Week 9 - Immune System

Question 1

What is the role of the lymphatic system?

Answer 1

1. Serves two roles:
   a) Drain fluid from cells and tissues back to the bloodstream
   b) Fight infection by distributing white blood cells

Question 2

Describe the innate immune system; Physical barriers

Answer 2

1. Barriers include the skin and mucous membranes of the respiratory, urinary, and reproductive tracts
2. Mucus traps and allows for the removal of microbes
3. Many body fluids including saliva, mucus, and tears are hostile to microbes
4. The low pH of skin and the digestive system prevents growth of microbes

Question 3

Describe the innate immune system; Cells

Answer 3

1. Macrophage:
   a) In tissues - originates from monocyte
   b) Roles in phagocytosis and intracellular killing, cytokine production, antigen presentation, and NET formation
   c) Phagocytosis is initiated when phagocyte receptors recognise an appropriate molecule that indicates the presence of a foreign cell or molecule
2. Mast cell:
   a) In tissues
   b) Roles in histamine production, production of chemotactic factors, cytokine production
3. Dendritic cell:
   a) In both lymph nodes (mature) and tissues (immature)
   b) Roles in antigen processing and presentation to T-cells, and cytokine production and T-cell polarisation
4. Neutrophil:
   a) Roles in phagocytosis and intracellular killing, degranulation and extracellular killing, NET formation, cytokine production
5. Eosinophil:
   a) Roles in parasite attack, degranulation and extracellular killing, histamine production, and cytokine production
6. Basophil:
   a) Roles in parasite attack, degranulation and extracellular killing, histamine production, and cytokine production
7. Natural killer cell:
   a) Large, granular, non-T, non-B lymphocytes
   b) Kill virus-infected cells and some tumours
   c) Have a large number of invariant activating and inhibitory receptors but do not rearrange immunoglobulin or T-cell receptor genes
   d) Important in innate immunity to viruses and other intracellular pathogens, and antibody dependent cell mediated cytotoxicity
   e) Works by antibody binding to antigens on the surface of target cells; receptors on NK cells recognise bound antibody; cross-linking of receptors signals the NK cell to kill the target cell; target cell dies by apoptosis

Question 4

How are pathogens recognised?

Answer 4

1. Pathogen-Associated Molecular Patterns (PAMPs) recognised by pattern recognition receptors
2. PAMPs are characterised by:
   a) Their expression on a large number of pathogens
   b) Their stability within the pathogen and the fact that they are essential for the survival of the pathogen
   c) The absence of PAMPs on host tissue, which avoids damage to host cells
3. PAMP-PRR engagement activates phagocytes
   a) Binding of PAMPs on microbial surfaces by PRRs on the surfaces of phagocytes activates the phagocytes to ingest and degrade the microbes

Question 5

Describe the innate immune system; chemical messengers

Answer 5

1. Interferons
   a) Chemical messengers that coordinate the defences against viral infections
2. In addition to the actions of whole cells, the innate immune system employs soluble molecules as weaponry for protection from;
   a) Viral infection, for lytic destruction of microbes
   b) For increasing the susceptibility of microbes to ingestion by phagocytic cells
3. IFN-alpha and IFN-beta are rapidly produced within 5 minutes, by cells when viral PAMPs interact with certain PRRs

Question 6

Describe the innate immune system; complement systems

Answer 6

1. A system of circulating proteins that assist antibodies in the destruction of pathogens
2. When stimulates by one of several triggers, proteases in the system cleave specific proteins to release cytokines and initiate an amplifying of further cleavages
3. Activation can occur spontaneously on certain pathogens or by antibody binding to the pathogen
4. The pathogen becomes coats with complement proteins that facilitate pathogen removal by phagocytosis and can also kill certain pathogens directly

Question 7

Describe the innate immune system; inflammation and fever

Answer 7

1. Inflammation is a localised, tissue-level response that tends to limit the spread of an injury or infection
2. Fever is an elevation of body temperature that accelerates tissue metabolism and body defences
3. These are recruiting necessary cells to combat issue of concern

Question 8

What differentiates the adaptive immune response with the innate immune response?

Answer 8

1. Tolerance
   a) The acquired inability to make an adaptive immune response to one’s own antigens
2. Specificity:
   a) The adaptive immune response is unable to recognise PAMPs
   b) It is much more specific and recognises certain antigens and epitopes
3. Memory
   a) Subsequent exposures to the same antigen result in rapid production of large quantities of antigen-reactive T cells or antibodies
4. Cell proliferation:
   a) Cells will not proliferate unless presented with an antigen (MHC) (only some cells are able to present antigen to the cells of the adaptive immune system which include dendritic cells, macrophages, B cells)

Question 9

How do cells proliferate in adaptive immune system?

