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PHAY00011 > Immunology II > Flashcards

Immunology II Flashcards

1
Q

What are the two types of immunisation?

A

Passive immunisation like from mother to fetus

Active immunisation like from vaccination or infection recovery

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2
Q

Definition of passive immunisation

A

Induction of protective immunity without the need for immune response

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3
Q

Examples of passive immunisation

A

Maternally-derived IgG

Secretory IgA through milk during breastfeeding

Administration of whole serum or concentrated IgG

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4
Q

What is the benefit of administration of Ig?

A

Immediate protection

Useful in compromised individuals

Useful in those with post-exposure risks

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5
Q

What is the limitations associated with administratiomn of Ig serum?

A

Pooled human serum - risk of viral transmission to receiver - purification required

Animal serum - increased risk of serum sick ness due to immune response

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6
Q

How does serum sickness from the use of animal serum arise?

A

Large complex formed in blood vessels

Activation of complements

Localised damaged inflammatory response -> fever, lymphadenopathy, joint pain, skin lesions

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7
Q

What are the main drawbacks of passive immunisation?

A

Very time-consuming

Only small amount

Not suitable for protection against whole big population

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8
Q

Name 2 types of vaccines.

A

Live attenuated vaccines - live organisms - virulence removed - immunity within 2 weeks - not for pregnant and immunocompromised

Killed vaccines - not as effective or long-lasting - immunity within several weeks - booster doses every 3 - 4 weeks

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9
Q

What are the individual and community benefits of vaccination?

A

Provide personal immunity against a particular infection

Limit the spread - obtain herd immunity

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10
Q

Requirements of herd immunity

A

Specific vaccination strategy

Threshold number (certain number of individuals vaccinated)

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11
Q

What does the threshold number of herd immunity depend on?

A

Infection virulence

Infection reproductive time

Infection shedding time

Vaccine efficacy

Period of protection

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12
Q

Common routes of administration of vaccines

A

S/C, IM or intradermal injection - majority

Oral and nasal delivery - a few

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13
Q

What is adjuvants for vaccines? Give some examples.

A

Substances that ehance immunogenicity or prolongs the antigen at the injection site -> more gradual release

Examples:
Aluminium hydroxide salts
Freund’s adjuvant (not used in human)
Squalene adjuvants (MF59)

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14
Q

Side effects of vaccines.

A

Local reactons at injection site

Fever

Allergies

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15
Q

What are the 3 main types of viral vaccines?

A

Live-attenuated vaccines (measles, mumps, rubella, varicella)

Inactivated vaccines (polio, influenzae, rabies)

Subunit vaccines (hepatitis B, influenzae)

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16
Q

What should be the considerations for attenuation of viruses for vaccines?

A

Applicable for viruses that are easily and readily inactivated

RNA viruses are easier to attenuate

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17
Q

Why is live attenuated vaccines the most optimal mean to obtain immunity?

A

Mimick the natural route of infection

Generate natural immune response

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18
Q

Main concerns of live-attentuanated vacccines?

A

Risk of viruses can revert to its pathogenic wildtype -> induce infection

Example: Polio from polio vaccines

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19
Q

What are the advantages and disadvantages of live attenuated vaccines?

A

Reproduce natural infection -> optimal immunity

Good level of protection

One dose only

Herd immunity uptake level does not need to be 100%

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20
Q

What are the disadvantages of the live attenuated vaccines?

A

Possible reversion of virulence

Limited shelf-life

Require refrigeration

Side effects due to media and culture

Cannot be used in T cells immunocompromised and pregnancy

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21
Q

What are the advantages of the killed vaccines?

A

Safe from reversion of virulence

More stable for transport and storage

Aceeptable for immunocompromised

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22
Q

What are the disadvantages of killed vaccines?

A

Less effective

More than 1 dose required

No herd immunity induced

Uptake level must ~100% for herd immunity

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23
Q

Considerations for viral subunit vaccines.

