Immune system Flashcards

1
Q

immune system responsible for?

A

complex system responsible for distinguishing self from non-self, for protecting against infections

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2
Q

primary and secondary lymphoid organs

A

primary lymphoid organs: bone marrow and thymus
(site of production and education of immune cells)

secondary lymphoid organs: spleen and lymph nodes (site of interaction immune system and foreign material)

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3
Q

lymph nodes and spleen function

what is lymph

A

lymph nodes and spleen monitor contents of fluid for potential pathogens

spleen filters blood
lymph nodes filter lymph

lymph is extracellular fluid that must be drained to prevent build up
less structured lymphoid tissue also exists, ie like tonsils, peyer’s patches

spleen is also site of WBC storage and destruction of old cells

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4
Q

WBCs make up what % of blood

A

1%

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5
Q

what proportion of WBCs are lymphocytes, monocytes, granulocytes

A

30% lymphocytes
5% monocytes
60% granulocytes

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6
Q

lymphocytes brief description

A

may live decades/ lifetimes
mostly found in lymph nodes and spleen
produce loads a day
B cells and T cells

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7
Q

monocytes brief description

A

circulate in blood 24 hours

if stimulated, develop into macrophages in tissue

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8
Q

granulocytes brief description

A

/polymorphonuclear leukocytes
only live a few days
neutrophil is the most common

neutrophils: multilobed nucleus, granules contain lysosyme, gransyme, defensins
eosinophils: bilobed nucleus, granules contain histamine, cytotoxic proteins
basophils: contain mainly histamine

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9
Q

contents of lymph nodes

A

where lymphocytes reside and first encounter foreign substances

T cells and dendritic cells in paracortex
B cells in outer cortex, germinal centre

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10
Q

what WBC do we see in tissues

A

low levels of T cells
dendritic cells if in contact w ext env
mast cells
macrophages

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11
Q

a leukocyte is?

A

another word for white blood cell

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12
Q

myeloid lineage?

A
haematopoietic stem cell 
myeloid progenitor cell:
- (RBCs and platelets)
- monocyte
- eosinophil
- neutrophil
- basophil
- mast cell

monocyte to

  • macrophage
  • dendritic cell
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13
Q

lymphoid lineage?

A

haematopoietic stem cell
lymphoid progenitor to

T cell progenitor to:

  • helper T cell
  • Cytotoxic T cell
  • memory T cell

Natural Killer cell

B cell progenitor to:

  • plasma cell
  • memory B cell
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14
Q

stages of infection?

A
entry into body
replication and spread
disease
exit from body
reinfection of someone else
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15
Q

how are extra vs intracellular pathogens spread

A

intracellular pathogens spread by cell to cell contact

extracellular pathogen spread by lymph/ blood

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16
Q

innate vs adaptive immunity, time difference

A

innate: immediate protection
0-4h preformed mediators
4-96h recruit innate immune cells

adaptive: after 96h

becomes more specific with time

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17
Q

innate immunity consists of

A

physical barriers
anti-microbial factors
pro- inflammatory factors, fever
phagocytes and NK cells

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18
Q

where are physical barriers important

A

anywhere in contact with external, included GI and genitourinary

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19
Q

name physical barriers of

respiratory tract
eyes
GI
skin
genitourinary
A

respiratory: mucus, ciliated epithelium
eyes: tears (flush), lysozyme, lactoferrin

GI: stomach acidity, intestinal pH, flora, lysozyme, mech flushing

Skin: dead layer barrier, sweat and sebum (also flush), antimicrobials, low pH, commensal bacteria, shedding

Genitourinary tract: washing by urine, vaginal secretions, urine acidity, lysozyme

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20
Q

what are the anti microbial factors, give examples

A

lysozyme and lactoferrin found in many barriers

complement proteins lyse/coat bacteria in blood to be phagocytosed

cells of innate produce anti-microbial peptides AMPs

cytokines- IFN

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21
Q

if cells of the innate immune system do not recognise specific pathogens, how do they identify self vs non self

A

express pattern recognition receptors (PRR) that respond to broad pathogen associated molecular patterns (PAMPs)

there are 4 main types of PRR

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22
Q

what are the cells of the innate immune system

A

the granulocytes, so the
basophil
eosonophil
neutrophil

mast cell
monocyte
macrophage
dendritic cell

Natural killer T cells

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23
Q

what are phagocytes

A

WBCs/ tissue dwelling cells able to ingest and kill microbes

monocytes- in blood
netrophils- in blood (most of)
macrophages- in tissues (most effective)

granules are toxic so kill bacteria
after eat a few, die and turn to pus

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24
Q

natural killer cells?

