TOPIC Q: Infectious Diseases

Question 1

What is the structure and function of a granulocyte?

Answer 1

Structure: Contains granules in the cytoplasm
Also known as polymorphonuclear leukocytes due to irregularly shaped nuclei.
Function: Circulates in the bloodstream, involved in cellular innate defences during innate immunity. Engulf pathogens via phagocytosis, pathogen is digested by hydrolytic enzymes upon fusion of phagocytic vesicle.
Neutrophils are one of the most important phagocyte in innate immunity, they are the most numerous WBC in blood, and are able to release antibacterial proteins stored in their cytoplasmic granules that kill surrounding microorganisms.

Question 2

What is the structure and function of antigen-presenting cells?

Answer 2

S: Carry the major histocompability complex molecule which is a membrane glycoprotein on the cell surface.
F:
APCs engulf pathogens through phagocytosis duringh innate immunity.
Main role is not pathogen clearance but to activate the adaptive immune response.
APCs digest the pathogenic proteins into peptides.
APCs present peptides on MHC complexes to T lymphocytes to activate adaptive immunity.
Antigen is any substance recognised by the B or T lymphocytes to activate adaptive immunity.
An antigen is any substance that is recognised by the B ot T lymphocyte of the adaptive immune system.

Question 3

What are the two types of APCs?

Answer 3

Macrophages reside in tissues and are the mature form of monocytes. Monocytes leave the bone marrow and circulate in the blood, continually migrating into tissues where they differentiated into macrophages.
Dendritic cells mostly reside in tissues and they are the most efficient at antigen presentations.

Question 4

What are the structure and function of lymphocytes?

Answer 4

S: Contains a large nucleus with a little amount of cytoplasm.
F: Non-antigen specific lymphocytes- Natural Killer Cells
NK cells recognise and kill abnormal cells such as tumour cells
They are not specific for a particular antigen and are involved in innate immunity.

Question 5

What are the different kinds of B and T lymphocytes?

Answer 5

B lymphocytes are produced in the bone marrow and they also mature there.
T lymphocytes are produced in the bone marrow but mature in the thymus.
Upon maturation, both B and T lymphocytes enter the bloodstream as naive lymphocytes where they circulate between the blood and the lymph.
CD4+ T lymphocytes which cell surface CD4 protein marker.
CD8+ T lymphocytes which have CD8 protein marker.
Each naive B and T lymphocytes have antigen receptor on their cell surface, which are specific for a particular anitgen.
Naive lymphocytes are lymphocytes that have not yet been activated by antigens.
Once naive lymphocytes have met their antigen, they become activated and further differentiated into fully functional lymphocytes aka effector lymphocytes.

Question 6

What is innate immunity?

Answer 6

Innate immunity is a set of non-specific that is active immediately upon infection and is the same regardless of whether the pathogen has been encountered before. Innate immunity comprises two forms: barrier defences and cellular innate defences.

Question 7

What is barrier defences in innate immunity?

Answer 7

Physical Barriers
- Protective covering
epithelial tissues forming the skin and mucus membranes lining the digestive respitory, urinary and reproductive tracts are held together by tight junctions, therefore blocking the entry of pathogens.
Mucus-covered epithelial tissues
Certain cells of mucous membrane produce mucus which enhances defences by trapping pathogens, allowing them to be removed effectively.
- Chemical barriers
Antibacterial enzymes in body secretions. Lysozyme in tears, saliva and mucus and secretions destroys cells walls of susceptible.
Hydrochloric Acid in the stomach Low pH enzymes of pathogens to be denatured and therefore kill the organisms.

Question 8

What are cellular innate defences?

Answer 8

If the first line of defense is unsuccessful and the pathogen enters the body, there is a second line of defense.
This line of defense involves WBCs, particularly phagocytes which are non-specific and will respond to any invading pathogen,
Phagoctyes that are involved in innate immunity include macrophages, neutrophils and dendritic cells.

Question 9

What happens when a pathogen breaches the epithelial barrier?

