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Phase 2a - Introductory Clinical Sciences COPY > Immunology > Flashcards

Immunology Flashcards

1
Q

list some of the consequences of immune system malfunction

A

immunodeficiency
allergy
autoimmune disease
graft rejection

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2
Q

what are the cells of the innate immune system?

A

phagocytes
NK cells
antigen presenting cells (dendritic cells, macrophages)

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3
Q

what are the cells of the adaptive immune system?

A

B lymphocytes

T lymphocytes

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4
Q

what are the features of the innate immune system?

A 
broad specificity, resistance not improved by repeat infection.
rapid response (hrs).
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5
Q

what are the features of the adaptive immune system?

A

SPECIFICITY + MEMORY.
highly specific. resistance improved by repeat infection.
slower response (days-weeks)

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6
Q

describe the main differences between the innate and adaptive immune system

A

innate = broad specificity, adaptive is highly specific. adaptive resistance is improved by repeat infection. adaptive takes days-weeks, innate is rapid.

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7
Q

what are the external barriers to infection?

A

keratinized skin; secretions; mucous; low pH; commensals

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8
Q

what soluble factors are involved in innate immunity?

A

lysosome,
complement,
interferons etc

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9
Q

what soluble factors are involved in adaptive immunity?

A

antibody

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10
Q

what is the purpose of pattern-recognition receptors?

A

to discriminate self from non-self by recognising unchanging patterns of microbes

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11
Q

how do pattern recognition receptors work?

A

recognise conserved polysaccharide molecular patterns on microbes - patterns that are constant across a group of bacteria for eg.

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12
Q

what do pattern recognition receptors activate?

A

innate immune system.

damage recognition receptors on dendritic cells.

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13
Q

what are cell-associated PRRs?

A

receptors present on cell membrane/in cytosol. recognise broad range of molecular patterns.

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14
Q

name some membrane-bound PRRs

A

TLRs are main family.
mannose receptor on macrophages - fungi
dectin-1 - phagocytes, beta glycans in fungal walls.
scavenger receptors on macrophages.

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15
Q

what does TLR4 bind to?

A

lipopolysaccharide in bacterial walls.

pneumolysin, viral proteins.

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16
Q

what do TLRs do, once activated?

A

induce signal transduction and cellular events, leading to induction of pro-inflammatory cytokines.

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17
Q

what causes a hyperacute rejection of a transplanted organ?

A

when there are preformed cytotoxic antibodies against the MHC class I antigens in graft (e.g. previous pregnancy that generated antibodies, or blood-group incompatibility)

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18
Q

describe acute rejection of a transplant

A

occurs weeks-months after. T lymphocyte mediated reaction against donor HLA, or can be antibody mediated.
febrile, tenderness, declining renal function.

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19
Q

describe chronic rejection (chronic allograft injury)

A

after 6m of transplant - progressive decline of renal function. proteinuria. hypertension.
immune and non-immune mechanisms.

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20
Q

how can we prevent transplant rejection?

A

tissue typing.
cross match.
immunosuppressive agents.
paired exchanges.

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21
Q

why are immunosuppressants given to transplant patients?

A

preventing rejection. must be taken indefinitely (non-compliance).

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22
Q

what gene codes for human leucocyte antigens (HLAs)?

A

MHC (major histocompatibility complex) on chromosome 6

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23
Q

describe the process of hyperacute rejection

A

preformed cytotoxic antibody reacts with MHC class I antigens. activation of complement. influx of PMN leukocytes. platelet aggregation. obstruction of blood vessels - ischaemia. microvasculature plugged with leukocytes/platelets - infarction.

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24
Q

how is acute rejection treated?

A

IV methylprednisolone, anti-CD3 antibody, or increase other immunosuppressive drugs

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25
Q

what are the two phases of transplant rejection?

A

afferent phase - initiation or sensitising component.

efferent phase - effector component.

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26
Q

what occurs in the afferent phase of transplant rejection?

