IS Lec Final - Diseases Flashcards
3 Disorders of Neutrophils
Noninfectious Neutrophil-Mediated Inflammatory Disease
Abnormal Neutrophil Function
Congenital Neutrophil Abnormalities
2 Types of Noninfectious Neutrophil-Mediated Inflammatory Disease
inappropriate phagocytosis
inappropriate activation of phagocytosis
prolonged activation of NADPH oxidase
inappropriate phagocytosis
phagocytes attempt to engulf particles that are too large, releasing oxygen radicals and granule contents onto the particle, but these escape into the surrounding tissues, generating tissue damage.
inappropriate phagocytosis
Ex: in response to dust inhalation and smoking (e.g., nicotine) and in persistent infections such as cystic fibrosis
inappropriate phagocytosis
Autoimmune diseases such as Grave’s disease, rheumatoid arthritis, multiple sclerosis
inappropriate activation of phagocytosis
4 types of Abnormal Neutrophil Function
Quantitative or qualitative defects of neutrophils
Impaired leukocyte mobility
Defective locomotion or leukocyte immobility
Defect in the cellular response to chemotaxis
high rate of infection
Quantitative or qualitative defects of neutrophils
Quantitative or qualitative defects of neutrophils examples
recurrent systemic bacterial infections (e.g., pneumonia), disseminated cutaneous pyogenic
lesions, and other types of life-threatening bacterial and fungal infections
too low (neutropenia) or too high (neutrophilia) both translates to high infection rate
defects in the granules and neutrophils
Impaired leukocyte mobility
Impaired leukocyte mobility ex
rheumatoid arthritis, cirrhosis, CGD
total immobility, prone to recurrent bacterial infections
Defective locomotion or leukocyte immobility
Defective locomotion or leukocyte immobility ex
Lazy leukocyte syndrome, patients in steroids
recurrent bacterial infection
Defect in the cellular response to chemotaxis
Defect in the cellular response to chemotaxis ex
Chediak Higashi anomaly, sepsis, Job’s syndrome (hyperimmunoglobulinemia E)
- qualitative disorder of neutrophils
- Autosomal recessive
- Abnormal granulation of platelets and neutrophils
- impaired chemotaxis and delayed killing of ingested bacteria
occurs during childhood
Chédiak-Higashi syndrome (anomaly)
group of disorders of oxidative metabolism affecting the cascade of events required for H2O2 production by phagocytes
Chronic granulomatous disease (CGD)
mutation in CYBB – required for microbicidal ROS production by neutrophils and monocytes
Chronic granulomatous disease (CGD)
Results to life- threatening infections and granulomatous complications
Chronic granulomatous disease (CGD)
- deficiency of CR3 on phagocytic cells presents as a leukocyte adhesion deficiency
Complement receptor 3 (CR3) deficiency
marked abnormalities of adherence-related functions
Complement receptor 3 (CR3) deficiency
Leukocyte adhesion deficiency type 1 (LAD- 1) - deficiency of CD18
LAD-2 - absence of sialyl–Lewis X (CD15s) blood group antigen
Complement receptor 3 (CR3) deficiency
innately present on the body and needed for leukocyte adhesion, adhesion is impaired, translates to LAD 1 and 2
Complement receptor 3 (CR3) deficiency
patient’s phagocytes manifest a mild to moderate defect in bacterial killing and a marked defect infungal killing in vitro
Myeloperoxidase deficiency
azurophilic granules are present but MPO are absent, MPO causes greenish coloration in pus, infancy to childhood, manifested by delayed separation in umbilical cord, sipon bacterial (greenish to yellowish) viral (watery & colorless, no medication, dengue has no antibiotics)
Myeloperoxidase deficiency
an iron- containing heme protein responsible for the peroxidase activity characteristic of azurophilic granules
Myeloperoxidase
azurophilic granules are also called ____
non specific bc they are found in all granulocytes
caused by a failure to synthesize specific granules and some contents of other granules during differentiation of neutrophils in the bone marrow.
Specific granule deficiency
Results to recurrent, severe bacterial infections of the skin and deep tissues, with a depressed inflammatory response
Specific granule deficiency
5 Primary and Secondary Abnormalities of Monocyte-Macrophage Function
Defect in phagocyte killing
Defective monocyte cytotoxicity
Defective release of macrophage-activating Factors
Depressed migration
Impaired phagocytosis
Defect in phagocyte killing examples
Chronic granulomatous disease, corticosteroid therapy, newborn infants, viral infections;
liver, lungs, spleen, lymph nodes
Defective monocyte cytotoxicity examples
Cancer, Wiskott-Aldrich Syndrome, TIE (thrombocytopenia, immunodeficiency, eczema)
Defective release of macrophage-activating Factors examples
Acquired Immunodeficiency Syndrome (AIDS), Intracellular infections (lepromatous leprosy, tuberculosis, visceral leishmaniasis)
In AIDS, what is dominant?
CD8 (cytotoxic cells) becomes more dominant than CD4 (t-helper cells)
Depressed migration examples
AIDS, burns, diabetes, immunosuppressive therapy, newborn infants
what is the state of blood in diabetes?
blood is viscous in diabetes and membranes are thickened which results to plug formation, impaired migration of phagocytes
Impaired phagocytosis examples
Congenital deficiency of CD11-CD18, monocytic leukemia, systemic lupus, erythematosus
Qualitative Monocyte-Macrophage Disorders aka ___
lipid storage disorders
systemic enzymatic defect permits the accumulation of cell debris normally cleared
by macrophages
lipid storage diseases
resistance to infection can be impaired, at least partially, because of a defect in macrophage function
lipid storage diseases
they store lipid products, which need to be degraded by certain enzymes
when they lack specific enzymes needed for lipid metabolism, it will accumulate
monocytes and macrophages
Deficiency of β-glucocerebrosidase, the enzyme that normally splits glucose from its parent sphingolipid, glucosylceramide
Gaucher’s Disease
Accumulation of cerebroside in histiocytes
Gaucher’s Disease
Cells are large, with one to three eccentric nuclei and a characteristically wrinkled cytoplasm
Gaucher’s Disease
Found in the bone marrow, spleen, and other organs of the mononuclear phagocyte system
Gaucher’s Disease
Production of erythrocytes and leukocytes decreases as these abnormal cells infiltrate the bone marrow
Gaucher’s Disease
Recessive deficiency of the enzyme
sphingomyelinase
Niemman Pick Disease
Accumulation of sphingomyelin in the
mononuclear phagocytes
Niemman Pick Disease
The characteristic cell is similar in appearance to Gaucher’s cell, although the cytoplasm of the cell is foamy
Niemman Pick Disease
lack of enzyme means that majority of the waste material remains in the lysosome
Gaucher’s Disease
Disease States Involving Leukocyte Integrins
Leukocyte adhesion deficiency (LAD)
what do you call the adhesive molecules?
integrins
leads to recurrent and often fatal bacterial and fungal infections
Leukocyte adhesion deficiency (LAD)
5 features of Leukocyte adhesion deficiency (LAD)
- Delayed separation of umbilical cord
- Gingivitis
- Recurrent and persistent bacterial or fungal skin infections
- Impaired wound healing
- Lack of pus formation
can affect people of all racial groups
LAD-1
a deficiency of the β2-integrin subunit (CD18)
LAD-1
The phenotypes are severe, moderate, and novel or variant
LAD-1
affects people from the Middle East and Brazil
LAD-2
failure to convert guanosine diphosphate (GDP) mannose to fructose
LAD-2
no deficiency, just failure of conversion
LAD-2
