Immune system Flashcards
(99 cards)
1
Q
immune system responsible for?
A
complex system responsible for distinguishing self from non-self, for protecting against infections
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)
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
4
Q
WBCs make up what % of blood
A
1%
5
Q
what proportion of WBCs are lymphocytes, monocytes, granulocytes
A
30% lymphocytes
5% monocytes
60% granulocytes
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
7
Q
monocytes brief description
A
circulate in blood 24 hours
if stimulated, develop into macrophages in tissue
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
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
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
11
Q
a leukocyte is?
A
another word for white blood cell
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
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
14
Q
stages of infection?
A
entry into body replication and spread disease exit from body reinfection of someone else
15
Q
how are extra vs intracellular pathogens spread
A
intracellular pathogens spread by cell to cell contact
extracellular pathogen spread by lymph/ blood
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
17
Q
innate immunity consists of
A
physical barriers
anti-microbial factors
pro- inflammatory factors, fever
phagocytes and NK cells
18
Q
where are physical barriers important
A
anywhere in contact with external, included GI and genitourinary
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
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
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
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
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
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
25
what are the 4 signs of inflammation
redness, swelling, heat, pain
26
how may infammation lead to a fever
inflammation is local to site of infection, if factors get into blood stream may develop an in parallel systemic infection- a fever
27
how is a fever caused and why
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
28
process of inflammation resulting from tissue damage?
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
29
inflammation in response to tissue damage therefore involves
```
vasodilation and increased permeability
accumulation of blood
leakage of clotting proteins
chemotaxis of neutrophils/ macrophages, phagocytosis
death of phagocytes, pus
initiation of tissue repair
```
30
adaptive immunity is?
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)
31
what cells make up the adaptive immune response
lymphoid lineage, so
helper T cell
Cytotoxic T cell
memory T cell
NK cell
plasma B cell
memory B cell
32
how does the adaptive immune system have memory/ space for so many different pathogens
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
33
selectiv clonal expression provides differentiated cells for antigen elimination, but what else?
immunological memory
a proportion of cells will become memory cells (long lived) whilst the others go on to become effector cells
34
how do T and B cells develop
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
35
quick recap- what is innate immunity
a rapid response to a challenge. not antigen specific, does not change.
36
B cells are responsibly for what type of immunity?
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
37
plasma cell define
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
38
antibodies are
soluble effector molecules produced by B cells
also called immunoglobulins
all antibodies produced by an individual B cell will have identical antigen specificity
39
antibody basic structure
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
40
antigens are
foreign molecules recognised by antibodies as non self
usually big, commonly proteins but may be other`
complementary to antibody
41
what type of antigen is most immunogenic
proteins have greater chance or producing an immune response as greater number of shapes poss
42
difference in functionality btwn constant and variable region? and fancy names
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
what are the 5 main classes of antibody, why are they classed as such
have different constant (Fc) regions so have different effector functions
```
IgG
IgM
IgA
IgE
IgD
```
44
IgG basic info
```
in blood and tissues
fixes complement, binds phagocytes, neutralises toxins
can cross placenta
classic 4 chain structure
found as a monomer
```
45
IgM basic info
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
IgA basic info
dimer
protected structurally from digestion so found at
mucosal surfaces and secretions
47
IgE basic info
extra long Fc region
HELMINTHS
allergy response
binds to receptors on mast cells and basophils
48
IgD basic info
expressed on naive B cell, function unknown
49
how do antibodies neutralise toxins? why do they need to do this? which type do it most
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
what is opsonisation and what are the opsonins
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
why is a capsule a virulence factor
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
how can antibodies kill bacteria
by activating complement
opsinise bacteria
complement binds to antibody Fc region
causes lysis
products ingested by phagocytes
53
what is agglutination of pathogens by antibodies
similar process as neutralisation of toxins- antigen-antibody complex binds several pathogens etc together in a clump so can't access elsewhere
54
so, antibody functions are?
neutralisation of toxins
agglutination of pathogens
opsonisation
complement activation for lysis of bacteria
passive immunity in transplacental transfer
55
if have no lymphocyte precursor you have
no T or B cells, have SCID
56
if have a problem with the B cell progenitors
have low antibodies, have Bruton's disease, have recurrent infections as can't opsonise
57
T lymphocytes are responsible for what type of immunity?
cell mediated immunity
58
what do T lymphocytes do
```
kill virus- infected cells
resistance against intracellular pathogens
activate macrophages
help antibody responses
immunoregulatory function
```
59
activation and differentiation of T lymphocytes
if specific antigen present, T cell undergoes clonal expansion and proliferation, somebecome memory cells, some become effector cells
60
what is the difference between T and B cell activation
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
what is the interaction between the T cell and antigen presenting cell called
the immunological interface
62
multi histocompatability comlex class 1 vs class 2
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
what is the only APC for primary immune response (innate)
dendritic cell
64
dendritic cell function
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
naive t cell requires signals to activate- what
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
how does the T cell bind to the antigen-MHC complex
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
why is there lots of diversity in antigen presentation
MHC= HLA, human leukocyte antigen, gene found on chromosome 6
HLA molecules are polygenic, polymorphic, codominant so lots of diversity in antigen presentation
68
how are T cells classified
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
which of T helper cells and T cytotoxic cells are MHC class 2 restricted?
T helper cells are MHC class 2 restricted
70
what do cytotoxic CD8+ cells do
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
how T helper cells promote proliferation of CD8+ cells
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
side not, what is an epitope
an epitope is the specific part of the antigen that is recognised by the antibodies
73
what do T helper cells do
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
how are T helper cells divided further
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
how do Th1 helper cells activate macrophages
- 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
how important is Th2 to antibody production
almost all antibody responses require Th2 help
| IgM can be produced independently
77
what are cytokines
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
what is the complement system
consists of about 20 serum proteins
| has several actions, including lysis of bacteria and fungi, inflammation, opsonisation of infected cells
79
basophils and mast cells, similarities and differences
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
how are mast cells/ basophils activated
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
what does a mast cell cause in response to pathogen/ allergen in skin
increased blood flow and permeability
leads to vasodilation
endothelial cell activation
recruitment neutrophils and eosinophils
82
what does a mast cell cause in response to pathogen/ allergen in airways
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
what does a mast cell cause in response to pathogen/ allergen in gastro tract
incr fluid secretion and peristalsis
causes expulsion of parasites, diarrhoea, immobilisation of pathogens, cytoprotection
84
what does a basophil cause in response to pathogem/ allergen in blood
incr blood flow and permeability, so tissue fluid goes into lymph nodes quicker
85
what doe eosinophils do and yeah
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
how do kinetics of antibody response change with time
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
MHC class 1 endogenous pathway
```
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
MHC class 2 exogenous pathway
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
receptor is always cell associated with a transmembrane region in a T or a B cell? what is the other like
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
how does immune system formulate so many unique receptors for every pathogen
what are the 4 sections
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
how does gene rearrangement work for receptors
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
what region is there none of in light chain of antibodies
D region
93
what is somatic hypermutation
in B cells- antigen receptors undergo further modification through somatic hypermutation once encounter antigen- high rate of point mutations to further diversity
94
what is the cost of being able to produce so many random receptors
may create self- reactive actigen receptors so now need mechanisms to prevent immune damaging tissue
95
how does selection of autoreactive cells work in B cells
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
how does selection of autoreactive cells work in T cells
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
what is central tolerance
the process of deleting any self reactive cells in early stage lymphoid development
98
what is peripheral tolerance
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
what is immunosurveillance
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
