I&I 2024 Flashcards
Sentinel cells in the skin
macrophages
mast cells
dendritic cells (DCs) including epidermal Langerhans cells.
dendritic cell (DC) subsets, including dermal DCs and plasmacytoid DCs (pDCs)
T cell subsets, including CD4+ T helper 1 (TH1), TH2 and TH17 cells, γδ T cells and natural killer T (NKT) cells.
TNF-α promotes a coagulable state by
increasing the shedding of the protein C receptor and inhibiting thrombomodulin production, inducing complement activation and stimulating the production of tissue factor by endothelial cells and mononuclear phagocytes.
Azurophilic granules contain
MPO (peroxidase-positive granules); proteases such as cathepsins, proteinase-3, and elastase; and antimicrobial proteins such as defensins and the BPI.
MPO, α-defensins, bactericidal/permeability-increasing protein (BPI), elastase, proteinase-3, and cathepsin G.
Specific granule neutrophil contain
Alkaline phosphatase
Lactoferrin
Lysozyme
NADPH oxidase
Collagenase
Cathelicidin
specific granule eosinophil contain
Cathepsin
Major basic protein
Eosinophil cationic protein
Eosinophil peroxidase
Eosinophil-derived neurotoxin
specific granular basophil contain
Heparin
Histamine
Citrullination
a post-translational modification (PTM) that involves the hydrolysis of the positively charged guanidium group on arginine to generate a neutral urea (Fig. 1a)1. Citrullination plays crucial roles in many physiological processes, including the epigenetic regulation of gene transcription, neutrophil extracellular trap (NET) formation or NETosis, and maintaining pluripotency
Citrullination is catalyzed by
the protein arginine deiminases (PADs) (Fig. 1a), a group of four catalytically active cysteine hydrolases (PAD1–4). PADs are Ca2+-dependent enzymes and the presence of calcium increases PAD activity by >10,000-fold. Calcium-binding leads to dramatic conformational rearrangements, particularly of the nucleophilic cysteine (C645 in PAD1, 4; C647 in PAD2; C646 in PAD3) to form a catalytically competent active site.
Aberrant protein citrullination is a hallmark of
multiple autoimmune disorders, including rheumatoid arthritis (RA), multiple sclerosis (MS), ulcerative colitis (UC), and lupus, as well as several neurodegenerative diseases and cancer.
BPI protein
Bacterial permeability-increasing protein
serous
of, relating to, or resembling serum
serous fluid
a clear to pale yellow watery fluid that is found in the body especially in the spaces between organs and the membranes which line or enclose them (such as the heart and pericardium or abdomen and peritoneum) and that when occurring in large quantities is indicative of a pathological condition (such as cirrhosis or heart failure) or surgical complication
Identifying the 5 exudate wound drainage types & differences
Serous exudate:
This type appears as a clear or pale yellow, thin, and watery plasma. During the inflammatory stage, serous is a regular part of healing, and small amounts are considered normal. However, if there are moderate to heavy amounts, this may indicate a high bioburden count.
Sanguineous exudate:
When fresh blood leaks from a wound, this is sanguineous drainage. This is most commonly seen in deep partial- and full-thickness wounds. In the inflammatory stage, a small amount is a normal occurrence. But if noted outside of this stage, sanguineous can be a result of trauma to the wound.
Serosanguineous exudate:
The most common type of secretion seen in wounds is serosanguineous. Appearing thin, watery, and pale red to pink in color, this occurs in the inflammatory stage. A small amount of this is considered normal in wound healing.
Seropurulent exudate:
When the secretion is thin, watery, cloudy, and yellow to tan in color, it is considered seropurulent. When this type is present, it is usually the first sign the body is fighting an infection, according to Dashner. She added that if an infection is present, honey with a foam border dressing can be used as a treatment method, although this depends on the size and location of the wound and the amount of exudate.
Purulent exudate:
Drainage that is thick, opaque, and tan, yellow, green, or brown in color is purulent. This is never a normal occurrence in the wound bed and is often associated with infection or high bacterial levels. Dashner stated that this type is considered the most severe because it can indicate an active infectious process and may need to be cultured.
“Negative” acute-phase proteins
decrease in inflammation. Examples include albumin, transferrin, transthyretin, retinol-binding protein, antithrombin, transcortin. The decrease of such proteins may be used as markers of inflammation. The physiological role of decreased synthesis of such proteins is generally to save amino acids for producing “positive” acute-phase proteins more efficiently.
Positive acute-phase proteins
serve (as part of the innate immune system) different physiological functions within the immune system. Some act to destroy or inhibit growth of microbes, e.g., C-reactive protein, mannose-binding protein,[3] complement factors, ferritin, ceruloplasmin, serum amyloid A and haptoglobin.
