_What do we mean by immunodeficiency?_ Infections that are....... O.. U.. Unusually ..., ... or not responding to ... ... F...

Infections that are....... Opportunistic Unusual Unusually severe, protracted or not responding to standard therapy Frequent

_General classification of immunodeficiency_ ... immunodeficiency ... immunodeficiency ...

Secondary immunodeficiency Immune defect is secondary to another disease process Very common Extremes of age Malignancies (esp myeloma, lymphoma) Metabolic eg diabetes Drugs eg chemotherapy, steroids Infection eg HIV Primary immunodeficiency syndrome (PID) Immune defect is intrinsic to the immune system itself Rare Often genetic, but not always Over 100 characterised PIDS Mostly are fairly ‘new’ diseases Fatal in pre-antibiotic era Characterisation required developments in technology

_Secondary immunodeficiency_ Immune defect is secondary to another disease process Very ... Extremes of ... ... (esp myeloma, lymphoma) ... eg diabetes ... eg chemotherapy, steroids ... eg HIV

Immune defect is secondary to another disease process Very common Extremes of age Malignancies (esp myeloma, lymphoma) Metabolic eg diabetes Drugs eg chemotherapy, steroids Infection eg HIV

_Primary immunodeficiency syndrome (PID)_ Immune defect is ... to the immune system itself ... Often ..., but not always Over ... characterised PIDS Mostly are fairly ‘...’ diseases ... in pre-antibiotic era Characterisation required developments in ...

Immune defect is intrinsic to the immune system itself Rare Often genetic, but not always Over 100 characterised PIDS Mostly are fairly ‘new’ diseases Fatal in pre-antibiotic era Characterisation required developments in technology

_More notes on immunodeficiency........_ CD... T cell defects affect B cells, as T cell help is need for B cell maturation This is particularly marked in ...; less marked in ..., Immunodeficiency syndromes affecting both antibody production and T cells are called ... ... In addition to infections, many immunodeficiency syndromes manifest with immune ...: uncontrolled ..., ... diseases

CD4 T cell defects affect B cells, as T cell help is need for B cell maturation This is particularly marked in infants; less marked in adults, who have already matured their B cells Immunodeficiency syndromes affecting both antibody production and T cells are called combined immunodeficiencies In addition to infections, many immunodeficiency syndromes manifest with immune dysregulation: uncontrolled inflammation, autoimmune diseases

_More notes on immunodeficiency........_ CD4 T cell defects affect B cells, as T cell help is need for B cell ... This is particularly marked in infants; less marked in adults, who have already ... their B cells Immunodeficiency syndromes affecting both ... production and T cells are called combined immunodeficiencies In addition to infections, many immunodeficiency syndromes manifest with immune dysregulation: ... inflammation, autoimmune diseases

CD4 T cell defects affect B cells, as T cell help is need for B cell maturation This is particularly marked in infants; less marked in adults, who have already matured their B cells Immunodeficiency syndromes affecting both antibody production and T cells are called combined immunodeficiencies In addition to infections, many immunodeficiency syndromes manifest with immune dysregulation: uncontrolled inflammation, autoimmune diseases

_Some immunological aspects of immunosenescence_ Thymic ... Telomere ... in stem cells reduces both quality and quantity of leucocyte output Reduced T and B cell receptor ... Reduced ... responses Reduced neutrophil function Reduced self-tolerance; inflammation switches from protection to damage Expansion of T cell pool responding to cytomegalovirus (current research focus)

Thymic involution Telomere shortening in stem cells reduces both quality and quantity of leucocyte output Reduced T and B cell receptor diversity Reduced vaccine responses Reduced neutrophil function Reduced self-tolerance; inflammation switches from protection to damage Expansion of T cell pool responding to cytomegalovirus (current research focus)

_Some immunological aspects of immunosenescence_ Thymic involution Telomere shortening in stem cells reduces both quality and quantity of leucocyte output Reduced T and B cell receptor diversity Reduced vaccine responses Reduced ... function Reduced ...-...; inflammation switches from protection to damage Expansion of T cell pool responding to ... (current research focus)

Thymic involution Telomere shortening in stem cells reduces both quality and quantity of leucocyte output Reduced T and B cell receptor diversity Reduced vaccine responses Reduced neutrophil function Reduced self-tolerance; inflammation switches from protection to damage Expansion of T cell pool responding to cytomegalovirus (current research focus)

