immunology

Question 1

type I immediate hypersensitivity reaction

Answer 1

Immediate and late phase: IgE antibodies bind to mast cells and cause degranulation (asthma, food allergies, hayfever).
<30 mins, late phase 2-12 hours

Question 2

type 2 hypersensitivity reaction

Answer 2

cytotoxic antibody: an antibody dependent reaction seen in conditions such as haemolytic disease of the newborn and transfusion reactions and well as goodpastures (IgM, IgG and IgA) haemolytic anaemia, blood transfusion reactions,

Question 3

Type 3 hypersensitivty reaction

Answer 3

insoluble antibody-antigen complexes are deposited in tissues which triggers complement activation causing causing tissue damage (e.g. RA, SLE, serum sickness, hypersensitivity pneumonitis).

Question 4

Type 4 hypersensitivity reaction

Answer 4

T Cell mediated reaction involving CD8+ cytotoxic T cells and CD4+ helper T cells. (contact dermatitis, type 1 DM, SJS, TEN, DRESS syndrome, rash).

Question 5

type I immediate hypersensitivity reaction timing?

Answer 5

<30 mins, late phase 2-12 hours

Question 6

type 2 hypersensitivity reaction timing?

Answer 6

minutes to hours

Question 7

type 2 hypersensitivity reaction effector molecule?

Answer 7

IgM, IgG and IgA

Question 8

type 2 hypersensitivity reaction target or antigen?

Answer 8

Red Blood Cells, platelets

Question 9

Type 3 hypersensitivity reaction timing?

Answer 9

1-3 weeks after exposure

Question 10

Type 3 hypersensitivity reaction effector molecule

Answer 10

antigen-antibody complexes

Question 11

Type 3 hypersensitivity reaction target or antigen?

Answer 11

Blood vessels, liver, spleen, kidney, lung

Question 12

type 4 hypersensitivity reaction timing

Answer 12

2-7 days after drug exposure

Question 13

type 4 hypersensitivity effector molecule

Answer 13

lymphocytes

Question 14

type 4 hypersensitivity reaction target or antigen

Answer 14

mycobacterium tuberculosis, chemicals

Question 15

live attenuated vaccines?

Answer 15

parenteral live attenuated viral immunisations(MMR, Varicella

Question 16

CGD:

Answer 16

X linked: most on the x chromosome : 91 PHOX

Autosomal recessive
nicotinamide-adenine-dinucleotide-phosphate oxidase (NADPH in low levels
neutrophils don’t have the ability to kill pathogens (no reactive oxygen.

1. pneumonia
2. abscesses
3. septic arthritis
4. osteomyelitis
   non disease causing normall: particularly suceptible to Nocardia/ Staph aureus/ serratia / burkholdia/ aspergillus**
   mulch pneumonitis is PATHOGNEMONIC

Question 17

LAD

Answer 17

3 types B-chain integrin called CD18: normal neutrophil aggregation but cannot extravasate,
- features: delayred cord separation, recutrrent skin infections, moral mucosa. UTI and ecthema gangrenosum.

A WBC differential will reveal extremely elevated levels of neutrophils (on the order of 6-10x normal) because they are unable to leave the blood vessels.

Question 18

Neutropenic (three conditions)

Answer 18

kostmans : HAXI OM/cellulitis/resp trat)
Neonatal alloimmune neutropenia: sepsis and oomphalitis
Schwachman diamon: steathorreah (pancreatic insufficiency/ FTT/ stomatitis, apthous ulcers and stomatitis secondary to clostridium

Question 19

X-linked agammaglobulimaemia (bruton’s tyrosine kinase)

Answer 19

well until 6 months
encapsulated (s. pneumo /hib)
rotavirus: chronic diarrhoea
enterovirus (chronic meningioencephalitis
protozoal: giardiasis
Paralytic polio with vaccine

attendance at 6 months, The diagnosis is probable when blood tests show the complete lack of circulating B cells (determined by the B cell marker CD19 and/or CD20), as well as low levels of all antibody classes, including IgG, IgA, IgM, IgE and IgD.

