Hormone-like Polypeptide secreted from Inflammatory Cells (lymph's & Mac's), C.T cells, Endothelial cells
- Regulate cellular immune response
- Play major role in Inflammation
Which Cytokines play a major role in Inflammation?
Regulates interaction btwn leukocyte & Lymphocytes
What are the Major Cytokines produced mainly by MACROPHAGES?
IL-1, 6, 12, 18, TNF
What are cytokines are produced by Th1 Cells?
What cytokines are prod. by Th2 cells?
IL-4, 5, 9, 10, 13
what other cells produce IL-1?
T, B cells; NK cells
What other cells produce IL-6?
T, B cells
Bone Marrow cells
What other cells produce IL-12?
ALL the major APC's
What cells also produce TNF?
T & B cells
Function of IL-1
- Co-stimulates Th2 cells
- Stimulates Acute phase response by acting on Neutrophils, Monocytes, Eosinophils, dendritic cells, Hepatocytes= Neutrophilia & Hematopoiesis
Function of IL-6
- Promotes B cell Maturation
- Stimulates Acute phase response
Function of IL-12
- Co-stimulates of Th-1 cells
what stimulates production of IL-18?
Bacteria & Bacterial products stimulate it's production
Function of IL-18?
Acts on Th1 cells to prod:
- IFN-y; forms + feedback on Mac's, IL-18, IFN-y
Function of TNF-a
- Regulates many Immune & Inflammatory rxns
- Activates Mac's to synthesize more cytokines: IL-1,6
- Triggers apoptosis in some tumor cells
- Key role in Control of Body Mass
What cytokines released by Mac's stimulate Th1 cells to produce their cytokines?
Function of IL-2
- Targets T, B, NK cells & Macrophages
Function of IFN-y
- Activates MAC's; enhance their fxn
- Enhance phagocytosis & ADCC
- Activates NK cells, respond to Ag by prod. IFN-y
- Inhibit Th2 cells from prod. IL-4; blocks IgE prod.
- Stimulates Th1(its prod. cell) to prod. IL-2
What IL's are produced by activated Th2 cells, as well as Mast Cells & Basophils?
IL-4 & IL-5
What is a similar function of IL-4 & IL-5?
Simulate B cell Growth
What other fxn does IL-5 have?
Stimulates GROWTH & ACTIVATION of Eosinophils
Hemapoietic Growth factor
Function of IL-9
Stimulates growth of:
- Th cells & Mast cells (derived from bone marrow)
- affects B cells to prod. IgE
Strong Immunosuppressive cytokine
Function of IL-10
Targets: Th-1, B, Mac's, NK, Mast, Thymocytes
What other cells prod. IL-13, besides Th2 cells?
CD8+ T cells
Function of IL-13
Stimulates B cells
Suppress MAC fxn
Induce Giant cell formation
What are the CHEMOKINES?
MIP-2 (Mac. inflamm. protein)
MCP-1 (Monocyte. chemoattractent. protein)
MDC (Mac. derived. protein)
MIP 1a & 1B
What cells prod. IL-8 (chemokine)?
Lymphocytes (T, B)
Fxn of IL-8; Chemokine?
- Chemotactic: to Neutrophils, Basophils, some Tcell
- Activates Neutrophils to express of CD11a/ CD18
- release granule contents
- stimulate Respiratory burst & Leukotriene
WHat produces MIP-2?
Function of MIP-2 ?
POTENT chemotactic for Neutrophils
MCP-1 produced by ?
Mac's, T cells, Fibroblasts, keratinocytes, endothelial cells
Function of MCP-1
Chemotactic for Monocytes; stimulates their Respiratory burst & release of Lysosomal enzymes
MDC (Mac-derived-chemokine) produced by?
activated Dendritic cells
Fxn of MDC?
Attracts T cells to sites of Ag-production
What produces MIP-1a & MIP-1B?
B & T cells
Fxn of MIP-1a & 1B
MIP-1a: chemotactic for B cells, CD8+ T cells, Eosinophils
MIP-1B: chemotactic for CD4+ cells
When are Inteferons (IFN's) produced?
in response to:
- Viral infection (inhibit viral rep.)
- Immune stimulation
- Chemical stimulators
How do IFN's inhibit viral replication?
Interfere w/ viral RNA & Protein synthesis
What are the 2 major groups of IFN's?
Type 1 & Type 2
Type 1= IFN-α, IFN-β, IFN-W, IFN-τ, IFN-δ
Type 2= IFN-Υ (cytokine of Th1 cells)
Where does IFN-α come from?
virus-infected Immature CD4+ cells
Where does IFN-β
What do both IFN-α & IFN-β have?
Where do IFN-W, IFN-τ & IFN-δ come from?
isolated from Trophoblasts of Ruminants, Pigs & Horses
What are IFN-W & IFN-τ used for?
CHECK PAGE 79 (summarizes important mediators & effects)
What cells are involved in the Cellular response?
Basophils & Mast cells
Monocytes, Large mononuclear cells, MAC's
What are Neutrophils a.k.a ?
What are 3 properties of Neutrophils?
1) Strong Amoeboid Movement
2) Strong Phagocytic activity
3) Intracellular digestion of certain matter
where are Neutrophils produced?
Are immature Neutrophils found in circulation?
No; in normal conditions ONLY MATURE neutrophils are released into Circulation
How long do Neutrophils circulate in the blood for, what is there 1/2 life?
- 10 hours (approx)
- Half life= 6-12hrs (spp. dependent)
What happens to Neutrophils once they have circulated the blood?
- enter tissue; destroyed by Apoptosis
- Lost from body by MIgration across Urogenital/
Respiratory/ Alimentary mucosal
- Destroyed by MAC's in Spleen, Liver, Bone Marrow
How long do neutrophils survive in Tissue?
1-4 days; need continuous production by bone-marrow due to short life
What is the most common Leukocyte in Blood of MOST carnivores?
What % of Leukocytes are neutrophils in Ruminants (cattle, sheep, goat), Lab Rodents, and Horses?
