Pbd - Week 7

Front 1

What 3 changes in lifestyle are thought to be associated with the current rise in allergic diseases?

Back 1

1. decrease intake of fruits & veg has lowered anti-oxidant levels
2. Some fatty acids are able to shift the I System towards allergic susceptibility
3. Preservatives may effect gut flora leading to allergic sensitization rather than tolerance

Front 2

Explain the hygiene hypothesis (include TH1 and TH2 in your answer).

Back 2

Over past 30yrs there has been a fall in the # of childhood infections and this has caused the immune system to over-react to benign substances. The TH2 pathways is dominant at birth (predisposes to allergies) but exposure to several Ag's will switch the ISystem to the TH1 mode which favors fighting pathogens and suppresses allergies.

Front 3

What medications are associated with allergic diseases and why?

Back 3

Proton pump inhibitors are b/c in lowering the gastric pH they reduce it's ability to hydrolyse food proteins and thus food allergens are not degraded before being absorbed into the blood stream

Front 4

What is the mechanism behind immunologic non-IgE mediated allergic reactions?

Back 4

Substances act directly on the mast cells (without activating the IgE) and induce mast cell activation and mediator release. Does NOT require specific IgE and therefore does NOT need prior exposure or sensitization.

Front 5

What is the mechanism behind non-immunologic reactions?

Back 5

Non-immunologic reactions are complement mediated (C3a & C5a).
E.g. reaction to blood products & dialysis membranes (no need for prior exposure or sensitization)

** in reality reactions occur along a spectrum from immune to non-immune and regardless all pathways converge to deliver similar presentations**

Front 6

If B cells are activated via CD___ and ____ (by T helper cells) they will produce IgE

Back 6

If B cells are activated via CD40 and IL4 (by T helper cells) they will produce IgE

Front 7

Explain the mechanism of IgE-mediated reactions:
- first exposure
- second exposure

Back 7

IgE-mediated reactions require a previous exposure to initiate IgE isotype switch.
First exposure: Allergen specific IgE gets produced by the plasma cells and release into circulation. IgE bind to high affinitiy receoptors on Mast cells & Basophils

Second exposure: allergen binding causes mast cell activation & release of mediators

Front 8

What is the effect of binding a Mast cell (FceR1) on the IgE?

Back 8

Binding the mast cell high-affinity receptor protects IgE from destruction by serum proteases and thus prolongs it's half life - sensitization can last for many months. (free IgE in the serum has a half life of a few days)

Front 9

Which is longer living and has a high histamine content... connective tissue mast cells or mucosal mast cells?

Back 9

CT mast cells live longer (>40days) and have a high histamine content

Front 10

What happens when a person is exposed to an Ag to which they are already sensitized (ie Ag:Ab binding & effects)

Back 10

On 2nd exposure the Ag enters the body and x-links IgE's bound to mast cells. This activated the mast cell triggering degranulation (causing the release of severe pre-formed and newly formed mediators)

Front 11

The granule of a mast cell is filled with a variety of different mediators all of which affect specific receptors on specific cells.
Histamine and lipid mediators are release immediately/over minutes. What are their effects?

Cytokines are release over hours. What are their effects?

Back 11

Histamine/lipid mediators
-vascular smooth muscle relaxtion, broncho constriction & coronary ><

Cytokines causes inflammation & the late phase reaction

Front 12

What is the effect of histamine on the following:
Skin
Eyes
Nose
Lung

Back 12

Skin - wheals, erythema, pruritis
Eyes - conjunctivitis, erythema, pruritis
Nose - d/c, sneezing, pruritis
Lung - brochospasm of smooth msk

Front 13

Which mediator causes life-threatening manifestation of immediate hypersensitivity?
What 5 things does it cause?

Back 13

Platelet activating factor causes:
HoTN
↑ vascular permeability
impaired myocardial contractility
bronchospasm
coagulopathy

Front 14

What is PAF acetyhydolase and what is it's significance?

