Immunology Exam 2 Lecture 6

Front 1

What are the two classes of Immunodeficiency disease?

Back 1

Primary Immunodeficiency
Secondary Immunodeficiency

Front 2

What is Primary Immunodeficiency?

Back 2

Immunodeficiency due to genetic defects in different components of immune system

Front 3

What are examples of Primary Immunodeficiency?

Back 3

deficiency in T cell
B cell or any other components of immune system

Front 4

What is Secondary Immunodeficiency?

Back 4

Acquired Immunodiciency Syndrome.
Immunodeficiency secondary to chemotherapy for maligancy or transplantation
Immunodefiency fue to infection and/or nutritional deficiency

Front 5

In Primary Immunodeficiency what is defective?

Back 5

defective antibody response (B cell defect)
Defective cell mediated immunity (T cell or T cell related defects)
Hereditary complement deficiencies or complement component defect (e.g. C! inhibitor deficiency)
Defects in phagocyte

Front 6

What happens in defects in phagocytes of Primary Immunodeficiency?

Back 6

defects in oxygen reduction pathway pf phagocytes
Leukocytes adhesion deficiency

Front 7

List the Primary B cell Defects

Back 7

X linked agammaglobulinaemia
IgA and IgG subclass deficiences
Hyper IgM syndrome
Common variable immunodeficiency
Transient hypoglobulinemai of infancy

Front 8

What does Primary B cell defect result in?

Back 8

inacan't clear extracellular pathogens; consequence if recurrent pyogenic infection such as pneumonia, otitis media and sinusitis

Front 9

What happen when recurrent pneumonia is untreated in Primary B cell defect?

Back 9

pt may lead to severe obstructuve lung disease such as bronchiectasis

Front 10

What is X linked agammaglobulinaemia?

Back 10

Model B cell deficiency disease

Front 11

What is the MOA of X linked agammaglobulinaemia?

Back 11

Defect in XLA is in cytoplasmic protein tyrosin kinase, which is called Bruton's tyrosine (BTtk)

Front 12

What is BtL involved in X linked agammaglobulinaemia?

Back 12

BtK is involved in intracellular signaling from B cell receptor and is necessary for growth and differentiation of pre-B cells.

Front 13

Btk belongs to what family?

Back 13

src oncogene family

Front 14

Who is affected by XLA more?

Back 14

X-linked disease
male offspring affected more than female.

Front 15

Why is males affected more than females in X linked agammaglobulinaemia?

Back 15

first 6-12 months protected by maternal IgG that crossed the placenta into fetus

Front 16

What are the clinical features of X linked agammaglobulinaemia?

Back 16

Very few or no B cells in blood or lymphoid tissue;
very small lymph nodes and absence of tonsils

Front 17

What antibodies are lacking in X linked agammaglobulinaemia?

Back 17

IgA
IgM
IgD
IgE
ONLY small amount of IgG

Front 18

Due to lack of antibodies, X linked agammaglobulinaemia patients are vulnerable to what?

Back 18

infection with extracellular pyogenic bacteria that have polysaccharide capsule resistent to phagocytosis

Front 19

What are the bacterias involved in X linked agammaglobulinaemia? d/t lack of antibodies

Back 19

Haemophilus influenzae
Streptococcus pneumoniae
Streptococcus pyogenes
Staphylococcus aureus

Front 20

What is also susceptible to viruses that are usually controlled by Ab in X linked agammaglobulinaemia?

Back 20

Enteroviruses

Front 21

What is the tx of X linked agammaglobulinaemia?

Back 21

periodical (monthly) infusion of large doses of gammaglobulin

Front 22

How is gamma globulin prepared?

Back 22

5% solution of gamma globulin made from plasma of large pool of blood which is fractionated into differernt component

Front 23

Use of gamma globulin in passive immunity

Back 23

passive immunity is transferred to XLA individuals as this preparation contains antibodies against the range of common pathogens

Front 24

Which is the most common form of deficiency? IgA or IgG?

Back 24

IgA deficiency (1 in 800 incidence rate)

Front 25

What does IgA deficiency pt also suffer from?

Back 25

20% pt suffer from IgG2 and IgG4 deficiencies, so susceptible to recurrent pyogenic infections

Front 26

What does IgA and IgG subclass deficiencies result from?

