Biochemistry 3-4: Immunodeficiency 1&2 Flashcards
1
Q
Definition: it is the absence or failure of normal function of one or more elements of the immune system.
A
Immunodeficiency.
2
Q
The consequences of a failure in the immune system leads to what?
A
Increased risk of infection, autoimmune disease, hypersensitivity, or even cancer.
3
Q
Definition: the failure of the immune system to protect against disease or malignancy.
A
Immunodeficiency.
4
Q
What causes primary immunodeficiency? And when does it show up?
A
Caused by genetic or developmental defects in the immune system. These defects are present at birth but may show up later on in life.
5
Q
Definition: the loss of immune function as a result of exposure to disease agents, environmental factors, immunosuppression, or aging.
A
Secondary or acquired immunodeficiency.
6
Q
List the 4 types of primary immunodeficiency diseases?
A
1- antibody production defects.
2- cellular or combined defects.
3- phagocytic cell immune defects.
4- complement defects.
7
Q
Give 4 examples of primary immunodeficiencies antibody production defects?
A
1- X-linked agammaglobulinemia (Bruton’s).
2- common variable immunodeficiency (CVID).
3- selective IgA deficiency.
4- X-linked or autosomal hyper IgM syndrome.
8
Q
Give 4 examples of primary immunodeficiencies cellular or combined defects?
A
1- severe combined immunodeficiency.
2- DiGeorge syndrome.
3- Ataxia Telangiectasia.
4- Wiskott-Aldrich syndrome.
9
Q
Give 4 examples of primary immunodeficiencies phagocytic cell immune defects?
A
1- Leukocyte adhesion defects.
2- Chronic granulomatous disease.
3- Chediak Higashi syndrome.
4- Cyclic neutropenia kostman diseases.
10
Q
Give 2 examples of primary immunodeficiencies complement defects?
A
1- C1 esterase inhibitor deficiency.
2- Complement component deficiency.
11
Q
List 8 factors that are contribure to secondary immunodeficiency?
A
1- HIV.
2- aging.
3- heart failure, liver failure, CKD/ESKD.
4- cancer.
5- TB and other chronic infections.
6- immunosuppressive drugs.
7- dysbiosis and gut disorders.
8- malnutrition.
12
Q
List the 4 classifications of secondary immunodeficiencies?
A
1- T cell disorders.
2- B cell defects.
3- phagocyte disorders.
4- complement disorders.
13
Q
Give examples of secondary immunodeficiencies that affect T cell disorders?
A
1- Severe combined immunodeficiency.
2- Wiskott Aldrich syndrome (Xp11).
3- Ataxia Telangiectasia (11q).
4- DiGeorge anomaly.
14
Q
Give examples of secondary immunodeficiencies that affect B cell defects?
A
1- XL agammaglobulinemia.
2- Common variable immunodeficiency.
3- Selective IgA deficiency,
4- AR agammaglobulinemia.
5- Hyper-IgM syndromes-XL.
15
Q
Give examples of secondary immunodeficiencies that affect phagocyte disorders?
A
1- Chronic granulomatous disease.
2- Leukocyte adhesion defect.
3- Chediac Higashi syndrome.
4- Myeloperoxidase deficiency.
5- Cyclic neutropenia (elastase defect).
16
Q
Give examples of secondary immunodeficiencies that affect complement disorders?
A
1- C1q deficiency.
2- Factor I deficiency.
3- Factor H deficiency.
4- Factor D deficiency.
5- Properdin deficiency.
17
Q
Recurrent streptococcus pneumonia and haemophilus influenza infections are indicative of which type of immunodeficiency?
A
Ig, C2 or IRAK-4 deficiency.
18
Q
Recurrent giardia intestinalis (lamblia) infections are indicative of which type of immunodeficiency?
A
Antibody deficiency syndromes.
19
Q
Familial clustering of autoimmune disorders (e.g. SLE,pernicious anemia) are indicative of which type of immunodeficiency?
A
Common variable immunodeficiency or selective IgA deficiency.
20
Q
Pneumocystis infections, cryptosporidiosis, or toxoplasmosis are indicative of which type of immunodeficiency?
A
T-cell disorders or occasionally Ig deficiency.
21
Q
Viral, fungal or mycobacterial (opportunistic) infections are indicative of which type of immunodeficiency?
A
T-cell disorders.
