Immunology/Microbiology Flashcards
1
Q
Which immune cells are polymorphonucleocytes?
A
- Neutrophils 2. Eosinophils 3. Basophils (granulocytes)
2
Q
How does the tetanus vaccination work?
A
Stimulates antitoxin production
Does not prevent the growth of C. tetani in wounds, but protects against the toxin produced by the organism
3
Q
Which tetanus vaccination is given to children?
A
DTPa
(diphtheria, tetanus, pertussis (acellular))
4
Q
Which tetanus vaccination is given to adolescents and adults?
A
dTpa
Contain substantially less amounts of diphtheria toxoid and pertussis antigens than DTPa
5
Q
When should adults receive a tetanus booster dose?
A
All adults aged 50 who have not had a tetanus booster in the previous 10 years
6
Q
When is tetanus immunoglobulin (TIG) given?
A
If there is any doubt about the adequacy of previous tetanus immunisation in a person with a tetanus-prone wound
e.g. immunodeficiency, <3 tetanus doses or uncertain
7
Q
Which organism causes tetanus?
A
Clostridium tetani
8
Q
Which cells are phagocytes?
A
- Monocytes (macrophages, dendritic cells)
- Mast cells
- Neutrophils
9
Q
What is the action of C5a?
A
Chemotaxis
10
Q
What is the action of C3b?
A
Opsonisation (with the action of C5a)
+ helps create MAC
11
Q
Which complement proteins are involved in the formation of the MAC?
A
C5b, C6, C7, C8, C9
12
Q
Which complement pathway requires the adaptive response for activation?
A
Classical
Activated by antigen-antibody complexes
13
Q
What are anaphylatoxins?
A
Bind to and stimulate mast cells and basophils to degranulate
Complement peptides C3a, C4a and C5a
14
Q
Which T helper cells are involved in autoimmune reactions?
A
Th1 or Th17
15
Q
Which T helper cells are involved in allergic reactions?
A
Th2
16
Q
What are 3 organisms people with asplenism particularly susceptible to?
A
Streptococcus pneumonia
Neisseria meningitidis
Haemophilis influenzae
Klebsiella
Pseudomonas aureginosa
17
Q
In which area of the spleen are APCs and specialised B cells found?
A
Marginal zone
Between the red and white pulp - area where APCs present blood-bourne antigens
18
Q
In which area of the spleen are T cells found?
A
Periarterial lymphatic sheath of the white pulp
19
Q
Which immunoglobulins are measured when investigating immunodeficiency?
A
IgA, IgG, IgM
20
Q
What are 3 congenital B-cell immunodeficiencies?
A
Brunton agammaglobulinemia (X-lined agammaglobulinemia)
Selective IgA deficiency (SIgAD)
Common variable immunodeficiency (CVID)
21
Q
In which immunodeficiency are B cells phenotypically normal but unable to differentiate into Ig-producing cells
A
Common variable immunodeficiency
22
Q
What is the most common congenital immunodeficiency?
A
Selective IgA deficiency
23
Q
Which congenital B cell immunodeficiency typically has an onset at 20-35 years of age?
A
Common variable immunodeficiency
24
Q
What type of infections are characteristic of complement deficiencies?
A
Infections from encapsulated organisms
25
What type of infections are characteristic of granulocyte deficiencies?
Skin and soft tissue infections
Catalase-positive organisms e.g. Staph aureus, Gram -ve bacilli
26
What type of infections are characteristic of T cell deficiencies?
"Benign" viruses (e.g. CMV, EBV), fungi, intracellular pathogens (e.g. mycobacteria)
27
What is the function of PRR and PAMPs?
Pattern recognition receptors (PRRs) recognise pathogen-associated molecular patterns (PAMPs) and induce cytokine release
PAMPs = products found in pathogens and not in mammals e.g. flagellin
PRR e.g. toll-like receptors
28
What is the common end point of the three complement pathways?