Back 14

PAF AH is an enzyme that breaks down Platelet Activating Factor (the life-threatening mediator)
Low levels of PAF - AH are associated with an increase risk of dying from anaphylaxis

Front 15

What is meant by the phrase "people will get stereotypic hypersensitivity reactions"

Back 15

Stereotypic means that the reactions all happen in the same order, ie starts with rash, then get nausea, then abdo cramps etc

Front 16

What are the top 3 most common allergens in north america?

Back 16

Venemous bug bites/stings
Drugs
Food proteins

Front 17

For type II hypersensitivity:
- what is the mediator (ie trigger & effector)
- What is an example of when it can occur?

Back 17

Type II hypersensitivity is mediated by the binding of IgG to cell or tissue matrix antigen ---> this creates new epitopes that are perceived as foreign when they are really just altered self.
E.g. Following the administration of drugs (penicillin, quinidine & methyldopa) which bind to self-proteins on RBC's or platelets

Front 18

As an example of a type II hypersensitivity reaction, outline what can happen when penicillin is administered. (4 steps - hint available)

Back 18

1. Penicillin modifies the RBC, creating an epitope --> RBC gets covered in Complement & phago'd by Mphages
2. Mphage presents RBC "Ag" to T cells which get activated & become TH2
3. B cells get activated by the "Ag" & the TH2 cells becoming plasma cells
4. The IgG they make coats the RBC's and activates complement leading to lysis or phagocytosis

Hint 18

1. modification
2. APC
3. Activation
4. 2 final outcomes

Front 19

What is the mediator/effector in a type III hypersensitivity? Is the Ag soluble in this case? What does the mediator/effector do? (ie what chain reaction does it cause?)

What are the 2 types of H type III?

Back 19

Type III hypersensitivity is mediated by soluble Ag's which lead to the formation & deposition of Ag:Ab immune complexes. The complexes activate complement, trigger the release of inflam mediators & induce mast cell degranulation. Causes local inflammation & movement of fluid & protein into tissue.
Effects are local or systemic.

Front 20

For the condition known as "Farmer's Lung" what is:
- the cause/instigator?
- the type of hypersensitivity
- mechanisms of disease (how does the reaction cause problems)

Back 20

- repeated exposure to high [hay dust] or mold spores leading to IgG production
- Type III
- IgG forms immune complexes that get deposited in alveolar walls --> accumulation of fluid, protein & cells that impair gas exchange

Front 21

For Serum sickness, explain the following:
- what happen a few days after the injection of foreign Ag into the system

- why is this a transient form of hypersensitivity?

- given that it resolves & the Ag gets cleared, how does it cause damage?

Back 21

- few days after injection of foreign Ag (e.g. horse serum) the foreign proteins appear in the circulation

- with time the titer of Ab's will rise & [Ag] will fall until all of the Ag is completely complexed with Ab's and eliminated

BUT - during the time of equilibrium (early in the infection) Ag-Ab complexes are soluble & get filtered through membranes, once trapped (deposited) they activate complement which forms chemotactic fragments attracting PMN's & causing acute inflammation.

Front 22

What 4 drugs are commonly associated with serum sickness?
(hint available)

Back 22

1. Antibiotics (penicillin, cefaclor, cipro, tetracycline, etc)
2. Antibodies
3. Enzymes (streptokinase)
4. Anti-venoms (prepared in horses)

Hint 22

A
A
E
AV

Front 23

What is the course & management of serum sickness?

Back 23

Self-limited provided that the drug is stopped
Tx is supportive (anti-histamines & anti-inflammatory) Rarely need steroids

Front 24

What causes chronic serum sickness?

Back 24

Chronic exposure to an Ag such as chronic subacute bacterial IE, or Hep B/C infections

Front 25

What is the difference between a primary and a secondary immune complex mediated vasculitis?

Back 25

In a primary immune complex mediated vasculitis the Ag is unknown, whereas in a secondary on the Ag is presumed to be known

Front 26

What are 5 causes of secondary vasculities?