Ruminants & Lab Rodents= 20-30%
What is the SHape, size, and contents of Neutophils?
Shape= Round; Size= 12um
- granular cytoplasm (stains NEUTRAL w/ dye)
- Lobed nucleus
- Granules (2 types):
- Small (lysosomal hydrolyses, lactoferin, myeloperoxidase)
- Large (Lysozomes, lacteroferin, Alkaline phosphatase)
WHat do the Neutrophil's granules do?
Larger ones: discharge enzymes into Alkaline pH (lowers pH) so, later acid pH helps smaller granules to act more effectively
WHich cells are the first to leave the blood vessel and reach site of inflammation?
What does the MIGRATION of neutrophils to site of inflamm. stimulate?
Release of "Colony stimulating factor"; stimulates bone marrow "Granulopoiesis"= release of neutrophils (inc. immature)
WHat does the increased production of neutrophils in inflammation cause in the blood?
With Neutrophilia what type of Neutrophils are seen in circulation?
Immature Neutrophils; a.k.a BAND cells
WHat are immature Neutrophils called?
What is the presence of Immature neutrophils known as?
If there is a left shift, but only immature neutrophils are increased, and mature stay as normal or decreased, is it regenerative or degenerative left shift?
Only immature (band forms)= DEGENERATIVE
if you see both increased Mature & Immature (band) forms of Neutrophils in blood what is this called?
Regenerative Left Shift
In a Degenerative Left shift what would you expect the Total no. of Neutrophils to be?
Normal or Decreased (neutropenia)
What does a degenerative left shift indicate?
What is Neutropenia?
Decrease in absolute no's of neutrophils
Causes of Neutropenia?
1) Acute Tissue damage (acute inflammation & sepsis; )
2) Decreased Bone Marrow
3) Increased Margination
What type of Acute Tissue damage causes neutropenia?
In ACUTE inflammation or Sepsis; migration rate of Neutrophils into tissue > prod. by Bone marrow, bands are released= Degenerative Left shift w/ Poor prognosis
E.g. Acute peritonitis/ enteritis/ metritis/ cellulitis
What could cause Neutropenia caused by Decreased bone marrow production?
ie, drug rxn, chemicals/plants, infectious agents, immune-mediated response
what types of infectious agents could cause decreased bone marrow prod resulting in Neutropenia?
Feline Leukemia virus (FLV)
What could be the cause of INcreased margination resulting in Neutropenia?
Anaphalaxis or Endotoxemia
(Shift of CP to MP)
What is Neutrophilia?
Increase in the no. of Circulating Neutrophils
Is Neutrophilia Pathological?
NO; Physiological Neutrophilia can occur in some spp. w/ excitement, fear, exercise, seizure activity; due to release of Epinephrine (adrenaline)
What is a physiological neutrophilia called; how long does it last, where do they come from?
Mature, Transient Neutrophilia; lasts for 1 hour; Shift of MP to CP
what happens w/ Corticosteriod/ Stress induced Neutrophilia?
Stress or Corticosteroid Neutrophilia:
Exogenous admin./ Endogenous secretion of Glucocorticoids= release of Mature neutrophils into circ.
What can cause endogenous release of Glucocorticoids resulting in neutrophilia?
Pain, trauma, Transport & other painful conditions
Causes of Acute inflammatory Neutrophilia
Inflammation, Sepsis, Necrosis, Immune-mediated disease
Effects of acute inflamm. on Neutrophils?
Increased demand & Increased release of segmented/ band Neut's from bone marrow
Causes & effects of ChRonic inflammation on Neutrophils?
Effects: Neutrophilia, due to bone marrow granulocytic hyperplasia; left shift w/ Monocytosis & Hyperglobulinemia
Chronic suppurative lesions: Pyometra/ Pyothorax/Pyoderma/ some neoplasms
What is the MAIN fxn of Neutrophils?
Capture & destruction of Foreign material by Phagocytosis
What are the 4 stages that Neutrophils capture & destroy (phagocytose) foreigners?
What types of foreign material do Neutrophils engulf (phagocytose)?
Carbon, Pigments, Cell debris, BACTERIA
What 2 mechanisms do Neutrophils destroy "digestible" material?
1) Respiratory Burst;
2) Digestion by Lysosomes
Respiratory Burst (neutrophils)
Oxygen-dependent killin of Bacteria/ digestible material
- burst of oxygen comsumption by Leukocytes
- activtation of leukocyte oxidase (NADPH);
oxidises NADPH & reduces O2= Superoxide ion;
converted to H202 (Hydrogen peroxide) in
H2O2 in lysosomes of Neutrophils is not enough to kill bacteria, so how do they destroy bacteria?
Myeloperoxidase (MPO) is in their Azurophilic granules, coverts H202 to MPO-Halide System; very efficient bacteriocidal system
How does Digestion by Lysosomes of Neutrophils occur?
non-oxygen dependent substances in Granules: ie,
- BPI Protein (bacterial permeability increasing)
- Defensin.... Kill microbes
After killing: acid Hydrolases (in azurophilic granules) degrade bacteria w/i phagolysosomes
What would be described as INDIGESTIBLE material to Neutrophils; what happens to these?
Carbon particles; released again after neutrophils die; and become repeatedly phagocytosed by other N/ Mac's
What enhances phagocytosis of bacteria by Neutrophils?
Presence of specific Ab's & complement fragments
1st line of Defense
Neutrophils (limited e. reserve; become exhausted very quickly after limited no. of phagocytic events)
2nd line of defense
Mononuclear Phagocytic System
What 2 other things can neutrophils do, besides Phagocytosis?
- in Acute inflamm. can activate Mast cell to release
Histamine & increase Permeability
- Release Chemotactic agent for Monocytes
LARGE, Amoeboid Phagocytic blood cells
Vary in appearance btwn spp.
Where are eosinophils produced?
What are the spp. differences of Eosinophils?
