Pbd - Week 6

Front 1

What type of B cell is exposed to a wide variety of self-Ag's in the bone marrow?

Back 1

Immature B cell! Only those that do not recognize self are allowed to mature and leave the bone marrow

Front 2

What 3 mechanisms are in place to ensure that self-reactive B cells don't leave the bone marrow?

Back 2

Self reactive B cells in the bone marrow will:
- die by apoptosis
- be made anergic (unreactive to Ag's)
- or successfully receptor edit and become no longer self-reactive

Front 3

What can and cannot happen to self-reactive B cells outside of the bone marrow?

Back 3

Self-reactive B cells that manage to escape the bone marrow either die by apoptosis or are made anergic ---> they are too late for receptor editing!

Front 4

Given the mechanisms in the bone marrow that prevent the development of self-reactive B cells, how is it that autoimmune diseases can still develop? ie how to self-reactive B cells survive?

Back 4

In situations of stress, trauma or disease, previously inaccessible self-antigens become accessible to non-tolerant B cells. This produces B cells that are self-reactive and can cause autoimmune disease

Front 5

Where does activation of B cells occur? Why here (ie what 3 things are found in this environment?

Back 5

B cell activation occurs in the secondary L-phoid tissues (spleen, lymph nodes & GALT), in these tissues B-cells, helper (CD4) T-cells and Ag's are all held together in close proximity

Front 6

Activation of a B cell requires what 3 things?

What does cognate mean?

Back 6

1. Cross-linking of Ag with Ig
2. Association of B-receptor with the B co-receptor
3. Additional signals provided by the cognate T-cell

Cognate = CD4 T-cell which recognizes the same Ag as a Bcell.

Front 7

How do Tcells recognize Ag?

Back 7

B cells phagocytoze Ag's, digest them and then present them on their surface, in association with MHC II. T-cells are only capable of recognizing Ag peptides in association with MHC II, when they do they activate the B cell that is presenting the Ag peptide (forming a cognate!)

Front 8

Bcells enter lymph nodes via the high endothelial venules. In what part of the node do they arrive? What are they likely to encounter here? What happens if they do encounter this?
Where do they go next?

Back 8

B-cells enter the T-cell zone where naive Tcells have be activated by Ag-presenting dendritic cells.

As Bcells pass through the T-zone they may contact an Ag, trapping them in the T-zone. The now activated Bcells, present the Ag to the activated Tcell of the same specificity.
They can then move to the medullary cords which is the primary focus for Bcell expansion (--> plasma cells)

Front 9

What are the 3 possible fates of a Bcell in the primary focus (of secondary lymphatic tissue)?

Back 9

The plasma cell can:
- undergo apoptosis
- differentiate into plasma cells and secrete IgM
- leave via the efferent lymphatics and migrate to a primary lymphoid follicle, proliferate there and form a GERMINAL CENTRE

Front 10

If a person had no T cells, what impact would this have on their Ab production?

Back 10

If you have no Tcell help, you can only ever make IgM, which aren't very good b/c they can't circulate well or get into tissues well

Front 11

Follicular dendritic cells are not the same as those in the T-zone of 2dary lymphoid tissue. Instead of presenting Ag to T cells, what do follicular dendritic cells do?

Back 11

Follicular dendritic cells provide a long-lasting depository of intact Ag that are available to interact with B-cell receptors.

Front 12

What causes swollen lymph nodes in a person?

Back 12

Germinal centres which appear about 1 week after the start of an infection

Front 13

What are the different roles of the germinal centre vs. the primary focus?

Back 13

The primary focus leads to ealy secretion of specific Ab, and provides early protection, whereas the germinal centre provides a more effective but later response to protect against persistent or repeat infection.

Front 14

Describe the process of somatic hypermutation. In what gene is the mutation occuring and what is the effect?

Back 14

Somatic Hypermutation:
With repeated division of activated Bcells (plasma cells) you get muatation in the V-gene of the Ig receptor. Some of these mutations will ↓ affinity and cause the B to die. Others will ↑ affinity causing the B to get more survival signals (and therefore survive & reproduce more!)

