Infection and immunity - Immunology

Question 1

Describe the mechanism of phagocytosis

Answer 1

1. Pathogen binds to receptor on phagocytic cell (neutrophils, macrophages, dendritic cells) membrane and is engulfed to form a phagosome
2. Phagosome fuses with phagocytic vacuoles with lysosomes to form a phagolysosome
3. Ingested particles within phagolysosome is destroyed by lysosomal enzymes and oxyen and nitrogen species

Question 2

Describe how pattern recognition receptors (PRRs) recognise microbe-associated molecular patterns (MAMPs) and damage associated-molecular patterns (DAMPs)

Answer 2

• PRRs are proteins capable of recognizing molecules frequently found in pathogens (PAMPs) also reffered to as microbe-associtaed molecular patterns (MAMPs). They also recognise molecules released by damaged cells (DAMPs)
• PAMPs/MAMPs are recognised by Toll-like receptor (PRR) which are found at the plasma membrane in phagosomes
• DAMPs are recognised by PRRs such as toll-like receptors. NOD-like receptors

Question 3

Describe the innate immune system’s barriers against infection

Answer 3

• Tight junctions in epithelial cells
• Mucosal surfaces trapsorganisms and dust. This is continuously moved by cilia (in the trachea of the lungs) away from yhe lungs
• Digestive enzymes epsecially lysozymes are secreted in sweat glands and tear ducts kills bacteria
• Acid environment in stomach and skin inhibits bacterial growth

Question 4

List the different cells of the innate system

Answer 4

• Dendritic cells
• Macrophages
• Mast cells
• Granulocytes e.g., neutrophils, eosinophils and basophils
• Natural killer cells

Question 5

Describe how dendritic cells respond to infection

Answer 5

Phagocytosis - ingestion and destruction of particles/microbes for recognition by immune cells

Question 6

Describe how macrophages respond to infection

Answer 6

They ingest particles/microbes via phagocytosis helped by opsonins (C3b) and destroy phagocytosed material using enzymes (lysozyme) in secondary granules (Oxygen-independent killing).

Question 7

Describe how mast cells respond to infection

Answer 7

• Actiavted by complement proteins 3a + C5a, tissue trauma and crosslinking of cell surface IgE by antigen
• Mast cells contain pre-formed histamine granules which can be quickly released causing vasodiation and blood to leak
• Mast cells also cause a delayed response by producing leukotrienes

Question 8

Describe how granulocytes specifically neutrophils, eosinophils and basophils respond to infection

Answer 8

Neutrophils - ingest microbes with the help of opsinins (LgG and C3b) which are then destroyed by lysozomal enzymes and oxygen and nitrogen species

Eosinophils and basophils - attach to parasites coated by IgE molecule and start degranulation and release toxic contents (histamine, proteases)

Question 9

Describe how natural cell killers repond to infection

Answer 9

• MHC on host cells inhibit NK cells while viruses down regulate MHC and the NK cell is activated
• NK cells have granules that contain toxic enzymes which are released to kill cells infected with viruses and some cancer

Question 10

List the cell mediators that are involved chronic inflammation

Answer 10

• Plasma cells
• B lymphocytes
• T lymphocytes

Question 11

Describe the mechanism of B cell maturation, activation and differentiation

Answer 11

B cell maturation

• Produced in bone marrow + undergo immunoglobulin gene rearrangement to become naïve B-cells, expressing IgM and IgD

B cell activation

• If the antigen is T independent , then it can directly bind to B cells to activate it
• T-dependant antigens (most antigens) are presented to helper T-lymphocytes to activate B lymphocytes. This occurs by:

1. Antigen binds to IgM or IgD on B-cells, causing maturation of IgM or IgD-secreting plasma cells
2. The CD40 receptor on the B cell then binds CD40 ligand on helper T-cells which provides the second activation signal

B cell diferentiation

• B cells differentiate into memory B cells and effector B cells aka as plasma cells (which secrete antibodies). The B cells undergo clonal expansion to produce more copies of B cells that share affinity with and specificity of the same antigen.

Question 12

Describe the theory of clonal selection

Answer 12

A hypothesis which states that an individual lymphocyte (specifically, a B cell) expresses receptors specific to the distinct antigen, determined before the antibody ever encounters the antigen.

Question 13

Describe the concept of immunoglobulin gene rearrangement (VDJ recombinatination)

Answer 13

• Immunoglobulin gene rearrangememnt (VDJ recombination) have many repeated sequences
• The repeated sequences code for variable region, diversity region and joining region
• Gene rearrangement allows one of the repeated sequences in each region to be used to make proteins
• Gene rearrangememnt provides divesity in the variable region. The constant (Fc) is constant
• T-cell receptor genes also rearrange to create diversity - Gene rearrangement only takes place in B and T-cells
• VDJ recombination provides antibody and T-cell diversity
• Gene rearrangeemnt is the key feature of adapive immune - it allows you to acquire an immune respone and allows your immune system to adapt

Question 14

Describe the structure of antibodies

Answer 14

• Y shaped
• Each antibody has two identical light and two identical heavy chains (4 total peptides)
• Each light chain consists of 2 domains - 1 variable region and 1 constant region domain
• Each heavy chain has 1 variable region domain and either 3/4constant region domains
• The chains are held together by disulphide bridges
• Light chains are classified as either kappa or lambda, while the heavy chains can be IgG, IgA, IgM, IgD, or IgE isotypes.

Question 15

a) Draw and label the structure of a generic antibody
b) Which part of the antibody binds to antigens?
c) What bonds are the chains held by?