Splitting of C3 into C3a and C3b
29
What is the function of C3a
Histamine degranulation → enhanced inflammation
30
What is a bacterial capsule?
Polysaccharide layer that lies outside the cell envelope
Prevents phagocytosis
A capsule-specific antibody is required
31
What is the structure of immunoglobulins?
Two heavy chains
Two light chains
The variable regions of the H and L chains are the antibody binding sites
32
Which immunoglobulin crosses the placenta and provides passive immunity to children?
IgG
33
Which immunoglobulin is least affected by loss of immunoglobulins in the renal or gastrointestinal tract?
IgM
Largest of the immunoglobulins
34
Which is the most potent cytokine?
IL-6
35
How do glucocorticoids suppress the immune system?
Decreased transcription of pro-inflammatory genes
→ Inhibits neutrophil binding to the vessel wall (less emigration to tissues)
→ Inhibits leukocyte activity
* Neutrophil infections - staph, strep, candida*
* Lymphocyte infections - herpes, mycobacteria, salmonella*
36
Delayed loss of the umbilical cord is associated with which immunodeficiency?
Leukocyte adhesion deficiency
*Poor migration of immune cells from the vessel wall, particularly neutrophils*
37
What is defective in chronic granulomatous disease?
Deficiency of superoxide production by polymorphoneutrophils and macrophages → ability to ingest but not kill microorganisms → granuloma formation
38
What is the mechanism of natalizumab?
Stops leukocytes from adhering to vessel walls
Cannot reach tissues to cause inflammation
39
What is the mechanism of fingolimod?
Blocks sphingosine-1-phosphate receptor
Lymphocytes accumulate in lymph nodes → not able to travel to tissues
40
When is infection a contraindication to vaccination?
Temperature \> 38.5 degrees
Minor coughs and colds are ok
41
Which test is used to assess the complement system?
CH100/50
42
How do immunomodulators affect infection risk?
They do not increase the risk of infection as they are not immunosuppressive
43
What is the mechanism of azathioprine?
Purine antimetabolite
Impairs lymphocyte proliferation, cellular immunity and antibody responses
44
What feature is unique to splenic macrophages?
Can detect and capture encapsulated bacteria
## Footnote
*Normal macrophages detect proteins, but the polysaccharide wall is a sugar*
45
What is a unique feature of B cells in the splenic marginal zone?
Can initiate T cell-independent immune reactions
46
What occurs in the cortex of lymph nodes?
B cell proliferation occurs in germinal centres
47
What lies in the paracortex of lymph nodes?
T cells
48
What is the role of dendritic cells in lymph nodes?
Dendritic cells are activated → enter lymph node → present antigen to T cells → T cells activate B cells → antibody production
49
Why are patients with diabetes immunocompromised?
Neutrophil dysfunction → bacterial and fungal infections
Poor peripheral circulation → ulceration + poor delivery of neutrophils
50
Which immunoglobulin(s) are affected by asplenism?
IgM
51
Which immunoglobulin is involved in type III hypersensitivity reactions?
IgG
52
Why do type I hypersensitivity reactions occur so rapidly?
IgE coats mast cells and basophils with initial contact with the antigen
Antigen readily binds to IgE with subsequent exposure and causes degranulation
53
Which immunoglobulin(s) are involved in type II hypersensitivity reactions?
IgM and IgG
Bind to antigens → complement activation → cellular lysis and phagocytosis
54
What is tryptase?
Specific marker of mast cell activation
If elevated → increased risk of anaphylaxis
55
What is the mechanism of montelukast?
Leukotriene receptor antagonist
## Footnote
*May be used for long-term asthma control*
56
What is the mechanism of complement-dependent type II hypersensitivity reactions?
1. IgG and IgM bind to antigens
2. Complement activation (classical)
3. Cellular lysis or phagocytosis
* E.g. autoimmune haemolytic anaemia, pemphigus vulgaris, drug reactions*
57
What is the mechanism of antibody-dependent cell-mediated cytotoxic type II hypersensitivity reactions?
