Lec 2 - primary immunodeficiency

Question 1

Define primary and secondary immune deficiency

Explain the classification of primary immune deficiency disorders.

Give examples of primary disorders of T cell, B cell, phagocyte and complement function.

Understand the causes of primary immunodeficiency

Illustrate the complications of immune deficiency disorders

List the clinical features of primary immunodeficiency

Understand the principles of the treatment of primary immunodeficiency

Answer 1

.

Question 2

Are babies born with immunoglobulins present in their blood

Answer 2

Yes - maternal IgG transferred but NO PRODUCTION OF OWN ANTIBODIES YET

Question 3

Primary immunodeficiency

• define
• causes
• predisposition to

Answer 3

Congenital defect in one or more components of the immune system

Causes

• Mutations (MAJORITY) –> either missing or abnormally functioning part of immune system
• Autoimmunity

Infections + tumours

Question 4

Secondary immunodeficiency =

Answer 4

Acquired defect in one or more components of the immune system

Question 5

Major consequence of immunodeficiency

Answer 5

Increased risk of INFECTION

Question 6

Abnormalities of primary immunodeficiency can arise from 3 places

Answer 6

Components of the innate immune system

Stages of lymphocyte development

Responses of mature lymphocytes to antigenic stimulation

OR

Simpler classification

• phagocyte defects
• complement defects
• defects of other innate components

Question 7

Examples of primary disorders of PHAGOCYTE function (3)

Answer 7

Chronic granulomatous disease

Leukocyte adhesion deficiency

Myeloperoxidase deficiency

Question 8

Examples of primary disorders of COMPLEMENT function (3)

Answer 8

Complement deficiencies

Hereditary angioedema

Question 9

Examples of primary disorders of T CELL function

Answer 9

DiGeorge syndrome

Chronic mucocutaneous candidiasis

Question 10

Examples of primary disorders of B CELL function

Answer 10

.

Question 11

B cell/antibody deficiency makes you susceptible to bacterial or viral infection more?

Answer 11

Bacterial, e.g. otitis, pneumonia, meningitis, osteomyelitis

Question 12

T cell deficiency makes you susceptible to what pathogen mostly + which others?

Answer 12

Viral (MOST), e.g. CMV, reactivation of HSV, VZV

Protozoa, e.g. pneumocystis
Fungal, e.g. candida
Atypical mycobacteria

Question 13

Repeated infection with encapsulated bacteria is a sign of defective production of what

Answer 13

Antibodies

Question 14

Phagocyte defects make you susceptible to what type of infection more

Answer 14

Fungal

Question 15

Severity of T cell immunodeficiency can be reflected in pattens of infection by what pathogen

Answer 15

Mycobacteria (an atypical bacteria)

Question 16

T cell immunodeficiency can activate viruses which induce tumours

Give some examples

Answer 16

Human herpesvirus 8 (HHV8) - kaposi’s sarcoma

EBV - non-hodgkin lymphoma

Question 17

3 broad causes of primary immunodeficiency

Answer 17

Mutations
-altered DNA sequence of a gene

Polymorphisms

• more than one allele of a gene
• very mild effect

Polygenic disorders

• i.e. more than one gene causing disease
• COMMON

Question 18

Classification of primary immunodeficiency disorders (4)

Answer 18

1) Severe Combined Immune Deficiency (SCID)
2) Predominantly antibody deficiencies
3) Predominantly T cell deficiencies
4) Other (usually combined T & B) deficiencies

Question 19

What is SCID (SEVERE COMBINED IMMUNE DEFICIENCY)

Answer 19

A group of disorders that affect both T and B cells (VERY LOW LYMPHOCYTES –> deficiency in cellular and humoral immunity)

Question 20

Infants with SCID die before age of 2 unless treated with what

Answer 20

Stem cell transplant

-can cure it but MUST BE GIVEN ASAP (i.e. within weeks of birth)

Question 21

Cause of SCID

Answer 21

Mutations leading to defects in pluripotent stem cells, lymphoid stem cells or T & B cells themselves

Question 22

Polymorphisms can occur in a gene which codes for MHC

Name this gene

Answer 22

HLA

Question 23

Examples of polygenic primary immunodeficiency disorders

Answer 23

IgA deficiency
Common variable immunodeficiency - commonest one requiring treatment
Specific antibody deficiency

Question 24

Some primary immunodefiencies are caused by autoimmunity

Name one

Answer 24

Autoimmune poly­endocrinopathy candidiasis ectodermal dysplasia (APECED)

Question 25

Complications of immune deficiency disorders

Answer 25

INFECTION

Other presentations

• malignancy
• immune dysregulation (–> autoimmunity, hypersensitivity etc)
• general unexplained features, e.g. failure to thrive, large spleen

Chronic tissue/ organ damage (arising from inflammation +/- delays in diagnosis/treatment)

Iatrogenic complications associated with the use of potent immune modulating therapies

Question 26

Clinical features of primary immunodeficiency

Answer 26

Recurrent INFECTION
-e.g. pneumonia, osteomyelitis, skin/mucous membrane infection, neisserial, bronchitis

Immune complex disease

Organ damage

Blood disorders

Delayed growth + development

Autoimmune disease

Question 27

Clinical features of SCID

Answer 27

Recurrent/severe/opportunistic infections
Failure to thrive
Diarrhoea
Diffuse rash
Absent thymus

Question 28

Clinical presentation of antibody deficiency

Answer 28

Most present later in life

Recurrent bacterial infections of resp tract

Question 29

Principles of the treatment of primary immunodeficiency

Answer 29

PREVENT INFECTION

• prophylactic antibiotics
• Ig replacement if severe deficiency

Treat underlying cause

Avoid live vaccines

Avoid blood transfusion in cell mediated immune defects

Genetic counselling

Specific therapies

• stem cell transplant
• Ig replacement
• gene therapy
• cytokine therapy

Question 30

Are primary or secondary immunodeficiency disorders more common?

Answer 30

Secondary

Question 31

Causes of secondary immunodeficiency disorders

Answer 31

Malnutrition
Malignancy
Immunosuppressive therapy
Splenectomy 
Chronic renal failure
Severe burns/surgery