Immunology test 3merlin123
Immunology Chapter 5 – Spring 2020
Read chapter 5. Below are some notes to help you organize the material.
What are the two major types of T cells?
· CD4 T cells and CD8 T cells will be the main two types of T cells we will discuss. The following section will go into more detail about these two types of T cells, but for now know that (Fig. 5.12)…
· CD4 T cells (aka helper T cells) have the co-receptor CD4 on their surface and recognize antigen bound to MHC class II.
· CD8 T cells (aka killer T cells) have the co-receptor CD8 on their surface and recognize antigen bout to MHC class I.
How do T cells recognize antigen?
· Via a T-cell receptor (TCR)
· A highly variable antigen-specific receptor
· Recognize mainly protein antigens bound to a human glycoprotein (aka MHC)
· Have similarities and differences to Immunoglobulin.
· Fig. 5.1 shows the structural difference between Ig and a TCR
· The T cell receptor consist of two separate chains (alpha and beta or gamma and delta (Fig. 5.7)
· There are actually two types of T cells based on TCR. We will focus primarily on α: β T cells because they are the primary T cells in circulation for most vertebrates.
· A few points to know about γ:δ T-cells:
1. They are more abundant in tissues compared to circulation
2. Behave differently from α: β T cells in that they can have effector functions
3. Antigen recognition is not dependent on antigen presentation in MHC
· Each chain has four basic parts
1. A cytoplasmic tail
2. A transmembrane region
3. A constant region
4. A Variable region
· A genomic recombination event (similar to that of somatic recombination in B cells) allows for variation in antigenic binding sites of T cells. (Fig. 5.3)
· You are not responsible for knowing this process in detail, but definitely know that it occurs.
· T-cell receptors form a T cell receptor complex with CD3 proteins (Fig. 5.6)
· A T cell receptor can recognize antigen but alone it is not going to be able to transduce a signal when antigen is bound.
· T-cell receptors can have major functions when activated by antigen (Fig. 5.13).
· Kill sick cells. (CD8 T cells)
· Send cytokine signals to activate macrophages. (CD4 T cells)
· Send cytokine signals to activate differentiation and further cell division of activated B cells. (CD4 T cells)
What are MHC molecules?
· MHC stands for major histocompatibility complex.
· Present peptide (protein) antigens to T cells.
· Antigen is processed within a cell, bound to MHC and then the MHC with antigen is inserted into the cytoplasmic membrane. Only then can a T cell recognize antigen within a MHC molecule. Refer to Fig. 5.10
· There are two types of MHC.
· Refer to Fig. 5.11: MHC class I and MHC class II
· MHC (HLA) class I
· Expressed by a broad range of cell types (Fig. 5.25)
· Presents antigen from intracellular pathogens (Fig. 5.27) for example viruses.
· Binds short fragments of peptides from the intracellular pathogens (8-10 amino acids in length).
· Exhibits promiscuous biding specificity
· Can bind thousands of peptides with different amino acids sequences
· Presents antigen to CD8 T-cells (Fig. 5.15)
· MHC (HLA) class II
· Expressed by a limited number of cell types (Fig. 5.25)
· Presents antigen from extracellular pathogens (Fig. 5.27). ie. most bacteria
· Binds large fragments of peptide (usually 13 to 25 amino acids in length)
· Exhibits promiscuous biding specificity
· Presents antigen to CD4 T-cells (Fig. 5.15)
· MHC molecules are encoded within the major histocompatibility complex
· The major histocompatibility complex
· According to your book, the major histocompatibility complex (MHC) is a large cluster of mainly immune-system genes present in all vertebrates that encode MHC molecules. Fig. 5.30
· In humans, it is referred to as the human leukocyte antigen complex (HLA)
· Human MHC molecules are called HLA class I and II molecules.
· MHC (HLA) molecules
· The basis of an individual’s tissue type.
· There is inherited diversity in HLA types between individuals.
· This diversity is not as great as for a TCR or Ig it is still very important for antigen binding and presentation as well as tissue rejection.
· Unlike B and T cell receptors, the diversity of HLA types is not a product of any type of genomic rearrangement.
· This diversity arises from two sources :
· 1. The presence of gene families
· There are multiple similar genes encoding the MHC class I and class II proteins.
· Protein products from these gene families are referred to as isotypes. Fig. 5.28
· Each isotype has a particular functions:
· HLA-A, HLA-B and HLA-C present antigen to CD8 T cells and NK cells
· HLA-E and HLA-G present antigen to NK cells
· HLA-F function is unknown
· HLA-DP, HLA-DQ and HLA-DR present antigen to CD4 t cells HLA-DM and HLA-DO help to load antigen onto the other 3.
· 2. Genetic polymorphism
· The presence within the population of multiple alternative forms of a gene or alleles.
· Different MHC isotypes display varying levels of polymorphisms
· Highly polymorphic human MHC isotypes have multiple alleles circulating within a population whereas less polymorphic isotypes have less alleles circulating within a population (Fig. 5.28).