Immunology Flashcards
1
Q
CD35
A
On RBC, monocytees, granulocytes, B cells
Provides entry for.mycobacteria and leishmania
2
Q
CD21
A
On B cells
Provides entry for EBV and HIV
3
Q
CD11b/CD18
A
Provide entry for mycobacteria
On macrophages, NK cell and polymorphs
4
Q
MAC Inhibitors on cells
A
DAF - delay accelerating factor bracks down C3
HRF - homologous resteiction factor - CD59 prevents formation of MAC on host cells
5
Q
NK cell killing mechanism
A
Release Perforin or Fas ligand binds to target cells and induces apoptosis
(Fas is also CD95)
6
Q
NK cell killing mechanism
A
Perforin or Fas ligand induce apoptosis
Fas is also CD95
7
Q
Alternative name for NK cells
A
Large granular lymphocytes
8
Q
What cells do NK cells target
A
Virally infected cells
Detect these cells when MHC I is down regulated, inhibiting receptor or activating receptors are on target cell.
Also induce killing by antibody dependent cell cytotoxicity
9
Q
Positive selection
A
T cells must be able to recognise and bind to self MHC
10
Q
Negative selection
A
T cells killed in the thymus if the bind too strongly to self MHC to avoid autoimmunity
11
Q
CRP in innate immunity
A
Binds to c peptide of pneumococcus and triggers complement pathway
acute-phase protein binds to phospholipid in foreign pathogens or damaged host cells
12
Q
TLR 4
A
Innate receptor that is assocaited with Gram neg septic shock in the setting of release of lipopolysacharride cell wall
13
Q
TLR 3
A
Deficiency assocuated with HSV encephalitis
-Controls the interferon respnse to dsRNA intermediates of HSV1
14
Q
IRAK 4 deficiency
A
(Innate)
Recurrent pyogenic infections
15
Q
Inflammasome Interleukins
A
IL 1
IL 18
16
Q
FMF gene mutation
A
MEFV (mutation in pyrin gene)
AR , gain of function
17
Q
NOD 2 in Crohns disease
A
Loss of function
-LEads to more susceptibility to bacteria and less killing of intracellular bacteria leading to granuloma formation
18
Q
Acute phase response monokines
A
TNF, IL1, IL6
19
Q
RIG 1 like receptor
A
For detection of cytoplasmic viral RNA
20
Q
Interferon Type 1
A
Released in response to viral infections
MAin source is plasmacytoid DCs
Interfere with viral replication
21
Q
TREX 1 gene mutatuon
A
SLE
22
Q
Lack of antibody response
A
Recurrent sinopulmonary and gut infections
Skin infections
By:
- polysaccharide-encapsulated pyogenic organisms (Strep pneumoniae, H influenza type B, Strep pyogenes, Branhamella catarrhalis)
- Staph aureus
- Giardia lamblia
- Campylobacter jejuni
23
Q
LAck of T cells
A
Intracellular organism infections
- Fungi e.g. mucosal Candida, not systemic; pneumocystis (Th17)
- Viruses e.g. CMV, VZV, HSV; protozoa (CD8)
- Listeria
24
Q
Lack of neutrophils/monocytes
A
High grade bacterial infections
- Staph aureus
- Gram negative bacteria (E coli, P mirabilis, Serratia marcescens, Pseudomonas aeruginosa and cepacia)
Fungi
- Invasive aspergillosis
- Systemic candidiasis
25
Lack of complement components
Classical pathway
- C1q, C1r, C1s: SLE
- C4: SLE, GN
- C2: SLE (50%), vasculitis, GN, recurrent pyogenic infections
- C3: Recurrent pyogenic infections, CN, immune complex diseases
Alternative pathway
- Properdin, Factor D: Neisseria infections
Terminal components
- C5/6/7/8/9: Disseminated Neisseria infections
26
Conjugate vaccines attached to a carrier protein and polysaccharide antigen have better efficacy than conjugated vaccine attached to polysaccharide alone. Reason?
