Immunodeficiency - Dr. Carpenter Flashcards by Brent Smith II

Primary Immunodeficiency: Defects in Lymphocyte Maturation (3 examples)

SCID, X-linked agammaglobulinemia, DiGeorge Syndrome

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Primary Immunodeficiency: Defects in Lymphocyte Activation and Function (3 examples)

X-linked hyper-IgM syndrome, Common variable immunodeficiency, Bare lymphocyte syndrome

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Primary Immunodeficiency: Defects in Innate Immunity (4 examples)

CGD, Leukocyte Adhesion Deficiency, complement deficiencies (SLE), Chediak-Higashi Syndrome

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Primary Immunodeficiency: Lymphocyte abnormalities associated with other diseases (2 examples)

Wiskott-Aldrich Syndrome, Ataxia-telangiectawsia

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Pyogenic bacterial infections, enteric bacterial and viral infections are common consequences of …

B-cell deficiencies (pyogenic bacterial infections and viral infections are common in compliment deficiencies too)

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Absent or reduced follicles and germinal centers in lymphoid organs are histopathological and laboratory findings in …

B-cell deficiencies

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Reduced DTH reactions to common antigens is a histopathological and laboratory finding in …

T-cell deficiencies

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T-cell deficiencies are seen in what area of lymph tissue?

paracortical

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Viral-associated malignancies are common consequences in …

T-cell deficiencies

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Viral and intracellular microbial infections (ex. pneumocystits jiroveci, fungi, atypical mycobacteria) are common consequences seen in …

T-cell deficiencies

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Cell type most important in pyogenic infections (encapsulated bugs for example)

B- Cells

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Cell mediated immunity / T- cell immunity is important in malignancy. True or false?

True

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Name three consequences of all types of immunodeficiencies:

1) Increased susceptibility to newly acquired infections
2) Reactivation of latent infections (CMV, EBV, TB)
3) Increased incidences of cancer

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Severe (hospital status), persistent, unusual, recurrent infections would make a good doctors suspect…

Immunodeficiency (haha i made this notecard just to piss off Jacob)

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Congenital primary immunodeficiencies are caused by a genetic defect that leads to block in maturation. Incidence is 1:500. The inheritance pattern can be AR but usually it is…

X-linked (ex: SCID)

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X- linked SCID functional deficiencies

Decreased: T-cells and serum IG

B cell: wnl (aka be cells are normal aka gucci AF)

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Most common form of SCID accounting for 50-60% of all cases?

X- linked SCID

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X- linked SCID mechanism of defect

Mutation/ missing common gamma chain receptor for cytokine: decreased T-cell maturation; No IL-7

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IL-7 is responsible for

development and maturation of pro-T-cells

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IL-15 is responsible for

Development of NK cells

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Low levels of IL-15 due to gamma chain mutation in cytokine receptor in X-linked SCID can result in what?

Decreased NK cells

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One rare but for some reason important type of Autosomal Recessive (AR) SCID to…

missing JAK3

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The most common AR SCID is due to …

ADA deficiency

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Function deficiencies caused by AR SCID ADA deficiency are:

Decreased: T-cells, Serum IG AND B-cells

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Deficiency in ADA enzymes causes accumulation of what toxic products/metabolites that affects DNA synthesis in proliferating cells? Lymphocytes are also very sensitive to these toxins.

dATP

Deficiency in PNP enzymes causes accumulation of what toxic products/metabolites that affects DNA synthesis in proliferating cells? Lymphocytes are also very sensitive to these toxins.

dGTP

AR SCID due to PNP deficiency causes what function defects?

Decreased T-cells ONLY

Ideal method for SCID treatment is

Stem Cell transplant (however must have compatible donor) Side note for curious Jacob...less ideal but still viable would be gene therapy (insert gene = correct defect) but this has only really been successful in ADA type treatment

There has been concern about using viral vectors in gene therapy treatment b/c of the development of T-cell Leukemia in some patients with X-linked SCID patients. What is used now instead?

Lentivirus

Disease with X-linked B-cell maturation defect?

XLA (Bruton's X-linked Agammaglobulinemia)

XLA is diagnosed at 5-6 months of age (later than SCID). This is because...

Maternal IgG protects baby for first 6 months of life. Unlike SCID, only B-cells are affected in XLA not T-cells.

