Lymphocytes Flashcards
What are the 2 types of immune response?
- Innate
- Adaptive
Which 2 cells are critical to the innate immune response?
- Neutrophils
- Macrophages
Which cells are critical to the adaptive immune response?
B and T lymphocytes
Why is the adaptive immune system needed?
- Clears infection (innate only contains it)
- Prevents reinfection
What do issues in adaptive immunity lead to?
Autoimmune diseases (eg. asthma and lupus)
What are the 5 main differences between the innate and adaptive immune system?
Innate
- quick
- no memory
- neutrophils and macrophages
- can recognise which pathogen (virus/bacteria etc)
- same everywhere in body
Adaptive
- slower
- memory
- lymphocytes
- specific to exact pathogenic organism
- specific to site of infection
Why is immunological memory so important?
Prevents reinfection
Why is the adaptive immune response to a primary infection slower? (2)
- Takes time to find specific lymphocyte
- Takes time to activate lymphocyte
Why is the adaptive immune response to a secondary infection faster? (2)
- Memory cells localised to where primary infection was —> quickly finds specific lymphocytes
- Memory cells are quickly activated
Which immune response is utilised for vaccinations?
Adaptive
Which adaptive immune response do T cells stimulate?
Cell-mediated
Which adaptive immune response do B cells stimulate?
Humoral
What are the 2 main roles of T cells in the cell mediated response?
- Produce cytokines (T-helper) —> help shape immune response
- Kill infected cell (cytotoxic T)
What is the main role of B cells in the humoral response?
Produce antibodies
How do T and B cells recognise pathogens?
T-cell receptors (TCRs)
B-cell receptor (BCRs)
What are the 2 important regions of TCRs and BCRs?
- Variable
- Constant
Where does the variable region of TCRs and BCRs lie?
Sticks out of cell
Where does the constant region of TCRs and BCRs lie?
Sticks into cell
What does the variable region of TCRs and BCRs do?
Recognise pathogen
What does the constant region of TCRs and BCRs do?
Activate its lymphocyte
How does the adaptive immune system recognise pathogens?
Antigens
What is an epitope?
Region of antigen which the lymphocyte receptor binds to
What to TCRs and BCRs bind to?
Epitope of antigen
What type of epitopes are recognised by T cells?
Linear —> recognises primary structure of epitope (10 amino acids)
What type of epitopes are recognised by B cell antibodies?
Structural —> recognises tertiary and quaternary structure of epitope
What is important about the lymphocytes interacting with an antigen?
Specific to antigen
- 1 lymphocyte to 1 antigen
What is stimulated when a lymphocyte receptor binds to its cognate antigen?
Clonal expansion
What is a cognate antigen?
The antigen that a lymphocyte has its specific response to
What is important about the cells produced by clonal selection?
Receptors are the same as the original lymphocyte’s
What is the issue that comes with the high specificity of the adaptive immune system?
Antigen diversity
How does the immune system deal with antigen diversity?
Huge repertoire of BCRs and antibodies
What would be the issue with the antigen receptor diversity and how is this overcome?
- Too many BCRs and antibodies (10^15-10^20) need coding for than the number of genes we have (25,000)
- Gene recombination
When are functional genes for antigen receptors generated?
During B lymphocyte development
What is each BCR chain encoded by?
Separate multigene families on different chromosomes
What are the 3 gene families that code for BCR receptor chains
- Kappa
- Lambda
- Heavy chain
What is immunoglobulin gene rearrangement?
Process of rearranging gene combinations and orientations to give a wider range of BCR and antibody proteins coded for
What are the 2 gene segments for each BCR light chain in humans?
- V (variable)
- D (diversity)
- J (joining)
What are the 2 gene segments for each BCR light chain in humans?
- V —> 40 different
- J —> 5 differenct
What is the function of TCRs?
Recognise antigen fragments presented by other cells (eg. dendritic) in the context of MHC
What type of signalling happens for a TCR to activate its T cells?
Enzyme-linked —> clustering
What is MHC?
Major Histocompatibility Comples
What are the 2 functions of MHC?
- Defining self and not self cells
- Present antigens to T cells
What are the 2 types of MHC?
1 and 2
Which cells is MHCI present in?
All nucleated cells
Which cells is MHCII present in?
Professional APCs (eg. dendritic)
Which 2 components make up MHCI?
- Variable alpha chain (3 subunits)
- Common beta chain (1 subunit)
Which 2 components make up MHCII?
- Variable alpha (2 subunits)
- Variable beta (2 subunits)
Which T cells does MHCII bind to?
CD4 (T-helper)
Which T cells does MHCI bind to?
CD8 (cytotoxic T)
What is the difference between the types of pathogens/antigens presented on MHCI vs MHCII?
- MHCI —> intracellular
- MHCII —> extracellular
What are the 3 main differences between MHCI and MHCII?
