How is the adaptive immune response initiated?
The adaptive immune response is initiated as activated dendritic cells present microbial antigens to t-cells.
What are the primary lymph organs?
Thymus and bone marrow.
Where do lymphocytes develop?
Bone marrow -> Thymus -> Secondary lymphoid organs
What are the three key players of the adaptive immunity? And what are their functions?
- B-cell, produce antibodies
- CD4+ t cell, produce cytokines
- CD8+ t cell, recognise and remove viruses
What antigens undergo clonal deletion, selection or expansion?
- Cells that recognize self-antigens undergo clonal deletion
- Cells that recognize foreign antigens undergo clonal selection and expansion
What are the two forms of immunoglobulin produced from b-cells?
- Surface Ig present on b-cell membrane (b-cell antigen receptor + transducer of activation signals)
- Secreted Ig - plasma cells once the b-cell has activated
How do B-cells recognise pathogens?
B-cells bind directly to the pathogen via their antigen receptor. They then release their antibodies.
What are the main structural components of an antibody?
- The fab region - where the antigen binds, has variation due to separate V,D,J
- Fc constant region - which can be 1/5 isotypes; IgM,D,G,A + E. Will determine if the antibody reacts with the antigen.
Has 2 binding regions, per antibody.
How is Ig diversity determined?
- Variability occurs as the variable region’s light chain has Variability and Joining
- While its heavy chain changes in Variability, Diversity and Joining.
- The light chain’s constant region is known as Alpha + Beta.
- Also nucleotides undergo gene deletion and insertion, creating more variability.
How are antibody isotypes determined?
Antibody isotypes are determined by the heavy chain constant region.
What are the functions of the IgG antibody?
The IgG antibody binds to Fc receptors on monocytes, macrophages and NK cells. This can activate the complement system.
*IgG can cross the placenta
The fab region will neutralize toxins.
The Fc region will cause opsonisation, trigger the classical pathway of the complement cascade and induce the release of cytotoxic products from macrophages/ NK cells.
What are the functions of IgE antibodies?
IgE antibodies respond during an allergic response and responds to parasites.
The Fc region triggers the degranulation of mast cells and eosinophils.
What are the functions of IgM antibody?
IgM is expressed on naive b-cells. Activate the complement system and forming the membrane attack complex so bacteria + mammalian cells undergo lysis.
The fab region will neutralize toxins.
The Fc region triggers the classical pathway of the complement system.
What are the functions of IgA?
IgA is found in mucous secretions in the airways, gut and breast milk.
What is the overall process of b-cell activation?
B cells develop in the bone marrow -> undergo gene arrangement + clonal deletion -> mature cells leave the bone marrow -> encounter an antigen -> clonal expansion -> isotype switching -> affinity maturation
What is isotype switching?
Isotype switching is when naive b-cells no longer express IgM once activated. With help from Th1 cells the mature b-cells will express IgG or with help from Th2, the mature b-cells will express IgE.
The quanity of IgG and IgE increase with secondary exposure to the same antigen.
What are the two major types of t-cells?
CD8+ / Cytotoxic t-cells - Lysis cells infected by the pathogen. Secrete antiviral and inflammatory cytokines (TFNy and TFN alpha)
CD4+ helper t-cells - secrete antiviral and inflammatory cytokines for b-cells, CD8 t cells and macrophages.
How do t-cells recognise antigenic peptides?
- Antigen is broken down into peptide fragments
- Epitode binds the MHC
- T-cell receptor binds to the complex of epitode + peptide.
How do t-cell receptors differ?
TCR genes can be rearranged, creating different t-cell receptors.
TCR alpha genes can vary V, J and C of gene segments
TCR beta genes can vary V,D, J and C of gene segments
What do MHCs do?
MHCs are recognised by t-cell and expresses peptide antigens. The T-cell with receptor binds to the MHC class I with the peptide.
What are the two types of MHC molecules? What do they include? And where are the peptides generated?
MHC I - includes; HLA-A, HLA-B, HLA-C
- Peptides are generated by proteolysis in the cytoplasm, load up onto the MHC in the lumen of the ER
MHCII - HLA-DR, HLA-DP AND HLA-DQ
- Peptides are generated in the endosomal network
What are the complementarity determining regions (CDRs) of MHCs?
The CDR connect the MHC and peptide. Are visible points on the PCR that recognise the MHC molecule and peptide
How do individuals have polymorphic variation in regards to MHCs?
MHCs have polymorphic variation due to haplotype (combination of MHC alleles). Ensures a pathogen is unable to go unrecognized.
What are the overall steps in a T-cells life?
T cell progenitors are produced in the bone marrow -> mature in the thymus -> TCR genes are rearranged / t-cell education -> mature cells leave the thymus -> t-cells encounter the LN on antigen presenting cells -> clonal expansion + differentiation -> effector functions -> t-cell memory is established
