Immune Cells

Question 1

1. what is the purpose of innate responses? (3)
2. When does the innate response occur?
3. Describe 3 mechanical non-immunological barriers to infection
4. describe 4 chemical non-immunological barriers to infection

Answer 1

1. prevent pathogen establishment and multiplication
   provides protection from early death during the
   expansion phase
   helps instruct the nature of the acquired response
2. at the beginning of the infection and is maintained throughout
3. tight junctions and epithelial linings
   low pH of stomach
   fatty acids on skin
   antibacterial peptides

Question 2

1. how is the alternate complement pathway activated?
2. how is the lectin complement pathway activated?
3. how is the classical complement pathway activated
4. what enzyme do all 3 pathways act on? What is the function of this enzyme?
5. how does the complement cascade promote phagocytosis?
6. how does the complement cascade promote inflammation?
7. how does the complement cascade cause cell lysis?

Answer 2

1. by interaction with pathogen surface
2. by interaction with pathogen surface
3. presence of antigen-antibody complexes
4. c3 convertase. It catalyses the breakdown of C3 into C3a and C3b
5. C3b binds to the microbe surface, thus marking it for phagocytosis (opsonisation)
6. C3b splits C5 into C5a and C5b. Both C3a and C5a bind to mast cells, causing them to release histamine, which promotes inflammation (histamine causes an increase in vascular permeability, leading to increased fluid and cell inflitration - extravasation). Complement also provides a chemotactic signal.
7. C5b binds to C6, C7, C8 and C9, forming the membrane attack complex. The membrane attack complex inserts into the plasma membrane of the pathogen/infected cell, enabling the influx of water thus cell lysis

Question 3

1. what is opsonisation?
2. how does opsonisation promote phagocytosis?
3. How does opsonisation help tailor the adaptive response?
4. name an example of an opsonin

Answer 3

1. the process whereby particles are targeted for destruction by phagocytosis. The opsonin sticks to a particle, which enables them to be recognised by phagocytes
2. phagocytes possess opsonin receptors to recognise opsonins bound to the particle
3. opsonin receptors found on innate cells differ to those found on adaptive cells. Therefore the adaptive response can be targeted to a particular pathogen by the opsonin
4. C3b

Question 4

1. Describe the principles of phagocytosis
2. how is the phagosome involved in the adaptive response?
3. Describe 6 microbicidal mechanisms of phagocytes

Answer 4

1. attachment by pattern recognition receptors. formation of phagosome. granule fusion and killing. release of microbial products
2. microbial products are released following phagocytosis; these are then available for recognition by adaptive cells
3. acidification
   production of toxic, oxygen derived products
   production of toxic nitrogen oxides
   production of antimicrobial peptides
   production of enzymes such as lysozyme
   production of lactoferrin and B12 binding protein which compete with bacteria for nutrients

Question 5

What is the role of:

1. monocytes
2. macrophages
3. neutrophils
4. dendritic cells
5. B lymphocytes
6. Helper T cells
7. cytotoxic T cells
8. Natural Killer Cells

Answer 5

1. differentiate into tissue macrophages and neutrophils. have roles in phagocytosis, antigen presentation and cytokine production
2. reside in tissues. perform phagocytosis and antigen presentation
3. circulate in blood stream. migrate towards site of inflammation. undergo phagocytosis and degranulation to release antimicrobial substances. Also set extracellular traps
4. main antigen presenting cells of the immune system. Perform phagocytosis; present antigens along with a co-stimulatory signal to activate the adaptive immune response.
5. humoral immunity - produce antibodies. Differentiate into plasma (effector) and memory cells.
6. facilitate the activation of the immune response and stimulate differentiation and division of various effector cells
7. cell mediated immunity. target and kill infected cells
8. cells of both the innate and adaptive immune systems; release perforin and granzyme. play a major role in host-rejection and virally infected cells.

