GROWTH ADAPTATIONS = , or in stress

hypertrophy +
stress = cell size
hyperplasia
involves gene activation + protein synthesis + production of
generally occur
organelles
together
*PERMANENT TISSUES = HYPERTROPHY ONLY
(cannot make new cells):
Ex: uterus during
(1) Cardiac Muscle (LV Hypertrophy due to systemic HTN)
pregnancy
(2) Skeletal Muscle
LV Hypertrophy
1st = hyperplasia
(3) Nerve
of smooth muscle
stress = # of cells
2nd = hypertrophy
involves production of new cells from stem cells
of smooth muscle
Physiologic Hyperplasia = does NOT risk of cancer
HYPERPLASIA Pathologic Hyperplasia = risk of cancer
Pathologic Hyperplasia Dysplasia Cancer
ex: Endometrial Hyperplasia
*EXCEPTION: Benign Prostatic Hyperplasia = no risk of cancer
stress = cell size + # of cells
ex: hormonal stimulation, disuse or nutrients/blood supply
ATROPHY
Apoptosis = # of cells
Ubiquitin-proteosome degradation (intermediate filaments of cytoskeleton destroyed) +
Autophagy (autophagic vacuoles fuse w/ lysosomes) = cell size
METAPLASIA
stress = cell type
involves surface epithelium:
Squamous (keratinizing or non-keratinizing)
squamous
Columnar (gut)
Urothelial (transitional)
columnar
occurs via reprogramming of stem cells which then produce new cell type
*REVERSIBLE (ex: tx of GERD)
Barrett Esophagus persistent stress Metaplasia Dysplasia Cancer
(ex: Barrett Esophagus Adenocarcinoma of Esophagus)
*EXCEPTION: Apocrine Metaplasia of Breast = no risk of cancer
Barrett esophagus
non-keratinizing squamous epithelium non-ciliated, mucin-producing columnar cells =
contains goblet cells

Keratomalacia
due to GERD
Keratomalacia = Vitamin A deficiency Metaplasia (or night blindness, PML)
Myositis Ossificans Vit A = necessary for differentiation of conjunctiva
thin squamous lining of conjunctiva thick stratified keratinizing squamous epithelium
Myositis Ossificans = Mesenchymal (connective) tissue Metaplasia
trauma to skeletal muscle inflammation metaplasia bone
NOT Osteosarcoma because bony growth is in muscle NOT coming off of bone
disordered cellular growth = proliferation of precancerous cells
Cervical Intraepithelial Neoplasia (CIN) = dysplasia = precursor to cervical cancer

DYSPLASIA
arise from longstanding pathologic hyperplasia (Endometrial Hyperplasia) or metaplasia
(Barrett Esophagus)
*REVERSIBLE
persistent stress Dysplasia Cancer (= IRREVERSIBLE)
APLASIA
failure of cell production during embryogenesis
Unilateral Renal Agenesis = failure to produce 1 kidney during embryogenesis
HYPOPLASIA
cell production during embryogenesis = small organ
Streak Ovary during Turner Syndrome
HYPERTROPY