Fibrinogen, prothrombin, factor VIII, von Willebrand factor,
Plasminogen activator inhibitor-1 (PAI-1)
Lipopolysaccharide
Endotoxin. a collective term for components of the outermost membrane of cell envelope of Gram-negative bacteria, such as E. coli and Salmonella[2] with a common structural architecture. Lipopolysaccharides (LPS) are large molecules consisting of three parts: an outer core polysaccharide termed the O-antigen, an inner core oligosaccharide and Lipid A (from which toxicity is largely derived), all covalently linked.
Endotoxin
Lipopolysaccharide. a collective term for components of the outermost membrane of cell envelope of Gram-negative bacteria, such as E. coli and Salmonella[2] with a common structural architecture. Lipopolysaccharides (LPS) are large molecules consisting of three parts: an outer core polysaccharide termed the O-antigen, an inner core oligosaccharide and Lipid A (from which toxicity is largely derived), all covalently linked.
PAMPs
Pathogen-associated molecular patterns.
DAMPs = damage-associated molecular patterns.
Bruton disease
X- linked Agammaglobulinemia
X- linked Agammaglobulinemia
First described by Bruton
X-linked disorder
Found in male babies expressed around 5 to 6 months of age (maternal IgG disappears)
In boys, pre-B cells did not differentiate into mature B lymphocytes
There is a mutation in the gene that encodes for a tyrosine kinase protein
A low level of all immunoglobulins (IgG, IgA, IgM, IgD, and IgE) is present
Infants with X-linked agammaglobulinemia suffer from recurrent bacterial infections: otitis media, bronchitis, septicemia, pneumonia, and arthritis, and Giardia lamblia causes intestinal malabsorption.
Intermittent injections of large amounts of IgG keep the patient alive, but a patient may die at a younger age if infection with antibiotic-resistant bacteria occurs.
Bone marrow transplantation is critical.
Selective Immunoglobulin IgA Deficiencies
IgA deficiency is more common than other deficiencies of immunoglobulins.[4]
These patients are more prone to recurrent sinus and lung infections.
A malfunctioning in heavy-chain gene switching may cause this problem.
Treatment should not include gammaglobulin preparations to prevent hypersensitivity reactions.
In the western world, selective IgA deficiency occurs in about 1 in 600 individuals.
In the rare subset of patients in whom IgE or IgG anti-IgA antibodies have formed, anaphylactic reaction to blood products may occur.
Anti-IgA antibodies have been detected in 76.3% of IgA deficient individuals who had a history of anaphylactic transfusion reaction versus 21.7% of asymptomatic IgA deficient individuals.
Currently, there are no universal guidelines for screening for anti-IgA antibodies.
DiGeorge syndrome
Congenital thymic aplasia (DiGeorge syndrome)[5]
Tetany is present.
Fungal and viral infections are common.
A transplant of the fetal thymus is needed to correct this deficiency.
Chronic Mucocutaneous Candidasis[6]
Selective defect in the functioning of T-cells.
Patients with this disorder usually have a normal T-cell mediated immunity to microorganisms other than Candida.
B-cell function is normal.
Disorders affect both genders, and it is inherited.
Patients, in addition to the above, will have other disorders like parathyroid deficiencies.
Antifungals are useful.
Hyper-IgM syndrome
This disorder is characterized by bacterial infections, including pneumonia, meningitis, otitis, among others that start in early childhood.
High levels of IgM.
Other immunoglobulins are defective.
Lymphocytes are normal in numbers.
The gene encoding the CD40 ligand on T lymphocytes is faulty.
B and T lymphocyte cooperation in the immune response are compromised.
The failure to interact with CD40 results in an inability of the B cell to switch from the production of IgM to the other classes of antibodies.
Immunoglobulin therapy is recommended.
Interleukin-12 receptor deficiency
Mycobacterial infections are frequent due to the lack of the interleukin-12 receptor.
Treatment involves selective antimicrobials.
Severe combined immunodeficiency disease (SCID)
There is a failure of early stem cells to differentiate into T and B lymphocytes.
Deficiency of the interleukin-2 receptor is the most prevalent.
Other problems are due to defective genes encoding ZAP-70, Janus kinase 3, and the genes involved in the DNA recombination of immune cells receptors: RAG1 and RAG2.
Clinically characterized by a variety of infections, including those caused by opportunistic pathogens.
Selective antibiotics, antivirals, and antifungals are available after the pathogen identification.
Immunosuppressive therapy is not needed after allograft transplantation.
Severe combined immunodeficiency disease (SCID)
Without HSC transplantation, death occurs in the first year of life.
Some patients develop a morbilliform rash shortly after birth due to maternal T cells transferred across the placenta and attack the baby causing GVHD.
Affected present with oral candidiasis (thrush), extensive diaper rash and failure to thrive.