Dogs & Horses: Bilobed nucleus, thin strand connects
Other spp: may be >2 lobes
Horse: large cytoplasmic granules
Cats: Rod shaped granules
Sheep/Goat/Cow/Pigs: Oval-shaped granules
Dog: Round & variable sized granules
How long do Eosinophils remain in Circulation before entering tissues; what is there Half-life?
In circulation: 30 mins
1/2 Life: 12 days (neut's=6-12hrs)
What % of leukocytes do eosinophils make up in the blood?
Is there a reserve supply of Eosinophils?
Yes; in Bone marrow, Lungs, Intestine, Skin (BLiS)
What do Eosinophil granules contain?
Peroxidase & Acid Phosphatase (enzymes)
Toxic Protein (basic) to parasites
1) Phagocytic (limited)
2) Cytotoxicity (kill): large targets like parasites
3) Augment Inflamm. rxn (esp. during intermediate hypersensitivity rxn)
4) Modulate allergic rxns
What materials do Eosinophils phagocytose?
Bacteria, Yeast, Protozoa, Ag-Ab complexes, Inert materials (but to lesser extent)
Large numbers of eosinophils in blood
Causes of Eosinophilia
Mast cell tumors
Lesser extents: Lymphomas
Large number of eosinophils in Tissues; Cause Unknown; mostly seen in migratory phase of metazoan parasites; they act as cytotoxic leuk's, destroy parasite by degranulation; release of enzymes
A type of Chronic inflammation; w/ dense infiltration of eosinophils; in response to parasites/ etiology (cause) unclear
Species affected by Eosinophilic Granuloma
Different types of Eosinophilic Granulomas
Eosinophilic granuloma complex (CATS)
Eosinophilic granuloma in oral cavity (DOGS)
Equin Collagenolytic granuloma (HORSES)
Eosinophilic granuloma sec. to parasite infection (all)
Eosinophilic Granuloma complex (cats)
in Cats; inc. 3 idiopathic skin lesions:
- Eosinophili plaque
- Linear granuloma
- Eosinophlic Ulcer
Eosinophilic plaque ( Eosin. Gran. complex) characterisitics
Common; Very Pruritic lesions in skin
Sharp demarcated erythematous
ulcerated, ooze serum
on abdomen & inner thigh
Microscope: diffuse infiltration of eosinophils in dermis, occas. extend into deeper subQ tissue
Lesions: like w/ atopic; flea/food allergy dermatitis
What does the Linear granuloma (Eosin. Gran. COmplex- cats) look like?
Pinkish/ yellow linear elevated firm lesions on THIGH
- Centre= brightly stained eosinophilic degenerated collagen, surrounded by large no's of eosinophils, Mac's. & foreign body giant cells
Charcteristics of Eosinophilic Ulcer (in Cat Eosinophilic granuloma complex)
Similar lesions to linear granuloma; except, involves tissues of ORal cavity, esp. tongue.
Eosinophilic Granuloma in DOGS
lesion like in Cats eosin. linear granuloma
in ORAL CAVITY, LIPS, other areas in Form of Ulcer & Vegetative masses
- centre: degenerated collagen surrounded by eosinophilic cells
What spp. affected by Eosinophilic Myositis?
Dogs, Cattle, Sheep
Dog: Eosinophilic Myositis
inflamm. of Muscles of mastication, painful swelling
* German Shephard
- SUDDEN onset, lasts 1-3 wks; leaves m. atrophy
- Marked peripheral Eosinophilia
- Late stages: extends to Esophagus= difficult swallowing
- Histo; eosinophilic mysositis; easy diagnosis; due to periodic nature & selective m. involvement
Cattle/ Sheep: Eosinophilic Myositis
Affects Skeletal & Cardiac M's
diagnosis mainly in Slaughter house
Focal, Greenish discoloration; fades in sunlight
Histo: eosinophilic myositis
Heart involvement: occas. sudden death (unknown)
where are MAST cells derived from?
WHich cells share several fxnal & morphological characteristics?
Mast Cells & Basophils
Where are MAST cells found in body?
Organs rich in CT; mostly at host-environmental Jxn, ie, Skin, GI, Respiratory tract
Next to small venules
MAST cell Lifespan in tissues
(eosin= 12 days; neut= 6-12hrs)
MASt cell Characteristics
Nucleus: Varies in spp.
- Round/Oval, Central/ Eccentric in Cytoplasm
- Basophilic & Metachomatic granules
What is released from MAST cells upon stimulation?
- Preformed Inflammatory prod's (heparin, histamine, serotonin)
- TNF (makes endothelium adhesive for leuk's)
What is synthesized in Mast cells?
PAF (plasmin activation factor)
Chemokines (initiate initial inflamm. response)
Similar to Neut's & Eosin's; mature in Bone marrow
Circulate in blood & recruit in tissues
Lifespan in tissue: several days
what is released from Basophils?
How are Mast cells and Basophils different in regards to what they release?
Basophils do not release Heparin; Mast cells do
What do both Mast cell & Basophils express on their surfaces?
high affinity receptors for IgE
What cause release of granules of Basophils & mAst cells, what is released?
Cross-linking of their IgE receptors by Ag's Eg. allergens, parasites= release of preformed chemical mediators: histamine, serotonin, TNF-a, proteases, proteoglycans
What inflammatory cells differ from most other inflammatory cells?
LYMPHOCYTES; they respond to SPECIFIC Ag's; ie, granulocytes & Mac's are not Specific
Where are Lymphocytes found in developing fetus?
Stem cells in Bone marrow then,reach Lymphoid organs: thymus, peyers patches (intestine)
* Birds: stem cells in Yolk Sac, then to Thymus & Bursa of Fabricus
What happens to stem cells of yolk sac(birds) or bone marrow in fetus?
Processed by lymphoid organs; then processed lymph's reach Lymph GLANDS & other Lymph tissue; and CLONES are prod. w/ specific fxn.
WHat are the 2 types of Lymphocytes (morphologically)?
Large Lymph's (fxn unknown; increase in some viral diseases; & recovery phase of pyogenic infections)
What are the functional groups of SMALL lymphs?