Back 26

1. Bacterial (Strep, Staph, etc)
2. Viral (Hep B &C, HIV, CMV, EBV etc)
3. Heterologous proteins
4. Drugs
5. Tumor Ag's

Front 27

What are the 5 clinical features associated with Polyarteririts nodosa?
(2 are organ systems involved)

Back 27

(Can have systemic features)
2. Arthritis
3. Neurologic - mononeuritis multiplex (multiple individual nerves being damaged = wrist & foot drop)
4. Kidney: vascular lesions lead to HTN, renal infarcts, microaneurysms
5.GI
6. Cardiac probs

Front 28

What is Cryoglobulinemia?
What are 90% of cases associated with?
It causes a vasculities that involves what size of vessels?

Back 28

Cryoglobulins are single or mixed immunoglobulins that undergo reversible precipitation at low temperatures

90% of cases are associated with Hep C

Vasculitis involves the small vessels (capillaries & venules)

Front 29

What are the 4 clinical features of Cryoglobulinemia?

Back 29

Skin - palpable purpura, Raynaud's
Arthralgia/arthritis
Kidney - GN
Neuro - peripheral neuropathy

Front 30

What happens when Ag is injected and a Type 4 HS reaction develops (as in the TB skin test!)

Back 30

1. Injected Ag is precessed by local APC's
2. A TH1 effector cell recognizes the Ag and releases cytokines which act on the vascular endothelium
3. Recruitment of inflam cells = local lesion

Front 31

What triggers "contact sensitivity" reactions? What type of HS reaction is this?
The damage that occurs is mediated by which cells?

Back 31

Type 4 HS reaction, triggered by self proteins that have been modified by small organic molecules or metal ions

Damage mediated by TH1 cells and the macrophages that they activate or by the direct action of antigen-specific cytotoxic CD8+ T cells.

Front 32

What type of HS reaction is poison Ivy? Do you need to be sensitized?

Back 32

Type IV Hypersensitivity

Requires sensitization

** Small highly reactive chemical that penetrates outer layers of skin and binds to proteins on the surface of skin (Ag can persist for days therefore can get a rash after 1st exposure)

Front 33

How long does sensitivity for type IV HS reactions last? What is the possible Tx for such a reaction?

Back 33

Sensitivity is lifelon once acquired.
Tx = corticosteroids that inhibit the inflammatory response by inhibiting the production of cyto & chemokines

Front 34

Celiac disease is an example of a chronic form of what type of hypersensitivity?
What is the immunologic mechanism of this disease?
How does the cell (activated in the above mechanism) kill mucosal epithelial?

Back 34

Celiac disease = chronic type IV hypersensitivity.
An intestinal enzyme tTG modifies the gluten peptide so that it can bind MHC II and when it does it activates gluten-specific CD4 T cells.
The activated T cell kills mucosal epithelium by binding Fas

Front 35

What are the 3 histological Xtics of celiac disease?

What is the test for Celiac?

Back 35

1. Loss of villi = malabsorption
2. Inflammation (T cells, Mphages, plasma cells)
3. Crypt hyperplasia

Test = the presence of anti-tTG Ab (IgA)

Front 36

What type of bacteria would be picked up on a "Ziehl-Nielsen" stain? What are they called?

What is a more sensitive test to detect them?

Back 36

Mycobacteriae (e.g. TB), aka acid fast bacili.

Fluorochrome dyes are more sensitive (bacteria more easily detected with a fluorescent microscope)

Front 37

Why don't mycobacteria stain with a gram stain?
O2? Spores? Motile?
Speed of growth?

Back 37

B/c the mycolic acid in their cell walls prevents the G-stain.
Aerobic, non-motile & non-spore forming.
They are very slow growing (M.leprae is not culturable in vitro!)

Front 38

Of M.Tuberculoses/M.Leprae and Non-tuberculous Mycobacterium, which is found only in humans & warm blooded animals and which is found in the environment (usually in watery environments)

Back 38

M-Tb and M. Leprae are found only in humans and warm blooded animals.

Non-tuberculous Mycobact are found freely in the env. Esp. watery habitats

Front 39

Epidemiology of TB:
- generally in older or younger pt's?
- relation to ppl with HIV? *hint*
- in canada what population group accounts for 66% of all reported TB?

