Immunology 2 Flashcards

1
Q

Lymphocyte target

A

Very specific regions = epitomes

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2
Q

Lymphocyte specificity

A
  1. Each lymphocyte will bear single type of antigen receptor
  2. Antigen binding to its receptor will trigger lymphocyte activation
  3. Cells derived from the same activated cell all have the same specific receptor = effector cell
  4. Self antigens are deleted during progenitor cell process
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3
Q

B cell antigen

A

antigen receptor = antibody that is a surface receptor known as a BCR (b cell receptor)

they can also secrete these antibodies/antigen receptors

these antigen receptors are:
antibodies
Ig = immunoglobulins

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4
Q

plasma cells

A

activated B cells which secrete antibodies specific for antigens and contain the same antigen receptor (as BCR)

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5
Q

antigen

A

any molecule, host derived or foreign that can trigger an immune response

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6
Q

immunogen

A

any molecule, host derived or foreign that always triggers an immune response

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7
Q

hapten

A

potentially antigenic but may not be big enough to trigger immune response

when added to macromolecule e.g. hapten carrier complex it can trigger an immune response and act as as immunogen

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8
Q

Fc effector region

A

base of the heavy chain at the transmembrane region which defines the subclass of the antibody

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9
Q

Fab region

A

binds to the antigen

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10
Q

Random recombination

A

diversity of Fab region/variable region

variable regions are inherited as sets of gene segments

information for the variable domains is present in 3 gene libraries:
V, D + J segments

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11
Q

b cell mutation

A

extreme rate of somatic hypermutation

B cells: 100 thousand fold higher than spontaneous mutation for other genes

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12
Q

antibody antigen binding mechansism

A
  1. neutralisation
  2. agglutination
  3. precipitation
  4. complement fixation
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13
Q

neutralisation

A

blocks viral binding sites

coats bacteria and/or opsonization

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14
Q

agglutination

A

coagulation of many pathogens

IgM with 10 binding sites allowing 5 different pathogens to be held together

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15
Q

precipitation of soluble antigens

A

binds them together so they can be precipitated out of solution also by phagocytosis

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16
Q

complement fixation

A

lysis of cell via C9

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17
Q

epitope types

A

linear epitopes formed by adjacent AA residues

discontinuous epitopes are the same protein antigen in different conformation allowing for all together different antibody to bind to it

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18
Q

2 types of light chains

A

kappa

lambda

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19
Q

5 types of heavy chains

A
IgA (secondary)
IgD -
IgG (secondary)
IgE - 
IgM (primary)
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20
Q

IgA

A

secondary immune response where antigens gain access to mucous membranes

associated with mucous membranes and has a secretory component

saliva
gastric fluid
sweat
tears
mucous
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21
Q

IgD

A

no well characterised biological function

22
Q

IgG

A

secondary immune response (dominant in memory cells)

80% of plasma Ig

it is the only Ig that can cross placental barrier and has role in neonatal immunity

very effective complement activator

4 isotypes (1 - 4)

23
Q

IgE

A

associated with type 1 hypersensitivity allergic response and immune response to parasites

24
Q

IgM

A

primary immune response (doesnt exist in secondary)