Elderly clearly more susceptible to infection, but immunity itself is not the only factor: Reduced ... n... ... healing Co-... (COPD, CCF, DM, cancer, depression etc) Reduced ... reserve All of these increase ... of infection AND risk of poor ... from infection See VZV immunisation slides: clear that older people can make a response to a specifically tailored immune booster

Reduced mobility Nutrition Wound healing Co-morbidities (COPD, CCF, DM, cancer, depression etc) Reduced physiological reserve All of these increase risk of infection AND risk of poor outcome from infection See VZV immunisation slides: clear that older people can make a response to a specifically tailored immune booster

_Predominantly antibody deficiency_ Low Ig...; other isotypes may be affected, but low IgA/ M with normal ... is rarely significant Manifests with recurrent ... infections of the upper and lower respiratory tract Sometimes ... infections in addition Infections typically respond to anti-..., but response may be sub-optimal and long courses required If untreated, leads to irreversible lung damage (...)

Low IgG; other isotypes may be affected, but low IgA/ M with normal IgG is rarely significant Manifests with recurrent pyogenic infections of the upper and lower respiratory tract Sometimes gut infections in addition Infections typically respond to anti-microbials, but response may be sub-optimal and long courses required If untreated, leads to irreversible lung damage (bronchiectasis)

_Predominantly antibody deficiency_ Low IgG; other isotypes may be affected, but low IgA/ M with normal IgG is rarely significant Manifests with ... pyogenic infections of the ...and ... ... tract Sometimes gut infections in addition Infections typically respond to anti-microbials, but response may be ...-optimal and ... courses required If untreated, leads to ... lung damage (bronchiectasis)

Low IgG; other isotypes may be affected, but low IgA/ M with normal IgG is rarely significant Manifests with recurrent pyogenic infections of the upper and lower respiratory tract Sometimes gut infections in addition Infections typically respond to anti-microbials, but response may be sub-optimal and long courses required If untreated, leads to irreversible lung damage (bronchiectasis)

_Some causes of antibody deficiency_ Physiological Transient ... of infancy Secondary Ig... loss: Renal: .. syndrome Skin: extensive .. Impaired production: Immunosuppressive drugs Primary X-Linked agammaglobulinemia X-Linked hyper-Ig... syndrome (Common variable immunodeficiency – module 302) Many others that are beyond scope

Physiological Transient hypogammaglobulinemia of infancy Secondary IgG loss: Renal: nephrotic syndrome Skin: extensive burns Impaired production: Immunosuppressive drugs Primary X-Linked agammaglobulinemia X-Linked hyper-IgM syndrome (Common variable immunodeficiency – module 302) Many others that are beyond scope

Immunodeficiency Diseases Flashcards by Chrissy Taaffe

What do we mean by immunodeficiency?

Infections that are…….
O..
U..
Unusually …, … or not responding to … …
F…

Infections that are…….
Opportunistic
Unusual
Unusually severe, protracted or not responding to standard therapy
Frequent

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Immunodeficiency - difficulty in defining

So there is no definitive definition…….
- The diagnosis is largely descriptive
- Infections more likely to be significant if……..
  - Infections are verified rather than simply reported
  - Organisms can be identified
  - End-organ damage has occurred

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Infections more likely to be significant if…. (3)

Infections are verified rather than simply reported
Organisms can be identified
End-organ damage has occurred

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General classification of immunodeficiency

… immunodeficiency
… immunodeficiency …

Secondary immunodeficiency
- Immune defect is secondary to another disease process
- Very common
- Extremes of age
- Malignancies (esp myeloma, lymphoma)
- Metabolic eg diabetes
- Drugs eg chemotherapy, steroids
- Infection eg HIV
Primary immunodeficiency syndrome (PID)
- Immune defect is intrinsic to the immune system itself
- Rare
- Often genetic, but not always
- Over 100 characterised PIDS
- Mostly are fairly ‘new’ diseases
- Fatal in pre-antibiotic era
- Characterisation required developments in technology

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Secondary immunodeficiency

Immune defect is secondary to another disease process
Very …
Extremes of …
… (esp myeloma, lymphoma)
… eg diabetes
… eg chemotherapy, steroids
… eg HIV

