Immunopathology 3 Flashcards
IMMUNODEFICIENCY DISEASES INTRODUCTION
Congenital B-cell defects are clinically conspicuous because of the reduced resistance to ______ infection that they involve.
In contrast, primary T-cell defects leave the patient unprotected against ____________
bacterial
viruses and fungi.
Patients with a combined B cell and T-cell deficiency are poor candidates for survival.
T/F
T
Among the acquired immunodeficiency disorders, gammopathy due to ____________ and AIDS due to __________ warrant special mention.
neoplastic proliferation of a plasma cell clone
infection with the human immunodeficiency virus (HIV)
Immunodeficiencies can be divided into the primary immunodeficiency disorders, which are almost always _______ determined
And secondary immunodeficiency states, which may arise as complications of _______ factors
genetically
External factors
Most primary immunodeficiency diseases are genetically determined and affect only INNATE IMMUNITY
T/F
F
Both INNATE IMMUNITY ACQUIRED IMMUNITY
Most primary immunodeficiencies manifest themselves in _____, between _____ and ____ of life, and they are detected because _____________________
infancy; 6 months and 2 years
the affected infants are susceptible to recurrent infections.
PRIMARY IMMUNODEFICIENCY
X-Linked Agammaglobulinemia (____
Agammaglobulinemia)
Due to ______
Bruton’s
disordered B-cell maturation
In Bruton’s Agammaglobulinemia
Naïve b cells can mature to plasma cells
T/F
F
Cannot
Bruton’s Agammaglobulinemia
Caused by mutations in a _______, called __________;
the gene that encodes it is located on the ____ arm of the ___ chromosome at ____.___.
cytoplasmic tyrosine kinase; Bruton tyrosine kinase (Btk)
long; X
Xq21.22
Bruton’s Agammaglobulinemia
The disease usually does not become apparent until about _____ of age, as _______
6 months
maternal immunoglobulins are depleted.
Bruton’s Agammaglobulinemia
Recurrent ____s infection (________)
BEG
bacterial IgG, enteroviruses IgA, giardia
Beware of live attenuated (eg polio) vaccines in patients suffering from Bruton’s Agammaglobulinemia
T/F
T
Bruton’s Agammaglobulinemia
Recurrent BEG infection
B Causative Organisms
•———-,———,———
enteroviruses, such as _____,_____,______
Haemophilus influenzae
Streptococcus pneumoniae, or
Staphylococcus aureus.
echovirus, poliovirus, and coxsackievirus
In Bruton’s Agammaglobulinemia
•B cells are ______________ in the circulation, and the serum levels of all classes of immunoglobulins are _______.
•Pre-B cells, are found in _____ numbers in the bone marrow.
• Germinal centers of ____,______,______, and ___ are underdeveloped.
• Plasma cells are (present or absent?) throughout the body.
• T cell–mediated reactions are ____.
absent or markedly decreased ; depressed
normal
lymph nodes, Peyer’s patches, the appendix, and tonsils
Absent ; normal
Autoimmune diseases, such as _______ and ______, occur with increased frequency, in as many as 35% of individuals with X-linked agammaglobulinemia disease, which is paradoxical ___________
arthritis and dermatomyositis
in the presence of an immune deficiency
The treatment of X-linked agammaglobulinemia is ___________
replacement therapy with immunoglobulins.
Common Variable Immunodeficiency
(Well or Poorly ?) defined entity
The feature common to all patients is _______, generally affecting all the ________ but ____
Poorly
hypogammaglobulinemia
antibody classes
sometimes only IgG.
Relatives of Common Variable Immunodeficiency patients have a high incidence of __________
selective IgA deficiency
In contrast to X-linked agammaglobulinemia, most individuals with common variable immunodeficiency have ________ numbers of B cells in the blood and lymphoid tissues.
These B cells, however, are _________
normal or near-normal
not able to differentiate into plasma cells.
