ACUTE INFLAMMATION

ABBAS. ADEL GROUP. 4

NATURAL BARRIERS: 1st line of defence
1. Physical barriers:
--- Epithelial cells = produces a layer which is rela2vely impenetrable for
microorganisms; on the skin & mucosa
2. Mechanical barriers:
--- Mechanical clearance of the epithelial surfaces = elimina2on of dead cells
--- Coughing & sneezing = clearance of upper respiratory tract
--- Produc2on of mucus
--- Movement of cilia in 1 direcLon
--- Flushing of urine
--- Low temperature on the body surface
3. Biochemical barriers:
--- Mucus
--- PerspiraLon
--- AnL---microbial pepLdes — they insert in the bacterial membrane & disrupts it
1. Cathelicidins
2. Defensins
3. Collec2ns
--- Presence of a normal bacterial flora:
· Diges2on = vitamin K produc2on, absorp2on of ions etc.
--- Normal vaginal flora:
· H 2O 2 produc2on
· Lac2c acid produc2on
· Some an2---microbial pep2des (bacteriocins)

ACUTE INFLAMMATION: 2nd line of defence

· It occurs together with hemostasis — it is localised at the site of injury
· The aim of acute inflamma2on is resoluLon & repair of the damaged Lssue
--- If this isn’t achieved, it evolves into chronic inflamma2on
--- Chronic inflamma2on is due to prolonged ac2on of an2genic s2muli & usually due to
irregulari2es in the immune response mechanisms
· These events involve:
1. Vascular changes
2. Biochemical phenomena (ac0va0on of plasma protein systems)
3. Cellular events with systemic parLcipaLon
· Causes for acute inflamma2on:
--- InfecLons
--- Mechanical or physical damage of 2ssues
--- Ischemia of 2ssues (CV diseases)
· Elements involved in acute inflamma0on:
PHASES OFACUTE INFLAMMATION:

1. VASCULAR EVENTS:
--- Endothelial cells are most oUen s2mulated by cytokines produced by mast cells, etc.
--- VasoconstricLon of the injured vessel
--- VasodilaLon of the microvessels (especially venues)
· Mediated by histamine, bradykinin:
--- Vasodila2on in the micro vessels ---
Vasoconstric2on in the large vessels
· Venule dilaLon is necessary for decreasing the blood flow to favour the interac2on
between the blood & the endothelial cells
--- Signs = Rubor (redness) & Calor (heat) due to decreased blood flow
--- It will produce stasis (speed of blood flow is decreased)
--- Increased vascular permeability:
· RetracLon/contrac2on of the endothelial cells, which produces larger gaps
between them
· These gaps contain kinin components, cloXng components & cytokines & it will
allow cells to pass through
· Leads to exudate formaLon (due to extravasa2on of fluid)
· Signs = Tumor (swelling)
--- General effects of vasodila0on:
· It is important for ini2a2ng & developing the inflammatory response because they
prepare the area of injury for the cellular effects that follow
· Favours the interacLon of the cells with the injured cells then with the 2ssular cells
at the site of injury
· Favours the interconnecLon of the plasma protein systems & the inflammatory
cells at the site of injury
· Also favours the interconnec2on of the cells of the adap2ve immunity
· Prepares the site for healing mechanisms
2. ACTIVATION OFPLASMAPROTEIN SYSTEMS:
--- COMPLEMENTSYSTEM:
· Classical pathway = ac2vated by immune complexes (Ag---Ab) formed on the surface
of foreign membranes
· LecLn pathway = ac2vated directly by bacterial carbohydrates
· AlternaLve pathway = ac2vated in the presence of bacteria & fungi
· MACs = destroys the foreign membrane
· Opsonins (C3b, IgG) = recognised by C3b receptors on membranes of macrophages
· Anaphylatoxins (C3a, C5a, C4a) = s2mulates inflammatory cells (mast cells)
· The first component of the complement system is C1
--- It can be ac2vated by = plasmin, Factor XIIa, kinin
--- CLOTTINGSYSTEM:
· Factor XIIa = ac2vates C1, plasminogen, coagulaLon cascade
· Fibrinogen = forms fibrin filaments & fibrinopepLdes A & B (are chemotac2c for
neutrophils)
· Fibrin = forms the fibrinoleukocyLc barrier & acts as a skeleton for the repair
process (migra2on of fibroblasts & endothelial cells to form new vessels)