B & T lymphocytes (SMALL; not differentiated on morph)
Size of T & B lymphs
8-10 um (diameter)
Nucleus & Cytoplasm of T & B cells (small Lymphs)
Round & Dense; Narrow rim of bluish stained cytoplasm
What are B lymph's responsible for?
Humoral Antibody response
where exactly are B cells produced?
Central part of Lymph follicles of Spleen, Lymph Glands, GALT
What % of Lymphs are B cells?
Do All B cells express Immunoglobulins on their cells surface?
WHat happens to B cells w/ correct Ag-stimulation?
Differentiate into PLASMA cells; important in INflamm. rxn
Are plasma cells found in blood circulation?
How long does it take for B cells to transform into Plasma cells?
Plasma cell lifespan
12 hours (does not divide further once it is formed)
They die once they have secreted Ab's
Plasma cell characteristics
Larger than small lymphs
Nucleus; on one side w/ "clock face" appearance
What gives Plasma cells their "clock-face" appearance?
Condensation of chromatin on nuclear wall
Plasma cell function
Where are Ab's secreted from by Plasma cells?
At Site of Inflammation or directly released into circulation
Which Ab's are highly effective?
Which Lymphocytes constitute the majority of lymph in peripheral blood?
Life span of T cells
Several MONTHS; travel from one lymphoid organ to other, making up: Recirculating lymphoid pool
Which Lymph's make up the "recirculating lymphoid pool"?
How do T cells differ to B cells?
T cells don't respond to Free Ag's; Ag's must be presented to T cell by APC w/ MHC mol's
WHat are the 2 types of MHC mol's?
MHC-I (all nucleated cells)
MHC-II (on specialized APC's)
WHat are the 2 sets of T cells and how are they divided into these groups?
- Surface expression of Accessory mol's
- Binding of MHC mol's
- CD4+ T cells; recognizes Ag-MHC-II-APC
(APC: langerhans of epidermis, dendritic cells of
LN's & other tissues, Macrophages)
- CD8+ T cells; Ag-specific; recognize Ag-MHC-I; involved in active lysis of target cell bearing Ag (CTL's)
What happens to CD4+ T cells when activated?
Proliferate & differentiate into Effector cells:
CD4+ T cells (helper/ inducers): to cells that prod. mediators that augment fxn/ provide help to other immune cells (ie, b cells to form plasma cells)
What is a type of Lymphocyte that does NOT express T cell receptors/ CD-3 on Ag expressed on surface of T cells?
What % of lymphocytes are NK cells?
Where do NK cells originate from?
Unclear; probably from same stem cells as T cells, w/o having undergone Thymic processing
Function of NK cells
Lysis of virus-infected cells & malignant cells (thus help in viral infections & cancer)
What do NK cells secrete?
Specialized granules; contain potent Cytotoxic mol's eg. Perforin= lysis of target cells on contact
What cells are termed Mononuclear phagocytic cells?
What common characteristic do Mononuclear phagocytic cells have?
Common Function; phagocytosis
LArge, Pale, have Golgi zones
More cytoplasm w/ SMALL nucleus (central/ at side)
Cytoplasm: pale pink stain w/ VACUOLES
SIze: 20-80um (LARGE)
Basically Mac's but in BLOOD; main source of Tissue Mac's in necrosis & inflamm.
DO Monocytes have same function as MAcrophages (tissues)?
No; ONLY in Severe conditions do they fxn as MAc's ie, in Intravascular hemolysis; phagocytic & absorb RBC's & degrade Hb.
WHat is Monocyte's normal function in INflammatory lesion?
Immigrate & change into Macrophages (ie, source), along w/ Neutrophils, but present in FEWER no's in early stages of acute inflamm.
Why are monocytes only present in small numbers in the early acute stages of inflammation, unlike Neutrophils?
- Lower overall no. in blood
- prod. at a lower rate
- sub's chemotactic to neutrophils are not to Mono's
- not as Amoeboid (changeable?) as neutrophils
WHat do Reticuloendothelial cells of RES (reticuloendothelial system) act as?
Phagocytic cells; can rapidly increase in no by division at local site/ or reach site from elsewhere when needed
what cell have recently been included in the Mononuclear phagocytic cell group?
Dendritic cells; ie,
Langerhan cells of epidermis
Follicular dendritic cells of splenic follicles & lymphocyte area of LN's & Spleen
WHy are dendritic cells grouped with the mononuclear phagocytic cells?
although poor at phagocytosis, they are:
POTENT APC' s (like Mac's)
What are the function of MACrophages?
2) Initiate Cell-mediated immune response (Processing & APC's)
3) Secretory Fxn:
- enzymes (lysozomes, lipases, protease; help kill org's, digest & remove dead tissue)
- Pro-inflamm. prod's: IL-1, TNF, PAF, prostaglandins, Complement components
- Growth factors: influence prolif. of cell types to aid in healing (FSF & Angiogenic factor)
4) Involved in regulation of body iron stores (physiological fxn)
How do MAC's Process Ag's before presenting them?
Degrade Ag into tiny fragments, which become incorporated into plasma membrane & complexed to MHC, so to be recognizable by T cells.
Reduced numbers of circulating monocytes; not a recognizable clinical entity
Monocytosis; what does it indicate?
Increased numbers of Circulating monocytes
Indicates Inflammation & Tissue necrosis
WHat increases when Macrophages are activated?
- membrane activity
- Lysosomal Enzymes
- Bactericidal activity
- MHC-II expression
WHat is an Epitheloid cell?
Macrophages that are Hypertrophied, vacuolated, & Foamy
"epitheloid" = shape looks like prickle cells of epithelium
When are epitheloid cells seen?
esp. in Tuberculosis & Johne's Disease
What are Giant cells?
Cells formed by fusion of Macrophages cytoplasm, caused by intergration of plasma membrane= cell w/ many nuclei; mech unknown
How are the many nuclei in Giant cells arranged?