Addition of the carrier protein to a polysaccharide vaccine makes a polysaccharide vaccine T cell dependent thus boosting the effect of the vaccine
27
Th1 cell pathway
IL 12: naive T cell to Th1
-Induction pathway: STAT4, STAT1, T-bet
Major cytokines
- IFN gamma
- IL2
- IL10
- TNF Beta
Role in infection:
Intracellular microorganism, AI, proinflammatory, invasive salmonellosis, severe viral infections
28
Th2 cell pathway
IL 4: Naive T cell to Th2
Induction pathway:
-STAT6, GATA3
Major cytokines:
-IL4, IL5, IL9, IL10, IL13, IL25
Role in infection:
-Parasitic, allergic
29
Th17 cell pathway
IL1 and IL6: Naive T cell to Th17
Induction pathway:
STAT3 and ROR
Major cytokines:
-IL17, IL21, IL22
Role in infection:
- Extracellular bacteria and fungi
- Autoimmunity
30
TREG Cell pathway
IL2 and TGF Beta: Naive T cell to TREG
Induction pathway:
-STAT 5, Foxp3
Major cytokines
-IL10, TGF Beta, IL 35
Role in infection:
-Tolerance, minimise autoimmunity/allergy/inflammation
31
Live Vaccines
```
Yellow fever
MR
Rotavirus
BCG
Japanese encephalitis
Oral Typhoid
VZV
```
32
PAracetamol allergy
* Also a weak inhibitor of cyclooxygenase 1 (COX 1)
| * Also a weak inhibitor of cyclooxygenase 1 (COX 1)
33
HLH
| haemophagocytic lymphohistiocytosis
- Excessive immune activation
- Common trigger: EBV
- macrophages become activated and secrete excessive amounts of cytokines, ultimately causing severe tissue damage that can lead to organ failure
- NK cells and/or CTLs fail to eliminate activated macrophages.
- This lack of normal feedback regulation results in excessive macrophage activity and highly elevated levels of interferon gamma and other cytokines.
34
Which immunoglobulins are inolved in ADCC
IgG and IgE
35
Isotype Definition
Variations in the Igs which are present in all members of the family species e.g. IgG1 and IgG2
36
Immunogen
Molecule that elicits an immune response
37
Hapten
Small molecule that alone will not elicit an immune response but will do so when linked to a larger one, called a carrier
38
Epitope
Portion of macromolecule to which Ab binds
39
CD20/21
Mature B cells (Not plasma cells)
| -CD1 also for EBV entry
40
CD19
All B Cells (including plasma cells)
41
CD40
T and B cell interaction
42
CD3
All T cells
43
Best T cells to use for T cell selection
Weak binding to MHC (Positive selection)
44
Best T cells for TREG cells for T cell selection
Slightly less strong MHC binding
| -Not the strongest - those are negative selection
45
Role of AIRE
Autoimmune regulator
| -Turn on expression of Tissue specific Antigen for T cell selection in thymus
46
APECED
Autoimmune Polyendocrine Syndrome 1
(Autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy)
AR
Due to mutated AIRE gene
47
APECED Triad for presentation
Chronic mucocutaneous candidiasis
AI hypoparathyroidism
AI Addisons disease + other AI manifestations
48
2 Signals needed for T cell activation
1. MHC and TCR
2. CD80/CD86 (B7 molecule) to CD28 for activation
or CTLA4 for downregulation
49
IPEX
Lack of Foxp3 - so no Treg cells
-Global overactivity of immune function (AI, allergy, lymphoproliferative)
DEath as a newborn
50
Superantigen
Antigens that stimulate a wide range of T cells - leads to massive cytokine release
-TSS, staph enterotoxins
51
Type 1 Hypersensitivity
- Allergy, immediate
- Atopy, anaphylaxis, asthma
- IgE mediated
Fast response (minutes). Free antigens cross link the IgE on mast cells and basophils causing release of Vasoactive biomolectules. Testing can be done with skin test for specific IgE.
52
Type 2 Hypersensitivity
- Cytotoxic, antibody-dependent
- Autoimmune haemolytic anaemia, rheumatic heart disease, Goodpasture’s, Grave’s, Myasthenia Gravis
- IgG, IgM, complement, MAC
Antibody inappropriately binds to target host cell (perceived as foreign), leading to cellular destruction via the MAC
53
Type 3 Hypersensitivity
- Immune complex disease
- Serum sickness, RA, post-strep GN, membranous GN, SLE, hypersensitivity pneumonitis
- IgG, complement, neutrophils
IgG binds to soluble antigen forming circulating immune-complex that can be deposited in tissues leading to local inflammatory response.
54
Type 4 Hypersensitivity
- Delayed-type hypersensitivity, antibody-independent
- Contact dermatitis, mantoux test, chronic transplant rejection, MS
- T-cell mediated
Th1 cells are activated by APCs. When antigen is presented again, the memory Th1 cells activate macrophages and cause inflammatory response.