Ab + Ag → activation of NK cells → cell lysis without phagocytosis
## Footnote
*Destruction of targets too large to be phagocytosed e.g. parasites, tumour cells, graft rejection*
58
What is the mechanism of antibody-mediated cellular dysfunction type II hypersensitivity reactions?
Antibodies directed against cell surface receptors → impaired or dysregulated cell dysfunction
## Footnote
*E.g. MG, Goodpasture's, pernicious anaemia, acute rheumatic fever*
59
What type of hypersensitivity is myasthenia gravis?
Type II (antibody-mediated cellular dysfunction)
Antibodies bind to post-synaptic ACh receptors, competing with ACh
60
What type of hypersensitivity reaction is Goodpasture's syndrome?
Type II (antibody-mediated cellular dysfunction)
Antibodies against type IV collagen (in basement membrane of glomerulus → glomerulonephritis + acute renal failure)
*Can also affect alveoli*
61
What type of hypersensitivity reaction is pernicious anaemia?
Type II (antibody-mediated cellular dysfunction)
Antibodies against intrinsic factor and/or parietal cells
62
What type of hypersensitivity reaction is autoimmune haemolytic anaemia and acute haemolytic transfusion reaction?
Type II (complement-dependent)
63
What type of hypersensitivity reaction is pemphigus vulgaris?
Type II (complement-dependent)
64
What type of hypersensitivity reaction is rheumatic fever?
Type II
Antibodies against streptococcal M protein
65
What type of hypersensitivity reaction is lupus?
III
66
What are the two forms of type IV hypersensitivity?
1. Delayed-type
2. T-cell mediated
67
What is the pathophysiology of delayed-type IV sensitivity?
Antigen exposure → CD4+ and MHC-II activation → CD4+ differentiation to TH1 → inflammatory reaction
## Footnote
*E.g. TB skin test, contact dermatitis, granulomatous inflammation*
68
What is the pathophysiology of cell-mediated cytotoxic IV sensitivity?
Sensitisation of CD8+ cells
## Footnote
*Graft rejection, viruses, tumour immunity, intracellular pathogens e.g. TB*
69
What type of hypersensitivity reaction is GBS?
Type IV
70
What type of hypersensitivity reaction is T1DM?
Type IV
71
What is the role of glucocorticoids in anaphylaxis?
Prevention of late phase reaction (limited evidence, but no harm)
72
What are 3 mechanisms of peripheral T cell tolerance?
1. Anergy (no second signal)
2. Block in activation (suppression)
3. Deletion (apoptosis)
73
What types of vaccination are given to asplenic patients?
Conjugate or recombinant
## Footnote
*Both contain have a protein component which stimulates T cell proliferation*
74
Which type of bones contain red bone marrow?
Flat bones e.g. pelvis
Long bones
75
What is positive selection?
T cells that generate a functional receptor and can bind with self MHC molecules proliferate
76
What is negative selection?
Removes thymocytes that bind to MHC self-peptides
77
What is the most common cause of angioedema from direct mast-cell activation (non-IgE mediated)?
NSAIDs
78
What is the risk of HIV transmission in MSM?
0.5% for a receptive partner
79
What is the risk of HIV transmission in male to female intercourse?
0. 1% for female partner
0. 05% for male partner
* HIV concentration is higher in male ejaculate than in vaginal secretions*
80
Which HIV proteins help the virus attach to CD4 receptors?
gp120 and gp41 (envelope proteins)
81
Which protein helps viruses convert viral RNA to DNA?
Reverse transcriptase
82
Which protein is required to insert viral genes into the host genome?
Integrase
83
What is the definition of a retrovirus?
Genome is stored in RNA rather than DNA
84
Which immune cells have CD4 receptors?
T lymphocytes
Macrophages
Monocytes
Dendritic cells
85
Which two things must be present for HIV virus to enter a cell?
CD4 receptor
Coreceptor (CCR4 in T cells and CCR5 in all other CD4 cells)
86
A mutation in what is associated with HIV immunity?
