Immuno Flashcards
(207 cards)
1
Q
Name three constitutive barriers to infection
A
Skin
- packed keratinised cells
- low pH, low oxygen tension
- sebaceous glands; oil repels water and organisms
Mucosal surfaces
- mucous physical barrier with lysozymes
- cilia traps pathogens and helps remove
Commensal bacteria
- compete with naughty organisms
- produce fatty acids inhibit other pathogens
2
Q
Which cells assist in the innate immune system and how?
A
Polymorphonuclear cells/granulocytes
- neutrophils, eosinophils, basophils
- release enzymes, histamine, detect immune complexes
Monocytes and macrophages
- circular in blood and migrate to tissues to differentiate to macrophages
- present antigens to T cells
Natural killer cells
- cause lysis of naught cells, cytotoxic; kill ‘altered self’
Dendritic cells
- peripheral tissue, detect immune complexes, express cytokines
3
Q
By which mechanisms does the innate immune system work?
A
Phagocyte recruitment
- macrophages, neutrophils, dendritic cells all attracted to chemokines released in inflammatory process
Recognising microorganism
- toll-like receptors and mannose receptors to help body trigger immune complexes
Endocytosis
- OPSONIN bridges pathogen and phagocyte receptor to allow for eating
Phagolysosome
- pathogen killed in phagosome which fuses with lysosome, cheeky
4
Q
Oxidative vs non-oxidative killing
A
Oxidative
- NADPH oxidase converts oxygen to ROS
- Myeloperoxidase catalyses production of hydrocholorous acid, effective oxidant and anti-microbial
Non-oxidative
- relase of lysozyme, lactoferrin in phagolysosome
- enzymes in granules
- broad coverage of bacteria and fungi
5
Q
Main components of the adaptive immune system
A
Humoral immunity
- B cells and antibodies
Cellular immunity
- T cells (CD4 + CD8)
Soluble components
- cytokines and chemokines
6
Q
Which T cells recognise which HLA class?
A
CD4+ T cells = HLA II (4x2 = 8)
CD8+ T cells = HLA I (8x1 = 8)
7
Q
Compare CD4+ and CD8+ T cells
A
CD4+
- recognise peptides HLA II
- trigger expression of cytokines
- develop full B cell response
CD8+
- recognise peptides HLA I
- kill cells directly via perforin and granzymes, Fas ligand
- secretes cytokines
8
Q
How are B cells activated?
A
B cell receptor Ig binds to antigen
Some mature to plasma cells secreting IgM
Others require CD4+ to trigger rapid proliferation
Undergo complex genetic rearrangements, switching to IgG, IgA or IgE
Further differentiation for plasma cells to produce IgG, IgA, IgE antibody and long-lived memory cells
9
Q
What interaction is needed for CD4+ cells to help B cell differentiation?
A
CD4+ T cells primed by dendritic cells
CD40L:CD40 interaction between T and B cells
10
Q
Complement involved in classical pathway
A
Antibody-antigen immune complex exposes binding site for C1 (acquired immune response)
Triggers activation of cascade; C2, C4
Major amplification step -> C3
11
Q
Complement involved in mannose binding pathway
A
Activated by direct binding to mannose binding lectin on cell surface
Stimulates classical pathway via C2 and C4 only
Leads to major amplification step via C3 activation
Doesn’t need acquired immune response
12
Q
Complement involved in alternative pathway
A
Direct trigger of C3 to bacterial cell wall components
Involves factors B, I, P
i. e. lipopolysaccharide of gram negative bacteria
i. e. teichoic acid of gram positive bacteria
Doesn’t need acquired immune system
13
Q
What does C3 convertase do in the complement cascade?
A
Triggers formation of membrane attack complex via C5-9
This punches holes in bacterial membranes
14
Q
Role of cytokines and examples
A
Small protein messengers with immunomodulatory function
Autocrine or paracrine dependent action
E.g.
IL-2, 6, 10, 12
TNF-alpha
TGF-beta
15
Q
Role of chemokines and examples
A
Chemotactic cytokines (attractive) thus directly recruits/hones in leukocytes in inflammatory response
E.g.
CCL19, 21 ligands for CCR7 (direct dendritic cells to lymph nodes)
IL-8, RANTES, MIP-1 alpha and beta
16
Q
How is HIV transmitted?
