PRC - Lecture 10 | Flashcards

Questão	Responda
Give 3 exampled of lymphoid cells.	T cells B cells NK cells
How are protein antigens present on/in pathogens recognised by T cells?	Once the protein antigens, and only when, are broken down into peptide fragments.
What are Major Histocompatability Complexes/ MHCs?	MHCs are a dedicated protein bound to the surface of cells which present antigenic peptide fragments on their surface to T cells.
What 2 receptors can T cells express on their surface? How do these determine the name of the T cell receptor?	T cell receptors can have either a CD4 or CD8 co-receptor, thus either CD8 T cells or CD4 T cells.
What does a ‘CD’ (4/8) receptor stand for?	Cluster Differentiation receptor
What are the FULL names of both types of T cells?	CD8 Cytotoxic T cells CD4 Helper T Cells.
Is it the co-receptors (CD4 or CD8) or the TCR/ T-cell receptors which recognise the MHC complex on pathogens?	T-cell receptor/ TCR
What does APC stand for?	Antigen Presenting Cell
Explain the function of MHC Class 1.	MHC Class 1 brings peptide fragments/ T cell epitopes to the surface of APCs whereby CD8 T cells are drawn towards it.
What is meant when CD8 T cells are referred to as ‘cytotoxic’?	They mediate the adaptive immune response against viruses and cancer cells.
Explain the function of MHC Class 2.	MHC Class 2 brings peptide fragments/ T cell epitopes to the surface of APCs whereby CD4 T cells are drawn towards it.
What is the function of CD4 T cells?	They HELP other innate and adaptive immune cells to execute their effector function.
On what types of cells are MHC Class 1 complexes expressed?	On most nucleated cells.
On what types of cells are MHC Class 2 complexes expressed? (3)	Dendritic cells Macrophages B cells
Describe the morphology of T cell receptors.	2 constant domains which sit in the membrane. 2 variable domains; one alpha chain and one beta chain.
What section of the TCR recognises the MHC complex?	The variable domain (made up of one alpha chain and one beta chain).
How many T cell receptors do T cells express?	1 TCR
Describe the morphology of both CD4 helper T cells and CD8 cytotoxic T cells.	CD4 = Monomer (4 segments). CD8 = Dimer (one segment each).
Where are T cells produced? Where are they ‘matured’ or ‘educated’?	T cells are produced in the bone marrow. T cells are educated in the thymus (lymph node).
When T cells first arrive at the thymus, how would you describe them?	- Double negative thymocytes (CD4-/ CD8-). > The CD4 or CD8 co-receptors are not expressed. - TCR-alpha/beta- > TCR not expressed.
What is meant by a Double positive thymocyte during the development of the T cells in the thymus?	CD4+/CD8+ = Both types of CD receptors are expressed because the T cell has not yet differentiated into the type of T cell it wants to be.
What is meant by a Single positive thymocyte during the development of the T cells in the thymus?	- The decision is made as to which type of T cell it will become… - Either CD4+ or CD8+ - it depends on the MHC class protein presented to the T cell (whether it is MHC class II or MHC class I). MHC Class 1 = CD8+ T cell MHC Class 2 = CD4+ T cell Both of these T cells will express T cell receptors however as these are what recognise the MHC class proteins.
Define MHC/ Major Histocompatibility Complexes.	Glycoproteins, on the surface of cells, which display peptides from pathogens in order to present them to T cells.
What determines whether the MHC receptors are class I or II on the surface of cells?	Depends upon the genetic loci which is expressed.
List the 3 different genetic loci of MHC Class II receptors in humans.	DP, DQ, DR
List the 3 different genetic loci of MHC Class I receptors in humans.	B, C, A
List the 2 different genetic loci of MHC Class II receptors in mice.	A, E
List the 3 different genetic loci of MHC Class I receptors in mice.	K, D, L
What is meant when we say Class I and Class II molecules display high allelic variability?	There are lots of different types of Major Histocompatibility Complexes/ MHCs across a population, and this high allelic variability means we can spread the risk of new diseases across everyone i.e. not everyone will be effected.
