Introduction to the Immune System III Flashcards
What are the steps and cell types involved in T cell activation?
- phagocytic cells (like dendritic cells, macrophages, and B lymphocytes) ingest foreign antigens and present them on their surface bound to MHC
- the APC takes teh particle on MHC to the secondary lymph tissues to present to T cells
- the T cell binds to the peptide on MHC with its T cell receptor (TCR) and costimulates with either CD4 or CD8
- the APC costimulates the T cell with another molecule; this activates the T cell
What are the structural and functional differences between MHC Class I and MHC Class II
Class I
- expressed by almost all cells in the body
- interacts with CD8 T cells
- most peptides from endogenous proteins
- has alpha 1, 2, 3 (heavy chain) and beta 2 (light chain) subunits; only alpha 3 attached to the cell membrane
- peptide binding in ER
Class IIi
- expressed by professional APCs
- interacts with CD4 T cells
- most peptides from exogenous proteins
- has beta 1, 2 and alpha 1, 2 subunits (2 equal chains). Both beta2 and alpha2 are attached to cell membrane
- peptide binding in endolysosomes
*both types have peptide-binding clefts and are presented on the cell surface
What MHC class do CD8 T cells interact with?
MHC class I
What MHC class do CD4 T cells interact with?
MHC Class II
Where are peptides bound to MHC in class I expressing cells?
most peptides from endogenous proteins, therefore, bound in ER
Where are peptides bound to MHC in class II expressing cells?
most peptides from exogenous proteins, therefore, bound in endolysosomes
How are MHC Class I peptides generated?
Protein material derived inside the cell, for example, viral proteins that are synthesized in the cytosol, are marked as foreign then broken down by proteasome. The fragments are taken to the ER where they bind with MHC I. From there they move through the Golgi to the surface of the cell to present to CD8 T cells. This can occur in virtually any cell of the body
How are MHC Class II peptides generated?
Antigen found outside the cell, either bacterial products or peptides from bacteria, first enter an APC through phagocytosis. The material merges with a lysosome which breaks down the polypeptides. Then the vesicle is merged with another vesicle containing MHC II. If the protein product binds, then MHC II will go to the surface of the cell and display the polypeptide to CD4 cells
What are the basic, unique genetic features of MHC molecules?
- the genes that encode for MHC I and II are highly polymorphic
- high frequency of alternate alleles for a given gene
- a single cell can display up to 6 different types of MHC I, all of which are capable of recognizing different protein segments
- a single APC can display at minimum 3 different MHC II, but could be many more due to polymorphism
- this allows MHC to recognize and bind to a much broader range of polypeptide groups
What are the effector functions of Cytotoxic T cells (CD8+)?
- reacts with antigenic peptides presented on MHC I
- when costimulated by T helper cells, they become cytotoxic and kill infected cells (virus-infected and tumor cells)
- peptides derived from endogenous sources
What are the effector functions of Helper T cells (CD4+)?
- reacts with antigenic peptides presented on MHC II of APC
- helps cytotoxic T cells to become cytotoxic and helps B cells to make antibodies (through cytokines and cell-cell interactions)
- helps APCs become active (cytokines)
- peptides derived from exogenous sources
What are the effector functions of Regulatory T cells?
- CD4+, CD25+, MHC Class II restricted
- regulate the immune response - mostly inhibitory, prevents autoimmunity
What are the characteristics of active immunization?
- acquired when one’s immune system responds to an antigen and launches an immune response
- after this point, you have memory of that antigen and can launch a much quicker response if exposed again
- this can occur through vaccination or illness
What are the characteristics of passive immunization?
- the acquisition of antibodies that provide temporary immunity from an antigen
- -> this can be natural, as through the placenta or breastmilk, or it can be artificial, as with the injection of antibodies from a donor(s). This is required for immunocomporomised patients, people exposed to deadly toxins, and for rapidly-progressing infections
What are some undesirable effects of the immune response? (explanations)
- immune response can be hyperactive; in the case of allergies, the immune response can be overwhelming and it can occur more and more frequently; the reaction is to innocuous substances
- autoimmunity occurs when the immune system responds against self antigens. there is disregulation and breakdown in the T cell and antibody response.
- transplant rejection: due to the different MHC Class I receptors present in every person (multiple possible combinations of genetic material to form them), it is difficult to match people exactly so that when the organ is transplanted, it is not recognized as foreign and rejected. Immunosuppression is needed to prolong the survival of the graft.