Recurrent otitis media (note: not that uncommon in "normal" people too), PNEUMONIA (recurrent infections rare in normal healthy kid), and sinusitis (often chronic) are indicators of ...

XLA

infectious agents that are most common in XLA patients are:

S.pneumonia or H.Flu (type b)

You will NOT see CD19 positive B cells in peripheral blood in what disorder?

XLA

You will see decreased serum IG, absence of plasma cells, increased autoimmune diseases, and underdeveloped germinal centers in LN, Peyer's patches, appendix, and tonsils in patients with....

XLA

True or False? In XLA T-cell reactions are within normal limit.

True. They are not fucked up at all. Remember this is a B-cell issue.

CD19 is a marker for?

Mature B-cells

DiGeorge Syndrome results from?

dysmorphogenesis of 3rd and 4th pharyngeal pouches

3rd and 4th pharyngeal pouches give rise to what?

- thymus and parathyroid (at 6-8 weeks) | - aortic arch and portions of lip and ears (at 12 weeks)

Name so diagnostic features of DiGeorge Syndrome

- Neonatal tetany - absent thymic shadow - decreased number of T-cells - decreased to absent antibody response (remember T-cells are needed for B-cells to function properly) - LN depletion of paracortical areas

Just a random thing to know for DiGeorge

Note: thymic tissue, if found (fat chance), does contain Hassals corpuscles, normal density of thymocytes and corticomedullary distinction.

DiGeorge Syndrome has a unique deletion found in 90% of diagnosed. The deleted region is responsible for development of brachial arch and great vessels. What is this deletion.

22q11 (spectrum of disorders resulting from small deletion of band q11.2 on long arm of chromosome 22)

Name the primary immunodeficiency associated with defects in lymphocyte activation that is characterized by: Mutation in CD40 Ligand on X chromosome resulting in the absence of CD40L on CD4+ T-cells.

X-linked hyper IgM syndrome

Lack of class switching and elevated IgM levels is associated with what syndrome?

``` X-linked hyper IgM syndrome Note: CD40L on T-cells cant bind to B-cells to induce class switching ```

X-linked hyper IgM syndrome can cause defects in CMI (DTH) leaving patient fucked/susceptible to what intracellular microbe?

pneumocystis jiroveci

Most common primary immunodeficiency?

Selective IgA defciency

Why can't you shoot up marijuana?

Because you will get a budclot

Lil' Timmy is for the most part asymptomatic, however recently he has had recurrent sinopulmonary infections and diarrhea. Upon a fullwork you notice his he has low serum IgA but normal levels of the other isotypes. What the hell is wrong with Lil' Timmy?

He has SELECTIVE IgA DEFICIENCY

Brent Smith just found out he has Common Variable Immunodeficiency. He is sad and his blood has low serum levels of what?

- IgA and IgG (both low) | - IgM is normal to low

Characterized by failure in maturation of B-cells into plasma cells.

Common Variable Immunodeficiency

Major associated problems with ________ are respiratory and gastrointestinal infections with pyogenic bacteria. _______ also has highly variable presentations and pathogenesis.

Common Variable Immunodeficiency

Mature B cells but absent plasma cells =

Common Variable Immunodeficiency

Clinical Triad WISKOTT-ALDRICH SYNDROME (X-linked multisystem syndrome)

-lowered platelet count (thrombocytopenia) -eczema/skin rashes -recurrent bacterial infections (can't respond to bacterial polysaccharides) Note: jacob did you know that recently this has been treated with gene therapy?

Wiskott-Aldrich Syndrome can also have low Ig__?

IgM

Ataxia Telangiectasia: This disease is not primarily an immunodeficiency. True or False?

True

Patient has low levels of IgA and IgG w/ a reduction in T-cells. Also patient has inability to respond to skin tests. What the hell is wrong?

Ataxia Telangiectasia

What is the multisystem disorder responsible for the following symptoms: Neurologic: staggering gate Vascular: abnormal dilation Immunogenic: Affects both B and T-cells

Ataxia Telangiectasia

Defects in innate immunity are characterized by what ?

-recurrent intracellular bacterial and fungal infections

An innate immunity defect characterized by defects in selectin ligand / beta chain of integrin

LAD (leukocyte adhesion deficiency)

Bacterial infections w/ out pus formation and limited recruitment of cells to site of inflammation (ex: during a pyogenic infection) is seen in ...

LAD

A protein trafficking defect (autosomal recessive) characterized by impaired phagolysosome formation and giant granules in leukocytes (due to fusion of granules arising from Golgi).

Chediak-Higashi syndrome

Patient presents with T-cell deficiency (lack of thymus); hypocalcemia (lack of parathyroid) and abnormalities of heart, great vessels, and face. What the hell is wrong?

DiGeorge Syndrome

A primary autoimmune deficiency characterized by complete lack of immunoglobulin due to disordered B-cell maturation. Pre- and Pro- B-cells can not mature. What the hell is wrong?

XLA -note: jacob...dont give these kids live vaccines.

Mutation is WASP gene; X-linked

Wiskcott-Aldrich

Phagocytes from patients have giant cytoplasmic granules; granules are dysfunctional. Phagocytes do not have ability to kill bacteria. Name the syndrome.

Chediak-Higashi Syndrome

Chronic Granulomatous Disease (CGD)

- Defective production of reactive oxygen intermediates (lack NADPH oxidase 02-->surpaoxide) - Intracellular survival of microbes results in granuloma formation

Nitroblue tetrazolium test (NBT) measures oxidative burst and is used in diagnosing what disease?

CGD

NBT dye turns blue if.... | NBT dye remains yellow/ colorless if...