A
Sexual contact
Infected blood
Mother-to-child (vertical: breastfeeding, in utero, intra partum)
17
Q
Pathogenesis of HIV
A
RNA retrovirus targets CD4+ T helper cells
Replicates via reverse transcriptase to convert RNA into DNA to go into host cell’s gene
CD4 molecule receptor for HIV and virus binds on other CD4+ cells
Leads to selective loss of CD4+ T cells in immune system
18
Q
Which receptors do HIV bind onto on CD4+ T cells?
A
gp120 = initial binding gp41 = conformational change
19
Q
Which coreceptors do HIV bind onto on macrophages?
A
CCR5
CXCR4
= both chemokine co-receptors
20
Q
Which protein leads to intrastructural support for HIV?
A
Gag protein
21
Q
What is the innate response to HIV?
A
Non-specific activation of macrophages, NK cells and complement
Stimulation of dendritic cells vita TLR
Release of cytokines and chemokines
22
Q
What is the adaptive response to HIV?
A
Neutralising antibodies: anti-gp120, anti-gp41
Non-neutralising antibodies: anti-p24 gag IgG
CD8+ T cells release chemokines: MIP-1a, MIP-1b, RANTES which block co-receptors
23
Q
What is the median time it takes to develop AIDS?
A
Typical progressors: 8-10 years
Rapid progressors: 2-3 years
Long term non progressors: stable and no sx after 10-15 years
24
Q
Screening test for HIV
A
anti-HIV ab via ELISA
25
Confirmation test for HIV
Detect ab via Western Blot after 10 weeks incubation period
| = patient needs to be seroconverted; start making abs
26
What is monitored after diagnosis?
Viral load via PCR to detect viral RNA
CD4 count via FACS/flow cytometry to assess course of disease
Resistance testing to antiretrovirals
27
How is resistance to antiretrovirals tested?
Phenotypic
- viral replication measured in cell cultures under selective pressure of increasing concentrations of antiretroviral drugs compared to wild-type
Genotypic
- mutations determined by direct sequencing of amplified HIV genome
28
Which drugs affect which part of the HIV life cycle?
1. Attachment/entry
=> attachment inhibitors
=> fusion inhibitors
2. Reverse transcription and DNA synthesis
=> reverse transcriptase inhibitors
=> NRTI, NNRTI, NrTRI
3. Integration to host DNA
=> integrase inhibitors
4. Viral transcription
5. Viral protein synthesis
6. Assembly and budding
=> protease inhibitors
29
Tx plan for HIV
Commence tx immediately after diagnosis
HAART = 2NRTIs + PI (or NNRTI)
- control viral replication
- increase CD4 T cell count
- improve host defence
Pregnancy
- zidovudine at antepartum IV
- PO to newborn for 6/52 to reduce transmission
30
What are the limitations of HAART?
```
Cannot eradicate latent HIV-1
Fails to restore HIV-specific T-cell responses
Toxicities
High pill burden
Adherence
Threat of drug resistance
Quality of life affected
High costs
```
31
Name a fusion inhibitor for HIV and its side effects
Enfuvirtide
= local reactions to injections
= hypersensitivity in 0.1-1%
32
Name an attachment inhibitor for HIV
Maraviroc
33
Name some NRTIs for HIV
```
Nucleoside reverse transcriptase inhibitors
= zidovudine
= didanosine
= stavudine
= abacavir
= emtricitabine
= epzicom
= zalcitabine
```
34
Side effects of NRTIs for HIV
```
Fever
Headache
GI upset
Peripheral neuropathy (zalcitabine, stavudine)
BMS (zidovudine)
Mitochondrial toxicity (stavudine)
Hypersensitivity (abacavir)
```
35
Name a nucleotide RTI for HIV and its side effects
Tenofovir
| = bone and renal toxicity
36
Name non-RTIs for HIV and their respective side effects
Nevirapine: hepatitis and rash
Delavirdine: rash
Efavirenz: CNS effects
37
Name integration inhibitors for HIV
Raltegravir
| Elvitegravir
38
Name some protease inhibitors for HIV
```
Indinavir
Nelfinavir
Ritonavir
Fosamprenavir
Lopinavir
Atazanavir
```
39
Name side effects of protease inhibitors for HIV
Hyperlipidaemia
Fat redistribution
Type II DM
40
Where are central and effector memory cells found?
Central
=> lymph nodes, tonsils
=> found in high endothelial venules (HEVs)
Effector
=> liver, lungs, gut
41
Which T cell activation markers are vital for central memory cells?