A

donor MHC molecules in the graft are recognised by CD4+ T cells - allorecognition

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27
Q

what occurs in the efferent phase of graft rejection?

A

CD4+ T cells recruit macrophages/CD8 T cells/NK cells/B lymphocytes to graft - tissue damage.

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28
Q

describe the structure of a typical antibody molecule

A

two Fab regions attached to an Fc region by a hinge.
Fab = variable sequence
Fc = constant.
2 light chains and 2 heavy chains

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29
Q

what do the Fab regions of antibodies bind?

A

antigens - specific

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30
Q

what does the Fc region of antibodies bind to?

A

complement, Fc receptors on phagocytes, NK cells etc

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31
Q

list the five classes of immunoglobulin

A 
IgG
IgM
IgA
IgD
IgE
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32
Q

what is the function of IgG immunoglobulins?

A

important in secondary/memory responses.

main effector of humoral immunity. binds complement. can cross placenta.

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33
Q

what is the function of IgM?

A

low affinity and specificty. important in primary response - first line defence. fixes complement well.

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34
Q

what is the function of IgA?

A

protects mucosal surfaces.

is found in serum and secretions.

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35
Q

what is the function of IgE?

A

present a very low levels.

involved in allergy and response to parasitic infection.

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36
Q

describe how the specific binding properties of antibodies (Fab) help protect against infection

A

neutralize toxins
immobilise motile microbes
prevent binding to host cells.
form complexes - (each Ig can bind 2 pathogens).

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37
Q

how do antibodies enhance innate mechanisms to protect against infection (Fc)?

A

Activate complement
bind Fc receptors on:
phagocytes - enhanced phagocytosis.
mast cells - inflammatory mediator release.
NK cells - enhance killing of infected cells.

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38
Q

give some uses of antibodies in research, diagnostics and therapy

A
  1. identify and label molecules in complex mixtures.
  2. serotyping of pathogens.
  3. identifying cell types.
  4. “humanized” antibodies are used in therapy
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39
Q

where do T cells mature?

A

the thymus

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40
Q

what are the major T cell subtypes?

A

T helper cells (CD4+).
cytotoxic T cells (CD8+)
T regulatory cells (CD4+)

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41
Q

what are the roles of T helper cells?

A

help B cells make antibody.
activate macrophages and NK cells.
help development of cytotoxic T cells.

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42
Q

what is the role of cytotoxic T cells?

A

recognise and kill infected host cells

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43
Q

what is the role of T regulatory cells?

A

suppress immune responses

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44
Q

describe the structure of the T cell receptor

A

a heterodimer of either alpha/beta or gamma/delta chains.
similar to Fab arm of antibody.
each one is specific to an antigen.

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45
Q

how do T cell receptors recognise antigens?

A 
as processed, cell-associated antigen.
recognise antigen peptides in context of  MHC class I and II antigens.
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46
Q

which MHC classes do T helper and cytotoxic T cells recognise respectively?

A 
T helper cells = MHC class II, use CD4 to enhance binding/signalling.
cytotoxic T cells = MHC class I, use CD8.
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47
Q

which cells are MHC I and MHC II expressed by?

A

MHC I = all nucleated cells.

MHC II = macrophages, dendritic cells, B cells

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48
Q

which T cells do MHC I and MHC II display antigens to, respectively?

A

MHC I displays them to CD8+ (cytotoxic) T cells.

MHC II = CD4+ (helper) T cells.

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49
Q

briefly describe the process of antigen presentation to cytotoxic T cells

A
  1. virus infects cell
  2. viral proteins are broken down in cytosol.
  3. peptides transported to ER, bind MHC I
  4. transported to cell surface
  5. activated cytotoxic T cells kill infected cell by inducing apoptosis
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50
Q

briefly describe the process of antigen presentation to T helper cells

A
  1. macrophage/dendritic cell/B cell internalises and breaks down foreign material
  2. peptides bind to MHC II in endosomes
  3. transported to cell surface
  4. activated T helper cells help B cells make antibody, and produce cytokines that activate/regulate other leukocytes
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51
Q

what are cytokines?

