IMMS weeks 6 and 7

8/7/2019 IMMS weeks 6 and 7

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IMMS weeks 7 and 8 8.11.10 19.11.10

1. Protozoa

y Describe what protozoa are

y Identify key diseases caused by protozoa

y Describe the transmission and basic lif e cycle of plasmodia spp.

y Recognise how a patient may present in the UK with Malaria

y List the initial critical steps in investigating and managing a potential case of Malaria Protozoa are single celled eukaryotic organisms which consume bacteria. Very diverse:

Body shapes & sizes

Motility mechanisms

Lif e cycles

Reproductive strategies

Nutritional strategies

Hosts

5 main groups:

i. Mastigophora (f lagellates): Reproduce by binary fission.

Intestinal f lagellates:

Giardia lamblia Loose stools, diarrhoea, f latulence, abdominal

cramps. Giardiasis

Haemof lagellates:

Trypanosoma spp. insect bite 2 years previous, f ever, lethargy,

myalgia, weight loss, personality change, daytime somnolence, coma.

African

Trypanosomiasis

(sleeping sickness)

Other body sites:

Trichomonasvaginalis

ii. Sarcodina (Amoebae): move by means of f lowing cytoplasm

E.g. E ntamoeba histolytic holiday, bloody diarrhoea, increasing

right hypochondrium pain, liver abscess.

Amoebiasis



IMMS weeks 7 and 8 8.11.10 19.11.10

iii. Apicomplexa (Sporozoans): all species parasitic

P lasmodium spp. transmitted by bite of f emale Anopheles

mosquitoes, lie dormant and cause late relapse by reactivating months later,

f ever, haemolysis, anaemia, jaundice, hepatoslenomagaly, dark urine,

coma, renal failure, ARDS, Hypoglycaemia, shock.Children: non-specific, anaemia, hypoglycaemia.

Malaria

Five species cause human disease:

P . falciparum- cerebral malaria, matures in RBCs, Parasite matures in

RBCs knobs on RBC surface, bind to receptors on endothelial

cells in capillaries &venules, bind to non-inf ected RBCs = Rosetting,

Sequestration in small vessels (including brain, lung),

microcirculation obstructed: tissue hypoxia. chills and sweats,

myalgia, fatigue, nausea and vomiting, diarrhea.

Children: coma, extended limbs, fixed screaming, convulsions.

P . ovale

P . vivax

P . malariae

( P . knowlesi)

300-500 million cases per year, increasing incidence (resistance of parasite,

resistance of mosquito, climate change, travel)

Lif espan of f emale: 3-4 weeks

Night biting indoors mainly

Merozoites released into blood stream

P .falciparum

Complicated falciparum malaria: IV Q uinine Un complicated falciparum malaria: PO Q uinine

Non-falciparum malaria: PO Chloroquine

Fever + exotic travel = Think Malaria!



IMMS weeks 7 and 8 8.11.10 19.11.10

Other:C ryptosporidium spp.

Toxoplasma gondii - Recent HIV +ve diagnosis, 2-week history of progressive

left sided weakness, headaches, visual disturbance.

Toxoplasmosis

iv. Ciliophora (Ciliates): 2 types of nuclei

Balantidium coli severe diarrhoea, ulceration of colon

v. Microsporidia: production of spores

E nterocytozoonbieneusi diarrhoea and immunocompromisation



IMMS weeks 7 and 8 8.11.10 19.11.10

2. Histology of bone and cartilage

y Rigid forms of connective tissue

y Both derived from undiff erentiated mesenchymal cells

y Cartilage : 3 types

Hyaline Elastic

Fibrous

: cells are embedded in a dense glycosaminoglycan rich matrix containing

elastic tissue and collagen (f lexible, compressible and hardwearing)

: formed by chondroblasts, these become trapped in the matrix and mature

in chondrocytes.

: surrounded by a fibrous capsule perichondrium. (can diff erentiate into

chondroblasts if needed)

Hyline = contains fine fibrils of collagen and elastic. Appears as glassy. (rings

of trachea, larynx and articular surfaces)

Elastic = irregular fibres of elastic in matrix. (epiglottis and pinna of ear)

Fibrous = distinct bands of collagen (inter-vertebral discs)



IMMS weeks 7 and 8 8.11.10 19.11.10

y Bone: synthesised by osteoblasts which initially secrete a collagen matrix (type 1)

osteoid, which becomes mineralise

dwith crystals of hy

droxyapetite, trapping the

cells within the bone and causing them to become less synthetically active.