55
Clinical features of CVID
```
REcurrent sinopulmonary infections
Chronic or recurrent diarrhea
AI disease
LYMPHOMA, stomach ca
Splenomegaly, granulomatous disease
Allergic disease
Bronchiectasis
```
56
MX of CVID
IVIG monthly
| AVOID live vaccines
57
Where does the problem occur in XLA
B cell development blockade at Pre B I stage due to BTK mutation
58
Hyperacute rejection
AMR pathway
59
Acute rejection
```
Recipient T cells activated by HLA class 1 donor tissue cells. So CD8 cells attack
-Usually days post transplant
```
60
Chronic rejection
REcipient dendritic cells and monocytes infiltrate the graft
61
What is GVHD
Donor T cells attack the patients organs and tissues
62
Clinical features of cryoglobulinemia
```
Skin purpura
Cutaneous necrotising ulcers
GN
Peripheral neuropathy
Non erosive arthritis
Acral ischemia
Raynaud's
```
63
Systemic MAstocytosis
Proliferative disorder of haematopoetic mast cell progenitors leads to more mast cells on organs
-Due to KIT mutation (D816V mutation)
Higher risk of more severe reactions in venom allergy
64
PEnicillin cross reactivity
Amoxycillin, cephalexin, and cefaclor all have the same R1 side chain
65
Hyper IgM Syndrome
X linked, CD40L deficiency
Failure of B cell isotype switching and memory B cell generation
Tx:
-IVIG, Bactrim prophylaxis (High risk of PJP), G-CSF
66
Combined immunodeficiency
Not as severe as SCID
Ab and T cell deficiency
Worse prognosis than CVID
Mx with IVIG, avoid vaccines
67
Chronic mucocutaneous candidiasis
OFten lack of Th17
Onset in childhood
Can be thymoma associated
68
Chronic Granulomatous disease
Deficiency in NADPH oxidasse (gp91 on X chromosome)
Clinical:
-Recurrent infections
Tx: Chronic antiboitics, immunisation
69
Activators of alternative pathway
Surface bacteria, viruses
Polysacharrides
IgA immune complexes
C3 nephritic factor
70
Activators of Classical pathway
IgM, IgG
CRP
C1q
71
Activators of Lectin pathway
MBL
| Ficolins 1-3
72
Function of complement
Cytolysis
Opsonisation (enhance uptake by phagocytes)
Activation of inflammatory response
Immune complex clearing
73
Anaphylatoxins
C3a, C4a, C5a
74
List the complements in the different pathways
Classical: C1, C2, C4, C3
Alternative: C3, B, D, Properdin (Factor P)
75
SERPING1 gene
Need homozygous genes for normal C1 inhibitor amount
76
Hereditary Angioedema
Type 1: Reduced C1 inh level
| Type 2: Dysfunctional C1 inh - normal level or increased
77
Acquired angioedema
Type 1: Associated with B cell lymphoproliferative disorders; Consumption of C1 Inh
Type 2: AI disoders or idiopathic; Ab against C1 inh
C1q levels reduced in acquired not in HAE
78
Tx of HAE:
Acute:
- Purified C1 Inh protein, FFP
- Icatibant - Bradykinin 2 receptor antagonist
- Ecallantine: Kallikrein inhibitor
Prevention:
-Anabolic sterodis
Tranexamic acid
C1 INH
79
Protein mutation that is assoicated with atopic dermatitis
Filaggrin
80
Why do ACE inhibitors cause angioedema
• Angiotensin converting enzyme has at least two physiologic functions.
1. It catalyses the conversion of angiotensin I to angiotensin II (a vasoconstrictor that increases blood pressure)
2. It degrades bradykinin (a potent vasodilator) to inactive metabolites
ACE inhibitors have the effects of DECREASING angiotensin II and INCREASING bradykinin.
81
Causes of Acquired C1 inhibitor deficiency
B cell lymphoproliferative disorders
MGUS
Malignancies
AI disorders
82
CD25 + CD4
Treg cells
83
IgA deficiency complications
Blood transfusions need to be screened
| NO LIVE VACCINES
84
Imiquimod TLR
TLR 7 agonist
| Used in BCC
85
CD16, CD56, CD8
NK cells
86
c ANCA
PR3
| GPA
87
p ANCA
MPO
| EGPA, microscopic polyangitis, UC, SLE
88
Vaccines recommended in aplenia
pneumococcus, meningococcus, haemophilus influzae b and yearly influenza recommended
89
ABx prophylaxis in aplenia
§ Amoxicillin daily (250mg) or phenoxymethyl penicillin 250mg BD
§ If allergic take 150mg roxythromycin daily
§ Immuno-competent person – take for 3 years or lifelong
Immuno-compromised- continue lifelong
90
Live Vaccines mneumonic
MMR BOYZ Japanese Diarrhea
- MMR
- BCG
- Oral Polio
- Yellow fever
- Zoster
- Japanese encephalitis
- Oral Typhoid/Rotavirus
