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Histology #5 (Immunology) Flashcards

1
Q

Primary Lymphoid Organs

A
  1. Thymus
  2. Bone marrow

BOTH - central loactions for blood and immune cell development

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2
Q

Bone Marrow

A

Red or Yellow Bone marrow - located in the cavity /center of most bones

Red marrow - blood stem cells
Yellow marrow -Stem cells that become bone acartdge or fat

Bone marrow vasculature composed of arterioles which transition into a dense network of fenestrated sinsusoids
- Have smooth porus bone + have areas with large gaps –> help move things
- Have perivascilar reticular cells + fibroblasts - aid in blood cell development

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3
Q

Function of Bone Marrow

A

Thymus and bone marrow = central points for lymphocyte development

Bone marrow - produces RBCs, + White blood Cells + Platlets
- IN sinusuidal space you have progenitor cells –> cells ca become lymphoctes + WBCs + RBCs –> go to blood –> go to body

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4
Q

Bone marrow Histology

A

Have Trobecular at the top –> then granulocytes (mature WBCs) –> Then megakaryocytes (elongated and round ; makes platlets) –> Then erthyorid island (makes RBCs)

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5
Q

Thymus Gland

A

Location - Suprior mediastinual retrostinial (Above the heart)

Thymus = split into two lobes with a cortex and medula

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6
Q

Layers of the Thymus

A

Outter = capsle - invaginates into the interlobal septum
- Has blood vessles + lymphatics + nerves

Cortext = has ympahtics and cortocal eithelial

Medulla - has medula epithiliary and DCs + has thymic cropsucle
- Helps with regeneration of the thymis

Interlobular space - has bu,py texture

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7
Q

Function of Thymus

A

Function - Development of T cells

Progentitor cells form bone marrow will enter thymic medulla by high endothelial venules (HEVs) –> get T cel development

T cell development - need binding to APC with good affinity for a positive signal ; self-reactive leads to negative sleective which causes apoptosis

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8
Q

Thymus Histology

A

Left - Fetal - high cell density (thick medual and cortical spaces + lots of squamous cels)
Right - Adult - Low density of cells + corpuscles are large
- Shows thymus shrinks as we age

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9
Q

Secondary Lymphoid Organs

A

Function - Secondary Lymphoid organs are where the lymphociytes are activated and do their jobs to fight pathogens

Organs:
1. Lymph Nodes (Encapsulated)
2. Spleen (Encapsulated)
3. Mucocal associated (Tonsils) + Peyer’s Patches + Bronchus-associated lymphoid tissues)

Arranges as a series of filters

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10
Q

Lymph Nodes

A

Encapsulated clumps of tissue (bean shaped)
- Encapsuladed by a dense college tossie + have trebecula

Contain Immune cells

Function - Filters debris and antigens + immune response
- imune cells trap pathogens and starts producton of AB

100-200 nodes throughout the body

Swoellen or painful lymph nodes = sign of active immune system

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11
Q

Layers of the Lymph Node

A

Layers of the Lymph nodes:
1. Corext - has B cells
2. Paracorext - has T cells
3. Medual (innermost) - has B and T cells

Vessels = branch to tissues around the body –> bring lymph to lymph nodes through afferebt vessles (leave and through efferent ; come in through afferent

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12
Q

Lymph Node histology

A

Outter layer = capsul –> Then have cortext and Paracorext

See germinal center - trasient stucture where Mature B cels will activate + proliferate + difefrentiate

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13
Q

Spleen

A

Largest Lyphoid organ

Encapsulated - trabeculae around spleen

Only lymph organ not supplied by lymphatic vessels

Location - Upper left abdomen beneath the diaphram

Compoased of two types of tissues - Red + white pulp

Function:
1. Filter for blood
2. Break down aged RBCs
3. Stores and breaks down platets

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14
Q

Red vs. White pulp

A

Red Pulp - Vacular Sinses filled with blood ; filters foreign sbstantes or damaged RBCs

White Pulp - Lymphatic tissue ; functions in immune resonse

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15
Q

Spleen Histology

A

See Red and White pulp + see srunded by capsul

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16
Q

Mucousa-Asscoiated lymphoid tissue (MALT)

