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55631
Adaptive Immune System
Description
Biochemistry (Immunity) Mind Map on Adaptive Immune System, created by zambrella on 24/04/2013.
No tags specified
biochemistry
immunity
biochemistry
immunity
Mind Map by
zambrella
, updated more than 1 year ago
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Created by
zambrella
over 11 years ago
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Resource summary
Adaptive Immune System
Humoral
Antibodies
Functions
Bind very specifically to an antigen
Neutralisaiton
Mark for phagocytosis
Activates complement system
Structure
5 isotypes: IgA, IgD, IgE, IgG and IgM
IgG most common
Y shaped
4 polypeptides
Heavy chains help together by covalent intermolecular-disulphide bonds
Heavy chain and light chain held together by covalent intermolecular-disulphide bonds
Antigen binding sites found at teh N-terminus of polypeptides
Variability found in the amino acids of the antigen binding sites
HV = hypervariable
CDR = complementarity determining regions
Epitope = region (small portion) of an antigen that the antibody recognises
Antigens
Antigenicity is the ability to combine with antibodies
Immunogenicity is the ability to induce humoral (or cell mediated) immune response
Foreigness
Molecular size (large molecules are generally more immunogenic than small ones)
Chemical composition
Heterogeneity
Generation of antibody diveristy
Can produce billions of different antibodies
Production of variable regions of light and heavy antibody genes by DNA rearrangement
In all cells apart form B-cells immunoglobulin genes are in a form that cannot be expressed
J = Joining, D = Diversity, V = variable
Random recombination of gene segments produces diveristy
Recombine signal sequences (RSSs) flank the 3' of V segment, both sides of D segment and 5' of J segement
Recombination can only occur between RSSs of different types
Ensures correct order of joining
RAG = Recombination activating gene - mediates recombination
Additional diversity is added by recombination enzymes
P-nucleotides generate palindromic sequences at the cut ends of DNA strands
N-nucleotides are added at random to the cut end by terminal deoxynucleotidyl transferase (TfT)
Overview
1. RAG complex binds to and cleaves recobination signal sequences to yield a DNA hairpin
2. RAG-mediated cleavage of hairpin generates palindromic P-nucleotides
3. N-nucleotide additions by TdT
4. Pairing of strands
5. Unpaired nucleotides are removed by an exonuclease
6. These gaps are filled by DNA synthesis and ligation to form coding joint
Naive B-cells use alternative splicing to yield IgM or IgD
Membrane bound immunoglobulins are complexed with other proteins to functional B-cell receptors
Each B-cell has a single antigen specificity
Immunoglobulin gene rearrangement tightly regulated so that only on H and on L chain are expressed
B-cells that don't produce functional immunoglobulin are eliminated from population
Development on B-cells
1. Generation of B cells in bone marrow
2. Elimination of self reactive B cells in bone marrow
3. Activation of B cells by foreign antigen in secondary limphoid tissues
4. Differentiation to antibody-secreting plasma cells and memory cells in the secondary lymphoid tissues
Stages of B-cell development are marked by steps in rearrangement and expression of immunoglobulin genes
Only B-cells that produce functional immunoglobulin can survive
Get a number of chances
55 billion B-cells per day are lost in the bone marrow because they fail to make functional Ig or are self reactive
Mature naive B-cells compete for access to lymphoid follicles
when mature B-cells leave the bone marrow they circulate between the blood and secondary lymphoid tissues (lymph nodes, spleen)
within these tissues B-cells congregate in primary lymphoid follicles
Naive B-cells must pause in these follicles in order to receive survival signal s form follicular dendritic cells (a specialised stromal cell)
B-cell
Before encountering an antigen, a mature B-cell expresses antibody in a membrane bound form
When a foreign antigen binds to this immunoglobulin, the B-cell is stimulated to proliferate and gives rise to plasma and memory cells
B-cells that encounter antigen
Mature naive B-cells encounter specific antigen in secondary lymphoid tissue
Activated by CD4 helper T-cells
These T-cells provide signals that activate the B-cells to proliferate and differentiate further
Some differentiate into plasma cells
Some migrate to primary follicle, change morphology and become secondary lymphoid follicle containing a germinal centre
Here activated B-cells become large proliferating lymphoblasts called centroblasts
Centroblasts mature into isotype switched somatically hypermutated non-dividing centrocytes
Those cells that have the highest affinity for antigen are selected for by affinity maturation