22
Q
Clinical infection due to live-attenuated vaccines (e.g. varicella, polio, BCG) are indicative of which type of immunodeficiency?
A
T-cell disorders.
23
Q
Graft-vs-host disease due to blood transfusions are indicative of which type of immunodeficiency?
A
T-cell disorders.
24
Q
Staphylococcal infections, infections with gram-negative organisms (eg. Serratia or klebsiella), or fungal infections (eg. Aspergillosis) are indicative of which type of immunodeficiency?
A
Phagocytic cell defects or hyper IgE syndrome.
25
Skin infections are indicative of which type of immunodeficiency?
Neutrophil defect or Ig deficiency.
26
Recurrent gingivitis are indicative of which type of immunodeficiency?
Neutrophil defect.
27
Recurrent neisserial infection are indicative of which type of immunodeficiency?
Complement deficiencies.
28
Recurrent sepsis are indicative of which type of immunodeficiency?
Complement deficiencies, or IgG deficiency.
29
Family history of childhood death or of infections in a maternal uncle that are similar to those in the patients are indicative of which type of immunodeficiency?
X-linked disorders (eg, sever combines immunodeficiency, X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, Hyper-IgM syndrome).
30
Which type of immunodeficiencies are inherited defects of the immune system?
Primary immunodeficiencies.
31
The inherited defects of primary immunodeficiencies may be in which type of immune mechanisms?
The defects may be in the specific or non-specific immune mechanisms.
32
Primary immunodeficiencies are classified on the basis of what?
the site of lesion in the developmental or differentiation pathway of the immune system.
33
Defects in cell interaction and signaling can lead to what?
Lead to severe immunodeficiency.
34
List the 5 defects that SCID may result from?
1- JAK-3: transduces signals from the gamma chain of the cytokine receptors; the gamma chain of receptors for IL-2,4,7,9 and 15 (IL-R).
2- XLA (X linked agammaglobulinemia): results from defective transduction of activating signals from the cell-surface IgM by Burton’s tyrosine kinase (BTK).
3- the recombination-activating genes (RAG-1 and -2): required for synthesis of the functional immunoglobulins and T-cell receptors that characterize mature B and T cells.
4- expression of the class 2 MHC molecules (bare lymphocyte syndrome).
5- XHM (X linker hyper IgM syndrome): results from defects CD40L that prevent normal maturation of B cells.
35
Identical clinical conditions are caused by what?
Caused by mutations in different immune system genes.
36
SCID is caused by what?
Caused by mutation in 12 different genes.
37
Hyper IgM syndrome results from what?
Results from 6 different gene mutations.
38
____________ presentation of mutations in a single gene can be quite different even within the same family.
Phenotypic.
39
Give an example of primary immunodeficiencies where genotype does NOT equate to phenotype, and how?
DiGeorge syndrome;
85% of patients have exactly the same mutation, but clinical presentation is very broad.
No heart defects vs. severe congenital heart defects.
Normal immune system vs. complete absence of T cells.
40
Most primary immunodeficiencies (PID) are diagnosed in which age group?
Most are diagnosed in childhood - 40% are not diagnosed until adolescence or early adulthood.
41
List the 8 warning signs for PIDs?
1- 8 or more otitis media infections per year.
2- 2 or more serious sinus infections per year.
3- 2 or more pneumonias per year.
4- recurrent deep infections or infections in unusual areas.
5- infections with opportunistic pathogens.
6- persistent thrush in patients older than 1 year.
7- family history of PID.
8- family history of early childhood deaths.
42
What is thrush?
Candida infection, characterized by white, adherent, painless, discrete or confluent patches in the mouth, tongue, or esophagus.
43
Defects in cellular immunity often present with what?
1- opportunistic infections (pneumocystis carinii, cryptococcus, candida spp).
2- disseminated viral infections (CMV, EBV, and VSV).
3- failure to thrive, chronic diarrhea, persistent thrush.
44
Defects in cellular immunity are clinically evaluated with what?
1- CBC with differential, lymphocyte subsets.
2- Vaccine titers (eg, tetanus, diphtheria).
3- Ig levels (IgA, IgE, IgM, IgG).
4- T cell proliferation assay (eg, PHA, ConA, PMA/ionomycin).
5- skin testing (eg, candida protein).
45
Defects in humoral immunity often present with what?
1- recurrent sinopulmonary infections.
