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Immunology > Lec9 Effector Mechanisms > Flashcards

Lec9 Effector Mechanisms Flashcards

1
Q

Functional roles of CD4 and CD8 Cells

A

CD4 helper cells secrete cytokines
- allow other cells of immune system to develop functional response

CD8 CTLs lyse cells
- destroy infected cells, limit spread infection, cause of autoimmune disease, transplant rejection, tumor destruction

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2
Q

TH1 T cell activity

A
  • macrophage activation [by release IFN-gamma and binding CD40L to CD40 on macro surface]
  • help cytotoxic T cells proliferate
  • complement-fixing antibodies
  • against intracellular microbes
  • role in autoimmune disease, tissue damage associated with chronic infection
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3
Q

TH2 T cell activity

A
  • anti-parasitic [holminthic] response
  • allergic response
  • IgE production
  • mast cell, eosinophil activation
  • alternate macrophage activation
  • secretes IL-4, IL5, IL-13, IL-10
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4
Q

TH17 T cell activity

A

inflammatory response

  • release IL-17: cause inflammation, neutrophil response and anti-microbial peptides
  • release IL-22: cause increased barrier function and anti-microbial response
  • against extracellular bacteria, fungi
  • can lead to organ-specific autoimmunity
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5
Q

T reg cell activity

A

suppress immune response

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6
Q

What is IFN-gamma? What does it do?

A
  • cytokine released from TH1 cells
  • secretion from TH1 is induced by IL-12 from macrophages

Function

  • increases expression of MHC and B7 on pAPC so induce activation of more T cells
  • enhances ability of macrophage to kill pathogen
  • helps B cells produce complement binding and opsonizing IgG antibodies [promotes opsonization and thus phagocytosis by macrophages]
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7
Q

What will naive T cell differentiate into in presence of IL-2?

A

TH1 cells

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8
Q

What does a macrophage do once it is activated by T TH1 cell?

A
  • produces ROS, NO, lysosomal enzymes: kill microbes in phagolysosomes
  • secretes cytokines [TNF, IL-1, IL-12] and chemokines: recruit leukocytes [inflammation]
  • increases expression MHC molec and costimulators: amplification T cell response, increase T cell activation
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9
Q

What causes naive T cell to differentiate into TH2?

A

presence of IL-4, source not clear

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10
Q

What is IL-4?

A
  • Cytokine that causes naive T differentiation to TH2, source not clear
  • then secreted by TH2 to activate B cells for antibody/IgE production
  • along wtih IL-13 also increases mucus secretion and peristalsis in GI, and activate macrophages
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11
Q

What is IL-5?

A

Cytokine secreted by TH2, causes eosinophil activation and release of toxic granules

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12
Q

Balance between TH1 and TH2

A

If start to develop TH1 response, it inhibits TH2 response and vice versa

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13
Q

Response to Lieshmania major

A
  • usually by TH1 get recovery

- BALB/c mice get response by TH2 leading to disseminated infection

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14
Q

Response to mycobacterium leprae

A
  • some patients TH1 response, get tuberculoid leprosy

- some patients have defective TH2, get lepromatous leprosy

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15
Q

3 signature transcription factors for differentiation naive T Cell

A

T-bet –> TH1
GATA-3 –> TH2
RORyT –> TH17

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16
Q

Two mechanisms of CTL differentiation and proliferation

A
  1. CD4 T cell produces cytokines that stimulate CTL differentiation [actual differentiation requires presence of CD4, cytokines come from the CD4]
  2. CD4 T cell enhances the ability of APC to stimulate CTL differentiation [actual differentiation part does not require presence of CD4, cytokines come from the pAPC]

If you have an efficient enough antigen presenting cell, can activate without costimulation of CD4

17
Q

Cytotoxic T Lymphocytes

A
  • mature activate CTl recognizes target cell that expresses MHC class I without costimulation
  • CTL delivers kiss of death = granules of perforin and serine esterases
  • CTL detaches and can go on to kill other cells
  • target cell undergoes apoptosis, takes time
18
Q

TAP

A

When virus infects cell, viral protein made and some goes through proteasome and broken down, goes through TAP and binds MHC-I in ER inducing MHC1 to be transported to surface

19
Q

What is CTLA-4?