- Clustered in Centre
- Distributed in cytoplasm
- Arranged in Ring form along the periphery
What is the shape of the Giant cell in inflammation
Round/ Oval/ Oblong/ Elongated
What are the 2 types of Giant cells?
1) Langhan's type: nuclei in ring along periphery
2) Foreign body Type: clustered nuclei in centre/ distributed in cytoplasm
Function of Giant cells
- Phagocytose BIGGER particles, that normal Mac's cannot
- Secrete Lysosomal enzymes
In what pathological conditions do Giant cells form by division of NUCLEI in cell, but no cytoplasmic division?
Congenital Dysplasias & Neoplasms
WHat are the Terms used to Classify INflammation?
MIcro: Fluid & Neutrophils
A stage btwn Acute & Chronic inflammation; involved EXUDATION, DEgenerating Neut's, Accumulation of mononuclear cells & development of young capillaries & fibroblasts
develops independently or sec. to acute inflamm.
Exudation subsides; process of REPAIR begins: phagocytosis of necrosed cells & cell debris by MAC's, development of capillaries in area, fibroblasts, & deposition of collagen= bed for regeneration of parenchymatous tissue
How long does Acute inflamm. last?
Few days/ weeks; then recovery/ patients dies
What determines the types of Exudate in inflammation?
- Causative nature of irritant
- organs & tissue involves
What is SEROUS Inflammation
Indicative of a MILD injury; serous exudate is Clear fluid (blood serum)
Where is SEROUS inflammation seen?
- Serous cavities lined by surface mesothelium
- Lungs (alveoli)
- Mucosal surfaces
What is the GROSS appearance of SEROUS inflammation?
Watery fluid, sometimes cloudy & blood tinges w/ small no. of RBC
What distinguished btwn SEROUS inflammation & edema?
Serous inflamm. contains protein & few neutrophils
What is the Microscopic appearance of SEROUS inflammation?
Homogenous, Pink stained Precipitate
FEW: RBC's & Neutrophils
Blood vessels in area are conjested
Causes of Serous inflammation
1) Serous cavities: infection w/ bacteria/ viruses
2) Joint cavities: trauma
3) Lungs: Bacterial & viral infections, chemicals (chloroform, ether), ANTU rat poison.
4) SKin: toxins from: bee stings, ant, scorpions, snakes (esp. american rattle), burns, trauma
5) Mucus membranes: viral/ bacterial infections. Eg. Vesicular stomatitis, Apthous fever, vesicular exanthema
Effects of Serous inflammation
Large amount of Exudate; in attempt to dilute irritant (defense mech)
Brings Ab's to area
Exudate= Swelling, pain, loss of fxn,
If cause remove: Exudate is absorbed; if not; progression to SUBACUTE stage= exudation remains
FIBRINOUS inflammation; what?, where?
Characterised by FIBRIN
mainly on Serous & mucus membranes:
- Pericardial surface
- Respiratory passage from pharynx to alveoli
- Synovial membranes
Gross appearance: Fibrinous INflammation
Smooth, Shiny surface of serous membranes becomes DULL & ROUGH
Fibrinous exudate= white, develops on surface
Thin film= "Fibrin membrane"
Thick film (like paper)= "Pseudomembrane"
Attached, underlying mucosa cant be separated= "Diptheritic membrane"
"bread n butter" look on Pericardium & PLeural surfaces
What is Diptheritic Inflammation?
Type of Fibrinous Inflammation:
has "diptheritic membrane"; forceful removal causes bleeding & damage to mucosa
eg. Calf Diptheria (Fusobacterium necrophorum)
What are fibrinous Casts
in Fibrinous Inflammation; large amounts of fibrinous exudates present in some organs; take shape of organs Eg. Bronchi & Intestines
Microscopic appearance: Fibrinous Inflammation
Dirty pink color; attached to surface of membrane/ over mucosal surfaces/ filling cavities like Lung alveoli
Exudate: made of Precipitated protein (fibrinogen), leukocytes & few RBC's
Healthy surrounding tissue= congested
What is fibrinous exudate mixed w/ serous exudate called?
What is fibrinous exudate mixed w/ Pus called?
Causes: Fibrinous Inflammation
- same as for Serous inflammation; casues need to last for longer to cause Fibrinous inflamm. effect
- Specific bacteria/ viruses cause it directly
eg. Calf diptheria, Salmenollosis (all spp.), Virus of malignant catarrhal fever, virus of Laryngotracheitis
Causes: Mild lesions of Respiratory Serofibrinous inflammation
- serous causes
- Feline infectious enteritis virus (panleucopenia)
- Feline infectious Peritonitis
Effects of Fibrinous Inflammation
1) protection of surface from loss of blood, further irritation & damage to underlying tissue (fibrin)
2) Chemotactic; attracts neutrophils (lyse fibrin, thus, recovery)
3)if inflamm. goes quick; fibrin dissolved & underlying tissue regenerates ("sloughs off" in bronchial & intestinal mucosa)
4) Persistent inflamm: fibrin is "organized"; fibroblasts come (underlying tissue)= Scar (common in Lung alveoli)
what happens if 2 serous surfaces are involved in Persistent Fibrinous Inflammation, ie, Pericardium, pleura, peritoneum?
Developing fibrous tissue causes "adhesion"= loss of function of affected organ
Catarrhal or Mucus Inflammation
Mucus; comes from cells (mucus glands & goblet cells; open onto mucus surface) instead of blood
- On mucus membranes of RESPIRATORY & DIGESTIVE tract
Which Inflammation is the most common?
