10. Cell mediated acquired immune responses Flashcards
where are intracellular vesicular pathogens?
phagocytosed in membrane-bound compartments
where are intracellular cytoplasmic pathogens?
cytosol
what are intracellular vesicular pathogens recognised by?
helper T cells
what are intracellular cytoplasmic pathogens recognised by?
Cytotoxic T cells
what are extracellular pathogens recognised by?
B cells
3 types of APC
- dendritic
- macrophage
- b cell
where are APcs?
secondary LT
steps of dendritic cell maturation
- pathogen phagocytosis
- dendritic cell matures in epidermis - express MHC, cytokines and TLR
- DC migration to lymph node
- T cell enters lymph node
- T cell receptor recognises Ag on DC (APC)
- T cell migration to site of infection
which cells detect MHC I?
CD8
which cells detect MHC II?
CD4
what is the TCR complex made of?
variable alpha and beta fragment
what is the MHC complex made of?
alpha 1,2 and 3
B2m fragments
what joins the TCR and MHC complexes together?
peptides
what type of pathogens do CD8 cells respond to?
intracellular cytoplasmic
what type of pathogens do CD4 cells respond to?
intracellular vesicular
3 connections between APC and CD8 Tc cell for activation?
- MHC I and CD8+
- B7 and CD28
- IL-12 and IL-2 released
steps in CD8 proliferation and differentiation?
- CD8 autocrine release of IL-2
- IL-2 binds to high affinity IL-2 receptors on T cell
- stimulates proliferation and differentiation
- differentiation into memory and effector cells
what occurs after CD8 proliferation and differentiation?
- Tc leave secondary LT and enter blood
2. Tc recognise MHC I/Ag complex on infected cells
2 ways CD8+ cells kill cels
- Fas
2. Perforin and granzyme
describe apoptosis by CD8 by fas
- fas ligand (Tc) binds to Fas on target cell
2. triggers extrinsic apoptopic pathway
describe perforin/granzyme steps in CD8 apoptosis pathway
- TCR attach to MHC I (target cell)
- Cell adhesion - LFA-1 (tc) binds to ICAM-1 (target cell)
- Tc releases granzyme and perforin into immune synapse
- perforin = induces granzyme uptake by cell and its cytoplasmic release
- granzyme B = cleaves pro-caspase - creates caspase 3
- apoptosis
4 diseases which causes resistance against Tc cell
- herpes simplex virus
- cytomegalovirus
- epstein-Barr virus
- Pox virus
Herpes simplex virus resistance against T cell
inhibition of Ag presentation
Cytomegalovirus resistance against T cell
inhibition of Ag presentation - removes MHC I
Epstein-Barr resistance against T cell
inhibition of Ag presentation - produces IL-10 - inhibits macrophage + DC activation
pox virus resistance against T cell
inhibition of effector cell activation - blocking cytokines
effector functions of Th
secrete cytokines which cause the stimulation of:
Tc cells, neutrophils, B cells, macrophages
3 examples of cytokines
- IL-17
- tumour necrosis factor
- chemokines
what type of chemicals are cytokines
glycoproteins
function of IL-17
secreted by Th cells to stimulate bone marrow to increase neutrophil proliferation by GM-CSF
what is GM-CSF
granulocyte -macrophage colony-stimulating factor
5 different type of Th cell?
Th1, Th2, Th17, TFH, Treg
which cell are all of the Th cells produced from?
Th0
which Th cell defends against intracellular bacteria?
Th1
what does Th2 provide defence against?
Heliminths
which Th cell defends against extracellular bacteria and fungi ?
Th17
what does ThFH defend against
extracellular pathogens
role of Treg
regulatory role of suppressing the immune system
what cytokines do Th1 produce?
IFN-gamma
what 3 cytokines do Th2 produce?
IL-4, IL-5 and IL-13
what 3 cytokines do Th17 produce?
IL-17a, IL-17F and IL-22
describe steps in TH1 production
- intracellular bacteria enters body
- APC interacts with TH0 cell
- B7 and CD28
- MHCII and CD4 - APC releases IL-12
- NK releases IFN-y
- differentiation of TH0 into TH1
3 effector functions of TH1
- macrophage activation
- B cell production of IgG
- Tc maturation
describe effector function of TH1 in terms of macrophage activation in steps
- TH1 releases IFN-y
- macrophage interacts with TH1 cell
- IFN-y and CD40L - macrophage activation
- enhanced phagocytosis
describe effector function of TH1 in terms of B cell activation in steps
- TH1 releases IFN-y
- activates B cell
- B cell produces IgG
- IgG used as adaptor molecule for complement and opsonisation
describe effector function of TH1 in terms of Tc cell activation in steps
- TH1 releases IFN-y
- causes APC to release cytokines which activate Tc maturation
- directly activates Tc maturation
describe steps in TH2 production
- helminth enters body
- interaction between APC and T cell (B7-CD28, MHC II, CD4)
- secretion of IL-4 from mast cells and eosinophil and autocrine Th
- differentiation into Th2
3 effector functions of Th2
- B cell production of IgG4 and IgE
- macrophage activation
- eosinophil activation
describe effector function of TH2 in terms of B cell activation in steps
- TH2 release Il-4
- stimulates B cell to produce IgG4 and IgE
- IgE causes mast cell degranulation against helminths
describe effector function of TH2 in terms of macrophage activation in steps
- Th2 release IL-4 and IL-13
- stimulate macrophage
- enhanced phagocytosis
describe effector function of TH2 in terms of eosinophil activation in steps
- Th2 releases IL-5
2. activates eosinophils
describe steps in TH17 production
- extracellular bacteria/fungi enter body
- interaction between APC and CD4 cell
- APC releases IL-6, IL-23, TGF-beta
- autocrine secretion of IL-21
- differentiation into TH17
2 effector functions of Th17
- leukocyte stimulation of neutrophils
2. antimicrobial peptides from tissue cells
describe effector function of TH17 in terms of neutrophil activation in steps
- TH17 secretes IL-17
- causes leukocytes to stimulate neutrophil production
- also causes BM to release GM-CSF which stimulates neutrophil production
- neutrophils cause inflammation
which cytokine is secreted from Th-17 to increase antimicrobial peptides ?
IL-22
2 effector functions of TFH
- B cell proliferation
2. B cell differentiation into plasma cells
how does TFh cause B cell proliferation
Tfh recognise Ag and MHC II
which cytokines does Tfh release to cause B cell differentiation into plasma cells
IL-21
function of Treg
down regulation of cytokines - losing cell function
what cytokine is released from Treg, what does it do?
TGF-beta
inhibits function of TH2 and TH1
which other 2 cytokines, apart from TGF-beta, are involved in Treg? what do they do?
- IL-4 (Th2)
inhibits function of TH1 and TH17 - IFN-y (TH1)
inhibits function of TH2 and TH17
which cell does HIV deplete?
CD4+ helper T cells
describe HIV pathophysiology in steps
- HIV attacks
- immune response (Anti-HIV Abs, HIV-specific Tc cells)
- clinical latency - virus trapped in LT by follicular DC- low levels of viral production
- increase in viral production
- virus kills LT and CD4 cells
3 consequences of HIV infection
- AIDS
- Infection /cancer
3, death