L7-8 Flashcards
Function of immunological tolerance
BCR/TCR repertoire random generation
self-reactive specificity production
prevention of autoreactivity pathology
3 outcomes of random TCR gene arrangement
- failing to recognize self-MHC
- recognizes self-MHC and Ag peptide from thymus
- recognizes self-MHC and peptide not present in thymus
what happens to the 3 outcome of random TCR arrangement
- die by neglect
2/3 expanded by positive selection
2 later on dies by negative selection
AIRE
Auto-Immune Regulator Protein
Auto-Immune Regulator Protein
txn factor
role in tolerance induction
tissue-specific antigen in thymus expression > negative selection
autoreactive B cell outcome
negatively selected/ deleted in bone marrow
or re-arrangement of receptor so light chain can remove self-reactivity
B cells in bone marrow
immature w no self-reaction will migrate to periphery to be rearranged (receptor editing)
ANERGY
unresponsive
production of anergic T cells
macrophage bacterial stimulation > co-stimulating signal to T recognizing bacterial antigen
> proliferation/ differentiation of T spec for bacterial protein
immunological ignorance
Ag not present at sufficient levels to activate T
priveleged sites
Ag hidden from immune via barriers/ suppressive cytokines
types of regulatory T cells
natural (arise in thymus)
induced (circulate in peripheral)
regulatory T cells
T specific for self-antigen
CD4+ Treg subset
suppresses immune response and prevents autoimmune responses
Treg deficiency
causes autoimmune syndrome
cytokines produced by Treg and function
IL-10 and TGF-beta
inhibit other self-reactive T or cell-cell contact in periphery
regulation B cell secretion
IL-10
cell regulation function
control quality and length of response
minimize damage
types of effector T
CD4+ Th 1/2/17/TregBreg/ Tfh
CD4+ TH1
Fas ligand induces apoptosis
releases bacteria destroyed by healthy macrophage
CD4+ th17
secrete IL-17
recruit neutrophils early in fungal infections
TH1 response cytokines
IL-12/ IFN gamma
intracellular pathogens w cell-mediated immunity
TH2 response cytokines
IL-4
pathogens> humoral immunity
TH1 cytokine polarisation
^TH1 commitment
inhibits TH2/17
TH2 cytokine polarisation
^TH2 commitment
inhibits TH1/TH17
TH17 cytokine polarisation
^ TH17 commitment
inhibits Treg development
Treg cytokine polarisation
inhibits TH1/2/17
allow successful pregancy
function of polarized responses
ensure correct responses for different pathogen types
prevents allergy (excess TH2)
controls autoreactivity/ pregnancy
rid need of co-stimulation
what do immunity effector mechanisms depend on
pathogen type
localisation
infection stage
types of host defence mechanisms
innate
acquired/ adaptive
innate defence mechanism
non-specific
rapid
barriers
(skin/ mucosa/ epithelium/ intestine)
complement (C3/ defensin/ RegIII)
innate immune cells > macrophages, granulocytes, NK cells
acquired/ adaptive immune response
slower
antibody action
cell-mediated
memory
CD4+ Th1
against intracel pathogens
macrophage activation
cyto T stimulation (CD8+)
CD4+ Th2
against extracel pathogens
produce antibodies
IgE class-switching
eosinophil/basophil/mast acivation
CD4+ Th17
against extracel bacteria/fungi
attract inflam cells
early response
2 types of bacteria
gram +
gram -
TLR
toll like receptors
binding sites on macrophages
no. TLR genes in humans
10
NOD-like receptors
nucleotide-binding oligomerisation somain
intracellular sensors in cytoplasm
PAMPs
pathogen associated molecular patterns
binds to TLR
PAMP effects
inflam promotion/ dendritic cell maturation
T differentiation influences
B activation
which TLRs bind nucleic acids
3,7,8 and 9
antibody opsonization
via Fc/ C3b receptor binding on phagocytes
complement activation
C3a/C5a inflam promotion
g- lysis
bind and neutralize toxins
prevent mucosal adherence
terminal complement defect outcome
neisseria spp
Th1 response
cytokines activate macrophages
^ efficiency of APC
stimulate inflammation
2 types of mycobacterium leprae
TB
Lepromatous
TB leprosy
strong th1 response
slow progression
granuloma formation
lepromatous leprosy
strong Th2 response/ antibody response
bacteria in macrophages disseminated
fatal
granuloma
when Th1 cells accumulate and secrete cytokines/ chemokines
