Lec 17: Cell Immunity and Tolerance Flashcards Preview

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Flashcards in Lec 17: Cell Immunity and Tolerance Deck (40)
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1
Q

Antibody mediated effector functions

four main types

A

neutralization

complement fixaiton

opsonization and phagocytosis

ADCC = antibody dependent cell mediated cytotoxicity

2
Q

Antibody neutralization

A

Neutralizing antibodies prevent pathogens from initating an infection

=bind pathogen surface and prevent receptor interaction

=bind receptor and prevent pathogen interaction

=block requisite interaction between pathogen and endosomal membrane proteins

=interfere with conformational changed required for viral-host membrane fusion

=inhibit release of progen pathogens

3
Q

igg and antibody neutralizaton

A

prevent toxin/ microbe by coating it with antibodies
prevents receptor interaction

note: not all igg is strong enough to completely coat the microbe

4
Q

Protection from toxins with antibodies

A

toxins of bacterial orgin = tetanus
toxins of venom = snake bites

serum therapy remains the only specific treatment against envenoming, but anti-venoms are still prepared by fragmentation of polyclonal antibodies isolated from hyper-immunized horse serum

5
Q

Agglutinatiion

A

clumping of particles/ pathogens

agglutination and enchained growth of pathogens can facilitate their clearance
-> slgA in teh intestinal tract can lead to pathogen removal

6
Q

immune complex

A

molecule formed by binding multiple antigens to antibodies

7
Q

complement fixation

A

complement fixation elicits formation of the membrane attack complex (MAC)

This forms a pore in the target cell or viron membrane, causing influx of extracellular fluid

lysis of target

antibody binds and triggers C1 = makes pores aftera signal cascade

8
Q

Complement cascade

A

CDC= complement dependent cytotoxicity

c5a is a chemoattractant for inflammatory cells

c5a upregulated activatihng FcRs and down regulated inhibitory FcRs

ADCC antibody dependent cellular cytotoxicity

ADCP antigody dependt cellular phagocytosis

outcomes of Fc receptors = more activation Fc and less inhibitory Fc

9
Q

CDC

A

complement dependent cytotoxicity

10
Q

ADCC

A

antibody dependent cellular cytotoxicity

11
Q

ADCP

A

antigody dependt cellular phagocytosis

12
Q

Fc receptors

A

a single antibody will not activate an FcR
-> requires multiple FcRs to be cross-linked (oligomerizeds) by binding complexed antibodies

FcR signalling is similar to Bcr signaling
-> Syk, Lyn and Btk signalling cascade

13
Q

There are many types of FcRs

A

each ohave specific antibody isotypes that bind them

select cells express different types of FcR

Fc signalling leads to specific cell functions
-> sytokine produciton, enhancement of phagocytic activity etc

14
Q

Opsonization - to make tasty

A

opsonization refers to the ability of antibodies to enhace the engulfment of pathogens by phagocytes

  • > antibodies interact with FcR on the surface of phagocytes
  • > induces antigen internalization and destruciton by phagocyte

mark with antibodies or complement

15
Q

C3B in complement cascade

A

oposonation -> complement -> bind FcR

16
Q

Antibody dependent cell madiated cytotoxicity

A

ADCC

antibody antigen complexed are bound by FcR on the surface of NK cells and granulocytes

  • > allows cells to adopt antigen specificty
  • -> once coated, NK or T cells recognixe coated FcR and mecdiate cytoxicity

Promotes direct cytotoxicity towards target cell
-> Release of cytoxic mediators such as perforin and granzyme B

(think about how this could be used theraputically or agaisnt cancer?)

17
Q

Cytotoxic effector responses

A

cytotoxic responses trigger apoptosis in the target cell

  • > clearance of virus and bacter infected cells
  • > elimination of tumor cells
mediated by:
CD8 (MHC1 endogenous antigen)
NKT cellls (CD1 lipid antigen)
NK cells (no MHC)
18
Q

how to Th cells assist in the activaiton of CTLs?