--- KININSYSTEM:
· The final product is bradykinin
· Starts with the acLvaLon of prekallikrein into kallikrein (via Factor XIIa + plasmin)
· Kallikrein ac2vates LMW kininogen into bradykinin
--- Kallikrein can also ac2vate plasminogen
· Bradykinin:
--- Produces endothelial cell retracLon = increases vascular permeability
--- VasodilaLon at low doses
--- Favours leukocyte chemotaxis
--- ContracLon of smooth muscles
-- Pain

3. CELLULAREVENTS:
--- Cells involved in acute inflamma0on:
· Primary = monocytes & (PMNs) & granulocytes
· Secondary = platelets & lymphocytes
--- Cellular receptors:
1. Paaern RecogniLon Receptors (PRRs):
--- Recognises molecular paaerns (PAMPs) on infec2ous agents
--- Recognises products of cellular damage (DAMPs) — necrosis/apoptosis
--- PRRs are found on cells located at the interface of the host &
environment (skin, mucosa of respiratory tract, GI tract, GU tract)
· Toll---like receptors (TLRs)
· Complement receptors (CRs)
· Scavenger receptors (SRs)
· Glucan receptors, Mannose receptors
2. Toll---like Receptors (TLRs):
--- Homodimers or heterodimers — have a large geneLc polymorphism
· Highly preserved in phylogenesis (comes from plants)
--- TLRs are expressed on:
· APCs (macrophages, dendri2c cells)
· Mast cells
· Mucosal epithelial cells
· Some popula2ons of lymphocytes
· Neutrophils
--- Being located at the mucosal surface, they have direct & early contact
with potenLal microbes
--- PAMP recogni-on:
· LPS (bacterial lipopolysaccharide) — endotoxin
· Pep2doglycans
· Lipoproteins
· Viral coat proteins
· Bacterial flagellin
· Microbial nucleic acid
· Host factors produced by damaged cells (chroma2n, EC matrix)
--- During their recogni2on, they oUen collaborate with other receptors
(BCR/TCR), which will result in the release of cytokines
--- TLRs represent one of the bridges between innate resistance & adap2ve
immune response

3. Complement Receptors (CRs):

--- CRs are expressed on:
· Granulocytes
· Monocytes / macrophages
· Lymphocytes
· Mast cells
· Erythrocytes
· Platelets
· Some epithelial cells
--- CRs recognise a variety of fragments produced through the ac2va2on of
the complement system
· CR1 = recognises immune complexes with complement fragments
(C3b + C4b) on the cell membrane
· CR2 = recognises C3b & its breakdown products; an2body
produc2on
· CR3 & CR4 = are integrins; they facilitate phagocytosis
--- CR4 is mainly found on platelets
4. Scavenger Receptors (SRs):
--- Primarily expressed on macrophages
--- They facilitate recogniLon & phagocytosis of bacterial pathogens and
especially damaged cells
--- They mediate the recogniLon of altered soluble lipoproteins (LDL?)
· SR---PSOX = recognises cell membrane PLs (phosphaLdyl serine)
· CD---14 = recognises the complex of LPS with LPS binding protein
 MAST CELLS:
· They have a central role in acute inflamma2on
· Are located in the loose connecLve Lssue, near the blood vessels
--- Large quan2ty in the skin, mucosa of the GI tract & respiratory tract
· There is a great number of sLmuli which can acLvate the mast cells:
1. Physical sLmuli:
--- Physical injury done by hit, mechanical traumas, irradia2on (UV, X---ray)
2. Chemical sLmuli:
--- Toxins (industrial, chemical, bacterial), snake venom, bee venom, proteoly2c
enzymes, an2---microbial pep2des
3. Immunological sLmuli:
--- Derived from the already ac2vated cells or ….????
--- Anaphylatoxins (C3a, C5a) + cytokines (IL---1β)
--- Immunoglobulins (IgE)
--- Several cytokines coming from the ac2vated cell
4. SLmuli of bacterial & viral molecules:
--- Ac2vates via the TLRs pathway — cytokine synthesis
· 2 types of reac0ons/responses occur:
1. Immediate release (degranulaLon):
--- Release of the content of their preformed granules
· Histamine:
H1 target cells: --- A vasoac2ve amine
--- smooth muscle cells
--- endothelial cells --- Produces rapid constric2on of large vessel walls & dila2on of
post---capillary venules — decreases the blood flow
--- neutrophils --
mast cell
--- S2mulates retracLon of endothelial cells = hyperpermeability
--- H1 receptors = pro---inflammatory effects; cGMP
H2 target cells: --- H2 receptors = an2---inflammatory effects; cAMP
-- eosinophils · TNFα:
--- neutrophils -- --- Increases vascular permeability
mast cells
--- lymphocytes
 --- Favours leukocyte emigra2on
· IL---4 = Ac2vates B cells
· NCF & ECF:
--- Important in akrac2ng neutrophils & eosinophils
--- Favours phagocytosis
2. Long term response:
--- New synthesis of lipid derived inflammatory mediators
· Leukotrienes: lipo---oxygenase pathway
--- Leukotrienes B4 = important chemotac2c factor for neutrophils
--- Leukotrienes C4, E4, D4 = vasodila2on & increased permeability
· IL---13 = B cells ac2va2on & · Prostaglandins: cyclo---oxygenase pathway
prolifera2on
 --- PG E = s2mulates sensi2ve nerve endings —> pain
· Platelet AcLvaLng Factor (PAF):
--- Ac2vates neutrophils, endothelial cells, mast cells, macrophages
· Growth Factors = VEGF + PDGF
--- Favours the acLvaLon of some phospholipases —> delivery of PGs, LTs & FAs
CELLULAR EVENTS IN ACUTE INFLAMMATION:

