Lecture 34 - T cells Flashcards
MHC-I antigen processing
Antigenic proteins are degraded in cytoplasm
Peptide loading of MHC-I takes place in the endoplasmic reticulum (ER)
MHC-II antigen processing
Antigenic proteins are degraded in acidic phagolysosome
Peptide loading of MHC-II takes place in phagolysosome
T cells
T cells are lymphocytes that arise in the bone marrow and fully develop in the thymus
T cells express T cell receptor (TCR) with co-receptors (either CD4 or CD8)
Recognise MHC/peptide complexes (sense the MHC peptide complexes on the surface of dendritic cells) (MHC are the protein complexes on the dendritic cell that presents the peptide)
These cells have evolved to give us memory to respond to vaccine and be more vigorous to an infection the second time around
Production of T cells
Occurs in the bone marrow, from stem cells and in the bone marrow these are young T cells and they are not functional at this stage and then they migrate via the blood to the thymus
T cell development
T cells migrate from the bone marrow via the blood to the thymus. The thymus is the site of T cell development and TCR (T cell receptor) rearrangement. T cell rearranges its DNA and a small part of the genome is rearranged in response to signals in the developing T cells so all T cells are different from one another in terms of the receptors. At the thymus the T cells learn how to respond appropriately to antigens within the thymus
The T cells then travel to lymphoid organs, blood and tissues
Thymus
T cells develop in the thymus which is located in the upper anterior part of your chest directly behind your sternum and between your lungs.
T cells express a unique T cell receptor
Immature T cells (TCR genes in germline state) in bone marrow. TCR gene rearrangement in the thymus (random but in a defined way therefore there is a lot of diversity in the T cell population). Mature T cells expressing unique antigen receptors (TCR)
Thymic gene rearrangement
Immature T cells (thymocytes) rearrange the ‘cariable’ parts of their TCR genes in the thymus
The rearrangement process is essentially random
This ensures that individual T cells are unique in terms of their TCR. Creates ‘diversity’ in T cell repertoire and this therefore enables recognition of many different microbes
The upper tip of the TCR is rearranged genetically in the thymus which is why we have an adaptive immune system because of the variety of shapes
T cell receptor
The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules.
T cells express a TCR that recognises peptide+MHC
CD4 and CD8
CD4 and CD8 are ‘co-receptors’ on T cells
CD4 T helper cells
Recognises MHC-II/peptide i.e. respond to antigens normally bought from the outside (the phagolysosome pathway)
Helps CD8 T cell become cytotoxic
CD4 T cells help B cells make antibody
In the lymph node or spleen
CD8 T cells
Recognise MCH-I/peptide
Develops into ‘cytotoxic lymphocyte’ (CTL) aka cytotoxic T cell
CD8 T cells become cytotoxic and kill virus infected cells and cancer cells
T cell differentiation
T cells that have not been activated by MHC/peptide are naive (havent seen antigens)
Activated T cells are also known as effector T cells (experience comes from being exposed to antigens)
Cytokines
Cytokines are produced by CD4 T cells help CD8 cells become activated therefore allow them to do their job
General term for mediators that influence cell development, differentiation and responses in the immune system
Cytotoxic lymphocytes (cytotoxic T cells)
Cytotoxic T lymphocytes (CTLs) represent one of several types of cells of the immune system that have the capacity to directly kill other cells. They play a major role in host defense against viral infection, as well as infection by other intracellular pathogens that replicate in the cytoplasm of the host cell.
Developed from CD8 T cells by exposure to cytokines
Helper T cells in humoral immunity
Also called antibody-mediated immunity, is provided by antibodies present in the body’s fluid (blood, lymph etc.) Though they are produced by lymphocytes, antibodies circulate freely in the blood and lymph where they bind primarily to extracellular targets inactivating them temporalily and marking them for destruction by phagocytes or complement
With assistance from helper T cells, B cells will differentiate into plasma B cells that can produce antibodies against a specific antigen
Helper T cells in cellular immunity
Cellular immunity is mediated by T lymphocytes/T cells. … This activation results in the expansion of the antigen-specific lymphocyte pool and the differentiation of these cells into effector and memory cells. Effector cells include helper T cells, and cytolytic or cytotoxic T cells.
Memory T cells
In addition to the formation of ‘effector’ cells, T cells activation result in the formation of memory T cells. Memory CD4 or CD8 T cells reside in the body for long periods of time. Memory T cells become effector cells much quicker than naive cells (respond more vigorously the second time around)
HIV full name
Human immunodeficiency virus (disorder)
HIV
HIV-receptor is CD4 molecule on CD4 T cells
Infection leads to loss of CD4 T cells
CD4 T cells help both humoral (B cell/antibody) and cytotoxic responses
HIV infection impacts on immunity to microbes (fungi, bacterial and virus) and to cancer. (due to decreased cytokine release)
The immune system is weakened by the destruction of CD4 T cells
The T cell receptor of CD4 T cells recognise
MHC -II/peptide complexes on antigen presenting cells
The T cell receptor of CD8 T cells recognises
MHC-I/peptide complexes on APC e.g. dendritic cells, macrophages, B cells
MHC-I/ peptide complexes on virus infected or cancer cells
Viral antigens are mostly presented on…
MHC-I but can also be present on MHC-II by APC e.g. dendritic cells
T cells express a diverse range of T cell receptors (TCRs) due to
Expression of rearranged TCR genes
The site of T cell germline TCR gene rearrangement is the…
Thymus
Immature T cell precursors arise in the …
Bone marrow
Antigen present cells include …
B cells
Macrophages
Monocytes
Dendritic cells
Lymphocytes that have not seen the antigen are termed …
Naive
Following stimulation via MHC-I, CD8 T cells become …
Cytotoxic T lymphocytes (aka cytotoxic T cells)
Long lived T cells (or B cells) that respond vigorously to a second encounter of antigen are …
Memory cells
Adaptive defences summary
Adaptive defences beginning with antigens identified by lymphocytes and antigen presenting cells trigger humoral immune response and cellular immune response.