CELLULAR INJURY = stress > ability to adapt

depends on:
(1) type of stress
inflammation growth adaptation NOT injury
(2) severity
Slowly developing ischemia of kidney (ex: Renal Artery Atherosclerosis or Fibromuscular Dysplasia of
renal artery) atrophy of kidney
Acute ischemia of renal artery (ex: Renal artery embolus) injury (infarction/death of kidney
parenchyma)
(3) type of cell affected
Neuron highly susceptible to hypoxia = ischemic injury
Skeletal muscle more resistant to hypoxia
common causes:
Inflammation (infection = pneumonia, autoimmune diseases), Nutritional deficiency or excess, Hypoxia =
(MIs, ischemic stroke), Trauma (gun shot wound to tissue), Genetic mutations
Low O2 delivery to tissue
HYPOXIA
O2 = final e- acceptor in ETC of ox phos
Low O2 impairs ox phos ATP cellular injury
(A) Na+/K+ pump fails = cell swelling = [Ca2+] + [H2O] in cytosol
(B) Ca2+ pump fails = [Ca2+] in cytosol = dangerous activates enzymes
(C) aerobic glycolysis anaerobic glycolysis = poor production of ATP +
production of lactic acid ( pH) denatures protein + precipitates DNA
Causes = (1) ischemia, (2) hypoxemia, (3) O2 carrying capacity
blood flow through organ
Due to:
(A) arterial perfusion (ex: atherosclerosis of coronary artery = angina)
(B) venous drainage
(1) ISCHEMIA
ex: Budd-Chiari Syndrome = infarction of liver due to:
Thrombosis = blockage of hepatic vein
Polycythemia = RBCs = thickness of blood Thrombosis
Lupus
(C) tissue perfusion = Shock hypotension (exs: cardiogenic, hypovolemic,
neurogenic, anaphylactic shock)
PaO2 of blood
FiO2 (environment) PAO2 (alveolus) PaO2 (artery) SaO2 (RBC)
(A) high altitude = FiO2 = PaO2
(B) hypoventilation = PACO2 = PAO2 = PaO2 (ex: COPD)
(2) HYPOXEMIA
(C) diffusion defect = thickness of diffusion barrier = normal PAO2 but
PaO2 (ex: interstitial fibrosis of the lung)
(D) VQ mismatch:
blood bypasses lung (ex: circulation problem, R L shunt)
O2 cannot reach blood (ex: ventilation problem, atelectasis)
Hb loss or dysfunction
(A) Anemia = RBC mass (PAO2 + SaO2 = normal)
(B) CO poisoning ( SAO2, PaO2 = normal)
CO binds Hb 100x more avidly than O2
Exposures = smoke from fires, exhaust from car or gas-heater
*CHERRY RED appearance of skin ( O2 delivery to tissues)
(3) O2 CARRYING CAPACITY
Early sign of exposure = headache
Significant exposure = coma + death
(C) Methemoglobinemia ( SAO2, PaO2 = normal)
Fe in heme oxidized = Fe2+ Fe3+ (cannot bind O2)
Due to oxidant stress = sulfa/nitrate drugs
Newborns = highly susceptible
*CHOCOLATE coloured blood + cyanosis
Tx = IV Methylene Blue reduces Fe3+ back to Fe2+

REVERSIBLE INJURY

(1)
(2)
(3)

initial phase of injury

*HALLMARK = CELLULAR SWELLING
loss of microvilli = effaced
membrane blebbing = due to [H2O]
swelling of RER = ribosome dissociation +
protein synthesis

IRREVERSIBLE INJURY
due to persistent injury
*HALLMARK = MEMBRANE DAMAGE
(1) plasma membrane damage
cytosolic enzymes leak into serum (ex: troponin)
[Ca2+] entering cell
(2) mitochondrial membrane damage
loss of ETC (= inner mitochondrial membrane)
cytochrome C leaks into cytosol (activates
apoptosis)
(3) lysosome membrane
hydrolytic enzymes leak into cytosol = activated
by [Ca2+] intracellularly
end result = death

CELL DEATH = NECROSIS + APOPTOSIS

*HALLMARK = LOSS OF NUCLEUS
(1) pyknosis = nuclear condensation
(2) karyorrhexis = nuclear fragmentation
(3) karyolysis = nuclear dissolution