A

large granular lymphocytes, activated by cytokines, recognise altered self cells

able to recognise and kill infected cells by apoptosis over miutes or hours. NK cell comes away unharmed

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25
Q

what are the 4 signs of inflammation

A

redness, swelling, heat, pain

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26
Q

how may infammation lead to a fever

A

inflammation is local to site of infection, if factors get into blood stream may develop an in parallel systemic infection- a fever

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27
Q

how is a fever caused and why

A

triggered by toxins from infecting organsim or by immune systems own inflammatory mediators

ie IL1 acts on hypothalamus (where thermostat)

higher temp inhibits bacterial growth and speeds metabolic actions- repair, antibody prod, phagocytosis

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28
Q

process of inflammation resulting from tissue damage?

A
  1. microbes gain entry to host via local epithelium, cause tissue damage as proliferate
  2. inflammatory mediators are released by macrophages- chemokines, cytokines, histamine. These diffuse through tissue into blood
  3. they cause vasodilation and incr permeability
  4. when exposed to inflamm mediators, neutrophils (instead of rolling along vesell wall w/o stopping) stop as adhesion molecule expression changes, stick to vessel wall
  5. neutrophils and macrophages squeeze through the now leaky vessel wall into tissue. Migrate up chemokine gradient coming from tissue damage to site of infection
  6. activated en route, arrive ready to phagocytose bacteria

serum proteins like clotting factors and RBCs also leak through causing swelling, oedema, redness

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29
Q

inflammation in response to tissue damage therefore involves

A
vasodilation and increased permeability
accumulation of blood
leakage of clotting proteins
chemotaxis of neutrophils/ macrophages, phagocytosis
death of phagocytes, pus
initiation of tissue repair
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30
Q

adaptive immunity is?

A

a dedicated system of tissues, cells, molecules that act in concert to provide specific immune responses

3 cardinal characteristics:
specificity
memory
discrimination (btwn self and non)

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31
Q

what cells make up the adaptive immune response

A

lymphoid lineage, so

helper T cell
Cytotoxic T cell
memory T cell

NK cell

plasma B cell
memory B cell

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32
Q

how does the adaptive immune system have memory/ space for so many different pathogens

A

selective clonal expansion

each lymphocyte has unique receptors for specific pathogen, there are 100 million different cells with different receptors

clonal expansion on contact with pathogen= lymphocyte with complementary receptor binds to pathogen, causes lymphocyte to deivide and differentiate to produce daughter cells

rapid expansion of population specific to infection

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33
Q

selectiv clonal expression provides differentiated cells for antigen elimination, but what else?

A

immunological memory

a proportion of cells will become memory cells (long lived) whilst the others go on to become effector cells

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34
Q

how do T and B cells develop

A

from common precursor- haematopoietic stem cell- in bone marrow

virgin, antigen naive cells are released,
pre T cells go to Thymus
pre B cells go to Bone marrow
(primary lymphoid organs)

self reactive cells are deleted, the rest will mature and be released into circ

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35
Q

quick recap- what is innate immunity

A

a rapid response to a challenge. not antigen specific, does not change.

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36
Q

B cells are responsibly for what type of immunity?

A

humoral immunity, ie antibody mediated immunity

following encounter with specific pathogen, B cells activate and differentiate into plasma cells which produce antibodies
some will become memory B cells

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37
Q

plasma cell define

A

effector B cells with synthetic/ secretory machinery for manufacture and export of large amounts of specific antibodies

have receptor specifc to pathogen, then secrete antibodies basically

ie antibody producing factories

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38
Q

antibodies are

A

soluble effector molecules produced by B cells
also called immunoglobulins

all antibodies produced by an individual B cell will have identical antigen specificity

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39
Q

antibody basic structure

A

2 identical heavy chains
2 identical light chains

linked together by intermolecular disulfide bonds

hinge region gives flexibility

constant region on one end

variable region on other end (AAs differ) determines specificity

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40
Q

antigens are

A

foreign molecules recognised by antibodies as non self
usually big, commonly proteins but may be other`
complementary to antibody

