Immunodeficiencies

Question 1

define immunodeficiency

Answer 1

The decreased ability of the body to fight infections and other diseases

when part of the immune system is absent

Question 2

define autoimmunity

Answer 2

When the cause of this deficiency is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents

Question 3

Define primary immunodeficiency disease (PIDD)

Answer 3

when the deficiency is hereditary/genetic

Question 4

primary immunodeficiencies

Answer 4

In the most common primary immunodeficiency diseases, different forms of these cells or proteins are missing or do not function

This creates a pattern of repeated infections, severe infections and/or infections that are unusually hard to cure

These infections may attack the skin, respiratory system, the ears, the brain or spinal cord, or in the urinary or gastrointestinal tracts

Question 5

examples of PIDD in specific organs,glands,cells,tissues

Answer 5

heart defects are present in some PIDDs

Other PIDDs alter facial features, some stunt normal growth and still others are connected to autoimmune disorders such as rheumatoid arthritis

Question 6

T or F: Serious PIDDs typically become apparent in infancy

Answer 6

T

For example, severe T-cell or combined immune deficiencies typically present in infancy

Some may present in older children or adults

in milder forms, it often takes a pattern of recurrent infections before PIDD is suspected

Question 7

important signs that may indicate PIDD:

Answer 7

-Recurrent, unusual or difficult to treat infections
-Poor growth or loss of weight
-Recurrent pneumonia, ear infections or sinusitis
-Multiple courses of antibiotics or IV antibiotics necessary to clear infections (can lead to resistance)
-Recurrent deep abscesses of the organs or skin
-A family history of PIDD
-Swollen lymph glands or an enlarged spleen
-Autoimmune disease

Question 8

Secondary immune deficiency

Answer 8

occurs when the immune system is compromised due to an environmental factor

ex: infection (HIV), medications (chemotherapy or systemic steroids), severe burns or malnutrition

Question 9

examples of treatments for primary immune deficiency

Answer 9

transplantation (bone marrow, stem cell, thymus), immunoglobulin replacement (antibodies to reinforce protection), preventative antibiotics and strategies to manage autoimmune disease

Gene therapy has been successful in specific types of PIDD

quality of life has improved drastically in these diseases

Question 10

What are characteristics of PIDDs?

Answer 10

susceptibility to infections, autoimmunity and inflammation

increased risk of malignancies due to impaired immune homeostasis + surveillance

Question 11

Depending on the nature of the immune defect, the clinical presentation may vary and may include…

Answer 11

recurrence of upper and lower respiratory tract infections, invasive bacterial and/or fungal infections, infections sustained by poorly virulent or opportunistic pathogens (“weak” pathogens)

Question 12

diagnostic approach to PIDD

Answer 12

-a detailed family hx
-clinical history
-physical examination
-appropriate laboratory tests

Question 13

steps 1-5

Answer 13

1: too many infections
2: rule out common causes of infection and secondary immune deficiency
3: consider PIDD
4: categorize patient and order appropriate screening
5: consider referral to immunology specialist and secondary testing

Question 14

Selective IgA deficiency

Answer 14

most common primary immunodeficiency disorder

estimated 1 in 500, many asymptomatic(!!)

(side note: IgA has potent antiviral activity)

Question 15

if symptomatic:

Answer 15

Patients are most susceptible to infections with encapsulated (extra protection) bacteria
-ex. Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitides

Frequent and recurrent sinusitis, otitis (ears), and bronchitis (IgA is found in secretions)

Question 16

diagnosis

Answer 16

Undetectable serum IgA levels (< 7 mg/dL) with normal levels of IgG and IgM

Some patients may have antibodies against IgA

Plasma and blood transfusions can contain IgA and cause anaphylaxis (shock)

Question 17

treatment

Answer 17

Antibiotics as needed for infections

Some cases of IgA deficiency may spontaneously remit

Question 18

Common Variable Immunodeficiency (CVID)

Answer 18

Most common symptomatic PID

Onset is generally in early adulthood

1 in 25,000 in the United States, most cases are sporadic; about 10–20% are familial

Question 19

CVID

Answer 19

-Frequent sinopulmonary infections (affecting the paranasal sinuses and the airway of the lungs)
-Low serum immunoglobulin levels
-Deficient functional antibody responses (vaccines don’t work. V for vaccines and Variable)
-Primary defect may be with B cells or T cells (cannot produce antibodies for a vaccine)
-Heterogeneous immunodeficiency disorder clinically characterized by an increased incidence of recurrent infections, autoimmune phenomena, and neoplastic diseases (lump)

Question 20

How to diagnose CVID

Answer 20

Diagnosis is made in patients who have reduced serum immunoglobulins (IgG, IgM, or IgA) and poor antibody response to vaccines, after exclusion of secondary causes, such as:
-Proteinuria
-Protein-losing enteropathy
-Drug effects (eg, rituximab, antiepileptics)
-Chronic lymphocytic leukemia, lymphoma, and plasma cell myeloma

Question 21

Treatment

Answer 21

Should be treated aggressively (because symptomatic) with antibiotics at the first sign of infection; antibiotic therapy should cover encapsulated bacteria
-As infections may be prolonged or associated with unusual complications such as meningitis or sepsis

Subcutaneous or intravenous immunoglobulin replacement therapy, typically provided every 1–4 weeks, with a typical monthly dose of 300–600 mg/kg
-Adjust dosage or infusion interval on the basis of clinical response and serum IgG levels

Question 22

which drugs are the choice to attack cell walls/encapsulated bacteria

Answer 22

penicillin and amoxicillin “all day”

