Immune System Histology Flashcards
what are primary lymphoid organs?
-bone marrow and thymus
-central locations for blood and immune cell development
bone marrow
-red or yellow bone marrow that are located in the center of most bones
-red marrow contains red blood stem cells
-yellow marrow contains fat
what is bone marrow vasculature composed of?
arterioles which transition into a dense network of fenestrated sinusoids
what is the function of bone marrow?
bone marrow produces blood cells: red blood cells, white blood cells, and platelets
thymus gland
superior mediastinal retrosternal organ split into two lobes with a cortex and medulla
what is the function of the thymus?
-development of T cells
-progenitor cells from the bone marrow enter thymic medulla by high endothelial venules (HEVs)
what are secondary lymphoid organs?
-where lymphocytes are activated
-lymph nodes, spleen, mucosal-associated lymphoid tissues like tonsils, peyer’s patches, bronchus-associated lymphoid tissues (BALT)
-arranged as series of filters
lymph nodes
-bean-shaped, encapsulated clumps of tissue
-contain immune cells
-filter, immune response
-100-200 lymph nodes throughout the body
-swollen or painful lymph nodes —> sign of active immune system
spleen
-largest lymphoid organ
-found in the upper left abdomen, beneath the diaphragm
-composed of two tissue types: red pulp with vascular sinuses filled with blood and white pulp with lymphatic tissue
-filter for blood, break down aged red blood cells, and stores/breaks down platelets
mucosa-associated lymphoid tissue (MALT)
-dispersed aggregates of nonencapsulated lymphoid tissue within mucosa
-local immune response at the mucosal surface
types of MALT
-gut-associated lymphoid tissue (GALT)
-bronchus-associated lymphoid tissue (BALT)
-nasal-associated lymphoid tissue (NALT)
peyer’s patches
-large masses of confluent lymphoid particles
-found in lamina propria and submucosa of ileum (part of the small intestine)
-protect against pathogenic growth in the intestine
bronchus-associated lymphoid tissue (BALT)
-intrapulmonary lymphoid tissue found in all lobes of the lungs and along the bronchi
-maintenance and regulation of lung mucosal immune homeostasis
circulatory system vs lymphatic system
-cardiovascular circulatory system is closed and contains a pump
-lymphatic system is open with no pump and lined with lymphatic endothelial cells (LECs)
-lymphatic drainage is facilitated by interstitial pressure, which is determined by a hydrostatic/oncotic equilibrium
high interstitial pressure —> lymphatic absorption
-when the interstitial pressure is greater than lymphatic pressure, fluid diffuses into the initial lymphatics
-facilitated by discontinuous basement membrane on the initial lymphatics
lymphatic absorption
initial lymphatics —> pre-collecting lymphatics —> collecting lymphatics
collecting lymphatics: morphology
-possess a continuous basement membrane, one-way valves, and SMCs
-muscle contraction drives fluid upstream and creates suction with pre-collecting lymphatics
overview of cells
multipotential hematopoietic stem cell (hemocytoblast) —> can become common myeloid progenitor or common lymphoid progenitor
common myeloid progenitor
can become a megakaryocyte, erythrocyte, mast cell, myeloblast
common lymphoid progenitor
can become a natural killer cell (large granular lymphocyte) or small lymphocyte
stain types
-hematoxylin and eosin (H&E)- nuclei stains purplish blue and the cytoplasm and extracellular matrix are pink
-toluidine blue stain- metachromatic properties and mast cell granules
-wright’s stain- mix of eosin and methylene blue, nuclei stains purplish blue, neutrophilic granules stain brown, eosinophilic granules stain red, erythrocytes stain pink, and lymphocyte cytoplasm stains pale blue
-immunohistochemistry- IHC antibody stains either nucleus or cytoplasm of a specific cell type and usually shows up brown but can be other colors
megakaryocytes
-largest cell in the bone marrow
-granular cytoplasm
-multinucleated with proplatelet extensions
-responsible for platelet generation- can form thousands of platelets from one cell, proplatelets are the extensions of long cytoplasmic processes, and fragmentation into platelets
megakaryocytes —> thrombocytes
-thrombocytes have an immune function
-form blood clots and stop bleeding
-express pattern recognition receptors (PRRs) to bind to pathogens
-cytokine and chemokine release