A

Using part of viruses -> induce immune response

Can be internal components, surface receptors

Require in-depth knowledge

Components used must be represented in all strains

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24
Q

Examples of HPV vaccines

A

Cervarix and Gardasil, 90% effective against infections caused by HPV type 16 and 18

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25
Q

Considerations for viral vaccines development, taking HPV as an example.

A

Check notes

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26
Q

How many types of bacterial vaccines are there?

A

Live attenuated vaccines - BCG for TB

Inactivated vaccines - Cholera vaccine (must contained all the likely strains)

Subunit or toxin vaccines

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27
Q

How are bacteria inactivated in the inactivated vaccines?

A

Heat treatment

Chemicals like formaldehyde and phenol

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28
Q

Why does subunit vaccine require additional components?

A

Some subunit vaccines contain bacterial antigens.

They require conjugation to a protein mole -> elicit T cells + effective antibody response

Convert T cell-independent -> T-cell dependent B cell activation

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29
Q

What types of vaccines do patients wtih sickle cell disease and splenectomised patients need?

A

Pneumococcal

Meningococcal

Haemophilus influenzae vaccines

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30
Q

What types of vaccines do the elderly need?

A

Influenzae

23 - valent pneumococcal polysaccharide vaccines

Diphtheria, pertussis and tetanus

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31
Q

What types of vaccines do children with HIV need?

A

Varicella-zoster immune globulin post-exposure

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32
Q

What types of vaccines do healthcare workers need?

A

Hepatitis B

Measles

Mumps

Rubella

Influenzae

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33
Q

Define hypersensitivity.

A

Repeated or prolonged exposure to antigen

Excessive or inappropriate immune

Damage to tissues

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34
Q

How many types of hypersensitivity reactions are there?

A

Four types

I, II, III are antibody-mediated

IV are cell-mediated

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35
Q

Pathologic immune mechanism of type I hypersensitivity reaction

A

IgE development

Respond to allergens or conditions

Immediate hypersensitivity

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36
Q

Describe the sequence of events in type I hypersensitivity reactions

A

Initial exposure - sensitation step - IgE produced

Allergens processed - epitopes on MHC II - free allergens -> lymph nodes

Present to B cells and T cells

T cells -> IL-4, IL-5, IL-13 -> plasma cells produce IgE

IgE bind to receptors on tissue mast cells + circulating basophils via Fc domain -> present on surface

Subsequent exposure -> allergens bind surface IgE -> cross-linking -> biphasic immune response

Degranulation -> release of mediators:+ release of cytokines -> symptoms

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37
Q

What mediators and cytokines released during subsequent exposure of allergens in type I hypersensitivity?

A

Vasoactive amines, lipid mediators

Prostagladins, leukotrienes, platelet-activating factors

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38
Q

What is the method used to diagnose immediate hypersensitivity?

A

Skin testing

Wheal and flare

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39
Q

How does anaphylaxis arise?

A

Massive release of histamine and other mediators

Vasoconstriction combined with gap formation between capillary endothelial cells (vasodilation)

Rapid fluid loss

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40
Q

How can penicillin cause type I hypersensitivity?

A

Act as hapten

Bind to host protein -> complex -> response

Sensitisation step produce penicilloyl-specific IgE antibody

Subsequent exposure -> massive release of histamine, leukotrienes, cytokines, chemokines

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41
Q

Clinical features of acute anaphylaxis

A

Bronchospasm

Facial and laryngeal oedema

Hypotension

N + V, diarrhoea

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42
Q

Management of acute anaphylaxis

A

Lying feet raise (on left)

Clear airway

Give O2, monitor BP

Venous access

0.5 mg IM adrenalone, repeat every 5 mins if shock persist

IV antihistamine (10 - 20 mg chlorphenamine) slowly

100 mg IV hydrocortisone

1 - 2L IV fluid (if persist hypotension)

Ventilation (if severe hypoxia)

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43
Q

Principles of desensitisation therapy.

