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Flashcards in REVIEW LECTURE Deck (33):
1

What is an unregulated Th1 response?
Example?

What are several reasons this can occur? (4)

Type IV Hypersensitivity
(TMMI response gone bonkers)
-uncontrolled and frustrated because there is something in the macrophages that it CANT kill

ex: partial removal of live M. Tuberculosis
(forms a granuloma)


1. Overexpressed inf-
genes and/or persistent Ag

2. Persistent antigen/in-
fection or Defective
regulation

3. Unbalanced downstream effects (TNf-a, Il-1, 6, 8)

4. Frustrated macrophages

2

If super antigens are the driver of the unregulated Th1 response, what can be the result?

What are 3 ways super antigens are different from normal antigens?

1. Increased TNF - a
IL-1,6,8

2. SEPTIC SHOCK


1) precent antigen UNPROCESSED in MHC II
2) bide on the "side" not in peptide binding groove (test - picture)
3) Massive immediate PRIMARY POLYCLONAL response in T cells

3

What is an effective strategy for infections of NON - APC type cells and mutations of host cells? (ex: bronchial, mucosa, gut skin)

1. NK cells
- recognize abnormal MHC I

4

NK cells sample cell surfaces and as long as they sense a normal MHC-I they keep their ____ receptors “on"

What are 2 ways the NK cells kill?

Where do NK cells have suppressive roles?

1. inhibitory

1) Direct cytotoxicity
2) FcR used to signal

3) PREGNANT UTERUS

5

CD8 will not be optimally functioning (as in HIV) unless what is present?

What does CD8 NOT require?

CD4 Th1 cell
(IFN - Y IL-21, Il-2)

2. CO-stimulation!
- somatic cells lack a B7 receptor
(gut mucosa or epidermis)

6

Antibodies are needed when toxins are not readily phagocytosed and are extra/intracellular?

What is the signature cytokine of Th2?

EXTRACELLULAR

T cell helper functions, the B cell internalizes the captured antigen, redisplays it in MHC-II and activates Th2 helper cells

2. IL- 4

7

What are the transcription factors and cytokines for the following

1. Th1
2. Th2
3. Treg
4. Th17

1. Th1
-T-bet
- IL-12

2. Th2
- GATA-3
- Il-4

3. Treg
FOXP3
TGF - B

4. Th17
ROR
- IL-23

8

What does the Th2 cell secrete?

What are 2 ways that Th2/B cells can phagocytose a toxin?

IL - 4, 5 , 6 , and 10

(needed for a toxin)
--> phagocytose via C3b or IgG

9

If there is a lot of FcGamma cross-linking and IgG is complexed in abundance, what signal is initiated?

What is the only Fc receptor that can bind antibody isotope without antigen present?

ITIM - inhibitory signal

2. IgE
- high affinity!
- high affinity (does not need allergen present)

on Mast cells, basophils, eosinophils

10

FcR crosslinking occurs on what cells? (7)

1. Neutrophils
2. Mac/DC
3. NK cells
4. Mast cell
5. Basophil
6. Eosonophil
7. B cell

11

If complement is being cleaved in excess due to a Type III hypersensitivity reaction, what can be measured that would indicate this?

Decreased levels of C3 and C4

If the disposal system is overwhelmed,
complexes will bind wherever the endothelium
Is rich in FcR and C3b receptors.
Skin, kidney & joints are prime targets

12

Antibody binding specific antigen (ex: in basement membrane of kidney glomerulus) this is an example of what hypersensitivity?

Type 2!!!

(type 3 is just the excess formation of Immune complexes)

13

If a patient has a defect in B cells, what is absent?

What if B cells are present but no plasma cell, how will the germinal center look?

1. No B cells
2. No Plasma cells
3. No germinal centers

Poorly organized germinal center!

14

What are the following reasons related to:

1.Higher standard of living
2. Lower # of siblings
3. Less daycare
4. MORE ANTIBIOTICS

Result?

HYGIENE HYPOTHESIS

Result: Abnormal Th1/Th2
Balance and higher
Incidence of reaction to allergens

15

What cytokine makes IgE?

What cytokine and cell is needed for allergic responses? (Type I hypersensitivity)

What happens once the second exposure occurs?

What cytokine recruits eosinophils?

IL - 13

1. IL -4 and Th2

3. Armed mast cells and basophils DEGRANULATE
- more Th2 cells
recruited through DC or B cell

IL-4,10,13 produced

- lots of IL-5 EOSINOPHILS!!! attracts EOTAXIN (cytokine)

produced the LATE RESPONSE

Eotaxin recruits eosinophils to area of allergic response

16

What is the basic strategy to Viral infections?

1. Use NK cells as 1st defense

2. TMMI in response (short burst)
- risky because can cause collateral damage

3. CD8 system

4. B cell system to make antibody to viral proteins

5. Promote T and B cell memory systems

17

Why are B cell responses necessary in viral infections?