CCR7+ and CD62L high
| => low in effector memory cells
42
What do central and effector memory cells produce?
Central
=> IL-2
Effector
=> perforin, IFN-gamma
43
T cell memory summary
CD45 RO = memory T cells
CD45 RA = naive T cells
CD4 and CD8 remain for long time after infection and proliferate at low rate
Exposure to subsequent antigen -> rapid proliferation
44
B cell memory summary
B memory cells differentiate into long-lived plasma cells
These cells produce quicker response, more abs, higher affinity abs, more IgG and better abs when B cells exposed to subsequent antigens
45
What do CD4+ Th1 cells do?
Cell-mediated; help CD8 and macrophages
| Produce IL-2, IFN-gamma, TNF
46
What do CD4+ Th2 cells do?
Humoral response; helper T cells
| Produce Il-4, IL-5, IL-6
47
What do CD4+ Th17 cells do?
Help neutrophil recruitment
| Produce IL-17, IL-21, IL-22
48
What passive vaccine do we give for hep A and measles?
Human normal Ig = HNIG
49
What passive vaccine do we give for hep B?
Hep B immunoglobulin = HBIG
50
What passive vaccine do we give for rabies?
Human rabies immunoglobulin = HRIG
51
What passive vaccine do we give for varicella?
Varicella zoster immunglobulin = VZIG
52
Which monoclonal antibody do we give for RSV?
Paviluzimab
53
How do passive vaccines work?
Give immunoglobulins to assist with immune response, only lasts for 3 weeks
54
How do you do the mantoux test?
Inject 0.1ml of 5 tuberculin (purified protein derivative) units intradermally
Examiner arm 48-72 hours later
55
What does a +ve mantoux result mean?
+ve = swelling at injection site at least 10mm in diameter
Implies previous exposure to tuberculin protein either previous TB exposure or previous BCG exposure
56
What different mechanisms of phagocyte deficiencies are there?
1. Failure to produce neutrophils
- reticular dysgenesis (production), Kostmann syndrome & cyclic neutropenia (maturation)
2. Defect of phagocyte migration
- leukocyte adhesion deficiency
3. Failure of oxidative killing mechanisms
- chronic granulomatous disease
4. Cytokine deficiency
- IL12, IL12-receptor, IFN-gamma, IFN-gamma receptor deficiency
57
What is leukocyte adhesion deficiency characterised by?
This is a phagocyte deficiency that results in:
1. Very high neutrophil counts in blood
2. Absence of pus formation
3. Delayed umbilical cord separation
58
What mutations results in the following?
a) reticular dysgenesis
b) Kostmann syndrome
c) cyclic neutropenia
a) autosomal recessive, mitochondrial metabolism enzyme adenylate kinase 2 (AK2)
b) autosomal recessive, HCLS1-associated protein X-1 (HAX1)
c) autosomal dominant, neutrophil elastase (ELA-2)
59
What ix are done for chronic granulomatous disease?
Nitro-blue tetrazolium test (NBT)
Dihydrorhodamine (DHR) flow cytometry test
Both negative in affected pts as deficient in NADPH oxidase needed to form free radical to give +ve result
60
What is chronic granulomatous disease characterised by?
Absent respiratory burst
Excessive inflammation
Granuloma formation
Lymphadenopathy and hepatosplenomegaly
Susceptible to bacteria, especially catalase +ve, and PLACESS
61
What are the PLACESS pathogens?
```
Pseudomonas
Listeria
Aspergillus
Candida
E. Coli
Staph aureus
Serratia
```
62
Tx for chronic granulomatous disease
Interferon gamma
63
Recurrent infections with NO neutrophils on FBC
Kostmann Syndrom
64
Recurrent infections with high neutrophils but no abscesses
Leukocyte Adhesion Deficienc
65
Recurrent infections with hepatosplenomegaly and abnormal DHR test (does not fluoresce)
Chronic granulomatous disease (CDG)
66
Infection with atypical mycobacterium, but normal FBC
IFN-g Receptor Deficiency
67
Severe chicken pox, disseminated CMV infection
Classical NK Cell Deficiency (recurrent viral infections common)
68
Severe childhood-onset SLE with normal levels of C3 and C4
C1q deficiency
69
Membranoproliferative nephritis and abnormal fat distribution
C3 deficiency with nephritic factor
70
Meningococcus meningitis with FHx of sibling dying of the same condition aged 6
C7 deficiency
71
Recurrent infections when neutropenic following chemotherapy but previously well
MBL deficiency
72
Characteristics of complement deficiencies
Increased susceptibility to bacterial infections, specially encapsulated bacterial infections (NHS)
1. Neisseria meningitis
2. Streptococcus pneumonia
3. Haemophilus influenza
73
Why do deficiencies of early classical complement pathway components result in SLE?