Answer 9

Phagocytes residing in the tissues such as macrophages, dendritic cells engulf the pathogen via phagocytosis.
Macrophages then release cytokines and chemokines which act to increase permeability of blood vessels and recruit cells such as neutrophils from the blood to the infected tissues.
Cytokines are proteins secreted by immune cells which acts as signalling molecules to enhance immune responses.
Chemokines are a specialised group of cytokines that act as chemoattractants to attract cells out of the bloodstream and into infected tissues.
This is known as inflammation which helps to remove the pathogen.

Question 10

What is an antigen?

Answer 10

An antigen is any substance that is recognised by the B or T lymhpocytes of the adaptive immune system. It is usually foreign to the host.
They are typically large molecules like proteins,peptides glycoproteins or polysaccharides from invading pathogens like viruses and bacteria.

Question 11

How are T lymphocytes activated?

Answer 11

Upon digestion of pathogenic proteins in antigen presenting cells during innate immune response, the peptides bind to MHC molecules to form a peptide MHC complex.
T-cell receptors bind to peptide MHC complex on cell surface of APCs, resulting in the activation of T lymphocytes.

Question 12

How are B lymphocytes activated?

Answer 12

The B-cell receptors can bind directly to intact antigens circulating in body fluids. Upon activation, antibodies produced are also able to bind directly to antigens found on pathogens.
Binding of T cell receptor to peptide MHC complex on the cell surface receptor of the B lymphocytes.
The portion of an antigen that binds to the antigen receptor or antibody is the epitope.

Question 13

What is antigen recognition and clonal selection and expansion in the innate immune response?

Answer 13

Naive T lymphocytes circulate the blood and lymph. They possess a repetoire of antigen receptor, each cell having receptors that are specific for a particular antigen.
The T-cell receptor of a naive T lymphocyte binds to the peptide MHC complex on a macrophage or dendritic cell.
CS+E: The naive T lymphocyte is activated to proliferate and produce many identical progenies, a process known as clonal expansion.

Question 14

What is differentiation in the innate immune response?
(After Clonal Expansion)

Answer 14

The progeny of clonal expansion then differentiates into one of the different types of effector T lymphocytes which carry out different functions when these cells subsequently detect the antigen.
These differentiated effector T lymphocytes inherit the same antigen receptor specificity.
Naive CD4+ T lymphocytes differentiate into memory helper T cells.
Naive CD8+ lymphocytes differentiate into cytotoxic T cells.
Helper T cells release cytokines which help in the activation of Naive CD8+ T lymphocytes to differentiate into cytotoxic T cells. Some CD8+ lymphocyte progeny differentiate into memory cyotoxic T cells.

Question 15

How are antigens eliminated in innate immunity?

Answer 15

Cytotoxic T cells carry out cell-mediated immune responses by killing infected cells.
T cells receptor of cytotoxic T cells recognises peptide MHC complex of infected cells.
Cytot T cells releases perforin which forms pores in the infected cell.
Cytot T cell releases cytotoxic proteins (granzymes) which enter the infected target cell by endocytosis, inducing apoptosis.
Releases cytokines which inhibits viral replication and induces expression of MHC molecules.
After destroying an infected cell, the cytotoxic T cell moves on and kill other cells infected with the same pathogen.

Question 16

What is the memory in innate immunity?

Answer 16

Most effector T lymphoyctes generated from clonal expansion in an immune response eventually die. After the antigen is eliminated, a significant number of activated antigen-specific T lymphocytes persist.
These are memory cells and form the basis of immunological memory.
They can be reactivated much more quickly than naive lymphocytes and are generated upon primary responses to antigen.
Memory cells provide lasting protective immunity and mediate a more rapid and effective secondary response to subsequent encounters with the antigen.

Question 17

What are the antigen recognition and presentation in humoral immune response?

Answer 17

Activation of B lymphocytes to carry out humoral (antibody) mediated immune response requires two distinct signals:
Antigen recognition and binding by the B-cell receptors.
Interaction with helper T cells
- Naive B lymphocytes circulate the blood and lymph.
- They possess a repertoire of antigen receptors, each cell having receptors that are specific for a particular antigen.
- The B-cell receptor of a naive B lymphocyte binds to an intact antigen in the blood or lymph.
- Antigen is taken up via endocytosis and digested into short peptides. The peptide is then presented on the MHC moleq forming a peptide-MHC complex.
- T-cell receptor of the helper T cell binds to the peptide MHC complex on the B lymphocytes.
- Secretion of cytokines by helper T cells

Question 18

What is differentiation in the humoral immune response?