Homozygous CCR5 mutation = immunity
Heterozygous CCR5 mutation = slower disease progression due to impaired viral spread
87
What is acute retroviral syndrome?
Acute HIV syndrome
Fever, fatigue, lymphadenopathy, myalgia/arthralgia, headache, rash, GI symptoms, sore throat, ulcerations, painful swallowing
*Similar to mono (rashes and diarrhoea more prevalent)*
88
What is HIV wasting syndrome?
Unintentional weight loss of \>10%, fever, fatigue, diarrhoea
89
What is kaposi sarcoma?
Tumour of the skin and mucosa caused by herpes virus 8
Most common HIV-associated tumour
90
What is the most common opportunistic bacterial infection in AIDS patients?
Mycobacterium avium complex (MAC infection)
91
What is progressive multifocal leukoencephalopathy?
Reactivation of JC virus → infects oligodendrocytes → aggressive replication within brain tissue → destruction of infected oligodendrocytes + demyelination
## Footnote
*Focal symptoms, seizures, impaired vigilance, cognitive disorders, behavioural changes*
92
What is the most common cause of death in AIDS patients?
Pneumocystitis pneumonia
## Footnote
* Caused by pneumocystitis jiroveci (fungus)*
* Occurs almost exclusively in immunocompromised patients*
93
What is the HIV window period?
Time between infection and detectability of HIV antibodies
2-6 weeks
94
List 10 AIDS-defining conditions
1. HIV wasting syndrome
2. Kaposi sarcoma
3. Invasive cervical cancer
4. Lymphoma (non-Hodgkin)
5. TB reactivation
6. Coccidioidomycosis
7. Cryptosporidiosis
8. HIV-related encephalopathy (AIDS dementia)
9. PML
10. Pneumocystitis pneumonia
11. Isosporiasis
12. Histoplasmosis
13. Cerebral toxoplasmosis
14. Cryptococcosis
15. Candidiasis
16. Herpes simplex infections
17. CMV infection (other than spleen, lymph nodes or liver)
18. MAC infection
95
A CD4 count less than what is definitive of AIDS irrespective of symptoms?
\<200 cells/uL
96
Which virus causes Kaposi sarcoma?
Herpes virus 8
97
What is the first-line investigation for diagnosing HIV?
HIV Ag/Ab
## Footnote
* Detects HIV antigen (p24) and anti-HIV antibodies*
* Near 100% sensitivity*
98
Which allele should be tested upon initiation of abacavir?
HLA-B\*5701
## Footnote
*Hypersensitivity*
99
What are 4 drug classes used in the treatment of HIV?
1. Nucleoside reverse transcriptase inhibitors
2. Non-nucleoside reverse transcriptase inhibitors
3. Protease inhibitors
4. Integrase inhibitors
5. Fusion inhibitor
6. Nucleoside analogues
7. CCR5-antagonist
100
What is the most common HIV retroviral regimen?
2 NRTI + 1 NNRTI / protease inhibitor / integrase inhibitor
101
Name 4 first-line nucleoside reverse transcriptase inhibitors
1. Tenofovir
2. Emtricitabine
3. Abacavir
4. Lamivudine
* 5. Zidovudine*
* 6. Stavudine*
* 7. Didanosine*
* mostly end in "-ine"*
102
What is the first-line non-nucleoside reverse transcriptase inhibitor?
Efavirenz
## Footnote
*Other: Nevirapine*
103
Name two first-line protease inhibitors
1. Atazanavir
2. Darunavir
* Indinavir*
* Ritonavir*
* Nelfinavir*
* Lopinavir*
* end in "-avir"*
104
Name two integrase inhibitors
Raltegravir
Dolutegravir
*end in "-gravir"*
105
What are 3 adverse effects of nucleoside reverse transcriptase inhibitors?