2- encapsulated bacteria (hemophilus influenza, pneumococcus spp).
3- parasitic infections (giardia).
4- some virus infections (enetrovirus, papillomavirus).
5- chronic diarrhea, poor growth,
46
Defects in humoral immunity are clinically evaluated with what?
1- vaccine titers (eg, tetanus, diphtheria).
2- Ig levels (IgA, IgE, IgM, IgG).
3- B cell subset analysis (eg, naive, memory, ect).
47
Defects in phagocytosis often present with what?
1- recurrent abscesses, abscesses in unusual areas.
2- recurrent oral ulcers.
3- severe pneumonias.
4- catalase+ organisms (eg, staph. Aureus, serratia, etc..).
48
Defects in phagocytosis are clinically evaluated with what?
1- CBC with differential.
2- nitroblue tetrazolium (NBT) test for production of oxygen radicals.
49
Give 2 example of non-specific immunity defects?
1- phagocytic cells: neutropenia, neutrophil, complement deficiency.
2- chronic granulomatous disease.
50
What is the inheritance pattern of chronic granulomatous disease? And when does it present?
Inherited X-linked recessive disorder, presenting in the first 2 months.
51
What happens in chronic granulomatous disease?
1- activated phagocytes cannot produce bactericidal O2 radicals.
2- impaired neutrophil killing of staphylococci.
52
What are the clinical manifestations of chronic granulomatous disease?
Skin sepsis (staphylococci, gram-negative bacteria or fungi), abscesses, regional lymphadenopathy, hepatosplenomegaly.
53
How is chronic granulomatous disease diagnosed histologically and which test is used?
Histology shows non-caseating giant cell granulomas.
Nitroblue tetrazolium test (NBT): precent of endotoxin stimulated neutrophils showing reduction of NBT is impaired (yellow to blue).
Chemiluminescence of neutrophils is stimulated by opsonized particles is impaired.
54
List the 3 types of primary immunodeficiency based on immune cells? And give examples?
1- B cell (antibody): eg, common variable immunodeficiency & selective IgA deficiency.
2- T cell (cell-mediated immunity): eg, DiGeorge syndrome & chronic mucocutaneous candidiasis.
3- B & T cells (combined): eg, severe combined ID (SCID).
55
List the clinical manifestations of common variable immunodeficiency?
1- low serum IgG, IgM, IgA (pan-hypogammaglobuliemia).
2- low antibody levels (e.coli, isochemagglutinin).
3- B cell and T cell number normal, T cell functions impaired.
4- affects adults (15-33 years); male and female.
5- lobar pneumonia, herpes zoster, diarrhea (giardia), recurrent pyogenic infection.
6- autoimmune diseases.
56
List the clinical manifestations of selective IgA deficiency?
(1:700).
1- serum IgA low or absent but IgM normal.
2- secretory IgA is absent in mucosal secretions.
3- circulating B cells (and IgA-B cells) normal.
4- recurrent infections, atopic allergies, autoimmune disorders.
57
List the clinical manifestations of Di George syndrome (thymic hypoplasia)?
1- caused by intrauterine damage to 3rd and 4th pharyngeal pouches and presents from brith.
2- cell mediated immunity (CMI): decreased T cells, with negative PHA or MRL response.
3- immunoglobulin levels normal (or low) but unable to make specific antibodies.
4- presents with hypoparathyroidism, cardiovascular defect, abnormal facies, recurrent infections.
58
What is the treatment for Di George syndrome (thymic hypoplasia)?
The treatment is fetal thymic transplants.
59
List the clinical manifestations of chronic muco-cutaneous candidiasis?
1- affects children and some with familial history.
2- CMI defect to candida.
3- candidiasis of mucosal tissues, nails and skin.
4- can be associated with endocrine abnormalities: hypothyroidism, addison’s disease, and diabetes.
60
List the 5 factors that decrease production of immune components that may cause secondary (acquired) immunodeficiencies?
1- malnutrition (starvation, alcoholics).
2- infections (EBV, HIV).
3- drugs (corticosteroids, cytotoxic drugs).
4- malignant diseases (lymphoma, leukemia, myeloma).
5- aging.
61
List the 3 factors that increase production of immune components that may cause secondary (acquired) immunodeficiencies?
1- protein loss enteropathy (celiac disease, crohn’s disease, ulcerative colitis).
2- nephrotic syndrome.
