Micro

Gram +ve Cocci :- Staph, Strep, enterococci

Gram +ve Rods: - listeria, Coreneybacterium, Bacillus, clostridium

(Branched Gram +ve Rods:- Actinomyces, Nocardia)

Gram -ve Cocci :- Nisseria, Moraxella

Gram -ve Coccobacillus :- Hemophilus influenzae

Gram -ve Rods :- Rest all microbes are gram -ve rods.

Actinomyces - sulfer granules

Cord factor - responsible for serpentine growth in vitro of M.tb

Calcium dipicolinate :- Endospores

Corineybacterium diphtheirae :- Gram +ve Rods with granules stained with Methyline
blue

Koilocytic cells - HPV

Clue Cells :- Chlamydiae

Owl Eye inclusions in cells :- CMV

Chlamydiae :- Elementry body and Reticulate body

Klebsiella :- Elderly Pt. with COPD/ Alcoholism, Gelatinous bloody sputum, PMNs, Gr
-ve rods

Eikenella - corrodes the agar, Bleach like smell (I-can-smell-a)

Anaerobes ABC :- Actinomyces, Bacteroides, Clostredium

lysogenic conversion - lysogeny changes the charaderistic of the lysogenized organism.

known host ell receptor-virion/virion protein :- - CD21 & EBV - gp350

- CD4 & HIV - gp120

- erythrocyte & prvovirus B19 - P

antigen(globoside)
Parvoviridae Family- Smallest viruses. ssDNA, non-enveloped

Parvovirus B19- Causes fifth Ds, Aplastic crisis in Sickle cell anemia Pt. ( low
reticulocyte count with low hematocrit) and Hydrops fetalis (particularly when infection
occures before 20th week of gestation).

Globoside is present mainly on Erythrocytes, and erythroid progenitors and also on

megakaryocytes, endothelial cells, placental trophoblasts and fetal liver and heart cells.

Bronchitis/bronchiolitis - Respiratory syncytial virus, Influenza virus and coronavirus.

these all are enveloped, RNA viruses.

Fifth Ds/ Erythema infectiosum - prodrome of low-grade fever, headache, malaise and
URTI f/b sudden appearance of an erythmatous malar rash with circumoral pallor
( slapped cheek) 2-5 days later. As the facial rash fades, an erythematous rash in a
reticular, lacelike pattern often appears on trunk and extremities.

EBV- Monospot test, detects heterogenous group of IgM antibodies that react with the
hetrophile antigen on the horse red blood cells.

HUS(Hemolytic Uremic Syndrome):- hemolytic anemia, thrombocytopenia and renal

insufficiency.

- occurs after GI infection with E. coli o157:h7.

pentamidine - T/t and Prophylaxis of Pneumocystis jiroveci.

- also for Leishmaniasis and african sleeping sickness.

Nifurtimox - T/t of Chaga's Ds (American trypanosomiasis).

Plasmodium - RBCs filled with multiple, round, smaller nucleated cells.

Primaquin - P. vivax and P. ovale liver schizonts.

Bacterial Vaginosis - no evidence of vaginal inflammation.

- by Gram Variable coccobacilli Gardenerela vaginalis

- grey white discharge with a fishy odor. +ve whiff test.

Clue cells - Vaginal squamous epithelial cells covered with multiple, small
adherent bacteria.

Rubella (german Measles) - fever, maculopapular rash with cephalo caudal progression
and Generalized lymphadenopathy esp. postauricular and occipital(unlike
Measles/Rubeola).
Unlike Measles/ Rubeola, the rash of rubella typically spreads faster and does not
darken or coalesce.

C. diphthriae AB-exotoxin [ A(active subunit) & B(Binding Subunit)]-> A subunit

transfers ribose residue from NAD to a histidine on EF-2-> ribosylation & inactivation of
EF-2-> termination of protein synthesis.

- toxin acts locally, causing respiratory cell necrosis with formation of fibrinous,
coagulative exudates (coalescing pseudomembrane). Coalescing pseudomembrane is
composed of C. dephtheriae bacteria, leucocytes, fibrin and necrotic mucosal epithelial
cells. It adheres tightly to the underlying mucosa and will cause bleeding if avulsed.

DPT vaccine- against B subunit.

Shigella's shiga toxin and EHEC's shiga like toxin- cause inactivation of 60s Ribosome.

Lecithinase - Clostridium perfringens

Dextrans, produced from sucrose by Viridens strep, helps them to adhere to fibrin-
platelet agregates. Thus it can colonize only on damaged valves.

Leptospirosis - can progress to Weil's syndrome i.e. jaundice, renal dysfunction,

thrombocytopenia and bleeding.

cat scratch fever - Bartonella henselae. In immunocompromissed, bacillary

angiomatosis (red-purple papules on the skin).

Rocky Mountain Spotted fever - Ricketsia rickettsiae.

-contact with dogs n wooded areas or grassy fields.

- palmoplantar erythmatous rash, macular or petechial eruptions that spread

proximally to involve trunk. a/w fever, headache n conjunctival hyperemia.

Alcohol- disorganize lipid structure in cell membrane n denature cellular protein.

alcohols require presence of water for maximal effect.

formaldehyde and glutaraldehyde:- alkylating and cross linking DNA and proteins.

iodine:- halogenation of proteins and DNA.

post herpetic neuralgia:- persistent localized stabbing pain, Lasts months. Mainly in
elderly.

Visual impairment- complication of Hepes zoster ophthalmicus i.e. VZV infection of the
trigeminal ganglion of CN V1.
Leprosy:-

- Transmission is through respiratory route.