Immune defect is secondary to another disease process
Very common
Extremes of age
Malignancies (esp myeloma, lymphoma)
Metabolic eg diabetes
Drugs eg chemotherapy, steroids
Infection eg HIV

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Primary immunodeficiency syndrome (PID)

Immune defect is … to the immune system itself
…
Often …, but not always
Over … characterised PIDS
Mostly are fairly ‘…’ diseases
… in pre-antibiotic era
Characterisation required developments in …

Immune defect is intrinsic to the immune system itself
Rare
Often genetic, but not always
Over 100 characterised PIDS
Mostly are fairly ‘new’ diseases
Fatal in pre-antibiotic era
Characterisation required developments in technology

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Immunological classification of immunodeficiency

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Immunological classification of immunodeficiency

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More notes on immunodeficiency……..

CD… T cell defects affect B cells, as T cell help is need for B cell maturation
This is particularly marked in …; less marked in …,
Immunodeficiency syndromes affecting both antibody production and T cells are called … …
In addition to infections, many immunodeficiency syndromes manifest with immune …: uncontrolled …, … diseases

CD4 T cell defects affect B cells, as T cell help is need for B cell maturation
This is particularly marked in infants; less marked in adults, who have already matured their B cells
Immunodeficiency syndromes affecting both antibody production and T cells are called combined immunodeficiencies
In addition to infections, many immunodeficiency syndromes manifest with immune dysregulation: uncontrolled inflammation, autoimmune diseases

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More notes on immunodeficiency……..

CD4 T cell defects affect B cells, as T cell help is need for B cell …
This is particularly marked in infants; less marked in adults, who have already … their B cells
Immunodeficiency syndromes affecting both … production and T cells are called combined immunodeficiencies
In addition to infections, many immunodeficiency syndromes manifest with immune dysregulation: … inflammation, autoimmune diseases

CD4 T cell defects affect B cells, as T cell help is need for B cell maturation
This is particularly marked in infants; less marked in adults, who have already matured their B cells
Immunodeficiency syndromes affecting both antibody production and T cells are called combined immunodeficiencies
In addition to infections, many immunodeficiency syndromes manifest with immune dysregulation: uncontrolled inflammation, autoimmune diseases

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Aging and immunity (‘immunosenscence’)

‘A combination of age-related changes in the immune system that result in greater … to infection and reduced response to …’

‘A combination of age-related changes in the immune system that result in greater susceptibility to infection and reduced response to vaccination’

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What is ‘immunosenscence’?

‘A combination of age-related changes in the immune system that result in greater susceptibility to infection and reduced response to vaccination’

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Some immunological aspects of immunosenescence

Thymic …
Telomere … in stem cells reduces both quality and quantity of leucocyte output
Reduced T and B cell receptor …
Reduced … responses
Reduced neutrophil function
Reduced self-tolerance; inflammation switches from protection to damage
Expansion of T cell pool responding to cytomegalovirus (current research focus)

Thymic involution
Telomere shortening in stem cells reduces both quality and quantity of leucocyte output
Reduced T and B cell receptor diversity
Reduced vaccine responses
Reduced neutrophil function
Reduced self-tolerance; inflammation switches from protection to damage
Expansion of T cell pool responding to cytomegalovirus (current research focus)

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Some immunological aspects of immunosenescence

Thymic involution
Telomere shortening in stem cells reduces both quality and quantity of leucocyte output
Reduced T and B cell receptor diversity
Reduced vaccine responses
Reduced … function
Reduced …-…; inflammation switches from protection to damage
Expansion of T cell pool responding to … (current research focus)

Thymic involution
Telomere shortening in stem cells reduces both quality and quantity of leucocyte output
Reduced T and B cell receptor diversity
Reduced vaccine responses
Reduced neutrophil function
Reduced self-tolerance; inflammation switches from protection to damage
Expansion of T cell pool responding to cytomegalovirus (current research focus)

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Elderly clearly more susceptible to infection, but immunity itself is not the only factor:

Reduced …
n…
… healing
Co-… (COPD, CCF, DM, cancer, depression etc)
Reduced … reserve
All of these increase … of infection AND risk of poor … from infection
See VZV immunisation slides: clear that older people can make a response to a specifically tailored immune booster

