Immunodeficiency disorders Flashcards
When do immunodeficiencies usually appear?
6 mo to 2 yo
What are the two causes of Pro-T cell deficiency?
ADA deficiency
X-linked SCID
What cells are the conductors of the immune system?
CD4 cells
What is the disease the prevents the maturation of T cells?
DiGeorge syndrome (hypoplastic thymus)
What is X-linked agammaglobinemia of Burton caused by?
XR mutation in a Y kinase responsible for pre to mature B cell signals
What is the protein that is deficient in X-linked agammaglobinemia of Burton?
Bruton tyrosine kinase
What is the characteristic finding of X-linked agammaglobinemia of Burton ?
No B cells in the blood
What are the clinical features of X-linked agammaglobinemia of Burton? What type of bacteria are particularly troublesome for these pts?
Recurrent infxs after maternal antibodies gone
pyogenic bacteria
What is the treatment for X-linked agammaglobinemia of Burton ?
Parenteral immunoglobulin replacement
Why is there an increase in autoimmune disorders with X-linked agammaglobinemia of Burton?
breakdown in self tolerance or to chronic infection
Why don’t you give live viral vaccines with X-linked agammaglobinemia of Burton?
No B cells to kill off live virus
When does common variable immunodeficiency present? What is the M:F?
2-3rd decade of life 1:1 M:F
What is common variable immunodeficiency?
Variable inheritance, but hypogammaglobulinemia of (usually) all IgG classes d/t B cell inability or lack of T cell stimulation
What happens to B cells in common variable immunodeficiency?
Increase number of B cells, because they can’t produce much antibodies
What are the symptoms of common variable immunodeficiency?
Recurrent bacterial infx d/t lack of IgA
True or false: patients with common variable immunodeficiency have a lower incidence of autoimmune disorders and CA
False–higher
What is selective IgA deficiency?
Lack of IgA production, leading to mild symptoms or recurrent sinus infx
selective IgA deficiency is associated with what two diseases?
Toxoplasmosis
Measles
True or false: there is still some IgA in selective IgA deficiency
True
Why do you have to be careful when giving IVIG to selective IgA deficiency pts?
40% have anti-IgA Ab
What is hyper IgM syndrome?
Disorder characterized by a failure of T cells to induce B cell isotype switching from IgM to other types.
How do B cells normally induce isotype switching?
signal between CD40/CD40 molecule link between T cells. This is altered in
True or false: hyper IgM syndrome is due to incorrect amount of B cells and/or T cells?
False–B and T cells couns normal
What is the inheritance pattern of hyper IgM syndrome?
X linked in 70% of cases, other AR
What is the mutation involved in hyper IgM syndrome?
CD40 gene mutation or the deaminase enzyme it needs
What are the symptoms of hyper IgM syndrome? (3)
Recurrent pyogenic infections
Autoimmune hemolytic anemia
GIT lymphoid hyperplastic accumulations
What causes the immune problems in DiGeorge syndrome?
Partial or complete interruption of the 3rd and 4th pharyngeal pouch = thymus aplasia
What are the features of DiGeorge syndrome?
Cleft palate
T cell defect
Hypocalcemia
Are immunoglobin levels altered in DiGeorge syndrome?
No–T cells deficiency, not B cells
What is the genetic mutation associated with DiGeorge syndrome?
22q11 Deletion
What are the types of infections that pts with DiGeorge syndrome have problems fighting off?
Viruses and fungi
What are the facial defects of DiGeorge syndrome?
Cleft palate
Micrognathia
What are the cardiac defects of DiGeorge syndrome?
VSD, right subclavian artery is derived from the pulmonary artery
What is the prognosis of DiGeorge syndrome if there is thymus hypoplasia? Aplasia?
Hypoplasia = immune defect resolves by age 5 Aplasia = death unless given thymus transplant
What is SCID?
Deficient cellular and humoral immune response d/t variable genetic transmissions
What is the more common form of SCID: T cell defect, B cell defect, or combined?
T cell is more common
What is the mode of inheritance of SCID?
X linked for 60% of cases
What is the mutation involved in SCID? in the X link recessive pattern?
loss of gamma chain subunit of cytokine receptors, leading to a loss in interleukin pathway
What is the mutation involved in SCID? in the AR pattern?
Adenosine deaminase deficiency, leading to build up of toxic metabolites in lymphocytes
What are the clinical features of SCID?
early onset opportunistic infections.
What is the treatment for SCID?
Bone marrow transplant, gene therapy for ADA
What is Wiskott-Aldrich syndrome? Mode of inheritance?
XR of males causing immunodeficiency, rash, and thrombocytopenia
What is the mutation involved in Wiskott-Aldrich syndrome? What is this protein involved in?
Xp11.23–responsible for cytoskeletal maintenance receptors, leading to depletion of T and B cells
What are the clinical features of Wiskott_aldrich syndrome?
Ab levels normal, except IgM, which is low
What are the clinical features of Wiskott-aldrich syndrome? (abs, T cells)
Ab levels normal, except IgM, which is low.
Abs do not function
T cell deficiency
What are the symptoms of Wiskott-Aldrich syndrome?
Hemorrhagic diathesis
Recurrent URIs
What is the treatment for Wiskott-Aldrich syndrome?
Bone marrow transplant
Why are immune deficiencies and autoimmunity linked? (2)
Lower regulatory T cells
Persistent microbial infx leads to altered immune response.
Which are more common, secondary or primary immunodeficiencies?
secondary
What are secondary immunodeficiencies?
Immune impairment in previously healthy people
Are secondary immunodeficiencies reversible?
Yes, if underlying condition is treated
What is the target of HIV?
Th4 CD4 cells
What does the gp120 protein of HIV bind to?
