Hyper- and Hypo- Immune Disorders Flashcards
What are the two branches of the immune system?
- Innate
2. Adaptive
What is the innate immune system?
non-specific response that targets many common pathogens;
NOT PATHOGEN SPECIFIC, limited diversity
Does the innate immune system need prior exposure?
NO
How does one develop an innate immune system?
passed on from previous generation;
does NOT need previous exposure to pathogen
What compromises the innate immune system?
- epithelial & mucous membranes
- complement factors
- neutrophils
- macrophages
- monocytes
What is the adaptive immune system?
system that must be developed individually; develops memory & is specific towards antigens
delayed response
Which is faster, the innate or adaptive immunity?
innate,
adaptive is delayed
What types of cells are involved in adaptive immunity?
lymphocytes;
B lymphocytes
T lymphocytes
What are the principle cells of the innate immune system?
myeloid cells
→ macrophages, neutrophils, dendritic cells
What is the innate immune system mediated by?
cells and plasma proteins that are ALWAYS present
Is the adaptive immune system weak or powerful?
powerful; usually “silent” until pathogen is found
What creates the receptors of the adaptive immune system?
rearrangements of antigen-receptor genes that occur during the maturation of the lymphocytes
What are the principle cells of the adaptive immune system?
KNOW!!
B lymphocytes
T lymphocytes
The adaptive immune system is mediated by what TWO mechanisms?
- Humoral Immunity
→ mediated by antibodies produced by B cells - Cell-Mediated
→ T cells activated by protein antigens from antigen presenting cells (APCs)
What type of cell mediates humoral immunity?
of the adaptive immune system
B cells.
antibodies
1. NEUTRALIZE MICROBES 2. opsonize microbes for phagocytosis 3. activate the complement system
What type of cell mediates, cell-mediated adaptive immunity?
T cells. [2 types]
→ activated by protein antigens from antigen presenting cells (APCs)
require repeat antigen stimulation
What are the 2 types of T cells?
CD4+ helper T cells [secrete cytokines to activate macrophages; helps B cells make antibodies; stimulates inflammation]
CD8+ helper T cells [kill infected & transformed cells]
The three dysfunctions of the innate immune system are:
- inadequate response
- excessive response
- misdirected response
What are 4 types of an inadequate innate immune system response?
- neutropenia
- abnormal phagocytosis
- deficient in the complement system
- hyposplenism
What are 3 types of excessive innate immune response?
- neutrophilia
- monocytosis
- asthma
*over-reaction
What is one example of a misdirected innate immune response?
angioedema
*body responds, but edema is sent to the wrong place
What are 6 dysfunctions of the adaptive immune system?
- defects in antibody production
- defects in T lymphocytes
- combined immune system defects (SCIDs)
- allergic reactions
- anaphylaxis
- autoimmune disorders
” -penia”
lack of, poverty, deficiency
” -philia”
affinity, attraction, fondness
allergy
reactions against normally harmless environmental antigens
hypersensitivity
excessive immunologic reactions to microbes or environmental agents dominated by inflammation
atopy
propensity or genetic tendency to develop allergic reactions
[ie. lots of food and/or environmental allergies]
Antibody (Ab) is also known as…
an immunoglobulin (Ig)
What is an antibody?
large, Y-shaped, protein USED by the immune system TO IDENTIFY and NEUTRALIZE FOREIGN OBJECTS such as pathogenic bacteria and viruses
Where do T cells come from?
Thymus
Where do B cells come from?
Immature cells are released from the bone marrow; mature in the circulation
How are neutrophils formed?
by stems cells in the bone marrow
What % of WBCs are neutrophils?
40-70%
What are neutrophils?
phagocytes that are found in the blood stream;
FIRST RESPONDERS TO INFLAMMATION
[especially bacterial]
*predominant cells in pus
What is neutropenia?
neutrophil count <1500/mm3
What are 5 types of neutropenia?