A

on T reg cells, binds B7 on APC and delivers negative signal to arrest T cell activation

20
Q

What is IL-10?

A
  • an inhibitory cytokine produced by some T-regs
  • inhibits expression co-stimulatory molecules and class II MHC on pAPC
  • also enhances b cell survival and proliferation and antibody production
21
Q

What is TGF B?

A

cytokine that suppresses T cell response

22
Q

?

A

Once you are exposed to antigen, T cell induced wtih somatic mutations

23
Q

Properties of antibodies

A
  • released in lymph nodes, bone marrow
  • function distal to point of release
  • use Fab [fraction antigen binding] portion to bind
  • Fc region dictates function
  • Produced during first exposure, larger amounts with additional exposure
  • isotype switching, affinity maturation, memory
24
Q

4 Functions of antibodies

A
  1. neutralize microbes and toxins
  2. bind microbes/antigens and act as opsonin [facilitate phagocytosis]
  3. antibody-dependent cellular toxicity: NK cells have Fc receptors, bind antibody and kill cells
  4. activate complement pathway: leads to lysis microbes, phagocytosis/opsonization, inflammation
25
Q

What is neutralization by antibodies? Which antibodies do this?

A

Antibody block ability of microbe to bind its receptor

  • – prevents microbe infecting cell
  • – prevents infected cell from binding and infecting adjacent cell
  • – prevents toxin binding cell receptor

All antibodies can do this

26
Q

Antibody as Opsonin – which antibodies do this?

A

Only IgG acts as opsonin

  • IgG binds microbe
  • Complex binds to Fc receptor on phagocyte surface and activates phagocyte
  • Phagocytosis and killing of microbe
27
Q

What is antibody dependent cellular cytoxicity [ADCC]? Which antibodies do this?

A

Only IgE or IgG
IgE: binds helminth, eosinophil binds IgE by high affinity FcR receptor, releases cytotoxic stuff that kills helminth

IgG: binds infected cell, NK cell binds IgG by low affinity FcR receptor, kills cell

28
Q

Difference in IgE vs IgG ADCC?

A

IgE: reacts to helminth, uses high affinity FcR on eosinophil

IgG: reacts to infected cell, uses low affinity FcR on NK cell

29
Q

Which antibodies initiate complement pathway?

A

IgG and IgM antibodies via classical pathway

30
Q

3 Major functions of complement pathway

A
  1. opsonization
  2. cytolysis
  3. inflammation
31
Q

Function of IgM

A
  • largest antibody, held together by J chain
  • first antibody produced, on surface of all naive B cells
  • activates complement
32
Q

Function of IgG

A
  • most important and universal
  • activates complement
  • can pass through placenta
  • binds Fc -gamma receptors on phagocytes
  • always monomer
33
Q

Function of IgA

A
  • monomer in blood stream or dimer in mucosal sites
  • connected by J chain [like IgM]
  • blocking antibody = blocks binding
  • doesn’t activate complement or act as opsonin
  • wrapped in secretory piece
  • primarily in secretions
  • protects against infections of mucous membranes
34
Q

Transport of IgA through epithelium

A
  • produced by plasma cells in mucosa of GI and respiratory tracts
  • binds poly-Ig receptor on epithelial cell and gets endocytosed into cell
  • when gets to luminal side of epithelial cell, IgA cleaved but keeps Poly-Ig receptor that becomes wrapped around it [secretory piece]
35
Q

What is the secretory piece in IgA?

A
  • the part that wraps around the IgA
  • made of leftover from Poly-Ig receptor of epithelial cell
  • protects IgA from environment
36
Q

Function of IgD

A
  • monomer
  • only found on B cell surface, not secreted
  • no effector function
37
Q

Function of IgE

A
  • 5 domain structure
  • binds mast cell Fc receptor
  • function in allergy and immunity to parasites/helminths
  • when you are exposed to allergen the second time, serves as receptor on surface of B cell causing them to release vasoactive substances

Immunology (17 decks)

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