Adaptive immune system I

Question 1

What are the 2 types of adaptive immune response?

Answer 1

• Cell mediated
• Humoral

Question 2

Briefly describe the innate response to new infection and why it’s important

Answer 2

• Response to new infection fast
• Acts on pre-determined non-self signals
• Sometimes can be primed/trained for intense reactivation (innate memory)

Question 3

What are the components of the cell mediated innate response?

Answer 3

• Phagocytes
• Natural killer cells (NK cells)
• T cells

Question 4

What are the components of the humoral response?

Answer 4

• Complement and pentraxins (CRP)
• Pattern receptors (soluble TLR- toll-like receptors, makes response quick)
• Enzymes (lysozyme)
• Cytokines releasing antimicrobials
• Binding proteins (Lactoferrin)

Question 5

Briefly describe the adaptive response to new infections

Answer 5

• Slow
• Selects for specific signals and generates memory

Question 6

Where are T and B cells made?

Answer 6

• Bone marrow with a randomly assigned antigen-binding specificity
• T and B cells can have the same specificity

Question 7

What cells and molecules are involved in the innate immune response?

Answer 7

• Dendritic cell
• Mast cell
• Macrophage
• NK cell
• Complement protein (mark pathogens to be destroyed)
• Neutrophil - granulocyte
• Eosinophil - granulocyte
• Basophil - granulocyte

Question 8

What cells and molecules are involved in the adaptive response?

Answer 8

• B cell
• Antibodies
• CD4+ T cell (T helper cell)
• CD8+ T cell (T cytotoxic cell)

Question 9

Where are T lymphocytes developed?

What happens to them there?

Answer 9

Migrate to Thymus gland, become CD8+, CD4+ or are destroyed if strongly recognise self antigens (central tolerance)

Question 10

Where are B lymphocytes developed?

Answer 10

• Bone marrow
• Developed and matured in bone marrow to express a single epitope antibody used as a receptor to bind to an antigen

Question 11

What is T cell priming?

Answer 11

The activation and clonal expansion of a naive T cell on initial encounter with antigen on the surface of an antigen-presenting cell

Question 12

Describe the endogenous pathway of T cell priming

Answer 12

• Endogenous antigen pathway leads to cytotoxic (CD8) T cell priming
• Antigen binds to APCs
• These cells are infected by the virus
• Viral proteins in the cytoplasm are detected and processed
• Viral antigens presented with MHC class I molecule on cell surface
• CD8+ cell recognises antigen, becomes cytotoxic, begins to make cytokines
• Cytotoxic T cell (CTL) proliferates making memory cells, and CTL cells looking for cells with presented antigen
• Infected cell destroyed by cytotoxic cell

Question 13

Describe the exogenous pathway of T cell priming

Answer 13

• Exogenous pathway leads to T helper cell priming
• Antigen (pathogen) engulfed by dendritic cell or macrophage via phagocytosis
• Antigen processed into small peptides
• Antigen presented with MHC class II molecule on cell surface
• CD4 T helper cell recognises presented antigen
• CD4 Th cell becomes primed and can help with either B cell activation or macrophage activation

Question 14

Describe antibody-antigen interaction

Answer 14

• Non covalent interactions
• Electrostatic, hydrophobic, van der Waals, Hydrogen bonds
• Depends on antibody binding site being exactly complementary sterically and chemically, with a site on the surface of the antigen
• A single antigen can have many possible binding sites (epitopes)

Question 15

Describe the structure of antibodies

Answer 15

• Immunoglobulin + glycoprotein
• 2 identical antigen binding sites
• ‘Y’ shaped
• A hinge ‘H” region - flexible space between binding sites
• Protease cleavage generates large fragments called Fab (variable region, antigen binding) and Fc (constant region, crystallisable)
• Fab region - At tips of Y, bind to specific antigens, have unique sequences
• Fc region - Located at base of Y, regions relatively consistent in sequence within antibody class, bind to immune cells and activate complement
• 4 polypeptide chains held together by non-covalent interactions by disulphide crosslinks between cysteine
• 2 identical Heavy chains
• 2 light chains
• Carbohydrates help assembly and binding to cells
• Antigen binding sites - The specific portion of the variable region that binds to a particular antigen

Question 16

What is the function of constant regions?

Answer 16

• Fc constant region allows binding of phagocytes to receptors of the antibody, activates complement

Question 17

What is complement?

Answer 17

System of plasma proteins activated directly by pathogens or indirectly by pathogen-bound antibody

They interact with pathogens and mark them so that phagocytes are able to detect and destroy them

Question 18

What is the function of the variable region?

