Adaptive Immunity Flashcards
what is an antigen and where are they found in
an antigen is a molecule (proteins, polysaccharide, lipids, nucleic acid etc) capable of inducing an adaptive immune response. Antigens may be complex with several ‘epitopes’
Pathogens are covered in a myriad of unique antigens which are recognised as ‘foreign’
list 3 key features of adaptive immunity
- Takes longer to develop adaptive responses than innate responses
Clonal expansion of adaptive immune cells (B and T) - Specificity - Conferred by antigen-specific receptors on B and T-cells and antibodies, with extraordinary diversity
- Memory - Maintained in T-cells and plasma cells after initial immune response so that response can be generated more rapidly if pathogen encountered again
cells found in APCs
Infectious agents can be outside and inside cells
How can the adaptive immune system recognise antigens in both settings?
- Antibodies can recognise antigens outside of cells
- T cells can recognise antigens ‘inside’ cells
- All cells present portions of their internal milieu on specialised molecules at the surface – particularly MHC molecules (bind peptides)
- Antigen-presenting cells ‘show’ T cells what is inside them
innate vs adaptive immunity
How the innate immune system helps the adaptive immune response
1. Pathogen Sensing:
- Cells in the immune system use Pattern Recognition Receptors (PRRs) to detect molecules on pathogens called Pathogen-Associated Molecular Patterns (PAMPs).
- Examples of PRRs include Toll-like receptors (TLRs) (e.g., TLR3 recognizes viral RNA).
2. Signalling Activation:
- PRRs trigger pathways like IRF3 or NFκB, which lead to the production of Type I Interferons (IFN-α & IFN-β).
- These interferons activate genes (called Interferon-Stimulated Genes, ISGs) that help fight infections.
3. Specialized Cells:
- Plasmacytoid Dendritic Cells (pDCs) are major producers of Type I IFNs.
4. Link to Adaptive Immunity:
After detecting pathogens, the immune cells mature by:
- Producing cytokines and chemokines (immune signalling molecules).
- Displaying pathogen fragments (antigens) to T cells, enabling the adaptive immune response.
where do T cells develop, give examples
- T cells - develop in the thymus
- Conventional (⍺β) T cells monitor cells for presence of infectious agents inside them
- Cytotoxic T cells (CD8+)
- T helper cells (CD4+)
where do B cells develop
- B cells- develop in bone marrow
- Can develop into plasma cells that produce antibodies (immunoglobulins)
- Different types: IgM, IgD, IgG, IgA and IgE
humoral immunity
Humoral Immunity
- Target: Extracellular microbes (outside cells, like bacteria).
- Key Cells: B lymphocytes (B cells).
- Mechanism: B cells produce antibodies that:
- Bind to microbes.
- Neutralize or block infections.
- Help eliminate extracellular pathogens.
- Function: Protects against infections by targeting microbes outside of cells.
cell mediated immunity
Cell-Mediated Immunity (Right Columns)
- Target: Intracellular microbes (inside cells, like viruses or bacteria in macrophages).
- Key Cells: T lymphocytes (T cells).
- Helper T cells: Activate macrophages to destroy phagocytosed microbes.
- Cytotoxic T cells: Kill infected cells to eliminate reservoirs of infection.
- Mechanism:
- Helper T cells enhance the ability of macrophages to digest microbes.
- Cytotoxic T cells directly kill infected cells.
- Function: Defends against infections hidden inside cells.
difference between cell mediated and humoral immunity
- Humoral immunity fights infections outside cells using antibodies.
- Cell-mediated immunity fights infections inside cells by activating macrophages and killing infected cells.
How do Lymphocytes Recognise Specific Antigens?
1. Antigen Receptors:
- T cells have T-cell receptors (TCRs).
- B cells have B-cell receptors (BCRs), which are antibodies on their surface.
Structure and Function:
- Both receptors have a variable region that determines specificity, acting like a “lock and key” to bind specific antigens.
- The constant region anchors the receptor in the cell.
Diversity:
- There are around 10¹⁸ different antigen receptors, created by genetic rearrangement.
- This process enables lymphocytes to recognize a vast number of antigens, far exceeding the amount of DNA in our genome.
How do B cells recognise antigens?
B Cells:
B cells recognize conformational epitopes, meaning they “see” the 3D shape of antigens as they exist on the surface of pathogens.
These do not require antigen processing.
How do T cells recognise antigens
T Cells:
T cells recognize linear epitopes, which are short pieces (peptides) of an antigen.
The antigen must first be broken down into these peptide fragments by the immune system and presented on MHC molecules.
The T cell receptor (TCR) then binds to the MHC molecule displaying the peptide.
B cells vs T cells in recognising antigens
B cells bind to whole antigens (shapes).
T cells bind to processed pieces of antigens (peptides).
What is VDJ recombination?
VDJ recombination is the process where DNA is cut and rearranged randomly using Variable (V), Diversity (D), and Joining (J) gene segments to create unique receptor combinations for each T or B cell.
How does VDJ recombination generate receptor diversity?
VDJ recombination generates diversity by random splicing of V, D, and J gene segments, creating unique combinations.
what do B cells do
How does imprecision in DNA joining increase receptor diversity?