A

Switch from IgE production to IgG

Prevent interaction with mast cell-bound IgE

Increase in regulatory T cells -> inhibit production of IgE

Monitor after and during therapy

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44
Q

What is anaphylactoid reaction?

A

Response from substances can trigger mast cell degranulation immediately

No IgE involement

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45
Q

Examples of drugs can trigger anaphylactoid reaction.

A

Codeine, morphine, vancomycin, constrast media

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46
Q

Management of anaphylactoid reaction

A

Withdraw trigger

Antihistamine

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47
Q

Pathologic immune mechanism of type II hypersensitivity reaction

A

IgM/Ig interacting with cell membranes or extracellular matrix -> damage

Complements involved (classical pathways)

Cell-specific or tissue specific damaged

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48
Q

How are tissues damaged by type II hypersensitivity?

A

IgG/IgM/complement opsonised the cells

Attract macgrophages, neutrophils

Frustrated phagocytosis -> release of granulated contents (defensins, reactive oxygen, nitric oxide, enzymes) -> damage

Conformational change of Fc domain -> recognised by NK cells -> perforin + granzymes -> Damage

Complements -> MAC -> damage

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49
Q

What drives the reaction against blood cells during blood transfusion?

A

Type II hypersensitivity

IgM against ABO system -> agglutination, complement activation, haemolysis

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50
Q

What happens in haemolytic disease of newborn (HDNB)?

A

RhD- mother give birth to RhD+ child

Leak back of foetal erythrocytes during birth - across placenta

IgG production against RhD+

Subsequent pregnancy with RhD+ child -> IgG cross placenta + attack

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51
Q

Management of haemolytic disease of newborn (HDNB)

A

Prophylactic approach after screening the first child

Pre-formed anti-RhD (+) Ig -> neutralise antibody

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52
Q

How do type II hypersensitity to drugs arise?

A

Drug + platelet -> complex -> antigenic -> immune Ig response

Ig bind complex -> activation of classical complement pathway -> MAC formation -> lysis of platelet

-> Immune thrombocytopenic purpura

Can induce destruction of RBCs -> anaemia -> mild jaundice

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53
Q

Pathologic immune mechanism of type III hypersensitivity reaction

A

Deposition of immune complex within blood vessels

Recruitment + activation of inflammatory cells promoted by Fc domain

Inflammation of the site

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54
Q

What causes the formation of harmful immune complex in type III hypersensitivity reaction?

A

Persistent infection

Autoimmune disease (RA and systemic lupus erythromatosus)

Inhalation of antigens

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55
Q

Sequence of events in type III hypersensitivity reactions

A

Formation of antigen-Ig complex

Deposit in walls of blood vessels

Activation of circulating complement -> neutrophils -> release chemicals -> damage

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56
Q

How do immune complexes trigger inflammation?

A

Fc receptors -> activate basophils -> release of vasoactive amines -> increased vascular permeability -> deposition of immune complex (to big to flow out)

Aggregation of platelets -> microthrombi -> blood flow compromise

Activation of macrophages -> cytokines release (TNF-alpha + IL-1)

Complement system activation -> C3a + C5a -> attract neutrophils, basophils etc -> release lysosomal enzyme -> damage

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57
Q

What is Arthus reaction?

A

IInjection of antigen S/C into previously immunised individual

Screen for local cutaneous vasculitis with tissue necrosis

Indicate type I, III and IV hypersensitivity based on time onset, appearance

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58
Q

What are the 3 types of type IV hypersensitivity?

A

Contact hypersensitivity

Tuberculin (delayed-type hypersensitivity)

Granulomas hypersensitivity

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59
Q

2 mechanism causing damage in type IV hypersensitivity

A

Cytokine-mediated inflammation: CD4+ T cells activation -> cytokine released -> activate neutrophils and macrophages -> release of content -> damage

T cell-mediated cytotoxicity: CD8+ cells activation - directly kill cells + damage tissue

60
Q

How does contact hypersensitivity arise?

