INNATE CELLULAR IMMUNITY
1. Phagocytosis by _________ & _______
2. often followed by intracellular killing
neutrophils and macrophages
INNATE CELLULAR IMMUNITY
dying neutrophils can release web-like structures called __________-
neutrophil extracellular traps
Innate Cellular Immunity NK Cell
-> belongs to innate lymphoid cells (non-B and non-T)
-> kills foreign looking cells
-> __________
perforin-granzyme
T CELLS
Origin _________
Matures ________
Mobility _________
Effector ____________
Circulation (blood): __________
Distribution in LN:__________
Other features:
1. No complement receptors
2. No surface Ig
3. No ______________
->Bone Marrow
->Thymus
->Longlived
->Highly mobile
->Cellular & humoral TCR, CD molecules, MHC I
->High numbers
->Paracortex
->no complement receptors, no surface Ig, and no antibody synthesis
T CELL DEVELOPMENT
Origin: ___________-
Site of Maturation: _______
expression of complete antigen receptor requires successful rearrangements of the alpha and beta chains (or y and δ delta chains) of the T cell receptor (TCR)
bone marrow
site of maturation is in the thymus
STAGES OF DEVELOPMENT
1. SR
2. PS
3. NS
somatic recombination
positive selection
negative selection
Stages of Development:
Somatic recombination
TCRs produced must:
1. be _________ of binding MHC complexes
2. _____________ our own cells which also expresses MHC proteins bound to normal self-peptides
Stages of Development:
TCRs produced must:
1. be capable of binding MHC complexes
2. Not recognize our own cells which also expresses MHC proteins bound to normal self-peptides
STAGES OF DEVELOPMENT
->Positive selection determines if a T cell will become a CD8+ T cell or a CD4+ T Cell
-> If TCR binds strongly to MHC Class II: induce expression of ThPOK -> reduce expression of RunX3 -> low CD8 -> high ___________
->If TCR does not bind strongly to MHC class II: low ThPOK & high Runx3 -> _________
Negative Selection
->___ binds strongly to MHC complexes in the thymus (thymic self-peptides)
-> self-reactive T cells induced to undergo apoptosis (negative selection)
TCRs
Positive selection
results in (+) ________- that can either lead to CD4+ or ________
double thymocytes
that can either lead to CD4 or CD8 T cells
What are the Peripheral T cells
1. NT cells
2. MT cells
3. RT cells
Naive T cells
Memory T cells
Regulatory T (Treg) Cells
PERIPHERAL T CELLS
—>Mature recirculating T cells that have not yet encountered their specific antigens
—> Requires __________ as APC
Naive T cells
Dendritic Cells as APC
Dendritic Cells
->In the LN present antigen: ______ to naive CD8+ T cells and antigen: _______ to naive CD4+ T cells
-> provide strong co-stimulatory signals via ______ molecules -> directly activate CD8+ T cells to make their own ______-
In the LN present antigen: MHC I to naive CD8+ T cells and antigen: MHCII to naive CD4+ T cells
provide strong co-stimulatory signals via B7 molecules -> directly activate CD8+ T cells to make their own IL2
Routes of antigen processing and presentation by dendritic cells
Both receptor mediated phagocytosis and Macro-pinocytosis
MHC molecules loaded: Class _____
Type of naive T cell activated: _____
Class II
CD4
Migration of naive T cells into lymphoid tissues depends on their binding to high endothelial venules (HEVs) through cell-cell interactions
-> Governed by cell -adhesion molecules
1. S
2. I
3. Members of ___________
4. M__________ molecules
selectins
integrins
members of Ig superfamily
mucin-like molecules
THREE SIGNALS INVOLVED IN ANTIGEN-SPECIFIC T CELL ACTIVATION
1. Signal 1: _____ of foreign peptide: MHC complex by TCR
2. ________ from the same APC (e.g. B7)
3. ___________ differentiation
EFFECTS OF CD28:B7 PATHWAY
Effects:
1. increased transcription of _____
2. increased _____-
3. Signal stabilization
4. enhanced differentiation into ______ & __________
REGULATION OF CD28
CD28 constitutively expressed on T cells:
enhanced by:
1. ________ (e.g. endotoxin)
2.__________ (e.g. IFN-y)
stimulate each other with CD40-CD40L pathway
inhibited by CTLA-4 (CD152):B7 interaction
CD28 constitutively expressed on T cells
enhanced by:
1. microbial products (e.g. endotoxin)
2. cytokines (e.g. IFN-y)
stimulate each other with CD40-CD40L pathway
inhibited by CTLA-4(CD152) : B7 interaction
CD40L:CD40 Pathway
Effects:
1. increase the expression of ______
2. Stimulate secretion of ________
CD4 T cells regulate both cellular and humoral immune system
its regulation reduces _______
autoimmunity
SUBSETS OF T-HELPER CELLS
1. ______: Intracellular pathogens and chronic inflammation
2.______: extracellular parasites and allergic disorders
3.______: self-tolerance
4. ______: extracellular pathogens and autoimmunity
5._______: wound healing and inflammatory diseases
T helper 1
T helper 2
T regulatory
T helper 17
T helper 22
PROTEINS IN GRANULES
1. _________- Aids in delivering contents of granules into the cytoplasm of target cell
Perforin
Granzymes
Granulysin