immunology

Question 1

A significant human Gram-positive pathogenic bacterium.

	More than 90 different serotypes

	Causes acute sinusitis, otitis media, meningitis, septic arthritis, endocarditis, 			peritonitis, pericarditis, cellulitis … as well as pneumonia.

Part of the normal upper respiratory tract flora but can become pathogenic under the right conditions (e.g., immunosuppression).

—- competes with Haemophilus influenzae (a Gram negative bacterium that can also cause pneumonia and meningitis) by attacking it with hydrogen peroxide.

H. influenzae responds by signalling to our immune system to attack the ——.

Answer 1

Streptococcus pneumonia

Question 2

Clostridium tetani – characteristics

Answer 2

Gram-positive, spore-forming anaerobic bacterium.

						Spores: extremely hardy, resistant to heat and most antiseptics, 				widely distributed in manured soils, on human skin and in 								contaminated heroin.

C. tetani produces a potent biological toxin, tetanospasmin. When released in a wound it is absorbed into the circulation and reaches the ends of motor neurons all over the body, interfering with neurotransmitter release, and causing tetanus.

Characteristic features: risus sardonicus (a rigid smile),
trismus (commonly known as “lock-jaw”), and opisthotonus (rigid, arched back).
Fatal in ~40% of cases

A typical dose of tetanospasmin is too small to provoke an immune response.

Question 3

how is sleeping sickness spread?

Answer 3

African trypanosomiasis, caused by a protozoan carried by Tsetse flies.
They acquire a dense layer of glycoproteins that continually change, allowing the parasite to dodge an attack from the host’s immune system.

Question 4

what symptoms are caused by Trypanosoma brucei

Answer 4

General symptoms include:

Drowsiness, sleepiness (may be uncontrollable)
Insomnia at night
Anxiety, mood changes
Fever, headache, sweating
Swollen lymph nodes all over the body
Weakness
Without treatment, death may occur within 6 months from cardiac failure

Question 5

explain how recombination lead to different types of flu

Answer 5

the Spanish flu originated from birds when it crossed the species barrier. this first one occurred in the 1918.
recombination = asian ‘flu epidemic’ 1957
rec= Hong Kong ‘flu’ 1968
rec = still exists today

Question 6

what are some examples of altered and non self that the immune system has to recognise?

Answer 6

‘Non-self’: Bacteria cell wall structures, protein and peptide structures/ sequences from pathogens, yeast carbohydrates, pathogen DNA, viral antigens on host cells
‘altered self’ = malignant cells, apoptotic cells, oxidised proteins.

Question 7

tissue specific responses

Answer 7

skin - keratin , lungs - mucus with pulmonary surfactants
brain = innate only

Question 8

what responses are apropriate?

Answer 8

Genetic immune deficiency, such as a C3 deficiency, leads to repeated bacterial infections
C3 is a component of the innate complement system (see lecture 10)

Pathogens that target immune cells, such as HIV infection of T cells and its subsequent disease AIDS, result in immunodeficiency, and this can lead to widespread infection by opportunistic pathogens

Clinically-induced immunosuppression post-transplant increases vulnerability to viral infection

Autoimmunity results from impaired regulation of powerful immune responses (e.g. Multiple Sclerosis, Rheumatoid Arthritis)

Question 9

How do defensins lyse pathogens, but not our own epithelial surfaces?

Answer 9

They are much more active on membranes that do not contain cholesterol (our membranes contain cholesterol)
Relatively non-specific action, and so it is difficult for pathogens to acquire resistance

Question 10

How does the innate immune system recognise pathogens that pass through the epithelial layer as ‘non-self’?

Answer 10

The innate immune system recognises molecules (pathogen-associated or microbe-associated immunostimulants) that are common to many pathogens, but essentially absent in the host.