Cells that survive affinity maturation proliferate and differentiate into plasma cells and memory B cells that persists for a long period of time
Cell mediated
T-cell receptor
Always membrane bound
Diversity is generated by gene rearrangmenet
Similar to rearrangement of iG genes
Uses RAG1 and RAG2
Addition of P and N nucleotides
Associates with other proteins
CD proteins (CD3)
Antigen processing and presentaiton
T cell receptors can only recognise antigens that are bound to MHC molecules
MHC = Major Histocompatibility Complex
Membrane glycoproteins
Function is to bind antigen and present it to T-cells
MHCI and MHCII have similar 3D structure but formed in different ways
MHC class I
Bind to CD8
Peptides are generated in the cytosol by proteasome
Transported into the ER by transporter associated with antigen processing (TAP)
Associate with MHCI
Transported to cell surface
MHC I molecules cannot leave the ER unless they have bound peptide
Almost all cells express MHC I molecules
Erythrocytes lack MHCI, a property that probably allows malarial parasites to persistently infect these cells
MHC class II
Bind to CD4
Antigens are taken up by phagocytosis or endocytosis
Degraded by proteases in lysosome
Do not bind peptides in the ER
Bacterial super-antigens
Bind simutaneously to MHCII and T-cell receptors
Can stimulate up to 20% of total CD-4 T-cell population
Results in systemic toxicity and suppression of adaptive immune response
2 main classes of T-cell
CD4 co-receptor needed for T-cell recognition of MHCII peptides
TH1 cells
Activate tissue macrophages to take up antigen
Stimulate B-cells to produce antibody
TH2 cells
TH2 stimulation of naive B-cells
During infection contain activated pathogen specific TH2 effector cells
Mature naive B-cells passing through lymphoid tissue pick up antigen, process it and present it on MHCII
When B-cell presents antigen recognised by T-cell (TH2), it become trapped
IFN-gamma can induce expression of MHCII molecules on cells that do not normally produce them
Presentation of antigen to CD4 T-cells can thus be increased in inflamed tissues
MHCII presents peptides derived from extracellular pathogens (antigens from outside the cell)
CD8 co-receptor needed for T cell recognition of MHCI peptides
Cytotoxic
MHCI responsible for presenting peptides derived from intracellular antigens (antigens produced without own own cytoplasm
Professional APCs (Antigen presenting cells)
MHC class II alert CD4 positive T-cell of infection (extracellular)
Expressed on professional APCs
Macrophages
B-cells
Dendritic cells
Supply co-stimulatory signal to T-cells
Generated by B7 on APC stimulating CD28 on naive T-cells
Macrophages
Phagocytic
Have receptors for bacterial carbohydrate
Inducible B7 expression
Dendritic Cells
Initiate T-cell responses against viruses
Possibly have specialised antigen processing
Immature dendritic cells do not have co-stimulatory acitivity
When they ingest antigens, they migrate to lymph node and become activated
T-cell Development
T-cells originate from stem cells in bone marrow
Mature in thymus
Thymus is a primary lymphoid organ as its concern is the production of useful lymphocytes and not with their applications to specific infections
Most active in young
Increases in size up to puberty
Immature CD3-4-8- (double negative)
Become immature CD3+4+8+ (double positive
Mature CD4+8- and CD4-8+
T-cell mediated immunity
Activation
Dendritic cells take up bacterial antigens in the skin and then move to a lymphatic vessel
Dendritic cells bearing antigen enter the lymph node, where they settle in the T-cell areas
T cells that do not encounter specific antigen leave a lymph node through lympatics
T-cells that encounter specific antigen proliferate and differentiate to effector cells
Naive T cells express the low affinity IL-2 receptor
Activated T-cells express the high affinity IL-2 receptor and secrete IL-2
Binding of IL-2 to the high affinity receptor sends a signal to the T-cell
The signal sent from the IL-2 receptor induces T-cell proliferation
Activated CD4 T-cells can differentiate in different ways that favour humoral or cell mediated immune response
Naive CD8 T-cells can be activated in different ways
Generally needs stronger co-stimulatory activity
Dendritic cells
APCs with help of CD4 positive T-cell
Effector T-cells
Can be stimulated by antigen in absence of co-stimulatory signal
Functions are performed by cytokines and cytotoxins
Selective killing
Collision and non-specific adhesion
Specific recognition redistributes cytoskeleton and cytoplasmic components of T-cell
Release of granules at site of cell contact
Apoptosis
Cytotoxic T-cell (CTL) recognises virus-infected cell
CTL programs target cell to die
Co-operation between B and T-cells occurs that are specific for the same antigen (usually different epitopes)
Responds to challenge with a high degree of specificity
Memory
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