Cell-Mediated Immunity Flashcards
What cells are involved in cell mediated immunity?
CD4+ T cell
CD8+ T cell
What is the difference between inflammation between CD4 effector cells (TH1) vs CD4 cells (TH17)?
TH1- activate macrophage to kill ingested microbe
TH17- induce neutrophils, a lot more destruction, kills microbes
What T cells deal with phagocytes with ingested microbes in vesicles? who deals with microbes in cytoplasm?
vesicles - CD4 T cells
cytoplasm- CD8 T (CTL) cells
Reactions of CD4 T cells in cell mediated immunity process?
- TCR engaged
- costimulatory molecule engaged
- provide cytokines
- express CD40 L
- naive T cells differentiate
- T cells exit, into systemic circulation
- TH1 pair with macrophages, activate
- TH17 migrate to site of infection, call in neutrophils
What CD4+ effector cells stay in secondary lymph tissue?
- T follicular helper cells remain associated with B cells, augment plasma cell function
- some will be set aside as memory cells
What occurs in secondary lymph tissue to T cells?
activation
proliferation
differentiation
-antigen carried from peripheral tissues by dendritic cells are primary stimulus
Upon clearance of infection, what population wanes and what remains?
- effector cells wane
- memory cells remain
- more CD8 memory cells than CD4
What is important in the contraction (homeostasis) phase of clonal expansion?
CD40L and CTLA4 (regulation of immune responses) on cell surface
-safeguards prevent immune response from continuing
Major T cell subpopulations involved in cell mediated immunity?
CD4 (TH1, TH2, TH17)
CD8
What influence the differentiation of adaptive immunity cells (CD4 T cells) and activate them? how?
- innate immune cells (macrophages)
- when macrophages process and present antigen via class 2 MHC
What is the major role of TH1 cells? how?
induce macrophage activation
-macrophages have receptors that bind to bacteria and other pathogens which facilitate phagocytosis, destruction, and intracellular degradation
Activation of macrophage induces what effects?
synthesis of reactive molecules:
- O2 radicals
- Nitric Oxide
- proteases
What signals are required for the macrophage activation from the TH1 cell?
- IFN-gamma
- primary signal
- made by TH1 (also NK cells, possibly macrophages) - CD40L
- secondary signal
- makes the cells responsive to IFN-gamma
Macrophage activation by TH1 cells induce expression of what?
- class 2 MHC
- B7
- CD40
- TNF-R
Classically activated macrophage (M1) lead to what?
ROS, NO, lysosomal enzymes:
- microbial actions
- phagocytosis and killing of bacteria and fungi IL1, IL12, IL23, chemokine:
- inflammation
Alternatively activated macrophage (M2) lead to what?
IL10, TGF-beta
- anti inflammatory effects
- wound repair
- fibrosis
What chemokine lead to production of TH17 cells? what does TH17 produce?
- IL6 from dendritic cells
- TGF-beta from many sources
TH17 produce IL17 mainly (also IL22)
Function of TH17 cells?
- stimulate production of chemokine that recruit neutrophils and other leukocytes
- increase production of antimicrobial peptides (defense’s)
- promote epithelial barrier functions
What is the role of helper T cells in the differentiation of CD8+ T cells? how?
promote CD8+ cell development:
-secrete cytokines that act directly on CD8 cells by activating antigen presenting cells to become more effective at stimulating the differentiation of CD8 T cells
IL-2 function?
promotes proliferation and differentiation of CD4+ and CD8+ cell into CTLs and memory cells
IL-12 and type 1 IFN function?
stimulate the differentiation of naive CD8+ T cells into effector CTLs
IL-15 function?
important in development of memory CD8
IL-21 function?
induction of CD8+ cell memory and prevention of CD8+ cell exhaustion
What is T cell exhaustion?
- over time CD8 T cells stop responding to an antigen because CTLA-4 engagement on surface of CD8 cell by target cells, begin to express costimulatory (B7) molecules that down regulate CD8 responses
- due to chronic infection
What happens with CD8 cells in acute infection as opposed to chronic infection, leading to T cell exhaustion?
acute- CD8 cells differentiate in CTLs that eliminate infected cells, antigen is cleared
chronic- response of CD8 cells is suppressed by the expression and engagement of PD-1 and other inhibitory receptors, antigen persists, T cell exhaust
Steps in CTL mediated lysis in targeted cells?
- target cell shows MHC class 1
- endogenous antigen form intracell infection is displayed on surface
- LFA1 and ICAM1 interact
- granule exocytosis
- detachment of CTL
- target cell death
How is a naive CD8+ T cell primed?
- TCR engages MHC class 1: peptide complex
- class 1 MHC may also present peptides derived from microbes that have been phagocytksed by dendritic cells:
- if they are transported from the phagosomes and into the cytosol
- cross priming or cross presentation
Once activated, CTLs must be able to recognize antigen as what?
non professional antigen presenting cell:
- true for virally infected cells
- tumor cells
How does CTL induce apoptosis?
Cytotoxins contained in lytic granules:
- perforin -protein analogous to C9 (membrane attack complex)
- polymerizes to create transmembrane channels
- allows granzymes to enter - Granzymes
- family of serine proteases
- cleave cell proteins
- activate endonuclease (activates effector caspases)
- induce apoptosis, inside cell - Fas-FasL interaction
- induce apoptosis
- happens on cell surface receptor in absence of granzymes and perforin
T/F CTLs can kill multiple target cells on repetitive fashion.
true
Difference between neutrophils and CTLs?
neutrophils- very destructive, release debris into extra cell environment
CTL- form tight pore with target, pulls it out, cell dies, very clean cell death
What cytokines can CD8+ effector cells produce?
- macrophage activating IFN-gamma
- similar to TH1
- inflammatory reactions from environmental chemicals
- arrive earlier than CD4 cells
What are NK cells? what do they lack? what do they express?
- mononuclear lymphocyte
- lacks CD3
- expresses CD56 (adhesion molecule)
- most are large granular lymphocytes (LGL)- well developed cytosol containing cytotoxic granules
- no rearrangements of TCR or Ig genes
- express IL-2Rb and IL-2Rg- allow response to IL-2
- 10-15% PBL
What do NK function? how?
- provide innate immunity against intracellular infections, viruses especially
- migrate from blood to tissue in response to inflammatory cytokines
- act fast, within 6-12 hours
- effective against tumors if drops MHC class 1
What happens if people lack NK cells?
suffer from persistent viral infections
-rare disorder -herpes
How do NK cells recognize what to attack?
- if virus expresses MHC class 1, NK cells are inhibited
- if virus inhibits the expression of MHC class 1, NK cells are activated, kills by perforin and granzymes
How can NK cells influence T cell differentiation?
If NK cells target a virus infection, they produce cytokines (IFN-gamma) which trigger IL-12 secretion from macrophage which will skew immune response to a T cell response (kill with perforin and granzymes)