How many MHC Class I molecules does a human cell express based on how many genetic loci for each type there is?	There are 3 genetic loci for MHC Class I (B, C, A). There is one parental allele each… 3 x 2 = 6 MHC Class I molecules.
How many MHC Class II molecules does a human cell express based on how many genetic loci for each type there is?	There are 3 genetic loci for MHC Class II (DP, DQ, and DR). There is one parental allele each… 3 x 2 = 6 MHC Class II molecules which can be expressed.
How many MHC Class molecules does a human cell express in TOTAL based on how many genetic loci there is?	There are 12 genetic loci for both MHC Class I and II together which can be expressed, therefore 12 MHC molecules can be expressed on the surface of a human cell.
Describe how you would name MHC Class I molecules in mice.	- You look at both the loci and alleles when determining the names. Alleles = b, d, k (and others) Loci = H-2D, H-2L, H-2K - Therefore… an example for the ‘B’ allele on the D locus = H-2D^b or H2D of B.
Describe how you would name MHC Class II molecules in mice.	Alleles = b, d, k (and others) Loci = I-A, I-E Therefore… an example for the ‘k’ allele on the E locus = I-E^k or IE of k.
Describe how you would name MHC Class I molecules in humans.	Alleles = Numbers Loci = HLA-A, HLA-B, HLA-C Therefore… an example for the number 2 allele on the locus HLA-A = HLA-A2 or HLA of A2.
Describe how you would name MHC Class II molecules in humans.	- Alleles = Numbers - Loci = HLA-DP, HLA-DQ, HLA-DR - Therefore… an example for the number 4 allele on the locus HLA-DP = HLA-DP4 or HLA of DP4.
MHC Class I molecules are found on most nucleated cells. What type of proteins are processed and presented by MHC Class I molecules?	Cytosolic proteins
Describe the transport of cytosolic proteins from the cytoplasm to the surface of the cell for presentation by MHC Class I complex. (4)	- Cytosolic proteins are processed into peptides in the proteasome. - Peptides then bind to MHC Class I molecules in the Endoplasmic reticulum. - This peptide/MHC Class I complex is then transported through the Golgi body. - This complex then moves out of the cell onto the cell surface.
Describe the morphology of MHC Class I molecules.	One heavy chain associated with beta-2 microglobulin. Binds short peptide (8-9 amino acids).
MHC Class II molecules are found on specialised antigen-presenting cells (dendritic cells, macrophages and B lymphocytes). What type of proteins are processed and presented by MHC Class II molecules?	Extracellular proteins
Describe the transport of extracellular proteins from the exterior of the cell, through the cell and then to its surface to be presented by MHC Class II complex.	- Extracellular proteins are taken into the cell by endocytosis into an endocytic vesicle. - These proteins are digested into peptides in endosomes. - Vesicles containing MHC Class II molecules move from transmembrane proteins (where they are synthesised) and then fuse with these endosomes. - This MHC Class II/ peptide complex moves to the cell surface and embeds itself.
Describe the morphology of MHC Class II molecules.	2 heavy chains. Has an extended groove. Binds longer peptides (13 – 17 amino acids).
What is meant by ‘positive selection’ in reference to the test for proper MHC binding?	- During T cell development in the thymus, positive selection ensures that the T cell receptor on the surface of T cells learns to recognise an MHC complex allele expressed by our own body’s cells. - Therefore, T cells can either mature in the presence of MHC Class II molecules, which allow the cell to express both CD4 receptors and TCR due to the recognition of the cytosolic protein. - OR, T cells can mature in the presence of MHC Class I molecules, which allow the cell to express both CD8 receptors and TCR due to the recognition of the extracellular protein.
List 3 properties of Innate immunity.	Low diversity in recognition = A large number of cells that can recognise a given antigen; they can patrol the entire body; are immediately available/ fast response.
List 3 properties of Adaptive immunity.	High diversity in recognition = A small number of cells that can recognise a given antigen; are initially anatomically restricted; require days of proliferation and differentiation/ slower response.