pentameric structure with 10 antigen binding sites

excellent complement activator

the only antibody made by foetus

25
B cell expansion
takes 4 - 5 days to complete naive to activated to effector effector cannot be maintained so eliminated eventually activated to memory B cells
26
selective IgA deficiency
commonest primary defect of specific immunity IgA is associated with mucous membrane so recurrent infections IgG can compensate but over reactive so linked to autoimmune disorders as produces autoantibodies also linked with allergies
27
primary antibody deficiencies
deficiencies born with and normally X linked or autosomal recessive
28
MHC
is a region of DNA that encodes a group of molecules known as MHC proteins it is the most gene dense region of the mammalian genome proteins encoded by MHC are expressed on cell surface in humans MHC genes = HLA human leukocyte antigen letters following HLA isotypes are termed based on different DNA sequences that encode the particular isotype
29
MHC proteins
present both self antigens and nonself antigens MHC class I and class II only have one peptide binding grove and each MHC molecule can only present one peptide at a time broad specificity
30
MHC class I
alpha chain complexed to beta 2 microglobulin isotypes: HLA - A/B/C/D/E/F/G etc present endogenous antigens (self antigens) + viral proteins presents to CD8 + cytotoxic T cells widely expressed on all nucleated cells and normally the MHC class I is complexed with self peptides
31
MHC class II
both alpha and beta chain isotypes: HLA - DM/DO/DP/DQ/DR present exogenous antigens (bacterial proteins) presents to CD4+ T helper cells expressed only by certain cells of the immune response e.g. dendritic cells, macrophages, B cells.
32
MHC class I Ag processing
the cell samples its own intracellular proteins and presents them on MHC I cytosolic proteosome which degrades proteins into peptide fragments the peptide fragments (5 - 15 aa in length) are transported to ER via protein TAP antigen (peptide fragment) + MHC are complexed physically in the endoplasmic reticulum
33
MHC class II Ag processing
exogenous peptide is phagocytosed in the cell and held in the phagosome phagosome fuses with lysosome and exogenous peptide is broken down into fragments endosomes containing MHC class II fuse with peptide fragments
34
HLA alleles and disease
not all individuals with at risk allele will develop the disease but most cases associated with obvious immune pathology: chronic inflammation arthritis autoimmune diseases are associated with specific HLA
35
ankylosing spondylitis
90% of affected have HLA - B27 10% of normal population has HLA - B27
36
B cell vs T cell adaptive immunity
T cell = cellular arm of adaptive immunity B cell = humoral arm of adaptive immunity BCR are specific for antigen TCR are specific for antigen/MHC combination TCR only exists as cell surface receptor TCR diversity is by gene rearrangement MCR diversity is by somatic hypermutation
37
T cell activation
fragmented LINEAR antigenic peptides
38
CD4+/T helper cell
secreted short range effector cytokines to recruit B cells and macrophages
39
CD8+/cytotoxic T cell
bind and directly kill
40
T reg cells/T suppressor cells
suppress response to self antigens and shut down T cells when infection cleared
41
TCR structure and genes
each T cell is specific for one antigen/MHC combination variability is achieved at the antigen binding region antigen binding domain has 3 hypervariable regions diversity is achieved by gene rearrangement
42
gene rearrangement of TCR genes
for alpha chain: V + J | for beta chain: V + D + J
43
thymocyte maturation
T cells are long lived thymocytes = immature, intrathymic T cell precursors thymocytes become educated and MHC restricted in the thymus to become = mature T cells mature T cells migrate to secondary lymphoid organs
44
thymus
large in children and shrinks with age subcapsular zone contains early progenitor cell cortex packed with developing T cells medulla contains fewer but more mature T cells thymus contains many epithelial cells, macrophages and dendrites for antigen presentation and T cell education all possible antigens in the body are produced by cortical epithelial cells and presented to developing T cells
45
thymic epithelium express
MHC class I + II growth factors
46
T cell development
step 1: naive thymocytes enter the thymus and undergo gene rearrangement to display different TCRs. They are double negative i.e. CD4 + CD8 step 2: positive selection double negative t cells undergo positive selection and co receptor engagement. only T cells that bind appropriately to MHC molecules on cortical epithelial cells survive. they are now double positive step 3: negative selection eliminates self reactive T cells when it encounters self peptides on dendritic cells in the medulla. results in single positive T cell step 4: maturation useful T cells that dont interact with host protein are single positive and are said to be mature, MHC restricted and antigen naive.
47
T cell development pathway
step 1: double negative in subcapsular region step 2: positive selection (removes useless) double negative --> double positive by cortical epithelial cells step 3: negative selection (removes self antigens) double positive --> single positive by dendritic cell + medullary macrophage step 4: maturation go to periphery
48
matured T cell activation
although mature they are said to be antigen naive as they have not encountered their antigen yet a positive interaction allows the activation of the T cell into an effector T cell
49
CD4+ T cells
helper cells produce many cytokines TNF alpha and IL - 1 cytokines in turn activate other immune cells: B cells, phagocytes, eosinophils, CD8+, macrophages 2 types: Th1 = viruses and bacteria via IFN gamma Th2 = parasites + worms via IL-4 and IL-5
50
CD8+ T cells
once activated --> effector CD8+ cytotoxic T cell lymphocytes within the cytoplasm there is a full range of cytotoxic protein e.g. perforin or granzyme B and other molecules pumped directly into infected or tumorigenic cells which will directly kill it
51
primary defects in cell mediated immunity
impairment in T cell function is associated with B cell dysfunction most defects are combined immunodeficiency
52
Di george's syndrome
neonates born with defect in T cell population will result in infants with major failure in both T and B cells failure to thrive chronic diarrhoea respiratory infections die before 2 years old cause: deletion of portions chromosome 22 development defects of: heart parathyroid + thymus