: also present are osteoclasts

:Compact bone is laid down as concentric layered cylinders called osteons

or Haversian systems. At the centre of osteons is anHaversian canal

containing blood vessels which carry nutrients and oxygen to the living

bone.

:Bones are surrounded by a fibrous capsule (collagen) called the periosteum

which contains progenitor cells capable of diff erentiating into osteoblasts

should the need arise.

:Mature (secondary) bone is well organised. It is laid down in layers with the

long axis of the hydroxyapetite crystals lying parallel to the collagen

framework. The collagen fibres of succeeding layers run at right angles to

each other thereby providing "plywood-like" strength to the bone.

:Internally many bones can be seen to consist of osteons. These are

cylindricals units composed of concentric layers of bone with a Haversian

canal at their centre. This canal contains blood vessels and nerves that

supply the osteocytes trapped within the bone. Osteones are continually

being eroded and replaced throughout lif e. Between osteons is interstitial

bone, the remnants of previous generations of osteons.

:Bones are surrounded by a fibrous capsule (mostly collagen) called the

periosteum. This contains progenitor cells capable of diff erentiating into

osteoblasts or condroblasts. These play an important part in bone healing

following a fracture.

3. Cellular regeneration

Due to:

y Wear and tear

y Continual loss of cells

y Hazardous environment

y Sub-lethal damage

y DNA damage

If not causes:

y Osteoarthritis

y Atheroma

y Osteoporosis

y Dementia



IMMS weeks 7 and 8 8.11.10 19.11.10

y Neoplasia

y Aging

y Death

Not:

y Permanent cells (skeletal muscle, neurones)

y Stable cells (hepatocytes, smooth muscle cells, renal tubular cells) y Labile cells (epidermal skin cells, gut enterocytes, bone marrow cells)

Stem cells:

y One daughter cell becomes a stem cell

y One daughter cell becomes a transit amplifying cell

y Fetal stem cells are pluripotent

Cell signalling:

y Autocrine acts on itself

y Paracrine acts on neighbouring cells

y Endocrine acts on distant cells (hypothalamus, pituitary, thyroid, pancreas, ovaries,

testes, adrenals, parathyroids, kidney)

Cell surface receptors:

y Ion channels ligand binding alters conformation of receptor, allows specific ion

movement (Ach at neuromuscular junctions)

y With intrinsic kinase activity extracellular binding site, ligand binding causes

dimerization and phosphorylation of receptor, receptor binds to other proteins,

signal cascade.

y G-protein coupled receptors 7 transmembrane segments, ligand binding causes

association with intracellular GTP-hydrolysing proteins (drug receptors)

y Without intrinsic enzymatic activity monomeric transmembrane molecules, ligand

biding causes intercellular conformational change

4. Wound healing and fibrosis

y Fibrosis?

y Forming a fibrous scar

y Healing incised wounds

y Healing after tissue loss

" Fibrosis=scarring

Damage to parenchymal cells

Damage to stromal framework

Parenchymal regeneration cannot repair def ect

Formation of granulation tissue (loops of capillaries surrounded by

myofibroblasts, gradually contracts)



I w s

" Forming a scar Help remove debris¡ f ig¢

t inf ection and stimulate f ibroblast

prolif eration

Inf lux of macrophages¡ mast cells¡ lymphocytes

Angiogenesis (breakdo£

n of parent vessel basement membrane¤

endothelial cell migration and prolif eration, lumen f ormation,

maturation and gro

£

th inhibition¥

Stimulated by basic f ibroblast gro

£

th factor, vascular endothelial gro£

th factor¥ P

¦ ODUCED BY

ST¦

OMAL CELLS)

Migration and prolif eration of f ibroblasts (stimulated by basic

f ibroblast gro§

th factor, platelet derived gro§

th factor,

transf orming gro§

th factor)

Deposition of extracellular matrix (f ibroblasts synthesise collagen,

induced by PDGF, bFGF, TGF, TNF, interleukin 1)

Remodelling (removal of collagen by matrix

metalloproteinaseseg ̈interstitial collagenases, gelatinases,

stromeolysins. Inhibited by Tissue inhibitors of mms (TIMPS) wound

contraction)



IMMS weeks 7 and 8 8.11.10 19.11.10

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IMMS weeks 6 and 7