3- autoimmune diseases.
62
What is SCID?
Failure of differentiations of stem cells into T and B cells and corresponding defects in infants.
63
List the 2 types of SCID?
1- X-linked.
2- autosomal recessive (swiss type).
64
Failure to thrive in SCID is because of what?
Chronic diarrhea, recurrent viral, bacterial, fungal and protozoal infection.
65
What happens to T and B cells functions in SCID?
T and B cells functions are absent or decreased; lymph nodes show T and B cell depletion
66
What is the treatment of SCID?
Bone marrow transplant.
67
List 2 primary B cell immunodeficiencies?
1- X-linked agammaglobulinemia (Burton’s disease).
2- selective IgA deficiency.
68
List 8 primary T cell immunodeficiencies?
1- Di George syndrome.
2- Ataxia - Telangiectasia.
3- Wiskott - Aldrich syndrome.
4- acquired immunodeficiency.
5- chemotaxis deficiency.
6- chronic granulomatous disease.
7- Chediak - Higashi syndrome.
8- leukocyte adhesion deficiency.
69
Common variable immunodeficiency associated with B cells, happens because of what?
Mature B cells failure to differentiation into mature plasma secreting cells (antibody forming cells).
70
X-linked agammaglobulinemia XLA/ Burton’s disease happens because of what?
Deficiency of b cell tyrosine kinase causing failure in the development of pre-B cell maturation to B cells.
71
Majority of XLA patients show what?
Profound hypogammaglobulinemia involving all immunoglobulin classes with <1% B cells in normal peripheral blood.
72
XLA is caused by mutations in the human _____ gene.
BTK gene.
73
_____% of BTK mutations are caused by what?
90% are caused by single base pair substitution and insertion or deletion < 5 base pair.
74
Mutation of B cell in the BTK gene will cause what in an XLA patient?
Mutation will cause B cells in the XLA patient remain in the pre-B stage with H chains rearranged but L chains in their germ-line configuration.
75
List the 3 clinical presentations of Bruton’s disease?
1- increased susceptibility to encapsulated recurrent pyogenic bacteria (S.pneumonia, and pseudomonas species).
2- skin infections (group A streptococci and S.aureus).
3- persistent viral or parasitic infections.
76
What is the treatment for Bruton’s disease (XLA)?
- missing immune globulin is injected IV or subcutaneously throughout life.
- antibiotics are promptly given to treat bacterial infections and may be given continuously.
77
What are the clinical manifestations that patients with IgA deficiency have?
- IgA levels <5mg/dL with normal levels of other Igs.
- 50% have chronic otitis, sinusitis or pneumonia.
78
IgA committed to __ lymphocytes:
Fail to _______ into IgA-secreting ______ cells caused by _____ ____ cell defect.
IgA committed to B lymphocytes:
Fail to mature into IgA - secreting plasma cells caused by intrinsic B cell defect.
79
Patients of IgA deficiency are susceptible to what?
1- allergic conjunctivitis, urticaria and asthma.
2- autoimmune and neurological disorders.
3- various gastrointestinal diseases (food allergy).
4- recurrent sinopulmonary infections.
80
SCID is characterized by what?
Deficiency in both B and T lymphocyte functions with markedly low IgG, IgA and IgE levels.
81
SCID is associated with what?
1- children failure to thrive.
2- chronic respiratory infections.
3- gastrointestinal and/or cutaneous infections particularly recurrent viral, bacterial, fungal and protozoan infections in 5 months infants.
82
SCID manifests early with what?
Persistent and recurrent diarrhea, otitis, thrush and respiratory infections in the first few months of life.
83
T cell defects in SCID is associated with what?
Candidiasis, CMV infection, measles and varicella leading to life threatening pneumonia, meningitis and sepsis.
84
SCID is managed through what?
Managed through Ig infusion, stem cell transplantation and gene replacement.
85
T cell congenital disorders display what?
Little or no cell mediated immunity and may involve B cell deficiencies.
86
Patients with T cell immunodeficiency diseases are particularly susceptible to what?
1- repeated fungal (candida) infection.
2- protozoan and viral infections.
87
Primary T cell immunodeficiencies include what?
1- Di George syndrome.
2- Wiskott - Aldrich syndrome.
3- cartilage hair hypoplasia.
4- Ataxia - Telangiectasia.
5- defective expression of class 2 MHC molecules.
