Exam #3: Immunodeficiency II Flashcards Preview

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Flashcards in Exam #3: Immunodeficiency II Deck (63):

What is Hyper IgM Syndrome?

This is a condition characterized by normal to elevated levels of IgM, BUT an absence of IgG, IgA & IgE isotypes


What causes Hyper IgM Sydrome?

- Failure of helper T cells to induce B-cell isotype switching from IgM to IgG, IgA, & IgE
- Failure to activate macrophages to remove intracellular microbes


What is the genetic basis of Hyper IgM Syndrome?

- X-Linked mutation for CD40L (on T-cells)
- Autosomal recessive mutation for CD40 or "activation induced demainase," an enzyme required for isotype class switching


What are the defects/ manifestations caused by Hyper IgM Syndrome?

- Lack of opsonization leads to recurrent infection
- IgM reactions against blood cells can cause hemolytic anemia
- Susceptibility to pneumocystis jiroveci


What is DiGeorge Sydrome?

Partial or complete disruption of the 3rd & 4th pharyngeal pouch development leading to aplasia or hypoplasia of the thymus/ parathyroid


What are the features of DiGeorge Syndrome?

- T-cell defect
- Hypocalcemia
- Cardiac abnormalities
- Cleft Palate


What is the genetic basis of Di George Syndrome?

22q11 deletion


What are the clinical manifestations of Di George Sydrome?

- Difficulty clearing VIRAL & FUNGAL infections
- Facial defects
- Cardiac defects


What are the facial defects seen in Di George Syndrome?

- Low set ears
- Midline clefts
- Small mandible


What are the cardiac defects seen in Di George Syndrome?

- Right subclavian artery derived from pulmonary artery


What is the difference between Di George Syndrome with hypoplasia vs. aplasia of the thymus?

Hypoplasia= immune defect resolves by age 5
Aplaisa= requires transplantation of fetal thymus


What is SCID?

Severe Combined Immunodeficiency, a constellation of different syndromes that all share common defects in humoral and cell-mediated immunity


What are the two genetic mutations that result in SCID?

- X-Linked
- Autosomal Recessive


What is the mutation in the x-linked form of SCID? What are the consequences?

Mutation of common gamma chain subunit of cytokine receptors that impair the ability for lymphocytes to develop & function


What is the autosomal form of SCID?

This is the form of SCID that is caused by adenosine deaminase deficiency; this enzyme breaksdown metabolites that are toxic to lymphocytes
- Deoxyadenosine
- Deoxy-ATP


What are the clinical features of SCID?

- Early onset thrush, diaper rash, failure to thrive
- Recurrent infections of all types


What is the treatment for SCID?

- Bone marrow transplant
- Gene therapy for ADA


What is Wiskott-Aldrich Syndrome? What are the characteristics of Wiskott-Aldrich Syndrome?

This is an X-linked disorder in male infants characterized by:
1) Thrombocytopenia
2) Eczema
3) Immunodeficiency


What is the genetic basis for Wiskott-Aldrich Syndrome?

- X-linked disorder in male infants
- Defect disrupts the ability to maintain cytoskeletal linkage of membrane receptors--> progressive depletion of T & B cells


What are the lab markers for WAS?

- Low IgM
- Normal IgG
- Elevated IgA & IgE
- No response to polysaccharide antigens
- Poor response to protein antigens
- Depletion of T-cells in the blood & nodal tissue


What are the clinical manifestations of WAS?

- Hemorrhagic diathesis
- Recurrent respiratory infections
- Pyogenic bacteria, viruses, fungi
- Early death w/out bone marrow transplant
- Increased lymphoid malignancies in survivors past 10


What is the link between immunodeficiency & autoimmunity?

1) Defects in T-cells also include defects in T-regulatory cells
2) Persistent activation increases the likelihood of aberrant T-cell activation, altered immune response, & generation of auto-reactive cells


What are secondary immunodeficiencies?

Immune impairments in previously healthy people caused by a variety of diseases & physiologic states


What are the states that impair immunity?

1) Extremes of age
2) Metabolic state
3) Drugs
4) Infiltrative & hematologic disorders
5) Trauma/ infection


What is vertical transmission of HIV?


*****I.e. from mother to infant


Describe the binding of the HIV virion.

1) HIV gp120 binds CD4+ molecule on target cell
2) Needs chemokine co-receptors:
- CCR5, macrophages
- CXCR4, T-cells
3) HIV gp41 inserts into the target cell membrane & fuses the viral envelope with the cell membrane for fusion


Outline the entry & transmission of HIV.

Once internalized:
1) Reverse transcriptase transcribes viral RNA genome to a DNA copy (cDNA)
2) Integrase (viral) causes "integration" of cDNA into host DNA in dividing cells
3) cDNA integrated into host DNA gets transcribed & produces new viral particle


What happens to CD4 cells when they're infected by HIV i.e. why are T-cells killed?

1) Viral replication kills the CD4 cell
2) Activation of uninfected to undergo apoptosis
3) Expression of HIV particle on the surface causes CD8+ cells to kill them


What are the immune effects of HIV infection?