- occurs in Pts. with weak cell-mediated (th1) response.

- M. leprae grows best at the temperature that are slightly less than core body
temperature (eg. skin, superficial nerve, eyes and testes).

Tuberculoid leprosy - least severe form.

Lepromatous leprosy - severe form.

Measles (CCCK) Cough, Coryza, Conjunctivitis and Kolik's spots (grains of sand on
erythematous base).

- small, whitish, bluish or greyis specks on the buccal mucosa adjascent to the
second molars.

- after these symptoms, maculopapular rashes appear in 1-2 days.

Complications - Pneumonia, laryngotracheobronchitis (croup).

Acute rheumatic fever - throat pain, fever, malaise, white exudates in tonsils and
swollen anterior cervical LN.

M/c pathogens causing nosocomial bloodstream infection -

- Coagulase VE Staph

- Staph Aureus

- enterococci

- Candida Sp.

Cyclosporin - Clcineurin inhibitor. Prevents activation of T helper cells.

POL Gene mutatoins are responsible for emergence of protease inhibitor resistance in
HIV-1. It is also responsible for structural changes in HIV-1 reverse transcriptase that
renders the enzyme resistant to standard nucleoside and Non-nucleoside reverse
transcriptase inhibitor.

Humoral immunity is against HIV-1 depends upon the structural glycoproteins encoded
by the env genes.

DiGeorge Syndrome - maldevelopment of 3rd n 4th pharyngeal pouch.

Acute graft rejection - by cell-mediated pathway, in 1-4 weeks following transplant.

Hyperacute rejection- acute cessation of blood flow through an organ immediately after
anastomosing the vessels.

MOA- d/t preformed antibodies in the recipient that are directed against donor
antigens.

Hypersensitivity myocarditis- perivascular infiltrate with abundant eosinophils on

histology.

Patchy necrosis with granulation tissue is indicative of ischemic damage to the donor
heart.

scant inflammatory cells and interstitial fibrosis is most characteristic of chronic

rejection.

Giardia:- cyst in stool having smooth well defined walls with 2+ nuclei.

CMV- "heterophile negative" Mononucleosis in immunocompetent persons.

Toxoplasma gondii - Mononucleosis like illness in immunocompetent & CNS

involvement

Intrabdominal abscess - Polymicrobial. but M/c B. fragilis, E. coli, Streptococci and

enterococci.

Virion receptor
EBV CD21 CR2
Rabies Nicotinic acetylcholine receptor
CMV Cellular Integrin
HIV CD4 or CXCR4/CCR5
Rhinovirus ICAM1 (CD54)

S.I Organism Toxin Mechanism and effect

.
1. Bacillus Anthrax Edema factor- increase cAMP concentration by
anthracis exotoxin acting as an adenylate cyclase, causing edema
and phagocyte dysfunction.
Anthrax Lethal factor- a Zn dependent protease, inhibits
exotoxin MAPK signaling causing apoptosis and
multisystem physiologic disruption.
2. B. pertussis Pertusis toxin Disinhibits adenylate cyclase trough Gi ADP
ribosylation, increases cAMP level, causing
 edema and phagocyte dysfunction
Adenylate increase cAMP concentration by acting as an
cyclase toxin adenylate cyclase, causing edema and
phagocyte dysfunction
3. C. botulinum Botulinum Blocks presynaptic release of Ach from
toxin neuromuscular junction, resulting in flaccid
paralysis
4. c. difficile Toxin A Recruits and activates neutrophils, leading to
release of cytokines that cause mucosal
inflammation, fluid loss and diarrhea.
Toxin B Induces actine depolymerization, causing
mucosal cell death, bowel wall necrosis and
pseudomembrane formation
5. S. Shiga Toxin Halts protein synthesis by disintegrating 60S
dysenteriae subunit. Causes cell death and diarrhea
6. S. pyogenes Pyrogenic Acts as a superantigen, causing fever, shock.
toxin A/w Scarlet fever and SSSS
Streptolysin O Damages erythrocyte membrane, causing beta
&S hemolysis

ETEC- causes Traveller's diarrhoea.attaches to gut mucosa by fibriae/pili.

- produces enterotoxins, Heat labile toxin(LT) n heat Stable toxin(ST). both these
r plasmid encoded.

LT:- cholera like toxin. heat labile coz large molecule

MOA:- inn gut mucosa activate stimulatory Gs membrane G protein-> activate

adenylate cyclase-> increases intracellular cAMP-> increases secretion from gut
mucosa.

ST:- Small/ stable toxin.

MOA:- increases cGMP by binding to and activating gunylate cyclase located on apical
membrane of hst gut mucosal cells.

Enteroaggregative E. coli (EAEC):- form a stacked brick intestinal adhesion to jejunal,

ileal and colonic mucosa. It Causes persistent diarrhoea to infants in developing
countries.

EHEC - produces shiga like toxin.

all of the enterobacteriacae contain the endotoxin Lipid-A, a component of their

lipopolysccharide outer membranes.
it is released in small amounts in normally dividing Gram-negative bacteria, but it can be
released in large amounts during wie spread bacteriolysis as with the initiation of
antibiotic therapy in a pt. with Gr. -ve sepsis.

Exotoxin released by S. aureus - TSS, SSSS, Gastroenteritis.

Trypanosoma cruzi - parasite, which produces a neurotoxin that destroys the myenteric
plexus and causes intramural, parasympathetic denervation of smooth muscle.