5- defective expression of CD3-T cell receptor (TCR) complex.
88
DiGeorge syndrome congenital disorder characterized by what?
1- lack of embryonic developmental or underdevelopment of the 3rd and 4th pharyngeal pouches.
2- thymic hypolasia, hypothyroidism and congenital heart disease.
3- patients susceptible to uncontrolled opportunistic infections: impaired in cellular mechanisms, profound lymphopenia (T cell <1200 uL).
4- the developmental defect is associated with the deletion in the embryo of a region on chromosome 22.
5- immune defects includes a profound depression of T-cell numbers and absence of T cell responses.
6- B cells are present in normal numbers but affected individuals do not produce antibody in response to immunization with specific antigens.
89
List 4 symptoms of DiGeorge syndrome?
1- congenital heart disorder.
2- undeveloped or no parathyroid glads (which help regulate calcium in the blood) > low levels of calcium > leading to muscle spasm (tetany) within 48 hours after birth.
3- unusual facial features, low set ears, wide-set eyes, cleft palate.
4- missing or underdeveloped thymus gland low number of T cells, limiting their ability to fight many infections.
90
How do we diagnose DiGeorge syndrome?
1- blood tests:
- to determine total number of blood, T and B cells, evaluate how well T cells and the parathyroid glad are functioning, determine how well the body produces Igs in response to vaccines.
2- chest X-ray: to check size of the thymus gland.
3- ECG: heart defects are common with DiGeorge.
4- chromosomal test: to look for abnormalities.
91
List the 3 types of treatment of DiGeorge syndrome?
1- children who have some T cells.
2- Children who have no T cells.
3- when the heart disease is worse than the immunodeficiency (we do surgery to prevent severe heart failure or death).
92
What is the treatment for DiGeorge for children who have some T cells?
Their immune system may function adequately without treatment.
Calcium and vitamin D supplements are given orally to prevent muscle spasms.
93
What is the treatment for DiGeorge for children who have no T cells?
The disorder is fetal unless transplantation of thymus tissue is done.
Stem cell transplantation may be done.
94
What is the inheritance pattern of Ataxia-Telangiectasia?
Hereditary disorder (autosomal recessive)
95
What are the defects in Ataxia-Telangiectasia?
The defects arise from a breakage in chromosome 11 at the site of TCR and Ig heavy chain genes.
Patients have defective mechanisms of DNA repair and are predisposed to leukemia and lymphomas.
96
What is the primary defect in Ataxia-Telangiectasia?
Kinase involved in regulation of the cell cycle.
97
What are the characteristics of Ataxia-Telangiectasia?
Leads to malfunction of B and T cells.
Low levels of IgA and IgE.
IgA is considerably reduced (in 70% of the cases).
Characterized by incoordination (Abnormalities in the cerebellum result in loss of coordination), dilated capillaries, and an immunodeficiency.
98
List 6 symptoms of Ataxia-Telangiectasia?
1- intellectual disability.
2- capillaries in the skin and eyes become dilated and visible between ages of 1 and 6.
3- endocrine system may be affected, results in small testes, infertility, and diabetes.
4- sinus and lung infections.
5- increased risk of cancers (especially leukemia, lymphoma, brain tumors, and stomach cancer).
6- progresses to paralysis, dementia, and death, typically by age 30,
99
How do we diagnose Ataxia-Telangiectasia?
Blood tests to measure the levels of IgA and genetic tests, help confirm the diagnosis.
100
What is the treatment of Ataxia-Telangiectasia?
1- antibiotic and Igs to help prevent infections.
2- these drugs don’t relieve the other problems.
101
What is the inheritance pattern of Wiskott-Aldrich syndrome (WAS)?
X-linked recessive disorder.
102
Wiskott-Aldrich syndrome (WAS) is associated with what?
Thyrombocytopenia and eczema.
103
Patients with WAS have what?
1- elevated IgA and IgE.
2- low IgM.
104
Variable T cell dysfunction of WAS is manifested by what?
1- severe herpex virus and pneumocystis carinii infections.
2- increased lymphomas and autoimmune disease.
3- recurrent pyogenic bacterial infections.
4- usually affecting ears, sinuses and lungs.
105
WAS is characterized by what?
An abnormal antibody (Ig) production, T-cell malfunction, a low platelet count (platelets are small and malformed, the spleen removes and destroys them, causing the platelet count to be low) and eczema.
