11. Immunodeficiency Disease Flashcards
Overview of immunodeficiency disease
• ____ (inherited/congenital) or ____ (acquired)
• Involve one or multiple cell types at any stage of differentiation
• Involve changes in cell ____ and/or function
• Involve ____ components of the immune system (e.g., Complement)
• Effects can be very subtle or extremely severe
• Clinical consequence:
– Susceptibility to infection and/or reactivation of latent infection; depends upon the element of ____ system affected
– Susceptibility to ____
* Immunodeficiency (ID) diseases are disorders that result from a lack of an immune response. * Historically, they were viewed as disorders that led to recurrent [bacterial, pyogenic infection, or terminal infections that involve viruses, or cancer] (we know that the immune system plays a surveillance role: NK cells detect abnormal cells and eliminate them early. To response to a tumor cell, it has to express a novel antigen). However, we now know that they are due to defects in the immune system. * Primary is at \_\_\_\_; secondary acquired later at life (\_\_\_\_ abuse, malnutrition, diabetes, infections [HIV, CD4]) * Immune deficiency can be defined by the \_\_\_\_ consequence
primary secondary number non-cellular immune cancer
birth
drug
clinical
Immune deficiency disease
• Primary immune deficiency disease (inherited or congenital) (10%)
– ____-cell, B-cell or macrophage
– Typically detected in ____ (6 mo-2 yr)
• Secondary immune deficiency disease (90%)
– ____
– Malnutrition
– ____
– Immunosuppression
– ____
• Increased susceptibility to ____ and cancer (lymphoma, skin/lip carcinoma)
• At birth, immune system is not fully developed - \_\_\_\_ via nursing, \_\_\_\_ from the placenta ○ 6 mo-2 year - severe recurrent infection - cannot terminate infection • Immunosuppressents do not suppress to individual antigen, they globally suppress > suffer all problems to immunodeficiency • Chemo > cytotoxic, anti-metabolic drugs, cell cycle inhibitors > stop prolfieration, and kill cells via apoptosis (don't want happening during immune response) • Immunodeficiencies occur at different points throughout the system; and the clinical manifestation are the result of which arm of the immune system is affected (\_\_\_\_ or \_\_\_\_). This is going to have an impact on the secondary recurrent infections the the patients develop ..but where the lesion occurs is going to have an impact on what you can detect in an ID patient. • Where lesion occurs will have impact in what you can detect in patients > if earlier enough, won't have \_\_\_\_ cells, etc. paracordical; deficient in germinal centers ○ Some lesions don't affect maturation > they affect class-switching > normal numbers of B cells, but abnormal amounts of \_\_\_\_
T infancy infection aging chemotherapy infection
IgA IgG humoral cellular T/B Ig
Patients with immune deficiency disease are more susceptible to infection
• T-cell defects
– Increased susceptibility to ____, fungi and intracellular bacteria
– May have indirect effect on ____ function
• B-cell defects
– Increased susceptibility to ____ bacteria
• Complement defects
– Increased susceptibility to ____ bacteria
• Phagocytic defects
– Increased susceptiblity to ____ bacteria
* B-cell defect > EC bacterial infection; pyogenic > \_\_\_\_-forming * Complement/phagocyte defect > look similar to B-cell defects (only produces Ab, which attacks EC infection; but it can't do everything by itself, needs \_\_\_\_ and \_\_\_\_)
virus B-cell pyogenic pyogenic pyogenic pus comp PMN
Primary Immunodeficiency disease
• Do not need to memorize tables! • But there will be a question from this slide! • In child > multiple infection (\_\_\_\_/year), and then other complications as well > may be immunodeficient • Middle: adults don't typically develop \_\_\_\_ infection > develop often > that's a sign; signs of recurrent infection, \_\_\_\_ loss • \_\_\_\_ history is critical in both! • Concern about immunodeficiency > immune system is evaluated > initially, just by \_\_\_\_ (one history + physical) ○ Normal ranges for \_\_\_\_; biopsy of lymph node may be necessary (for quantitative/qualitative) • Response to immunization ??? • In-vitro conditions > cell-responsiveness, looking for specific \_\_\_\_
4+ ear weight family enumeration Ig enzymes
Primary ID (congenital defects)
• Two broad categories
– Defects associated with ____ immune system
– Defects associated with ____ immune system
• Mainly inherited or result of ____ mutation:
– Missing (or decreased numbers of) cells
– Dysfunctional cells
— missing or dysfunctional ____
– missing or dysfunctional ____ (i.e. cytokines, complemetn)
• Defects of Adaptive Immunity
– ____ Deficiencies
– ____ (B, T, Macrophage) deficiencies
•Innate immunity: – \_\_\_\_ Deficiencies – Phagocyte Defects – \_\_\_\_ Defects – NK Cell Defects – Defects in \_\_\_\_ and lL-12 – Signaling
• May occur due to an \_\_\_\_ accident that makes it congenital • Skip defects associated with \_\_\_\_ immunity ○ Complement also involved here
adaptive innate somatic enzymes components antibody cellular
complement
IFN-gamma
intrauterine
innate
T-cell deficiencies
• Mucocutaneous candidiasis
• DiGeorge syndrome
• Present with recurrent \_\_\_\_, viral or protozoan infection (\_\_\_\_ infections requiring cytokines, \_\_\_\_ activation)
fungal
intracellular
macrophage
Mucocutaneous candidiasis
• Immune deficiency: underlying T-cell defect (abnormal ____ function)
• Chronic refractory disease/infection
• Most common sites of infection:
– ____ membranes, skin, hair and ____
– May be susceptible to other infectious disease
• Th17 > cytokines that drive inflammation ○ No Th17 > copmonent that's missing > important with respect to \_\_\_\_ infection > leading to the development of \_\_\_\_ disease. • The disease is prolonged and does not respond to \_\_\_\_.