Reduced mobility
Nutrition
Wound healing
Co-morbidities (COPD, CCF, DM, cancer, depression etc)
Reduced physiological reserve
All of these increase risk of infection AND risk of poor outcome from infection
See VZV immunisation slides: clear that older people can make a response to a specifically tailored immune booster

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Predominantly antibody deficiency

Low Ig…; other isotypes may be affected, but low IgA/ M with normal … is rarely significant
Manifests with recurrent … infections of the upper and lower respiratory tract
Sometimes … infections in addition
Infections typically respond to anti-…, but response may be sub-optimal and long courses required
If untreated, leads to irreversible lung damage (…)

Low IgG; other isotypes may be affected, but low IgA/ M with normal IgG is rarely significant
Manifests with recurrent pyogenic infections of the upper and lower respiratory tract
Sometimes gut infections in addition
Infections typically respond to anti-microbials, but response may be sub-optimal and long courses required
If untreated, leads to irreversible lung damage (bronchiectasis)

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Predominantly antibody deficiency

Low IgG; other isotypes may be affected, but low IgA/ M with normal IgG is rarely significant
Manifests with … pyogenic infections of the …and … … tract
Sometimes gut infections in addition
Infections typically respond to anti-microbials, but response may be …-optimal and … courses required
If untreated, leads to … lung damage (bronchiectasis)

Low IgG; other isotypes may be affected, but low IgA/ M with normal IgG is rarely significant
Manifests with recurrent pyogenic infections of the upper and lower respiratory tract
Sometimes gut infections in addition
Infections typically respond to anti-microbials, but response may be sub-optimal and long courses required
If untreated, leads to irreversible lung damage (bronchiectasis)

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Some causes of antibody deficiency

Physiological
- Transient … of infancy
Secondary
- Ig… loss:
  - Renal: .. syndrome
  - Skin: extensive ..
- Impaired production:
  - Immunosuppressive drugs
Primary
- X-Linked agammaglobulinemia
- X-Linked hyper-Ig… syndrome
- (Common variable immunodeficiency – module 302)
- Many others that are beyond scope

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Physiological
- Transient hypogammaglobulinemia of infancy
Secondary
- IgG loss:
  - Renal: nephrotic syndrome
  - Skin: extensive burns
- Impaired production:
  - Immunosuppressive drugs
Primary
- X-Linked agammaglobulinemia
- X-Linked hyper-IgM syndrome
- (Common variable immunodeficiency – module 302)
- Many others that are beyond scope

What is shown here?

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Irreversible lung damage (bronchiectasis) as a result of untreated predominantly antibody deficiency

What is shown here?

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Irreversible lung damage (bronchiectasis) as a result of untreated predominantly antibody deficiency

Secondary causes of antibody deficiency:

IgG loss:
- Renal: … syndrome
- Skin: extensive …
Impaired production:
- … drugs

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IgG loss:
- Renal: nephrotic syndrome
- Skin: extensive burns
Impaired production:
- Immunosuppressive drugs

Primary causes of antibody deficiency

X-Linked …
X-Linked hyper-… syndrome
(Common variable immunodeficiency – module 302)
Many others that are beyond scope

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X-Linked agammaglobulinemia
X-Linked hyper-IgM syndrome
(Common variable immunodeficiency – module 302)
Many others that are beyond scope

Maturation of antibody production

In healthy infants there is normally a period of relative antibody deficiency around 6 months known as ‘transient … of infancy; this is a physiological state but can be correlated with increased …
Infants with antibody deficiency usually present after 3-6 months; up until this time they are protected by … IgG antibody

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In healthy infants there is normally a period of relative antibody deficiency around 6 months known as ‘transient hypogammaglobulinemia of infancy; this is a physiological state but can be correlated with increased infections
Infants with antibody deficiency usually present after 3-6 months; up until this time they are protected by maternal IgG antibody

_Maturation of antibody production_ * In healthy infants there is normally a period of relative antibody deficiency around 6 months known as ‘... hypogammaglobulinemia of infancy; this is a ... state but can be correlated with increased infections * Infants with antibody deficiency usually present after ...-... months; up until this time they are protected by maternal IgG antibody