E. histolytica - Amoebic liver abscess

Candid albicans- from infection resulting from perforation of the proximal bowel, eg.
perforated peptic ulcer.

The superior infectivity of shigella is attributed to its unique binding site on intestinal
mucosal M cells, which r usually unoccupied by the normal flora of the gut.

Organisms which can cause diarhoes with only a small inoculum :-

- Shigella ( as small as 200)

- C. jejuni ( as small as 500)

- E. histolytica ( 1)

- giardia lamblia

Campylobactor- transmitted by pet animals(cattle, dog, sheep, chicken) and feco-oral

route.

O157:H7 shiga-like toxin producing E. coli:- doesnt ferment sorbitol on MacCOnkey

agar and does'nt produce glucuronidase.

- shiga-like toxin is phage encoded and its production is enhanced by iron

deficiency.

- it incativates 60S ribosomal subunit.

Bacterias that produce toxins capable of activating adenylate cyclase:- B. pertussis, B.

anthracis, ETEC(Labile toxin; LT), Campylobacter Jejuni, Bacillus cereus, & V. cholerae.

Bacterias that produce toxins capable of activating guanylate cyclase are:- ETEC (ST),
Yersinia enterocolitica

Bacterias that produce toxins capable of inactivating EF2, by catalyzing ADP-

Ribosylation of EF-2:- Corynebacterium dephtheria & Pseudomonas aeruginosa.
Clostridium difficile produces a toxin (toxin B/ cytotoxin), capable of disrupting
cytoskeleton.

cell mediated immunity:- for organisms which are intracellular eg.legionella, Neisseria
gonorrhoea, Listeria monocytogenes, viruses, and protozoans like Leishmania.

Clostridium defficile:- Enterotoxin A- causes watery diarrhoea.

enterotoxin B - causes colonic epithelial cell necrosis& fibrin deposition.

Dx- detection of toxin genes in the stool via polymerase chain reaction.

S. typhi- phagocytosed by M cells in peyer's patches-> taken up by macrophages,

where these grow.

DNAse:- produced by Group A strep. it degrades DNA in pus to facilitate spread of

organism

Septic shock - by Endotoxins (eg.- lipid A, a part of Lipopolysaccharide cell wall).

Lipid-A-> activates Macropphages and granulocytes -> synthesis of endogenous

pyrogens eg. IL-1, prostaglandins and inflammatory mediators eg. TNF-alpha, and
interferon-> these induce a febrile response by action of IL-1 on hypothalamus.

O-antigen:- cellwal outer membrane polysccharide antigen used to classify gram -Ve
bacteria.

E. coli starins that cause neonatal meningitis synthesize K-1 capsular antigens.

Reactive arthritis- triad of Arthritis, uveitis/conjunctivitis and Chlamedial urethritis.

Pseudomonas- oxidase +Ve, non-lactose fermenting, Gr. -Ve bacteria.

Klebsiella - Lactose fermenting Gr. -Ve rod

Staph saprophyticus - Catalase +ve, Coagulase -Ve, Gr. +ve coccus

E. coli- Lactose fermenting Gr. -Ve rod

Acyclovir:- in infected host cells, acyclovir( a nucleoisde analog) is converted to

acyclovir monophosphate principally via virus encoded thymidne kinase. Cellular
enzymes then convert monophosphate into triphosphate. When viral DNA polymerase
incorporates acyclovirtriphosphate into viral dna chain, viral DNA synthesis is
terminated.

in HIV :- gag genes code for- p24, p7 protein.

 - pol gnenes- reverse transcriptase

- env- envelop glycoproteins gp160 ( gp160 cleaaves down to-> gp120,, gp 41)

- nef gene appears to enhance viral replication, by downregulation of CD4 &

MHC class1 expression.

- tat gene codes a protein that transcriptionally activates other viral genes.

Corynebacterium diphtheriae - Gr. +, Catalase +ve, aerobic, club shaped rods, non-
motile and unencapsulated.

- Grow on cystein-tellurite agar as dark black, slighlt iridescent colonies.

- also on Loeffler's media.

- it has cytoplasmic, metachromatic granules, which are visualized after staining

with an aniline dye eg. methylene blue.

- It's toxin has 2 subunits- A & B. B is a pentamer n A is in middle of it.

- B ( binding) Subunit, binds specifically to the heparin binding epidermal growth

factor receptor found on cardiac and neural cells.

- B subunit, also induces endocytosis of the toxin.

- C. diphtheriae aquires virulence via bacteriophage mediated infection with the

TOX gene, which codes for the diphtheria AB toxin.

Bordet-Gengou medium- for bordetella pertusis.

Lumbar puncture- for cryptococcal meningitis. India ink staining of CSF reveals the
classic encapsulated yeast of cryptococcus neoformans.

for Allergic Bronchopulmonary Aspergillosis (ABPA)-Serologic staining

- increased titers of IgE and antibodies to Aspergillus fumigatus are diagnostic.

- also Skin hypersensitivity testing.

Ophthalmoscopy- for Candida endophthalmitis.

Blood Culture - for Dx of disseminated mycoses(eg. candida)

CMV, HHV6 & toxoplasmosis - Cause monospot -Ve Mononucleosis like syndrome.

JC virus - Progressive Multifocal Leucoencephalopathy (PML)

Coxasakie A - Herpangina & aseptic Meningitis in children

Pseudomonas- Motile, aerobic, gram -Ve rods, non-lactose fermenting, oxidase +Ve.

- produces Pyocynin ( blue-green) pigment.