Front 15

What is missing in pt's with Hyper IgM Immunodeficiency and what is the effect of this (2 things)?

As a result the body can only make what? What would be seen in the blood of the pt and what effect would this have on their immunity?

Back 15

Pt lack functional CD40L therefore cannot get productive interactions between B and helper T and cannot isotype switch.

As a result the body can only make IgM in response to thymus dependant Ab's, leaving the pt with high circulation [IgM] but severe humoral immunodeficiency.

Front 16

What does the Fc region on an Ab contain? What does it do (3)?

Back 16

The Fc region of the Ab contains binding sites for other proteins & cells of the immune system. It's function is to:
- deliver the Ab to anatomical sites that are otherwise inaccessible
- link bound Ag to molecules or cells that will effect its destruction
- depending on its isotype it will recruit nonspecific effector cells in different ways

Front 17

The neutralization of toxins is an Ab effector function. How do Ab do this?

Back 17

Ab's bind to toxis and block them from binding to cell surface receptors (by blocking this binding they block them from getting endocytosed)

** same idea for viruses who, once inside the cell, acidify their endosomes and escape into the cytoplasm

Front 18

What is the immunologic basis to an allergy? (what Ig is involved and how does it work?)

Back 18

An allergy is a detrimental mast cell response to a non-threatening antigen (allergen)
Body makes IgE to an allergen like peanuts so that any future encounters with this antigen lead to massive degranulation and a potentially +++ damaging response (anaphylaxis)

Front 19

What Ab composes 75% of the total Ig in serum? Can this Ab activate complement? What is it's advantage?

Back 19

IgG, can activate Complement (and does so effectively).
Advantage: it's small size faciliates diffusion into tissues

Front 20

Ig__ is the "first responder" of the immune system. What can and can't it do? What is the effect of it's shape?

Back 20

IgM is the first responder of the IS. It cannot recruit phagocytes/leukocytes directly, but CAN activate complement.
IgM is a big old pentamer making it hard to diffuse into things, but it is able to bind strongly to Ag's

Front 21

What Ig is involved in allergies? Where can this Ig be found?
What does the Ig do?

Back 21

IgE
only a trace amount in serum; most found bound to mast cells beneath the skin/mucosa.
When IgE binds an Ag (x-linking) it causes degranulation of the mast cell = release of +++ inflammatory mediators that cause sneezing, coughing vomiting (expulsion of the Ag)

Front 22

Where is IgA made and where is it found?
What does it do poorly?
shape?

Back 22

Ig is made in the 2o lymphoid tissue under the mucosa. It is the primary Ig of secretions and protects the surfaces of the resp & GI tract.
Weak opsonizer and weak complement activator
Dimeric

Front 23

What are the 3 ways of activating complement (Ab dependant & Ab independant).

What are the 3 outcomes of Ab activation?

Back 23

To activate complement
Classical Pway - Ab-Ag complexes
Ab independant ways:
- MB-lectin (lectin binds to pathogen surfaces)
- alternate pway (pathogen surfaces)

Complement activation causes: opsonization of pathogen, recruitment of inflam cell and/or the killing of pathogens

Front 24

What happens when a person is deficient of C4 and other early complement components? What is this associated with?

What happens if a person is deficient of late complement components (C5-9)?

Back 24

Early complement deficiencies do not predispose a person to severe infections but C4 deficiency is associated with lupus

Late deficiency causes increase susceptibility to bacterial infections of the genus Neisseria (gonorrhea & meningitis)

Front 25

What happens if a person is deficient in C3 (or other factors that hinder _____)

Back 25

If a person is deficient in C3 (or other factors that hinder opsonization) then they get recurrent pyogenic infections with a high rate of morbidity & mortality.

Front 26

A deficiency in what causes hereditary angioneurotic edema?
What is the function of this substance that is deficient and how does a lack of it create problems?