Question 20

Selective IgA

Answer 20

It is defined as an undetectable serum IgA level in the presence of normal serum levels of IgG and IgM, in persons older than 4 years.
sinopulmonary infections, autoimmune, allergy
- increased ractions to blood transfusions

Question 21

Hyper IGM

Answer 21

CD40 ligand signalling defect - unable to class switch - so heaps of IgM and no IgM, IgA or iGE.
susceptible to T cell and macrophage infections, such as PCP and cryptosporidium. usually in people’s lungs however hyper IgM not able to fight it off without bactrim.
x linked recessive

Question 22

Diagnostic test for CGD?

Answer 22

The nitroblue-tetrazolium (NBT) test is the original and most widely known test for chronic granulomatous disease. the higher the blue score. the better the cell is at producing reactive oxygen species.

Dihydrorhodamine (DHR) 123 test: respiratory burst capacity of neutrophils

Question 23

complement disorders

Answer 23

Deficiencies of early components of the classical complement pathway, including C1, C4, and C2, are associated with encapsulated bacterial infections like Streptococcus pneumoniae and Haemophilus Influenza type b and hereditary angiodeme due to the clotting pathway

C3 deficiency is associated with severe recurrent pyogenic

Alternative (properdin deficiency, Factors D and B): Properdin deficiency increases the susceptibility to bacterial infections of the Neisseria family of organisms. The most prominent in the group is N. Meningitis, the cause of a serious form of meningitis

Question 24

T Cell deficiencies

Answer 24

Severe Combined Immune Deficiency (SCID), Ataxia-Telangiectasia, Wiskott-Aldrich Syndrome and DiGeorge Syndrome

Question 25

X-linked Lymphoproliferative (XLP) Syndromes 1 and 2

Answer 25

XLP is characterized by life-long vulnerability to Epstein-Barr virus (EBV) infection, which can lead to severe and fatal infectious mononucleosis, lymph node cancers (lymphomas), combined immunodeficiency and, less commonly, aplastic anemia (inability to produce red blood cells) or vasculitis (inflammation in the blood vessels). XLP is associated with a defect on the X chromosome termed SH2DIA. As it is X-linked. hemophagocytic syndrome

Question 26

X-linked Immune Dysregulation with Polyendocrinopathy (IPEX) Syndrome

Answer 26

x linked
IPEX is characterized by multiple autoimmune endocrine diseases (particularly diabetes and thyroid problems), chronic diarrhea and a rash resembling eczema.
severes CROHNS/diabetes/coeliac
FOXP3. activated T cells which stimulate autoimmune problems.
immunosuppressive medications

Question 27

Veno-occlusive Disease (VODI)

Answer 27

extremely rare form of immunodeficiency inherited in autosomal recessive fashion with impairment of both T-cells and B-cells. Patients with VODI have a predisposition to leaving the patient subject to fungal infections such as Pneumocystis jiroveci infection. Patients may also have thrombocytopenia (low platelet counts) and enlarged livers. Intravenous immunoglobulin (IVIG) and Pneumocystis jiroveci prophylaxis as soon as the diagnosis of VODI is established is important.
also secondary to BMT

Question 28

Hoyeraal-Hreidarsson Syndrome (Dyskeratosis Congenita)

Answer 28

This syndrome has X-linked inheritance, and patients have poor growth inside the womb, microcephaly (small head), pancytopenia (low numbers of all blood cells), and especially decreased natural killer cells. Patients experience a progressive loss of cellular and humoral immunity and are thus susceptible to infections by virtually any pathogen

Question 29

Immunodeficiency with Centromeric Instability and Facial Anomalies (ICF)

Answer 29

ICF syndrome is a very rare disorder inherited from both parents due to defects in the DNA methyl transferable gene DNMT3B. Abnormal facial features are prominent such as macroglossia (large tongues). T-cell and B-cell numbers and serum immunoglobulins are all low and patients are susceptible to bacterial and opportunistic infections.