Back 39

It is now seen more commonly in older pt's than in children.
Ppl with HIV have a 400x greater incidence and 1/3 ppl with HIV die of TB.
In canada, foreign born ppl account for 66% of all reported TB

Hint 39

For HIV - what is the incidence & # of HIV + ppl that die from TB?

Front 40

What is condition is required for the transmission of TB?
For how long is the air infections after TB person has left?
What mode poses no risk for TB transmission?

Back 40

Repeated prolonged exposures
Air remains infection 1-2hrs after the infected person has left the room.
Large droplets & contaminated surfaces pose no risk (b/c have to inhale the bug!)

Front 41

What are the 3 most important determinants of TB transmission?

Back 41

1. Closeness of contact
2. infectiousness of the source
3. ventilation in the contact area

Front 42

Describe the pathogenesis of TB:
inhalation of the droplet --> 1o focus (where?) ---> Immune response & result (ie what is a Ghon complex?) --> 2o focus (how & where?) --> final result (2 things occur/form)

Back 42

inhalation of the droplet --> 1o focus forms in the MID lung zones ---> Mphages engulf the TB (which keep replicating) and get carried to L-nodes where they make Ghon complexes --> Tb then spreads throughout the entire body via blood creating 2o foci in the lungs, nodes vertebra & meninges
--> Tubercle formation & caseous necrosis

** initially growth of M-TB is uninhibited -- takes weeks for Lcytes & monocytes to arrive

Front 43

What are the 3 possible outcomes of a primary TB infection?

Back 43

1. NO disease (91% of pts) - Mtb lives but doesn't replicate, causing +ve skin test. Lesions heal by fibrosis --> calcification

2. Clinical disease (6%) occurs when immune response fails to contain the disease (young, old AIDS)

3. Disseminated disease (3%) = death

Front 44

A defect in what is related to reactivation of TB?

Back 44

A defect in cellular immunity = reactivation of TB (3-4% of pt's get active TB in first year, 5-15% do so after)

Front 45

Is a person with latent TB infectious? What will their skin test be? How will their CXR & sputum samples look?

Back 45

Latent TB = NOT infectious

They will however have a +ve skin test but a normal CXR & sputum

(ppl with active TB also have +ve skin test but they are infectious and will have +ve sputum & an abnormal CXR)

Front 46

What type of immune response plays a major role incontaining TB?

Back 46

Cell-mediated response controls TB. Ab production has no role b/c TB is intracellular

Front 47

What type of T cell (CD & TH) is responsible for containing TB?
What does TNF a do?

What does IL - 10 do?

Back 47

CD4 - TH1 will help contain TB
TNF a activates monocytes to effectively inhibit the intracellular replication of TB.

IL-10 production may suppress the immune response leading to disease progression

Front 48

What defines a positive Mantoux test?

Under what 2 circumstances could you get a false --ve

Back 48

>10mm of induration (raised)

Can be falsey --ve b/c
- pt is one of the 15% who randomly test --ve even though they have active disease
- OR, the person could be immunocompromised

Front 49

What would you see on Xray of a person with acute primary TB? What about someone with reactivation?

Back 49

Enlarged hilar lymph nodes & pulmonary infiltrates in the mid-lung zones
Reactivation: infiltrate in apical posterior area of upper lobes w/cavities, nodules & calcifications (productive cough, malaise, night sweats, wt loss)

Front 50

The BCG (TB) vaccine is what type of vaccine? What can it do and not do?

When is it given?

Back 50

BCG = live attenuated virus
Can NOT prevent the disease but can prevent progression to a clinical disease & dissemination
Given only in high prevalence situations

Front 51

While the exact transmission of M. Leprae is unknown, what is required for infection? What is not infectious

Back 51

Prolonged repeated eposures are needed to transmit M. Leprae. Direct contact with skin lesions are NOT contagious
(thought to airborne b/c found in nasal secretions)

Front 52

M Leprae infects & multiplies in what cell? How does it survive there?

Why does it tend to multiply in superficial tissues?

