Immunodeficiency Flashcards
1
Q
Which immunodeficiency in common? primary or secondary?
A
Secondary immunodeficiency (due to disease or medication)
(It is encountered by physician on a daily basis in routine practice)
2
Q
What are the pattern of infection in immunodeficiency?
A
- Neutrophil defects
- Complement deficiency
- B cell/antibody deficiency
- T cell deficiency
3
Q
Primary Immunodeficiency: Classification >> Major categories
A
- Neutrophil disorders/deficiencies
- Complement deficiencies
- B cell/antibody disorders/deficiencies
- T cell disorders/deficiencies
- Combined B & T cell disorders/deficiencies
4
Q
Primary immunodeficiency: Neutrophil defects
A
Mnemonic ‘CCL’
- Chronic granulomatous disease
- Chediak-higashi syndrome
- Leukocyte adhesion deficiency
5
Q
Primary immunodeficiency: complement defects
A
The most importants are >>
- C1q deficiency
- C1INH deficiency
- Final common pathway defects
- & many others
6
Q
Primary immunodeficiency: B cell/Antibody disorders
A
Mnemonic ABC
- IgA** deficiency**
- Bruton’s congenital agammaglobulinaemia
- Common variable immunodeficiency (CVID)
7
Q
Primary immunodeficiency: T-cell defects
A
DiGeorge syndrome
8
Q
Secondary immunodeficiency >> Example by categories
A
-
Neutrophil defect:
- Diabetes mellitus
-
Complement deficiency:
- Eculizumab therapy
-
B cell/ Antibody defect:
- Chronic lymphocytic leukaemia (CLL)
- Rituximab
- Phenytoin
- Gold
-
T-cell defect:
- HIV infection
- Ciclosporin
- Anti-CD3 therapy
9
Q
Primary immunodeficiency: Combined B and T cell defects
A
Mnemonic: SCID WAS Ataxic
- SCID (Severe combined Immunodeficiency)
- Ataxia Telangiectasia
- Wiskott-Aldrich syndrome
10
Q
Neutrophil defects are associated with-?
A
Recurrent bacterial or fungal skin infection (Cellulitis/Abscess)
11
Q
Neutrophil defects: Examples
A
-
Primary: CCL
- Chronic granulomatous disease
- Chediak-higashi syndrome
- Leukocyte adhesion deficiency
- Secondary: Diabetes mellitus
12
Q
Complement deficiency: identification
A
It may be uncovered incidentally (as NOT always symptomatic)
13
Q
The most important clinical association with complement deficiency-?
A
- Hereditary angioedema (C1-inhibitor deficiency)
- SLE (C1q deficiency)
14
Q
What does happen if there is “final common pathway” defect?
A
Recurrent/invasive Neisseria spp. infections
15
Q
Complement deficiency: Examples
A
-
Primary:
- C1q deficiency
- C1-INH deficiency
- ‘final common pathway’ deficiencies
- Secondary: Eculizumab treatment
16
Q
Eculizumab >> mechanism
A
C5 inhibitor
17
Q
Eculizumab >> Indication
A
PNH (Paroxysmal nocturanl haemoglobinuria)
(Its a complement mediated RBC cell lysis)
18
Q
Eculizumab: Main side-effect
A
Secondary complement deficiency
19
Q
B-cell/antibody deficiency >> results in??
A
- Sinopulmonary infections
- Bronchiectasis
20
Q
B-cell/antibody deficiency: Examples
A
-
Primary ABC
- Selective IgA deficiency
- Bruton’s agammaglobulinemia
- Common variable immunodeficiency
-
Secondary
- Chronic lymphocytic leukaemia (CLL)
- Rituximab
- Gold
- Phenytoin
21
Q
Chronic Granulomatous Disease: Inheritance
A
Variable pattern of penetrance
Mainly X-linked recessive
22
Q
Which is more common between IgA deficiency and IgG2 deficiency?