41
Q

what type of antigen is most immunogenic

A

proteins have greater chance or producing an immune response as greater number of shapes poss

42
Q

difference in functionality btwn constant and variable region? and fancy names

A

variable region has 2 antigen binding sites, Fab, antibody binding fragments

contant region, 2 ends align to form the Fc, the constant fragment, has effector function, binding cells and things, ie complement

43
Q

what are the 5 main classes of antibody, why are they classed as such

A

have different constant (Fc) regions so have different effector functions

IgG
IgM
IgA
IgE
IgD
44
Q

IgG basic info

A
in blood and tissues
fixes complement, binds phagocytes, neutralises toxins
can cross placenta
classic 4 chain structure
found as a monomer
45
Q

IgM basic info

A

pentomer of standard unit, so too big to get into tissues (unless inflamed) so it is a
blood antibody
fixes complement w great avidity
acts as B cell receptor

46
Q

IgA basic info

A

dimer
protected structurally from digestion so found at
mucosal surfaces and secretions

47
Q

IgE basic info

A

extra long Fc region
HELMINTHS
allergy response
binds to receptors on mast cells and basophils

48
Q

IgD basic info

A

expressed on naive B cell, function unknown

49
Q

how do antibodies neutralise toxins? why do they need to do this? which type do it most

A

some pathogens produce toxins that interact w cell receptors. to neutralise, antibody must bind to the toxin. prevents it binding with receptor and being internalised by target cell

bind to form antibody toxin- complex/ immune complexes. this is targeted for destruction by phagocytosis

IgG v small, diffuses rapidly and has high affinity toxins
IgA similar at mucosal surfaces

50
Q

what is opsonisation and what are the opsonins

A

the coating of bacteria by antibodies to target for phagocytosis by macrophages and neutrophils (which have Fc receptors)

opsonins are IgG and IgM and complement cascade fragments

important for immunity against encapsulated bacteria

51
Q

why is a capsule a virulence factor

A

capsule is a polysaccharide layer that has lies outside cell envelope, not easily washed off and can cause various diseases

enhances bacteria ability to cause disease as prevents phagocytosis

a capsule specific antibody may be required for phagocytosis to occur

52
Q

how can antibodies kill bacteria

A

by activating complement

opsinise bacteria
complement binds to antibody Fc region
causes lysis
products ingested by phagocytes

53
Q

what is agglutination of pathogens by antibodies

A

similar process as neutralisation of toxins- antigen-antibody complex binds several pathogens etc together in a clump so can’t access elsewhere

54
Q

so, antibody functions are?

A

neutralisation of toxins
agglutination of pathogens
opsonisation
complement activation for lysis of bacteria
passive immunity in transplacental transfer

55
Q

if have no lymphocyte precursor you have

A

no T or B cells, have SCID

56
Q

if have a problem with the B cell progenitors

A

have low antibodies, have Bruton’s disease, have recurrent infections as can’t opsonise

57
Q

T lymphocytes are responsible for what type of immunity?

A

cell mediated immunity

58
Q

what do T lymphocytes do

A
kill virus- infected cells
resistance against intracellular pathogens
activate macrophages
help antibody responses
immunoregulatory function
59
Q

activation and differentiation of T lymphocytes

A

if specific antigen present, T cell undergoes clonal expansion and proliferation, somebecome memory cells, some become effector cells

60
Q

what is the difference between T and B cell activation

A

B cells may see the antigen in isolation and activate

T cells cannot see the antigen in isolation, must see in the context of an antigen presenting cell AND multihistocompatability complec (MHC) of either class 1 or 2

61
Q

what is the interaction between the T cell and antigen presenting cell called

A

the immunological interface

62
Q

multi histocompatability comlex class 1 vs class 2

A

MHC class 1 found on all nucleated cells

MHC class 2 only found on antigen presenting cells: monocytes, dendritic cells, macrophages, B cells
therefore has restriccted distribution
63
Q

what is the only APC for primary immune response (innate)

A

dendritic cell

64
Q

dendritic cell function

A

major function= link innate and adaptive immune systems
immature dendritic cells travel in bloodstream and tissues constantly sampling pathogens through macropinocytosis
phagocytoses and matures, migrates to lymph node to present antigen to T cell to activate clonal expansion

if thhere is an infection when the DC experiences the antigen, DC will recognise PAMPS and upregulate costimulatory molecules and cytokines