B cell helps capture virus that is exposed once the virus kills cell and exposes itself
- tries to kill via FcR

18

What are the following examples of:

1. Cytokine inhibitors
2. Cytokine mimics
3. Complement inhibitors
4. Protease inhibitors

Viral Ingenuity
- sites that can be exploited to allow viral survival

19

How can viruses meddle with TLR?(2)

1. upload bacterial lipopolysaccharides that INHIBIT the TLR on DC that will recognize them and thus prevents activation the immune system

2. Force cell to produce "small" RNA that inhibit RNA interference mechanisms (microRNA)

20

What are 2 areas that Tregs arise from?

What 2 cytokines are critical?

What cytokine is necessary for their survival?

What do they express on their surface that can suppress T cell activation by competing with what?

1.Thymus and Periphery

2. TGF - B and AIRE
-T regs can also dampen reactions with IL-10 & TGF-beta


3. IL-2

4. CTLA - 4, competes for B7 with CD28

21

What controls CTLA 4 expression?

As ____ becomes dominant, FoxP3 up-regulates CTLA-4 which then inhibits the ‘second signal” from APC to the T cell

FOX P3

2. TGF-B

22

What are 6 strategies the fetus uses to induce tolerance in the uterus?

1. downregulate MHC 1/II
Upregulate HLA G (public antigen)

2. NK cells migrate and convert to suppressive/regulatory functions

3. GAMMA DELTA cells infiltrate = regulatory function

4. COMPLEMENT control proteins to control any potentially damaging paternal antibody

5. MATERNAL LYMPHOCYTES in gravid uterus - predict it will be a Treg

23

What cells in the fetus have tolerogenic &
regulatory functions & are
critical for fetal survival
.

What is the majority of cells in the mom?

NK!!!


2. Th2!

-she can reverse her strong Th2 bias within 24 hour of birth

Newborn also has strong immunosuppressive milieu

-(T regs and TGF-β) which has to reverse rapidly or will be at risk for infection

24

If RANKL is unregulated or OPG down regulated, what increases?

What ratio is critical in Adipose tissue?

What is the normal milieu in CNS?

1. Increased Osteoclastogenesis

2. M1/M2

3. Anti-inflammatory M2

- if switches to M1 this will produce IL - 1 and 6

25

What is the function of Leptin?

Adiponectin?

What cytokine of WAT is pro-angiogenic?

1. Leptin - decreases appetite and is PRO-INFLAMMATORY
- increases IL-1, and 6, and TNF - Y

2. Adiponectin - anti-finlammatory and suppresses TNF a

3. Pro-angiogenic and pro-inflammatory = VISFATIN

26

Plaques in the heart act as what type M1 or M2?

M1

- bad inflammatory effects accumulating M1 macrophages and monocytes
- plaque will rupture = Myocardial Infarct

27

Autoimmune disease may be secondary to a deficiency or malfunction of Tregs that allows proliferation of ____ promoted inflammation

Where are AIRE genes found? What is their function?

Th17

2. Portico-Medullary junction
- display endocrine and neurologic antigen

ex: hypoparathyroid due to AIRE defect (low calcium)

28

What awesome major reasons for HIGHLY VARIABLE immune responses? (5)

1. Polymorphic MHC
2. Polymorphism of cytokine genes
3. Polymorphism of TLR genes
4. Polymorphism of CTLA4
5. And probably many other factors-especially epigenetic ones

29

What organisms especially create Th17?

What trio of cytokines activates it?

Strongly suppressed by ____ and ___

Nuclear activating factor is?

What is bad about it?

1. Fungi

2. IL-6 , TGF - B, and IL-23

3. IL -4 and IFN - Y

4. ROR

5. Chronic inflammation and AUTOIMMUNITY

30

What cytokine generates LOTS OF NEUTROPHILS and LONG STANDING INFECTION?

What is low in autoimmunity? What dominates?

IL - 17

2. IL-2 and TGF/IL-6 ratio is low

3. Th17 and IL17 dominate

31

What are 2 strategies the tumor uses to thwart the immune system via Tregs?

What chemokine specifically attracts CD8 cells?

1. TGF - B to convert cells to Tregs

2. CCL21
- takes CD8 cells and brings them to the tumor and converts them to Tregs!

32

Where are several areas the immune system can fail in a patient with malignancy?

1. CD8 blocked attack
2. Tregs


NK cell activity is retained (slight)

33

What are 2 ways the tumor inactivates T cells?

What are treatments for this?

What is this called?

1. CTLA-4
2. PD-1/2



a)MONOCLONAL antibodies
anti - CTLA 4 (keep CD28 free to bind to B7)

b)Monoclonal anti-PD1

IMMUNE CHECKPOINT THERAPY