Th17
mucous
nails
fungal
chronic refractory candidiasis
treatment
Mucocutaneous candidiasis
- ____ areas that harbor an infection in general
- White lesions > gauze and grab the tongue > it’ll ____ off
- ____ is involved with candidiasis
- ____ or ____ use > candidiasis; if not on antibiotics should be concerned about other problems*** [???]
moist come thrush immunodeficiency antibiotic use
Thymic Hypoplasia: DiGeorge Syndrome
• Immune defect:
– Congenital defect in ____-cell maturation
– Due to microdeletions in chromosomal region ____ (~40 genes)
• Findings:
– Thymic hypoplasia (minimal to virtually complete)
– Lymphoid tissue lack ____-cells
– No circulating ____-cells in blood
• Clinical presentation:
– vulnerable to ____, fungal and intracellular infections
– Vulnerable to intracellular ____ infections
– Other developmental abnormalities:
• ____ hypoplasia (hypocalcemic tetany
• ____ developmental abnormalities
• Cleft lip
• Treatment:
– Management of associated conditions
– ____ or thymic transplant
• Third/fourth pharyngeal pouches develop > if there's an accident > will not develop a thymus > thymic hypoplasia • Large thymic shadow in normal; with DG > no \_\_\_\_ shadow • \_\_\_\_ - eyes are further set apart • Parathyroid may not develop > \_\_\_\_ tetany > contraction of muscles due to deficiency of abnormal levels of calcium • Infections won't be terminated and will be lethal, or they will be recurrent ○ Can be treated by managing the infection - BM transplant or thymic transplant
T
22q11.2
T
T
viral
bacterial
parathyroid
midline
bone marrow
thymic
hypertelorism
hypocalcemic
B-cell deficiencies • \_\_\_\_ Agammaglobulinemia • Common Variable Immune deficiency • Isolated \_\_\_\_ Deficiency • Hyper \_\_\_\_ Syndrome
* Divide ID into primary - primary defect involves immune system; secondary ID, where secondary defect is due to secondary event (systemic disease); 90% are secondary, 10% are primary * Primary - \_\_\_\_ cell deficiency (chronic muco candidiasis, and digeorge syndrome) > many ID can be diagnosed by fact of \_\_\_\_ infection; type of infection is indicative of component of immune system that is defective * ID recurrent and cannot be terminated * \_\_\_\_ - deficiency that involves failure of producetion of Ig * \_\_\_\_ - lack of Ig, but for diff reasons
X-linked
IgA
IgM
T
recurrent
XLA
CVI
X-Linked Agammaglobulinemia
(Bruton Disease)
• Immune deficiency: failure of pre-B- cells to differentiate into ____ B- cells
– Mutations in ____ (Brutons, BTK) (no Ig-____ chains); failure of BCR (Ig) to properly develop
– Absence of mature B-cells
– Absence of ____ globulin in blood
– Reduced ____ of B-cells in circulation
– Lack ____ centers in lymphoid tissue
– No ____ cells
• Clinical presentation: – \_\_\_\_ bacterial infection: acute and chronic pharyngitis, sinusitis, otitis media, bronchitis and pneumonia • \_\_\_\_ influenzae • \_\_\_\_ pneumoniae • \_\_\_\_ aureus
• Treatment: ____ immunization with pooled human serum; manage associated problems
○ Light chains do not join the \_\_\_\_ chains ○ Important role in development of pre-B cell > very few/no B cells (won't have normal levels of IgM/IgG) • \_\_\_\_ - sore throat • Pulmonary/aerodigestive infection • \_\_\_\_ pooled serum used! • In diagnosing, may involve lymph node biospy/WBC count, and history will show form of recurrent infection
mature tyrosine kinase light gamma numbers germinal plasma
recurrent
haemophilus
streptococcus
staphlyococcus
passive
heavy
pharyngitis
hyperimmune
Common Variable Immune deficiency
• Immune deficiency: inability of mature B-cells to differentiate into ____ cells
– B-cell defects
– ____ defect
– ____ defect
• Normal number of mature B-cells, but absence of ____ cells
• Hypogammaglobulinemia
– Impaired ____ response to infection and vaccination
• Clinical presentation:
– increased susceptibility to ____ (similar to Bruton disease)
– Increased risk to autoimmune disease(?)