Question 30

Schimke Syndrome

Answer 30

very rare primary immunodeficiency with autosomal recessive inheritance that results in decreased circulating T-cells but normal levels of B-cells and serum immunoglobulins. Features associated with this syndrome are short stature, intrauterine growth retardation, kidney disease, bone marrow failure and problems fighting all types of infections. It is caused by a mutation in the gene responsible for chromatin remodeling (SMARCAL1). Additional features include ischemic cerebral attacks, migraine-like headaches, hematologic abnormalities of leucopenia, anemia and thrombocytopenia, enteropathy, hyper-pigmented skin macules, unusual hair and small teeth.

Question 31

Comel-Netherton

Answer 31

This is a very rare disorder with an autosomal recessive inheritance pattern. Patients have normal T-cell numbers but reduced numbers of B-cells. Patients exhibit increased IgE and IgA levels with variable-specific antibody function. Newborns exhibit ichthyosis (scaly skin), bamboo type hair (thin, tubular and fragile), an increased incidence of bacterial infections and growth failure. The hallmark of C-NS is trichorrhexis invaginata (bamboo hair), but other abnormalities, including pili torti (twisted hair) and trichorrhexis nodosa (hair of varying diameter) have been observed. Markedly elevated IgE levels, allergic reactions to food and common antigens, malnutrition, and increased susceptibility to skin, respiratory tract or systemic infections are also characteristic.

Question 32

Cartilage Hair Hypoplasia (CHH)

Answer 32

CHH is an autosomal recessive immunodeficiency associated with dwarfism and other medical problems. It is particularly common among the Amish because of family intermarriage. Most patients have very fine brittle hair and an unusual susceptibility to viral infections. The degree of immunodeficiency is variable and usually involves both antibody and cellular immunity. Some patients have been treated by bone marrow transplantation, but this will not correct their hereditary short stature.

Question 33

Chronic Mucocutaneous Candidiasis (CMC)

Answer 33

CMC is characterized by persistent Candida (fungus) infections of the mucous membranes, scalp, skin and nails. Rarely, the infection may spread to the blood stream or internal organs. CMC is usually hereditary and presents soon after birth with persistent oral Candida infections (thrush). Later, the nails and skin become chronically infected. These infections respond to anti-Candida treatment but recur when the treatment stops.

Question 34

APECED Syndrome

Answer 34

a hereditary form of mucocutaneous candidiasis: (autoimmune polyendocrinopathy-candidiasis-ectodermal dysplasia) associated with multiple endocrine problems (for example, hypothyroidism, diabetes or Addison disease) due to an AIRE gene defect on chromosome 21. However, the CMC in this disease is also partly due to autoantibodies directed against critical Candida fighting molecules made by the disordered immune system.

Question 35

Severe Combined Immune Deficiency (SCID),

Answer 35

serious primary immunodeficiency disease (PI) in which there is combined absence of T lymphocyte and B lymphocyte function. these infants all have an absence of T cells and severe deficiencies in both T cell and B cell function. The most common form of SCID, affecting nearly 30% of all cases, is due to a mutation in a gene on the X chromosome that encodes a component (or chain) called IL2RG shared by the T cell growth factor receptor and other growth factor receptors. This component is referred to as the common gamma chain (γc). Changes in this gene result in very low T lymphocyte and NK lymphocyte numbers, but the B lymphocyte count is normal or high (a so-called T-, B+, NK- phenotype). Despite the presence of B lymphocytes, there is no B lymphocyte function, since the B cells have abnormal receptors for growth factors on their cell surfaces.

Question 36

Ataxia-Telangiectasia

Answer 36

ATM gene on chromosome 11.
first presenting symptom of A-T is generally ataxia. Children with A-T usually have a delayed onset of walking and when they do, they sway, stagger and wobble. A-T causes progressive decline of motor neurologic function, which may not be apparent until age 4 or 5 years. It is the deterioration that most often leads to the correct diagnosis, as neurologic deterioration does not happen to people with cerebral palsy.
IgG, IgA, IgM and/or IgG subclasses.
reduced numbers of T- and B-lymphocytes, an abnormality that can be easily measured by a blood test. They may have problems with warts and a skin infection called molluscum, but they do not usually get opportunistic infections.
Patients with A-T are at an increased risk for developing all types of cancers, but particularly cancers of the immune system (lymphomas or leukemias). Cancer occurs in about 1/4 of all patients with A-T.