APOPTOSIS = cellular suicide

death of single cells or small groups of cells
ATP dependent + genetically programmed cell death
Exs:
(1) endometrial shedding during menstruation
(2) removal of cell during embryogenesis
(3) CD8+ T cells mediated killing of virally infected cells
Morphology
(1) cell shrinks cytoplasm = eosinophilic = concentrated cytoplasm
(2) nucleus condenses (pyknosis) + fragments (karyorrhexis)
(3) apoptotic bodies = fall from cell + removed by macrophages
(4) *NO INFLAMMATION
CASPASES = mediate apoptosis activated by multiple pathways
(1) activate proteases = breakdown cytoskeleton
(2) activate endonuclease = breakdown DNA
inactivation of BCl2 cellular injury, DNA damage or loss of hormonal
(A) INTRINSIC MITOCHONDRIAL
stimulation
PATHWAY
lack of BCl2 cytochrome C leaks from inner mitochondrial matrix into
cytoplasm ACTIVATES CASPASES
FAS ligand binds FAS receptor (CD95) on target cell
Negative selection of thymocytes in thymus (T cells produced in
bone marrow + modified in thymus)
(B) EXTRINSIC RECEPTORLIGAND PATHWAY
Positive selection = bind self antigen? yes, T cell survives
Negative selection = bind self antigen strongly? yes, death of T cell
via apoptosis (eliminates autoimmune disorders)
Tumor Necrosis Factor (TNF) binds TNF receptor on target cell
CD8+ T cells recognize antigen on MHCI + kill cell which expresses antigen
via apoptosis
(C) CYTOTOXIC CD8+ T CELL
PATHWAY
CD8+ T cells secrete perforin = creates pores in target cell membrane
granzyme enters pore + ACTIVATES CASPASES

NECROSIS = murder
death of large group of cells followed by ACUTE INFLAMMATION
due to underlying pathologic process

COAGULATIVE NECROSIS

necrotic tissue
= firm

nuclei
disappear

normal
tissue

Red
Infarction

cell shape + organ structure = preserved by coagulation of proteins

*ISCHEMIC INFARCTION OF ANY ORGAN EXCEPT BRAIN
infarcted tissue = wedge-shaped (points to area of vascular occlusion) + pale
Red Infarction (hemorrhagic) = blood re-enters loosely organized tissue (ex:
pulmonary or testicular infarction cord twists: vein collapses, artery = fine
blood cannot exit)
necrotic tissue = liquefied due to enzymatic lysis of cells + proteins
Brain infarction = proteolytic enzymes from microglial cells (= macrophages of
brain) liquefy brain
LIQUEFACTIVE NECROSIS Abscess (walled area of dead tissue) = proteolytic enzymes from neutrophils
liquefy tissue
Pancreatitis (liquefactive + fat necrosis) = proteolytic enzymes from pancreas
liquefy parenchyma
Dry Gangrene = coagulative necrosis ~ mummified tissue
ischemia of lower limb + GI tract
GANGRENOUS NECROSIS
ex: atherosclerosis in diabetics
Wet Gangrene = liquefactive necrosis
Dry Gangrene
superimposed infection of dead tissue
necrotic tissue = soft + friable ~ cottage cheese-like
CASEOUS NECROSIS
coagulative + liquefactive necrosis
Caseous Necrosis
ex: granulomatous inflammation due to TB
of lung
or fungal infection
necrotic tissue = adipose tissue w/ Ca2+ deposition ~ chalky-white
due to:
Trauma to fat (ex: breast) FAs released by trauma + join w/ Ca2+ via
FAT NECROSIS
Saponification = dystrophic calcification
Pancreatitis-merited damage of peripancreatic fat
FAs released by lipases + join w/ Ca2+ via
Fat Necrosis
Saponification = dystrophic calcification
necrotic damage to blood vessel
leaking of proteins (fibrin) into vessel wall = bright pink staining of wall
ex: Malignant HTN = BP, headache, renal failure, papilledema = MEDICAL
FIBRINOID NECROSIS
EMERGENCY necrosis of BV wall due to BP
(Benign HTN = long-term progressive damage)
ex: Pre-eclampsia = fibrinoid necrosis of placenta Fibrinoid Necrosis
of vessel
ex: Vasculitis = fibrinoid necrosis of vessel

DYSTROPHIC CALCIFICATION
NORMAL serum [Ca2+] + [PO4]
calcification occurs in necrotic tissue = nidus
ex: psammoma bodies in:
Papillary Thyroid Carcinoma
Meningioma
Papillary Serous Carcinoma of Ovary

METASTATIC CALCIFICATION
HIGH serum [Ca2+] or [PO4]
calcification occurs in normal tissue
ex: Hyperparathyroidism = nephrocalcinosis
ex: Bone Metastatic Cancer = metastatic calcification