Back 26

Hereditary angioneurotic edema is caused by a lack of C1 INH (which inactivates C1 complex), thus low levels of C1INH lead to high levels of active C1 and thus fragments of C2 & C4, can get excessive activation of C1 during stress causing the release of vasoactive substances and susequent ++ swelling.

Front 27

Lupus is characterized by the excessive formation of what? Why is this excess a problem?
What tends to be low in the serum when the disease is active?

Back 27

Lupus is characterized by the excessive formation of immune complexes that get deposited in the Glomerular basement membrane of the kidney. Serum C3 & C4 tend to be low when the disease is active,

Front 28

What part of the virus acts as the antigen?

Does an evelope improve or impede the survival of a virus in the environment?

Back 28

The capsomeres that make up the viral capsid serve as antigens.

Viruses with envelopes do NOT survive well in the environment whereas viruses with just a protein coat do.

Front 29

What are the 5 DNA viruses?

Back 29

Hepatitis, HPV, Herpesviridae
Adenovirus
Parvovirus B19

Hint 29

HHH
A
P

Front 30

Can any virus infect any type of cell? Why or why not?

Back 30

Viruses contact host cells through random collisions and to get into the cell, viral surface proteins must interact with host cell receptors. However, viruses are only able to infect a limited spectrum of cell types (host range).
** Not all cells carrying a receptor for a particular virus can be productively infected by that virus!

Front 31

During what phase of the viral life cycle would you be likely to get a false --ve when testing for the presence of the virus? (ie when is it undetectable)

Back 31

During the uncoating phase while cell enzymes strip the viral protein coat, the virion can no longer be detected = "eclipse period" b/c you can't see any DNA or RNA on electron M-scope.

Front 32

Where does transcription & translation occur for RNA vs. DNA viruses?

Back 32

DNA viruses - replicate their DNA in the nucleus and their proteins in the cytoplasm
RNA : +ve sense RNA acts as mRNA in the cytoplasm w/viral enzymes, --ve sense must first be changed to +ve sense

Front 33

Where in the cell do different viruses assemble? (3 virus types)

Back 33

DNA viruses assemble in the nucleus
RNA viruses assemble in the cytoplasm
Enveloped viruses assemble at the plasma membrane before budding out :)

Front 34

What are 4 ways that viruses evade the immune system?

Back 34

1. Antigenic variation
2. Reduce the expression of MHC 1 (e.g. HIV) and this decreases the ability of NK cells to kill virally infected cells
3. Express receptors for immune mediators (IL1 & TNF) which block the mediator's ability to interact with their targets
4. Direct cell-to-cell propagation (removes extracellular phase)

Front 35

How are most viruses like cold & flu transmitted?

Back 35

Direct or indirect contact. The cold & flu are NOT aerosolized.

Front 36

When testing for a viral infection why is timing critical?

Back 36

B/c if you don't test right away the virus will get covered in Ab and won't be able to get into the cells that you are trying to grow it in.

Front 37

The frequency of HSV 1 or 2 recurrent infections depends on what 3 things?

What factors precipitate an infection? (5)

* hint available *

Back 37

Sex
HSV type
titre of Ab

Precipitated by: sunlight
Fever
Local trauma
menstruation
emotional stress

Hint 37

Precipitators:
S
F
LT
M
ES

Front 38

How do you diagnose HSV?
(3 ways, 2 of which are lab based)

Is it possible to distinguish btwn 1 & 2? How about primary vs reactivation?

Back 38

Hx & P/E
Vesicle fluid: culture EM, ImmFlur
Serology: difficult to distinguish 1 from 2; no IgM test so can’t tell primary from reactive

Front 39

What are the 2 Tx options for Herpes simplex 1 & 2?
*hint*

Is there a vaccine?