106
WAS results from which mutation?
A mutation in a gene of the X chromosome, which codes for a protein needed by T and B cells to function.
107
WAS usually affects which gender?
Only boys.
108
What does the defect in WAS involve?
The defect WAS involves a cytoskeletal glycoprotein present in lymphoid cells called “sialophorin (CD43)”. The WAS protein is required for assembly of actin filaments required for the formation of microvesicles and required for B, T and platelet function.
109
List 5 symptoms of WAS?
1- bleeding problems because of low platelet count, usually bloody diarrhea, may be the first symptom.
2- susceptibility to viral and bacterial infections, particularly of the RTI is increased.
3- the risk of developing cancers (such as lymphomas an cancers).
4- risk of autoimmune disorders (such as hemolytic anemia, IBS, and vasculitis).
5- life expectancy is shortened.
110
What is the treatment of WAS?
1- stem cell transplantation, necessary to preserve life. Without it, most die by age 15.
2- antibiotic are given continuously to prevent infections, and Ig is given to provide the missing Abs.
3- an antiviral drug (Acyclovir) is given to prevent viral infections.
4- platelet transfusions are given to relieve bleeding problems.
111
What is the inheritance pattern of chronic granulomatous disease?
X-linked recessive, sometimes also inherited as an autosomal recessive disorder.
112
What happens in chronic granulomatous disease?
Phagocytes malfunction.
They can ingest but cannot produce the substances (such as hydrogen peroxide and superoxide) that kill certain bacteria and fungi.
113
List symptoms of chronic granulomatous disease?
1- chronic infections occur in the skin, lungs, lymph nodes, mouth, nose, urinary tract, and intestines.
2- abscesses can develop around the anus and in the lungs and liver.
3- children may grow slowly.
114
How do we diagnose chronic granulomatous disease?
1- blood tests - measures the activity of phagocytes in response to microorganisms.
2- genetic tests - check for the specific mutations that cause this disorder.
115
What is the treatment for chronic granulomatous disease?
1- antibiotics (trimethoprim/ sulfamethoxazole) given regularly to prevent infections.
2– antifungal (itraconazole) given regularly to prevent fungal infections.
3- interferon gamma, injected 3 times a week, reduce the number and severity of infections.
4- transfusions of granulocytes can be lifesaving.
5- stem cell transplantation has cured some people.
116
What is the inheritance pattern of Chediak-Higashi syndrome?
Very rare autosomal recessive disorder.
117
What is the defect in Chediak-Higashi syndrome?
Patients are more susceptible to infections because phagocytes do no function normally.
The defect is a mutation in a protein (LYST) involved in the regulation of intracellular trafficking.
The mutation impairs the targeting of proteins to secretory lysosomes which makes them unable to lyse bacteria.
118
List symptoms of Chediak-Higashi syndrome?
1- albinism.
2- vision problems: acuity, photosensitivity, nystagmus.
3- infections in the respiratory tract, skin, and membranes lining the mouth.
4- fever, jaundice, an enlarged liver and spleen, swollen lymph nodes, and a tendency to bleed and bruise easily. It can also affect the nervous system.
5- respiratory burst is normal.
119
What is the inheritance pattern in leukocyte adhesion deficiency?
Autosomal recessive disorder.
120
What happens in leukocyte adhesion deficiency?
WBCs don’t function normally.
WBCs are lacking a protein on their surface, so they are less able to travel to sites of infection and to kill and ingest bacteria and other foreign invaders.
121
What is the defect in leukocyte adhesion deficiency?
Cell surface molecules belonging to the intergrin family of proteins function as adhesion molecules are required to facilitate cellular interactions.
Three of these, LFA-1, Mac-1 and gp150/95 (CD11a, b and c, respectively) have a common chain (CD18) and are variably present on different monocytic cells; CD11a is also expressed on B cells.
An immunodeficiency related to to dysfunction is rooted in a defect localized to the common chain and affects expression of all WBC.
122
List symptoms of leukocyte adhesion deficiency?
1- in severely affected infants, infections develop in soft tissues, such as the gums, skin, and muscles. No pus forms. Infections become difficult to control.
2- wounds do not heal well.
3- umbilical cord is slow to fall off, taking 3 weeks or more after birth (normally, it falls off in 1 or 2 weeks after birth).
4- most children with severe disease die by age 5.