FREE RADICAL INJURY

free radicals = unpaired e- in outer orbit = induces injury
O2 (oxygen) O2 (superoxide) H2O2 (hydrogen peroxide) OH (hydroxyl radical) H2O (water)
physiologic generation of free radicals during ox pos
cyt C oxidase (complex IV) transfers e-s to O2
partial reduction of O2 (does not receive 4e-s) yields: superoxide + hydrogen peroxide + hydroxyl radicals
pathologic generation of free radicals
(1) ionizing radiation = H2O hydrolyzed OH = *MOST DAMAGING
(2) inflammation neutrophils kill microbe via O2 dependent mechanism:
NADPH oxidase: O2 O2 = oxidative burst

(Superoxide Dismutase: O2 H2O2)

(Myeloperoxidase: H2O2 HOCl = bleach)
O2 independent mechanism
(3) metals (Cu + Fe) Fenton Rxn = OH generated
Hemachromatosis = build up of Fe generates free radicals
Wilsons Disease = build up of Cu generates free radicals
(4) drugs + chemicals
ex: Acetaminophen free radicals generated via P450 = tissue damage in liver
free radical damage via:
PEROXIDATION of lipids (damages lipid membranes)
OXIDATION of DNA (oncogenesis) + proteins (= cellular damage)
elimination of free radicals via:
ANTIOXIDANTS = Vitamin A, C, E + glutathione
METAL CARRIER PROTEINS = transferrin tightly binds Fe in blood to deliver to liver + macrophages
where Fe is bound to ferritin
ENZYMES
SOD = Superoxide Dismutase (in mitochondria) removes O2
Catalase (in peroxisomes) removes H2O2
Glutathione Peroxidase (in mitochondria) removes OH
organic solvent used in dry cleaning industry
converted to CCl3 = free radical via P450 system of hepatocytes:
damages hepatocytes = reversible injury
(A) Carbon Tetrachloride (CCl4)
cellular swelling
RER swells
ribosomes pop off
protein synthesis
lack of apolipoproteins = fatty of liver
return of blood to ischemic tissue = production of O2 derived free radicals
(B) Reperfusion Injury
leads to continued cardiac enzymes (ex: troponin) in infarcted myocardial
tissue

AMYLOIDOSIS
amyloid = misfolded protein deposits in extracellular space = tissue damage
common characteristics:
pleated sheet
congo red stain
apple-green bifringence
amyloid deposits in multiple body systems
Primary Amyloidosis
systemic deposition of AL amyloid = derived from Ig light chain
ex: Multiple Myeloma = plasma cell dyscrasias = abnormalities of plasma
cell = over production of Ig light chain leaks out into blood misfolds
deposits into tissues
Secondary Amyloidosis
systemic deposition of AA amyloid = derived from SAA = serum
associated amyloid
SAA in:
chronic inflammatory states
malignancy
Familial Mediterranean Fever (FMF) = dysfunction of neutrophils
SYSTEMIC AMYLOIDOSIS
neutrophils activate + create attack = acute inflammation
fever + acute serosal inflammation
can mimic MI = serosal surface of heart or acute
appendicitis = serosal surface of abdomen
acute inflammation = SAA = AA = secondary amyloidosis
Classical findings:
*KIDNEY = most common organ
Nephrotic Syndrome
Restrictive Cardiomyopathy or arrhythmia = compliance no filling =
cardiac failure
tongue enlargement, bowel-wall thickening (malabsorption)
Hepatosplenomegaly
Diagnosis:
biopsy of abdominal fat pad + rectum mucosa = easy targets
*AMYLOID CANNOT BE REMOVED = damaged organ must be transplanted
amyloid deposits localized to single organ system
Senile Cardiac Amyloidosis
amyloid = serum transthyretin deposits in heart
asymptomatic 25% of people > 80 yo
Familial Amyloid Cardiomyopathy
amyloid = mutated serum transthyretin deposits in heart
leads to restrictive cardiomyopathy heart = compliance no filling =
cardiac failure
5% african americans carry mutated gene
Type II Diabetes Mellitus (insulin resistance = insulin production)
LOCALIZED AMYLOIDOSIS
amyloid = amylin (derived from insulin) deposits in islets of pancreas
Alzheimer Disease
amyloid = A amyloid = deposits in brain
plaque in brain (derived from amyloid precursor on protein = gene on
chromosome 21 pts w/ Down Syndrome develop early onset alzheimer)
Dialysis-associated Amyloidosis
amyloid = 2-microglobulin = deposits in joints
Medullary Carcinoma of Thyroid
amyloid = calcitonin = deposits in tumour = tumour cells in amyloid
background
tumor of thyroid derived from c-cells = produce calcitonin