``` blue= NADPH normal colorless= NADPH absent (CGD) ```

C5-C9 compliment deficiencies are at risk for ...

Neisseria Infection (N gonorrhoeae and N meningitidis)

C2 and C4 compliment deficiencies are at risk for ...

- increased incidence of immune complex diseases (resembling SLE) - Rheumatoid issues

C1 and C3 deficiencies are at higher risk for...

infections with encapsulated organisms

Compliment regulation defect example is

Hereditary angioedema

Hereditary angioedema cause?

Deficiency if C1 inhibitor. Results in excessive C4 and C2 activation. Leads to localized edema / swelling (linked to increased levels C2 kinin-->swelling)

Deficiency in DAF (Decay Accelerating Factor), host cells not protected from activation of compliment, characterized by intravascular hemolysis (hemolytic anemia) at night.

Paraoxsymal Nocturnal Hemoglubulinemia

Secondary or Acquired immunodeficiencies are not genetic but rather they are acquired during life. An example is...

AIDs

Acquired Immunodeficiencies linked to immunosuppression from another disease process include: name 3

- protein calorie malnutrition - advanced widespread cancer - certain parasitic and viral infections (ex measles virus can infect lymphocytes)

Herpes virus can secrete proteins similar to

IL-10

Trypansoma cruzi is associated with reduced expression of ____ receptors on T-cell and thus can cause an acquired/ secondary immunodeficiency.

IL-2

Secondary Immunodeficiencies linked to complications of therapy include:

- drugs that kill or inactivate lymphocytes (anti-inflammatory and immunosuppressive drugs) - absence/surgical removal of spleen (decreased phagocytosis of microbes and increased susceptibility to encapsulated microbes.

A self limited disorder characterized by a prolongation of physiologic hypogammaglobulinemia (usually prolonged to 9-15 months of age but may take 2-4 years to become normal)

Transient Hypogammaglobulinemia of Infancy (THI)

Maternal derived IgG declines after birth and disappears by 3-6 months. At this time infant's production of IgG is not fully developed. The neonate depends significantly on _______ immunity.

innate

Maternal derived IgG declines after birth and disappears by 3-6 months. At this time infant's production of IgG is not fully developed. Overall function of neonate immune system is reduced. Development of Th1 and CD8+ T-cells also delayed. Baby is most susceptible to infection during 6 mo to one year. Name the term.

Physiologic Hypogammaglobulinemia

Immunosenescense

refers to the changes in immunity with increasing age

Features of immunosenescense: (GULI)

- Greater propensity for autoimmune response - Unsustained memory response - Lingering low grade inflammation - Impaired ability to respond to new antigens

Clinical Consequences of immunosenescense:

Cancer, increased infections, and autoimmune diesease

Prevention or compensation for age-related immunological defects are needed for healthy aging. True or false?

True

Brent's sister is hotter than Jacob's mom. True or False.

im into bleached buttholes... I have to give the edge to brents sister...but both are solid first round draft picks.