65
Q

naive t cell requires signals to activate- what

A

signal 1: T cell receptor binding to antigen-MHC complex
signal 2: presence of costimulatory molecules
signal 3: cytokines

requires all 3 in order to activate so as to ensure productive response only when necessary

66
Q

how does the T cell bind to the antigen-MHC complex

A

T cell receptor binds to both the antigen and MHC
so the receptor must have affinity for both

antigen sits in groove of MHC, T cell receptor hugs around it
(MHC is attached to APC)

67
Q

why is there lots of diversity in antigen presentation

A

MHC= HLA, human leukocyte antigen, gene found on chromosome 6
HLA molecules are polygenic, polymorphic, codominant so lots of diversity in antigen presentation

68
Q

how are T cells classified

A

according to pattern of cluster of differentiation (which CD molecules they express

ALL T cells express CD3

T helper cells CD4+

T cytotoxic cells CD8+

69
Q

which of T helper cells and T cytotoxic cells are MHC class 2 restricted?

A

T helper cells are MHC class 2 restricted

70
Q

what do cytotoxic CD8+ cells do

A

kill virally infected cells (also important in killing of intracellular bacteria, fungi, viruses)

T cytotoxic cells recognise viral antigen-MHC class 1 complex
triggers CD8+ cell to release death signals
causes cell death of virally infected cell by apoptosis

for most effective proliferation, requires 2 signals-
signal 1: viral antigen- MHC class 1 comples
signal 2: from CD4+ T helper cells

71
Q

how T helper cells promote proliferation of CD8+ cells

A
  1. dendritic cell brings antigen to lymph node, if presented on MHC class 2 stimulates antigen specific CD4+ cells
  2. activated CD4+ T helper cells secrete IL-2
  3. IL-2 acts as T cell growth factor for both antigen specific CD4 and CD8 cells
  4. both sets proliferate and become effector cells (and some memory)
  5. effector T cells leave lymph node, migrate to source of infection
72
Q

side not, what is an epitope

A

an epitope is the specific part of the antigen that is recognised by the antibodies

73
Q

what do T helper cells do

A

determine which epitopes are targeted by immune system
determine nature of immune response directed towards target antigens (eg CD8 cell or antibody)
required for normal B cell function

74
Q

how are T helper cells divided further

A

divided into 5 subsets on basis of which cytokines they secrete

most common:

Th1

  • broadly: cell mediated response
  • activating macrophages
  • responses to intracellular pathogens
  • cytotoxic t cell activation

Th2

  • broadly: humoral response
  • promote B cell activation (antibody prod)
  • target parasitic organisms
  • induces rise in IgE via IL-4

the cytokines they release are antagonistic to eachother so one is always dominant over the other

75
Q

how do Th1 helper cells activate macrophages

A
  • activate macrophages to kill intracellular micro-orgasims

infected macrophage expresses antigen and MHC class 2, they all bind,
Th1 cells secrete IFN gamma,
activates macrophage to kill pathogen

76
Q

how important is Th2 to antibody production

A

almost all antibody responses require Th2 help

IgM can be produced independently

77
Q

what are cytokines

A

in both innate and adaptive

small, secreted proteins
act locally via cell surface receptors
can cause activation/ proliferation of immune cells
mediate inflammation
interferons can produce antiviral state in cells

78
Q

what is the complement system

A

consists of about 20 serum proteins

has several actions, including lysis of bacteria and fungi, inflammation, opsonisation of infected cells

79
Q

basophils and mast cells, similarities and differences

A

basophils in blood
mast cells in tissues

have similar functions and morphology but different locations

basophils are the least common polymorphonucleocytes, can only survive a few days in blood

mast cells in high numbers close to blood vessels, skin, mucosal membranes, survive months/ years

common precursor. both have biogenic amines, lipid mediators, cytokines, enzymes preloaded

important in elimination helminths and parasites and big players in autoimmunity

80
Q

how are mast cells/ basophils activated

A

vasoactive mediators and cytokines are stored in granules (histaminem heparin etc)
degranulation occurs instantly when activated by pathogen/ endogenous products
signify infection to host
type of response depends on location of stimulus

81
Q

what does a mast cell cause in response to pathogen/ allergen in skin

A

increased blood flow and permeability

leads to vasodilation
endothelial cell activation
recruitment neutrophils and eosinophils

