T-Cell Mediated Immunity Flashcards
Two ways that an intracellular infection may occur
Phagocytose to become an intracellular vesicular pathogen (generally bacterial)
Invading the cell to become an intracellular cytosolic pathogen (generally viral)
When is a helper T cell required and when is a cytotoxic T cell required
Helper T cell for Intracellular Vesicular infection
Cytotoxic T cell for Intracellular Cytosolic infection
Difference between immunity from B cells and T cells
B cell recognise microbes in the cell’s native form; directly recognised, then cell is activated and differentiates into plasma cell to target microbe
T cells cannot recognise pathogens directly and must instead have antigens processed and presented to them; depending on antigen presentation, the T cell will either differentiate into a helper T cell and produce cytokines or become a cytotoxic T cell and release cytotoxic mediators
T Cell Receptor Structure
T cell receptor (TCR) consists of two chains; alpha and beta
Each is made of two domains - 1 constant and 1 variable
Antigen combining site is made of variable domains from the alpha and beta chain
B Cell Receptor
B Cell receptor made of 4 domains - two light, two heavy
**Antibody structure covered elsewhere
Antigen Combining Sites of B vs T Cell Receptor
B cell receptors have 2 antigen combining sites while T cells have 1
How does TCR affect activation of T cell
It does not affect cell activation, only functions for recognition
Other molecules are needed for activation
What are CD4 and CD8 T Cells
CD4: T Helper Cells
CD8: T Cytotoxic Cells
Compare the two types of T cells
CD4 T Helper cell
- Help B cells produce the most appropriate class of antibodies, especially for extracellular infection
- Helping macrophages that have phagocytosed pathogens by producing cytokines to help macrophage to better phagocytose and digest the infectious agent (intracellular vesicular infection)
CD8 T Cytotoxic Cells
Killing infected cells - e.g. cells taken over by viruses
Compare which receptors are on helper and cytotoxic T cells
All T cells express normal TCRs
Additionally, Helper T cells express the CD4 receptor while cytotoxic cells express the CD8 receptor
MHC vs HLA Proteins
HLA - Human Leukocyte Antigen
MHC - Major Histocompatibility Complex
HLA is the term for MHC proteins in humans
It is the protein on The APC presented to T Cells
What determines which type of T cell is activated
The type of Human Leukocyte Antigen (HLA) is presented on the APC to the T cell
- CD8 has antigen presented via HLA Class I
- CD4 has antigen presented via HLA class II
Peptide Binding Groove
Where antigens are presented on HLA proteins after processing the pathogen
Compare HLA class I and II molecules
HLA class I is made of an alpha chain with 3 α domains and one β2 microglobulin Peptide binding groove made of alpha I and alpha II
HLA class II is made of one α chain and one β chain each with two domains Peptide binding groove made of alpha and beta chains
How are cytotoxic T cells activated
When HLA I molecule binds antigen to the TCR on CD8, the CD8 receptor interacts with the α3 domain of HLA class I but only if there is binding
Leads to Tc activation
How are helper T cells activated
When an Intracellular cytosolic infection is processed and presented on HLA II, the Th TCR binds to the antigen and CD4 molecule interacts with β2 domain of HLA II after binding leading to Th activation
Reiterate which HLA Class and Domain does the CD8 Receptor Bind to and which does the CD4
CD8 - HLA Class I; Interacts with α3 domain
CD4 - HLA Class II; Interacts with β2 domain
Describe the processing of antigens for HLA class I
A virus has invaded a cell and is degraded by proteasome in cell’s cytosol into small peptide fragments which are transported from the cytosol into the Endoplasmic Reticulum
They bind onto newly synthesised HLA I molecules which leave once bound (via golgi apparatus) and get transported onto cell surface
CD8 Receptor then binds and Tc does what it does and kills that cell
Describe the processing of antigens for HLA class II
Exogenous Antigen finds itself in a cell vesicle; degraded by low pH into small peptides
HLA II is found in ER whose peptide binding groove is pre-bound to invariant chain
HLA II leaves the ER (via golgi apparatus) and the invariant chain is degraded to allow peptides to instead bind to the peptide binding groove and be expressed on cell surface
CD4 recognises peptide on surface and does its shit so the cell is activated to help B cell produce more antibodies, or help a macrophage enable better intracellular infection
T helper I vs T helper II cell
T Helper I for activating macrophages
T Helper II cell to activate plasma cells to make antibodies
Action of Activated Cytotoxic T Cells
**Left
Signals sent to T cells to activate them
CD3 - Protein complex in T cells that send a signal to T cells to activate them once the TCR interacts with MHC Class 1/2
Joining of B7 on external molecule and CD28 on T cell sending signal 2
Signal sent by cytokines produced by APC or by cytokines in micro-environment. This 3rd signal determines which type of CD4 helper cell we will get
**Don’t bother with this ffs
Discuss how signal 3 affects type of T helper cell
We don’t really care about Th17 and Treg
**Don’t bother with this ffs