1. Bone marrow suppression (neutropenia, anaemia)
2. Mitochondrial toxicity (lactic acidosis, myopathy, neuropathy)
**3. HIV-associated lipodystrophy**
4. Hypersensitivity (abacavir)
5. Pancreatitis (didanosine/stavudine)
106
----- is a CNS protozoal infection that presents with brain abscesses in HIV patients, that are seen as ring-enhancing brain lesions on CT/MRI
Toxoplasmosis
107
Which protozoa causes toxoplasmosis?
Toxoplasma gondii
108
How is toxoplasmosis transmitted?
The oocytes are excreted in the faeces of cats and are orally ingested by other mammals such as humans, hoofed animals, and birds. Primary modes of transmission therefore include:
Cat feces
Raw or insufficiently cooked meat
Unpasteurized milk (especially goat milk)
109
Which opportunistic fungus causes pneumonia in HIV patients?
Pneumocystic jirovecii
110
Which type of vaccination should not be given to immunocompromised patients?
Live attenuated
111
------ is a dermatological infection caused by EBV in HIV patients that commonly presents on the lateral tongue
Hairy leukoplakia
112
------ is a protozoa that causes GI infection in HIV patients that presents with chronic, watery diarrhoea
Cryptosporidium spp
Acid fast cysts are seen in the stool
113
------- is an opportunistic fungus that causes meningitis in HIV patients
Cryptococcus neoformans
114
Which immune cells can a monocyte differentiate into?
1. Macrophage
2. Dendritic cells
3. Microglial cell
* Monocyte in blood, other cells in tissue*
115
When is HIV transmission greatest?
Acute infection
Viral load is high
116
Which 4 features are most discriminatory between acute HIV infection and EBV?
1. Profound malaise
2. High fever
3. Weight loss
4. Mouth ulcers
117
How is oral candida distinguished from hairy cell leukoplakia?
Oral candida is not adherent and can be removed with scratching
Leukoplakia is more adherent
118
Which organism causes hairy cell leukoplakia?
EBV
119
Candidiasis involving which organs is an AIDS-defining illness?
Bronchi, trachea, lungs, or oesophagus
120
Retinitis of which pathogen is an AIDS-defining illness?
CMV retinitis
121
Primary CNS lymphoma is an AIDS-defining illness associated with which infection?
EBV
122
What prophylaxis is given to HIV patients for pneumocystis pneumonia and when?
Trimethoprim-sulfamethoxazole
CD4 \< 200 cells/mm3
123
What prophylaxis is given to HIV patients for toxoplasma gondii and when?
Trimethoprim-sulfamethoxazole
CD4 \< 100 cells/mm3
124
What prophylaxis is given to HIV patients for TB and when?
Isoniazid + pyridoxine
Positive tuberculin skin test or interferon-gamma release assay (i.e. latent)
125
What prophylaxis is given to HIV patients for MAC disease and when?
Azithromycin or clarithromycin
CD4 \<50
126
Why is the majority of CD4+ death in HIV from non-infected cells?
1. HIV attracts T cells to lymph nodes
2. HIV virus releases an interleukin which promotes intracellular inflammation in T cells
3. T cells undergo **PYROPTOSIS**
4. Debris from pyroptosis induces inflammation in surrounding T cells
5. Cascade of pyroptosis and inflammation
127
Name 5 non-AIDS HIV syndromes
1. Immune thrombocytopaenia purpura
2. GBS
3. Bell's palsy
4. Psoriasis
5. Seborrheic dermatitis
6. Oral hairy leukoplakia
7. Oral candida
8. HSV
9. HZV
10. Gingivitis
11. Molluscum contagiosum
128
What adverse effect(s) are associated with tenofovir?
Nephrotoxicity
Osteoporosis
129
What adverse effect is associated with efavirenz (NNRTI)?
CNS toxicity (give before bed)
130
What adverse effect(s) are associated with atazanavir (PI)?
Jaundice
Renal stones
131
What adverse effect is associated with integrase inhibitors?
Myositis
132
What is a toxicoid vaccine?
