4.5 - Lymphocytes Flashcards
1
Q
White blood cell types
A
Innate immune cells:
- macrophages - eats stuff
- neutrophil - kills stuff
Adaptive immune cells - lymphocytes:
- T cell - orchestrates immune response / kills infected cells
- B cell - makes antibody
2
Q
Adaptive immunity
A
- improves efficacy of innate immune response
- focuses a response on the site of infection and the organism possible
- has memory
- needs time to develop
- specific and can differentiate within families
- absence of adaptive immunity results in inability to clear infections
- protects us from repeat infections with the same pathogens
- not without costs - autoimmunity
3
Q
Immunological memory
A
- once the immune system has recognised and responded to an antigen, it exhibits memory
- memory responses characterised by a more rapid and heightened immune reaction that serves to eliminate pathogens fast and prevent diseases
- reduction in severity on re-exposure
- antigen-specific lymphocytes (T and B) are the cellular basis
- basis for vaccines
4
Q
Types of adaptive immune response
A
T cells - cell mediated response
- produce cytokines to help shape immune response (CD4)
- kill infected cells (CD8)
B cells - humoral response
- produce antibodies
5
Q
Antigens
A
- antigens are molecules that induce an adaptive immune response (mostly proteins)
- antigens are how the adaptive immune system sees pathogens
- epitope: the region of an antigen which the receptor binds to
- T cells recognise linear epitopes in the context of MHC: cells can chop up proteins into fragments, which the MHC can display –> recognised by T cells
- antibodies recognise structural epitopes - recognise the tertiary structure of a protein
6
Q
Cell mediated response
A
- involves mostly T cells and responds to any cell that displays unusual MHC markers, including cells invaded by pathogens, tumour cells or transplanted cells
- APCs displaying foreign antigens bind to T cells
- interleukins (secreted by APCs or helper T cells) costimulate activation of T cells
- if MHC-1 and endogenous antigens are displayed on the plasma membrane, T cells proliferate, producing cytotoxic T cells. If MHC-II and exogenous antigens are displayed on the plasma membrane, T cells proliferate, producing helper T cells
- helper T cells release interleukins (and other cytokines), which stimulate B cells to produce antibodies that bind to the antigens, and stimulate nonspecific agents (NK and macrophages) to destroy the antigens
7
Q
Humoral response
A
- controlled by activated B cells and antibodies
1. antigens bind to B cells
2. interleukins or helper T cells costimulate B cells (usually both antigen and costimulator needed to activate B cell and initiate proliferation)
3. B cells proliferate and produce plasma cells which bear antibodies with the identical antigen specificity as the antigen receptors of the activated B cells
4. antibodies are released and circulate through the body, binding to antigens
5. B cells produce memory cells (secondary response)
8
Q
Clonal expansion
A
- each lymphocyte bears a single, unique receptor
- interaction between a foreign molecule and that receptor leads to activation and clonal expansion (multiple copies of the same cell)
- differentiated effector cells of that lineage will bear the same receptor
9
Q
The problem of antigen diversity
A
- we are exposed to a large amount of different microbes and other antigenic determinants - immune system must be able to respond to all
- but - adaptive immune system is highly specific = to respond to all these different antigens, we need to have a very large pool of cells with specific receptors that can recognise these huge array of antigens
- we need to encode a massive repertoire of lymphocyte receptors
- each antibody is produced by a specific B lymphocyte expressing a specific BCR
- clonal selection: each lymphocyte bears a single, unique receptor; a specific antigen only activates its counter-specific cell, which then induces that particular cell to multiply, producing identical clones for antibody production
- generated through recombination
- 10^15 different antibodies, only 25000 genes
10
Q
Immunoglobulin gene rearrangement
A
- functional genes for antigen receptors do not exist until they are generated during lymphocyte development
- each BCR receptor chain (kappa, lambda and heavy chain genes) is encoded by separate multigene families on different chromosomes
- during B cell maturation these gene segments are rearranged and brought together
- this process generates the diversity of the lymphocyte repertoire
11
Q
T cell receptor
A
- part of a complex of proteins on the cell surface
- the variable region is made by gene reassortment