Complement deficiency results in a deposition of immune complexes due to ineffective promotion of phagocyte-mediated clearance of apoptotic/necrotic cells
This stimulates local inflammation in skin, joints, and kidneys -> SLE
74
Which early classical pathways are described in SLE?
C1q, C1r, C1s, C2, C4
C2 most common with almost all C2 patients having SLE
75
What is MBL deficiency associated with?
Increased infection in immunocompromised patients:
- premature infants
- chemotherapy
- HIV infection
- antibody deficiency
76
How are complement deficiencies diagnosed?
CH50 test
- classical pathway test
AP50 test
- alternate pathway test
77
C3 +
C4 +
CH50 -
AP50 +
Which complement deficiency?
C1q deficiency
78
C3 +
C4 +
CH50 +
AP50 -
Which complement deficiency?
Factor B deficiency
79
C3 +
C4 +
CH50 -
AP50 -
Which complement deficiency?
C9 deficiency
80
C3 +/-
C4 -
CH50 +/-
AP50 +
Which complement deficiency?
SLE
81
Mx of complement deficiencies
Vaccinations
Prophylactic abx
Treat infection aggressively
Screen family members (risk of meningococcal septicaemia)
82
Classical NK deficiency
Absence of NK cells within peripheral blood
Abnormalities described in GATA2 or MCM4 genes in subtypes 1 and
83
Functional NK deficiency
NK cells present but function is abnormal
Abnormality described in FCGR3A gene in subtype
84
What are the mechanisms by which T cell immunodeficiencies can occur?
Failure of lymphocyte precursors
- SCID
Failure of thymic development
- DiGeorge syndrome
Failure of expression of HLA molecules
- bare lymphocyte syndromes
Failure of signalling, cytokine production and effector function
- IFN-gamma or receptor deficiency, IL12 or receptor deficiency
85
Severe recurrent infections from 3 months of age, CD4 and CD8 cells are absent, B cells present, immunoglobulin are low. Normal facial features and echocardiogram
X-linked SCID
86
Young adult with chronic infection with Mycobacterium marinu
IFN-gamma receptor deficiency
87
Recurrent infections in childhood, abnormal facial features, congenital heart disease, normal B cells, low T cells, low IgA and low IgG
22q 11.2 deletion syndrome/DiGeorge syndrome
88
6-month old baby with two recent serious bacterial infections. T cells present - but only CD8+. B cells present. IgM present but IgG low
Bare lymphocyte syndrome type II
89
What are the mechanisms by which B cell immunodeficiencies can occur?
Failure of lymphocyte precursors
- SCID
Failure of B cell maturation
- Bruton's X-linked hypogammaglobulinaemia
Failure of T cell costimulation
- X-linked hyper IgM syndrome
Failure of production of IgG antibodies
- common variable immune deficiency, selective antibody deficiency
Failure of IgA production
- selective IgA deficiency
90
Adult with bronchiectasis, recurrent sinusitis and development of atypical SLE
Common variable immunodeficiency
91
Recurrent bacterial infections as a child, episode of PCP, high IgM, absent IgA and absent IgG
X-linked hyper IgM syndrome due to CD40L mutation
92
1-year old boy. Recurrent bacterial infections. CD4 and CD8 T cells present. B cells absent. IgG, IgA and IgM absent
Bruton's X-linked hypogammaglobulinaemia
93
Recurrent respiratory tract infections, absent IgA, normal IgM and normal IgG
IgA deficiency
94
Characteristics of SCID
```
Unwell by 3 months of age
Infections of all types
Failure to thrive
Persistent diarrhoea
Poorly developed lymphoid tissues (germinal centres) and thymus
Family history of early infant death
```
95
Most common mutation of SCID
X-linked SCID
Mutation of gamma chain of IL2 receptor on chromosome Xq13.1
96
What is ADA deficiency?
16.5% of all SCID
Adenosine deaminase deficiency (autosomal recessive), required for lymphocyte cell metabolism so phenotype is low in everything (T, B, NK cells)
97
What protects the SCID neonate in the first 3 months of life?