1) Lymphopenia i.e. selective T-cell lymphopenia with diminished T-cell function
2) Polyclonal B-cell activation & hypergammaglobulinemia
3) Altered macrophage function with decreased MHC II expression & Ag presentation


What are the five effects of T-cell lymphopenia on the immune system?

1) CD4= decreased response to soluble antigens
2) CD8= decreased specific cytotoxicity
3) NK= decreased killing of tumor cells
4) B-cell= Decreased Ig production in response to new antigens
5) Macrophage= diminished cytotoxic ability, less IL-1, & poor APC


What are the phases of HIV infection?

1) Early, acute phase
2) Middle, chronic phase
3) Final, crisis phase


What are the characteristics of the early acute phase of HIV?

- Viral replication
- Viremia
- Viral seeding of lymphoid tissue

*****All lead to: Fever, sore throat, myalgias i.e. flu-sx


What are the characteristics of the middle, chronic phase of HIV?

Continued viral replication in lymphoid tissue

*****Lymphadenopathy, weight loss, night sweats, fatigue, fever


What are the characteristics of the final, crisis phase of HIV?

- Marked viral replication
- Depletion of T-cells leading to profound immune suppression

*****Fever, fatigue, weight loss, opportunistic disease, & neoplasm


Outline the timeline of immune response to HIV.

- CTL response 2-3 weeks post infection
- Humoral response starts roughly 6 weeks post infection

BOTH responses reach their peak ~12 weeks after infecition


What are the AIDS defining neoplasms?

1) Kaposi sarcoma
2) B-cell lymphomas
3) Primary lymphoma of the brain
4) Invasive carcinoma of uterine cervix & anus


What is are the mechanisms of B-cell lymphomas in HIV?

There are two mechanisms:
1) HIV infection increases follicular T-cells initially, signaling germinal B-cells (immature) to proliferate & become hyperplastic--leads to lymphoma
2) T-cell depletion leads to the acquisition of other viral infections that drive lymphoma


How does pnemocystitis jirveci pneumonia appear on microscopy?

- Alveoli filled with foamy exudate
- Interstititium thickened by a chronic inflammatory infiltrate


How does pnemocystitis jirveci pneumonia appear on silver staining?

"Coffee bean"


What does mycobacterium avium-intracellulare infect in AIDS patients?

Small intestinal villus that leads to problems with malabsorption

****Will also be present in the spleen


Where do Toxoplasma abscesses occur in AIDS patients?

Putamen & thalamus


What are the characteristics of HIV encephalitis?

Mutlinuclear giant cells


What is pulmonary cytomegaloviurs? How does this appear under microscopy?

Lung infection that leads to thickened interstitum
- Microscopy there is a hallmark "HUGE" nucleus


What is Progressive Multifocal Leukoencephalopathy (PML)?

Oligodendrocytes "drop-out" causing demyelination--drives AIDS dementia


What do the lesions associated with Kaposi Sarcoma look like?

Painful purple or brown cutaneous nodules


What are the different classes of drugs that are used to treat AIDS?

1) Reverse transcriptase inhibitors
2) Fusion & entry inhibitors
3) Integrase inhibitors
4) Protease inhibitor s


What are the characteristics of HIV encephalitis?

Mutlinuclear giant cells


What is Kaposi's Sarcoma?

Endothelial/ vascular tumor seen on the skin


What causes Kaposi Sarcoma?



What is Amyloidosis?

This term refers to a broad group of disorders characterized by the extracellular accumulation of amyloid, a mis-folded protein that cannot be degraded


What is amyloid?

Amyloid= a pathologic proteinaceous substance deposited int the extracellular space
- Forms continuous non-branching fibrils
- cross-B-pleated sheet conformation


What does amyloid stain with?

H & E:
- amorphous
- eosinophilic
- hyaline

Congo red= pink/ red color in tissue deposits

Congo red + birefringence=
- yellow green fluorescence


What are the three most common pathologic forms of amyloid protein?

1) AL, amyloid light chain
2) AA, amyloid associated
3) AB amyloid


What is AL derived from?

Ig light chains produced by plasma cells


What is AA derived from?

Acute phase protein synthesized by the liver, SAA


What is AB derived from?

B-amyloid precursor protein found in cerebral lesions of Alzheimer's Disease


What is Amyloidosis?

This term refers to a broad group of disorders characterized by mis-folded protein that cannot be degraded & accumulates


How is amyloidosis classified?

- Distribution
- Presence of absence of pre-exisiting disease
- Chemical type


What is AL associated with?

Multiple myeloma or some other disorder of B-cells


What is secondary amyloidosis?

Amyloidosis that occurs secondary to a chronic inflammatory state


What disease states is AA associated with?

- RA
- Subcutaneous drug abuse
- Renal cell CA
- Hodgkin's Lymphoma


What is ATTR? What ATTR associated with?

Autosomal dominant deposition of a mutant transthyretin that is associated with PERIPHERAL NEUROPATHY


What is AB 2-microglobulin?

Amyloid protein deposited in synovium, joints, & tendon sheaths in long-term dialysis