lecture 12 - adaptive immunity Flashcards
How are T cells and B cells activated?
through surface receptors
B cell receptor is a membrane-bound antibody same as the antibodies it secretes
What are antigens and epitopes?
Pathogen molecule recognised by T + B cells is ANTIGEN
- Originally “antibody generators” (i.e. targets of B cells)
- Now refers to both T + B cell targets
- For T cells = protein fragment (specific peptide)
- For B cells = protein… sugar… lipid…
- Antigen binding to TCR/BCR causes T/B activation
- Specific part of antigen recognised by T & B cells is EPITOPE
B cells bind to both linear and conformational epitopes whereas T cells only bind to linear epitopes
Describe how clonal selection takes place
- Each lymphocyte has multiple copies of single antigen receptor
- Antigen binding causes cell activation + clonal expansion
- All daughter cells have same antigen receptor specificity
How does the adaptive immune response start?
- Dendritic cells migrate from infected tissues along lymphatic cells to draining lymph node
- Pathogens / pathogen molecules also drain to lymph node
- T cells + B cells constantly circulate through secondary lymphoid organs via blood + lymph to search to specific antigens
Why can B cells bind both linear and conformational epitopes whereas T cells can only bind linear epitopes?
Within the secondary lymphoid organs:
• Antigen can bind DIRECTLY to BCR on surface of B cells
Because BCR is a surface Ab, and Ab can bind intact targets directly
This means B cells can bind both linear + conformational epitopes
• T cells only bind antigen that is PRESENTED to them as PEPTIDES
So TCR only recognise linear epitopes (short peptides)
How are B cells activated?
Pathogen moves into lymph node from lymphatic vessel
Its antigens are recognised by a specific B cell in the B cell area of the lymph node
The antigen binds to the B cell receptor
This causes clonal expansion of the B cells - B cells proliferate and produce specific antibodies
What do antibodies do?
- Ab directly neutralises pathogen molecule (e.g. toxin) so toxin cannot bind to its receptor on host cell preventing disease
- Ab “opsonises” pathogens increasing phagocyte uptake
Antibodies have two regions:
Variable = “Fab”(fragment antigen binding) portion
Non-variable “Fc” (fragment crystalline) portion
Innate immune cells express “Fc receptors” = FcR
so if the variable region of an antibody is bound to the pathogen the Fc region can bind to an Fc region on an innate cell which will phagocytose the pathogen
How are T cells activated?
Unlike B cells, T cells cannot bind antigen directly…
… TCR binds peptide antigens presented by MHC proteins
(= “Major Histocompatibility Complex” proteins)
The interaction of an MHC with a particular peptide that is recognised an antigen by a particular protein results in T cell activation
How does the model differ between CD8 and CD4 T cells?
- Cell type that presents antigen
- MHC molecule that presents peptide (MHC I or II)
- Origin of peptide (cytosol vs. extracellular)
- Consequences of T cell activation (“kill” or “help”)
How are CD8 (cytotoxic) T cells activated?
Main role of CD8 Tc cells is to kill cells infected with
cytosolic pathogens e.g. virus
• As most cells can be infected with viruses, need general mechanism to alert CD8 Tc cells of infection:
All cells display a sample of their cytosolic proteins on
their surface in form of peptides bound to “MHC class I”
If infected by a virus both host and viral proteins displayed
CD8 is co-receptor for MHC1 and stabilises the interaction between MHC1 with a viral peptide and specific T cell
both TCR and CD8 protein initiate an intracellular signalling cascade into the T cell and activate the T cell
The T cell will kill the virus-infected cell by releasing toxic substances into it
How are CD4 (helper) T cells activated?
- Dendritic cells present antigenic peptides on their surface using “MHC class II”
- These peptides derive from extracellular pathogens
- T cell with CD4 protein binds to MHCII cell presenting peptide initiating signalling cascade
How do CD4 Th cells “help” immune responses?
CD4 Th cells do not directly kill pathogens
(unlike macrophages or CD8 Tc cells)
CD4 Th cells do not directly neutralise pathogens
(unlike B cell antibodies)
1. CD4 T cells “help” B cell antibody production - activated CD4 T cells secrete cytokines which bind to cytokine receptors on B cell
the activated T cell also displays on its surface particular proteins which aren’t found on naive T cells which it can use to interact with and stimulate proteins on a B cell
This results in higher affinity antibodies and antibody class-switch (different isotopes: from IgM to IgG, IgA, IgE)
2. CD4 T cells “help” macrophages kill pathogens
secreted cytokines bind to cytokine receptors on macrophages leading to increased production of
anti-microbial factors and better microbial killing
How is receptor diversity generated?
- TCR + BCR encoded in gene segments
- Each segment of variable region has many different variants
- Gene segments brought together through random gene
rearrangement
Compare innate and adaptive immune receptors
Innate immune cells (macrophages, dendritic cells):
has pattern recognition receptor
small number of different receptors (10s)
receptors broad specificity e.g. LPS from G-ve bacteria, RNA from viruses
individual cell has multiple different kinds of PRR
Adaptive immune cells: B and T
massive number of different receptors
receptors highly specific e.g. specific protein sequence
individual cell has only one receptor specificity
