Immunology 2 - Primary Immunodeficiency

Question 1

what are the different cells that make up the immune system?

Answer 1

B cells are responsible for secreting antibodies

And once they begin secreting antibodies they become plasma cells

Question 2

Different types of immunity important for counteracting different types of infections and microorganisms

what are the different types of immunity and what do they protect our bodies against?

Answer 2

Antibodies made by B cells

Cellular immunity mainly through T cells and antigen presenting cells

Complement system is part of specific and nonspecific immunity

Question 3

what make sup the babies immune system?

Answer 3

Main source of antibodies is maternal antibodies in first 6 months of life and immunity to babies

Gradually they build their own antibodies that increase with age

Question 4

Integrity of the immune system is essential for defence against infectious organisms and their toxic products

what is immunodeficiency?

Answer 4

•Defects in one or more components of the immune system can lead to serious and often fatal disorders, which are collectively called immunodeficiency diseases

Leads to different disorders, some are fatal and non compatible with life

Question 5

what are the types of immunodeficiency?

Answer 5

• Primary, or congenital, immunodeficiencies
• Secondary, or acquired, immunodeficiencies

Primary = very serve, disorders of the immune system

Secondary = can be severe also, result from defects in other parts of the body

Question 6

• The major consequence of immunodeficiency is increased susceptibility to ________
• Patients with immunodeficiencies are also susceptible to certain types of ______
• Certain immunodeficiencies are associated with an increased incidence of __________

Answer 6

infection

cancer

autoimmunity

Question 7

what is primary immunodeficiency due to?

Answer 7

• Genetic, congenital disorders
• Part of the immune system is either missing or functioning abnormally
• It is not secondary to other disease processes, toxins, or drugs
• Primary immunodeficiencies are mainly caused by genetic aberrations
• A smaller number of primary immunodeficiencies are caused by autoimmunity (Small amount can be caused by autoimmunity damaging parts of the immune system but mostly genetic)

Collection of different diseases, not just one disease

Question 8

what does primary immunodeficiency cause?

Answer 8

•Primary immunodeficiency predisposes to infections and tumours.

Be suspicious if recurrent or difficult to treat

Question 9

in primary immunodeficiency, where may the abnormality be?

Answer 9

• Components of the innate immune system
• Stages of lymphocyte development
• Responses of mature lymphocytes to antigenic stimulation

Can affect any part of the immune system, can effect innate or adaptive immune system

Question 10

Defects can happen in development of lymphocytes at any level

is it worse if they are earlier or later?

Answer 10

The earlier the defect is in the development, the more severe the disease is

Question 11

Is it important to know when the defect happens and at what stage? and why?

Answer 11

yes

If you know what part of the immune system isn’t working then you will know what diseases the patient is more susceptible too

Question 12

The type of opportunist infection present also gives clues to the ______ and _____ of immunodeficiency.

Answer 12

degree

cause

Question 13

•Repeated infection with encapsulated bacteria is a sign of defective what?

Answer 13

antibody production

Means there is a defect in B cells and the complement system

Question 14

Antibody deficiency (IgG and IgA) leads to recurrent respiratory infection caused by what?

Answer 14

pneumococcus or Haemophilus spp.

Question 15

Infections with staphylococci, gram-negative bacteria, and fungi are associated with what?

Answer 15

with reduced number or function of phagocytes

Talking about defects in phagocytes, weather that is in number or function

Question 16

•Some complement defects predispose to meningitis caused by what?

Answer 16

Neisseria meningitidis

Question 17

•Defects in T cells or macrophages predispose to infection with ___________ organisms such as protozoa, viruses, and intracellular bacteria, including mycobacteria.

Answer 17

intracellular

Question 18

•The severity of T-cell immunodeficiency is also reflected in patterns of mycobacterial infection:

how?

Answer 18

• Mycobacterium tuberculosis is a virulent organism that causes lung infection in immunocompetent people
• In mild T-cell immunodeficiency, the same organism is able to invade the body outside the lungs
• More severe immunodeficiency predisposes to widespread infection with mycobacteria of low virulence normally found in the environment (e.g., M. avium intracellulare complex)

Question 19

• Reactivation of latent herpesvirus infection is linked to _-cell immunodeficiency.
• Recurrent attacks of cold sores (herpes simplex) or shingles (herpes varicella zoster) may suggest mild immunodeficiency.

Answer 19

T

Question 20

•Recurrent Candida infection is suggestive of defects in the ____ pathway

Answer 20

TH17

Question 21

•Herpesvirus-induced tumours, notably Kaposi sarcoma (human herpesvirus 8 [HHV8]), and non-Hodgkin lymphoma (Epstein-Barr virus [EBV]) are characteristic of _-cell dysfunction.

Answer 21

T

If patients have these tumours and it is unexplained then test for immunodeficiency

Question 22

what are the causes of primary immunodeficiency?

Answer 22

• Mutations
• Polymorphisms
• Polygenic disorders

Question 23

Causes of Primary Immunodeficiency:

what are mutation?

Answer 23

• A gene mutation is a permanent alteration in the DNA sequence that makes up a gene, such that the sequence differs from what is found in most people
• Mutations affecting the immune system are rare and can affect any part of the immune system and cause severe disease

Question 24

Causes of Primary Immunodeficiency:

what are polymorphisms?

Answer 24

• Polymorphism involves one of two or more variants of a particular DNA sequence. The most common type of polymorphism involves variation at a single base pair. Polymorphisms can also be much larger in size and involve long stretches of DNA
• Polymorphisms in the immune system are common traits that affect any part of the immune system and cause a moderate increased risk for infection

More common than mutations. Not as severe as diseases associated with mutations

Question 25

Causes of Primary Immunodeficiency: what are polygenic disorders?