Back 26

failure in terminal differentiation of B cells

Front 27

What does IgA and IgG deficiency also suceptible to?

Back 27

susceptible to infectio with pyogenic organisms

Front 28

What is the tx of IgA and IgG deficiency?

Back 28

XLA

Front 29

What is Hyper-IgM syndrome?

Back 29

X-linked disease
Diminished antibody production

Front 30

In Hyper-IgM syndrome, the diminished antibody production results from what type of defect?

Back 30

results from inherited defects in T cell help

Front 31

What is the MOA of Hyper IgM syndrome?

Back 31

CD40 ligand on T cells interact with CD40 on B cells; crucial for antibody isotype switching. Hyper-IgM syndrome pt has a deficiency of CD40L

Front 32

What is the result of CD40L deficiency?

Back 32

these patient have very high levels of IgM and low levels of IgG, IgA, IgE
LACK isotype switching

Front 33

In Hyper-IgM syndrome what organs are absent?

Back 33

absence of germinal center in lymph nodes and other secondary lymphoid organs

Front 34

Hyper-IgM syndrome pt are susceptible to what type of infection?

Back 34

highly susceptible to pyogenic infection

Front 35

What is the tx for Hyper-IgM syndrome?

Back 35

antibiotic
periodic infusion with gagablobulin

Front 36

What is required for activation of macrophages?

Back 36

Interaction of CD40L on T cells with CD40 on macrophases is required for activation of macrophages. This is what Hyper-IgM syndrome lacks

Front 37

What happens when there is lack of T cell CD40L? in Hyper-IgM syndrome pt

Back 37

lack of T cell CD40L leads to reduced macrophage function. (GMCSF production)

Front 38

What is the treatment for Hyper-IgM syndrome, with lack of macorphage activation?

Back 38

GM- CSF

Front 39

When does MAternal IgG go away during infancy?

Back 39

first few months of infancy

Front 40

When does synthesis of antibodies occur?

Back 40

start around 3 months of age.

Front 41

When does antibodes against bacterial capsular polysaccharides start synthesis?

Back 41

2nd year of life

Front 42

What is Transient Hypogammglobulineamia of Infancy?

Back 42

In some infants, IgG synthesis delyed as long as 36 months

Front 43

What happens to the cells of a Transient Hypogammglobulineamia of Infancy pt?

Back 43

B cells normal
IgG production is impaired due to proper T cell help

Front 44

What is the tx of Transient Hypogammglobulineamia of Infancy?

Back 44

Infection should be treated with abx

Front 45

Is Common Variable Immunodeficiency (CVID) hereditary disease?

Back 45

No, acquired during 3rd or 4th decade of life

Front 46

Which sex is more affected by Common Variable Immunodeficiency (CVID) ?

Back 46

Males and females affected equally.

Front 47

What virus if sometimes associated with Common Variable Immunodeficiency (CVID)?

Back 47

Epstein-Barr virus (EBV)

Front 48

Individuals with Common Variable Immunodeficiency (CVID) are susceptible...

Back 48

pyogenic bactera
intestinal protozoan
Giardia lamblia

Front 49

What is MOA of Common Variable Immunodeficiency (CVID) ?

Back 49

B cells are not defective
They don't get proper T cell help

Front 50

What do Common Variable Immunodeficiency (CVID) pt suffer from?

Back 50

autoimmune disease mostly pernicious anemia

Front 51

List the Defective cell-mediated immunity, T cell ot T cell related defects.

Back 51

Severe Combine immunodeficiency (SCID)
MHC molecule deficiency
DiGeorge's syndrome
Hereditary ataxia telangiectasia
Wiskott-Aldrich syndrome

Front 52

List the Severe Combine immunodeficiency (SCID) disease

Back 52

X linked SCID
Autosomal SCID: Adenosine deaminase (ADA) deficiency, Purine nucleoside phosphorylase (PNP) deficiency, RAG gene deficiency

Front 53

What are the cardinal features of Severe Combine immunodeficiency (SCID)?

Back 53

lymphocyte deficiency and failure of thymus development resulting in profound deficiency in cell mediated immunity and recurrent infections in early life (contract with XLA)

Front 54

What do Severe Combine immunodeficiency (SCID) suffer from?