A

small secreted proteins involved in communication between cells of the immune response.
produced/act locally.

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52
Q

how do cytokines act?

A

by binding to specific receptors on surface of target cells

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53
Q

list some of the main groups of cytokines, and their general action

A

interleukins - made by T cells
interferons - respond to viral infections
chemokines - chemotaxis, e.g. IL-8
colony stimulating factors (CSFs) - leukocyte production

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54
Q

what do TH1 cells do?

A

activate macrophages, cause inflammation.
promote production of cytotoxic T cells (cell-mediated immunity)
important in intracellular infections.
induce B cells to make IgG antibodies.

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55
Q

what do TH2 cells do?

A

activate eosinophils and mast cells.
important in helminth infections and allergy.
induce B cells to make IgE - promotes release of inflammatory mediators e.g. histamine from mast cells.

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56
Q

describe the properties and roles of T memory cells

A

survive after infection, in greater numbers than naive cells. respond to antigens rapidly.

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57
Q

what two things are needed for T cell activation?

A

antigen presentation in the form of a peptide presented on MHC.
a costimulatory signal.

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58
Q

what is the “epitope” of an antigen?

A

the portion of the antigen that is bound by antibody

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59
Q

list the types of bonds that may form between antibody and antigen?

A

charge interactions.
hydrophobicity.
van der waals.
hydrogen bonds.

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60
Q

what are the main effector functions of antibodies?

A

opsonisation.
complement activation.
ADCC (antibody dependent cell mediated cytotoxicity).
allergic responses and IgE.

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61
Q

what is opsonisation?

A

coating of pathogens by antibody, leading to increased phagocytosis.

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62
Q

describe the process of B cell development

A

arise from lymphoid progenitor cells in fetal spleen/liver.

produced in bone marrow in adults.

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63
Q

what is active immunisation?

A

challenge subjects immune system to induce immunity. production of high affinity antibodies against immunogen. induction of immunological memory.

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64
Q

what is passive immunisation?

A

transfer of preformed antibodies to the circulation.

can be natural or artificial.

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65
Q

what is natural passive immunity? what does it protect against?

A

transfer of maternal antibodies across placenta to foetus.

diptheria/tetanus/strep/rubella/mumps/poliovirus

66
Q

what are the indications for use of artificial passive immunity?

A

individuals with agammaglobulinaemias (B cell defects) - given normal human IgG.
exposure to disease at risk of complication.
when there’s no time for active immunisation to give protection - pathogen with short incubation period.
acute danger of infection.

67
Q

how do anti-toxins work?

A

give passive immunity, as for some pathogens the main hazard is not the primary infection, but the toxins released by the pathogen.
e.g. tetanus, botulinum, diptheria.

68
Q

what are anti-venins?

A

substances that provide passive immunity to venoms

e.g. snake bite, insects, jellyfish

69
Q

what are some disadvantages of passive immunisation?

A

doesn’t active immunological memory - no long term protection.
may react to anti-sera used.

70
Q

define inoculation

A

vaccination involving introduction of a viable microorganism into the subject

71
Q

what are the aims of a “perfect” vaccine?

A
  1. achieve long term protection from a small number of immunisations (compliance)
  2. stimulate B and T cells
  3. induce memory B and T cells
  4. stimulate protective high affinity IgG production
72
Q

describe the primary immune response

A

relies on innate immune system.
IgM predominates.
low affinity.

73
Q

describe the secondary immune reponse

A

rapid and large reaction.
high affinity IgG.
T cell help.
doesn’t rely on innate immune system.

74
Q

name some different types of vaccine

A

whole organism - live attenuated pathogen; killed, inactivated pathogen.
subunit - toxoids; antigenic extracts; recombinant proteins
peptides
DNA vaccines
engineered virus

75
Q

what are some advantages of live attenuated vaccines?