Imprecision during DNA joining, such as adding or removing nucleotides, creates even more receptor variety.
How do VDJ recombination and somatic hypermutation contribute to immune diversity?
VDJ recombination creates a vast number of unique receptor combinations, while somatic hypermutation fine-tunes receptors for better antigen binding.
What are the three main processes that generate diversity and specificity in adaptive immunity?
VDJ recombination, somatic hypermutation, and affinity maturation.
What happens during somatic hypermutation?
Lymphocytes mutate their DNA after encountering an antigen, creating more receptor diversity.
What is affinity maturation?
The process of selecting the strongest lymphocyte clones with high-affinity receptors to survive.
What is class switch recombination (CSR)?
CSR is the process where the constant region of an antibody changes, allowing the same antigen-binding site (variable region) to attach to different antibody types (e.g., IgG, IgE, IgA).
Why is class switch recombination important?
It enables antibodies to perform different effector functions, like better pathogen neutralization or allergy responses.
What determines the immunoglobulin (Ig) class during CSR?
Rearrangements in the constant (C) gene regions determine the Ig class (e.g., IgG, IgE, IgA).
What is required for class switch recombination to occur?
CSR requires help from CD4+ T cells.
Does class switch recombination change the antigen-binding site of the antibody?
No, the variable region (antigen-binding site) remains the same during CSR.
Which antibody is produced first in an immune response?
IgM, which has low affinity, high avidity, and activates complement.
Which antibody provides mucosal immunity in the gut and lungs?
IgA.
Which antibody is the most abundant in circulation?
IgG, which is used to diagnose past or persistent infections and has high affinity.
What is the function of IgD?
It acts as a receptor on immature B cells.
Which antibody is involved in allergic reactions and binds to mast cells?
IgE, which is present in low serum concentrations.
What are the key properties of IgG?
It is >80% of circulating antibodies, has 4 subclasses (IgG1-4), and provides high-affinity responses.
What are the key regions of an antibody?
The variable region binds the target antigen, and the constant region interacts with effectors.
What is the role of IgM antibodies?
IgM is effective at neutralising and agglutinating antigens.
What is the role of IgG and IgA antibodies?
IgG and IgA are good at opsonising (promoting phagocytosis) and fixing complement.
What happens when antibody production is defective?
It can lead to bacterial respiratory infections.
What is antibody neutralisation?
Antibodies cover biologically active portions of a microbe or toxin, preventing their function.
What is complement fixation?
The Fc region of an antibody binds complement proteins, activating them to lyse bacteria.
What is agglutination?
Antibodies cross-link cells (e.g., bacteria), forming a clump for easier clearance.
What is opsonisation?
Antibodies bind to receptors on phagocytic cells, triggering pathogen engulfment and destruction.
What is immunological memory?
It allows a rapid and stronger immune response upon subsequent exposure to an antigen.
How are memory cells formed?
A small proportion of high-affinity B and T cells differentiate into long-lived memory cells after activation.
Where do memory cells reside?
In lymph nodes or tissues.
How do memory cells differ from naïve cells?
Memory cells have a longer lifespan, respond faster and stronger, and have high-affinity receptors.
What happens during a secondary immune response?
High-affinity antibodies are produced in greater quantities compared to the primary response.
What is the difference between the primary and secondary immune responses
- Primary response: Slow, with low-affinity antibodies produced.
- Secondary response: Faster and stronger, with high-affinity antibodies produced in larger quantities.
What role do memory B and T cells play in subsequent responses?
Memory T cells orchestrate the secondary immune response, while memory B cells produce large amounts of high-affinity antibodies.
What is the origin and function of the B cell precursor?
Located in the bone marrow; undergoes VDJ rearrangement to prepare for antigen recognition.
What is the mature naïve B cell, and where is it found?
Circulating in the bloodstream; it is antigen (Ag) naïve.
Where does the activated B cell reside, and what does it signify?
Found in lymph nodes; it has been exposed to an antigen.
What is the function of a plasma cell, and where is it located?
Found in bone marrow or lymph tissue; it secretes antibodies
What are memory B cells, and what is their role?
Located in the bone marrow; they enable rapid differentiation into plasma cells during future antigen exposure.
What do naïve T cells require for activation?
Two signals in secondary lymphoid tissues:
Signal 1: TCR recognition of peptide-MHC.
Signal 2: Interaction between costimulatory molecules on T cells and mature dendritic cells (DCs).
What happens if naïve T cells only receive Signal 1?
They undergo anergy (inactivation) or deletion.
What are the two main domains of the T-cell receptor (TCR)?
Variable domain (Vα, Vβ)
Constant domain (Cα, Cβ)
What regions determine TCR specificity?
Complementarity-determining regions (CDRs).
How does TCR diversity compare to B-cell receptor (BCR) diversity?
TCR diversity mechanisms are similar to BCR, except there is no somatic hypermutation in TCRs.
What components make up the variable domain of TCR?
V (Variable)
D (Diversity)
J (Joining) segments for the β chain.
V and J segments for the α chain.
What can drive effector T cell responses at infection sites?
‘Signal 1’ alone can drive responses at peripheral sites of infection.