A
Primary IgA deficieny is more common than IgG2 deficiency in population
23
Q
IgA deficiency: main pathophysiology
A
Maturation defect of B cell
24
Q
IgA deficiency: Features
A
NO sign-symptoms
can cause bronchiectasis
25
**Time period of \>\>**
**Bruton's congenital agammaglobulinaemia**
**Common variable immunodeficiency (CVID)**
* **Bruton's agammaglobulinaemia: within 1st 18months**
* **CVID: late teenage**
26
**Bruton's congenital agammaglobulinaemia: Inheritance**
**X-linked recessive**
27
**Bruton's congenital agammaglobulinaemia: pathophysiology**
* **Mutation in Bruton's kinase**
* **Defective maturation of B cell ( = NO/less formation of plasma cells = less Ig production)**
* **Immunoglobulin (Ig) deficiency**
28
**Common variable immunodeficiency (CVID): manifestations**
* **Impaired function of antibody response \>\>\> recurrent sino-pulmonary infections**
* **2 or more Ig are reduced among \>\>\> IgA, IgM, IgG**
* **More common: IgA reduction**
* **More reduced: IgG** (than IgM)
* **No sign-symptoms**
29
**T-cell deficiency \>\> results in-?**
**The following opportunistic infections**
* **Pneumocystis jirovecii**
* **Invasive virus (e.g. CMV: Cytomegalovirus)**
* **Intracellular bacteria (e.g. Salmonella)**
* **Mycobacteria**
30
**T-cell deficiency: Examples**
* **Primary**
* **DiGeorge syndrome**
* **Secondary**
* **HIV infection**
* **Cyclosporin**
* **Anti-CD3 therapy**
* **Combined B + T cell deficiencies (primary)** *Mnemonic: SCID WAS Ataxic*
* **Severe combined immunodeficiency (SCID)**
* **Wiskott-Aldrich syndrome**
* **Ataxia telangiectasia**
31
**DiGeorge syndrome \>\> type of genetic disorder**
**Microdeletion syndrome**
32
**DiGeorge syndrome: type of infections**
**Viral and fungal infections** (high risk)
(As it is a T-cell defect)
33
**DiGeorge syndrome: genetic defect**
**Chromosome 22 deletion (chromosome 22q11 anomaly)**
34
**DiGeorge syndrome: Features**
*Above downwards*
* **Learning disabilities**
* **Hypertelorism (increased distance between 2 orbits)**
* **Abnormal ear**
* **Cleft palate, short philtrum**
* **Micrognathia**
* **Maldevelopment of pharyngeal pouch**
* **NO parathyroid development \>\>\> hypocalcaemia \>\>\> tetany**
* **NO development of normal thymus**
* **Normal B cell (rests are low)**
* **Reduced T cell production**
* **Reduced _IgG_ response**
* **Reduced _IgA_ response**
* **Congenital heart disease**
* **Defect in great vessels**
* **Hypocalcaemia (low calcium level)**
35
**Combined B-cell and T-cell disorder: Inheritance**
* **Severe combined Immunodeficiency (SCID): X-linked recessive**
* **Wiskott-Aldrich syndrome: X-linked recessive**
* **Ataxia telangiectasia: Autosomal recessive**
36
**SCID (Severe combined Immunodeficiency): Enzyme defect**
**Reduced ADA (Adenosine deaminase) enzyme**
37
**SCID (Severe combined Immunodeficiency): Pathophysiology**
**ADA (Adenosine deaminase enzyme) normally converts \>\>\>**
* **Deoxyadenosine to deoxynosine (AND, also)**
* **Adenosine to inosine**
**In SCID \>\>\> reduced ADA \>\>\>** **so,**
* **High deoxyadenosine, low inosine etc.**
**\>\>\> deoxyadenosine is toxic to lymphocytes (both B and T cells) [especially immature T cells of thymus]**
38
**Wiskott Aldrich Syndrome: gender ratio**
**Mainly male (as X-linked recessive)**
39
**Type of Immunoglobulin deficiency in Wiskott-Aldrich syndrome and Ataxia telangiectasia**
* **Wiskott-Aldrich syndrome \>\>\> IgG, IgM deficiency**
* **Ataxia telangiectasia \>\>\> IgA deficiency**
40
**Wiskott Aldrich syndrome and Ataxia telagiectasia: Common features**
* **Recurrent chect infections**
* **Haematological malignancy (lymphoma, leukaemia, non-lymphoid tumours)**
* **Melignancy**
41
**Wiskott Aldrich syndrome: genetic defect**
**mutation in "WASP" gene**
42
**Wiskott Aldrich syndrome: Features**
* **Thrombocytopaenia**
* **Low IgG, Low IgM**
* **Humoral immunodeficiency**
* **Recurrent chect infections**
* **Severe bacterial infection**
* **Eczema**
* **Autoimmunity**
* **Malignancy**
* **Haematological cancer (leukaemia, lymphoma etc.)**
43
**Wiskott Aldrich syndrome: Life expectancy**
**6 to 30years**
44
**Wiskott Aldrich syndrome: Main cause of death**
**Bleeding** (maybe due to thrombocytopaenia)
45
**Ataxia telangiectasia: Features**
* **10% risk of developing maligancy**
* **Lymphoma**
* **Leukaemia**
* **Non-lymphoid tumours**
* **Recurrent chest infections**
* **Low IgA**
46
**Job syndrome \>\> Another name?**
**Hyper-IgE syndrome**
47
**Job syndrome is named after whom?**
**It is named after Job in the Bible**
**who was plaged with boils**
48
**Job syndrome: pathophysiology**
**Failure of intracellular signalling in JAK-STAT pathway \>\>\> Multiple immune failures \>\>\> both: innate & adaptive responses**
49
**Job syndrome: Clinical features**
Mnemonic: *FATED*
* **F**acies: Coarse or leonine
* **A**bscess: Cold abscess by staphylococcus spp.
* **T**eeth: Retention of primary teeth
* **E**: High Ig**E**
* **D**ermatological problems: Eczema
**Manifestations are heterogenous **
**It is one of the very few diseases that is associated with \>\>\> Cryptococcus pneumonia (Cryptococcus neoformans)**
50
**Job syndrome: 2 main organisms & their manifestations**
* **Staphylococcus spp. \>\>\> cold abscess**
* **Cryptococcus neoformans \>\>\> Cryptococcal pneumonia**
51
**Why is Job syndrome important regarding pathophysiology?**
It has **failue in 'intracellular signalling'** in the **JAK-STAT pathway**
**& JAK-STAT pathway** has been earmarked as the **next major immune pathway to inibit** in the treatment of **autoimmune diseases**
52
**JAK inhibitor \>\> Indication**
**Cryptococcal pneumonia**
FDA licensed the first JAK inhibitor in 2012