• Treatment:
– ____ immunization with pooled human
immunoglobulin
– Manage associated problems
• Mature B cells cannot become activated ○ Will see fairly reasonable numbers of B cells, opposite of \_\_\_\_ • Multifactorial problem - B cells respond to native antigen in absence of T cells > produce IgM; typically B cells require T cell activation (via APC), Th cells produce cytokines that facilitate activation of B cells, and maturation to plasma and diff classes of Ig • T-suppressor may be \_\_\_\_! • Same \_\_\_\_ organisms as in Bruton
plasma T-helper T-supporesor plasma antibody infection passive
bruton’s
overactive
pyogenic
Isolated IgA Deficiency
• Immune deficiency: block in terminal differentiation of IgA secreting B-cells to ____ cells
– No serum or secretory ____
– Normal ____ and ____ levels normal
• Clinical presentation:
– Most patients are ____
– Weakened ____ defenses predispose to recurrent sinopulmonary infections and diarrhea
• IIgAD - block in terminal differentiation of B cells into IgA producing cells; most of IgA producing B cells > differnetiatte in diffuse lymphoid tissue (peyer's patches, or BALT) > IgA is part of defense mech of mucosal surfaces, IgA is a dimer (two Fc is linked that has 4 antigen combining sites > potent Ig for agglutinaiton > what you need for these surfaces); no serum IgA, and no secretory IgA; other subtypes are normal; the patients are asymptomatic - suggests that host defense is \_\_\_\_ (innate and humoral system, can compensate for lack of IgA) > these individuals have weakened defenses > become susceptible to \_\_\_\_ defense (sinuses, GI treet and tract)
plasma IgA IgM IgG asymptomatic mucosal
redudant
sinopulmonary
Hyper IgM Syndrome
• Immune deficiency: failure in \_\_\_\_-chain class switching – \_\_\_\_ deficiency associated with class switching and T-cell contact – No \_\_\_\_, \_\_\_\_ or \_\_\_\_
• Clinical presentation:
– Recurrent ____ infections
– Increased susceptibility to ____ pathogens
* Failure to class swithc - B cells that mature into plasma, only produce plasma cells that are capable of producing \_\_\_\_; defect here involves T cells so they can't make proepr contacts > the help these cells provide is not there * IgM is reasonably potent - cannot carry out all functions of G/A - recurrent pyogenic infections, and icnrease susceptibly to intracellular pathogens > likely a T-cell associated defect in these patients * Primary defect - failure ot produce subclasses of I
heavy enzyme IgG IgA IgE pyogenic intracellular
IgM
Severe Combined Immune Deficiency both T and B cell defect
• Immune deficiency: defects in both humoral and cell mediated immunity
– X-linked (xscids): mutations in ____ receptors (~50%)
– Adenosine deaminase (ADA) deficiency (autosomal ____;~ 50%)
• Accumulation of ____
• inhibit ____ synthesis and lymphotoxic
– MHC class ____ expression
• Lymphoid tissue are atrophic
• No serum ____
• Clinical presentation: recurring infection: ____, pneumonia , bronchitis, thrush and diarrhea; general wasting
Susceptible to \_\_\_\_, fungi and protozoans Recurrent (or fatal) \_\_\_\_ infections: • \_\_\_\_ (thrush) • Pneumocystis • \_\_\_\_ • Pseudomonas
• Treatment: bone marrow transplantation and ____ therapy
cytokine recessive adenosine, deoxyadenosine DNA II Ig
otitis media
viruses
opportunsitc
candida
CMV
gene