INFLAMMATION
inflammatory cells + plasma cells + fluid exit BV + enter interstitial space
*NEUTROPHILS = ACUTE INFLAMMATION
*LYMPHOCYTES = CHRONIC INFLAMMATION

acute inflammation
w/ neutrophils

chronic inflammation
w/ lymphocyte +
plasma cells

(1) ACUTE INFLAMMATION

EDEMA + NEUTROPHILS
edema = fluid from BV tissue
neutrophils = key inflammatory cell in BV tissue
In response to:
INFECTION = eliminates pathogen
TISSUE NECROSIS = clears necrotic debris
immediate response (w/i 24 hrs) w/ limited specificity (generalized response) = INNATE IMMUNITY
(eosinophils, neutrophils, macrophages, mast cells, complement system, mucous, epithelium)
mediators = (A) TLRs, (B) arachidonic acid, (C) mast cells, (D) complement, (E) Hageman factor
present on cells of innate immunity = macrophage + dendritic cells
recognize PAMPs (pathogen associated molecular patterns) on microbes
ex: CD14 (TLR) on macrophages recognizes LPS (PAMP) = on outer membrane
(A) TLRs
of Gram negative cells
TLR activation NF-KB = nuclear transcription factor activates immune response
genes production of multiple immune mediators
also present on adaptive immunity cells = lymphocytes therefore important role
in mediating chronic inflammation
released from phospholipid cell membrane via PLA2
acted on via:
CYCLOOXYGENASE
produces prostaglandins = PGI2 + PGD2 + PGE2 (mediate fever + pain)
mediate:
vasodilation of arterioles
vascular permeability of post-capillary venule
(B) Arachidonic Acid
5-LIPOXYGENASE
produces leukotrienes = LTC4 + LTD4 + LTE4 = slow reacting
substances of anaphylaxis
mediate:
vasoconstriction (contraction of smooth muscle)
bronchospasm
vascular permeability (pericytes contract)
LTB4 = attracts + activates neutrophils
* LTB4 + C5a + IL8 + bacterial products = attract + activate neutrophils
throughout connective tissue
activated by:
(1) tissue trauma
(C) Mast Cells
(2) complement proteins = C3a + C5a
(3) cross-linking of cell surface IgE by antigen
Immediate response via release of preformed histamine granules = mediate:
vasodilation of arterioles
vascular permeability of post-capillary venule
Delayed response via leukotrienes = arachidonic acid metabolites

(D) Complement

(E) Hageman Factor

help inflammation = proinflammatory serum proteins

circulate as inactive precursors
activated by:
(1) Classical pathway = C1 + IgG or IgM bound Ag
(2) Alternative pathway = microbial products activate complement
(3) Mannose-binding lectin pathway = MBL + mannose on microbe
result:
C3 convertase: C3 C3a + C3b
C3b C5 convertase: C5 C5a + C5b
Membrane Attack Complex (lyses microbe = creates holes in cell membrane):
C5b C6-9
C3a + C5a = mast cell degranulation
C5a = chemotactic for neutrophils
C3b = opsonin for phagocytosis
inactive proinflammatory protein
produced in liver
activated upon exposure to subendothelial tissue or collagen
activates:
(1) coagulation + fibrinolytic systems = DIC
(2) complement
(3) kinin system cleaves HMWK (high molecular weight kininogen) to bradykinin
+ mediates: vasodilation, vascular permeability (~ histamine), mediates pain
(PGE2 + bradykinin)

STEP 1
Margination

(1)
(2)
(1)

STEP 2
Rolling
(2)
(3)
(1)