A

Chemically active compound absorbed through skin

Bind to skin proteins -> neoantigen at skin tissues

Second exposure -> symptoms

Localised inflammation of dermis by macrophages and neutrophils by effector T helper-1 cells

61
Q

How does delayed type hypersensitivity arise?

A

Bacteria, fungi, viruses -> enter intracellular areas of skin tissues

Impact not limited to dermis, can happen at any sites - systemic circulation

Same mechanism of damage as contact hypersensitivity

62
Q

How does granulomatous hypersensitivity arise?

A

persistence macrophage activation - microorganism resistant or unable to deal with

chronic stimulation of T cells -> constant release of cytokines - contant activation

granulomas formulation -> tissue injury + impair function + fibrotic tissue replacement

63
Q

Composition of granulomas

A

Central: collection of epitheliod cells derived from macrophages + macrophages

Fusion of activated macrophages -> giant cells

Fibroblast covering around

64
Q

Mechanism of cytotoxic T cells - mediated type IV hypersensitivity.

A

Chemicals like 2,4 dinitrophenyl (hapten) - pass thru dermis

Bind to self-proteins (MHC class I)

Trigger release chemical singals to attract immune cells

CD8+ cells recognise MHC-hapten complex -> kill the cells

65
Q

Define immunological tolerance

A

Mechanism to control the B cells and T cells to not respond to epitope of an autoantigen

Failure - autoimmunity

66
Q

How many levels of immunological tolerance? Where?

A

2 levels.

Centrally in bone marrow

Peripherally tissues

67
Q

Describe the central tolerance mechanism,of T cells

A

In thymus

Regulated by mechanism involved medullary thymic epithelial cells that have tissue restricted antigens

2 outcomes if recognise autoantigen:
+ Apoptosis (majority)
+ Develop into regulatry T cells

68
Q

What mechanism controls central tolerance of T cells in thymus?

A

Medullary thymic epithelial cells that have tissue restricted antigens

69
Q

Describe the central tolerance mechanism of B cells.

A

Within bone marrow

Outcomes dependent on the avidity towards autoantigen

High avidity -> apoptosis or variable region modified

Low avidity -> anergy

70
Q

What are the 3 methods of peripheral tolerance of T cells?

A

Anergy

Suppression

Apoptosis

71
Q

Describe the anergy mechanism of peripheral tolerance of T lymphocytes

A

TCRs bind to non-APCs -> no secondary signals

No recognition by activating receptors on T cells of co-stimulators.

-> Anergy state

72
Q

How do T cells go into anergy state when no additional signals are produced?
<Hint: 2 ways>

A

Blockage of signals from TCR-MHC complex - phosphatase + activation of ubiquitin ligases - break down signalling protein

Enlargement of inhibitory receptors like CTLA-4 -> bind to B7, inhibit CD28

73
Q

Describe the suppression mechanism of peripheral tolerance of T lymphocytes

A

Regulatory T cells from thymus or conversion in peripheral

Inhibit T cell activation

Suppress activities of T cells

Inhibit production of antibody from autoreactive B cells

Via cytokines or cell contact

74
Q

Describe the deletion mechanism of peripheral tolerance of T lymphocytes

A

Triggering apoptosis through two pathways:

+ Intrinsic (mitochondrial pathways) - detected by Bcl-2 family sensors

+ Extrinsic: expression of Fas and FasL (on activated T cells) -> bind -> caspase activation -> apoptosis

75
Q

What are the 2 outcomes of peripheral tolerance of autoreactive B cells?

A

Apoptosis

Anergic - trigger inhibitory receptors like CD22 upon recognition

76
Q

How many factors to influence susceptibility to autoimmune disease?