Question 37

Wiskott-Aldrich Syndrome

Answer 37

x linked, WASp: Wiskott-Aldrich syndrome (WAS) should be considered in any boy who has unusual bleeding and bruises, congenital or early onset thrombocytopenia, and small platelets. TIncreased tendency to bleed caused by a significantly reduced number of platelets
Recurrent bacterial, viral and fungal infections
Eczema of the skin
severe autoimmune disease and have an increased incidence of malignancy (cancer), particularly lymphoma or leukemia.
These infections may include upper and lower respiratory infections such as ear infections, sinus infections and pneumonia. meningitis and severe viral infections are less frequent but can occur
Red blood cell destruction is called hemolytic anemia and platelet destruction is called idiopathic thrombocytopenic purpura (ITP).
Lymphomas or leukemias that arise from B-lymphocytes are the most common with Non-Hodgkins lymphoma making up the majority of cases

Question 38

common mutations that cause SCID

Answer 38

1. common gamma chain
2. Recombinase Activating Gene 1 and 2 (RAG1 and RAG2). RAG1 and RAG2 are enzymes critical to development of T and B cells, but not NK cell, Adenosine Deaminase Deficiency
3. Another common type of SCID is caused by mutations in a gene that encodes an enzyme called adenosine deaminase (ADA). ADA is essential for the metabolic function of a variety of body cells but especially T cells.. ADA deficiency is the second most common cause of SCID, accounting for about 15% of cases. Babies with this type of SCID can have the lowest total lymphocyte counts of all because T, B, and NK lymphocyte counts are all very low. This form of SCID is inherited as an autosomal recessive trait.
4. alpha chain of the IL-7 receptor (IL-7Rα).
5. Janus Kinase 3

Question 39

specific susceptibilities for SCID

Answer 39

death <1 year if not treated: Pneumocystis jiroveci that can cause a rapidly fatal pneumonia (PJP) if not diagnosed and treated promptly. Another very dangerous organism is the chickenpox virus (varicella).. Since vaccines that infants receive for chickenpox, measles and rotavirus are live virus vaccines, infants with SCID can contract infections from those viruses through these immunizations.Persistent diarrhea resulting in failure to thrive is a common problem in children with SCID. It can lead to severe weight loss and malnutrition. Infants with SCID may also have a rash that is mistakenly diagnosed as eczema, but it is actually caused by a reaction of the mother’s T cells (that entered the SCID baby’s circulation before birth) against the baby’s tissues. This reaction is called graft-versus-host disease (GVHD) due to maternal engraftment.

Question 40

diagnosis of SCID

Answer 40

The presentation of SCID is changing rapidly in the U.S. because of the introduction of nationwide newborn screening for SCID using the detection of T cell receptor excision circles (TREC) to identify infants at risk before the onset of infections.

Question 41

considerations with blood transfusions:

Answer 41

your infant with SCID needs to have a blood or platelet transfusion, your infant should always get irradiated (CMV-negative, leukocyte-depleted) blood or platelets. This precaution is necessary in order to prevent fatal GVHD from T cells in blood products and to prevent your infant from contracting an infection with CMV.

Question 42

autoimmune conditions in PID

Answer 42

Autoimmune complications have been reported in a wide range of primary immunodeficiency diseases. However, certain primary immunodeficiency diseases have autoimmune disease as their primary problem. These include Autoimmune Polyendocrinopathy; Candidiasis; Ectodermal Dysplasia (APECED or APS-1); Autoimmune Lymphoproliferative Syndrome (ALPS); and Immune dysregulation; Polyendocrinopathy, Enteropathy, and X-linked (IPEX) syndrome

Question 43

secondary immune dysfunction conditions seen with autoimmune features

Answer 43

Certain other immune disorders are frequently associated with autoimmune complications. These include Common Variable Immune Deficiency (CVID), Wiskott-Aldrich Syndrome (WAS), IgA deficiency, Good Syndrome, Hyper IgM Syndrome, Idiopathic T-cell Lymphopenia (ICL) and Complement disorders.