Answer 9

1. The binding of a mature lymphocyte to an antigen induces the lymphocyte to divide rapidly into either short-lived effector cells or long-lived memory cells
2. The first exposure to a specific antigen represents the primary immune response
   a) During this time, effector B cells called plasma cells are generated and T cells are activated to their effector forms
3. The second exposure to a specific antigen is the secondary immune response
   a) During this time, memory cells facilitate a faster, more efficient response

Question 10

What is the cell-mediated immune response?

Answer 10

1. Multipotent stem cells found in bone marrow form T-cell precursor
2. T-cell precursor migrates to thymus gland where it converts to either cytotoxic T cell (CD8) or Helper T cells (CD4)
3. These T cells then bind to MHC to remove antigen
   a) CD4 binds MHC II
   b) CD8 binds MHC I
4. Once T cell is bound, it becomes activated
   a) In CD4 cells, this indicates the presence of pathogens, toxins, or foreign protein
   b) In CD8 cells, this indicates that the cell is infected or abnormal
5. CD4 cells then convert to either Helper T cells or Memory T cells whilst CD8 cells convert to Cytotoxic T cells, Memory T cells, or Suppressor T cells

Question 11

What do CD4 Helper T cells do?

Answer 11

1. Secrete cytokines which help stimulate B cells to make antibodies in response to antigenic challenge
   a) TH cells are required for the activation of B-cells and CTLs and can skew the resulting immune response

Question 12

What is the humeral immune response?

Answer 12

1. Humoral immunity is due to antibodies and can be transferred to unimmunised recipients by the transfer of serum containing specific antibodies
2. Antibodies are produced by B-cells in response to infection or immunisation
   a) B-lymphocytes develop in bone marrow from progenitor cells, they have a B cell receptor (BCR) which consists of a membrane bound immunoglobulin (Ig)
   b) Each B cell is specific for a single Ag, due to random rearrangements of the variable regions of the Ig genes, allowing the human body to possess a vast repertoire of different BCRs

Question 13

How are antibodies produced?

Answer 13

1. Production begins with antigen exposure and culminates in the production and secretion of an antigen-specific antibody
2. Antigen-stimulated B cells multiply and differentiate to form antibody-secreting plasma cells and memory cells (primary antibody response)
3. Memory B cells generated may live for years and quickly transform into antibody-secreting cells (secondary antibody response)

Question 14

What are the Major Histocompatibility Complex?

Answer 14

1. MHC molecules are also called human leukocyte antigens (HLAs) in humans
2. MHC Class 1 are found on all nucleated cells
   a) They present internal antigen to CD8+T cells
   b) Cytoplasmic antigen can originate from viral proteins or cancer proteins
   c) The cell is then targeted for destruction by T cells
   d) MHC I class proteins are the major antigen barriers for tissue transplantation
3. MHC Class II proteins are found on professional antigen-presenting cells, such as dendritic cells, macrophages, and B cells
   a) Present the internalised antigen to CD4+T cells
   b) Activate Helper T cells
   c) Receive T cell help

Question 15

Describe immunoglobulin - Ab/BCR:

Answer 15

1. Antibodies do not interact with an entire antigen, but only with a distinct portion of the molecule called an antigenic determinant or epitope
   a) Because antigens need to be associated with MHC to be recognised by T cell receptors, only short peptide sequences are recognised by TCRs
2. B cells have approximately identical 100, 000 B cell receptors on each cell
   a) These BCRs encounter antigen and internalise it
   b) They may present the antigen to helper T cells on MHC molecules
   c) With T cell help, they proliferate and differentiate into plasma cells and memory cells, which provide long term protection

Question 16

Describe Ab diversity:

Answer 16

1. Variable domains of different antibodies are different from one another, especially in complementarity-determining regions
2. The antigen-binding site of an antibody is large enough to accommodate the binding of an epitope with both the heavy and light chain variable regions
3. Different antibodies bind their epitopes with different strengths, called binding affinities
4. Ability to produce almost limitless antibody diversity is due to:
   a) Somatic recombination
   b) Random heavy and light chain reassortment
   c) Coding for joint diversity
   d) Hypermutation

Question 17

What is the genetic organisation of the immunoglobulin molecules?