A

Genetic factor -> genetic modification -> failure of self-tolerance

Environment factors -> infection and injury -> expose hidden antigens -> autoreactive lymphocytes

77
Q

What does it mean by autoimmunity chronicity? 2 mechanism underlying this

A

Upon autoimmune develop, amplification mechanism

Self-reactive T cells release cytokines (IFN-gamma) - activate macrophages -> release more cytokines (IL-12) -> activate more immune cells

Epitope spreading - hidden self-antigens are exposed due to tissue damage

78
Q

How can infection cause autoimmunity?

<Hint: 3 ways>

A

Microbes - activate co-stimulatory receptors like B7 -> self-reactive activation

Molecular mimicry - similar conformation

Inflammation result -> high levels of released cytokines -> activation of T cells without APC interaction

79
Q

What are the two conditions associated with molecular mimicry mechanism causing autoimmune?

A

Type I diabetes

Reactive athritis

80
Q

How does rheumatic heart disease arise?

A

Beta-haemolytic strains of Streptococcus pyogenes -> strep throat

M protein on surface - similar to molecules found in valves of heart, cells in joints and kidney

IgM and IgG produced against M protein -> attack those tissues

Damage of the heart cannot be resolved

Require antibiotic therapy for strep throat

81
Q

Explain how epitope spreading can induce autoimmune.

A

Cytotoxic damage -> release of hidden autoantigens

These antigens are not screened during central tolerance

Generate response

The stimulating epitope changes with time -> futher damage -> release of new epitopes

82
Q

Name some conditions associated with epitope spreading mechanism.

A

Systemic lupus erythematous

Crohn’s disease

Multiple sclerosis

T1DM

83
Q

What are the 3 main possible mechanisms leading to the loss of suppression related to T cells?

A

Absence of regulatory T cells

Insufficient functions of regulatory T cells

Effector T cells resistance to regulatory T cells

84
Q

Name some immunologically privileged sites

A

Brain

Cornea

Anterior chamber of the eyes

Testicular tube

Uterine environment during pregnancy

85
Q

What is neoantigen?

A

Self-antigens bind to some molecules -> recognised as foreign

Not true autoantigen

86
Q

Main differences of the immune response between neoantigens and true autoantigens

A

Neoantigen - subside when agent removed

True autoantigen - persist for lifetime

87
Q

Humoral associated autoimmune response is result from what reactions?

A

Self-reacting IgG -> from type II and type III hypersensitivity reactions

88
Q

Cell-mediated associated autoimmune disease arises from what reactions?

A

Type IV hypersensitivity reactions

Note: Antibodies might still present

89
Q

How does systemic lupus erythematosus develop?

A

Sensitisation phase, effector phase

Ineffective clearance of apoptotic cells -> lymphocytes, Ig against the fragments of DNA and chromosal proteins

Ig binds -> complex -> not efficiently cleared -> deposition of blood vessles -> damage

90
Q

What are the symptoms of SLE?

A

Neurological and psychiatric morbidity

Renal failure

Serosal inflammation

Vasculitis

Impaired haemopoiesis

91
Q

Name some drugs like can promote lupus-like syndrome

A

Procainamide

Quinidine

Hydrazaline

Minocycline

Methydopa

Etanercept, Adalinumab, Infliximab

Isonazid, Chlorpromazine

92
Q

Treatment options for organ-specific autoimmune disease.

A

Correction of metabolic control

Transfection of FasL gene

Tissue grafts and implantation

Immunosuppressive therapy with glucocorticoids - risk of infection

93
Q

Based on genetic relationships, classification of transplant

A

Autograft = same person, from different part

Isograft = from genetically identical individuals or siblings

Allograft = from not genetically identical, but same species

Xenograft = from animal

94
Q

Based on origins and destination, classification of transplant

A

Orthotopic grafts = from same site

Heterotrophic grafts = from non-original sites

95
Q

What are the genes that govern the tolerance or rejection of tissues?