Question 11

complement activation targets pathogens for lysis

Question 12

list the classes of pamps:

Answer 12

N-formylmethionine (fMet) is used for bacterial translation initiation. Proteins containing fMet also attract neutrophils

Peptidoglycans from bacterial cell walls

Bacterial flagellae

Lipopolysaccharide (LPS) from Gram-negative bacteria

Mannans, glucans and chitin from fungi

‘CpG’ (5’-A/G p A/G p C p G p C/T p C/T-3’) motifs in bacterial or viral DNA

Question 13

explain what toll like receptors are and their function at killing pathogens

Answer 13

Toll is a Drosophila trans-membrane protein with a large extracellular domain with repeating motifs (leucine-rich repeats) that are versatile binding motifs for a variety of proteins.
Binding to pathogenic fungi sends a signal to the nucleus that results in expression of antifungal defensins.
Toll-like receptors have the same overall structure – and do very similar jobs

Question 14

how does gonoria evade the human immune system?

Answer 14

N. gonorrhoeae can utilize host-derived sialic acid to sialylate its LOS
Human cells also display sialylated glycoproteins, so in effect, N. gonorrhoeae can masquerade as us, evading the innate immune system

Question 15

‘granules’ =

Answer 15

dense membrane-bound lysosomal derivatives.
They fuse with the phagosome membrane and release their contents (lysozyme, acid hydrolases) in an attempt to digest the pathogen’s cell walls.
The granules also contain defensins, ⇒ destabilise the pathogen’s membranes.

Question 16

how do T cells get activated?

Answer 16

by dendritic cells in the lymphoid tissue.
DC present peptides to T cells
T cells recognise non self antigen –> activation, mitosis and clonal expansion of SPECIFIC T cells

Question 17

Why do APCs only present to T cells?

Answer 17

① Co-stimulatory molecules on APC ‘dock’ with T-cell specific co-stimulatory molecules
② Peptide is held in the groove of an APC presenting protein and is ‘scanned’ by the TCR
③ No recognition: no action. Cells undock.
Recognition: T cell activated.

Question 18

name and describe function of Different t cells

Answer 18

Regulatory /suppressor (inhibit helper T cells, cytotoxic T cells, dendritic cells) , Cytotoxic (kill infected host cells by - apoptosis), Helper (activate macrophages, dendritic cells, B cells, maintain cytotoxic T cell activity by secreting a variety of cytokines)

Question 19

How do cytotoxic T cells kill?

Answer 19

The TC cell recognises the antigens that were used to activate it on the target cell membrane, and so binds specifically to a target cell. The contact points form an immunological synapse.

Question 20

How are bacterial toxins and disseminated disease recognised?

Question 21

what is the main difference between B cells and T cells?

Answer 21

B cells recognise their antigens as soluble proteins

Question 22

what is the difference between resting B cells and activated B cells?

Answer 22

Resting B cell:
Has membrane-bound antibodies that constitute the B cell receptor
Effector B cell (plasma cell):
Massive increase in ER allows secretion of ~ 5000 antibodies per second

Question 23

what is the main advantage for a simple structure of antibodies?

Answer 23

If an antigen has 2+ identical antigenic determinants, antibodies can CROSS-LINK the antigens making: (2) small cyclic complexes or linear complexes, (3+) large 3-dimensional lattices, antibodies with different specificity can co-operate

Question 24

what is an advantage of antibodies having a flexible hinge region?

Answer 24

allows different spatial geometries of antigen binding = soluble antigens and viruses can be trapped in large cross-linked networks that often precipitate.

These large networks make it easier for phagocytes to engulf pathogens or soluble antigens, –> degraded and re-presented to T cells, amplifying the immune response

Question 25

how do different Immunoglobulins get selected?

Answer 25

There is ONE antibody H chain gene, with an unusual arrangement:

The Ig H chain gene encodes a variable (VH) domain and all the H chain constant regions, separated by non-coding introns.

Question 26

How can there be so many antibodies capable of recognising antigens that have never before been encountered?

Answer 26

variable domains that encode antigen specificity.
1. 3 antibody genes. There are two classes of light chains, which increases diversity. (Thus the same VH domain can be partnered with variable domains from two classes of light chain, increasing the repertoire of possible binding sites, allowing different antigens to be recognised.)
2. There are multiple gene segments encoding V domains that can be combined with C domains by somatic recombination