* In healthy infants there is normally a period of relative antibody deficiency around 6 months known as ‘**transient** hypogammaglobulinemia of infancy; this is a **physiological** state but can be correlated with increased infections * Infants with antibody deficiency usually present after **3-6** months; up until this time they are protected by maternal IgG antibody

_XLA – a prototype antibody deficiency syndrome_ * Signalling via Bruton’s tyrosine kinase (btk) required for signal ... at pro-... stage * ... arrest occurs if absent: no ... chain rearrangement, no B cells leave marrow, no immunoglobulin production * Disease is called ...-linked agammaglobulinaemia (XLA); also known as Bruton’s disease, Btk deficiency or Bruton’s XLA

* Signalling via Bruton’s tyrosine kinase (btk) required for signal **transduction** at pro-**B** stage * **Maturation** arrest occurs if absent: no **heavy** chain rearrangement, no B cells leave marrow, no immunoglobulin production * Disease is called **X-**linked agammaglobulinaemia (XLA); also known as Bruton’s disease, Btk deficiency or Bruton’s XLA

_XLA – a prototype antibody deficiency syndrome_ * Signalling via Bruton’s ... kinase (btk) required for ... transduction at pro-B stage * Maturation arrest occurs if absent: no heavy chain rearrangement, no B cells leave ..., no ... production * Disease is called X-linked agammaglobulinaemia (XLA); also known as Bruton’s disease, Btk deficiency or Bruton’s XLA

* Signalling via Bruton’s **tyrosine** kinase (btk) required for **signal** transduction at pro-B stage * Maturation arrest occurs if absent: no heavy chain rearrangement, no B cells leave **marrow**, no **immunoglobulin** production * Disease is called X-linked agammaglobulinaemia (XLA); also known as Bruton’s disease, Btk deficiency or Bruton’s XLA

_X-Linked hyper IgM syndrome (CD40L deficiency)_ * Failure of B cell ... from primary to secondary * Low IgG & IgA, raised (or normal) Ig... * Recurrent ... infections * Presents age 3-6 months * The immunological ... actually resides on the T cell * CD40 ligand (also known as CD154) * Interaction with CD40 on B cells required for affinity maturation

* Failure of B cell **maturation** from primary to secondary * Low IgG & IgA, raised (or normal) **IgM** * Recurrent **bacterial** infections * Presents age 3-6 months * The immunological **lesion** actually resides on the T cell * CD40 ligand (also known as CD154) * Interaction with CD40 on B cells required for affinity maturation

_X-Linked hyper IgM syndrome (CD40L deficiency)_ * Failure of B cell maturation from ... to ... * Low Ig... & Ig..., raised (or normal) IgM * Recurrent bacterial infections * Presents age ..-.. months * The immunological lesion actually resides on the T cell * CD40 ligand (also known as CD154) * Interaction with CD40 on B cells required for ... maturation

* Failure of B cell maturation from **primary** to **secondary** * Low **IgG & IgA**, raised (or normal) IgM * Recurrent bacterial infections * Presents age **3-6** months * The immunological lesion actually resides on the T cell * CD40 ligand (also known as CD154) * Interaction with CD40 on B cells required for **affinity** maturation

_Treating antibody deficiency_ * Early recognition before ... damage occurs * Aggressive treatment of intercurrent ... * Replace ... * Long-term suppressive anti-...

* Early recognition before **lung** damage occurs * Aggressive treatment of intercurrent **infections** * Replace **immunoglobulin** * Long-term suppressive anti-**microbials**

_X-Linked Hyper-IgM syndrome_

_Cellular immunodeficiency_ * Poor terminology; used to mean CD4 T cell deficiency * When ..., antibodies will also be affected (combined immunodeficiency) * Manifests particularly with: * ... infection * ... infection * ... infection * ... infection * Classic secondary cause is ... infection

* Poor terminology; used to mean CD4 T cell deficiency * When **congenital**, antibodies will also be affected (combined immunodeficiency) * Manifests particularly with: * **Opportunistic infection** * **Viral infection** * **Fungal infection** * **Mycobacterial infection** * Classic secondary cause is **HIV** infection

_Cellular immunodeficiency_ * Poor terminology; used to mean CD4 T cell deficiency * When congenital, antibodies will also be affected (... immunodeficiency) * Manifests particularly with: * ... infection * Viral infection * ... infection * Mycobacterial infection * Classic ... cause is HIV infection