Mucus/ Catarrhal inflammation
Gross appearance: catarrhal Inlfammation
- Exudate: Clear & Cloudy; sometimes pink when mixed w/ RBC's
- Subacute/ CHronic: White-grey mucus, mixed w/ yellow-white strands of fibrin
- Inflammed surface= Red (Hyperemia)
Microscopic appearance: Catarrhal inflammation
-PALE BLUE stained exudate (Hemotoxylin & Eosin);
attached to surface of mucus membrane
-Exudate: contains cell debris, neutrophils, fibrin,
-Goblet cells: Hyperplastic
-Underlying mucosa: congested
-Desquamation of surface epithelium
Causes: Catarrhal Inflammation
1) LOW virulent Bacterial/Viral Infections
(canine distemper/ feline viral rhinotracheitis)
2) Mild chemicals: inhaled formalin, Cl, Chlorpicrin
3) Irritating food
4) Inhalation: dust, foreign protein: (hayfever,
humans; COPD, horses; Allergic
5) Chronic irritation of mucus surfaces by Parasites
Effects: Catarrhal Inflammation
- Protective; mucus washes away irritant
- Quick removal of cause: inflamm. subsides &
epithelium goes back to normal
- Cause persistent: (ie, microorg)= inflamm. becomes
Large no. of RBC's in Exudate; usually occurs in Organs w/ Rich blood supply;; eg. Lungs, mucus membrane of GIT
Blood OOZES from inflamed tissue (unlike hemorrhage; from cut vessels)
GROSS; Hemorrhagic Inflammation
Exudate: Blood colored; Bright red/ Dark red
Present in LUMEN/ Attached to Mucosa
MICROSCOPIC; Hemorrhagic Inflammation
Large no. RBC's, Fibrin, Leukocytes (exudate)
Necrotic & Hemorrhagic lesions in affected tissue
RBC's come out of damaged permeable vessels by DIAPEDESIS; out onto Inflamed tissue??
Causes: Hemorrhagic Inflammation
- HIGHLY virulent Microorg's: Clostridia, Pasteurella,
Antrax, Leptospira, viral diarrhea viruses (cattle),
Newcastle disease, Infectious laryngotracheitis
- Acute Poisoning (chemicals: phenol, arsenic,
Effects: Hemorrhagic Inflammation
Cause quickly removed; recovery
Not removed: FATAL
-PUS; Seen in: Mucosal & Serosal surfaces, over the
Skin, Solid organs
-Pyogenic bacteria in tissues: Attract Large no's
Neutrophils; neut's & bacterial effect=
NECROSIS; lesion= "micro-abscess"
-Increase in Neut's then causes: enlargement of
microabscesses; fibrous capsule forms around
= "Abcsess" (microscopic-cm's in size)
Gross: Purulent Inflammation
- Lesion w/ pus; Yellow cream-Bluish green- Black
- Pus: Liquid/ watery/ Semisolid Caseous
- In Body cavities= "Empyema"
- Lung: Pus present in Su
In what condition is Purulent inflammation (Pus) seen in LUNG?
Micro: Purulent Inflammation
- Large no's of Neutrophils; many undergo necrosis &
are smaller in size, darker, w/ Pyknotic nuclei &
- Neighboring area of inflamm shows Hyperemia &
Causes: Purulent Inflammation
- Pyogenic Bacteria: Corynebacteria, Pseudomonas,
E.coli, Strept, Staph,
- Fungal Infections: Aspergillosis, Bastomycosis,
Effects: Purulent INflammation
Most effective method of Defense against bacteria & fungi; Abscess may rupture:..
If on surface of organs: Liver, Kidney, Resp, digestive
& repro mucous membrane= Serious &
If on Skin: beneficial; drains pus, & tissue heals
If on Bloodstream: bacteria disseminate to tissues=
"Metastatic abscesses" (metastatis)
If toxic sub's from abscess absorbed into body=
poss. Toxemia & Death
-Prolonged duration; Active inflamm., tissue
destruction, healing occur,
What are the CAUSES of Chronic inflammation?
- Acute Inflamm. (w/ persistant stimulus)
- Repeated bouts of acute inflamm.
- (Mostly) Low grade response, thats does
NOT follow acute inflamm. ie,
- Persistant intracellular microbial infect.
- Prolonged exposure to toxic sub's (Exog:
silica, dust) or (Endog: lipids, uric acid,
- Immune reaction; autoimmune diseases
What are the main differences btwn chronic & Acute inflammation?
Usually ABSENT in Chronic inflammation:
- Vascular changes
- Heat, Redness
- Neutrophilic infiltration
What characterizes Chronic Inflammation?
- Mononuclear Infiltration (Mac's, Lymphs, plasma
cells; ie, a persistent rxn to injury)
- SOmetimes: Eosinophils & Mast cells infiltrate tissue
- Tissue Destruction (induced by inflamm. cells)
- Attempted Healing/ repair by CT.
Special Type of Chronic INflammation; wide variety of inflammatory cells, majority: Lymphs & Mac's, & Fibrous tissue
Swelling & lumps (resembles tumor, hence name)
- Indigestible agents that Mac's cannot digest
- Cell mediated immune mech.
Where does the name of "granuloma" come from in Granuloma inflammation?
From Gross & microscopic appearance (Granulation tissue is the tissue)
What is the function of the Granulation tissue in Granuloma inflammation, what does it comprise?
Repair of wound
Made of: Fibroblasts & Blood capillaries
What stimulates MAcrophage Production & infiltration in Granulomatous inflammation?
Lymphocytes; stimulate MAc Production & infiltration into site of infiltration
How does a granuloma form in Granulomatous Inflammation?
Repeated process of stimulation of prod. & infiltration of MAC's by Lymph's, causes focus to enlarge= granuloma
Gross Appearance: Granulomatous inflammation
Single granuloma/ Diffuse enlargement
- Hard, white w/ mature fibrous tissue
- Yellow/creamy & soft in Immature fibrous tissue
- may have small foci of pus w/ caseous necrosis
Microscopic Appearance: Granulomatous Inflammation
Causative agent in centre of granuloma surrounded by Zone of necrosed tissue, then a zone of inflammatory cells surrounding necrotic tissue, enclosed in CT.
- Inflamm cells= Mac's, Lymphs, Plasma cell
- Neutrophils may be present in necrotic area
Causes: Granulomatous inflammation
1) Infectious Granuloma:
- bacteria/ fungi/ parasite
2) Non-infectious Granuloma;
- Small foreign bodies accidentally buried in
tissue ie, surgical sutures, minute wood,
metal/plant pieces, spores, inert sub's
How are granulomatous inflammation's classified?? What are the 2 groups?