A

Histocompatibility genes

Major histocompatibility antigens = MHC I + MHC II molecules

Minor histocompatibility antigens = any peptide fragment displayed on MHC

96
Q

How can T cells reject foreign cells?

A

Recognise foreign peptide bound to self MHC

Recognise to allogenic MHC molecule presenting a peptide.

97
Q

What type of T cells do each MHC molecules present peptides to?

A

MHC I - present proteins in cytoplasm - CD8+ T cells

MHC II - present engulfed peptides - CD4+ T cells

98
Q

What are the two processes through which the recognition of histocompatibility antigens occur?

A

Direct recognition

Indirect recognition

99
Q

Describe the direct recognition pathways of histocompatibility antigens

A

mediated by DONOR’s dendritic cells

Migrate from graft - 2nd lymphoid tissues

Recognition -> immune response

100
Q

Describe the indirect recognition pathways of histocompatibility antigens

A

mediated by RECIPIENT’s dendritic cells

host Dcs migrate into transplant -> acquire donor antigen -> host 2nd lymphoid

Stimulate immune response

101
Q

Mediation of acute rejection of transplantation

A

Direct recognition pathways

Activation of T cells into CTLs and T helper cells.

CTLs - apoptosis of doner cells

Both cells - cytokines - activate macrophages + neutrophils -> tissue damage

102
Q

What caused hyperacute rejection?

A

Preformed anti-donor antibodies

103
Q

Pathological immune mechanism of chronic rejections.

A

Ig, released cytokines -> inflammation

Released growth factors -> smooth muscle proliferation -> occlusion

Occlusion of blood vessels -> shortage of oxygen supply to organs

104
Q

What can cause chronic rejection?

A

Indirect recognition pathway

Antibody response

Response of graft to injury during transplantation

Recurrence of underlying disease

Drug-related toxicity

105
Q

What conditions are haemotopoietic stem cells transplants used for?

A

Treat children who have inherited immune deficiences

Treat patients with leukaemia

106
Q

Procedures of haemotopoietic stem cells transplant in patients with leukaemia.

A

Collection of stem cells

Chemotherapy + radiotherapy -> kill all leukaemic cells

Transfuse stem cells back

107
Q

What is the main risks of haemotopoietic stem cells transplant?

A

Presence of leukaemic cells when colelction

108
Q

What is the main risk of haemotopoietic stem cells transplant from donor?

A

Graft versus host disease (GVHD)

109
Q

Mechanism of Graft veruse Host disease

A

Grafted T cells reject the host cells.

Presence of mature T cells from the donor -> recognise host antigens -> activated -> damage

110
Q

What are the two major methods used for preventing rejection during transplantation?

A

Donor and recipient matching

Use of immunosuppressive drugs

111
Q

What are the immunosuppressant agents used for transplant?

A

Corticosteroids

Calcineurin inhibitors like ciclosporine and tacrolimus - bind to ciclophilin - inhibit IL-2 transcription -> no T cell stimulation

Antibodies - muromonab (inhibit T cells) + basiliximab/daclizumab (IL-2 receptor blocker)

112
Q

What is oncofoetal genes?

A

Genes re-expressing the proteins that are only found in the foetus

Host not tolerant to these antigens

113
Q

What are the antigens that can be considered as tumour antigenicity?

A

Mutated cell surface protein

Oncofoetal antigens

Antigen induced by virus infection

114
Q

How can tumour antigens be identified?

A

Serologic analysis of recombinant cDNA expression (SEREX)

115
Q

What are the steps done in SEREX?

A

Resection and collection of tumour cells -> culture

Mononuclear cells from tumour cells are collected -> culture -> separate CD8+ tumour-specific CTLs -> clone

Expression libraries of tumour cDNA from tumour cell RNA

Trasnfect cDNA into MHC I positive cell line -> culture with CTLs

Lysis -> deduce the cDNA -> deduce gene coding for tumour antigen

116
Q

What does the immune surveillance theory imply?