Back 39

Supportive – education analgesia, keep clean & dry. Antiviral (topical, PO, IV) in primary to ↓ shedding & duration. Minimal effect on recurrent attacks.
NO VACCINE

Hint 39

One Tx option is only available in primary infections↓

Front 40

How is Varicella zooster diagnosed using:
serology
Direct detection
isolation of the virus

Back 40

Mainly a clinical dx but can use:
Serology for immune status.
Direct detection: EM, ImmunoFluro
Isolation from vesicular fluid

Front 41

What is the Tx for varicella zooster? Is there a vaccine?

Back 41

Lifelong immunity but virus in nerve root. Acyclovir if severe. IG to prolong incubation. Vaccine (live attenuated)

Front 42

Which herpes virus is associated w/ Burkitt’s Lphoma & Nasopharyngeal carcinoma?

Back 42

EBV
MONO!!!

Front 43

What are the effects of an intrauterine CMV infection of a fetus?
*hint*

Back 43

Jaundice
HSmegaly
microcephaly
Petechial rash
cerebral calcifications
chorioretinitis
May develop symptoms (hearing loss, behavioural changes, mental retardation) years later!

Hint 43

J
H
P
C
C

Front 44

How is EBV diagnosed?
Can you distinguish acute from chronic?

How is it treated? Is there a vaccine?

Back 44

Monospot (Ab’s)
Serology: IgM IgG (G better)
No isolation!
Supportive – protect spleen from trauma.
NO VACCINE

Front 45

How is CMV transmitted?
*hint*

What are the symptoms of infection? In what two pt populations would you get different symptoms?

Back 45

Sex
perinatal/intrauterine
blood
Tissue/organ Tplant
close contact

Acute infection usually asymp. Mono-like + hepatitis.
Severe if: AIDS, Tplant or neonate. Congenital: symptoms years later in life

Hint 45

5 ways

Front 46

What is the difference between acute & chronic hepatitis?

Back 46

acute <6mo
chronic >6mo

Front 47

What are the infectious causes of hepatitis? (8)
*hint*

Back 47

Hep A B C D E F
CMV
HSV
EBV
Coxsackie
Yellow fever & Ebola
Toxoplasma
Marburg & Q fever

Hint 47

H
C
H
E
C
Y
T
Marburg & Q fever

Front 48

How can Hep A be prevented? (3 ways) Is there a vaccine? What type is it?

Back 48

1. Cook food & wash hands
2. Ig prevents infection
3. Vaccine (killed virus) immunity >5yrs

Front 49

What in addition to geography, puts you at high risk for Hep B? (3)
What puts you at medium risk (3)?

Back 49

High risk:
- residents of mental institutions
- IVDU
- Homosexual men

Medium risk:
-prisoners (men)
- Medical/dental w/exposure to blood
- heterosexual w/multiple partners

Front 50

What bodily fluids have high concentrations of Hep B? (2)
What have moderate (2)
What have low/undetectable? (4)

Back 50

High [HepB]
- Blood/serum
- wound exudates

Medium
- semen & vaginal fluid
- saliva

Low:
- urine & feces
- sweat
- tears
- breast milk

Front 51

What is the % risk of acquiring an infection following a needlestick injury for:
- Hep B
- Hep C
- HIV

Back 51

Hep B = 30%
Hep C = 3%
HIV = 0.3%

Front 52

Explain the role of the following serological markers in the dx of Hep B (ie what do they indicate):
- HBsAg
- HBsAb
- HBcAb
- HBeAg
- HBeAb

Back 52

- HBsAg: if +ve person is infectious

- HBsAb: indicates immunity to Hep B

- HBcAb: past or active infection, present whether person is immune or chronic carrier (IgM indicates acute) **NOT PRESENT AFTER VACCINATION!**

- HBeAg: indicates person is highly infectious

- HBeAb: prognostic for resolution of the infection & that person is less infectious

Front 53

What is Hep B Ig used to tx?
When must it be given to neonates? Others?

After how long will it have no effect?

Back 53

Used for post-exposure prophylaxis

Given w/in 12hrs to exposed neonates, 48-72hrs in other situations

No effect if given > = 7days post-exposure

Front 54

What type of vaccine is the Hep B one?

Back 54

purified Hep B surface Ag