Where do T cells become activated?	Lymph nodes
Describe the process between infection and adaptive immunity in stages (7).	- Pathogenic adherence to epithelium. - Local infection; penetration of epithelium. - Innate immune cells are drawn to the site of infection i.e. dendritic cells. - Lymphatic spread (dendritic cells migrate to the lymph node where they present antigens to immature T cells). - T cells are educated. - Adaptive immunity kicks in – T cells leave lymph nodes and target the infected tissue.
What is meant by a naïve T cell?	A cell which has not seen its particular antigen… it traffiks and waits in the lymph node.
Why is it that as T cells become educated, the number of T cells with a given recognition specificity proliferate rapidly?	- Because the number of cells present for a given recognition specificity is low… and therefore, once the antigen is detected, more of these cells are required to be present during the adaptive immune response if fighting the foreign cell is going to be effective.
Why is it naïve T cells have a high amount of different recognition specificities before they are educated?	Because each cell has a high diversity and can recognise multiple antigens – it has options.
Why is it that effector cells have a low amount of different recognition specificities after they are educated?	Because each cell recognises a specific antigen.
What is the function of a naïve T cell?	Await initial antigen encounter – no effector function.
What is the function of effector T cells?	Eliminate antigen.
Where and how do dendritic cells become activated?	Dendritic cells take up microbial antigens and become activated in peripheral tissues by PRRs.
Where do activated dendritic cells travel to?	Lymph nodes
What do dendritic cells do once they arrive at the lymph node? (4)	Become mature by switching on the expression of MHC Class II complex.
How are dendritic cells activated?	By their Pattern Recognition Receptors binding to PAMPs at the site of infection.
What is the function of CD4 helper T cells?	They coordinate the adaptive immune response – they don’t directly eliminate pathogens.
Name the 3 groups of CD4 helper T cells?	T helper cells (Th1) T helper cells (Th2) T helper 17 cells (Th17)
What are CD4 T regulatory cells?	CD4 T helper cells that have a different function to help control and reduce T cell responses.
What diseases can you suffer from if you lack CD4 T regulatory cells?	Auto-immune diseases.
In what way is the innate immune response made more effective by the adaptive immune system?	Enhancement of effector function by CD4 T cells.
In order for the CD4 T helper cell to carry out efficient effector cell function, what must it be able to do?	To be able to recognise an antigenic peptide.
In order for the CD4 T helper cell to carry out its efficient effector cell function, what must the cell being helped have?	Engagement innate or adaptive antigen receptors.
Which CD4 T helper cell helps macrophages carry out their function?	Th1 cells
Where are macrophages found?	In the tissues.
Can macrophages phagocytose invading organisms and kill them without help from T cells?	Yes.
What type of bacterium is an example of one which can evade its own death by entering macrophages?	Mycobacterium tuberculosis.
In what way can bacteria which have invaded macrophages be killed?	By macrophage activation by cytokines from T helper cells.
Describe dual recognition between CD4 helper T cells and macrophages.	- CD4 helper T cell’s TCR recognises MHC Class II complexes on macrophages. - CD4 helper T cell’s co-receptor molecule CD40L recognises co-receptor molecule CD40 expressed by macrophage/ APC.
List 5 mechanisms which are initiated in macrophages through the help of T helper 1 cells.	- Increase intracellular killing. - Increase production of oxygen radicals. - Increase costimulatory molecules to activate T cells. - Increase production of cytokines. - Recruit other macrophages.
Name 2 costimulatory molecules which activate T cells.	CD80 CD86
What is meant by ‘feedback communication’ by macrophages when they are carrying out their function?	- Macrophages engulf and digest bacteria. - The phagosomes ingested fuse with lysosomes – phagolysosomes. - Bacteria are degraded in phagolysosomes. - Peptides from the degradation are then presented on MHC Class II molecules to T helper 1 cells – this is feedback communication since this will trigger the activation of more macrophages, thus further degradation of bacteria.
