocytes produced and where do they mature?
Both produced in bone marrow
T cells mature in thymus –> self selection –>
B cells mature following contact with antigen
More T cells in the blood than B cells
What is it important that the B and T cells accumulate in the lymphoid tissue?
Maximum interaction can happen in these tissues
What is lymphadenopathy?
Swelling of the lymph nodes
Occurs when B and T cells are activated by antigen
Cervical, axillary and groin
How are antigens recognised by T lymphocytes?
T cell receptor (TCR) recognises MHC associated peptide
Class I–> 9aa peptide
Class II–> 20/30aa peptide
The variable subunit consists of α and β chains–> recognise the peptide, accommodate an array of different peptides
Constant region–> doesn’t change
Part of bigger complex
–> CD3 complex (all T cells) ( signal transduction)
–> Accessory molecule CD4 or CD8
How much diversity is there in the TCR?
Combinational diversity–> 10^16
Limiting factor is the number of MHC molecules
Which cells recognise which class of MHC molecules?
Helper T cells (CD4+) –> peptide presented by MHC II
Cytotoxic T cells (CD8+) –> peptide presented by MHC I
Remember 1 x 8= 8 so CD8 is MHC I
2 x 4= 8 so CD4 is MHC II
What role does costimulation play in the activation of T lymphocytes?
APC travels to lymph node–> T cell zone (parafollicular cortex)
MHC I (CD8+) or MHC II (CD4+) activated
APC also has costimulatory protein B7 (upregulated when activated)
Binds to CD28 (structure) on T cell to activate the T cell
APC also release cytokines which determine form of T helper cell the T cell becomes
Once activated what do the naive CD4+ T cells become?
Depends on cytokine release IL-12 --> TH1 IL-4 --> TH2 IL-1 or IL-6--> TH17 IL-10 or TGFβ --> THreg
What is the best form of T cell for a cell mediated immunity? Why?
Intracellular* and extracellular pathogens
TH1 (IL-12)
Activates:
CD8+ differentiation into cytotoxic T cells
Macrophage recruitment and activation
B cells produce IgG or IgA
(*intracellular can activate both CD4+and CD8+)
What is the best for of T cell for a humoral immunity? Why?
Extracellular--> Humoral Immunity (parasites and worms) TH2 (IL-4) Activates: B cells --> IgE production --> only one that can activated eosinophils and mast cells Eosinophils --> Killing of pathogens Mast cells --> Allergies
What is TH17 important for?
IL1/ IL6
Humoral immunity–> bacterial and fungal infection and autoimmune problems (unsure how)
Activated:
Neurtophils–> recruitment and activation
What are the cells responsible for regulation of the immune response?
T reg cells IL10/ TGFβ Activated: Tolerance (unresponsiveness?) Immune suppression
What are the effector function of the CD8+ cells?
Intracellular microbes activate MHC I which activate naive CD8+ cells
Naive CD8+ –> Effector T cells and Memory CD8+ T cells
However they also activate MHC I–> CD4+ cells –> TH1 cells (IL-12) as they are needed to convert Effector T cells –> Cytotoxic T cells (release cytokines which result in conversion)
How does the cytoxic T cells (CD8+) kill the infected APCs?
Bind to MHC I associated peptide
Release cytokine
Also 2 enzymes produced intracellularly
–> Perforin–> forms perforin pore in infected cell
–> Granzyme–> enters through pore–> apoptosis
How do B cells recognise antigen?
B cell receptor (BCR)–> membrane bound antibody
Unique specificity for each cell
Variable–> accommodate different antigens
Constant region
Signal transduction Ig alpha and Ig beta next to BCR
How many different types of B cell receptors are there?
Combinatorial diversity –> 10^11
What is different about BCR compared to TCR?
Can recognise whole microbe
Do not need APCs
How are B cells activated?
Antigen activates two B cells receptors
1st signal–> BCR engagement (two BCR inteact)
–> signal transduction (Ig alpha and Ig beta in membrane)
–> Antigen processing and presentation–>Antigen taken into endosome and processed
–> Increased B7 protein (costimulator) –> becomes an APC–> Microbial peptide presented in MHC II (except virus–> presented MHC I and killed)
2nd signal–> TCR engagement
–> antigen specific
–> Role of B7 costimulator –> fully activated T cell
3rd signal–> B cells produce IgM- T helper cell independent
–> Isotype switch- require T helper cell–> different antibodies produced
–> Require CD40 ligands (CD40L) on T helper cell
–> Bind to CD40 receptor on B cell
–> Proliferation and differentiation–> isotype switch IgM- IgG
–> Antibody production
–> Heavy chain class switching
Label the different parts of the antibody?
Slide 13
1- Fab region (variable region contains antigen binding region)
2- Fc region (binds to receptors on immune cell)
3- Light chain
4- Heavy chain (determines isotype)
5- Antigen binding region
6- Hinge regions
What antibodies are produced first?
IgM
Independent of T helper cell
Thymus independent antigens
What antibodies are produced second?
IgG, IgA and IgE Depedent on T helper cell Thymus dependent antigens Isotype switch - Cytokines - CD40 activation
What happens after prolonged or repeated exposure to antigen?
Maturation of antibodies
Increased binding affinity
Upon re-challenge what cells are produced?
B memory cells
Faster, stronger and longer antibody response