Wiskott-Aldrich syndrome
X-linked
Thrombocytopenia, eczema and marked vulnerability to recurrent infection resulting in early death.
This syndrome is associated with normal T-cell numbers with reduced functions, which get progressively worse.
IgM concentrations are reduced, but IgG levels are normal.
Both IgA and IgE levels are elevated.
These patients have a defective WASP, which is involved in actin filament assembly.
V(D)J recombination
(variable–diversity–joining rearrangement) is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire of antibodies/immunoglobulins and T cell receptors (TCRs) found in B cells and T cells, respectively. The process is a defining feature of the adaptive immune system.
Immunodeficiency with ataxia-telangiectasia
Autosomal recessive
Ataxia (abnormal gait)
Telangiectasia (vascular malformation)
Increased incidence of tumors esp. lymphoma
May effect both B and T cells.
Thymic hypoplasia
Defective isotope-switched antibodies mostly IgA and IgG2.
Chromosome 11, encodes a protein kinase called ATM (ataxia telangiectasia mutated) activates p53, important in response to DNA damage (double-strand breaks) important in V(D)J recombination.
Immunodeficiency with ataxia-telangiectasia
This is a deficiency of T-cells associated with a lack of coordination of movement (ataxia) and dilation of small blood vessels of the facial area (telangiectasis).
T-cells and their functions are diminished to various degrees.
B-cell numbers and IgM concentrations are normal to low.
IgG is often reduced, and IgA is considerably reduced.
There is a high incidence of malignancy, especially leukemias, in these patients.
MHC deficiency (Bare leukocyte syndrome)
This subjects have fewer CD4+ or CD8+ T lymphocytes that predispose these individuals to be prone to recurrent infections.
Antibody production is affected and predispose to bacteremia.
Hereditary angioedema
autosomal dominant genetic pattern.
Caused by C1 inhibitor deficiency
Clinically characterized by generalized edema including the one leading to acute suffocation
Therapy with oxymetholone and danazol can be helpful in correcting the defect.
C3 deficiency.
Frequent infections by extracellular bacteria
C5 deficiency predisposes to
viral infections.
deficiency of the membrane attack complex (MAC) are particularly susceptible to
bacteremia caused by Neisseria species.
C2 and C4 deficiencies
Autoimmune diseases caused by C2 and C4 deficiencies and mimics systemic lupus erythematosus.
Chronic granulomatous disease (CGD)
mostly an X-linked disorder.
It is clinically characterized by a defective NADPH that interferes with the intracellular ability of neutrophils to kill engulfed bacteria species.
NADPH oxidase is required for the generation of peroxidase and superoxides that will kill the organisms.
The intracellular survival of the organisms leads to the formation of a granuloma, an organized structure consisting of mononuclear cells.
These granulomas can become large enough to obstruct the stomach, esophagus, or bladder.
Patients with this disease are very susceptible to opportunistic infections by certain bacteria and fungi, especially with Serratia and Burkholderia.
Nitroblue tetrazolium (NBT) dye reduction test confirms the diagnosis of CGD and the dichlorofluorescein (DCF) test is also useful.
Aggressive therapy with wide-spectrum antibiotics and antifungal agents is required.
Leukocyte adhesion deficiency syndrome
characterized by pyogenic infections, including pneumonia and otitis.
It is an autosomal recessive disease, and the faulty gene encodes for an integrin.
There is an impaired adhesion and defective phagocytosis of bacteria.
Treatment involves the use of selective antibiotics.
DiGeorge anomaly defect
defect in the third and fourth pharyngeal pouches
DiGeorge anomaly chromosome
have partial monosomy of 22q11-pter or 10p.
In the bare leukocyte syndrome, there is a mutation in the gene that encodes
for the MHC class II transactivator (CIITA), resulting in the absence of class-II MHC molecule on antigen-presenting cells including macrophages and dendritic cells. A mutation in the gene that encodes for a transport-associated protein (TAP) results in the lack of class-I MHC molecule expression, which is manifested by a deficiency of CD8+ T lymphocytes.
Isohemagglutinin
The strict definition of this term is an antibody that agglutinates red blood cells from others of the same species. So, technically, we could call any alloantibody identified in human plasma an “isohemagglutinin.” However, blood bankers use the term only in reference to the naturally occurring antibodies in the ABO blood group system:
Anti-A in a group B person
Anti-B in a group A person
Anti-A, anti-B, and anti-A,B in a group O person
A negative Mantoux test shows
A negative Mantoux test shows the T-cell deficiency.
Enlarged spleen will produce dullness in
Enlarged spleen will produce dullness in Traube’s space and the clinical features suggest infectious mononucleosis.
cause a widespread erythematous rash in patients with infectious mononucleosis
Amoxicillin is known to cause a widespread erythematous rash in patients with infectious mononucleosis. Therefore, it should not be prescribed to patients with sore throats.