Answer 17

1. The encoding each immunoglobulin is constructed from several immunoglobulin gene segments
2. Once one antibody rearrangement is successful, the process stops
   a) This causes each B cell to rearrange and express only one antibody even though B cells are diploid and could potentially express two different alleles
3. Antibody diversity is exacerbated in B cells by somatic hypermutation which leads to small changes in variable regions
   a) Somatic hypermutation causes changes in binding affinity that, when combined with decreasing antigen concentration, cause affinity maturation, or the strengthening of antibody binding as the immune response progresses

Question 18

Describe T cell receptor diversity:

Answer 18

1. MHC proteins expressed on the cell surface reflect the composition of the proteins inside the cell
   a) Cells that have ingested foreign proteins or pathogens and cells infected with a virus produce peptides that interact with MHC proteins
   b) TCRs of a given T cell bind only to MHC molecules that have foreign antigens embedded in the MHC structure
   c) T cells do not interact with a foreign antigen unless it is presented in the context of an MHC protein
2. TCRs bind both self MHC and foreign peptides
   a) TCRs and MHCs bind directly to peptide antigen
   b) The CDR3 regions of the alpha and beta chains bind to the epitope, whereas the CDR1 and CDR2 regions bind to the MHC protein
3. TCR diversity is generated by a variety of genetic mechanisms including:
   a) Somatic recombination
   b) Random chain reassortment
   c) Coding for joint diversity

Question 19

Describe the two molecular signals for B and T cell activation:

Answer 19

1. First signal is interaction with antigen through immunoglobulins
2. Second signal is necessary for them to respond to antigens and involves several molecules
   a) Interaction between B cell CD40 protein and CD40L on the T cell causes release of cytokine
   b) Cytokine IL-4 stimulates antibody production
3. T cells not yet exposed to antigen are naïve or uncommitted T cells
   a) Must be activated by an APC to become competent effector cells
4. B cell activation is initiated by interaction between antigen and surface immunoglobulin

Question 20

Describe cytokines and chemokines:

Answer 20

1. Intracellular communication in immune system occurs via cytokine
   a) Regulate cellular functions and activate various cell types
   b) Cytokines produced by lymphocytes are called lymphokines or interleukins (ILs)
   c) Interferons (IFNs) and tumour necrosis factors (TNFs) act on cells other than B and T lymphocytes
2. Chemokines are a small group of proteins that attract phagocytes and T lymphocytes
   a) Produced by macrophages, lymphocytes, and other cells in response to bacterial products, viruses, or other agents that cause cell damage

Question 21

What are immunoassays?

Answer 21

1. Clinicians often identify an infection by measuring the patient’s antibody levels
2. Types of tests performed are Agglutination and ELISAs
   a) Skin testing is also used for determining exposure to a pathogen
3. Serological reactions are used for many diagnostic immunology tests and often use monoclonal antibodies
   a) Monoclonal antibodies are produced by isolating single clones of B cells that are fused with cancer cells to make immortalised cell lines that produce a single type of antibody

Question 22

What is precipitation, agglutination, and immunofluorescence?

Answer 22

1. Precipitation:
   a) Precipitation is the interaction of a soluble antibody and soluble antigen to form an insoluble complex
   b) The insoluble complex only occurs when antigen and antibody are in equivalent concentrations
2. Agglutination:
   a) The visible clumping of a particular antigen when mixed with antibodies specific for the particulate antigens
   b) Used to identify blood group antigens and many pathogens and pathogen products
   c) Types include direct agglutination and passive agglutination
3. Immunofluorescence:
   a) Antibodies that are chemically modified with fluorescent dyes to help detect antigens on intact cells
   b) Two common fluorescent dyes are rhodamine B (red) and fluorescein isothiocyanate (yellow-green)

Question 23

What are enzyme immunoassays (EIA), rapid tests, and enzyme-linked immunosorbent assays (ELISA)?

Answer 23

1. EIAs are a very sensitive immunological assay
   a) EIAs employ covalently bonded enzymes attached to antibody molecules
   b) Both allow detection of antigen-antibody complexes
2. Four types of EIA:
   a) Direct EIA - detection of antigen
   b) Indirect EIA - detection of antigen
   c) Sandwich EIA - detection of antibody
   d) Combination EIA - combination of direct EIA and sandwich EIA
3. Rapid tests are tests in which reagents are absorbed to support material
   a) Body fluid is applied to the support matrix; matrix contains a soluble antigen conjugated to a coloured molecule (chromophore); matrix also contains a line of fixed antigen; antibodies bind to antigens; colour forms when concentration of chromophore gets high enough

Question 24

What are types of Nucleic Acid-Based Clinical Assay?

Answer 24

1. Nucleic acid hybridisation
   a) Hybridisation methods identify specific pathogens in patient samples by using unique nucleic acid probes to detect pathogen DNA
2. Quantitative and reverse transcription PCR
   a) Presence of amplified gene segment confirms presence of pathogen
   b) Reverse transcriptase PCR uses pathogen-specific RNA to make cDNA
   c) Quantitative real-time PCR uses fluorescently labelled PCR products and produces almost immediate results