Answer 18

The progeny differentiate into plasma cells and Mem B lymphocytes.
Plasma cells are the effector form of B lymphocytes.
Plasma cells then secrete antibodies that have the same antigen specificity as the B-cell receptor found on the Naive B lymphocyte previously.
Antigen that activated the Naive B lymphocyte now become the target of the antibodies produced by the differentiated plasma.

Question 19

What is antigen elimination in the humoral immune response?

Answer 19

Antibodies provide humoral immunity by protecting against pathogens or their products.
Neutralisation of bacterial toxin and virus particles.
- Antibodies bind to the toxins and virus particles to prevent them from interacting with host cells.
- Antigen-antibody complex is then phagocytosed and degraded by macrophages.
Opsonisation and phagocytosis of bacterial cells
- Antibody binds to antigens on the bacterial cell.
- The antibody then binds to receptors expressed on macrophages and other phagocytes, facilitating phagocytosis.
Agglutination of bacterial cells
- As each antibody has 2 antigen binding sites, one antibody can bind to two bacterial cells and cause clumping.

Question 20

What is the memory of the humoral immune response?

Answer 20

Most plasma cells generated from clonal expansion in an immune response will eventually die.
After the antigen is eliminated, a significant number of activated antigen specific B lymphocytes persist.
These cells known as memory cells and form the basis of immunological memory.
They can be reactivated much more quickly than naive lymphocytes and are generated upon primary response to antigen.
They provide lasting protective immunity and mediate a more rapid and effective secondary response to subsequent encounters with the antigen.

Question 21

What is the structure and function of lgG?

Answer 21

• Large quartenary protein composed of 4 polypeptide chains.
  It consists of two identical heavy chains and two identical light chains.
  The two chains are linked by disulfide bonds and each heavy chain is linked to a light chain by a disulfide bond.
• Heavy and light chains have variable and constant regions. Variable regions of heavy and light chains at the amino terminus form the antigen binding site. Hypervariable loops in both Vh and Vl are brought together to form a single hypervariable site at the tip of each arm. This forms the antigen-binding site which determines the antigen specificity of the antibody. There are two identical antigen-binding sites, allowing antibody to bind to two identical antigens simultaneously, increasing total strength of the interxn.
• The two arms of the antibody molecule that contain the antigen binding site are known as the Fab fragments and the trunk is known as Fc fragment.
• The flexible stretch of polypeptide chain joining the Fab and Fc fragments is known as the hinge region. Allows flexibility in the movement of the two Fab arms to bind to antigens.

Question 22

What is somatic recombination?

Answer 22

The variable regions of the immunoglobin are coded by gene segments which are rearranged by the process of somatic recombination during the development of each naive B lymphocyte.
Dvlpment of B lymphocyte begins with rearrangment of the heavy-chain gene locus followed by the rearrangement of the light chain gene locus.
It is encoded in 3 gene segments, Vh, Dh and Jh.
A complete immunoglobin heavy chain mature mRNA is formed when the variable region exon is joined to the constant region sequenced by RNA splicing after transcription.
The variable region of light chain is encoded in only 2 gene segments, Vl and Jl. Joining of a Vl and Jl gene segment forms and exon that codes for Vl region. A complete immunoglobin light chain mature mRNA is formed when the variable region exon is joined to the Cl sequence by RNA splicing after transcription.
There are multiple different copies of the V,D,J gene segments in germline DNA at the ig heavy and light chain gene loci.
Somatic recombination is the random selection of 1 gene segment of each type produces different combinations of gene segments of the variable region.

Question 23

What is somatic hypermutation?

Answer 23

Somatic hypermutation occurs in activated B lymphocytes during clonal expansion.
It introduces point mutations into the rearranged variable region genes.
Resulting in a change of one to a few amino acids in the Ig, producing closely related B lymphocytes progeny with B cell receptors that differ slightly in specificity and antigen affinity. Mutations that improve the affinity of a B cell receptor for antigen will allow these B lymphocytes to be selected via a process called affinity maturation.