A

Overall - Dispersed aggregates of nonencapsulated lymphoid tissue within mucosa

Funcation - Local immune response at the mucosal surface

Types:
1. Gut associated lymphoid tissue (GALT)
2. Bronchus associated lymphoid tissue (BALT) - immune response in lung
3. Nasal-asscoiated lymphoid tissue (NALT) - immune response in nose (Ex. Tonsils)

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17
Q

Peyer’s Patches

A

Large masses of confluent lymphoid follciles

Location - found in lamina propria and submucosa of ileum (part of small intestine)

Function - Protext against pathogenic bacteria growth in intestine (provides immune response in small intestine)

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18
Q

Peyer’s patch histology

A

Image - histology of the ilum –> peyers is in teh submucosal area

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19
Q

Bronchus assoaited lymphoid tissues (BALT)

A

Overall - Intrapulmonary lympoid tissue found in all lobes of the lungs and along the bronchi

Function - maintence and regulation of lung mucosal immune homeostasis (gives immune response in lung mucosa)
- Similar to Peyer’s patch but in lung

Histology - See lymphotic follicle

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20
Q

Ciculatory Vs. Lymphatic system

A

Ciculatory - Closed system + contains a pump (heart)

Lymphatic system - open system + lined by lymphatic endothelial cells (LECs) that have a different morphology + no pump

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21
Q

How does lymphatic draignage occur

A

Lymphatic drainage is facilitated by interstitial pressure which is determined by hydrostatic/oncotic equilibrium

Process:
Arterial to venous blood you have gas exhnage in the capilies = fluid going in/out of the capailies AND fluid going into he interstitiom = interstial pressure rises –> interstitial pressure move fluid into lymphatic system

When interstital pressure is graeter than the lymphatic pressure fluid diffises into the INTITIAL lymphatics
- Movement into intial lymphatics is facilitated by discontinous basement memebrane on the intial lymphatics (Lymphati enodthlial at begnining of vessle has discontinous basement mambrane which allows for fluid uptake)

ONce interstial pressure increases and flud goes into the lymphatics the fluid goes towards the collecting lymphatics
- Collecting lymphatics posses a continous basememnt memebrane + one way valve and smooth mucle – alows the collecting lymhatics to hold the liquid and prevents the liquid from going back to intial lymphatics

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22
Q

Function of smooth mucle in Collecting lymphatics

A

Contractinon of the smooth muscle drives fluid upstream/prevents the fluid from going back and creates suction within the pre-colecting lymphatics to get the fluid to go towards the collecting lymphatics

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23
Q

Lymphatic histology

A
  • = Lymphatic vessel

See artery (has thick exterior) and veins which ahve thicker exterior compared to the lymphatic vessels
- If have RBCs in the middle = know it is NOT a lymph vessel