CD4
What is the genome type of HIV?
dsRNA (retroviridae)
What is the attachment protein of HIV? Fusion protein?
Attachment = gp120 Fusion = gp41
What are the two coreceptors for HIV?
CCR5
CXCR4
Which cofactor of HIV gp120 protein do some patients have protection against?
CCR5
WHat is the protein that aids in HIV’s entrance into a cell?
Integrase
What are the three routes of CD4 T cell death in HIV?
- viral escape
- Apoptosis
- CTL attack
What are HIV’s effects on polyclonal B cells ?
Polyclonal B cell activation with hypergammaglobulinemia, yet impaired specific B cell response to new antigen
How are macrophages affected in HIV?
Decrease in MHC class II expression, and Ag presentation
What is the effect of HIV on NK cells?
Decreased killing of tumor cells
What is the effect of HIV on CTLs?
Decreased specific cytotoxicity
What are the acute phase symptoms of HIV?
Viral replication, viremia, viral seeding of lymp tissue
What are the chronic phase symptoms of HIV?
Weight loss, night sweats
When are the anti-envelope antibodies to HIV elevated?
Throughout the course of the disease
When are the anti-p24 antibodies to HIV elevated?
High throughout
What are the four neoplasms associated with the HIV?
- Kaposi’s sacroma
- B cell lymphoma
- Primary lymphoma of the brain
- Carcinomas of the uterine cervix and anus
What is the pathogenesis of B cell lymphoma in HIV?
increased stimulation of germinal B cell centers, causing hyperplasia
What are the histological characteristics of pneumocystis pneumonia seen in AIDs pts?
Alveoli filled with foamy exudate white interstitium is thickened by a chronic inflammatory infiltrate
SIlver stain of pneumocystis pneumonia produces what histological characteristics?
Coffee bean appearance
What are the histological characeristics of oral candidiasis?
Pseudohyphae
What are the histological characteristics of mycobacterium avium-intracellulare in the intestines? What is the stain to use?
Widening and thickening of intestinal villi
Acid fast
What is the stain utilized to diagnose HIV cells?
anti-p24
What are the histological characteristics of CMV? (2)
HUGE cells
Perinuclear halo
What happens to the brain in HIV?
Progressive mutlifocal leukoencephalopathy caused by demylination
What is the causative agent of Kaposki’s sarcoma?
HHV8
Why does Kaposki’s sarcoma appear red/blue?
Highly vascularized
What are the histological characteristics of Kaposki’s sarcoma?
Highly vascularized/endothelial cells
What are the 4 different types of HIV medications?
- Fusion/entry inhibitors
- Reverse transcriptase inhibitors
- Integrase inhibitors
- Protease inhibitors
What is amyloidosis?
Diverse group of disorders characterized by extracellular deposition and accumulation of abnormal, misfolded proteins
True or false: amyloidosis is a disease
False
What is the stain for amyloid? What is significant about this stain?
Congo red–causes fluorescence under polarized light
What are the two components of amyloid?
- Fibrils
2. Pentagonal components (glycoprotein)
What is the secondary structure that amyloid forms?
Beta-pleated sheets
What is amyloid derived from?
Soluble circulating protein precursors into insoluble fibrillar forms
Amyloid fibril types are designated by two letters. What are they?
A for amyloid, followed by letters for the chemical type
What produces AL proteins?
B cells in B cell lymphoma
What produces AA proteins?
Liver cells produce acute reactive proteins forming chronically
Occurs in chronic diseases
What is the ATTR protein, and what is it’s function?
Anti Transthyretin protein
Transports thyroxin and retinol
How is amyloidosis classified? (3)
By distribution
Presence of disease
Chemical type
Abeta amyloid is associated with what/where?
Cerebral blood vessels in Alzheimers
Where do deposits of amyloid go in the liver?
Space of disse
Abeta2-microglobulin is seen in pts with what? Where does it depost?
Dialysis pts
Synovium/joints
Abeta amyloid is associated with what/where?
Cerebral blood vessels in Alzheimers
What are the complications of amyloidosisin the heart? Where, histologically, in the heart are these deposits found?
Rigid ventricles
Between myocytes
How do you diagnose amyloidosis?
Biopsy of mucosa
What are the clinical features of amyloidosis?
Depends on how much and where, but more = worse function
Amyloid light chain type is derived from what? What diseases is this seen in?
from the lambda Ig chain from B cells
Multiple myeloma, or other B cell disorder
Where is amyloid light chain deposited in the body?
Usually generalized, but tends to involve the heart, GI, peripheral nerves
What diseases is the AA type of amyloid found in?
Inflammatory or infectious states e.g. RA
What is the AA amyloid derived from?
SAA (acute phase reactive proteins)
Where are AA amyloid deposits found in the body?
Systemic, but tend to involve kidneys, liver, spleen, lymphs, adrenals
ATTR amyloid is caused by what? Where is it deposited?
An AD mutant tranthyretin, despositing in peripheral nerves
What can cause a decrease in size of an organ in amyloid deposit?
Ischemic atrophy
Which primary immunodeficiency is caused by a lack of a Y kinase, causing a failure of B cell to undergo furtehr differentiation?
X-linked agammaglobulinemia of Bruton
What disease has no B mature cells in circulation, and thus no immunoglobin?
X-linked agammaglobinuemia of Bruton
Which primary immunodeficiency is caused by an intrinsic inability of B cells to undergo differentiation, or a lack of T cell signalling to B cells?
Common variable immunodeficiency
Which primary immunodeficiency is caused by a failure of T cells to induce B cells to isotype swtich d/t a lack of CD40 ligand?
Hyper IgM syndrome
What is the inheritance pattern of hyper IgM syndrome?
X-linked or AR