Back 54

Diarrhea (Rotavirus or GI bacteria)
Pneumonia (Pneumocystis carinii)
Oral thrush or skin infection (Candida albicans)

Front 55

Specifically, what do you see in a thymus of a Severe Combine immunodeficiency (SCID) pt?

Back 55

Absence of lymphocyte infiltration in the stroma and lack of Hassall's corpuscles

Front 56

What are the common finding in Severe Combine immunodeficiency (SCID)?

Back 56

Blood lymphocyte < 3000/ml
Lymph node and thymust contain few lymphocyte
Thymus has fetal appearance

Front 57

What happens if you vaccinate a SCID child with BCG and Polio caccine (any live vaccine)?

Back 57

SCID infants will develop a full blown disease and may die.

Front 58

Which SCID is accounts for 50% of SCID cases?

Back 58

X-linked SCID

Front 59

Which sex is affected by X-linked SCID?

Back 59

Males because a gene on X-chromosome is defective

Front 60

In X-linked SCID, where in the X chromosome is defective?

Back 60

in the gene that encodes the y chain of IL-2 receptors on T cells. (y-chain problem)

Front 61

What does y chain do?

Back 61

form part of the receptors for IL-4, -7, -11 and -15;

binding od IL7 to its receptor is critical for T cell maturation; therefore, defective y chain lead to severely impaired maturatio nof T cells.

Front 62

What is the cause of Autosomal SCID?

Back 62

defect in recessive genes on autosomal chromosomes
- deficiency of Adenosine deaminase (ADA)
- deficiency of Purine nucleotide (PNP)
-deficiency of RAG-1 or RAG2

Front 63

What happens if there is deficiency of Adenosine deaminase (ADA)?

Back 63

this is a purine degradation enzyme and deficiency of ADA leads to accumulation of toxic metabolite dATP leading to inhibition of ribonucleotide reductase, an enzyme required for DNA synthesis

Front 64

What happens if there is deficiency of Purine Nucleotide phosphorylase (PNP)?

Back 64

another purine degradation enzyme and deficiency= accumulation of toxic metabolite, dGTP lead to inhibition of ribonucleotide reductase, and inhibits DNA synthesis

Front 65

What happens if there is a deficiency of RAG 1 and RAG 2?

Back 65

deficiency of the gene, can't cleavage and repair DNA during somatic recombination of T cell and B cell receptor = cause failure to develop T and B cell.

Front 66

Why only lymphocyte are defective in ADA and PNP deficiency?

Back 66

Relative deficiency of 5' nucleotidade (a compensatory enzyme) in lymphocyte.

Front 67

What are the two types of MHC molecule deficiency?

Back 67

MHC class I molecule deficiency
MHC class II molecule deficiency

Front 68

What is the cause of MHC class I molecule deficiency?

Back 68

mutation in TAP gene
-fail to make CD8 T cells

Front 69

What do MHC class I molecule deficiency pt suffer from?

Back 69

recurrent intracelluar bacteria and viral infections called Bare lymphocyte syndrome

Front 70

What is Bare lymphocyte syndrome?

Back 70

Seen in MHC Class I and II Deficiency and it is recurrent intracelluar bacteria and viral infections

Front 71

What is MHC Class II molecule deficiency caused by?

Back 71

defects in transcriptional regulators essental for expression of MHC class II (or LA class II)
Give rise to Bare Lymphocyte syndrome

Failure to make CD4 T cell

Front 72

In MHC Class II molecule deficiency What are the 4 transcriptional proteins involved?

Back 72

Class II transactivator (CIITA)
The other 3 is RFX components:
tranceiptional complex that binds to sequence in promotor of HLA class II gene called the X box

Front 73

Pt with MHC II deficiency fail to make CD4 T cells will suffer from what?

Back 73

recurrent infeciton with fungi and other extracellular pathogens

Front 74

Where is the defect for Wiscott-Aldrich Syndrome (WAS)?

Back 74

defect on gene X chromosome that encodes Wiscott-Aldrich Syndrome (WAS) protein

Front 75

What cell is Wiscott-Aldrich Syndrome (WAS) involved in?

Back 75

involved in cytoskeltal reorganization of T cells, required for cytokine secretion by T cells
delivering signals from T cells to B cells, macrophase and other target cells needed for immune responses.