-can activate macrophages, neutrophils, and dendritic cells
platelets
-small
-disk shaped or spikey based on activation
-anucleate
-stain purplish blue in H&E due to granules
mast cell function
-mediate inflammatory response
-contain granules loaded with histamine and heparin
-when activated, histamine is released
-histamine causes the blood vessels to expand and become more permeable —> leads to redness, warmth, and swelling often seen in allergic reactions
mast cell histology
-round or oval shaped 8-20 micrometers
-cytoplasm filled with granules
-round to oval nuclei
-typically found in connective tissue
-in toluidine blue stain, the granulocytes are an intense purple color
neutrophil function
-granulocytes that have broad antimicrobial properties
-phagocytosis- engulfs pathogens, destruction through oxidative reagents
-degranulation- antimicrobial peptides (e.g. defensin) and enzymes for production of reactive oxygen species
-NETosis- decondense chromatin, secretes from the cell to trap and kill microbes
neutrophil histology
-multilobed nucleus (2 or 3-5)
-~12-14 micrometer diameter (smaller than eosinophils or macrophages)
-cytoplasm pale pink color under H&E
-stains for blood smear (e.g. Wright)- pale blue-pink cytoplasm, many granules
-in IHC it stains CD66b and myeloperoxidase (MPO)
eosinophil function
-granulocytes that primarily mediate the response to parasitic infection and allergens
-release contents of granules through exocytosis
what are in the granules of eosinophils?
-major basic protein (cytotoxic)
-eosinophilic peroxidase (reactive oxygen species)
-eosinoplilic cationic protein (ribonuclease)
-eosinophil-derived neurotoxin (ribonuclease)
eosinophil histology
-bilobed nucleus
-~12-17 micrometers in diameter —> larger than neutrophils, smaller than macrophages
-acidophilic granules (stain red or reddish purple)
-stains: any stain containing eosin (H&E), congo red (azo dye with pH indicator properties), and IHC markers (antibodies against secreted factors (e.g. major basic protein),IL5Ra, CCR3
macrophage and monocyte function in immunity
-antigen presentation with active lymphocytes
-phagocytosis where you engulf pathogens, destroy through oxidative reagents
-amplification of the immune response by secretion of chemokines and pro-inflammatory cytokines
-repair and resolve after inflammation with secretion of anti-inflammatory cytokines and tissue repair factors
macrophage and monocyte role in maintenance of homeostasis
iron recycling and bone remodeling
macrophage and monocyte histology
-eccentric nuclei, often indented
-round to oval shape
-large, 10-30 micrometers in diameter
-“foamy” looking cytoplasm (secondary lysosomes)
-stains: H&E, stains for blood smears like Wright’s (pale blue cytoplasm, few granules), and IHC markers (CD68, CD11b, CD14)
lymphocyte function
-natural killer (NK) cells, T cells, and B cells
-NK cells are involved in the innate immune response
-T and B cells are in the adaptive immune response
function of NK cells
-recognize ‘missing self’ on cells where the self are MHC Class I molecules
-destroy infected cells with perforin and granzymes
-release cytokines to tell other immune cells to help
function of T cells (cell-mediated)
-ID specific features of pathogens
-helper T cells (CD4+) and cytotoxic T cells (CD8+)
-CD8+ will directly kill infected cells via apoptosis
-CD4+ will influence other cells via cytokines and cell-cell interactions
function of B cells (humoral)
-antigen-presenting cells
-form memory cells
-produces antibodies
lymphocyte histology
-similar in size to red blood cells
-spherical nuclei
-scant cytoplasm
-IHC markers for T cells: CD3, CD4, and CD8 then for B cells: CD19
how are NK cells stained?
-Wright’s
-bigger than lymphocytes (15-18 micrometers)
-large nuclei with coarse chromatin
-small granules in cytoplasm
-IHC marker of CD56
plasma cell function and histology
function:
-differentiated B cells
-secretes immunoglobulin/antibodies in response to antigens
histology (wright’s):
-slightly larger than lymphocytes (14-20 micrometers)
-round nucleus with coarse chromatin
-abundant deep blue cytoplasm
-IHC marker of CD138
-paler part of the cytoplasm near the nucleus
severe combined immunodeficiency (SCID)
-group of rare inherited disorders that cause infants to be born without a working immune system
-SCID infants appear healthy at birth but become highly susceptible to severe infections
when do symptoms of SCID appear and what are they?