A

sets up a transient infection. full immune response activated. prolonged contact with immune system. stimulation of B and T cell memory.
often single immunization.

76
Q

what are some disadvantages of live attenuated vaccines?

A

can cause infection in immunocompromised patients.
complications.
can occasional revert to a virulent form, can cause a serious outbreak in poor sanitation.
refrigeration and transport are issues.

77
Q

what are some advantages of whole inactivated pathogen vaccines?

A

no risk of infection.
storage less critical than a live vaccine.
good immune response possible.

78
Q

what are some disadvantages of whole inactivated pathogen vaccines?

A

tend to just activate humoral response - lack of T cell response.
immune response can be quite weak - booster vaccinations needed, compliance can be a problem.

79
Q

what are some advantages of subunit vaccines?

A

safer than live/inactivated pathogens.
no risk of infection.
easier to store/preserve

80
Q

name some types of subunit vaccine?

A

toxoids.
capsular polysaccharides
purified proteins
recombinant proteins

81
Q

what are some disadvantages of subunit vaccines?

A

immune response less powerful than to live attenuated vaccines.
repeat vaccinations/adjuvants needed.

82
Q

give examples of adjuvants that could be added to a vaccine to stimulate the immune system?

A

whole killed organisms.
toxoids.
proteins
chemicals - aluminium salts, paraffin oil.

83
Q

how do DNA vaccines work?

A

transiently express genes from pathogens in host cells. generates immune response - T and B cell memory.

84
Q

what are some advantages/disadvantages of DNA vaccines?

A

easy to store/transport
simple delivery (DNA gun).
BUT - no transient infection, likely to produce mild response and require boosters.

85
Q

how do recombinant vector vaccines work?

A

imitate effects of transient infection with pathogen, but using a non-pathogenic organism.
genes for pathogen antigens introduced into non-pathogenic microorganism and introduced to host.

86
Q

what are some advantages/disadvantages of recombinant vector vaccines?

A

can create ideal stimulus to immune system - memory.
flexible and safe.
BUT - need refrigeration. can cause illness in immmunocompromised.

87
Q

what is cancer immunosurveillance?

A

idea that immune system can recognise and destroy newly transforming/transformed cells

88
Q

what is cancer immmunoediting?

A

immune system can protect you from cancer by killing tumour cells. but they’re very genetically unstable - so immune responses to tumours can cause changes in tumour cells, allowing tumour escape and recurrence

89
Q

what are tumour specific antigens?

A

found only on tumours. result of point mutations/gene rearrangement. derive from viral antigens.

90
Q

what are tumour associated antigens?

A

found on normal and tumour cells - overexpressed on cancer cells.

91
Q

what are two methods by which tumours can “escape” the immune system?

A
  1. immune responses change tumours so tumours are no longer “seen” by immune system - tumour escape
  2. tumours change immune response by promoting immune suppressor cells - immune evasion
92
Q

what type of immunoglobulin is typically involved in allergy?

A

IgE

93
Q

what are the cells involved in allergy?

A

mast cells, eosinophils, lymphocytes, dendritic cells.

effectors of allergic response - smooth muscle, fibroblasts, epithelia

94
Q

what cells express low-affinity IgE receptors?

A

B cells, T cells, monocytes, eosinophils, platelets, neutrophils

95
Q

what cells express high-affinity IgE receptors?

A

MAST CELLS

basophils, eosinophils

96
Q

describe the development of mast cells

A

derived from specific cell lineage. require c-kit protein to develop. immature mast cells circulate, mature in tissues

97
Q

what activates mast cells?

A

indirect activators act via IgE - allergens, some bacterial/viral antigens.
phagocytosis.
direct activators - cold. aspirin, NO2, proteases, C3a, C5a

98
Q

describe anaphylaxis

A

occurs within mins-hrs.
mast cell or basophil activation - IgE or direct activation.
histamine and tryptase are elevated.
vasodilation, vascular permeability, low BP, bronchoconstriction, rash, swelling, GI pain, vomiting etc.