A

bro isk

19
Q

CTLS for immunologic synapse to mediate target cell killing

A

microtubule ortganizing cener MTOC, golgi apparatus and secretory granulers containing peroforin and serine proteases (granzymes) are polarized toward the immunological synapse and target cell

contraction of teh granules and extrusion of contents into the synaptic cleft

20
Q

CTL activity agaist neruron

A

CTLS can mediate aconal transection of neruons

results in deirupstion of neural signalling

wallerian degeneration of axon

neuronal death

21
Q

Central tolerance

A

deletion of b cells and T cells before they are allowed to mature

occures in the primary lymphoid oragns

second chance = receptor editing (with b cells)
-> autoreactive t cells can become Treg

22
Q

central tolerance is not perfect

A

weakly/ moderatly bind to self become Treg cells

self-reactive lymphocytes find their way to the periphery and secondary lymphoid tissues

23
Q

Read

A

ch 16 central tolerance

p 594-600

24
Q

Peripheral tolerance

A

regulates autoreactive cells in circulation

backup control mechanisms

  • > regulation by Tregs
  • > anergy ( when a t cell sees its antigen but does not recieve CD86 costimulatory signals)
  • > apoptosis
25
Q

nTreg

A

natural regulatory T cells

inhibit the proliferation of CD25- T cells (non-activated)

26
Q

iTreg

A

inducible populations of regulatory T cells secrete IL-10 and or TGF-beta to supress the activity of T cells

27
Q

Treg

A

once in the periphery, they can inhibit the activation of other T-cells

If a Treg anda CTL are activated from the same antigen on a DC, the activated Treg can inhibit the CTL

28
Q

IL-109 and or TGF-beta`

A

downplays CTL activity

29
Q

CTLA-4

A

is a crucial inhibitory molecule expressed on Tregs

multiple modes of activation to inhibit effector T cell activaiton

has a much higer affinity (can outcomplete CD28 for CD80/86 binding)

BLocks actrivation of fellow T cell with the same APC

  • > metabolic starvation (low tryptophan)
  • > secreation of inhibitory cytokines - TGFb and IL10
30
Q

Cd28

A

inhibitory singnal for T cells

31
Q

Rheumatoid arthritis

A

autoimmunity manifests with the production of antigoes specifc for IgG (known as rheumatoid factors) or specific for cyclic citrullinated peptides
-> recall IgG leads for formation of large immune complexes

risk factors = smoking and DR4+ individuals ( RA in HLA)

after onset of clinical disease, inflamed synovium invades adjacent cartilage and promotes articular destruction
-> articular damage likely generates a rich source of neo-antigens ro promote further autoimmune reactivity

32
Q

Immune cell infiltration in rhumatoid arthritis

A

(usually not a ton of immune cells ins the joints)

  • > normally hypocellular synovial membrane becomes hyperplastic
  • > cellular infiltrate includes synovial fibroblasts, macrophages, mast cells, CD4, CD8, NK, NKT, B and plasma cells

invades adjacent cartilage and promotes articular destrucion, which is mediated by the activities of osteoclasts, chondrocytes and synovial fibroblasts

33
Q

Priming defects occur in the thymus

A

autoreative T cells dont become T regs

can subsue self reactive cells in the periphery

34
Q

Cell-mediated immunity in RA

A

Th17 cells may orchestrate synotitis and damage
->funciton of tregs is impared in RA

macrophages secrete pro-inflamatory mediators

synovial fibroblasts secrete matic metalloprotinases (MMP) and cathepsisn via activation by the inflammatory microenvrionment but subsequently take on a semi-autonomous auasi-malignant phenotype

bone damage is caused by differentation and maturation of osteoclasts

35
Q

Proposed mechanism of induction of autoimmunity

A

failure to control self reactive lymphocytes (even with AIRE)

release of sequestered antigens and breaak of self rolerance
-> ag that was never presented in the first place

or endogenous retroviruses

36
Q

compare and contrast the following anti-body mediated responses

A

neutralization

complement fixation

opsonization

ADCC

37
Q

describe the steps CTLs take to destroy their target

A

???

38
Q

what is the difference between central and peripheral tolerance

A

???

39
Q

How is CTLA-4 involved in Treg activity

A

???`

CD28 / CD80/86 thingy

40
Q

Give and example of dysregulated cell-mediated immunity in Rheumatoid arthritis

A

and why is leads to pathogenesis