Back 52

M Leprae infects & multiplies in M-phages & survives b/c surface phenolic g-lipid resists oxidative killing.

Grows best at lower temps therefore multiplies in periphery & superficial tissues

Front 53

I tuberculoid leprosy severe or mild?

What are the symptoms (2)?

What is the immune response?

Back 53

Tuberculoid is the less mild of the two
Causes: red blotche lesions & localized anaesthesia (b/c it thickens nerve sheaths w/its multiplying).
Delayed Hsensitivity reaction to lepromin = vigorous cell-mediated reaction

Front 54

I lepromatous Leprosy severe or mild?

What are the symptoms (2)?

What is the immune response?

Back 54

Lepromatous is the more severe of the two disease,

Large # of lesions involves skin & nerves, loss of sensation leads to traumatic lesions causing 2dary bacterial infections

Little or no delayed Hsensitivity

Front 55

Are fungi eukaryotes or prokaryotes?
What is so special/unique about their cell wall?

Back 55

Eukaryotes with complex organelles.
Their cell was has unique polysaccharides and is not made out of peptidoglycan (uniqueness makes them highly resistant!)
** also have ergosterol instead of cholesterol!

Front 56

Yeasts:
- shape
- reproduces how?
- divides how?
- what type form a pseudohyphae ("long bud")?

Back 56

Yeasts:
- spherical/ovoid
- reproduce via mitosis
- divide by binary fission or budding
- candida species form pseudohyphae
(some have a polysaccharide capsule)

Front 57

What are moulds?

Back 57

Large multicellular aggregates of hyphae (filaments)
** give rise to spore forming structures**

Front 58

What 3 diseases can candidiasis cause?

Do you need to be immunocompromised to get these infections?

Back 58

Oral thrush (usually babies who are temporarily unable to mount immune system / neutropenics)
diaper dermatitis
vaginitis

** all surfaces colonized by yeast
Do NOT need to be immunocompromised

Front 59

What are the 2 main causes of cutaneous fungal infections?

How are these infections spread(3)?
What conditions favor the spread?

Back 59

1. Filamentous fungi (moulds) cause dermatophyte infections (named for body part affected)
2. Yeast (Tinea Vesicolor)

Spread via direct contact from humans, soil or animals
Heat & humidity favor spread

* will NEVER invade the SQ tissue!!*

** must differentiate btwn the 2 b/c the treatment is DIFFERENT! **
Tinea caused by yeast

Front 60

What is the only type of infection that can affect skin, hair & nails?

Back 60

Dermatophyte moulds

Front 61

What is the most common fungal infection of the SQ tissue in Canada?
What is the pgenesis? (starts as, spreads via?)

Back 61

Sporotrychosis - requires a breach of the skin barrier!!
Starts as granuloma & spreads via lymphatics.

Front 62

What do chromoblastomycosis & mycetoma cause?

Back 62

granulomatous tumors in the feet of ppl who live in the tropics (black moulds)

Front 63

Dimorphic mycoses are geographically limited. What is the spectrum of disease they produce (&where)?

Where are they found?

Who do they infect? (ie do you need to be Icompromised?)

Back 63

Produce asymptomatic to severe disease 1o pulmonary infection +- dissemination.
Come from the soil
infect both normal & immunocompromised
E.g. Blastomycosis in northern ontario

Front 64

Where does systemic candidiasis get it's start? How does it spread?

What are the 5 places affected by infection with opportunistic systemic mycoses (yeasts)?

Back 64

GI overgrowth & dissemination via bloodstream

Affects:
- Eye
- Hepato-splenic candidiasis
- skin
- brain
- kidney

Front 65

What 2 diseases does cryptococcosis cause?

Back 65

1. Asymptomatic pneumonia
2. Meningitis

Front 66

What type of infection do Aspergillosis &. Zygomycosis cause?
What is the primary infection? What does this lead to?
How effective is treatment?

Back 66

Opportunistic systemic mycoses
Primary infection = pulmonary with wide dissemination throughout the body.
Tx is very rarely effective in severely I-compromised hosts (high case mortality rates!)