What are the 3 reasons which support why dual recognition is essential between pathogenic cells, macrophages and CD4 T helper cells?	- So that the macrophage can engage with either the Fc receptor or the Pattern Recognition Receptors/ PRRs on pathogenic cells a.k.a. recognise antigen. - So that the CD4 T helper cell can recognise an antigenic peptide on surface of macrophage (MHC Class II complex and TCR + CD40 and CD40L co-receptors). THUS… for efficient adaptive macrophage function.
Which 2 types of T helper cells help B cells to produce antibodies?	Th1 and Th2 cells.
What are the 2 main functions of B cells?	Produce antibodies. Process and present antigens to CD4 T helper cells.
What 2 types of antibody do T helper 1 cells stimulate B cells to produce?	Th1 cells > B cells > IgG2 and IgG3
What 2 types of antibody do T helper 2 cells stimulate B cells to produce?	Th2 > B cells > IgG1 and IgE
Describe the 4 stages which B cells go through upon antigen recognition.	- Antigen recognition through B cell receptor on the cell surface. - Extracellular pathogens/ toxins taken up by endocytosis. - Proteins are broken down in endocytic vesicles. - Peptides are presented at the cells surface by MHC class II complexes to T helper cells.
Give 3 examples of diseases whereby the immune response is strongly B cell-dependent.	Polio Clostridium tetani Staphylococci
How do T helper cells activate B cells in order to stimulate their antibody production? (3)	- T helper cells recognise the antigenic peptide presented by B cells. - T helper cell’s TCR binds to the MHC Class II/ antigenic peptide complex, and with dual recognition, the co-receptor molecules CD40L on the T helper cell’s surface also recognises the co-receptor molecule CD40 on the surface of the B cell. - This binding initiates the release of cytokines, which activates the B cell.
Once the B cell is activated, what can the T helper cell then stimulate the B cell to do?	The T helper cell can tell the B cell which antibody isotype to switch to.
When B cells are activated and are producing antibodies, what other name are they given?	Antibody-producing plasma cells.
What 3 functions do the antibodies (produced by B cells) have?	Neutralise toxins. Opsonize pathogens. Activate complement.
What are the 3 main reasons why dual recognition is essential between CD4 helper T cells and B cells?	- So that the B cell’s B cell receptor can engage with an antigen. - So that the CD4 helper T cells can recognise an antigenic peptide on the surface of the B cell (MHC Class II complex and BCR, and CD40 and CD40L co-receptors). - THUS, for efficient adaptive B cell function (activation and production of antibodies).
What is the function of CD8 cytotoxic T cells?	The CD8 cytotoxic T cells kill cells infected by cytosolic pathogens (as well as many tumour cells) by recognising antigenic peptides processed and presented by MHC Class I complexes.
In what way are cytotoxic CD8 T cells similar to NK cells?	They have specialised lysosomes that contain cytotoxic proteins, otherwise known as perforin, granzymes and granulysin. Perforin forms pores in the cell membrane of infected host cell causing cell lysis. Granzymes enter the cells and stimulate apoptosis.
What happens to the cytotoxic granules within CD8 Cytotoxic T cells when they recognise a target cell (infected host cell)?	The cytotoxic granules move and become polarised. They are then released at the site of cell contact.
What are the 2 reasons which support why dual recognition is essential between CD8 cytotoxic T cells and host target infected cells presenting MHC Class I complexes?	The CD8 cytotoxic T cell has to recognise an antigenic peptide presented by MHC Class I on the surface of host-infected cells. THUS, for efficient CD8 cytotoxic T cell function.
What is meant by cell-mediated immunity?	Cell-mediated immunity is an immune response that does not involve antibodies, but rather involves the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen.
What is meant by humoral immunity?	Humoral immunity, also called the antibody-mediated immune system, is the aspect of immunity that is mediated by macromolecules (as opposed to cell-mediated immunity) found in extracellular fluids such as secreted antibodies, complement proteins and certain antimicrobial peptides.

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