Front 76

What antibodies does Wiscott-Aldrich Syndrome (WAS) results will you see?

Back 76

increased IgA and IGE
normal levels of IgG
decreased IgM

Front 77

What does Wiscott-Aldrich Syndrome (WAS) also suffer in?

Back 77

impaired platelet function and thrombocytopenia
pyogenic and opportunisitic infections
severe eczema

Front 78

What is the cause of DiGeorge Syndrome?

Back 78

defective development of third and fourth pharyngeal pouches
And t cell deficiency depend on how badly thymus is affected

Front 79

What do neonates with DiGeorge Syndrome suffer from?

Back 79

other organs from same embryological origin also affects, so neonates may suffer tetany d/t hypoplasia or aplasia of parathyroid gland

Front 80

What are the distinictive features of affected child with DiGeorge Syndrome?

Back 80

Hypertelorism (widely set eyes)
Low set ears
Shortened philtrum of upper lip

Other features: cardiac &/or aoric anomalies

Front 81

What is Hereditary ataxia-telangiectasia (AT)?

Back 81

autosomal recessive immunodeficiency disease

Front 82

What does the infant develop if they have Hereditary ataxia-telangiectasia (AT)?

Back 82

develop wobbly gait (ataxia) at 18 months
Dilated capillaries (telangiectasia) at school age.

Front 83

What cell deficiency is variable in Hereditary ataxia-telangiectasia (AT) pt?

Back 83

T cell deficiency

Front 84

What antibody deficiency does a Hereditary ataxia-telangiectasia (AT) pt have?

Back 84

Deficiency:
IgA
IgG2
IgG4

Front 85

What does patient with Hereditary ataxia-telangiectasia (AT) suffer from?

Back 85

severe sinus
lung infection

Front 86

What defect seen in Hereditary ataxia-telangiectasia (AT) pt is due to what?

Back 86

chromosomal break in chromosome 7 and 14 at site of TCR gene and genes encoding heavy chains of immunoglobulin

Front 87

T cell related defect: What happens when there is a deficiency of IFN-y or IL-12 receptors?

Back 87

lead to defective cell mediated immune responses

Front 88

IFN-y is critical for what?

Back 88

critical for macrophage activation and killing pathogens infecting macrophage

Front 89

IL-12 made from infected macrophase is critical for what?

Back 89

critical for activating secretion of:
IFN-y
NK
CD4
CD8 cells

Front 90

What do patients with T cell related defect (IFN-y and IL-12 receptors deficiency) suffer from?

Back 90

comon intracellular bacterial infection such as ubiguitous, nontuberculous strain of mycobacteria, Mycobacterium avium intracullulare complex

Front 91

Vaccination with BCG vaccine of patients with IFN-y and IL-12 receptors deficiency) may lead to what?

Back 91

precipitate disseminated infection and disease

Front 92

What is X-linked lymphoproliferative syndrome (XLP) caused by?

Back 92

failure to control normal proliferation of CTL
lead to infection w/Epstein -Barr virus (EBV) which cause infectious mononucleosis

Front 93

What does Epstein Barr Virus (EBV) cause?

Back 93

infectious mononucleosis

Front 94

What defect is seen in X-linked lymphoproliferative syndrome (XLP)?

Back 94

SH2D1A gene on x-chromosome

Front 95

What is the function of SHD1A gene?

Back 95

encodes for an adapter protein of T and B cells called SLAM-associated portein (SAP);
SLAM expressed on surface of T and cells

Front 96

What is the function of SAP?

Back 96

regulator protein that regulate proliferation of cytotoxic T cells

Front 97

What happens when there is defect in SAP production?