1) Diffuse (lepromatous):
- diffuse sheets of Mac's
- few lymphs & plasma cells
- lesions occur mostly by Th 2 response
2) Nodular (tuberculoid);
- Th 1 dominant response
- have central core of necrotic debris
Effects: Granulomatous inflammation
- Type of defense against these agents that are difficult to remove/ deal with in the normal inflammatory way
- Most cases are FATAL
What cells may be present in "infectious" Granulomatous inflammation in the Inflammatory area?
Epitheloid & Giant cells
In Granulomatous inflammation, caused by certain bacterial (Actinpbacillus/ Actinomycosis) & fungal infections (Coccidioidomycosis), what may be seen microscopically?
Zone of Eosinophilic material around the pathogens= "Club colony" or "Asteroid body"
What type of bacteria may cause granulomatous inflammation?
Mycobacterium, Actinobacillosis, Actinomycosis
What types of bacteria cause the DIffuse (lepromatous) Form of Granulomatous INflammation?
Mycobacterium leprae in Humans
-(paratuberculosis): "john's disease" in Cattle
What types of microorganisms cause the NODULAR (tuberculoid) form of Granulomatous inflammation?
Mycobacterium tuberculosis & deep fungal infections
What is granulomatous inflammation able to do that the normal inflammatory mechanisms don't?
Localizes the infection
WHen is Lymphocytic infiltration in Certain Inflammatory Lesions seen?
- Many infections of CNS (viral/ parasitic)
- Certain Liver conditions
- Occasionally in Mucous membranes
- Kidney Infections
What is the Gross appearance of Lymphocytic inflammations like?
Usually not seen grossly; but sometimes might see WHITE SPOTS on surface of tissues
WHat is the Microscopic appearance like of Lymphocytic inflammation?
- Lymphocytes seen in CLUMPS in affected tissue:
- in mucus membranes (esp. in Lamina propria of intestine)
- in portal triad of Liver & Kidney cortex
- in Brain (around blood vessels)
- in Lungs (around bronchi)
What is "Perivascular Lymphocytic Infiltration" or "Perivascular Cuffing"?
Lymphocytic infiltratory Inflammation in Brain; lymphocytes infiltrate around blood vessels.
What is "Bronchial Cuffing"?
Occurs in certain Lymphocytic inflammation in Lungs, where the lymphocytes infiltrate around the bronchi
Process of replacement of Damaged/ necrosed tissue
1) removal of dead tissue & exudate(by inflamm.cells)
2) Then healing begins (replacement)
What are the 2 ways Healing is done?
1) Healing by Regeneration
2) Healing by Repair
What is Healing by Regeneration?
When cells of SAME kind replace damaged cells/ tissues
What is Healing by Repair?
When damaged cells/ tissue replaced by (CT)- FIBROUS TISSUE
WHat are the 3 groups of cells based on their capacity to regenerate necrosed cells in Healing?
- Labile cells
- Stable cells
- Permanent cells
- continuously dividing cells; multiply throughout life
- Epithelial cells of skin & mucus membranes
- Lympho-hemapoietic cells (Cells of Bone
Marrow & Lymphoid organs)
a.k.a Quiescent cells;
- Cells of parenchymatous organs (liver, kidney, pancreas, adrenal, bone, tendon, nerve, smooth m)
- Their power of regeneration decreases w/ age
NON-dividing cells; cells that have lost cell cycle & lost power of regeneration
- Neurons of CNS
- Cardiac & Skeletal m's
Which labile cells indefinately always regenerate?
Epithelial cells of GIT, Respiratory/ Urogenital tract & Skin
Which type of labile cells regenerate once there are at least some living cells, ie, not too badly damaged?
Secretory cells of Glands
Cells of Sweat glands, sebaceous glands & hair follices
ie, 1st & 2nd burns= regeneration (not all tissue damaged); 3rd degree burns: all dermis destroyed= healing by scar tissue
How does regeneration of epithelial cells take place?
By Multiplication of MATURE cells from margin of wounds, which then migrate to damaged area, & later differentiate into new epithelium
In normal physiological conditions which cells would normal multiply in regeneration of epithelial cells?
How does regeneration of stable cells take place?
Mitotic division; although normally they do not regenerate (multiply) in adult life in normal circumstances.
Which parenchymal cells have a GOOD power of regeneration?
LIVER parenchymal cells; ASLONG as framework of liver parenchyma is NOT destroyed
- Large no. of bile ducts proliferate
- Liver cells regenerate from Irregular hepatic nodules
What happens if liver parenchyma framework is destroyed?
there is some regeneration, but, NORMAL liver structure is NOT formed
Which animals can survive on a 10% liver mass (ie, 10% of liver is functional)
DOGS; & most other spp.
What happens w/ regeneration of kidney parenchymal cells (stable cells)?
Cell of renal tubular epithelium regenerate, BUT, NO new nephron is formed
What are the stable cells that are referred to as Mesenchymal derivatives?
Muscle, Nerve, Cartilage, bones, Blood vessels
Describe the regeneration of Skeletal Striated muscles, Cardiac m. cells (stable,mesenchymal cells), what does regeneration occur from?
Skeletal; Regeneration has Limited Capacity; occurs
from Satellite cells found attached to
Cardiac; very little regenerative capacity; most injuries
follow w/ CT scarring
What happens to nerve regeneration if nerve is cut out (stable cells)?
The lower part DEgenerates & upper part REgenerates from cell body of origin
How does regeneration of Cartilage & Bone (stable cells of mesenchymal origin) takes place?
w/ Activity of multipotential fibroblasts, capable of differentiation into osteoblasts (bone) & chondroblasts (cartilage)
Describe regeneration of Blood vessels in Healing (stable, mesenchymal origin)?
they regenerate, but they are larger in size w/ little Medial coat
What type of injuries does CT repair?