99
Q

what is a type I hypersensitivity reaction?

A

immediate hypersensitivity (‘allergy’) - due to activation of IgE antibody on mast cells or basophils.

100
Q

what is a type II hypersensitivity reaction?

A

antibody to cell-bound antigen - triggered by antibodies reacting with antigenic determinants on cell membrane of target tissue. often involves drugs/their metabolites binding to RBC.

101
Q

what is a type III hypersensitivity reaction?

A

immune complex hypersensitivity - results from deposition/formation of immune complexes in tissues

102
Q

what is a type IV hypersensitivity reaction?

A

delayed-type hypersensitivity. mediated by T lymphocytes reacting with antigen - sensitisation. secondary challenge results in delayed-type reaction - local inflammation taking 2-3d to develop.

103
Q

what causes primary immunodeficiency?

A

an intrinsic defect in the immune system

104
Q

what causes secondary immunodeficiency?

A

an underlying condition - much more common than primary.

occurs when synthesis of key immune components is suppressed or their loss accelerated.

105
Q

how would a patient with an antibody deficiency present?

A

recurrent bacterial infections of resp tract

106
Q

how would a patient with defects in cellular immunity present?

A

invasive and disseminated viral, fungal and opportunistic bacterial infections involving any organ

107
Q

what is panhypogammaglobulinaemia?

A

a silly word.

also, defects in antibody synthesis that involves different classes of Igs

108
Q

what is selective antibody deficiency?

A

defects in antibody synthesis involving only one class/subclass of Ig

109
Q

what are the presentations of primary antibody deficiencies?

A 
recurrent infections of upper and lower resp tract.
congenital forms present between 4m-2yrs due to passive protection provided by maternal IgG.
skin sepsis
gut infection
meningitis
arthritis
splenomegaly
purpura
110
Q

what are the most common infecting organisms in antibody deficiency?

A

pyogenic bacteria:
staph
H influenzae
strep pneumoniae

111
Q

why aren’t patients with primary antibody deficiency unduly susceptible to viral/fungal infections?

A

cell mediated (T cell) immunity is preserved

112
Q

describe the features of X-linked agammaglobulinaemia (XLA) - bruton’s disease

A

boys present w/ recurrent pyogenic infection between 4m-2yo.
infections similar to other antibody deficiency + enteroviruses.
no mature B cells circulating.
very low serum Ig.
gene found on long arm of x chromosome, produces Bruton’s tyrosin kinase (Btk) - cytoplasmic enzyme - which is needed for B cell development. mutations = XLA.

113
Q

describe the features of hyper-IgM syndrome

A

normal/high serum IgM in absence of other types.
X linked mutation in CD4+ T cell.

bacterial infections and Pneumocystis jirovecii neumonia.

replacement Ig therapy needed, bone marrow transplant is gold standard.

114
Q

describe the features of selective IgA deficiency

A

normal IgG and IgM, no IgA.
IgA deficiency = asymptomatic. selective IgA deficiency predisposes to other disorders. prompt Abx therapy for infection, immunisation against respiratory pathogens.

115
Q

describe the features of common variable immunodeficiency (CVID)

A

group of disorders presenting as antibody deficiency in late childhood/adults. recurrent bacterial infections, higher risk of autoimmune disease (purpura, pernicious anaemia etc). granulomas can cause end-organ damage.
replacement Ig therapy

116
Q

name some primary antibody deficiencies

A 
panhypogammalgobulinaemia.
transient hypogammaglobulinaemia of infancy.
XLA - bruton's disease.
hyper-IgM syndrome.
selective IgA deficiency.
common variable immunodeficiency.
117
Q

describe the features of severe combined immunodeficiency (SCID)

A

seen in infants - major failure of T cell (and variable B/NK cell) function.
genetic variables.
first few weeks/months - failure to thrive, chronic diarrhoea, respiratory infections. lymphopenia.
avoid live vaccines and blood transfusions.
SCID patients die before reach 2yo without haemopoietic stem cell transplants.