* Poor terminology; used to mean CD4 T cell deficiency * When congenital, antibodies will also be affected (**combined** immunodeficiency) * Manifests particularly with: * Opportunistic infection * **Viral** infection * Fungal infection * **Mycobacterial** infection * Classic **secondary** cause is HIV infection

_Some conditions seen in cellular immunodeficiency, particularly advanced HIV_

* **Top left hand - candida oesophagitis** * **Right hand - Cytomegalovirus retinitis** * **Bottom left - Kapsosi's sarcoma (malignancy) - driven by Human herpes virus infection** * **Middle - pneumocystis carinii pneumonia (bilateral pneumonitis)** * **Bottom right - compression of brain tissue - cerebral toxoplasmosis**

_Severe combined immunodeficiency_ * ..., life-threatening ... immunodeficiency * Absent ... cells * ... cells may be present, but are non-functional * All basically present in a similar fashion * Usually soon after ... * ... (graft versus host - maternal lymphocyte engraftment) * Failure to thrive * Chronic diarrhoea * Infections, especially opportunistic * Bacterial * Mycobacterial (esp BCG) * Viral (esp CMV, EBV) * Fungal (PCP, oral thrush)

* **Rare**, life-threatening **primary** immunodeficiency * Absent **T** cells * **B** cells may be present, but are non-functional * All basically present in a similar fashion * Usually soon after **birth** * **Rash** (graft versus host - maternal lymphocyte engraftment) * Failure to thrive * Chronic diarrhoea * Infections, especially opportunistic * Bacterial * Mycobacterial (esp BCG) * Viral (esp CMV, EBV) * Fungal (PCP, oral thrush)

_Severe combined immunodeficiency_ * Rare, ...-... primary immunodeficiency * Absent T cells * B cells may be present, but are ...-... * All basically present in a similar fashion * Usually soon after birth * Rash (graft versus host - maternal lymphocyte engraftment) * Failure to ... * Chronic ... * Infections, especially ... * Bacterial * ... (esp BCG) * ... (esp CMV, EBV) * ... (PCP, oral thrush)

* Rare, **life-threatening** primary immunodeficiency * Absent T cells * B cells may be present, but are **non-functional** * All basically present in a similar fashion * Usually soon after birth * Rash (graft versus host - maternal lymphocyte engraftment) * Failure to **thrive** * Chronic **diarrhoea** * Infections, especially **opportunistic** * Bacterial * **Mycobacterial (esp BCG)** * **Viral (esp CMV, EBV)** * **Fungal (PCP, oral thrush)**

_Severe combined immunodeficiency (SCID)_ * Variety of molecular causes, only three considered this year: * ... .... chain deficiency * JAK... deficiency * RAG.../... deficiency

* Variety of molecular causes, only three considered this year: * **Common gamma** chain deficiency * **JAK3** deficiency * **RAG1/2** deficiency

_Severe combined immunodeficiency (SCID)_ * Variety of molecular causes, only three considered this year: * Common gamma chain deficiency * ... deficiency * ... deficiency

* Variety of molecular causes, only three considered this year: * Common gamma chain deficiency * **JAK3** deficiency * **RAG1/2** deficiency

_Common gamma chain deficiency and JAK3 deficiency_ * Common gamma-chain deficiency * ...-linked SCID * Common gamma chain forms part of membrane receptor for several ..., some of which are required for ... cell maturation * Absent ...cells * ... cells present but non-functional * JAK-3 deficiency deficiency * Autosomal ... SCID * JAK-3 is downstream of common gamma chain; deficiency likewise prevents signalling * Immunologically ... to gamma chain deficiency

* Common gamma-chain deficiency * **X**-linked SCID * Common gamma chain forms part of membrane receptor for several **cytokines**, some of which are required for **T** cell maturation * Absent **T** cells * **B** cells present but non-functional * JAK-3 deficiency deficiency * Autosomal **recessive** SCID * JAK-3 is downstream of common gamma chain; deficiency likewise prevents signalling * Immunologically **identical** to gamma chain deficiency

_Common gamma chain deficiency and JAK3 deficiency_ * Common gamma-chain deficiency * X-linked ... * Common gamma chain forms part of membrane receptor for several cytokines, some of which are required for T cell ... * Absent T cells * B cells present but non-... * JAK-3 deficiency ... * Autosomal recessive ... * JAK-3 is downstream of common gamma chain; deficiency likewise prevents signalling * Immunologically identical to gamma chain deficiency