- emits a grape like fruity odor

- Produces Endotoxin( fever,shock) & exotoxin-A(inactivates EF-2)

Tzank Smear - wright-Geimsa Stain. Multinucleated Giant cell

C. dephtheriae- Diphtheria toxin- Inactivates EF-2 via ribosylation. Thus inhibits host cell
protein sunthesis.

P. aeruginosa - Exotoxin-A - Inactivates EF-2 via ribosylation. Thus inhibits host cell
protein sunthesis.

S. aureus- enterotoxin - Superantigen, that acts locally in the GI tract causing vomitting.

- TSST- SUperantigen that stimulates T-cells leading to widespread cytokine

release and shock.

C. difficile - Cytotoxin-B - Induces actin depolymerisation leading to mucosal death,

necrosis of colonic mucosal sufaces and pseudomembrane formation.

C. botulinum - Botulinum toxin - Blocks the presynaptic release of Ach at the

neuromuscular junction resulting in flaccid paralysis.

B. Pertusis- pertusis toxin - Disinhibits adenylate cyclase via Gi ADP ribosylation,

increasing cAMP production in the host cell; causes increased histamine sensitivity &
phagocyte dysfunction.

Actinomyces israelii - Gr. +Ve, component of normal oral flora.

Actinomycosis - in the setting of recent oral trauma/ tooth extraction. slwly growing
mass, pus extraction through cutaneous sinus tract.

Pasturella multocida- Gr. -Ve rods, normal oral flora of pets. Causes acute soft tissue
infection. Leds to draining cutaneous sinus tracts, lymphadenopathy, osteomylitis and
septic joints.

Rocky Mountain Spotted fever - palmoplantar erythematous macules that migrate

centripetally toward trunk.

Acute bronchitis Bacterial causes- Mycoplasma pneumoniae, Bordetella pertussis.

In children :-

Acute otitis media- Streptococcus pneumoniae

sinusitis - Nontypable Haemophillus influenza

Bacterial conjuctivitis- Moraxella catarhallis

Calcivirus:- Norwalk virus- AGE

Paramixovirus:- Parainfluena ( croup in children), RSV 9( bronchitis in Infants), Measles

and mumps virus.

Arenavirus:- Lymphocytic choriomeningitis Virus(LCV). causes a febrile aseptic

minigoencephalitis / mild influenza like illness in humans exposed to Hamster or mice.

Hep B virus:- Enveloped virus. The Mature virion ( called Dane Particle) consists of a
hexagonal protein core (capsid) covered with a lipid bilayer envelope, studded with
proteins and carbohydrates.

- HBV genome is partially double stranded circular DNA molecule, housed within
the capsid.

- Ds DNA-> template +sRNA-> Progeny Ds DNA

Only Anti HBsAg +ve - Vaccinated

also Anti HbCag +ve-> Recovered from infection

HBV infected Infants- 90% chances of progressing to chronic hepatitis and show only
mildly elevated liver enzymes.

- M/C finding- persistent serum antigens and mildly elevated liver enzymes.

HCV:- HCV has 6 or more genotypes and multiple subgenotypes. this genetic variation
has led to the development of a hypervariable region of the envelop glycoprotein that is
specifically prone to mutation.

- there is no proofreading 3'-5' exonucleas activity built into the virion-encoded

RNA polymerase.

Hep D Virus- HDAg- the internal polypeptide assembly of HDV.

- has very short single stranded circular RNA.

- Needs coating of HBV.

Fever @48 Hours- tertian malaria. By P. Vivax, P. Ovale.

Most enveloped nucleocapsid viruses acquire envelope by budding through the plasma
membrane. However, the HSV & CMV, bud through and acquire the lipid bilayer envelop
from the host cell nuclear membrane.

Chediak-Higashi Syndrome:- Albinism, Immunodeficiency and neurological

Disorder( nystagmus/Peripheral/cranial neuropathy). Immunodeficiency- Phagosome-
lysosome fusion dysfunction. Produces abnormal, giant lysosomal inclusions.

Albinism- Abnormal melanin storage in melanocytes.

Wiskott-Aldrich syndrome- X-linked disorder. - Immunodeficiency (combined B & T

Cell Disorder), eczema and thrombocytopenia.

Pneumocystis infection usually manifest from T-cell deficiency.

CGD - Phagocytic defect, recurrent Cutaneous disease

Complement Deficiency- C5-C9-> Nisseria,

C1,C3,C4 Def.-> lupus like syndrome

Immotile cilia syndrome- Respiratory distress in newborn

SCID- recurrent infectoins with bacteria, virus & fungi; Failure to thrive, and chronic
diarrhoea with in first year of life.

Langhans cells- Monocyte derived cell

- multinucleated giant cell with nuclei in horse-shoe shaped arrangement.

- Role in granulomatous inflammation.

Langerhans cells- Dendritic cell derived APC, so they interact closely with T-cells.

-express MHC class II & B7 Surface molecue.

-derived from myeloid cell line. Myeloid stem cells-> granulocyte-monocyte

progenitor cell-> dendritic cells.

Birbeck's Granules - Characteristic intracytoplasmic "racquet shaped" cells.

Kuppfer's cells- macrophage, Within the hepatic sinusoids.

Merkel's cells - neuro-endocrine cells in basal layer of epidermis.

Melanocytes- Neural crest cell.

 - have dendritic processes, that intercalate with between the remaining cells of
the epidermis and facilitate the delivery of pigment-laden melanosomes to
keratinocytes.

- Darkening of skin is due to increase in melanin, not melanocytes.

