Immunodeficiencies Flashcards
(105 cards)
1
Q
What are the differences between primary and secondary immunodeficiencies?
A
Primary are genetic diseases that cause immunodeficienies
Secondary are usually caused my something else like malnutrition, renal disease, transplants, diabetes etc. mostly preventable
2
Q
Main cells that function in innate immunity?
4
A
- complements
- macrophages
- neutrophils
- NK cells
3
Q
Main cells that funciton in acquired immunity?
4
A
B cells
Helper T cells
Antibodies (made by plasma/effector cells)
Cytotoxic T cells
4
Q
What is the predominant feature of impaired immune function?
A
infection
5
Q
What specifically about infections lead us to believe there is an immune impairment?
3
A
More severe and persist longer
Frequent recurrences
Not responsive to ordinarily effective Rx
6
Q
What is the nomral amount of respiratory tract infections per year for normal healthy kids?
A
4-8
7
Q
In primary care what are we mostly prescribing for patients with immunodeficiency disorders?
What dont we give?
A
prohylactic treatment
NO LIVE VIRUSE Vaccines
8
Q
What are the live virus vaccines?
5
A
rotavirus, varicella, MMR, intranasal influenza, and oral polio
9
Q
If we have to give a patient with an immunodeficiency a blood transfusion what kind of blood should we give them?3
A
irradiated, leukocyte poor, virus free product
10
Q
What kind of labs would we test for immunodeficiency disorder?
5
A
Complete Blood Count (cbc) with peripheral smear Lymphocyte immunophenotyping B and T cell types Quantitative Immunoglobulins IgA, IgG, IgM Antibody Titers Protein Electrophoresis Serum Protein (SPEP)
- CBC with smear
- Lymphocyte typing
- Igās
- Antibody titer
- SPEP (protein)
11
Q
What is XLA/Brutonās characterized by?
3
A
- Humoral immunodeficiency
- Severe hypogammaglobulinemia(low antibodies/ all kinds are low)
- Increased susceptibility to infection
12
Q
What demographic is XLA/Brutons found in most often?
A
Mostly young boys
Females are carriers
13
Q
What cell is virtually missing in XLA/Brutons?
A
B cells
14
Q
What response is normal in XLA?
A
Normal cell mediated T cell response
15
Q
Common infections in XLA?
3
A
otitis media, sinusitis, and pneumonia (caused by Strep pneumonia and H. Flu)
16
Q
When do symptoms start in a child who has XLA?
A
6 months, when the mother stops breast feeding and baby isnt recieving her antibodies anymore
17
Q
What may XLA babies be missing?
A
Tonsils and cervical lymph nodes
18
Q
Warning signs: How many infections of... UTIs? Serious sinus infections? Pneumonia? Skin infections?
A
- 4
- 2
- 2
- 2
19
Q
What are the treatment options for XLA?
And in what ways can we accomplish that? 2
A
Replacement of immunoglobulin is the cornerstone of treatment of XLA.
- IV immunoglobin
- Subcutaneous injected Ig
20
Q
What is Selective IgA Immunoglobulin Deficiency?
A
Decrease in serum levels of IgA (no other Igs are affected)
no other immunodeficiency disorders either
21
Q
When can we make the diagnosis for Selective IgA Immunoglobulin Deficiency and why?
A
After 4 because antibody levels in younger children can be depressed normally
22
Q
Whats the most common immunodeficiency in adults?
A
Selective IgA Immunoglobulin Deficiency
23
Q
What is the pathology of Selective IgA Immunoglobulin Deficiency?
A
Defect in ability of B cells to terminally differentiate and mature into IgA secreting plasma cells
24
Q
What infections would you find whit an IgA deficiency?
A
Sinus infections
Pulmonary infections
Intesines
Skin..?
Anywhere there are things being secreted
25
What is the clinical presentation of Selective IgA Immunoglobulin Deficiency?
4 common infections
Not much. Usually found incidentally
Usually an increased incidence of recurrent
1. sinopulmonary infections
2. GI tract infections
3. Conjunctiva
4. Respiratory tract infections
26
Besides infections what else increases in risk in Selective IgA Immunoglobulin Deficiency?