Maternal IgG high present in colostrum first 3 months of life
Eventually diminishes over time, however, SCID baby does not make neonatal IgG
98
Characteristics of DiGeorge Syndrome
CATCH-22
```
Cardiac abnormalities (TOF)
Abnormal facies (high forehead, low set ears)
Thymic aplasia (T cell lymphopenia)
Cleft palate
Hypocalcaemia/hypoparathyroidism
22- chromosome affected
```
99
What mutation causes DiGeorge syndrome?
Deletion at 22q11.2
100
What causes BLS type II?
Bare lymphocyte syndrome type II
Defect in one of the regulatory proteins involved in class II gene expression
101
Clinical features of T cell deficiencies
```
Viral infections (CMV)
Fungal infections (pneumocystis, cryptosporidium)
Some bacterial (intracellular - myco TB, Salmonella)
Early malignancy
```
102
How are lymphocyte deficiencies diagnosed?
1. WCC
2. Lymphocyte subsets
3. Serum immunoglobulins (if CD4 deficient, IgG surrogate marker for function) & protein electrophoresis
4. Functional tests
5. HIV
103
```
CD4 T cell -
CD8 T cell -
B cell +/-
IgM +/-
IgG -
```
Which T cell deficiency is this?
SCID
104
```
CD4 T cell -
CD8 T cell -
B cell +
IgM +
IgG +/-
```
Which T cell deficiency is this?
DiGeorge
105
```
CD4 T cell -
CD8 T cell +
B cell +
IgM +
IgG -
```
Which T cell deficiency is this?
Bare lymphocyte syndrome type II
106
Mx of T cell deficiencies
```
Infection prophylaxis & treatment
Ig replacement
Haematopoietic stem cell transplantation
Gene therapy (experimental)
Thymic transplant in DiGeorge syndrome
```
107
Mx of B cell deficiencies
Aggressive tx of infection
If replacement every 3 weeks (pooled plasma w diverse IgG
Bone marrow transplant
Imms in selective IgA deficiency (not effective if no IgG)
108
What is WAS?
Wiskott-Aldrich syndrome
X-linked recessive, mutation in WAS gene, needed for T cell-APC interaction
Results in low platelets, IgM, lymphocytes
Results in increased IgA, IgE and risk of malignant lymphoma
109
What causes Bruton's X-linked hypogammaglobulinaemia?
Abnormal B cell tyrosine kinase (BTK) gene
Results in no mature B cells in circulation thus no antibody production
110
Clinical characteristics of Bruton's X-linked hypogammaglobulinaemia
Only boys
Recurrent infections during childhood
Absent/scanty lymph nodea and tonsils (primary follicles and germinal centres absent)
Failure to thrive
111
What causes hyper IgM syndrome?
Mutation in CD40 ligand gene
Results in CD4+ T cells UNABLE to signal to B cells thus B cells unable to enter germinal centre reaction to undergo isotype switching and affinity maturation
112
Clinical characteristics of hyper IgM syndrome
```
Boys present with failure to thrive in first few years of life
Recurrent bacterial infections
Pneumocystis jiroveci infection
Autoimmune disease
Malignancy
```
113
What is common variable immune deficiency defined by?
Marked reduction in IgG with low IgA/IgM
Poor/absent response to immunisation
Absence of other defined immunodeficiency
114
Clinical features of common variable immune deficiency
Recurrent bacterial infections with severe end-organ damage
- Pneumonia, persistent sinusisit, gastroenteritis
Pulmonary
- bronchiectasis, ILD
GI
- IBD, sprue like illness bacterial overgrowth
Autoimmune
- AIHA, RA, pernicious anaemia, thyroiditis, vitiligo
Malignany
- non-Hodgkin lymphoma
115
Clinical features of antibody deficiency (or CD4 T cell deficiency)
Bacterial infections (Staph, Strep)
Toxins (tetanus, diptheria)
Some viral infections (enterovirus)
116
```
CD4 T cell +
CD8 T cell +
B cell -
IgM -
IgG -
IgA -
```
Which B cell deficiency is this?
Bruton's X-linked hypogammaglobulinaemia
117
```
CD4 T cell +
CD8 T cell +
B cell +
IgM ++
IgG -
IgA -
```
Which B cell deficiency is this?
Hyper IgM X-linked
118
```
CD4 T cell +
CD8 T cell +
B cell +
IgM +
IgG +
IgA -
```
Which B cell deficiency is this?