Answer 15

b) Variable region
c) Disulphide bridges

Question 16

Describe the structure of T cell receptors

Answer 16

• Made up of two polypeptide chains (alpha and beta chains) that together compose one variable (antigen binding) region and constant region
• The structure is maintained by a disulphide bridges linking the two chains together.

Question 17

Draw the structure of a generic T cell receptor

Answer 17

Question 18

Where does the constant region of the antibody bind to?

Answer 18

Binds to receptors within the immune system called Fc receptors toactivate immune defences

Question 19

What are the two types of immunological recognition

Answer 19

1. Soluble: humoral immunity
2. Cell-mediated immunity

Question 20

Describe the cellular and soluble components of the adaptive immune response

Answer 20

Soluble: humoral imunity

• B-cell responses are soluble and do not sediment and do not need cells
• Immunoglobulins e.g., IgG, IgM, IgA, IgD and IgE

Cell-mediated immunity

• T-cell responsed sediment with cellular fraction
• Naïve T cells, helper T cells, killer T cells, and macrophages

Question 21

Describe the process to form antibody isotypes

Answer 21

1. Once VDJ recombination is complete the B -cell can get signals to undergo a 2nd recombination (antibody class switching)
2. Different antibody types have different coding for the constant regions – the Greek letters correspond to M, G, A and E
3. Signals from the B-cell receptor and cytokines can trigger the removal of the membrane anchor and add the mu region to generate IgM (seen in primary immune response – low affinity, broad specificity)
4. A 2nd class switch can replace the membrane anchor w/ the gamma sequence to generate secreted IgG (seen in secondary immune response – high affinity, narrow specificity). Further switching can generate IgA and IgE
5. The constant domains can be switched during recombination to generate isotypes using the same variable regions
6. Isotype switching is controlled by cytokine secretion from T helper cells

Question 22

Describe the function of IgG

Answer 22

• Major antibody that is secreted into the blood supply and removes pathogens from the blood and tissues.
• Subclasses 1,2 and 3 activate classical complement pathway

Question 23

Describe the function of IgA

Answer 23

• IgA is made by B-cells in response to infection of mucosal surfaces
• IgA binds an IgA receptor and is secreted across epithelial cells to protect mucosal surfaces. The secreted IgA can bind pathogens that have not yet entered the body.

Question 24

Describe the function of IgE

Answer 24

• IgE is most important to defend against parasites that try to live in mucosal surfaces or the skin.
• IgE is secreted into the blood supply and binds IgE receptors on mast cells and eosinophils
• Binding of IgE to IgE receptors result in release of inflammatory mediators such as histamine
• IgE is also the cause of allergies

Question 25

Describe the function of IgM

Answer 25

• Acts as an antigen receptor on B cells
• Activates classical complement pathway

Question 26

Describe the function of IgD

Answer 26

Acts as an antigen receptor on B cells

Question 27

IgE can cause allergies. Describe how this occurs.

Answer 27

If the body makes an IgE that recognises an allergen it will bind the allergen and trigger histamine release from mast cells

Question 28

Discuss the activation and function of helper T cells and how they contribute to the adaptive immune response

Answer 28

• Extracellular antigens are ingested and processed by APCs and presented on MHC II on the cell surface
• B7 on the APC membrane is the molecule which provides the second activation signal for T helper cells
• The T-cell receptor complex binds to antigen on MHC II and CD28 binds to B7, providing the second signal
• T-helper cell 1 – secrete interferon gamma to recruit macrophages
• T-helper cell 2 – involved in allergy in that they recruit eosinophils and cause B-lymphocytes to produce lgE

Question 29

Describe the role of helper T cell subtypes 1 and 2

Answer 29

T-helper cell 1 – secrete interferon gamma to recruit macrophages

T-helper cell 2 – involved in allergy in that they recruit eosinophils and cause B-lymphocytes to produce lgE

Question 30

Discuss the activation and function of cytotoxic T cells and how they contribute to the adaptive immune response

Answer 30

• Intracellular antigens (proteins derived from proteins in the cytoplasm) are presented on MHC class I (which are expressed by all nucleated cells and platelets)
• The cytotoxic T-cell receptor with its CD8 co-receptor binds to MHC I
• IL-2 produced by CD4+ T helper 1 cells provides the second activation signal
• Kill occurs by:

Secretion of perforin and granzymes. Perforin creates pores and granzymes enter and destroy target cell

By binding FAS ligand to FAS on a target cell. The cell is attacked by apoptosis or programmed cell death

Question 31

What do T cells recognise

Answer 31

T-cells do not recognise antigens directly. They recognise MHC protein on infected cells.

Question 32

Describe the origin, developmey, maturation and differentiation of T cells

Answer 32

• T cells originate in bone marrow
• Progenitor T-cells enter thymus where adhesion molecules on medullary epithelial cells stimulate
• T cells undergo go DVJ rearrangement in thymus
• Thymic medulla cells use MHC to educate T-cells by presenting self-proteins (peptides) to immature T-cells
• If immature T-cells have weak binding for MHC self-peptide they survive - known as positive selection and go to lymph nodes
• If strong binding, they under go apoptosis die - known as negative tolerance

Question 33

What are effector cells?

Answer 33

Relatively short-lived activated cells that defend the body in an immune response

Question 34

What are the effector cells of the humoral response and describe their role

Answer 34

Effector B cells are called plasma cells and they secrete antibodies

Question 35

What are the effector cells of the cell-mediated response and describe their role

Answer 35

Effector T cells fall into three functional classes that detect peptide antigens derived from different types of pathogen.

They help produce Helper T cells subtype 1 and 2 and cytotoxic T cells