Stimulates immunity to toxins, not to the organism itself
Vaccine contains toxoids (inactivated toxins)
e.g. tetanus, diptheria
133
What is a subunit vaccination?
Vaccine presents an antigen to the immune system without introducing the pathogen
Includes toxoid, polysaccharide, conjugate and recombinant vaccines
134
What is a conjugate vaccine?
Polysaccharide from encapsulated bacteria + carrier protein
B cell responses to capsular polysaccharides are T cell indepednent
By conjugating the polysaccharide to a protein carrier, a T cell response can be induced
T cells stimulate a more vigorous immune response and have more rapid, long-lasting immunologic memory
135
What is a recombinant vaccine?
Genes that encode antibody formation are inserted into the DNA of other cells e.g. yeast
When this harmless cell replicates in the body, antibody production occurs
E.g. hepatitis B, HPV
136
What is a polysaccharide vaccine?
Contains part of the polysaccharide shell of encapsulated bacteria
E.g. Pneumovax (*Streptococcus pneumoniae*)
137
What is the function of protease?
Cleavage of viral proteins into functional polypeptides (core proteins)
These proteins then form the viral capsid
138
What is an arthus reaction?
Antibody/antigen complex formation in the skin --\> local inflammation +/- necrosis (type III hypersensitivity)
Most commonly following booster vaccinations
More likely if boosters are given close together and circulating antibodies are high
139
How are B cells activated?
1. Antigen is presented to B cells
2. B cells express antigen on MHC-II
3. Helper T cells provide costimulation
140
What constitutes a complete tetanus immunisation schedule?
3 primary (2, 4 and 6 months of age)
+ 2 booster (ideally 18 months and 4 years)
141
A person in ARV therapy for HIV develops jaundice and renal stones
Which drug is likely to have caused these effects?
Atazanavir
142
A person in ARV therapy for HIV develops myositis
Which drug is likely to have caused these effects?
Raltegravir
Dolutegravir
143
Which medications are in TRUVADA (for PrEP)?
Emtricitabine and tenofovir
144
Why do patients with CVID have low immunoglobulin levels?
B cell dysfunction and poor differentiation → impaired antibody production
145
What type of infections are most common in patients with B cell immunodeficiencies?
Sinopulmonary (pneumonia, bronchitis, sinusitis, otitis, conjunctivitis)
Chronic diarrhoea (norovirus, campylobacter jejuni, salmonella)
146
What is the difference between humoral and cellular immunity?
Humoral = antibody-mediated. Acts on extracellular microbes
Cellular = T cells, NK cells, macrophages. Acts on intracellular microbes
147
What is the pathophysiology of allergic contact dermatitis?
1. Allergen enters the dermis and is picked up by a dendritic cell
2. Allergen is presented on MHC-II
3. T helper cells recognises antigen and binds to MHC-II with CD4 coreceptor
4. Dendritic cell releases IL-12, stimulating maturation and differentiation of the CD4 cell to a Th1 cell
5. Th1 cell releases inflammatory mediators
Repeated contact with allergen stimulates memory T cells
148
What is the pathophysiology of urticaria?
1. Allergen is picked up and presented in lymph nodes by APCs
2. CD4 cell binds to APC and differentiates into a Th2 cell
3. Th2 cell stimulates class switching of B cells, so IgE (not IgM) is produced
4. IgE binds mast cells **(sensitisation)**
5. Mast cell activation → inflammatory reaction
6. Subsequent exposure to allergen → quick reaction due to preformed IgE
149
When is the onset of x-linked agammaglobulinemia?
\>4 months after birth
150
What is defective in x-linked agammaglobulinemia?
Complete B cell deficiency
151
Which non-infectious conditions are associated with selective IgA deficiency?
Coeliac
IBD
152
Which non-infectious conditions are associated with CVID?
Lymphoma, gastric cancer
Autoimmune disorders e.g. RA, autoimmune haemolytic anaemia, immune thrombocytopenia, vitiligo
153
What is the RAST?
Radioallergosorbent test
Detects specific IgE antibodies