MHCI
- Pathogen processed in cytosol
- Intracellular pathogens
- Presented to CD8 T-cells
MHCII
- Pathogen processed in endosomes
- Extracellular pathogens
- Presented to CD4 T-cells
Which genes encode MHC proteins?
HLA genes
Why are HLA genes polygenic?
3 different classes
How many classes of HLA genes are there?
3
What type of genetic expression occurs for HLA genes?
Co-dominant
What is the maximum number of HLA genes a person can have and why?
6
- If heterozygous for at 3 classes of HLA genes
What are the 2 types of T cells?
- T-helper cells (Th cells) —> CD4
- Cytotoxic T cells (CTLs) —> CD8
Which APCs do T-helper 1 cells bind to?
Virus-infected cells
Which APCs do T-helper 2 cells bind to? (2)
- Macrophages
- B-cell (antigen-specific)
What chemicals do T-helper cells produce?
Cytokines
What are cytokines?
Proteins/glycoproteins acting as signalling molecules in the immune system
What are the 5 types of T-helper cell?
- Th1
- Th2
- Th17
- Treg (Th0)
- Tfh (follicular)
What are the 2 functions of T-helper 1 cells?
- Pro-inflammatory
- Boost cellular immune response
What are the 2 functions of T-helper 2 cells?
- Pro-inflammatory
- Control bacterial and fungal infections
Which 3 cytokines are produced by T-helper 1 cells?
- IFN-γ
- TNF (tumour necrosis factor)
- IL-12
Which 3 cytokines are produced by T-helper 2 cells?
- IL-17
- IL-6
- IL-23
think 17 + 6 = 23
Which 2 pathogens do T-helper 1 cells respond to?
- Viruses
- Intracellular bacteria
Which 3 pathogens do T-helper 2 cells respond to?
- Helminth parasites
- Bacteria
- Fungi
What are CTLs?
Cytotoxic T Lymphocytes
What do CTLs do and how?
Kill infected cells
- Apoptosis
What are stored in CTL cytotoxic granules? (3)
- Perforin —> holes in membrane
- Granzymes —> stimulate apoptosis
- Granulysin
What happens when the CD8 of a CTL binds to the MHCI of a cognate pathogen?
Release chemicals in cytotoxic granules
What are the 4 steps of how CTLs kill virus-infected cells?
- Virus infects cell —> cell displays non-self MHCI
- CD8 of TCR on CTL binds to MHCI of infected cell
- CTL activated —> releases chemicals in cytotoxic granules on infected cell
- Infected cell undergoes apoptosis —> killed
What is the structure of an antibody? (5)
- Variable region (top half)
- Constant region (bottom half)
- 2 Heavy chains (long inner)
- 2 Light chains (short outer)
- 3 Disulfide bridges (between 2 heavy chain + between each heavy and long chain pair)
What are the 3 roles of antibodies?
- Neutralisation —> covers binding sites of pathogen
- Opsonisation —> allows for macrophage phagocytosis
- Complement activation
What are the 5 classes of antibody?
- IgG
- IgM
- IgA
- IgD
- IgE
What is the shape of each 5 antibody class?
- IgG —> normal (Good)
- IgM —> 5 together (Mum likes flowers)
- IgA —> short/2 together/3 together (Acrobatics)
- IgD —> normal (gooD)
- IgE —> normal but longer (Elongated)
What is the function of each 5 antibody class?
- IgG —> opsonisation and neutralisation (Good)
- IgM —> first produced (Mum first before baby)
- IgA —> in mucosal tissue
- IgD —> ?
- IgE —> allergy (Eosinophils and IgE)
What are the 4 subclasses of IgG antibodies?
IgG1, IgG2, IgG3, IgG4
When are the binding sites of a BCRs made?
Before cell ever encounters an antigen
How many BCRs are on each B lymphocyte?
Thousands
What do BCRs bind to?
Soluble antigens
How are B cells activated? (2)
Accesory signals from…
1. Microbial consituents
2. T-helper cells
What are the 2 pathways of antibody production by B cells?
- Thymus-independant (direct microbial constituents)
- Thymus-dependant (T-helper cells)
What are the 3 differences between the thymus-dependant and thymus-independant antibody production?
Thymus-independant
- Direct microbial constituents activate B-cell
- IgM antibody production
- No memory
Thymus-dependant
- T-helper cells activate B-cell
- IgG production (all classes)
- Memory
How does thymus-independant antibody production work?
- BCRs bind to antigens antigen often on polysaccharide (repeated structure) —> first signal
- Other receptors on B cell bind to PAMPs (Pathogen-Associated Molecular Patterns eg. LPS) —> second signal
How does thymus-dependant antibody production work? (5)
- BCR recognises antigen —> binds
- Antigen internalised and degraded —> peptides
- Peptides associate with self MHCII —> expressed on surface
- T-helper cell binds to complex —> activates B cell
Why does the innate immune response occur as well as adaptive immune response?
Adaptive system takes time —> innate buys time by containing the infection