In contrast to X-linked agammaglobulinemia, common variable immunodeficiency affects (male or female?) , and the onset of symptoms is in ______ or _____
both sexes equally
childhood or adolescence
common variable immunodeficiency
Histologically the B-cell areas of the lymphoid tissues (i.e., lymphoid follicles in nodes, spleen, and gut) are _____.
hyperplastic
Isolated IgA Deficiency
Most common in the _____ world. It is far less common in _______
westerns; blacks and Asians
Isolated IgA Deficiency
Characterized by _____ levels of _________
It may be familial, or acquired in association with toxoplasmosis, measles, or some other viral infection
extremely low
both serum and secretory IgA
The basic defect in isolated IgA deficiency is ______________
impaired differentiation of naive B lymphocytes to IgA-producing cells
Most individuals with isolated IgA deficiency disease are symptomatic.
T/F
F
asymptomatic
Isolated IgA deficiency
Because IgA is the major Ig in ________ , ______ are weakened, and infections occur in the ______,____, and ——- .
external secretions
mucosal defenses
respiratory, gastrointestinal, and urogenital tracts
Celiac dx is associated with ___ deficiency
IgA
IgA-deficient patients have a high frequency of respiratory tract allergy and a variety of autoimmune diseases, particularly _____ and ______
SLE and rheumatoid arthritis.
When transfused with blood containing normal IgA, some of these isolated IgA deficient patients develop _____________ reactions, because ________
severe, even fatal, anaphylactic
the IgA behaves like a foreign antigen (since the patients do not produce it and are not tolerant to it)
Hyper-IgM Syndrome
affected patients make ___ antibodies but are deficient in their ability to produce ________ antibodies
IgM; IgG, IgA, and IgE
Approximately 70% of individuals with hyper-IgM syndrome have the _____ form of the disease, caused by mutations in the gene encoding ______ located on Xq26. Or ___________.
X-linked
CD40L
CD40 receptor
Hyper-IgM Syndrome
Remember that Bcells can be activated to plasma cells in 2 ways-
1)_______ on the surface of naïve Bcells to ___________
2)_____ Antigen and presenting through ______ to T helper cells with _____ as 2nd stimulus. Activated CD4+ produce _____ and ____ which cause heavy chain class switch and production of Ig E, Ig G, Ig A
IgM receptors; IgM producing plasma cells
Internalising; MHC class II; CD40
IL4 and IL5
Hyper IgM syndrome
In the remaining persons the disease is inherited in an autosomal recessive pattern.
Most of these patients have mutations in the gene encoding _____ or the enzyme called ________
CD40
activation-induced deaminase
Hyper IgM syndrome
The serum of persons with this syndrome contains ________ levels of IgM but ______ IgA or IgE and ______ levels of IgG.
The number of B and T cells is ______.
normal or elevated
no; extremely low
normal
In hyper IgM syndrome
Many of the IgM antibodies react with elements of blood, giving rise to _______,_______, and _______.
In older patients there may be uncontrolled proliferation of IgM-producing plasma cells with infiltrations of the _____ tract.
autoimmune hemolytic anemia, thrombocytopenia, and neutropenia
gastrointestinal
DiGeorge Syndrome (Thymic Hypoplasia)
T-cell deficiency that results from failure of ___________________
Due to __q__ —————
development of the third and fourth pharyngeal pouches.
22q11; microdeletion
DiGeorge Syndrome
Thus, individuals with this syndrome have a variable loss of T cell–mediated immunity (resulting from ___________), tetany (resulting from lack of the _______ ), and congenital defects of the __________. In addition, the appearance of the _________ may be abnormal
hypoplasia or lack of the thymus
parathyroids
heart and great vessels
mouth, ears, and facies
DiGeorge syndrome is a familial disorder.
T/F
F
not
DiGeorge syndrome
It results from the ____ of a gene that maps to chromosome ___
Absence of _______ immunity is caused by low numbers of T lymphocytes in the blood and lymphoid tissues and poor defense against certain _____ and ______ infections.
deletion; 22q11
cell-mediated
fungal and viral
In Digeorge syndrome
The T-cell zones of lymphoid organs—_______ areas of the lymph nodes and the ____________ of the spleen—are depleted.
Ig levels may be __________, depending on the _________________
paracortical; periarteriolar sheaths
normal or reduced; severity of the T-cell deficiency.