-present at < 3 months of age
-failure to thrive
-recurrent bacterial, viral, fungal, and protozoal infections
-chronic diarrhea
-thrush in mouth and diaper area
-seborrheic dermatitis
-alopecia
-absent lymphatic tissue, including tonsils and thymus
SCID immune system
-SCID affects both the B and T arms of the adaptive immune system
-newborn screening test- measures T cell receptor excision circles (TRECs), a byproduct of T cell development
what are the most common types of SCID?
-X-linked SCID- low levels of T cells and natural killer cells (NK cells) due to defective regulatory T cell development
-recombinase activating genes 1 and 2 (RAG1/2) SCID- no T and B cells due to missing lymphocyte receptor formation
-adenosine deaminase (ADA) deficiency SCID- low levels of T, B, and NK cells due to toxic metabolite
SCID treatment
most common treatments:
-antibiotics
-immunoglobulin replacement therapy (IVIG)
-patient isolation
-allogenic bone marrow transplant
other treatments:
-enzyme replacement therapy
-gene therapy
hashimoto’s overall
-autoimmune disease causing destruction of thyroid cells —> decreased production of thyroid hormone (hypothyroidism)
-chronic autoimmune thyroiditis or chronic lymphocytic thyroiditis
-caused from genetic and environment
-
normal thyroid function
thyroid hormone affects:
1. how the body uses energy (metabolism)
2. maintaining body heat
3. supporting organ function (heart, brain, muscles, CNS, GI)
hashimoto’s pathophysiology
overall: gradual thyroid failure
1. destruction of thyroid gland via autoimmune mechanisms
2. lymphocytic infiltration
what does thyroid peroxidase do?
thyroid peroxidase and thyroid globulin —> block the function of the antigens —> damage thyroid —> get inflammation of the thyroid —> overtime the thyroid gland gets bigger and damaged and can’t make thyroid hormone
hashimoto’s diagnosis
-elevated levels of thyroid stimulating hormone
-low thyroxine levels
-high anti thyroid peroxidase antibodies
-high anti thyroglobulin antibody
what are symptoms of hashimoto’s?
-larger thyroid gland
-exhaustion
-weight gain
-muscle weakness
-constipation
-dry skin and hair
-epithelial thinning
-slowed hair growth
-increase vascular resistance in periphery and reduced cardiac output
how is hashimoto’s treated?
levothyroxine- works by replacing normal thyroid hormone that is usually present in the body
chronic myeloid leukemia (CML)
-cancer of the bone marrow and blood
-10% of all new leukemia cases —> 50% of newly diagnosed patients are asymptomatic
-slowly progressing usually presents during or after middle age
what are the phases?
-chronic- the earliest phase with best response to treatment
-accelerated- transitional phase where the disease becomes more aggressive
-blast- severe, aggressive phase becoming life-threatening
what are blast cells?
immature blood cells that build up in the bone marrow and blood
philadelphia chromosome
-found in nearly all cases of CML
-reciprocal translocation between chromosomes 9 and 22
-BCR-ABL1 fusion gene
what is reciprocal translocation?
a genetic rearrangement that occurs when two parts of chromosomes are exchanged, without net loss of genetic info
CML pathophysiology
-BCR-ABL1 oncogene (abnormally expressed or mutated genes that cause cancer by inducing cells to grow and divide uncontrollably)
-constitutively active tyrosine kinase (enzymes responsible for the activation of many proteins by signal transduction cascades)
-granulocyte over-proliferation
-extra cells in blood and bone marrow
CML diagnosis
-leukocytosis (high WBC)- anemia (low RBC) in advanced disease
-bone marrow biopsy (cytogenic analysis with detection of the philadelphia chromosome)
-fluorescence in situ hybridization or qPCR for detection of the BCR-ABL gene
-reverse transcriptase for detection of the BCR-ABL protein
what are some treatments of CML?
-TKI inhibitors- target the tyrosine kinase protein from the BCR-ABL gene
-chemotherapy- combined with targeted therapy for aggressive CML
-bone marrow transplants- only treatment that can cure CML but high risk and rate of serious complications