Selective IgA deficiency
119
```
CD4 T cell +
CD8 T cell +
B cell +
IgM +
IgG -
IgA -
```
Which B cell deficiency is this?
Common variable immune deficiency
120
Immunopathology in absence of infection possibilities
Autoinflammatory
Mixed
Autoimmunity
121
Periodic fever lasting 48-96 hours with abdo pain, chest pain, rash and arthralgia
Mutation found in MEFV gene
Familial Mediterranean fever
- gene encodes for pyrin-marenostrin
- needed for activation of neutrophils
122
Long term risk of Familial Mediterranean fever
AA amyloidosis
- kidney, liver, spleen
- nephrotic syndrome -> renal failure
123
Tx of MEFV gene mutation condition
Familial Mediterranean Fever
- colchicine (affects neutrophils)
- anakinra (IL-1 R antagonist)
- etanercept (TNF-alpha inhibitor)
124
Defect in AIRE leading to hypoparathyroidism, Addison's, hypothyroidism, diabetes, vitiligo, enteropathy condition
Auto-immune polyendocrine syndrome type 1 (APS1)
Auto-immune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED)
125
Defect in Foxp3 leading to diabetes mellitus, hypothyroidism, enteropathy condition
Immune dysregulation polyendocrinopathy enteropathy (IPEX)
126
Defect in FAS pathway leading to high lymphocyte with large spleen and lymph nodes leading to autoimmune cytopenias and lymphomas
Autoimmune lymphoproliferative syndrome (ALPS)
127
IBD1 gene on chromosome 16 identified as NOD2 (CARD-15) is associated with which condition?
Crohn's
128
Which gene is associated with Crohn's?
IBD1 gene on chromosome 16 identified as NOD2 (CARD-15)
129
The genetic polymorphism PTPN22 is associated with which conditions?
Rheumatoid arthritis
SLE
T1DM
130
The genetic polymorphism CTLA4 is associated with which conditions?
SLE
T1DM
Autoimmune thyroid disease
131
HLA-B27 associated condition
Ankylosing spondylitis
132
HLA DR15/DR2 associated condition
Goodpasture's syndrome
133
HLA DR3 associated conditions
Graves disease
SLE
T1DM
134
HLA DR4 associated conditions
Rheumatoid arthritis
| T1DM
135
Type 1 hypersensitivity diseases
```
Atopic dermatitis (infantile eczema)
Food allergy
Oral allergy syndrome
Latex food syndrome
Allergic rhinitis
Acute urticaria
```
136
Which food allergies to latex allergy sufferers have typically?
```
Chestnut
Avocado
Banani
Potato
Tomato
Kiwi
Papaya
Eggplant
Mango
Wheat
Melon
```
137
Common Ig-E mediated mast cell degranulation triggers
Peanut
Penicillin
Stings
Latex
138
Common non Ig-E mediated mast cell degranulation triggers
NSAIDs
IV contrast
Opioids
Exercise
139
Anaphylaxis mx
```
Elevate legs
100% oxygen
IM adrenaline 500 mcg
Inhaled bronchodilators
Hydrocortisone 200mg IV
Chlorphenamine 10mg IV
IV fluids
Seek help
```
140
Ix in allergy
Skin prick tests
Quantitative specific IgE to putative allergen (RAST)
Component-resolved diagnostics
Challenge Test
Measure mast cell tryptase during acute episode (lol)
141
Which mediators are indicated in the following hypersensitivity disorders?
a) Type 1
b) Type 2
c) Type 3
d) Type 4
a) Ig-E - mast cell degranulation
b) IgG or IgM antibody - reacts with cell/matrix associated self-antigen
c) IgG or IgM immune complex - Ab vs soluble Ab mediated tissue damage
d) T-cell mediated - delayed hypersensitivity
142
Type 2 hypersensitivity diseases
```
Haemolytic disease of newborn
Autoimmune haemolytic anaemia
Autoimmune thrombocytopenic purpura
Goodpasture's syndrome
Pemphigus vulgaris
Graves disease
Myasthenia Gravis
Acute rheumatic fever
Pernicious anaemia
Churg-Strauss syndrome (eGPA)
Wegener's granulomatosis (GPA)
Microscopic polyangiitis (MPA)
Chronic urticaria
```
143
Type 3 hypersensitivity diseases
Mixed essential cryglobulinaemia
Serum sickness
Polyarteritis nodosa (PAN )
Systemic lupus erythematosis (SLE)
144
What is Evan's syndrome?