Question 6

Describe the histology of:

1. erythrocytes
2. platelets
3. neutrophils
4. eosinophils
5. basophils
6. monocytes
7. lymphocytes
8. mast cells

Answer 6

1. stain pink with a paler centre. most numerous cell (usually)
2. small fragments
3. multi-lobed nucleus. contain granules
4. bilobed nucleus. red stained granules
5. filled with fewer, larger granules
6. horse-shoe shaped nucleus
7. dense nucleus; no granules; very little cytoplasm
8. histological similarities to basophils; found in tissues rather than circulating in blood

Question 7

what is extravasation assisted by? (2)

Answer 7

1. DIAPEDESIS - neutrophils and endothelial cells in injured tissues express adhesion molecules that act to slow down circulating neutrophils. Once bound to the endothelium, neutrophils can squeeze through the gaps between adjacent endothelial cells
2. chemotaxis

Question 8

1. to which cells is MHC class I presentation restricted to?
2. on which cells are MHC class I molecules expressed?
3. what type of antigens to MHC class I molecules present?
4. to which cells is MHC class II presentation restricted to?
5. on which cells are MHC class II molecules expressed?
6. what type of antigens to MHC class II molecules present?

Answer 8

1. CD8+ cytotoxic T cells
2. all nucleated cells
3. look for altered self antigens and viral antigens, sampled from the cytoplasmic space
4. CD4+ helper T cells
5. antigen presenting cells
6. foreign material found in phagosomes/endosomes

Question 9

1. describe co-stimulation of T cell activation
2. what is the role of helper T cells?
3. what is the role of cytotoxic T cells and how do they do this?
4. what is required for B cell activation?
5. How does this occur?

Answer 9

1. an antigen specific signal is provided to the T cell receptor by MHC molecules. A second, co-stimulatory signal is antigen unspecific and provided by the interaction between co-stimulatory molecules on the APC and T cell
   e.g. CD28 on the T cell interacts with CD80 or CD86 on the membrane of the APC
2. activation of other immune cells, including cytotoxic T cells, B cells and phagocytes
3. kill cancer cells, virally infected cells or damaged cells.
   They release TNF-alpha and IFN gamma which have anti tumour and antimicrobial effects. They also release perforin and granzyme
4. physical interaction between B and T helper cell.
5. B cell binds antigen (via B cell receptor), which induces the B cell to engulf, process and present the antigen (via MHC class II). Antigen is recognised by Th2 cells. This induces the synthesis of CD40L on the Th2 cell which binds to CD40 on the B cell leading to co-stimulation.

Question 10

What is the role of the following:

1. Th1 cells
2. Th2 cells
3. Th17 cells
4. Treg cells

Answer 10

1. clearance of intracellular bacteria and viruses by activating macrophages and CD8 cells
2. clearance of extracellular parasites by activating basophils, mast cells and B cells
3. respond to extracellular bacteria and fungi by recruiting and activating neutrophils
4. suppressing inflammation and down-modulation of immune response.

Question 11

1. what is isotype class switching?
2. how is class switching accomplished?
3. what is somatic hypermutation?
4. How do we make antibodies of infinite specificity? (3)

Answer 11

1. a change in the type of antibody produced by B cells that is adapted for various locations in the body and the type of antigen
2. by cytokines produced during the innate response and by T cells.
3. mutation of the variable region of genes to produce different versions of the same specific antibody. These are then “tested” and the ones with the highest affinity for the receptor are encouraged to proliferate via affinity maturation.
4. germ line diversity - lots of genes encode different parts of antibodies
   somatic recombination - diversity from combinatorial diversity and junctional diversity
   somatic hypermutation

Question 12

Name 4 ways in which antibodies can kill (indirectly and directly) pathogens

Answer 12

1. mediating cellular responses via Fc receptors of effector cells such as phagocytes, mast cells and natural killer cells
2. neutralising microbes and/or their toxins
3. opsonisation
4. clearance of antigens.

Question 13

1. what type of epitopes to B cell receptors/antibodies recognise?
2. what type of epitopes do T cell receptors recognise?

Answer 13

1. conformational epitopes (tertiary structures)

2. linear epitopes (enzymatically digested out of antigens, produced by the innate response)

Question 14

1. What is passive immunity?
2. Give an example of passive immunity
3. What is active immunity?
4. Give an example of active immunity

Answer 14

1. the transfer of active immunity in the form of ready made antibodies
2. transfer of antibodies across placenta or in breast milk
3. the process of generating an adaptive immune response when exposed to an antigen
4. infection or vaccination.