3
1. Allergies
2. Asthma
3. Autoimmune diseases
27
Treatment for Selective IgA Immunoglobulin Deficiency?
| 2
1. Avoid giving meds that lower IgA levels such as penecillamine and valproate
2. Antibiotics for infections and sometimes prophylactic antibiotics if its a severe case
28
What should we avoid in patients with Selective IgA Immunoglobulin Deficiency?
Should not be transfused
Should not be treated with gamma globulin
---Anaphylactic Hypersensitivity may occur
--body wont recognize the IgA since there is such low levels and will create an antibody for it
29
What is Common Variable Immunodeficiency?
| 2
(CVID) is impaired B cell differentiation with defective immunoglobulin production
1. Don't differentiate into plasma/effector cells and helper cells
2. Thus they dont made antibodies. Effector cells doesnt know its an effector cell
30
What is CVID defined by?
| 3
1. Very low serum concentrations of IgG (and usually in combination of IgA and IgM)
2. Little or no response to immunizations
3. No other immunodeficiency disorders
31
CVID is not a single disease, its a collection of hypoimmunoglobulin syndromes resulting in many genetic defects
Usually presents between 20-40s
32
What is the pathology behind CVID?
Normal numbers of B lymphocytes but they remain immature. They can still bind to antigens and respond with proliferation but they wont become mature plasma cells or mature memory B cells ever
33
What is the clinical presentation of CVID?
Recurrent infections:
Sinopulmonary such as...
---sinusitis, otitis, bronchitis, pneumonia, TB and fungal infections
34
What is the main cause of death in CVID?
respiratory failure
35
What other things can CVID lead to besdies infections?
| 3
Autoimmunity
Inflammatory disorders
Malignant disease
```
(chronic lung disease
gastrointestinal and liver disorders
granulomatous infiltrations of several organs
lymphoid hyperplasia
splenomegaly
malignancy)
```
36
Describe the time between onset of symptoms and diagnosis of CVID?
CVID affects so many organ systems so its often not clearcut. Usually have been evaluated by a lot of specialists before they are diagnosed. 5-7 years before they know
37
With what symptoms specifically should we consider CVID?
| 3
adults with:
1. Chronic pulmonary infections (widening of the bronchi)
2. Chronic intestinal diseases (infections and malabsorption in the GI tract)
3. Lymphoid malgnancy
38
How would we treat CVID?
| 3
1. IV or Sub-Q Igs (premedicate)
2. Antibiotics (can use to premedicate or at very early signs of infection)
3. Wait until they are a little older to immunize them but make sure you do it!
39
XLA specific deficiency?
| 2
Absence of B cells; very low Ig levels
40
XLA molecular defect?
Mutant tyrosine kinase
41
XLA clinical features?
Pyogenic infections
42
Selective IgA specific deficiency?
Very low IgA levels
43
Selective IgA molecular defect?
Failure of heavy-chain gene switching
44
Selective IgA clinical features?
Sinus and lung infections
45
CVID specific deficiency?
Very low IgG
| And/Or IgA, IgM levels
46
CVID molecular defect?
A combination of immunodeficiency issues
47
CVID clinical features?
Sinus and lung infections
48
What are the functions of T cells?
| 4
1. Control viral disease
2. Control fungal disease
3. Monitor/control development of dysplastic (abnormal development) cellular changes
4. Provide helper function to B cells for effective humoral response
49
What is Thymic aplasia (DiGeorge's syndrome) ?
Defective development of the pharyngeal pouch system
| - No development of thymus, thyroid and parathyroid
50
What does the pharyngeal pouch system give rise to?
1 main thing to remember involving immune system
1. thymus,
2. thyroid,
3. parathyroids,
4. maxilla, mandible, aortic arch, cardiac outflow tract, and external/middle ear
51
What are most cases of hymic aplasia (DiGeorge's syndrome) caused by?