Monocyte derived cells- Kupffer cells in Liver, Osteoclast in the bone, Microglial cells in
the CNS, Mesangial cells in kidney, Alveolar macrophages in Lung.

Contact dermatitis- all forms are dervied from Type IV (delayed type) hypersensitivity
reaction.

Graft versus host disease(GVHD)- after allogenic transplant of Bone marrow, Liver or
transfusion of non-irradiated blood i.e. organs rich in lymphocytes.

Types-

1.) hyperAcute:- within minutes. Tissue reciepient has antibodies against donor
ABO antigens.

- spasm and occlussion of graft vessels-. ischemia and necrosis.

2.) Acute:- within a week.

- d/t graft T-cells (CD4+ n CD8+), as host is immunosuppressed.

- manifest as vasculitis.

- damages Liver( raised ALT & AST etc.), SKIN(desquamation) & GI

( Diarrhoea, abdominal cramping, intestinal bleeding & ileus).

3.) Chronic:- months later.

- host T-cells sensitized against Graft MHC.

- manifest as Fibrosis.

First tetanus vaccine is given at 2 months of age. Earliest it can be given by 4-6 weeks
of age, because before that the immune systeme is immature & unable to mount any
proper response.

Latent EBV infection is strongly associated with AIDS-related primary CNS Lymphoma.

Neurotropic Ds DNA viruses - Herpesviruses & JC virus

JC Virus- cause chronic CNS demylination through infection of oligodendrocytes

(progressive Multifocal Leucoencephalopathy, PML).
Tabes Dorsalis- degeneration of dorsal column and nerve roots in pts with tertiary
syphilis.

Polio- ssRNA Enterovirus, damages the anterior horn of lower motor neuron cell bodies-
> hyporeflexic Paralysis.

-presents with Aseptic meningits i.e. fever, headache, photophobia and painful
extraocular movements.

Anthrax- Chains of large gram +ve rods.

Rabies encephalitis- restlessness, agitation, insomnia and dysphagia progressing to

coma, 30-50 days following an exposure to cave bats.

Cryptococcal Sporidium:- Yeast form only.

- THICK POLYSACCHARIDE CAPSULE.

- RESPIRATORY TRANSMISSION

infection-> Primary -lung.M/c - Meningoencephalitis

Dx:- CSF- lumbar puncture shows low glucose & increased protein.

- Latex agglutination of CSF

- methenamine (GMS), mucicarmine stains of tissue

- India ink stain of CSF

- cultured on Sabouraud agar.

T/t-

1. Initial T/t-> amphotericin B & flucytosine

2. Maintainance therapy - Fluconazole

Listeria monocytogenes:- facultative intracellular, gram +Ve rod, that produces a very
narrow zone of beta-hemolysis on blood agar.

- gram +Ve rod with V or L formations resemblind corynebacterium

- tumbling motility at 22 Degree c.

- multiply at 4 c.
 - escapes from phagosome through the action of listeriolysin O, a pore forming
toxin that is selectively activated within acidified phagosomes.

- Cell-mediated immunity is essential for the elemination of the bacterium from

the body.

- neonates upto 3 months of age are especially vulnerable as their cell-mediated

immunity is not yet fully developed.

transmitted through- 1.)- Food in immunocompromised adults

2.)- vaginal/ transplacentally in Neonates

Staph. epidermidis- mechanism of toxicity biofilm production

Foreign body (IV cannula/catheter)-> coated with layer of host proteins i.e. fibrin and
fibronectin-> binding sites for S. epidermidis-> bacteria multiply & synthesize
extracellular polysccharide matrix that encases the bacteria.

Encapsulated bacteria- spleen helps to opsonize thes

- eg. Strep pneumoniae, H. influenzaee type B, N. meningitis.

Bacterial meningistis- fever,nuchal rigidity, headache, Altered mental status and seizure.

Staph sp.- clusters of gr. +Ve cocci

Staph. aureus- Proteiin A binds with the Fc portion of IgG antibodies ar the complement
binding site, leading to opsonization & phagocytosis.

Waterhouse-Friderichsen SYndrome- Complication of meningo cocciemia ( N.

meningitidis).

- adrenal gland destruction, DIC, and shock.

NECROTIZING FASCIITIS - strep. pyogenes, Staph. aureus, Clostridium perfringens,

Polymicrobial

Strep. pyogenes- Pyrrolidonyl arylamidase +Ve.

C. Perfringens- on blood agar, it produces double zone of beta-hemolysis.

CAMP Test- For S. Agalactiae.

- colonies produce a narrow zone of beta-hemolysis that emhances when plated

perpendicular to S. aureus.
B. anthracis- aerobic organism. forms nonhemolyzing adherent colonies. On
microscopy it forms long chains that r described as being "serpentine" or "Medusa
head".

- antiphagocyric capsule, containing D-glutamate instead of polysaccharide.

Salmonella contains Vi antigen capsule, which protects it from opsonization and

phagocytosis.

Salmonella is M/c cause of osteomylitis in sickle cell anemia, followed by E. coli(k

antigen Capsule) then S. aureus.

N. meningitidis- virulent factor is Lipooligosaccharide(LOS), which is analogus to

Lipopolysaccharide(LPS) of enteric Gr. -Ve rods.

- LOS differs from LPS in that it lacks the repeatting "O" antigen of LPS.

- LOS is responsible for Sepsis, meningitis, Meningoencephalitis and

waterhouse-Friedrichsen syndrome.

Sporothirx- dimorphic fungus.In natural environment, in mold form

- Biopsy oof lesion would reveal a granuloma consisting of histiocytes,

multinucleated giant cells and neutrophils, surrounded by plasma cells.