Answer 18

• Fab variable region allows for antigen binding, contributes to antigen-binding site

Question 19

Describe the B cell activation pathway that is independent of T cells

Answer 19

• B cell receptors bind to antigen on pathogens
• Activation initiates proliferation with some cells being memory cells and other cells being committed to antibody production
• Activated B cells convert to plasma cells and begin making antibody
• This pathway is restricted to specific antigens (will always make only 1 type of antibody)
• Can lead to problems such as toxic shock syndrome (too much antibody)

Question 20

Describe the B cell activation pathway that is dependent on T cells

Answer 20

• B and Th cell interact, this activates the B cell
• Activation initiates B cell proliferation with some cells being memory cells, others being committed to antibody production
• Antibody production required co-stimulation with a Th cell that was already screened against self, hence avoided autoimmune response

Question 21

Define epitope

Answer 21

• A single antigen that has multiple binding sites

Question 22

Why is the immune system classed as polyclonal?

Answer 22

• More than 1 clone of B cells is generated
• More than one immunoglobulin is synthesised
  This is because:
• Multiple antigens on organism
• Multiple epitopes on each antigen
• More than one immunoglobulin may recognise the same epitope

Question 23

How do antibodies fight infection?

Answer 23

• By coating and neutralising a pathogen- if a virus is coated with antibody, it can’t bind to its receptors on the cell surface
• By activating complement - which can then form holes in a bacterial cell membrane, activates classical pathway
• By opsonisation - phagocytes have Fc receptors on their cell membrane, bind to pathogens coated with antibody and phagocytose them

Question 24

Describe the 2 structures of the IgM antibody

Answer 24

Structure 1: Membrane bound
- Monomer of basic subunit B cell receptor
- Extra heavy chain domain that is membrane bound in the B cell

Structure 2: Secreted
- Pentamer of basic sub=unit in plasma (secreted + highly antigenic - many antigens)
- Contains a J chain - a polypeptide involved in pentamer polymerisation

Question 25

What is the order of Ig production?

Answer 25

IgM - first antibody class made IgG - second antibody class made

Question 26

What is the function of IgG?

Answer 26

- Major class overall (75% of Ig) - Major class made by secondary responses - Only antibody class able to cross placenta and protect the developing foetus - Good at activating complement via classical pathway (removing the pathogen) - Acts as opsonin inducing phagocytosis - Fc region recognised by 'Fc receptors' on surface of immune cells, e.g. neutrophils and macrophages - Can be present for long periods in serum, so may indicate past exposure, not current infection

Question 27

What is the function of IgM?

Answer 27

- Presence indicates a recent primary response to that antigen - Implies a current primary infection - Activates complement via classical pathway (due to pentameric structure) - Higher valency of pentameter increases overall affinity (by binding higher number of epitopes) - Binds to immune cells via Fc receptor (ie, inducing phagocytosis)

Question 28

What is the primary response?

Answer 28

- Body's first response to unfamiliar infection - Slow, specific response - Produces lasting memory cells

Question 29

What is the process of isotope switching?

Answer 29

- Biological mechanism that changes a B cell's production of an immunoglobulin from one type to another

Question 30

What is the secondary response?

Answer 30

When a pathogen that has already infected the body before reinfects the body Much faster and stronger response due to memory cells

Question 31

What is the function of IgA? Which one is serum IgA and which is secretory IgA?

Answer 31

- 2 forms IgA1, IgA2 (differ in constant regions) - IgA1 is predominant in serum - Plays a role in activating the complement system and can also bind to and neutralize pathogens. - IgA2 is predominant in secretions- Primarily functions to neutralize pathogens and toxins in mucosal secretions, preventing them from entering the body through the mucosal surfaces. SIgA's dimeric structure allows it to bind to multiple antigens simultaneously, enhancing its ability to neutralize pathogens. - Monomer - This is Serum IgA - Most abundant class in external secretions (milk, sweat, tears, saliva, gut fluids etc) - Serves as opsonin (eosinophils, neutrophils, some macrophages) - Main immunoglobulin in mucosal sites; sometimes occurs as dimer - This is secretory IgA First line protection at external surfaces: - Initiates localised mucosal response different from more general circulating immune response - Neutralises pathogens, prevents binding to cell surface receptors - Secretory components protects IgA from degradation, hence it can work in harsh environments (eg. GI tract)

Question 32

What is the function of the IgE antibodies? Are they normally in high or low concentration?

Answer 32

Harmful function in allergies: - Binds to specific Fc receptor on mast cells and basophils releasing histamine Useful function is response to parasitic worms - Release chemicals from mast cells - Activates eosinophils (via Fc receptor binding) Normally low concentration in circulation - Raised in allergic patients - Raised in infections with large parasites - Over response can cause anaphylactic shock