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24
Q

Differentiation of Immune cells

A

Immune cells = come from hematopeotic stem cells

Immune cells are created through Hematopeosis

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25
Stain Types
1. H and E 2. Touline Blue stain 3. Wrights stain 4. IHCs
26
H and E stain
Stains nulceo purple and cytoplasm/ECM pink
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Touline Blue Stain
Metachromtic properties Stains mast cell granuals
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Wrights stain
Mix of Eosin and methylene blue Nuceli stain purple/blue Nuertophilic granules stain brown Eosinophilic granuales stain red Erthrocytes stain pink Lymphocytes cytoplsm stains pale blue
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IHC
IHC antibody stains either nucleus or cytosplams of a specific cell type Usually shows up brown but can be other colors
30
Megakeryocyts
Location - located in bone marrow Function - Responsble for platlet generation - Can form thousands of platlets from one cell - Proplatlets - extenstion of long cytoplasmic porcesses - Fragmentation into platlets - Form granuales that have cytokines and surgars that help the platlets function Mature megakaryocytes = form protoplatlents into blood vessels THEn pitch them off and rform platlets themselves
31
Megakaryocytes Histology
See larger + multinucleated + cytosol stains blue because of granuals
32
Platlets (Thrombocytes)
Immune function Small Form blood clots and stop bleeding (restors barrier against outside) Expressing pattern Recignition receptors (PRRs) - bind to pathoges Cytokine and chemokine release to bring in other immune cells Histology - Platlets = small disc shap
33
Thromocytes + macrophages
Platlets (Thrombycotes) can actibate otehr immune cells - activate macrophages + nuetrophils + dendritic cells
34
Megakeryoctyes + platlet histology
Megakeryocytes - largest cell in bone marrow - Granular cytoplasm - Multi nucelated - Poplatelet extension PLatlets - Small - Disk shaped (inactivated) or spiky (Activated) - Anuceluated - Stain purple/blue on H and E due to granuals Image - megakeyyocyte with platlet budding off
35
Mast cell
Function - mediate the inflamatory repsonse - Associated function with alllergs becase the granuals they contain Contain granuales loaded with histamine and heprin - When activated granials are released --> Histamine is release --> histamine causes teh blood vessles to expand/become more pemable --> get allergy response - Responsible for redness + warmth + swelling often seen in allergic reactions
36
Mast cell histology
Round or oval shaped Cytoplasm filled iwth granals Round/Oval nuceli Typically found in connective tsisues Granuals stain purple Can idetify them using Toluine blue
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Mast Cell histology (Touline Blue)
Touline blue stain - Metachomatic granuals - Stain granulocytes an intesne purple - See connective tissue + interaction wih Mast cells
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Nuertophils
Overall - Granulocytes that have broad antimicrobial propertes Function: 1. Phagocytosis - engluf pathigens + detsroy pathogens through oxidative agents 2. Degranulation - Releases antimicrobial pepetides - Enzymes for production of ROS to kill pathogen 3. NETosis - decoindense chromiatin + secretes from the cell to trap and kill microbes
39
Neutrophil Histology
Image - shows a multi lobal nuceli Multi lobular nucelus (2 or 3-5) 12-14 um (smaller than eosenphils or macrophages ; large than RBCs) Cytoplams pale pink in H and E Stains used: 1. H and E 2. Stains for blood smear (Wright' stiain) - Pale blue/pink cytoplams + many granual 3. IHC
40
Neutrophil Histology (Wright's stain)
Pale blue/pink cytoplams
41
Neutrophil Histology (IHC)
For IHC use CD66b and myeoperoxidase (MPO)
42
Eosenophils
Overall - Granulocytes that primarily mediate thr repsonse to parasitic inefction + allergens Eosenophils releae contents of granuals through exocytosis
43
Contents of eosenophil granuals
1. Major basic protein (citotoxic) 2. Eosenphilic peroxidase (Make ROS) 3. Eosenophilic catanoic proteins (ribonuclease) 4. Eosenophilic derived neurotoxin (ribonuclease)
44
Eosenophil Histology
Bilobal Nucelus Larger than nuertophils ; smaller than macrophages Acidophilic granials stain red/purple Stains used: 1. Any stain containing Eosin 2. Congo Red 3. IHC
45
Eosenophil Histology (Congo red)
Congo Red = Azo dye with pH indicator properties Image - nuertophils are a dark orange/brown
46
Eosenophil Histology IHC
IHC markers = AB against secreted factors (Ex. against major basic protein) OR ILR5a or CCR3
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Macrophage and Monocyte function
Overall - play broad roles in immunity and tissue homoestasiis Immunity: 1. Antigen presntation --> Activates lymphocytes 2. Phagocytosis --> engulfing pathoges + destrction of pathigen through ROS 3. Amplification of the immune system - through secretion of chemockines and proinflamatory cytokines 4. Repair and resolution after inflamation - thorugh secretion of anti-inflamatory cytokines and tissue repair factors Maintain of homeostasis - Tissue specific function - iron recycling (liver) + bone remodeling (mediate bone repair)