Question 24

What is class switching?

Answer 24

Upon encountering its specific antigen, activated B lymphocyte undergoes class switching to produce Ig of several different classes, depending on constant regions of heavy chain. Regulated by signals from T helper cells.
Class switching is the process where the same rearranged VDJh gene segment is linked to different heavy chain constant regions at the DNA level, resulting in Igs with the same antigen specificity but different effector functions.

Question 25

What is passive and active immunity?

Answer 25

Passive: Acquired from the introduction of antibodies from another individual. Immunity is instant but it is generally short lived.
Active immunity is immunity resulring from the activities of an individuals own immune system. There is a delay before the immune response is complete but it is generally long lasting.

Question 26

What is the primary response after vaccination?

Answer 26

Primary response is when a person is vaccinated against a specific disease. Vaccine contains usually attenuated or killed pathogen.
The vaccine which contains the modified pathogen is no longer able to cause disease but can still elicit an immune response because a particular surface antigen of the pathogen is still retained and is recognised by a specific B lymphocyte.
The B lymphocyte then undergoes clonal expansion by dividing repeatedly to form memory cells or antibody-secreting plasma cells.

Question 27

What is the secondary response in vaccination?

Answer 27

Vaccination prevents diseases by generating a more rapid and intense immune response.
When exposed to the same virulent pathogen again, memory cells in a previously vaccinated individual will quickly recognise the surface antigen of the pathogen.
Memory cells quickly undergo rapid clonal expansion and develop into antibody secreting plasma cells.
These plasma cells are then able to produce large number of antibodies which bind and inactivate the virulent pathogen to prevent them from infecting healthy host cells.

Question 28

What is the live, attenuated vaccine?

Answer 28

Attenuation is the weakening of a pathogenic virus or bacteria used in the vacccine, making it less virulent. Attenuated pathogens are still viable, can replicate and can cause infections, but do not cause disease.
A: Closely mimics a natural infection, eliciting a strong immune response with just a low dosage
It confers longer term protection.
D:
Possibility of reversion of full pathogenicity by mutatioms either in the vaccine stock or in the vaccinated individual.
Needs refrigation to stay positive.

Question 29

What is the killed or inactivated vaccine?

Answer 29

Pathogenic bacteria or virus used in the vaccine is killed or inactivated with chemicals, heat or radiation so that they are no longer infectious.
A: Should not revert to virulent for, and thus should not cause disease.
Usually do not require refrigeration and thus can be easily stored and transported in a freeze-dried form making such vaccines easily accessible to people in the developing countries.
D: Vaccines stimulate good responses but generally require more than a single does to maintain protection.
As the inactivated virus no longer infectious, it may not stimulate cell-mediated immunity. Immune response is usually humoral.

Question 30

What are the benefits of vaccination?

Answer 30

1. Vaccines protect individuals against potential future diseases that may cause long term health problems.
2. Vaccines protects individuals and communities through herd immunity.
3. Vaccination protects future generations as immunisation has eliminated many diseases that killed or severely disabled people just a few generations ago.

Question 31

What are the risks of vaccines?

Answer 31

Vaccines can cause some side effects. However side effects are usually mild and they include redness, soreness and swelling where the vaccine was injected.
There is a risk of reversion to virulence where attenuated live vaccines are used.

Question 32

What is the acute infection phase of HIV?

Answer 32

HIV has very strong affinity for and binds to CD4 surface proteins on T helper cells. Period is marked by an abundance of virus circulating in the blood and the rapid decline of CD4 T cells.
CD4 T cells are killed by viral cytopathic effects. Macrophages and dendritic cells are not destroyed by the replicating virus and act as reservoirs to the virus.
As the HIV infects increasing numbers of T helper cells, the level of T helper cells started to fall as these infected cells are destroyed.
There is a window period during the primary infection phase where an infected person may test HIV negative because antibodies against HIV are not yet detectable.
However, as CD T cells specific for HIV antigens develop and kill HIV infected cells, virus specific antibodies become detectable in the serum.
Towards the end of this phase the cytotoxic T cell response results in early control of the virus.
This results in a decline in the number of HIV particles on the blood stream and rebound of CD4 T cells.