82
Q

what does a mast cell cause in response to pathogen/ allergen in airways

A

decreased diameter, increased mucus to immobilise

factors released cause cellular recruitment, bronchial constriction

coughing, immobilisation of pathogen in mucus, destroyed by mast cell enzymes

83
Q

what does a mast cell cause in response to pathogen/ allergen in gastro tract

A

incr fluid secretion and peristalsis

causes expulsion of parasites, diarrhoea, immobilisation of pathogens, cytoprotection

84
Q

what does a basophil cause in response to pathogem/ allergen in blood

A

incr blood flow and permeability, so tissue fluid goes into lymph nodes quicker

85
Q

what doe eosinophils do and yeah

A

in blood. low amounts but increase dramatically for helminths/ parasites

contain cationic granule proteins and enzymes
release preloaded contents onto pathogen to kill it

also involved in tissue remodelling, damaged tissue and pathogen debris clearance

86
Q

how do kinetics of antibody response change with time

A

1st infection (usually IgM, ow affinity), slower response, 2nd infection with high affinity Ig, little to no symptoms, 3rd infection no symptoms, big spike Ig production, immunological memory

vaccination takes advantage of immunological memory

87
Q

MHC class 1 endogenous pathway

A
way in which APC processes and presents antigen with MHC  class 2
endogenous pathway= intracellular antigen

antigen is already within cell at start, is fragmented by proteosome
transported through RER/SER and binds with MHC class 1 to form MHC-antigen complex
that is transported to and presented at surface
CD8+ cell will recognise

88
Q

MHC class 2 exogenous pathway

A

way in which APC processes and presents antigen with MHC class 2

exogenous pathway =extracellular antigen

exogenous antigen internalised by phago/endocytosis and is fragmented by proteases
MHC class 2 brough to surface and associates with antigen and is presented
CD4+ cell will recognise
89
Q

receptor is always cell associated with a transmembrane region in a T or a B cell? what is the other like

A

T cell receptor always cell associated, always has a transmembrane region

B cell receptor initially with transmembrane region, but this is lost when molecule is secreted as antibody

90
Q

how does immune system formulate so many unique receptors for every pathogen

what are the 4 sections

A

if encoded in full in genome then would be more genes than we have

instead have random recombination events and gene rearrangement- a complete variable region of receptor formed

consists of

Variable region
Diversity region
Joining region
Constant region

91
Q

how does gene rearrangement work for receptors

A
  1. D to J recombination event
  2. V to DJ recombination event

a gene is selected in each selection and unwanted are removed

random selection of V, D, J segments from large gene pool generates all diverse numbers receptors needed
as such, each B/T cell receptor is product of several genes

92
Q

what region is there none of in light chain of antibodies

A

D region

93
Q

what is somatic hypermutation

A

in B cells- antigen receptors undergo further modification through somatic hypermutation once encounter antigen- high rate of point mutations to further diversity

94
Q

what is the cost of being able to produce so many random receptors

A

may create self- reactive actigen receptors so now need mechanisms to prevent immune damaging tissue

95
Q

how does selection of autoreactive cells work in B cells

A

negative selection occurs in bone marrow, only 10% will survive selection.

receptor gene rearrangement
if recognise self antigens in bone marrow
B cell apoptosis/ may be rescued and receptor edited/ made anergic (unable to respond to activation)

h/e if don’t see its antigen in bone marrow will escape process

96
Q

how does selection of autoreactive cells work in T cells

A

undergo 2 rounds in thymus. 98% T cells die.

  1. positive selection for MHC recognition. failure= apoptosis. depending which interact best with becomes cd8/cd4
  2. negative selection, if bind with self antigen with MHC then receive death signal

again, some will escape

  • may never see their antigen
  • anergic, see antigen but not with danger signals
  • apoptosis
97
Q

what is central tolerance

A

the process of deleting any self reactive cells in early stage lymphoid development

98
Q

what is peripheral tolerance

A

ensure T B cells that escaped central tolerance won’t damage.
regulated by Treg cells and maybe T helper cells

if the T/B cell becomes activated in the periphary, Treg produces cytokines that inhibit nearby cells (regardless of antigen receptor)
this therefore dampens immune responses, VIP in reducing autoimmune and allergy

99
Q

what is immunosurveillance

A

the processes by which cells of the immune system look for and recognise foreign pathogens, such as bacteria and viruses, or pre-cancerous and cancerous cells in the body