Heterzygous chromosomal deletion at 22
52
What does the absense of the development of thymus, thyroid and parathyroid cause?
tetany
| Can also cause palate defects
53
What kind of infections will we see with thymic aplasia?
Severe viral, fungal, and protozoal infections
54
When does thymic aplasia arise?
early in life/infants
55
Two common infections in tymic aplasia?
Pneumonia by P. jirovecii
| Thrush by C. albicans
56
What is the clinical presentation at birth of thymic aplasia?
3
1. Cardiac abnormalites &
2. hypocalcemia w/ possible tetany
3. Facial abnormalities
57
If patients with thymic aplasia survive how would you describe their immune system?
Can have a normal humoral immune system but profound T cell absense and reduced CD4 T cells
58
What other symptoms can present with thymic aplasia?
| 4
Esophogeal dysmotility
GU tract anomalies
GI anomalies
Autoimmune disease
59
How do we manage thymic aplasia?
| 4
1. Immediately treat cardiac abnormalities if there
2. Control hypercalcemia(other metabolic abnormalities)
3. Give only irradiated blood (helps prevent rejection/death)
4. Can do a thymus transplant
60
What is Severe combined immunodeficiency (SCID)?
SCID is a group of inherited diseases caused by mutations in different genes whose products are crucial for the development and function of both T and B cells
61
When are combined immunodeficiencies considered severe?
When they lead to death in the first year due to overwhelming infection
62
What is the pathology behind SCID?
| 3
1. Absense of thymic tissue and other lymph tissue (no lymphocytes)
2. Ig levels are very low
3. Tonsils and lymph nodes are absent
63
Describe B and T cell function in SCID?
| 2
1. Both are defective and sometimes completely absent in children
OR
2. The number of cells are normal but they dont function properly
64
What are the two main types of SCID and What is the most common?
X-linked
-constitutes about 75% of cases
Autosomal
-25% of cases
65
What are the characteristics of X linked SCID?
| 2
1. Normal B cells and greatly reduced T cells
| 2. Low levels of IgG and IgA, can make IgM (still usually fatal)
66
Characteristics of Autosomal SCID?
could be multiple mutations that affect B and T cells
67
Clinical presentation of SCID?
Failure to thrive (die within 1-2 years, usually pneumonia)
68
What is the best way to manage SCID?
| 2
1. Isolation is really the only way
| 2. Live attenuated viral vaccines CANNOT be given
69
Possible treatments for SCID?
| 3
1. Bone marrow or cord transplant could restore immunity (have to do in three first months of life to have high success)
2. IV Ig
3. Enzyme replacement therapy
70
What are Wiskott-Aldrich and
| Ataxia-Telangiectasia?
immunodeficiency diseases
71
Specific deficiency of Severe combined immunodef-iciency (SCID) ?
Deficiency of both
| B-cell and T-cell function
72
Molecular defect of SCID?
| 4
1. Either defective IL-2 receptor,
2. defective recombinases,
3. defective kinases,
4. absence of MHC proteins
73
What is the specific deficiency of Wiskott-Aldrich?
IgM and cellular immunity impaired X-linked disease and thus occurs only in males
74
What is the molecular defect in Wiskott-Aldrich?
X-linked disease and thus occurs only in males
75
What is the clinical features of Wiskott-Aldrich?
Recurrent pyogenic infections, eczema, and bleeding
76
What is the specific deficiency in Ataxia-telangiectasia?
Lymphopenia and IgA deficiency
77
What is teh molecular defect in Ataxia-telangiectasia?
Autosomal recessive disease
78
What is the clinical features of Ataxia-telangiectasia?
Recurrent infections appear by 2 years of age
79
What is hereditary angioedema?
A complement-associated immunodeficiency disease that is autosomal dominant and lacks C1 inhibitor. Without this inhibitor, capillary permeability occurs and edema.
80
Where is the swelling most often seen in hereditary angioedema?
4
```
Happens in episodes of the:
hands
feet
face
AIRWAY PASSAGES!