STEP 3
Adhesion

STEP 4
Transmigration +
Chemotaxis

(2)
(3)
(4)

(1)
(2)
(1)
(2)

STEP 5
Phagocytosis

(3)

(1)
(2)
(3)

STEP 6
Destruction of
Phagocytosed Material
(4)

(5)
STEP 7: Resolution

(1)

(2) ACUTE INFLAMMATION

vasodilation slows blood flow in post capillary venule
cells marginate from center of flow to periphery
selectins (= speed bumps) upregulated on endothelial cells
P-selectin = release from Weibel-Palade bodies mediated by histamine
E-selectin = induced by IL-1 + TNF
selectins bind sialyl lewis X on leukocytes
interaction = rolling of leukocytes along vessel wall
cellular adhesion molecules = ICAM + VCAM are upregulated on endothelium by IL-1
+ TNF
integrins are upregulated on leukocytes by C5a + LTB
CAMs + integrins = firm adhesion of leukocytes to vessel wall
Leukocyte Adhesion Deficiency = most commonly due to autosomal recessive
defect of integrins (CD18 subunit)
clinical features = separation of umbilical cord + circulating neutrophils (due
to impaired adhesion of marginated pool of leukocytes) + recurrent bacterial
infections that lack pus formation
Leukocytes transmigrate across endothelium of post capillary venule + move toward
chemical attractants = chemotaxis
Neutrophils are attracted by = bacterial products + IL-8 + C5a + LTB4
consumption of pathogens or necrotic tissue = enhanced by opsonins = IgG +
C3a
pseudopods extends from leukocytes to form phagosomes = internalized + merge w/
lysosomes to produce phagolysosomes
Chediak-Higashi syndrome = protein trafficking defect (autosomal recessive) =
impaired phagolysosome formation, clinical features:
risk of pyogenic infections
neutropenia = due to intramedullary of neutrophils
giant granules in leukocytes = due to fusion of granules arising from golgi
defective primary hemostasis = due t abnormal dense granules in platelets
albinism
peripheral neuropathy
O2-dependent killing = most effective mechanism
HOCl generated by oxidative burst in phagolysosomes
Chronic-granulomatous disease (CGD) = poor O2-dependent killing
due to NADPH oxidase defect = x-linked or AR
leads to recurrent infection + granuloma formation w/ catalase positive
organisms = S. aureus + Pseudomonas + Serratia + Nocardia + Aspergillus
nitroblue tetrazolum test = used to screen for CGD
normal leukocytes = turn blue, defective leukocytes = colourless
Myeloperoxidase deficiency = defective conversion: H2O2 HOCl
risk of Candida infections (most pts = asymptomatic)
nitroblue tetrazolum test = normal because respiratory burst = intact
O2-independent killing (less effective than O2-dependent killing) = occurs via
enzymes in leukocyte secondary granules (ex: lysozyme in macrophages)
neutrophils undergo apoptosis/disappear w/i 24 hrs after resolution of inflam.
stimulus

REDNESS (RUBOR)
+

WARMTH (CALOR)

SWELLING

(TUMOR)
PAIN (DOLOR)
FEVER

(3) CARDINAL SIGNS OF ACUTE INFLAMMATION

due to vasodilation = blood flow
via relaxation of arteriolar smooth muscle
key mediators = HISTAMINE + PROSTAGLANDINS + BRADYKININ
due to leakage of fluid from post-capillary venues into interstitial space = EXUDATE
key mediators:
(1) HISTAMINE = causes endothelial cell contraction
(2) TISSUE DAMAGE = results in endothelial cell disruption
due to BRADYKININ + PGE2 = sensitize nerve endings
PYOGENES (ex: LPS from bacteria) cause macrophages to release IL-1 + TNF =
cyclooxygenase activity in perivascular cell of hypothalamus = PGE2 = temp
set point