Question 23

Specific (functional) Antibody Deficiency

Answer 23

Characterized by decreased or absent IgG(!) antibody response to vaccines
-In the setting of normal or mildly decreased serum immunoglobulin levels

Can range from mild symptoms managed with antibiotics and vaccination to more rarely to recurrent infections with features very similar to CVID

Question 24

side note:

Answer 24

small nuggets of difference between many of these

Question 25

Immunoglobulin Subclass Deficiency

Answer 25

Incidentally found in 2% of the population
There are four subclasses of IgG:
IgG1: able to fix and activate complement (complement won’t work as well)
IgG2: important in the defense against encapsulated bacteria
IgG3: able to fix and activate complement
IgG4 (nothing in particular, just test low)

Question 26

Severe Combined ID (SCID)

Answer 26

Includes a heterogeneous group of genetic disorders that are characterized by a severe impairment of T-LYMPHOCYTE development and function

disorder can be anywhere along a complex pathway to the creation of T-lymphocytes

Question 27

classification of SCID:

Answer 27

Depending on whether the development of B and/or NK lymphocytes is also affected, SCID can be classified into four distinct immunologic phenotypes:
T–B+NK– (the most common variant)
T–B+NK+
T–B–NK+
T–B–NK–

Question 28

HSCT

Answer 28

Without treatment by allogeneic hematopoietic stem-cell transplantation, SCID is inevitably fatal

Question 29

Secondary (acquired) Immunodeficiencies

Answer 29

result from various immunosuppressive agents:
-Malnutrition
-Aging
-Environmental toxins like mercury and other heavy metals
-Pesticides
-infections (HIV, Sepsis)
-chemotherapy
-immunosuppressive drugs after organ transplants
-anti-psychotic meds
-glucocorticoids

Question 30

therapy of secondary hypogammaglobulinemia:

Answer 30

treatment of underlying condition or removal of offending medication

(gamma globulins are immunoglobulins)

Question 31

HIV

Answer 31

AIDS pandemic mainly caused by HIV-1 M

Question 32

HIV

Answer 32

An RNA virus with the high-affinity to the host cell surface, the CD4 molecule(CD4 says: “hey, I’ll open the door 4 ya”!!)

Found predominantly on a subset of T lymphocytes that are responsible for helper function in the immune system

The virus then mutates the T lymphocyte DNA to continually produce more HIV virus

Question 33

Diagnosis of HIV

Answer 33

depends on presence of antibodies to HIV or direct detection of HIV/components of HIV

antibodies appear 3-12 weeks following infection

Question 34

Screening for HIV

Answer 34

Commonly use ELISA (enzyme immunoassay [EIA]) the appropriate test for HIV (!!!!!!)

The Western blot assay allows for detection of antibodies to specific HIV antigens of known weight (to be used for confirmation of diagnosis!!!!)

(ELISA aka EIA: tests designed to detect antigens or antibodies by producing an enzyme triggered color change. ELISA is quicker and cheaper than western blot but is subject to error, so should always be step 1)

Question 35

What if EIA is negative?

Answer 35

the diagnosis is ruled out and retesting should be performed only if there is a high suspicion

Question 36

What if EIA is indeterminate or +?

Answer 36

Repeat the test!

If repeat is indeterminate or positive, one should proceed to the HIV-1 western blot
-If the western blot is positive, the diagnosis is HIV-1 infection
-If the western blot is negative, the diagnosis of HIV-1 infection is ruled out

Question 37

Laboratory Monitoring of HIV

Answer 37

The CD4+ T cell count is the laboratory test generally accepted as the best indicator of the immediate state of immunologic competence of the patient with HIV infection

Measures the amount of CD4+ T lymphocytes that are still unaffected by the HIV virus and are functional

Question 38

Ex: ELISA test is positive, what’s the next best step?

Answer 38

Another ELISA (and if it’s also positive…)

THEN western blot (which is very accurate, if - then they don’t have it DESPITE the first two + ELISA’s)

Question 39

Classification of HIV stages:

Answer 39

-0 (negative test in first 6 months after diagnosis following an early + diagnosis)
-1 (determined by CD4+ T lymphocyte level and immunologic criteria)
-2 (determined by CD4+ T lymphocyte level and immunologic criteria)
-3 (opportunistic infection present)
-Unknown

-classification system based on clinical conditions and CD4+ T cell count
-Question on this would more likely be about what constitutes a 0 or 3, since 1 and 2 are memorization/lab work

Question 40

Cutoff for AIDS in laboratory results

Answer 40

<200/μL CD4+ T cell count considered AIDS, any higher is HIV

Question 41

HIV prophylaxis

Answer 41

Education, counseling, and behavior modification (stigma) are the cornerstones of any HIV prevention strategy

A major problem is that many infections are passed on by those who do not know that they are infected

“Safer sex”: monogamy and/or condom use
“Safer injectable drug use”: needle exchange programs

Question 42

HIV prophylaxis cont.

Answer 42

Pre-exposure prophylaxis (PrEP) using oral antiretroviral drugs such as Truvada & Descovy (tenofovir + emtricitabine) a single daily pill in uninfected men who have sex with men and transgender women is highly efficacious in preventing acquisition of HIV infection

The degree of efficacy can be >95% if subjects adhere strictly to the regimen

side effects?

Question 43

Post-exposure HIV prophylaxis

Answer 43

Post-exposure prophylaxis (PEP) means taking medicine to prevent HIV after a possible exposure

PEP should be used only in emergency situations and must be started within 72 hours after a recent possible exposure to HIV (3 or more antiretroviral drugs taken for 4 weeks)

After an exposure, the wound should be cleansed immediately, and antiseptic applied, follow up 4-6 months later