Autoimmune haemolytic anaemia + ITP
sad times
145
Type 4 hypersensitivity diseases
```
T1DM
Multiple sclerosis
Rheumatoid arthritis
Contact dermatitis
Mantoux test
Crohn's disease
```
146
CREST syndrome
```
Limited cutaneous scleroderma:
Calcinosis
Raynaud's
oEsophageal dysmotility
Sclerodactyly
Telangiectasia
```
147
Sx seen in diffuse cutaneous scleroderma
CREST
GIT
Interstitial pulmonary disease
Renal problems
148
42 year old lady presents with dry mouth and eyes, swelling on the sides of her face and issues with her kidneys
What antibodies do you expect to be present?
Anti-Ro and anti-La
= Sjorgen's syndrome
149
Which skin condition is seen with coeliac disease?
Dermatitis herpetiformis
150
What autoantibodies are seen in antiphospholipid syndrome?
anti-cardiolipin
anti-beta-2-glycoportein
anti-lupus anticoagulant
151
What autoantibodies are seen in autoimmune hepatitis?
anti-smooth muscle
anti-liver kidney microsomal-1 (anti-LKM-1)
anti-soluble liver antigen (anti-SLA)
152
What autoantibodies are seen in autoimmune haemolytic anaemia?
anti-Rh blood group antigen
153
What autoantibodies are seen in autoimmune thrombocytopenic purpura?
anti-glycoprotein IIb-IIIa
154
Which conditions would you see p-ANCA in?
```
Churg-Strauss syndrome (eGPA)
Microscopic polyangiitis (MPA)
```
155
What autoantibodies are seen in coeliac disease?
anti-tissue transglutaminase
| anti-endomysial
156
What autoantibodies are seen in congenital heart block in infants of mothers with SLE?
anti-Ro
157
What autoantibodies are seen in dermatitis herpetiformis?
anti-endomysial
158
What autoantibodies are seen in dermatomyositis?
anti-Jo-1 (t-RNA synthetase)
159
What autoantibodies are seen in diffuse cutaneous scleroderma?
anti-topoisomerase/Scl70
anti-RNA Pol I, II, III
anti-fibrillarin
160
What autoantibodies are seen in Goodpasture's syndrome?
anti-GBM
161
What autoantibodies are seen in Graves disease?
anti-TSH receptor
162
What autoantibodies are seen in Hashimoto's thyroiditis
anti-thyroglobulin
| anti-thyroperoxidase
163
What autoantibodies are seen in limited cutaneous scleroderma?
anti-centromere
164
What autoantibodies are seen in mixed connective tissue diease?
anti-U1RNP
165
What autoantibodies are seen in pernicious anaemia?
anti-parietal
| anti-intrinsic factor
166
What autoantibodies are seen in myasthenia gravis?
anti-Ach receptor
167
What autoantibodies are seen in polymyositis?
anti-Jo-1
168
What autoantibodies are seen in primary biliary cirrhosis?
anti-mitochondrial
169
What autoantibodies are seen in rheumatoid arthritis?
anti-cyclic citrullinated peptide
| anti-RF (less specific)
170
What autoantibodies are seen in systemic lupus erythematosis?
anti-dsDNA
| anti-Ro, La, Sm, U1RNP
171
What autoantibodies are seen in T1DM?
anti-glutamate decarboxylase
| anti-pancreatic beta cells
172
What autoantibodies are seen in Wegener's granulomatosis (GPA)?
c-ANCA
173
What actions boost the immune response?
1. Vaccination
2. Replacement of missing components
3. Cytokine therapy
4. Blocking immune checkpoints - for
advanced melanoma
174
What suppresses the immune response?
1. Steroids
2. Anti-proliferative agents
3. Plasmapheresis
4. Inhibitors of cell signaling
5. Agents directed at cell surface antigens
6. Agents directed at cytokines
175
Why doesn’t vaccination work effectively in the elderly?
Immune senescence: Increased frequency of terminally differentiated effector memory T cells in
the elderly; Increased expression of senescence markers; Much reduced production of recent
thymic emigrants which drive the naïve T-cell repertoire.