118
Q

describe the features of primary C1, C4 or C2 deficiency

A

malar rash (facial rash), arthralgia, glomerulonephritis, fever or chronic vasculitis - immune complex deposition in tissues

119
Q

describe the features of C3 deficiency

A

occurs as primary, or secondary to factor H or factor I deficiency.
increased susceptibility to life-threatening bacterial infections (pneumonia, septicaemia, meningitis)

120
Q

describe the features of C5, C6, C7 or C8 deficiencies

A

recurrent bacterial infection.

121
Q

what are some causes of secondary immunodeficiency?

A

nephrotic syndrome/protein-losing eteropathy - severe protein loss causing hypogammaglobulinaemia (seen in Crohn’s, ulcerative colitis).
malnutrition (protein, energy) - impaired synthesis of immune system components.
immunosuppressive drugs.
splenectomy.
some microorganisms - CMV, measles, rubella, viral hep, HIV.

122
Q

what is autoimmunity?

A

immune response against a self-antigen.

123
Q

what is autoimmune disease?

A

tissue damage resulting from an autoimmune response

124
Q

what are the criteria to show a disease is caused by autoimmunity?

A
  1. demonstrate immunological reactivity to a self-antigen
  2. characterise/isolate the autoantigen
  3. induce immunological reaction against same antigen by immunisation of experimental animals
  4. show pathological changes in the organs/tissues of an actively sensitised animal
125
Q

how does immunological tolerance ensure not everyone has autoimmune disease?

A

there will always be T cell receptors and Ig molecules produced that react to self-antigens - the T/B cells bearing these self-reactive molecules are eliminated/downregulated to make the immune system tolerant to self-antigens.
induction of specific tolerance occurs in or out of thymus (thymic tolerance/peripheral tolerance).
there must be a breakdown of tolerance for autoimmune disease to occur.

126
Q

How does thymic tolerance work?

A

T cell development occurs in thymus - those bearing self-reactive molecules are negatively selected for. this is only partially successful.

127
Q

how do regulation and suppression work in the context of peripheral tolerance?

A

self-reactive T cells may be actively suppressed by regulatory T cells recognising the same antigen

128
Q

how does B cell tolerance (a peripheral tolerance) work?

A

production of self-reactive antibodies is limited by lack of T cell help for self-antigens

129
Q

how might peripheral tolerance be overcome?

A

inappropriate access of self-antigens to APCs.
inappropriate/increased expression of co-stimulatory molecules.
alterations in way the self-molecules are presented to the immune system.

130
Q

what makes peripheral tolerance more likely to be overcome, leading to autoimmune disease?

A

inflammation and/or tissue damage

131
Q

how does “molecular mimicry” lead to a breakdown of tolerance?

A

structural similarity between self-proteins and microbial antigens, triggering an autoimmune response

132
Q

what are some environmental triggers of autoimmunity?

A

hormones
infection
drugs
UV radiation

133
Q

what are the mechanisms of tissue damage in autoimmune disease?

A

activation of macrophages/cytotoxic T cells.
or,
autoantibodies can also cause disease by binding to functional sites of self-antigens (e.g. hormone receptors, neurotransmitter receptors) - causing function abnormalities without damage/inflammation.

134
Q

how are autoimmune diseases treated?

A

replacement of function of organ damaged.
suppression of autoimmune response - immunosuppression before irreversible tissue damage is vital (early detection is a challenge)

135
Q

what is the complement system?

A

complex series of interacting plasma proteins acting as an enzymatic cascade - major effector system for antibody mediated immune reactions

136
Q

what are the 3 pathways complement can be activated by?

A
  1. classical pathway - by antibody
  2. alternative pathway - by bacterial cell walls
  3. lectin pathway - by mannose-binding lectin
137
Q

what are the effects of complement activation?