Question 33

What is the clinical latency phase of the HIV infection?

Answer 33

Following the initial events of the acute phase, the symptoms disappear and the infected person becomes asymptomatic.
This phase lasts 8 to 10 years, CD4 T cell numbers gradually decline during this period.
Virus continues to actively replicate in some infected cells continue to produced during this time but the immune system is still capable of managing the free viruses.

Question 34

What is acquired immune deficiency syndrome?

Answer 34

AIDs refers to a set of symptoms and illness that occur at the very final stage of HIV.
Characterised by an onset of immune suppression where the immune system wearsdown and symptoms result from the failure of the immune system to defend against pathogens as well as a direct attack by virus on host cells.
CD4 T cell numbers decline below a critical level, thus cell-mediated immunity is lost.
Full-blown AIDs occurs when the infections become unmanageable and the immune supression becomes worse, with fatal results.

Question 35

What is antiretroviral therapy?

Answer 35

It is not a cure but can control the virus reproduction, so the infected person can live a longer healthier life.
ART involves taking a combination of HIV medicines every day as prescribed.
ART generally includes the administration of 3 or more HIV medicines from at least two different drug classes.
There are currently 24 approved retroviral drugs in 6 HIV drug classes that are being used in ART.

Question 36

How is tuberculosis developed?

Answer 36

Minimum infectious dose for lung infection is 10 bacterial cells.
Alveolar macrophages phagocytose the bacteria and form phagosomes containing M. tuberculosis.
Inside the phagosome, M. tuberculosis inhibits the fusion of the phagosome with lysosomes.
No phagolysome is formed, no lysosome enzymes are available to kill the bacteria.
A tubercule is formed, cell death by necrosis occurs at the center of the tubercule. The disease may be arrested and remain latent for several years.
The tubercule cavity enlarges to form an air-filled cavity for the aerobic bacteria to multiply outside the macrophages.
The tubercule ruptures, allowing the bacteria to enter into a bronchiole and spread throughout the lungs. This results in development of a productuve cough that facilitates the airborne spread of the infectious bacteria cells.
The lungs will be progressively destroyed by the formation of cavities due to the rupture of the tubercules.

Question 37

How is tuberculosis treated?

Answer 37

Daily treatment with a combination of least 2 antibiotics for 6 months.
A combination of antibiotics are used during treatment to minimise risk of development of resistance, achieve additive effect against the bacteria.
Regimen for latent and active TB is different in terms of intensity.
Incomplete TB treatment may result in development of resistance in the infection.
Mutant TB strains are deadlier and harder to treat.

Question 38

What are antibiotics?

Answer 38

They can be bactericidal (kill bacteria when bacteria are undergoing cell division) or bacteriostatic (Inhibit cell division).
Different diseases are treated with different antibiotics. Some are completely resistant to particular antibiotics.
Antibiotics are effective against bacteria but have no effect on human cells.

Question 39

What are the 4 metabolic pathways that antibiotics disrupt?

Answer 39

Cell wall synthesis
Without support from a cell wall, pressure in the cell becomes too much and membrane bursts.
Protein synthesis.
Binds to the 30S of the bacterial chromosome such that initiator tRNA cannot bind to the small subunit.
Some work by blocking aminoacyl-tRNA from attaching to the A site to the bacterial ribosome.
Nucleic acid synthesis.
Inhibits RNA synthesis by binding to bacterial RNA polymerase, preventing transcription.
Metabolic pathways.

Question 40

How does penicilin work on bacteria?

Answer 40

Disrupts the cell wall synthesis during cell division, making penicilin only effective in actively growing bacterial cells.
Peptidoglycan is deposited with the cell wall as the cell wall stretches and grows.
The beta-lactam ring in penicilin inhibits certain enzymes required for the synthesis and assembly of the cross-links between the peptidoglycan polymers in the cell walls of bacteria.
This weakens the cell wall of bacteria cells, making them unable to withstand pressure.
When water enters naturally by osmosis the cell lyses and dies.