Back 97

uncontrolled CTL proliferation in EBV infected patients

lead to:
fatal infectious mononucleosis
Or agammaglobulinemia, then destroy B cells
Or fatal lymphoid malignancy
Or aplastic anemia

Front 98

List the complement proteins

Back 98

C1, C2, C4
C3
C5-C9
Factor D, properdin (factor P)
Factor I
DAF, CD59

Front 99

Defect in complement protein C1, C2, C4 lead to:

Back 99

immune complex disease

Front 100

Defect in complement protein C3 lead to:

Back 100

susceptibility to capsulated bacteria

Front 101

Defect in complement protein C5-C9 lead to:

Back 101

Only effect is susceptibility to Neisseria

Front 102

Defect in complement protein Factor D, properdin (factor P) lead to:

Back 102

Susceptibility to capsulated bacteria and Neisseria but no immune complex disease

Front 103

Defect in complement protein Factor I lead to:

Back 103

Similar effects to deficiency of C3

Front 104

Defect in complement protein DAF, CD59 lead to:

Back 104

Autoimmunelike conditions including paroxysmal nocturnal hemoglobinuria

Front 105

A Defect in complement regulatory protein (C1 inhibitor C1INH) and overproductio of C2a fragment results in what clinical condition?

Back 105

Hereditary Angioneurotic Edema

Front 106

In Hereditary Angioneurotic Edema, Absence of C1 inhibitor C1INH leads to:

Back 106

uncontrolled activation of classical pathway

Front 107

In Hereditary Angioneurotic Edema, what happens when there is a overporduction of C2a fragment?

Back 107

accumulation of fluid in tissues (eg. face, respiratory tract and gastrointestinal tract)

Pt can die from suffocation d/t epiglottal swelling

Front 108

List the defects in phagocytes

Back 108

Leukocyte adhesion deficiency
Chronic granulomatous disease (CGF)
Glucose 6 phosphate dehydrogenase (G6PD) deficiency
Myeloperoxidase deficiency
Chediak-Higashi syndrome

Front 109

What is the cellular abnormality of Leukocyte adhesion deficiency?

Back 109

Defective CD18 (cell adhsion molecule)

Front 110

What is the immune defect of Leukocyte adhsion deficiency?

Back 110

Defective migration of phagocytes into infected tissues

Front 111

What is the associated infections/other diseases with Leukocyte adhesion deficiency?

Back 111

Widespread infections with capsulated bacteria

Front 112

What is the cellular abnormality of Chronic granulomatous disease (CGD)?

Back 112

Defective CD18 (cell adhesion molecule)

Front 113

What is the immune defect seen in Chronic granulomatous disease (CGD)?

Back 113

impaired killing of phagocytosed bacteria

Front 114

What is the associated infections and disease seen in Chronic granulomatous disease (CGD)?

Back 114

chronic bacterial and fungal infections.
Granulomas

Front 115

What is the cellular abnormality in Glucose 6 phophate dehydrogenase (G6PD) deficiency?

Back 115

deficency of glucose 6 phosphate dehydrogenase.
Defective respiratory burst

Front 116

What is the immune defect of Glucose 6 phophate dehydrogenase (G6PD) deficiency?

Back 116

Impaired kiling of phagocytosed bacteria

Front 117

What is the associated infections and other disease seen in Glucose 6 phophate dehydrogenase (G6PD) deficiency?

Back 117

Chronic bacterial and fungal infections
Anemia induced by certain agents

Front 118

What is the cellular abnormality seen in Myeloperoxidase deficiency?

Back 118

Deficiency of myeloperoxidase in neutrophil granules and macrophase lysosomes and impaired production of toxic oxygen species

Front 119

What is the immune defect in Myeloperoxidase deficiency?

Back 119

Impaired killing of phagocytosed bacteria

Front 120

Waht is the associated infections and other disease seen in Myeloperoxidase deficiency?

Back 120

Chronic bacteria and fungal infections

Front 121

What cellular abnormaility is seen in the Chediak Higashi syndrome?

Back 121

Defect inveicle fusion

Front 122

What immune defect is seen in Chediak Higashi syndrome?

Back 122

Impaired phagocytosis due to inability to endosomes to fuse with lysosomes

Front 123

What is the associated infections and other disease seen in Chediak Higashi syndrome?

Back 123

Recurrent and persistent bacterial infections
Granulomas
Effects on many organs

Front 124

How can you corred immunodeficiencies due to defect in the genes that affect hematopoietic stem cells?

Back 124

transplantation of stem cells ontained from bone marrow or peripheral blood

Front 125

How do you correct genetic defect?

Back 125

somatic gene therapy

Front 126

What is somatic gene therapy?

Back 126

a functional copy of defective fene is introduced into stem cells (obtained from patients bone marrow) and is re-infused into patient.