Answer 25

* These are disorders caused by the combined action of more than one gene * Polygenic disorders of the immune system are relatively common and affect mainly antibodies * Some of these polygenic conditions may be caused by autoimmunity

Question 26

•Many mutations result in severe combined immunodeficiency (SCID), a group of disorders that affect both T and B cells. what is the effect of SCID in infants and what treatment is needed?

Answer 26

* Infants with SCID die in the first few months of life unless treatment is given * Stem cell transplant can cure SCID but it has to be done quickly. If it is performed very soon after birth, 90% infants survive; if it is delayed for a few months, only 50% infants survive the transplant procedure

Question 27

what causes SCID?

Answer 27

* Some are autosomally inherited and there may be a history of consanguinity. * Other types are X-linked and there may be a history of early deaths in maternal uncles.

Question 28

•Genetic polymorphisms are _______ (different forms) of the same gene occurring at a single locus in at least 1% of the population.

Answer 28

alleles

Question 29

what are some relatively common polygenic disorders that affect antibody production?

Answer 29

Common variable immunodeficiency (CVID), IgA deficiency, and specific antibody deficiency

Question 30

what is Common variable immunodeficiency (CVID)?

Answer 30

* CVID is the most common primary immunodeficiency requiring treatment and occurs in about 1 in 20,000 young people affecting men and women equally * Patients have low levels of total IgG. Levels of IgA and IgM and numbers of B and T cells are variable * CVID causes recurrent respiratory tract infections * Autoimmunity is common in CVID One example is CVID, a group of diseases and no just one disease

Question 31

•Some primary immunodeficiencies are caused by autoimmunity what is an example?

Answer 31

* For example, patients with autoimmune polyendocrinopathy candidiasis ectodermal dysplasia (APECED) frequently experience severe recurrent Candida infection * Patients with APECED have a defect in central tolerance and experience many types of autoimmunity * Some patients with APECED produce autoantibodies against interleukin 17 (IL-17), which results in impaired responses to Candida APECED is an antibody related immunity

Question 32

examples of different genetic primary immunodeficiency disorders

Answer 32

Mutations affecting B cells affect the antibodies

Question 33

examples of different genetic primary immunodeficiency disorders (continued)

Answer 33

If problem in complement system then patients get neisseria associated meningitis

Question 34

Diagnosis of Primary Immunodeficiency: how would a child present with Severe combined immunodeficiency?

Answer 34

* Children with SCID have defective T cells and B cells and therefore develop infections in the first few weeks of life * Unusual or recurrent infection * Diarrhoea * Unusual rashes

Question 35

Diagnosis of Primary Immunodeficiency: what would the history of someone presenting with Severe combined immunodeficiency look like?

Answer 35

* Family history of neonatal death * Family history of consanguinity

Question 36

Diagnosis of Primary Immunodeficiency: what would the lymphocyte count of someone presenting with Severe combined immunodeficiency be like?

Answer 36

* very low total lymphocyte count (less than 1 × 109/L [106/mL]). * Lymphocyte numbers should be measured by flow cytometry.

Question 37

Diagnosis of Primary Immunodeficiency: what is the clinical presentation of antibody deficiency?

Answer 37

* Antibody deficiency presents later in life * Babies are born with maternal immunoglobulin transferred across the placenta * Some forms of antibody deficiency, such as CVID, do not present until adulthood * Chronic or recurrent bacterial respiratory infection

Question 38

Diagnosis of Primary Immunodeficiency: what are antibody levels like in antibody deficiency?

Answer 38

* IgG, IgA, and IgM should be measured * With low levels of immunoglobulins, causes of secondary immunodeficiency should be excluded * If total Igs are normal, specific antibodies against Haemophilus spp. and pneumococcus should be measured * If these tests are all normal, it is important to check no problems are apparent with complement or neutrophil function

Question 39

what is the Treatment of Primary Immunodeficiency?

Answer 39

* The aim of treatment is to prevent infection * In mild immunodeficiency, prophylactic antibiotics may be adequate * In more severe antibody deficiency, immunoglobulin replacement therapy: - Antibodies against a wide range of pathogens - Ig pooled from thousands of normal donors - Ig replacement can be given intravenously or subcutaneously - Plasma screened for HIV and hepatitis B and C antibodies

Question 40

how do you manage SCID?

Answer 40

* If SCID is confirmed, definitive treatment should be given * Until definitive treatment, simple steps are taken to avoid serious infection: - Avoiding live vaccines (eg, measles, mumps, rubella, polio) - Prophylaxis against opportunist infections such as Pneumocystis jiroveci

Question 41

In SCID and most T-cell deficiencies, what is the treatment?

Answer 41

* Stem cell transplantation [SCT] may be required * SCT is most successful if it can be done within a few weeks of birth, before the infant has developed any infections * If this is possible, SCT carries a 90% success rate and is curative * When SCT is not an option, gene therapy may be attempted

Question 42

Treatment of Primary Immunodeficiency: what is gene therapy?

Answer 42

* Gene therapy uses recombinant technology to correct the genetic defect in the patient’s own stem cells, which can then reconstitute the immune system * used in patients with SCID for whom no suitable stem cell donor was available. Don’t want to activate oncogene Take stem cell form patient, put a dead virus in the cell and this is taken up by DNA of patient and hopefully stem cell will be corrected and then repopulate the immune system Put functional stem cells back in the patient and they will begin to proliferate in the patient

Question 43

For gene therapy to be successful, several criteria must be met - what is it?

Answer 43

1. The genetic mutation for each patient must be identified, and there must be evidence that correcting the mutation will improve his or her condition 2. The transfected gene must confer a proliferation or survival advantage 3. Gene therapy must not cause malignancy (If the part of the gene you want to fix is close to an oncogene then you can cause a disease)