```
81
What is the clincal presentation of hereditary angioedema?
| 3
- Episodes of swelling lasting 24-72 hours
- non-itching
- increase risk of other autoimmune disease
82
How would we manage hereditary angioedema?
| 4
1. IMMEDIATE ASSESSMENT OF THE AIRWAY
2. First line therapy: human plasma-derived C1 inhibitor.
3. Icatibant
4. Ecallantide
83
Molecular defect of hereditary angioedema?
Too much Cā3a, Cv4a, and Cā5a generated
84
Secondary immunodecificiencies?
| 7
```
Malnutrition
Infection
Cancer
Renal disease
Sarcoidosis
Transplantation recipients
Diabetes Mellitus
```
85
What is the most common cause of immunodeficiency world wide?
Malnutrition
86
What does Protein Energy Malnutrition (PEM) associate with to cause immunodeficiencies?
5
1. Impairment of cell-mediated immunity
2. Phagocyte function
3. Complement system
4. Secretory immunoglobulin A antibody concentrations
5. Cytokine production
87
What does vitamin A deficiency causes in the immune system?
| 3
1. Deficiency interferes with epithelial cells function
2. Ability of certain immune cells to kill organisms and
3. production of B-cells and T-cells are dependent on VA
88
What does vitamin C deficiency cause in the immune system?
| 3
1. Decrease in collagen synthesis
2. Phagocyte oxidative burst activity impaired
3. Inability of B-cells and T-cells to work properly
89
What does vtamin B12 deficiency cause in the immune system?
| 2
Lowers T-cell counts and lower natural killer cell activity
90
What does vitamine B6 deficiency cause in the immune system?
| 2
Decreased T-cell responsiveness and natural killer cells ability to kill organisms
91
How does malnutrition affect the number of circulating T cells and NK cells?
declines T cells
| INcreases NK cells
92
How are serum immunoglobin levels and specific antibody response affected in malnutrition?
Serum immunoglobulin is normal or increased; however, specific antibody responses are impaired.
93
How are lymphoid organs affected in malnutrition?
Primary and secondary lymphoid organs are depleted of cells,
94
Bacteria strategies against acquired immunity?
| 4
1. Molecular mimicry
2. Suppression of antibodies
3. Hiding inside cells- dont present to the antigen. hide wtihin the body until they have produced a higher number to fight
4. Releasing antigen into bloodstream- renders antibody unable to attack the cell
95
Bacteria strategies against phagocytes?
| 4
1. Inhibit chemotaxis
2. Inhibiting phagocytosis- produce toxins that inhibit it- staff
3. Killing the phagocyte
4. Colonising the phagocyte
96
What does HIV attack?3
CD4 lymphocytes, macrophages, dendritic cells
97
What does measles do and what is the result?
Attacks T cells and dendritic cells directly
| -Causes low T cell count and low antibody production
98
Immunological abnormalitites that are associated with cancer (either from the cancer itself or from the chemo) 3
Chronic Lymphocytic Leukemia
Multiple myeloma
solid tumors
99
What does chronic lymphocytic leukemia do?2
1. hypogammaglobulinemia 60%
| 2. decrease complement activity
100
What happens in multiple myeloma?
| 3
CD4 cells decrease
Deficits in complement function
deficits in neutrophil function
101
What happens when solid tumors affect the immune funtion?
| 3
1. decrease function of normal lymphocytes
2. increase suppressor lymph activity
3. decrease T cell lymphocytes
102
Why would renal disease affect immune function?
decrease in protein = decrease in immunoglobulins
103
How does dialysis affect the immune system?
| 3
reduced t cell fucntion
reduced neutrophil function
dimished antobody production
104
renal patients are often on glucocorticoids. how do these affect the immune system?
2
supress phagocytes
| decrease circulating T cells
105
What is sarcoidosis characterized by?
3
How does it affect immune cells?4
by accumulation of T lymphocytes, mononuclear phagocytes and pulmonary granulomas
1. decreased CD4+ T cells
2. Hypergammaglobulinemia - B cell hyperactivity
3. Decreased CD4+/CD8+ T cell ratio
4. Sarcoid granulomas made up primarily of CD4+ T cells
