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Pathology > Immunology 2 > Flashcards

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
Q

B cell expansion

A

takes 4 - 5 days to complete

naive to activated to effector

effector cannot be maintained so eliminated eventually

activated to memory B cells

26
Q

selective IgA deficiency

A

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
Q

primary antibody deficiencies

A

deficiencies born with and normally X linked or autosomal recessive

28
Q

MHC

A

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
Q

MHC proteins

A

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
Q

MHC class I

A

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
Q

MHC class II

A

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
Q

MHC class I Ag processing

A

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
Q

MHC class II Ag processing

A

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
Q

HLA alleles and disease

A

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
Q

ankylosing spondylitis

A

90% of affected have HLA - B27

10% of normal population has HLA - B27

36
Q

B cell vs T cell adaptive immunity

A

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
Q

T cell activation

A

fragmented LINEAR antigenic peptides

38
Q

CD4+/T helper cell

A

secreted short range effector cytokines to recruit B cells and macrophages

39
Q

CD8+/cytotoxic T cell

A

bind and directly kill

40
Q

T reg cells/T suppressor cells

A

suppress response to self antigens and shut down T cells when infection cleared

41
Q

TCR structure and genes

A

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
Q

gene rearrangement of TCR genes

A

for alpha chain: V + J

for beta chain: V + D + J

43
Q

thymocyte maturation

A

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
Q

thymus

A

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
Q

thymic epithelium express

A

MHC class I + II

growth factors

46
Q

T cell development

A

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
Q

T cell development pathway

A

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
Q

matured T cell activation

A

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
Q

CD4+ T cells

A

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
Q

CD8+ T cells

A

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
Q

primary defects in cell mediated immunity

A

impairment in T cell function is associated with B cell dysfunction

most defects are combined immunodeficiency

52
Q

Di george’s syndrome

A

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

Pathology (13 decks)

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