A

Tumour cell consistently arise

But immune system effectively control before detectable

Immune system -> selective pressure -> resistant cells develop -> tumour

117
Q

How does innate system tackle against tumour?

A

NK cells - recognise MHC I molecules - via killer inhibitory receptors (KIRs)

NK cells - recognise stress molecules - via killer activation receptors (KARs)

Tumour cells - reduced MHC I molecules + increased stress molecules -> kill signal generated, no inhibit signal -> kill

Macrophages - secrete cytokines - kill tumour

118
Q

What are the cytokines released from macrophages that can have antitumour activities?

A

TNF-alpha, TNF-beta -> necrosis stimulation

TNF-alpha -> inhibit angiogenesis

IFN-alpha, IFN-beta, IFN-gama -> increase expression of MHC I molecules -> susceptible to CTLs (but reduced susceptible to NK cells)

119
Q

How does adaptive immune system tackle tumour?

A

Specific antigen-dependent immune responses

Ig generated

CTLs

Delayed hypersensitivity reaction -> recruuitment and activation of macrophages

120
Q

How can tumour cells become resistant to immune responses?

<Hint: 6 ways>

A

Reduce expression of MHC I molecules -> reduce CTLs but increase NK cells

Reduce expression of positive co-stimulators (B7)

Increase expression of negative co-stimulator (PD-L1)

Induction of regulatory T cells

Interfere with TCR signalling

Secretion of immunosuppressive cytokines (IL-10 or TGF-beta)

121
Q

How can the activity of antibodies enhance tumour growth?

A

Ig bind to antigens

Mask the antigen -> block CTLs from binding + block binding of Fc receptors on macrophages, DCs and NK cells

122
Q

What are the different methods attempted to manage tumour growth?

A

Interleukins and interferons - enhance local immune response

Monoclonal antibodies

Vaccines -> only for viral cause cancer like hepatitis B virus or HPV

123
Q

What are the consequences of immunodeficiencies in general?

A

Increase risk of infection, cancer, autoimmune disease and hypersensitivities

123
Q

What are the classes of immunodeficiences?

A

2 classes

Primary deficiencies - present at birth - caused by single gene defect

Secondary deficiences - develop as consequence of disease, therapy or malnutrition

124
Q

What is chronic granulomatous disease?

A

Primary immunodeficienes

Neutrophils cannot produce respiratory burst - defect in enzyme NADPH oxidase -> no H2O2 formation to kill ingested microbes

Infection -> formation of granulomas -> abscesses

125
Q

What microbes are patients with CGD susceptible with?

A

Bacteria that is resistant to non-oxidative killing

Staph.aureus
Burkholderia cepacia
Sematia marcescens
Nocardia species
Aspergilleus species

126
Q

Why do patients with CGD can still manage organisms like pneumococci and streptococci?

A

They generate own H2O2

CGD neutrophils still have active myeloperoxidase

Use H2O2 to kill

127
Q

What antibiotics prophylaxis is given to patients with CGD?

A

Co-triamoxazole -> prevent bacterial infection

Itraconazole - prevent fungal infection

Short course corticosteroid - skin lesion (if present)

128
Q

What happened in severe combined immunodeficiency (SCD)?

A

Absence of T cells, B cells population may be normal

Susceptible to intestial infection, interstitial pneumonias

Develop fatal disseminated infection if taking live-attenuated vaccines

129
Q

What prophylaxis regimen and treatment should be given to patients with SCD?

A

Co-trimoxazole

Aciclovir

Ig replacement therapy

Treatment of all infections aggressively

Only possible cure = early allogenic bone marrow transplanation

130
Q

Name possible treatments for primary immune deficiences.

