Lecture 9: Immune activation, helper cells and regulation Flashcards
Write some notes on antigen transport and presentation:
Typically dendritic cells are sampling all the proteins in their environment and present these to immune cells in the lymph nodes. Majority of presentations do not illicit a response.
What are the properties of HLA exogenous pathway class 2?
- Found on B cells and specialized APCs
- Co-dominant
- Polymorphic
- Present peptides to CD4 T cells
What are the properties of HLA endogenous pathway class 1?
- Found on virtually all nucleated cells
- Co-dominant
- Polymorphic
- Present peptides to CD8 cells
Describe the relationship of antigens and class 1 HLA:
Class 1 HLA is present on all nucleated cells and will present samples from the cellular environment i.e self and non-self such as viral proteins.`
Whats the MHC 1 structure?
Alpha chain + B2 microglobulin
Describe the relationship of antigens and class 2 HLA:
Phagocytic cell ingests and breaks down pathogen, peptides are presented on surface by class 2 MHC (HLA-DP, DQ or DR)
Also some cross representation by MHC class one (present on all nucleated cells) (HLA-A,B or C)
Describe MHC stucture:
Alpha chain and beta chain
Write some notes on the peptide groove for MHC1&2:
HLA is unique to everyone. It can determine which parts of an antigen are presented and this in turn influences response.
Write some notes on the process of CD8 T cell antigen recognition:
Cytotoxic T cells:
CD8 (essential for class one recognition) TCR(alpha,beta) - Recognises peptide and part of HL CD3 (When TCR bound, this undergoes conformational change to relay back to internal cell)
Target cell:
Class 1 MHC with peptide being presented
Write some notes on the process of CD4 T cell antigen recognition:
CD4+TCR+CD3 <-> Class 2 MHC + Peptide
What happens to patients with defects in TAP genes?
- Poor endogenous antigen processing
- Low HLA-A, B, C expression
- Few CD8 T cells, normal CD4 T cell numbers
- Recurrent resp. viral infections
= (tells us that HLA class 1 is required for CD8 t cell development, and CD8 t cells are important in viral infections)
What prevents CD8 T cells from reacting to the presentation of self peptide?
Accessory molecules: Adhesion, co-stimulators, checkpoint regulators, cytokines
What are the extravasation adhesion molecules?
Selectins (Weak interactions, direct cell traffic around body, like velcro)
Integrins (Strong cell:cell adhesion, hold cells in tissues together, hold lymphocytes together for activation)
What are the weak adhesion molecules involved in extravasation?
L-Selectin: Circulating non-memory lymphocytes
P-selectin: Platelets, endothelial cells and neutrophils
E-selectin: Vascular Endothelium, induced by proinflam cytokines (i.e IL1, TNFa), b/w leukocytes
Low affinity, Rapid association and dissociation
Write some notes on integrins: how are immunoglobulin superfamily molecules related (IgSF)?
- Strong adhesion, tissue integrity, site-specific addressins, involved in lymphocyte activation
IgSF - Ligands for integrins, contain Ig-like domain
Describe extravasation:
Neutrophil
- Weak binding to endothelium via selectins
- Triggers integrin expression
- Strong binding triggers migration and diapedesis
Neutrophils follow chemotactic gradient
What are cadherins?
Cadherins
- Embryogenesis
- Tissue development
- Homophilic interactions
Whats the first step of lymphocyte activation?
Integrin/IgSF interaction
i.e T cell, LFA-1 interact with APC ICAM-3
Allows MHC class 2 and TCR to test for affinity
Whats the second step of lymphocyte activation?
Co-stimulators or checkpoint regulators are upregulated following TCR-MHC2 strong affinity
Write some notes on checkpoint regulators / costimulators:
- Pairs of surface molecules expressedin cell-cell interactions
i. e B7 on APC <-> CD28 on T cells
i. e CD40 on B cells <-> CD40L on T cells
- Expressed transiently
- Modulate immune activation processess
- Prevents reacting against self antigen because the APC wont upregulate their checkpoint regulators without DAMP/PAMP being present in the protein
How do T cells help B cells?
Ig binds many things, B cells which recognize Ig Fe regions require T helper cell co-stimulation to initiate action
i.e B cells endocytose Ig-AB complex. Breaks down AB and presents it on MHC-2. This interacts with T cell, Co-timulators/checkpoints upregulated and if responses needed Th releases cytokines to activated the B cell, expansion etc.
What are some co-stimulators and co-inhibitors?
Costimulators:
- Interaction = activation i.e CD28:B7, CD40:CD40L
Co-inhibitors
- Interaction = switch off respoinse i.e CTLA-4:B7, PD-1:PD-L1
Describe CD4 t cell clonal activation:
MHC class 2 : CD4 t cell (Costim+Cytokines)
- > Gets Th cytokine signal
- > Proliferate and differentiat4e into memory cells and cytokine secreting cells
What are cyotkines?
- Small glycoprotein messenger molecules
- Paracrine, endocrine and autocrine
- Specific receptors
What are cytokine properties?
Pleiotropic : B and Th cell proliferation, mast cell activation
Redundant : B cell proliferation
Synergistic : AB class switch to IgE
Antagonistic : Block IL-4 induced IgE class switch
What is cytokines synonymous with?
Interleukins: Between leukocytes
Interferon : Interferes with viral replication
CSF : Colony stimulating factor