1. Leukocyte rolling:
--- A normal, physiological & permanent phenomenon
--- The rolling is possible due to some adhesion molecules which produces a temporary
binding (not strong) between the leukocyte & endothelial cells
--- In this way, they produce a permanent, reversible surveillance of the endothelial cells
--- Molecules involved in this process are selecLns:
· L---selecLns = expressed on leukocyte surfaces
--- Works by binding to the GLYCAM 1 ligand
--- It is a transmembrane GP formed by an extracellular por2on (terminal lec2n
binding protein) which interacts with GLYCAM 1
· P---selecLns = expressed on platelet surfaces
· E---selecLns = expressed on endothelial cells (not always expressed)
--- They are expressed when endothelial cells start to become acLvated
--- They will interact with the N---acetyl---lactosaminoglycated protein ligand on
the leukocyte??
--- Binds to the E---selecLn ligands

2. Firm adhesion of leukocytes/ pavement:

--- It ini2ates the cell ac2va2on
--- The group of adhesion molecules involved are the family of integrins:
· β2 integrins = on neutrophils, monocytes, macrophages, leukocytes
--- Are heterodimers with α & β2 chains
--- Interacts with = ICAM 1 & 2 on leukocytes
--- Types:
· MAC 1 (CD11b CD18) = interacts with ICAM 1+2, fibronec2n, GPS, C3b
· LFA 1 (CD11a CD18) = interacts with ICAM 1 & 2

· β1 integrins:
--- Types:
· VLA4 = on monocytes, lymphocytes, neutrophils
--- Interacts with:
· RGD ligand = contains L---arginine, glycine, aspar2c acid
· RGDS ligand = contains L---arginine, glycine, aspar2c acid + serine
· VitronecLn & fibronecLn in the EC matrix

· β3 integrins = present on the surface of platelets

3. Chemotaxis & transmigraLon:
--- Chemotaxis = direc2onal movement of the cells along a chemical gradient formed by a
chemotac2c factor
· It is receptor mediated
--- One chemotac2c factor could bind to several receptors & one receptor can
bind to several chemotac2c factors — has relaLve selecLvity
· AUer binding on the subendothelial surface, the chemotac2c factor can diffuse/pass
through the endothelial cell & can be expressed on the intraluminal surface, calling
leukocytes to the area
--- The leukocytes are ac2vated & start moving to that area
--- Chemotac0c agents:
· Endogenous = C3a, C5a, C5C6C7 complex, TNFα, IL---1, IL---α
· Exogenous = chemokines; Leukotriene B4, kallikrein, PAF, fibrinopepLdes A + B

4. Leukocytes acLvaLon:
--- Chemokines have 2 binding sites:
· 1 for leukocytes
· 1 for macromolecules on endothelial cells
--- Adhesion molecules coupled with chemokines will acLvate the leukocytes
· This leads to the ac2va2on of G---protein which ac2vates phospholipase C
· Phospolipase C will transform PIP2 —> IP3 + DAG
--- PIP2 = locally ac2vates the ac2n---myosin apparatus
· Leads to cell shape modifica2ons — pseudopod formaLon
· This will facilitate the migraLon of the leukocyte, allowing them to pass through
the endothelium by changing their shape
-- IP3:
· Release of Ca2+ from sER (contrac2lity)
· AcLvaLon of the acto---myosin apparatus (shape modifica2ons, cell mo2lity)
· DegranulaLon of lysosomes
-- DAG:
· AcLvates Protein kinase C —> phosphoryla2on
· AcLvates NADPH oxidase —> ini2ates the free oxygen radical cascade