A

Administration of deficient components (Ig, cytokines, enzymes) -> need repeated doses

Bone marrow transplantation - careful for GVHD

Genetic engineering -> repair defective cells -> only stem cells can provide permanent solution

131
Q

What are the possible major causes of secondary immunodeficiency?

A

Malnutrition

Infection

Leukaemias, cancer metastases

Chemotherapy, radiotherapy

Surgery or trauma

Chronic disease or stress

Old age

132
Q

How can malnutrition result in immunodeficiencies?

A

Promote risk of infection -> further enhance malnourished state

Affect Ig production (esp IgA) and innate immune system

Atrophy of lymphoid tissue (thymus esp) -> reduce circulating T cells

Impairment of wound healing

Reduce level of complement, reduce production of inflammatory cytokines (IL-2 and TNF-alpha_

Increase binding of bacteria

Affect trace element absorption

133
Q

What is the relationship between trace elements and immunodeficiencies?

A

Iron level and susceptibility to infection - co-factor of many enzyme in immune system (reactive-oxygen enzymes) - growth of microbial

Zinc - peptide hormone thymulin + transcriptional activators - deficiency -> reduction weight of thymus -> reduced cell-mediated response and NK cells

Vitamin A, B1, B6, B12, C, D and E -> affect immune reaction

134
Q

What are the treatments that can lead to immunodeficiency?

A

Ionising radiation -> damage replicating cells

Cytotoxic drugs in chemotherapy (etanercept, infliximab, alemtuzumab -> kill and damage replicating cells

Anti-inflammatory drugs (glucocorticoids) -> interfere with cytokines -> both innate and cellular respnse

Immunosuppressive drugs (methotrexate, ciclosporins, tacrolimus) -> interfere with cytokines production

135
Q

Definition of neutropenia

A

Reduced neutrophil count to less than 0.5 x 10^9 cells/L or less than 500 cells every mm3

136
Q

What can cause neutropenia?

A

Haematological disorders like acute leukaemia and aplastic anaemia

Use of cytotoxic chemotherapy

137
Q

Association between infection and neutropenia

A

Reduced Gram-negatoive - due to use of fluoroquinolones -> increased number of enterococci-associated infections

Gram-positive more frequent

Skin-derived like Staph and Corynebacterium also problem

Oral strep -> oral mucositis

138
Q

How are fever in neutropenic patients treated?

A

Piperacillin or azocillin + aminoglycosides (amikacin)

OR meropenem

Add vancomycin if needed

-> cover Pseudomonas and local resistance pattern

Amphotericin or caspofungin -> manage fungal infection if present

GM-CSF and G-CSF to stimulate neutrophil production

139
Q

What agent is used to restore neutrophil production?

A

Filgrastrim

140
Q

The preventative regimens for infections in neutropenia.

A

Isolation

Sterile water, food

Filtered air supplies (HEPA)

Good ward hygiene + stream-pressed linen + handwashing + use of sterile gloves

Suppressive antimicrobial regimes (quinolones + antifungal like nystatin with amphotericin or itraconazole or caspofungin)

141
Q

What infection is related to solid organ transplantation?

A

Related to surgial procedures and Hospital-acquired infections

Gram negative bacili like Pseudomonas

Gram positive like S.aureus and VRE

Rarely: West Nile Virus, Brucellosis, Trypanosomiasis, Toxoplasmosis

Related to the use of immunosuppressive regimens (HPV, Listeria, pneumocystic pneumonia, pneumococcal…)

142
Q

Roles of spleen in the body

A

secondary lymphoid organs

Involved in Ig production

Clearance of encapsulated organisms from blood

143
Q

What can affect the function of spleen?

A

Autoimmune diseases

Haematological disorders

GI disorders

Age

Malnutrition

Alcohol excess

144
Q

What normally cause post-splenectomy sepsis?

A

Streptoccocus pneumoniae

Haemophilus influenzae

145
Q
A

PHAY00011 (9 decks)

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