48
Macrophage and Monocyte Histology
Eccentric nuclei (central nucleaus ; indented nucelus) Round/oval shape large (10-30 um) Foamy looking cytoplams (because of seondary lysosome) Stains: 1. H and E 2. Stains for blood smears (Wrights) 3. IHC markers
49
Macrophage and Monocyte Histology (Wright stain)
Have pale blue cytoplasm + few granuales
50
Macrophage and Monocyte Histology IHC
AB = CD68 + Cd11b + CD14
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Lymphocytes
Includes: NK cells + T cells + B cells - NK = innate immune response - T and B cells = Key players in adpative
52
Function of NK Cells
1. Recognize misisng self on cells (recignize when cells lack MHC I moleculaes) 2. Destroy infected cells using perforin and granzymes 3. Release cytokines -- recruits other immune cells to help
53
T cell function
Overall - idetify spcific features of pathogens T cells are divided in CD4 helper and CD8 cytotocis - CD8 = directley kill inefcted cells via apoptosis - CD4 - Infleunce other cells via cytokines and cell-cell interactions
54
B cell Function
1. Antigen presenting cels 2. Form memory cells 3. Produce Antibodies Function in Humoral immunity
55
T and B cell histology
T and B cells = similar in side to RBCs + have spheric nuclei + scant cytoplasm - In H and E it is hard to distigush betwen T and B cel;s - Key featire = sherical nucleus with scant cytoplasm (dark dot because mostlu nucleus and less cytopslam) IHC: - T cells = CD3 + CD4 (for CD4 T cells) + CD8 (for CD8 T cells) - B Cells = CD19
56
NK cell histology
Image - Wright's stain NK cells = Bigger than T and B cells Larger nuclei (conatins course chromatin) Smaller granuales in the cytoplasm (surroudning nuclei) IHC marker - CD56
57
Plasma Cells
Differentiated B cells Function - secrete imunoglobulin/antobodies in repsonse to antigens
58
Plasma Cell histology
Larger than lympphocytes Round nucelus with coarse chromatin - Nuclei = arranged in "clock face/art wehen" pattern + have perinucelus clearing (white/lighter pruple next to the nucleus) Abundent deep blue cytoplasm IHC marker = CD138
59
Immune Disease
1. SCID 2. Hasimotos 3. Chronc myeloid leukemia (CML)
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SCID
Group od rare inherited disordered that acuse infants to be born without working immune systems Ex. David vetter (bubble boy) SCID infants = appear healthy at birth (because have AB from mom) but become suceptible to sever infections Smpytoms (present at <3 months) 1. Failire to thrive 2. Recurent bacteria + vural + fngal + protozoal infection 3. Diahria 4. Physical examination - Thrush in mouth and diapper area + seboric dermititis + alopecia + absent lymphatic tossie including toniles and thymus
61
What does SCID affect
SCID = affects both B and T arms of tha daptive immune system New born screening test - meausre T cell receprto exicsion circles (TRECs = byproduct of R cell development)
62
Most common types of SCID
1. X linked - low levels of T cells and NK cells due to defective regulatory T cell development 2. RAG1/RAG 2 SCID - no T and B cells due to missing ymphocute receteptor formation 3. Adenosine deaminsae deficiencey SCID - Low levels fo T. B, and NK cells due to toxic metabolite
63
Treatment of SCID
1. Antibiotic 2. Immunoglobulin replacment 3. Pateint isoltaion 4. Allogenic bone marrow transplant 5. Enzyme replacment therapy (less common) 6. gene threapy
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SCID Histology
65
Hashimotos
LOOK OVER MY SLIDES
66
Chronic Myloid Leukemia (CML)
Overall - cancer of the bone marrow and the blood 10% of all new luekmia pateints 50% of new diagnosed pateints are asymptomatic Slowly progresses + usually presenyed after/during middle age (rarley in kids)
67
CML phases
Chronic --> Associated --> BLAST pahse
68
Cause of CML
Philidelphia chromsome Found in nearly all cases Forms by a reciprical tranlsoation betwen chromosme 9 and 22 --> get BCR-ABL 1 Fusion gene
69
CML pathophysiology
BCL-ABL 1 is an oncogene --> leads to constitutivleu active Tyrone Kinase Result - Granulcytic overproduction - get extra cells in the blood and bone marrow
70
Philideplphia chromosme karytoptype
71
CML Diagnosis
Luekocytosis (High WBCs) + Anemia (low RBCs) in advanced stages Comeplete a Bone marrow biposy - cytogenic analysis (detection of the philidelphia chromsome) Complete FIS or qPCR to look for BCR-ABL gene) Comeplete Reverse Transriptase to detect BCR-ABl protein
72
CML Histology #1
See a TON of cells (No white spaces between cels)
73
CML Histology #2
A - bone marrow Aspirate B - Bone marrow biopsy C - Bone marrow biposy D - Myofibrosis in bone marrow Biopsy
74
CML Treatments
TKI Inhibitors - taregts the tyrosin kinase protein from BCR-ABL gene Chemotherapy - combined with traget teharpy for agressive CML Bone marrow trasnlats - only treatment that can cure CML but has High risk and rate of serious complicatons
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Human Body (31 decks)

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