Most, w/ exception of: few damaged stable & liable cells w/ PERFECT HEALING (loss of fxn)
What is the effect of CT repair?
Permanent loss of specialized function of involved tissue, ie, fibrous replacement of kidney after infarction/ abscess formation= renal failure
also, extensive myocardial infarction= heart failure
What are the 2 ways repair occurs by CT?
1)Primary union, Primary healing, or healing by 1st intention
2)Secondary Union, Healing by 2nd Intention
What is Primary union healing?
Occurs w/ healing of a clean surgical wound, where tissues opposed by surgical sutures/ tape (brought together), thus has minimal tissue loss
What are the steps involved in Healing w/ Primary union (repair by CT)?
1) Clot formation
2) Inflammatory Response
3) Fibroblast response
4) Endothelial response
5) Epithelial regeneration
6) Collagen formation
What does "Clot formation" involve in Primary union mech of Repair by CT?
Blood fills gap btwn sutures, becomes coagulated to form a clot; consists of Fibrin, platelets, RBC's, WBC's, which seals the defect
What occurs in the "inflammatory response" in Primary CT repair?
Vascular congestion, edema, infiltration of: leukocytes, neutrophils & later monocytes appear at the edge of the lesion
The Phagocytes progressively digest dead tissue; the digest is then absorbed into the bloodstream
("resolution of exudate")
What occurs in "Fibroblast response" in Primary CT repair?
simultaneously to phagocytes mech in inflamm. response, Fibroblasts at the edge of the lesion begin to divide & migrate into clot; eventually opposing fibroblasts on each side of lesion meet (2-3 days)
What goes on in the "Endothelial response" in primary CT repair?
Blood vessels grow in the area to supply blood; the bud of new capillaries forms from remaining blood vessels in area; continuity of blood flow btwn 2 margin occurs w/i 2-3 days (lymphatic channels undergo similar changes)
what is the "Epithelial Regeneration" response in Primary repair by CT?
Surface epithelium grows over the newly formed CT; re-epitheliasation & differentiation into appropriate layers is complete in 7 days
What happens in "Collagen formation" in Primary unions repair by CT?
collagen fibres are deposited w/ proliferation of fibroblasts; begins at 4-5 days; it strengthens the wound; vascularization begins to diminish; later collagen shrinks= contraction of fibrous scar; Nerve fibres slowly grow into CT tissue
When does Secondary union, healing by 2nd intention, occur?
extensive damage to area, where edges of lesion cannot be opposed; eg. Extensive INflammatory ulceration, surgical wound, infarction, abscess.
What is the difference btwn the 2 processes: Primary & secondary union repair by CT?
They are similar, except, there is a necessity to remove large amounts of dead cells, tissue debris, & exudate in Secondary union repair
In secondary union repair what removes the dead cells, debris etc?
Phagocytosis & Digestion
During healing in Secondary union repair by CT what occurs?
Highly vascularized CT slowly grows from bottom of the wound
What are the 3 distinct layers of the lesion that occur w/ Secondary union repair by CT?
- Superficial layer of cell debris
- Layer of newly formed blood vessels arranged at
right angles to lesion
- Deep layer of fibroblasts w/ collagen fibers
running parallel to lesion
Healing by second intention (union) forms large amounts of what?
Scar tissue; process known as: "CICATRIZATION"
What happens if the wound is small in 2nd union healing?
epithelium grows from one side & covers the surface
What happens w/ Large wounds in 2nd union healing?
Homografts/ Homogafts? are needed to cover wound surface
What factors affect the Adequacy & Quality of repair?
1) Stimuli to proliferation of cells
2) Systemic factors
3) Local factors
What are the different hypothesis that exist to explain what types of stimuli induce cell division & proliferation in Repair?
A) Cytokines & Wound Hormones
B) Chemical stimulants
C) Pressure gradient
How may cytokines stimulate proliferation of cells in repair?
- Protein breakdown prod's of cells may stimulate cell
- Locally released cytokines & Growth factors for
co-ordination of division & differentiation of cells
Give an example of Growth factors that may influence coordination & division of cells in wound healing?
- EGF (epithelial growth factor)
- PDGF (platelet deriv. growth factor)
- FGF (fibroblast growth factor)
- B-TGF (transforming growth factor)
- VEGF (Vascular endothelial growth factor)
- Arg (angiopoietins)
- HGF (hepatocyte growth factor)
- CSFS (CT growth factor)
- MCSF (Myeloid colony stimulating factor)
- Cytokines (IL, TNF, IFN- a & B)
What do the growth factors do in physiological circumstances in resolving cell proliferation?
1) bind to it's receptor on cell membrane
2) activates several signals, transducing proteins
on inner leaflet of plasma membrane
3) signal transmitted across cytosol to nucleus via
4) Nuclear regulatory factors induced & activated
initiating dna transription
5) Cell enters cell cycle & cell division
How does the "Pressure Gradients" (contact inhibition) Hypothesis explain how proliferation is stimulated?
Pressure of one cell on another produces a restraint on cells causing absence of constant tissue growth in adults; therefore, if tissues are destroyed, these restraints are removed, disturbing the pressure gradient, stimulating proliferation (tissue growth)
How does Systemic Factors influence Adequacy & quality of repair?
a) Physiological condition of the host; (age, health)
old age & bad health= inadequate blood supply to
b) Nutrition; ie, Vit. C v. helpful in wound healing,
protein def. (esp. Sulphur) may cause delayed
c) Endocrine Factors; Adrenal steroids hinder repair;
imp. to consider when treating w/ steroids
How does Local Factors have influence on Adequacy & Quality of repair?
- Blood supply; repair ineffective in poorly
- Infection; major obstacle to repair
- Mobility of tissues; ie, (bones, muscle, tendons
(mobile); healing would be faster if
broken ends are in correct opposition & are
- Site of injury; ie, where? perfect healing can occur
in tissues made up of stable & liable cells; but
permanent cells= scarring