- neonatal sepsis
- Kostmann syndrome (autosomal recessive)
- acquired defects (chemo, antivirals)
- autoimmune (Lupus, RA)
- Infection [rate of production is inadequate for consumption]
What are the treatments for neutropenia?
- stop causative agent
- granulocyte stimulating factor (filgrastim)
- bone marrow transplant
What does the spleen do?
primary creator of RBCs in fetal life (up to 5 months old)
- removes old RBCs
- blood reservoir (250mL)
- recycles iron
- metabolizes hemoglobin
- stores 1/4 circulating lymphocytes
- stores & clears platelets
- synthesizes antibodies in the white pulp
- removes antibody-coated bacteria
How is hemoglobin broken down?
globin is degraded into amino acids
heme is metabolized into bilirubin [which is removed by the liver]
How do the spleen & liver “work together”?
the spleen “eats” bacteria, blood flow goes to the liver where toxins are removed & “cleansed” from the blood
What is the size of the spleen?
healthy adult:
2.8in x 5.5in
between 1oz-8oz
Asplenia
absence of normal spleen function;
type of immuno-dysfunction
** sepsis risk is increased 350-fold d/t inability to clear bacteria from the blood [S.pneumoniae, E.coli, H.flu, malaria]
Hyposplenism
reduced spleen function
How can sickle cell affect the spleen?
sickle cell can cause auto-infarction, resulting in vaso-occlusive disease
What is leukocytosis?
WBC count is above normal range;
normal reaction as an inflammatory response but can be from
- tumors - leukemias - stress - pregnancy - convulsions - medications [corticosteroids, lithium, beta agonists]
What are the 5 types of leukocytosis?
- neutrophilia
- eosinophilia
- basophilia
- monocytosis
- lymphocytosis
What is eosinophilic esophagitis?
chronic immune system disease in which a type of WBC (eosinophil) builds up in the lining of the esophagus
→ reaction to foods, allergens or acid reflux
- inflame or injure esophageal tissue; can lead to difficulty swallowing or food to get stuck
*food aversion or non-specific s/s
Neutrophilia
> 7000/mm3
4 causes of neutrophilia
- pancreatitis
- pyelonephritis
- peritonitis
- pneumonia
Leukostasis; count & blood
> 100,000/mm3;
thick blood flow and WBC clumping, can lead to TIAs & strokes
Myeloproliferative disorder or hematologic malignancy
> 50,000/mm3
What is asthma?
exaggerated bronchoconstrictor response to stimuli
Cause of extrinsic asthma:
IgE production, allergens
Cause of intrinsic asthma:
triggers are unrelated to the immune system:
- ETT placement
- cold
- exercise
- stress
- inhaled irritants
When does extrinsic asthma typically develop?
childhood or early adulthood
When does intrinsic asthma typically develop?
later in adulthood
Having a personal and/or family history of asthma is most related to which kind of asthma?
extrinsic asthma
What type of asthma is considered a hypersensitivity reaction to an allergen?
extrinsic
Increased IgE levels are most often found in what kind of asthma?
extrinsic
Does intrinsic asthma include recognizable allergens? elevated IgE levels?
no recognizable allergens;
normal IgE levels
When do s/s of intrinsic asthma appear?
after respiratory infection, emotional reactions, exercise, handling chemicals, taking aspirin, etc.
What is the hallmark sign of misdirected innate immunity?
angioedema
What are the two types of misdirected innate immunity?
- hereditary
2. acquired
What two types of edema form in misdirected innate immunity?
SQ and submucosal
What structures are involved in misdirected innate immunity angioedema?
face, extremities, GI tract
What is the most important thing to remember about acquired misdirected innate immunity?
it will NOT respond to epinephrine
Deficiency in ___ is the most common form of hereditary angioedema.
C1 esterase inhibitor
[autosomal dominant deficiency/dysfunction]
C1INH deficiency is Type 1.
C1INH dysfunction is Type 2.