--- Cellular locomoLon:

· Neutrophils move in amoeboidal movements, done by the acLvity of acLn---myosin
microfibrils
--- It is regulated by Ca2+ & IP3
--- It gives the leukocytes the ability to move in a certain direcLon (in the
direc2on of chemotac2c factor gradient)
· 2 processes occur:
1. Pseudopods formaLon; based on the forma2on of an ac2n gel
2. Acto---myosin contracLon in the cellular core
--- Ac2vators:
· Profilin = forms the acLn filaments; cyclic acLvity s2mulated by PIP2
Gel form
· AcLn Binding Protein (APB) = forms the acLn net
--- Inhibitors: Produces swelling of the membrane, forming pseudopods
Solid form · Gel---soline = inhibits polymerisaLon; ac2ve when the cell is at rest
 5. Phagocytosis:
1. Contact phase (Fast phase) = recogni2on & binding of foreign pep2de
--- The phagocyte (neutrophils & macrophages) makes contact with the foreign
parLcle in the inflammatory focus via expression of surface receptors
· Neutrophils have some receptors (CRs, TLRs, mannose receptors, glucose
receptors, scavenger receptors) which can recognise some oligosaccharides
from the bacterial wall
--- The most important receptors are the receptors for opsonins:
· C3b opsonin
· IgG opsonin = Fc fragment of IgG

2. Engulfing phase = forming a phagosome (vesicle with foreign body parts)

--- AUer the recogni2on & binding of the foreign par2cles, the phagocytes will
con2nue their acLvaLon & start forming pseudopods
· Possible due to the acLvaLon of the acLon filaments beneath the cell wall
--- These pseudopods will surround the parLcles:
· First a pocket of invaginaLon around the foreign par2cles forms
· The invaginaLon closes, forming a vesicle (phagosome) containing the
foreign pep2de
--- The phagosome will move to the centre of the cell becoming the endosome
--- The endosome later binds to the lysosomes, forming endolysosomes
· This ac2vates the microbicidal mechanisms (NADPH oxidase etc.)

3. DigesLon / Microbicidal acLvity = killing or destroying the foreign body

--- O2 dependent mechanisms:
1. NADPH oxidase acLvaLon
2. Myeloperoxidase acLvaLon
3. GeneraLon of Nitrogen derivaLves (NO)

--- O2 independent mechanisms:

1. Acidic pH in the endosomes & lysosomes
2. CaLonic proteins = lysozymes, defensins, cathelocidin

Neutrophils = involved in free O2 radicals produc2on & cytotoxicity

Macrophages = involved in clearing
 Ceruloplasmin & C ReacLve Protein neutralises free O2 radicals

NADPH Oxidase AcLvaLon:

--- NADPH oxidase is present at the level of organ membranes & cellular membranes
--- It has 5 subunits:
· Transmembrane α and β chains
--- Rivescin transports α and β chains form the secondary granules when needed
--- It is mediated according to Phospholipase C (PLC)
· Glycoproteins (GP 67PFAS & GP 47PFAS)
· Response Associated Component (RAC) — ac2vated by GTP
--- Exposed sites on the β chain binds to FAD & NADPH2:
· Involved in the respiratory burst & will favour the transfer of electrons to O2
--- NADPH oxidase catalyses:
· The transforma2on of NADPH —> NADP + H+
· The electrons are transferred to O2, forming superoxide (‧O2---)
· Superoxide is transformed into H2O2 which later transforms into OH---
--- OH--- = involved in immunoac2ve reac2ons in the myeloperoxidase system
--- Superoxide = precursor for the other 3 free oxygen radicals
Myeloperoxidase acLvaLon:
--- In the presence of myeloperoxidase, H2O2 will react with Cl---, Br---, I--- compounds, forming
very ac2ve halide species
· HClO--- (hypochlorous acid)
--- The free oxygen radicals are toxic for bacteria, viruses, tumour cells, parasites,
parenchymal cells, eryhrocytes, fibrocytes, etc.
--- Free oxygen radicals:
· Can produce lipid peroxidaLon, which can disrupt the membrane of the bacteria
· Favour the carboxylaLon & nitrosilaLon
· Produce oxidaLon of structural proteins —> affects the DNA structure
· Are important in immunity due to their toxic effects & because of their influence on
the evoluLon of acute inflammaLon
· Produce the degradaLon of the EC matrix, acLvaLng proteolysis (collagenase &
elastase ac2va2on)
· Are involved in the generaLon of L---arginine metabolites
--- NO---synthetase converts L---arginine into cytuline —> NO (nitric oxide)
--- Effects of NO = vasodilaLon & cytotoxic effects (acts as a free oxygen radical)
· Ac2vates complements?
RESOLUTION &REPAIR:
· The process of healing starts in the acute inflammaLon & could finish over a long period
(several years; ~2 years)
· ResoluLon = a type of restoring of the 2ssue & func2ons:
--- It can occur aNer a simple, sterile injury:
· Paper cuts, scalpel cuts by surgeon
· Healing occurs by primary intenLon — no complica2ons or infec2ons
· No scar
· FuncLons are restored fully
--- It can occur with a complica-on (infec0on):
· Healing occurs by secondary intenLon
· Restora2on of the normal 2ssue by restoring the conLnuity
· Leaves a scar (not the original 2ssue)
--- It can produce scars on vessels causing stenosis
· FuncLons may not be restored fully

· RegeneraLon & repair occurs in the last stages of acute inflammaLon (phagocytosis)
1. ReconstrucLve phase: filling of injured area with a clot
--- Mainly done by macrophages:
1. Transforming Growth Factor β (TGFβ) = chemotac2c factor for
fibroblasts to produce & secrete collagen
2. Growth Factors (VEGF, PDGF, FDGF) = akracts & s2mulates
endothelial cells to form new capillary beds growing into the lesion
3. Matrix metalloproteinases (MMPs) = degrada2on & remodelling of
EC matrix proteins
--- Debridement (scavengers) & clearing of the injured/infected area
--- Fibroplasia = fill in, seal & shrink the wound
· Angiogenesis — chemotaxis, mo2lity & ac2va2on
· Wound contracLon = fibroblasts can transform into myofibroblasts
which can contract, bringing the edges of the
wound together, shrinking it
· Remodelling
· GranulaLon & epithelialisaLon

2. MaturaLon phase
--- Scar remodelling
--- Mediated by MMPs
· Fibroplasia:
--- Depends on fibroblasts
--- MigraLon of the fibroblasts from the surrounding 2ssues via chemotaxis (specific or
non---specific (degrading products))
--- AcLvaLon & proliferaLon of fibroblasts
--- SecreLon of EC matrix proteins by the fibroblasts
DysfuncLons During The Inflammatory Response:
1. Hemorrhage: local factor
--- If there is a big hemorrhage at the site of injury & it is extensive, it is not beneficial
--- Increased number of erythrocytes = cleaning of the addi2onal erythrocytes by the
macrophages will require more 2me & effort
--- FormaLon of a big clot = larger space the granula2on 2ssue has to fill/replace
· This clot will also be a barrier for O2 diffusion at the site of injury (low
perfusion) which is not good
--- Increased amount of fibrin = needs to be fibrinolysed & later on absorbed
· Too much fibrin will favour fibrosis (increased granula2on 2ssue)
· The fibrin scar can impair the func2on of the organ
--- Increased accumulaLon of blood at the site of injury = if it stays there for a long
period of 2me it could be a poten2al culture medium for bacteria

2. Hypovolemia: systemic factor

--- Peripheral vasoconstricLon = leads to ischemia & hypoxia which impairs the acute
inflamma2on & repair process
--- Favours the insufficiency of O2 & amino acids (used by fibroblasts)
3. Metabolic diseases (diabetes mellitus): systemic factor
--- Glucose entry into the cells is impaired = produc2on of ATP is impaired
--- Microangiopathy = hypoxia in peripheral 2ssues
--- Protein glycosylaLon = hypoxia
· Glycated Hb = has a high affinity to O2; less O2 is transported to the 2ssues
4. Venous stasis: systemic factor
--- Usually occurs in cardiac failure
--- Hypoxia & no nutrients in the affected area
--- Cleanage is impaired at the site of injury
5. Hypoproteinemia: systemic factor
--- Occurs in hepaLc failure, malnutriLon, nephroLc syndrome, burns
--- Not enough amino acids are available for protein synthesis
6. AnL---inflammatory steroid treatment: systemic factor
--- Affects chemotaxis & adhesion