Tetanus toxin- toxin first binds to receptors on the presynaptic membranes of the motor
neuron. from there, toxin moves retrograde axonal transport system to cell bodies to
CNS. here it inhibits the release of inhibitory Neurotransmitters, glycine and GABA.

MacConkey agar- selective and diffrential medium,for Gr. -Ve organism

Antiphagocytic capsule- N. meningitisdis, Strep. pneumoniae, H. influenzae.

Corynebacterium diphtheriae- intracellular polyphosphate granules, evident with

methylene blue staining.

Lecithinase/ phopholipase C/ alpha toxin- main toxin of C. perfringens.

Congenital toxoplasmosis- Hydronephrosis, intracranial calcifications and chorioretinitis.

Strep pneumoniae- M/c cause of adult bacterial meningitis.

Staph sp.- meningitis in neurosurgical pt.

Nisseria sp.- produces IgA protease enzyme to facilitate mucosal penetration.

impairment of opsonization and phagocytosis- by capsule formation. Eg. N.
meningitidis, S. pneumoniae, H. influnzae & cryptococcus neoformans.

Chlamydia and rickettsia- obligate intracellulR ORGANISMS, which are uniquely able to
survive within the host cell cytoplasm.

promotion of intracellular survival is accomplished by inhibition of phagosome-lysosome

fusion or resistance to lysosomal enzymes.

eosinophil damage helminth larvae via an Antibody dependent cellular cytotoxicity

(ADCC).

Antiinflammatory cytokins - TGF-beta, IL-10.

PUS formation- IL-8 is chemokine produced by macrophages that induces chemotaxis

and phagocytosis in neutrophils. other significant chemotactic agents include n-
formylated peptides, LTB-4, 5-HETE(leukotriene precursor) and complement
component C5a.

C3 deficiency- recurrent infection of encapsulated organism

C5-9,the component of membrane attack complex, leads to recurrent Nisseria sp.

infection.

MHC II at APC binds to TCR at T-cells to initiate T-cell Activation.

initiation of T-cell activation also requires co-stimulatory binding of T-cell bound CD-28
to APC bound B7.

*Cryptococcus neoformans- infects only immunocompromised (depressed cellular

immunnity)

- in soil n pigeon droppings.

- transmitted by respiratory route n not by person to person.

In immunocompetent- Asymptomatic Lung infection

Dx- Cryptococcal yeast appears "red" on mucicarmine statining of Bronchopulmonary

washing shows .

In Immunocompromised- Meningitis.
Dx- CSF staining with India Ink

- serologic testing( latex agglutination) for the detection of Capsular antigen in

CSF.

* H. influenzae- 90% are Non-typable i.e. they dont form antiphagocytic capsule.

- vaccination with H. influenzae type b does not provide immunity against these.

- None of these strains produce Exotoxin.

* Mycobacterium kansasii- atypical mycobacteriumthat can cause disease similar to T.B.

- acid fast rod

- water contaminant like Legionella pneumophila

*Coccidioides immitis- fungal organism responsible for "San Jaquin fever".

*Hib epiglottitis has been shown to occur in immunized children as well.

*Mycoplasma Pneumoniae- Needs cholesterol in culture medium to grow, as their cell

membrane is composed of cholesterol-rich single phospholipid Bilayer.

*Fungi also use sterol in their cell wall as sterol ergosterol.

* Q fever- D/t inhalation of Coxiella burnetii spores from animal hides.

- Obligate intracellular parasite.

* Perinatal Group B prevention guidelines - Vaginal and rectal culture for Strep. agalciae
at 35-37 weeks gestation. if culture is +ve or history of previous infected infant,
Intrapartum Penicillin is recommended.

* COrd Factor- the growth of thick rope like cords of Mycobacterium, suggest the
presence of COrd factor. It's a Mycoside, meaning it's composed of two mycolic acid
molecules bound to disaccharide trehalose. +nce of cord factor correlates with
virulence as cord factor is responsible for inactivating neutrophils, damaging
mitochondria and inducing release of TNF.

Acid-fastness - a property inherent to all mycolic acid containing organisms (Viz.

Mycobacterium, Nisseria)

* Sulphatides- inhiubit the fusion of phagososmes with lysosomes, thus are essential for
intracellular growth of mycobacterium.

- Virulence Factor.
*Functional cell mediated immunity is required to eliminate Intracellular organisms eg.
Salmonella,Legionella, Neisseria gonorrhoea, CHlamydia(obligate) and
Rickettsia(obligate).

*Enzyme defficiency causing anemia:- G66PD Defficiency, Pyruvate Kinase Defficiency.

* Mycoplasma pneumoniae- hemolysis d/t cold agglutinins against mycoplasms show

cross reactivity with erythrocytes.

* M. pneumoniae can also cause Stevens-Johnson syndrome, joint pain.

* M. pneumoniae predominantly causes Tracheobonchitis in children, with pneumonia

(walking pneumonia) being less common.

* CHloremphenicol- inhibit 50S subunit.

ADR- Myelosuppression, causing Anemia, Aplastic Anemia.

* 50S subunit inhibition- By Macrolide, Linezolid, Chloramphenicol.

* 30 S subnit inhibitor - Tetracyclins And Aminoglycosides.

* Histoplasma capsulatum- in the immunocompetent persons.

oval bodies in the macrophages.

- granulomata formation.

-as the FUngus targets listeocytes and RES, it may cause Hepatosplenomegaly
and lymphadenopathy.