How does a lack of C1 esterase inhibitor lead to edema?
absence of C1 esterase inhibitor leads to the RELEASE of VASOACTIVE MEDIATORS that increase vascular PERMEABILITY…… producing edema via bradykinin
How long will edema d/t C1 esterase deficiency last?
24-72 hours
How do ACEi cause bradykinin induced angioedema?
ACEi block bradykinin catabolism leading to elevated levels of bradykinin.
How does a person develop acquired bradykinin mediated angioedema?
Patients with lymphoproliferative disorders can develop antibodies to the C1 inhibitor… giving rise to a syndrome that closely resembles hereditary angioedema.
Angioedema can be caused via two different physiological mechanisms, these two pathways are…
- release of mast cell mediators
2. bradykinin release (no allergy symptoms)
Angioedema caused by the release of mast cell mediators is associated with what other s/s?
urticaria, bronchospasm, flushing, hypotension
What is the treatment of mast cell mediated angioedema?
drugs usually used to treat allergy & anaphylaxis.
- epinephrine
- antihistamines
- glucocorticoids
What is the treatment of bradykinin mediated angioedema?
C1 inhibitor concentrate (is the preferred treatment).
- kallikrein inhibitor
- bradykinin receptor antagonist
FFP can be administered if the above are unavailable [it contains the deficient enzyme]
What is the treatment of ACEi mediated angioedema?
STOP offending drug & administer supportive care.
→ glucocorticoids have been noted to INCREASE the expression of ACE = accelerate bradykinin METABOLISM
[opposite of the ACEi]
What do kallikrein inhibitors do?
block the conversion of kininogen to bradykinin
What medication blocks the conversion of kininogen to bradykinin?
plasma kallikrein inhibitor
How does FFP treat bradykinin induced angioedema?
provides the deficient enzyme
What two medications are NOT effective in acute episodes of bradykinin-mediated angioedema?
catecholamines & antihistamines
When are catecholamines & antihistamines NOT effective?
in bradykinin mediated angioedema
What are the two types of immunodeficiency disorders?
aka. inadequate adaptive immunity
- Primary (congenital)
2. Secondary
What causes primary (congenital) immunodeficiencies?
gene mutations that are usually inherited
Gene mutation that causes a defect in T lymphocytes is known as ____ syndrome.
DiGeorge syndrome
What are secondary immunodeficiencies encountered in high income countries?
- chemotherapy
- radiation
What are secondary immunodeficiencies encountered in low-income countries?
- malnutrition
- acquired immunodeficiency syndrome (AIDS)
Gene mutations that cause dysfunction in T- B- or NK- cell functions, cause ____ syndromes.
severe combined immunodeficiency syndromes
What is the treatment of severe combined immunodeficiency syndromes?
(SCID)
bone marrow or stem cell transplant
gene therapy
enzyme replacement
What organ causes the immune deficiency in DiGeorge Syndrome?
How does this affect severity?
Thymus hypoplasia
→ degree of immunocompromise correlates with the amount of thymus tissue present
What organs can be affected in DiGeorge Syndrome?
thymus, thyroid, parathyroid
(hypoplasia)
Can also have cardiac defects & facial dysmorphisms
- truncus arteriosus
- TOF
- cleft palate
What gene deletion causes DiGeorge Syndrome?
22q11.2
What cell level is abnormal in DiGeorge Syndrome?
T cells are decreased;
B cells are normal
Complete absence of the thymus results in what sundrome?
severe combined immunodeficiency syndrome (SCID)
Severe combined immunodeficiency syndromes (SCID) affect what cells?
T cells
B cells
NK cells
SCID is linked to what chromosome?
X-linked.
boys are affected
girls are carriers
What is the abnormality in the most common form of severe combined immunodeficiency syndrome?
mutation in the gene that codes for interleukin receptors
lack of interleukin receptors → lack of interleukin signaling → lack of T, B, NK cell differentiation/maturation
What are four categories of excessive adaptive immunity?
- anaphylaxis
- bronchial asthma
- allergic rhinitis, sinusitis
- food allergies