DysfuncLons During The ReconstrucLve Phase:

1. Impaired collagen matrix assembly:
--- Due to Ca2+ deficiency, Fe2+ deficiency, Protein deficiency
2. OverproducLon of collagen:
--- Hypertrophic scar = keloids (a big scar which extends around the scar’s edge)
3. Impaired wound contracLon:
--- Intense, extensive contracLon of wound —> deformi2es
--- Wound dehiscence (bursLng) = wound is not closed (obesity, sep2c complica2ons)
4. Impaired epithelialisaLon:
--- Due to hypoxia, hypovolemia, hypoproteinemia
PATHOLOGICALINFLAMMATORYREACTIONS:
· The efficiency of acute inflamma2on is done by the normal func2oning of the inflammatory
cells or mediators
· There is no defence if there is a pathological acute inflamma2on present
· The pathological reac2ons are classified into 3:
1. Disturbances of adhesion of micro & macrophages to the endothelial layer
2. DysfuncLons in chemotaxis
3. Decreased phagocyLc capacity

1. Disturbances of Adhesion:
--- Leukocyte Adhesion Deficiency (LAD):
· It is a disease with autosomal recessive transmission
· The leukocytes can not adhere to the endothelial layer, thus can’t get ac2vated
· Leukocytosis s2ll occurs but leukocytes are not present at the site of injury
· No adhesion, transmigra2on or ac2va2on of leukocytes —> no repair processes
· Leads to ulceronecroLc lesions
--- LAD1 = defect in the gene responsible for β2 chain synthesis of the β2---integrins
· Neutrophils & macrophages aren’t ac-vated

--- LAD2 = structural defect of the Lewis oligosaccharide in the leukocyte’s membrane
· There is a deficiency in the fucosila0on and/or glucosila0on
· Adhesion using E---selec-ns is impaired

2. DysfuncLons in Chemotaxis:
--- Dysfunc-ons of the microfibrillar ac-n:
· Autosomal dominant transmission
· It evolves with LAD1 & LAD2
· The leukocytes aren’t responsive because G---acLn can’t transform into F---acLn
· Leukocytes adhere, but can’t form pseudopods
· It can also be seen in complicated diabetes mellitus

--- C3 deficiency:
· Can be acquired or hereditary (hepa2c failure)
· C3a deficiency = impaired vasodila2on & chemotaxis
· C3b deficiency = impaired opsonisa2on & phagocytosis

--- C5 deficiency:
· Inherited (autosomal dominant) or acquired (leukemias, nephro2c syndrome)
· C5a deficiency
· C5b deficiency = impaired MAC forma2on
3. Decreased PhagocyLc Capacity:
--- Opsonisa-on deficiencies:
· C3b deficiency = impaired opsonisa2ob & phagocytosis

· Ig deficiency = primary immunodeficiency syndromes

1. Bruton X---linked Agammaglobulinemia:
· Lymphpoiesis is blocked at the pro---LyB stage
· So there is no maturaLon of the lymphocytes
· Mostly encountered in men
2. Common Variable Immunodeficiency (not X---linked):
· Hypogammaglobulunemia
· There is an impaired maturaLon of the B lymphocytes
--- They can mature, but are not able to recognise anLgens
· Due to the impaired receptor formaLon for the an2gens
3. Severe Combined Immunodeficiency (SCID):
· Blockage of the unipolar stem cell due to a deficiency of the enzyme
involved in the synthesis of DNA
· No producLon of B & T lymphocytes — aplas2c 2ssues/organs
· There is no anLbody producLon

--- Bactericidal deficiencies:

· NADPH oxidase deficiency:
--- Inherited disease
--- It could lead to chronic granulomatous disease
--- Mostly associated with diabetes mellitus
--- The microbe can sLll survive in the macrophage due to NADPH oxidase
deficiency
· The bacteria forms granulomas (surrounds the infected cells)
--- NADPH oxidase deficiency will lead to impairment of the myeloperoxidase
system (no H2O2)
· Decreased NADPH2 —> decreased free oxygen radicals producLon

· Chediak---Higashi disease:
--- An autosomal recessive disease
--- Dystrophy of the granules (altered shape) of neutrophils & macrophages
--- This causes lack of mediators (myeloperoxidase, lysozymes, cytochromes,
collegenase deficiency)
--- This will impair the microbicidal acLvity during phagocytosis