* Cryptococcus- thickk capsule

- causes meningitis and lung infection, IN IMMUNOCOMPROMISED.

* Candida - Pseudohyphae and blastoconidia.

* Blastoconidia- spores that grow as buds on the fungal hyphae.

* Aspergillus - septate hyphae with dicotomous (V shaped) branching.

* Epiglotitis - acute fever, inspiratory stridor, drooling, odynophagia and +ve thumb sign
on X-Ray.

* Pyelonephritis - E. coli ( in both, young and adults)

* Mycolic acid in mycobacterial cel wall make it to retain initial red color of carbolfuchsin,
even after washing with alcohol and hydrochloric acid.
* Mycolic acid- waxy long chain faty acid that is covalently bound to the sugar in cell
wall.

* N-Acetylmuramic acid and N-acetylglucosamine are the saccharides that combine with
an amino acid chain to form peptidoglycan layer in both the Gr. +Ve and the Gr. -Ve cell
wall.

* Teichoic acid- linked to peptidoglycan cell wall of gram-positive bactgeria. It's antigenic
determinant for organism identification in the laboratory and an antigenic target for the
human immune system.

* LPS- component of outer cell envelope of Gr. -Ve bacteria.

* ABPA - wheezing, fever and migratory pulmonary infiltrates

* The pthogens most often responsible for secondary bacterial pneumonia post viral
infection:- Strep. pneumoniae, Staph. aureus, H. influenzae.

* Quelung reaction- When viewed under microscope, the capsule swells when specific
anti-capsular antibodies are added.

-this reaction can be used to identify S. pneumoniae and to serotype the isolate.

* Pneumolysin- Toxin produced by pneumococcus, which destroyes the cilited epithelial

cells.

- it also helps to survive phagocytosis by suppressing the phagocytes oxidatove

burst.

* DiGeorge Syndrome- 3rd and 4th pharyngeal pouch maldevelopment.

*Parts of Lymphnode-

1. Paracortex- region of LN populated primarily by T-cells and dendritic cells.

Poorly developed in DiGeorge syndrome due to deficiency of mature T-cells.

2. Medulla consists of medullary cords and sinuses.

(i)- Medullary cords- B-cells, Macrophages, plasma cells.

(ii)- Medullary sinuses- reticular cells and macrophages.

3. Cortical Follicles- in outer cortex. Sites of B-cells localization and proliferation

(i)Primary follicles dense and Dormant
(ii)- Secondary follicles pale germinal centre, containing proliferating B-cells
and follicular dendritic cells.
( In Agammaglobulinemia, germinal centers and primary liphoid follicles do not form
due to an absence of B-cells.)

*T-cells- Mature in Thymus in first trimester. Here there become double Ve , i.e.
lacking both CD4 & CD8, TO double +Ve i.e. both CD +nt by the synthesis of a
productive rearrangement of b chain of the TCR leads stimulation of production of both
CDs.

* Eaton-Lambert Syndrome- Paraneoplastic syndrome, often A/w Small cell lung

cancer.

- antibodies against presynaptic calcium channels prevent the release of Ach

from presynaptic neurons causing Symptoms very similar to those of Myasthenia
Gravis.

*Polymyositis Symmetrical proximal muscle weakness.

-Muscle biopsy reveals inflammation, necrosis and regeneration of muscle fibers.

- Preceding damage to myocytes with subsequent over-expression of MHC Class

1 proteins on the sarcolemma leads to infiltration with CD8+ T-cells and myocyte
damage.

*CD8+ - Against Viral infection, tumor cells, rejection reaction.

*Macrophages against intracellular organisms. Principal cell type responsible for

garnuloma formation.

*Lysozyme- In tears, saliva and in granules of neutrophils.

MOA- hydrolyzes the bonds in peptidoglycan cell walls of bacterias.

*Hypersensitivity reactions:-

Type of reaction Humoral Cellular Example

component component

Type 1 IgE Basophils, Mast Anaphylaxis,

Cells Allergies

Type 2 IgG, IgM Auto- Phagocyte- Autoimmune

Antibodies complement Hemolytic Anemia,
mediated Cell Injury Goodpasture
 Syndrome

Type 3 Deposition of Neutrophils, Serum sickness,

Antigen-Antibody Complement PSGN, Lupus
complexes activation nephritis

Type 4 NONE T-cells, Contact Dermatitis,

macrophages PPD

Selective IgA deficiency- failure of B-cells to switch from IgM to IgA.

- Recurrent Sinopulmonary infection, Otitis Media By encapsulated
bacteria viz. H. influenza, S. pneumonia. GI infection by G. lamblia.
- Gamma globulin preparations should not be used to these Pts as it
may increase the synthesis of anti-IgA antibodies.

*SCID- Defeciency of Adenosine deaminase. ADA is necessary for purine degradation

and without this enzyme, toxic concentrations of purine metabolites accumulate within
lymphocytes causing failure of DNA synthesis and eventual cell death.

- Deficiency of both cell mediated and Humoral immunity.

* Intra-alveolar and interstitial CD4:CD8 ratio High (5:1-20:1) in Sarcoidosis n low in

Hypersensitive Pneumonitis and AIDS patients with lymphocytic interstitial pneumonia.

*B-cell surface markers- CD19, 20, 21.

*CD16- NK cell

*CD15 Neutrophils, Reed-Sternberg cells(thus a cytological markermuseful in in the

diagnosis of Hodgkins Lymphoma).

*Myeloperoxidase deficiency- Nitroblue Tetrazolium test would cause blue staining.