* Common gamma-chain deficiency * X-linked **SCID** * Common gamma chain forms part of membrane receptor for several cytokines, some of which are required for T cell **maturation** * Absent T cells * B cells present but non-**functional** * JAK-3 deficiency * Autosomal recessive **SCID** * JAK-3 is downstream of common gamma chain; deficiency likewise prevents signalling * Immunologically identical to gamma chain deficiency

_RAG 1&2 deficiency_ * An autosomal ... form of SCID * RAG 1/2 required for ... ... events between V(D)J gene segments * No RAG1/2 means no ... and ... cell receptors

* **An autosomal recessive form of SCID** * **RAG 1/2 required for somatic recombination events between V(D)J gene segments** * **No RAG1/2 means no T and B cell receptors**

_SCID therapy_ * What is no longer used? * Now: * ... ... transplant * .. ... harvested from ...-matched donor: * Given to recipient by ... * Engraft in ... ... * ... of T and B cells

* Treatable - **bubbles** no longer used * **Stem cell transplant** * **Stem cells harvested from HLA-matched donor:** * **Given to recipient by infusion** * **Engraft in bone marrow** * **RECONSTITUTION of T and B cells**

_Another combined immunodeficiency syndrome: DiGeorge syndrome_ * Failure migration 3th/ 4th ... arches * Full phenotype: * Absent ... (low calcium, tetany) * ... palate * ... heart defects * ... aplasia (low T cell numbers, immunodeficiency) * Most patients have microdeletions chromosome 22 * Variable presentation * Huge spectrum of immunodeficiency from mild-SCID-like * Autoimmunity is also common * Patients with 22q11 microdeletions may have none of the above, all of the above and anything inbetween

* Failure migration 3th/ 4th **branchial** arches * Full phenotype: * Absent **parathyroids** (low calcium, tetany) * **Cleft** palate * **Congenital** heart defects * **Thymic** aplasia (low T cell numbers, immunodeficiency) * Most patients have microdeletions chromosome 22 * Variable presentation * Huge spectrum of immunodeficiency from mild-SCID-like * Autoimmunity is also common * Patients with 22q11 microdeletions may have none of the above, all of the above and anything inbetween

_Another combined immunodeficiency syndrome: DiGeorge syndrome_ * Failure migration ...th/..th branchial arches * Full phenotype: * Absent parathyroids (low calcium, t...) * Cleft palate * Congenital heart defects * Thymic aplasia (low ... cell numbers, immunodeficiency) * Most patients have microdeletions chromosome ... * ... presentation * Huge spectrum of immunodeficiency from mild-...-like * ... is also common * Patients with ... microdeletions may have none of the above, all of the above and anything inbetween

* Failure migration **3th/ 4th** branchial arches * Full phenotype: * Absent parathyroids (low calcium, **tetany**) * Cleft palate * Congenital heart defects * Thymic aplasia (low **T** cell numbers, immunodeficiency) * Most patients have microdeletions chromosome **22** * **Variable** presentation * Huge spectrum of immunodeficiency from mild-**SCID**-like * **Autoimmunity** is also common * Patients with **22q11** microdeletions may have none of the above, all of the above and anything inbetween

_Terminal complement deficiency_ * Deficiency of terminal complement components ...-... leads to specific susceptibility to ... Species * Otherwise immunologically robust * Diagnose by functional complement ... (speak to your immunology laboratory)

* Deficiency of terminal complement components **C5-C9** leads to specific susceptibility to **Neisseria** Species * Otherwise immunologically robust * Diagnose by functional complement **assays** (speak to your immunology laboratory)

_Terminal complement deficiency_ * Deficiency of terminal complement components C5-C9 leads to specific susceptibility to ... Species * Otherwise immunologically robust * Diagnose by functional ... assays (speak to your immunology laboratory)

* Deficiency of terminal complement components C5-C9 leads to specific susceptibility to **Neisseria** Species * Otherwise immunologically robust * Diagnose by functional **complement** assays (speak to your immunology laboratory)

Immunodeficiency Diseases Flashcards

(46 cards)