Lymphocytes Flashcards
Why do we need adaptive immunity
Protects us from repeat infections
Absence would lead to inability to clear infections
1)Has memory
2)needs time to develop
3)improves efficacy of innate immune response
What is immunological memory
Once an immune response has occurred it exhibits memory
More rapid andheightened immune response occurs
Reduction in severity on re exposure
Basis of vaccines
2 types of adaptive immune response
Cell mediated response: produces cytokines to help shape immune response (cd4),kill infected cells (cd8)
Humoral response:produces antibodies
Antigen
Molecule that induces an adaptive immune response
Epitope
Region of antigen which the receptor binds to
Which structure of epitopes do T cells recognize
Linear epitopes
What structure of epitopes do B cells recognize
Structural epitopes - the 3D structure of the antigen in space (recognise tertiary structure of antigen)
How is the adaptive immune response specific
Each antibody recognizes only one antigen
Clonal expansion
Occurs when an interaction between a specific foreign molecule and receptor happens
antigen receptor diversity problem
- We need to encode a large repertoire of lymphocyte receptors to deal with antigen diversity
- 10^15 different antibody molecules can be generated, each by a specific B cell expressing a specific BCR, therefore we need 10^15 different genes (which is impossible if 1 gene per function- we only have 25k genes in total for everything)
How is antigen receptor diversity generated
- Through genetic recombination
- Functional genes for antigen receptors don’t exist until they’re generated during lymphocyte development → each BCR receptor chain (kappa, lambda and heavy chains) is encoded by separate multigene families on different chromosomes
- During B cell maturation (in the bone marrow) these gene segments brought together and rearranged- in a process called Immunoglobulin gene rearrangement (aka VDJ recombination)
- This generates the diversity of the lymphocyte repertoire
What presents antigens to T cells
Major histocompatibility complex which is critical in donor matching and surgeey
What is the role of MHC
To bind peptide fragments derived from pathogens and display them on the cell surface of APC for recognition by the appropriate T cells
- Plays a central role in defining self and non-self
Critical in surgery and donor matching
What gene in humans encodes for MHC
HLA genes
MHC expression
MHC is polygenic - 3 class I and 3 class II loci
- Expression is codominant (maternal and paternal genes both expressed)
Each person can have up to 6 of the variations of the gene if completely heterozygous (3 from mother and 3 from father)
- 17k MHC variants- is why matching people for surgery complicated- doctors trying to match 6 different things
MHCI
single variable alpha chain and common beta microglobulin
Found on all nucleated cells
Present intracellular pathogen to cd8 T cells in the cytosol
MHCII
alpha and beta chains
On professional antigen presenting cells
Presented to Extracellular pathogens to cd4 T cells
Apoptosis
Characterized by fragmentation of nuclear dna
What do cytotoxic T cells (cd8) cells store and release
Perforin granzymes granulysin
Perforin makes holes then granzymes are injected causing a cascade of events
- How do CD8 cells recognise and kill infected cells?
1) In uninfected cells, MHC I molecules show self-peptides
2) CD8 cell scans cells, looking for non-self MHC and if it doesn’t find anything it does nothing
3) A virus infects the cell and releases its contents
4) The cell now starts making viral proteins
5) It displays these as non-self MHC
6) The CD8 cells detects the non-self MHC and attacks
7) The CD8 cell kills the virally infected cell
CD4 helper cells types
Th1 - pro-inflammatory (boosts cellular immune response)
Th2 - pro allergic (boosts multi-cellular response)
Th 17 - pro-inflammatory (controls bacterial and fungal infection)
Treg (Th0) - anti-inflammatory (limits immune response)
Tfh - pro-antibody
State the functions of IL-1, IL-2, IL-3, IL-4, IL-5, IL-6 (HOT T-BONE STEAK), and which T helper cell class are they each produced by
- IL-1: fever (hot) (Th1)
- IL-2: T cell stimulation (Th1)
- IL-3: Bone marrow stimulation (and myeloid progenitor cells) (Th1)
- IL-4: class switching to IgE, promote antibody production (Th2)
- IL-5: IgA, eosinophils promote antibody production **(Th2)
- IL-6: aKute-phase protein production, and fever (Th17
Structure of antibodies
Y shaped molecule made of 2 (identical) heavy and 2 (identical) light chains- they’re divided into 2 areas- constant and variable regions- huge potential for diversity in variable region
A natural immunoglobulin molecule can have any one of five classes of heavy chain.
3 main antibody functions
- Neutralisation - antibody prevents bacterial adherence to host cell
- Opsonisation - promotes phagocytosis
- Complement Activation - enhances opsonisation and lyses some bacteria
List antibody classes
- IgG most abundant
- IgM produced upon antigen invasion increases transiently
- IgA expressed in mucosal tissues forming dimers after secretion
- IgD
- IgE involved in allergy and parasitic infection
Which antibody class has highest opsonisation activity?
IgG
Which antibody class has highest neutralization activity
IgG
What name is given to cellular receptors that bind to antibodies
Fc receptors
Bind to fc region if antibodies
What are the antibodies the B cell makes the same s
The BCR have unique binding site that binds to an epitope
What do native cells need to be activated
Accessory signal
1) directly from microbial constituents
2)from a T helper cell
T cell helper thymus dependant pathways
Antibodies made
All iG classes and memory made
How are B cells activated by T cells
1) The membrane bound BCR recognises antigen
2) The receptor-bound antigen is internalised and degraded into peptides
3) Peptides associate with ‘self’ molecules (MHC II) and is expressed at cell surface of B cell
4) This complex is recognised by matched CD4 T helper cell (that has been activated by recognising an antigen presented via MHC II by an APC like a dendritic cell)
5) B cell activated by co-stimulation markers and cytokines that Tfh release
Thymus independent path
Thymus Independant antigens directly activate B cells without help of T cells
Second signal provided by PAMP
Makes only igM and no memeoy
What class of bacterial molecules provide primary and secondary stimuli for B cell activation
polysaccharides OR lipopolysaccharides
MHC/TCR interactions
Intracellular:processed in cytosol,presented on MHCI,presented to CD8 cells
Extracellular: processed in endosomes,presented on. MHCII,presented to CD4 cells