*Cytochorome C Oxidase deficiency- Autosomal recessive Disease, that causes

Mitochondrial dysfunction.

Symptoms-> Weakness, Hypotonia and encephalopathy.

*Pyruvate Kinase deficiency Common cause of hemolytic anemia.

*Wiskot-Aldrich syndrome- Both T and B cells impaired, along with thrombocytopenia.

- Only IgM is decreased.

* Common Variable Immunodeficiency General deficiency of immunoglobulins 2 0 to
failed B cell differentiation.

- cell mediated immunity is not severely impaired.

* Sarcoidosis- non-caseating Granuloma. TH1 cells, secrete IFN-Gamma and IL-2 ,

which activate Macrophages and promote granuloma formation and stimulate Th1 cells
proliferation, respectively.

*TH2 type CD4+ helper T cells predominantly drive humoral immune responses. Their
products include IL-4, which promotes IgE antibody production by B-cells, and IL-5,
which promotes the production and activation of eosinophils and B-cell synthesis of IgA.

*CGD- Pts are not able to produce NADPH Oxidase ant not able to kill Catalase +ve
organisms.

*RER Synthesize secretory, membrane bound and lysosomal proteins

Ribosomes attach to RER via Riboporins, receptors for large subunits.

*Type II Pneumocytes functions 1. Surfactant production;

2. Regeneration of the alveolar lining following injury.

* Dynein Retrograde transport, Kinesin Aterograde transport in neurons.

*Dynein also function in cilliary and flagellar movement.

*When there are insufficient surfactant in the alveoli, the result is patchy atelectasis of
alveoli due to increased surface tension.

*MI-In Final stage of healing, Type 1 collagen is deposited.

*Elastase neutral proteases found in intra-alveolar fluid of lungs is produced by

alveolar macrophages or azurophilic/ primary granules of infiltrating Neutrophils.

- Neutralized by alpha-1 antitrypsin.

- increased in Centriacinar and Panacinar Emphysema.

*Proteasome- Multicomponent proteases that degrade various proteins in the cell

cytoplasm.
*Amphotericin B ADR Nephrotoxicity -> decreased GFR and direct toxic effect on on
the tubular epithelium-> increase in the membrane permeability of the distal tubule->
hykalemia and hypomagnesemia. Also Causes Anemia.

*Hypokalemia T-wave flattening,ST-segment depression, prominent U-waves and

premature atrial and ventricular contractions.

*After entering the target cell, MTX is converted to polyglutamate form. Polyglutamation,
prevents the movement of the MTX out of the cell.

*PABA esters block UVB (290-320 nm), which r main culprit for UV radiation damage.

*Etoposide and Podophyllin - derived from plant alkaloid, podophyllotoxin. targets

Topoisomerase II, which breaks DNA double strands. Etoposide, doesnt let
Topoisomerase II to seal the broken strands.

Etoposide Uses- Testicular cancer and Small cell lung cancer.

Podophyllin Uses- Genital Warts.

*Irinotecan and topotecan Inhibit Topoisomerase I

*Vinca Alkaloids and Taxens - Cause Microtubue Dysfunction in M phase of Mitosis.

ADR- Peripheral Neuropathy (M/C by Vincristin) d/t Microtubule disruption in

Axons.

*Calcineurin- Protein phosphatase that is activated upon stimulation of the appropriate

cell receptor.

-Activated Calcineurin-> dephosphorylation of NFAT( Nuclear Factor of Activated

T-cells)-> (in the Nucleus) Promotes IL-2-> IL-2 stimulates growth and differentiation of
T-cells.

-Calcineurin inhibitors- eg. CYclosporin and tacrolimus. Impoortant in Renal

transplant.

*Thiazide Diuretics Hypocalciuric.

*Cyclophosphamide/Ifosphamide (Nitrogen mustard Based agents)-> Metabolized by

kidney into Acrolein, which is toxic to uroepitelial cells. Causes Hemorrhagic Cystitis.

T/t- Mesna (2-mercaptoetanesulfonate).

*Acyclovir, valacyclovir, famciclovir and ganciclovir are all nucleoside analogues that
require both, herpes virus and cellular kinases for conversion to their active nucleoside
triphosphate form i.e. nucleotide form. So, can not be used for Thymidine kinase
deficient VZV starins.

- Cidofovir (Cytidine monophosphate, a nucleotide) and Foscarnate ( a

pyrophosphate inhibitor that does not require viral kinase activation), require only
cellular kinases for activation. So, these can be used for Thymidine kinase deficient
VZV starins.

* Li causes DI by its antagonizing effect on the activation of Vasopressin on principal

cells within the collecting Duct system.

*5HT3 Receptor antagonists prevent vomiting by 2 mechanisms:- 1. By blocking Vagus-

mediated nausea and vimiting 2. Blocking Serotonin in the CTZ (area Postrema) and
Solitary Nucleus.

*Filgrastim- Granulocyte-colony stimulating factor (G-CSF)analogue. Used to minimize

myelosuppression , post-chemotherapy.

*Psoriasis T/t- Topical Vit. D analogues (calcipotriene, Calcitriol and tacalcitol) bind to
the Vit. D receptor and inhibit keratinocyte proliferation and stimulate keratinocyte
differentiation.

*Loop Diuretics Ototoxicity occurs with higher dosages, rapid I/V administration or
when used in combination with other ototoxic agents.

*Folinic acid (leucovorin can reverse the toxicity of methotrexate in non-cancerous cells
in GI mucosa and bone marrow if administered at the appropriate time.