A

increased vascular permeability.
chemoattraction of leukocytes.
enhanced phagocytosis.
cell lysis.

138
Q

what letter is the major fragment of a complement component, and describe the functions of its active sites.

A

“b”.
2 active sites:
triggering complex - binds to cell membranes.
other is for enzymatic cleavage of the next complement component.

139
Q

how is complement activation controlled?

A

spontaneous decay of any exposed attachment sites. inactivation by specific inhibitors.

140
Q

what is the major purpose of the complement pathway?

A

remove/destroy antigen - by direct lysis or by opsonisation

141
Q

what are the two sequential phases of complement activation?

A
  1. activation of C3 component

2. activation of the ‘attack’ or lytic pathway

142
Q

what is the critical step of complement activation?

A

cleavage of C3 by complement-derived enzymes (C3 convertases).
C3b mediates vital activities, especially opsonisation.
C3 cleavage is achieved via 3 pathways, all generate C3 convertases but in response to different stimuli.

143
Q

what activates the classical pathway of complement activation?

A

when binding of IgM/IgG to antigen causes conformational change in Fc of antibody, revealing C1 binding site

144
Q

which types of Ig activate the classical pathway?

A

IgM and IgG

145
Q

what occurs once C1 is activated in the classical pathway? what regulates this?

A

enzyme activity generated that splits C4 and C2 into a and b fragments.
regulated by C1 esterase inhibitor.

146
Q

what complex is the classical pathway C3 convertase?

A

C4b2b

147
Q

what is the action of C4b2b?

A

cleaves C3, with C3a being anaphylatoxic and chemotactic, and C3b binding to the initiating complex - C4b2b3b complex is a C5 convertase, initiating the final lytic pathway

148
Q

what initiates the final lytic pathway following the classical pathway?

A

C4b2b3b - C5 convertase

149
Q

what are the most important activators of the alternative pathway?

A

bacterial cell walls and endotoxin

150
Q

what is responsible for innate defence against invading organisms?

A

the alternative pathway of the complement system

151
Q

what causes initial cleavage of C3 in the alternative pathway?

A

occurs spontaneously, generating low levels of C3b

152
Q

once formed, what does C3b do in the alternative pathway?

A

uses factors D and B to produce active enzyme C3bBb, which is stabilised by properdin

153
Q

what is the action of C3bBb in alternative pathway? what stabilises it?

A

breaks down more C3, providing more C3b.

properdin.

154
Q

what regulates the breakdown of C3 in the alternative pathway?

A

factor H and I

H competes with factor B for binding to C3b, then I cleaves and inactivates displaced C3b

155
Q

what initiates the lectin pathway?

A

mannose-binding lectin - circulating protein, binds to carbohydrate of surface of some microorganisms

156
Q

what are the two ways in which C5 convertase is produced?

A

in classical = C3b, C4b and C2b

in alternative = C3b, Bb and properdin

157
Q

describe the final lytic pathway of complement?

A

once C5 convertase is produced, C5 is cleaved into C5a and C5b.
successive addition of C6/C7/C8/C9 forms the MEMBRANE ATTACK COMPLEX.
- lysis of cell via pore formation.

158
Q

how does complement-dependent phagocytosis work?

A

microorganisms are coated with C3b - can then be bound by possessing complement receptors (CR1) - present on phagocytic cells

159
Q

what pro-inflammatory mediators does complement activation release? what are their effects?

A

C5a, C4a and C3a.
act as anaphylatoxins.
increased vascular permeability, release vasoactive amines, induce smooth muscle spasm.

160
Q

what is the action of C5a?

A

acts as anaphylatoxin.
also, a potent chemoattractant, and it stimulates neutrophils and macrophages to synthesise cytokines, undergo oxidative metabolism and release degradative enzymes.

Phase 2a - Introductory Clinical Sciences COPY (6 decks)

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