- recognises antigen fragments presented by other cells in the context of MHC
- components: carbohydrates, variable region, constant region, cytoplasmic tail (through transmembrane), disulphide bond between alpha and beta chain (if class II)
12
Q
The major histocompatibility complex
A
- plays a central role in defining self and non-self
- presents antigens to T cells
- critical in surgery and donor matching
- in humans, MHC is encoded by HLA genes
- the MHC is polygenic - several class I and II loci
- expression is codominant (maternal and paternal genes both expressed)
- MHC class I - all nucleated cells, although at various levels during infection / by cytokines. Has a single variable alpha chain plus a common beta-microglobulin. Communicates with CD8 cells
- MHC class II - normally only on professional APCs. Has two chains - alpha and beta. May be regulated by cytokines. Communicates with CD4 cells
13
Q
MHC / TCR interactions
A
intracellular pathogen/antigen –> processed in cytosol –> presented on MHC I –> presented to CD8 T cells (cytotoxic / killer cells)
extracellular pathogen/antigen –> processed in endosomes –> presented on MHC II –> presented to CD4 T cells (helper cells)
14
Q
CD4 T helper cell classes
A
- T helper cells produce cytokines (a family of inflammatory mediators)
- cytokines have diverse actions on a wide range of cells
- cytokines influence the outcome of the immune response
- Treg (Th0) - anti-inflammatory, limits the immune response
- Th1 - pro-inflammatory, boosts cellular immune response
- Th2 - pro-allergic
- Tfh - pro-antibody
- Th17 - pro-inflammatory, controls bacterial and fungal infection
15
Q
CD8 (cytotoxic T lymphocytes)
A
- kill their targets by apoptosis / programmed cell death
- apoptosis is characterised by the fragmentation of nuclear DNA
- CTL store perforin, granzymes, granulysin in cytotoxic granules released after target recognition
- perforin molecules polymerise and form pores
- CD8 cells detect non-self MHC and attacks, killing any infected cells
16
Q
Antibodies
A
- produced mainly by plasma cells
- used by the immune system to neutralise pathogens like viruses
- recognises antigen via the fragment antigen-binding (Fab) variable region
- each tip of the ‘Y’ of the antibody contains a paratope that is specific for one particular epitope
- two heavy and two light chains joined by disulphide bonds, constant region (interacts with other cells, functional part of molecule), variable region (specificity), hinge region
- 3 core protective roles: neutralisation (prevents bacterial adherance), opsonisation (promotes phagocytosis), complement activation (enhances opsonisation and lyses some bacteria)
17
Q
Antibody classes
A
- IgG - highest opsonisation and neutralisation, classified into four subclasses (1-4)
- IgM - 5 joined together in ring, produced first upon antigen invasion, increases transiently
- IgA - 1/2/3 units, expressed in mucosal tissues, forms dimers after secretion
- IgD - unknown function
- IgE - involved in allergy
18
Q
B cells
A
- B cell generation and maturation occur in the bone marrow in the absence of antigen
- derived from stem cells in bone marrow
- migrate into circulation (blood, lymphatic system) and into lymphoid tissues
- mature B cells specific for particular antigen
- specificity resides in BCR for antigen
19
Q
B cell receptor
A
- surface bound antibody - encodes the antibody the cell will make
- BCR have a unique binding site which bind to a portion of the antigen called the epitope / antigenic determinant
- made before the cell ever encounters the antigen
- is present in thousands of identical copies on the surface of the B lymphocyte
- B cells bind soluble antigen
- has a light and heavy chain
- each is encoded by an individual gene, which is made by recombination of building blocks
- occurs in bone marrow before B cell is released
20
Q
Antibody production by B cells
A
- naive antigen-specific lymphocytes (B / T) cannot be activated by antigen alone
- naive B cells require accessory signal:
1. directly from microbial constituents (thymus-independent, only IgM, no memory)
2. from a T helper cell (thymus-dependent, all Ig classes, memory)
21
Q
Thymus-independent antigens
A
- directly activates B cells without help of T cells
- often polysaccharide, needs to have repetitive structure e.g. bacterial surface sugars
- the second signal is provided by a microbial PAMP e.g. LPS (or by an accessory cell)
22
Q
Thymus-dependent pathway
A
- membrane bound BCR recognises antigen
- receptor-bound antigen is internalised and degraded into peptides
- peptides associate with ‘self’ molecules (MHC class II) and is expressed at the cell surface
- this complex is recognised by matched CD4 T helper cell
- B cell activated