Nutrition: insufficient energy because of poor nutrition; Reduced availability of trace elements and
minerals (reduced gut absorption)
176
Drugs that block immune checkpoints for advanced melanoma
Ipilimumab
Pembrolizumab
Nivolumab
177
Side effects of immunosuppresives therapies
```
Chronic infection
- TB, HIV, Hep B, C, JCV
Malignancy
- lymphoma, melanoma, HPV
Autoimmunity
- SLE, vasculitis, AIH
```
178
Injection site reactions
Peak reaction at ~48 hours
May also occur at previous injection sites (recall reactions)
Mixed cellular infiltrates, often with CD8 T cells
Not generally IgE or immune complexes
179
Infusion Reactions
Urticaria, hypotension, tachycardia, wheeze – IgE mediated
Headaches, fevers, myalgias – not classical type I hypersensitivity
Cytokine storm
180
Use of human normal immunoglobulin (IVIG)
1. primary and secondary immunodeficiency
2. ITP
3. MG
4. GBS
5. Kawasaki disease
6. toxic epidermal necrolysis
7. pneumonitis induced by CMV following transplantation
8. low serum IgG levels following haematopoietic stem cell transplant for malignancy
9. dermatomyositis
10. chronic inflammatory demyelinating polyradiculopathy
181
Anti-proliferative agent action
Inhibit DNA synthesis with cells with most rapid turnover most sensitive to it
182
Anti-proliferative agent examples
Alkylates:
Cyclophosphamide
Anti-metabolites:
Mycophenolate
Mofetil
Azathioprine
Anti-folate:
Methotrexate
183
Calcineurin inhibitors used in prophylaxis for transplant pts
Tacrolimus
Cyclosporin
*Inhibits cell signaling*
184
IL-2 inhibitors used in prophylaxis for transplant pts
Sirolimus
185
Anti-CD20 agent used against lymphoma, RA, and SLE
Rituximab
186
Anti-CD25 agent used in allograft rejection
Basiliximab
187
IL-2 receptor antibody that targets CD25 used in organ transplant rejection prophlyaxis
Daclizumab
188
anti-TNF alpha agents
Infliximab
Adalimumab
Certolizumab
Golimumab
189
Which conditions require anti-TNF alpha agents?
```
Rheumatoid arthritis,
Ankylosing spondylitis,
Psoriasis, psoriatic
arthritis, Inflammatory
bowel disease
```
190
What is denosumab and when is it used?
anti-RANK ligand antibody
Osteoporosis, multiple myeloma, bone metastases
191
How does recognition in the immune system occur?
Immune Recognition:
- T-Cells (TCs) recognise antigen with MHCs on APCs
- B-Cells (BCs) can recognise just antigen
192
Most important HLA classes in transplants
DR > B > A
193
Types of recognition in tranplants
1. Direct
Donor APC presenting antigen and/or MHC to recipient T-cells. Acute rejection mainly involves
direct presentation.
2. Indirect
Recipient APC presenting donor antigen to recipient T-cells – i.e. the immune system working
normally, as it would for an infection. Chronic rejection mainly involves indirect presentation.
194
Phases of immune response to transplant
Phase 1: recognition of foreign antigens
Phase 2: activation of antigen-specific lymphocytes;
proliferation and maturation of B cells with Ab production
Phase 3: effector phase of graft rejection
Involves CD4+ cells, cytotoxic T cells, macrophages, Abs binding to graft endothelium
195
How should acute transplant rejections be treated?
Cellular – Steroids, OKT3/ATG
Ab-mediated – IVIG, plasma exchange, anti-C5, anti-CD20
196
GVHD prophylaxis
Methotrexate/cyclosporine
197
GVHD treatment
Corticosteroids
198
Post-transplantation complications
Infection
- CMV, BK virus, Pneumocystis carinii
Malignancy
- Kaposi's, EBV, melanoma
Atherosclerosis
- HTN, hyperlipidaemia, MI
199
What are the pathogenic antibodies in bullous pemphigoid?
Anti-Hemidesmosome
200
What is the target of the antibody p-ANCA?
Myeloperoxidase
201
What is the target of the antibody c-ANCA?
Proteinase-3
202
Which vaccines are avoided in pregnancy and immunocompromised patients?
Live attenuated
203
What type of vaccines are typically used for viruses?
Subunit (recombinant)
204
What type of vaccines are typically used for encapsulated bacteria?
Conjugate
205
Which vaccines include pathogens that have been rendered inert - usually by heat killing or formaldehyde?
Inactivated
206
Which primary immunodeficiency is diagnosed with Nitroblue-tetrazolium (NBT) or dihydrorhodamine (DHR) tests?
Chronic granulomatous disease
207
Mutation in what cell surface receptor may confer immunity from HIV?
CCR5