(4) MACROPHAGES

predominate after neutrophils

peak 2-3 days after inflammation begins
derived from monocytes in blood
arrive in tissue via margination + rolling adhesion + transmigration sequence
ingest organisms via phagocytosis (augmented by opsonins) + destroy phagocytosed material using
enzymes (Ex: lysozymes) in secondary granules (O2-independent killing)
manage next step of inflammation process
outcomes include:
resolution + healing = anti-inflammatory cytokines produced by macrophages = IL-10 + TGF-
continued acute inflammation = persistent pus formation (IL-8 from macrophages recruits additional
neutrophils)
abscess = acute inflammation surrounded by fibrosis (macrophages mediate fibrosis via fibrogenic
growth factors + cytokines)
chronic inflammation = macrophage present antigen to active CD4+ helper T cells = secrete cytokines
that promote chronic inflammation

CHRONIC INFLAMMATION
LYMPHOCYTES + PLASMA CELLS
delayed response + more specific (ADAPTIVE IMMUNITY) than acute inflammation
Stimuli:
persistent infection = MOST COMMON CAUSE
infection w/ viruses + mycobacteria + parasites + fungi
autoimmune diseases
foreign material
some cancers
produced in bone marrow as progenitor T cells
develop in thymus where T-cell receptor (TCR) undergoes rearrangement + progenitor
cells become CD4+ helper T cells OR CD8+ cytotoxic T cells
(1) T cells use TCR complex = TCR + CD3 for antigen surveillance
(2) TCR complex recognizes antigen presented on MHC molecules
CD4+ cells MHC class II, CD8+ cells MHC class I
(3) activation of T cells requires: binding of antigen/MHC complex + additional 2nd signal
CD4+ helper T cell activation:
(1) extracellular antigen (ex: foreign protein) phagocytosed + processed +
presented on MHC II = expressed by antigen presenting cells (APCs)
(2) B7 on APC binds CD28 on CD4+ helper T cells providing 2nd activation signal
(3) Activated CD4+ helper T cells secrete cytokines = help inflammation + divided
into 2 subsets:
(A) T LYMPHOCYTES
(1) TH1 subset secretes IL-2 (T cell growth factor + CD8+ T cell activator)
+ TFN- (macrophage activator)
(2) TH2 subset secretes IL-4 (facilitates B-cell class switching to IgG + IgE)
+ IL-5 (eosinophil chemotaxis +
CD8+ cytotoxic T cell activation:
(1) intracellular antigen (derived from proteins in cytoplasm) processed +
presented on MHC I = expressed by all nucleated cells + platelets
(2) IL-2 from CD4+ TH1 cells provides 2nd activation signal
(3) Cytotoxic T cells are activated for killing
(4) Killing occurs via:
secretion of perforin + granzyme apoptosis
expression of FasL which binds Fas on target cells apoptosis
immature B cells produced in bone marrow + undergo Ig rearrangements to
become naive B cells that express surface IgM + IgD
B-cell activation occurs via:
(1) Antigen binding by surface IgM or IgD = maturation to IgM- or IdD-secreting
(B) B LYMPHOCYTES
plasma cells
(2) B-cell antigen presentation to CD4+ helper T cells via MHC II
CD40 receptor on B cell binds CD40L on helper T cells via MHC II
providing 2nd activation signal
Helper T cell secretes IL-4 + IL-5 (mediates B-cell isotype switching +
hypermutation + maturation to plasma cells)
(C) GRANULOMATOUS subtype of chronic inflammation
characterized by granuloma = collection of epithelioid histiocytes (macrophages w/
INFLAMMATION
abundant pink cytoplasm) = surrounded by giant cells + rim of lymphocytes
divided into noncaseating + caseating subtypes:
(A) NONCASEATING GRANULOMAS = lack central necrosis + etiologies = rxn to
foreign material + sarcoidosis + beryllium exposure + Crohn disease + cat scratch
disease
(B) CASEATING GRANULOMAS = exhibit central necrosis + characteristic of
tuberculosis + fungal infections
steps involved in granuloma formation:
(1) macrophages process + present antigen via MHC II to CD4+ helper T cells
(2) macrophages secrete IL-12 inducing CD4+ helper T cells to differentiate into TH1 cells
(3) TH1 cells secrete TFN- = converts macrophages to epithelioid histiocytes + giant cells