INTRODUCTION TO IMMUNOLOGY

Question 1

Discuss the first line of defense against a pathogen

Answer 1

Physical barriers prevent pathogens such as bacteria and viruses from entering the organism.

Mechanical: Skin, coughing and sneezing clears the airways and lungs of organisms; flushing by tears; flushing by urine; mucus traps organisms in GIT and respiratory tract.

Chemical: secretions contains antimicrobial agents, enzymes e.g. defensin in respiratory secretions; lysozyme and phospholipase A2 in tears, saliva; acid secretions in vagina; gastric acid secretion in stomach

Biological: commensals in GUT and GIT; skin

Question 2

What occurs if a pathogen breaches these barriers?

Answer 2

If a pathogen breaches these barriers, the innate immune system provides an immediate, but non-specific response. Innate immune systems are found in all plants and animals

Question 3

What if pathogens successfully evade the innate response?

Answer 3

If pathogens successfully evade the innate response, vertebrates possess a second layer of protection, the adaptive immune system, which is activated by the innate response.

The adaptive immune system adapts its response during an infection to improve its recognition of the pathogen.

This improved response is then retained after the pathogen has been eliminated, in the form of an immunological memory.

The adaptive immune system allows the organism to mount faster and stronger attacks each time this pathogen is encountered.

Question 4

The human immune system has three key properties which are?

Answer 4

A highly diverse antigen receptor that enables recognition of an infinite number of pathogens

Immune memory, to mount rapid recall immune response

Immunologic tolerance, to avoid immune damage to normal cells

Question 5

What is immunity and the types of immunity?

Answer 5

Immunity is the ability of the human body to tolerate the presence of material indigenous to the body (“self”), and to eliminate foreign (“nonself”) material.

Active immunity
Protection that is produced by the person’s own immune system
This type of immunity is usually permanent.

Passive immunity
Protection by products produced by an animal or human and transferred to another human, usually by injection.
Passive immunity often provides effective protection, but this protection wanes (disappears) with time, usually within a few weeks or months.

Question 6

Types of immunity/ immune response

Answer 6

Innate (natural) immunity: inborn, general processes that does not depend on the body being attacked by organism or toxins
Phagocytes etc.
Early, rapid responses, but limited & ‘non-specifc’

Adaptive (acquired) immunity: developed after the body has been attacked by an organism or toxin
Lymphocytes (B & T cells)
Take time but powerful - ‘specificity + memory’

Question 7

Differences between/characteristics of innate and adaptive immunity

Answer 7

Innate Immune System:
* Response is non-specific
* Exposure leads to immediate maximal response
* Cell mediated and humoral component
* No immunological memory
* Found early in all form of life

Adaptive Immune System:
* Pathogen and antigen specific response
* Lag time between exposure and maximal response
* Cell mediated and humoral components
* Exposure leads to immunological memory
* Found only in jawed vertebrates

Question 8

What are the Organs of the immune system (primary and secondary)?

Answer 8

The Organs of the immune system fall into two groups based upon their role in host defense:

Primary (or central) create and educate them during their differentiation into mature cells:
Bone marrow
Thymus gland.

Secondary(peripheral) immune organs look after mature cells that are an active part of defense:
Spleen
Lymphatic system
Lymph nodes

Question 9

Bone Marrow

Answer 9

Bone Marrow
All the cells of the immune system are initially derived from the bone marrow.

They form through a process called hematopoiesis.

During hematopoiesis, bone marrow-derived stem cells differentiate into either mature cells of the immune system or into precursors of cells that migrate out of the bone marrow to continue their maturation elsewhere.

The bone marrow produces B cells, natural killer cells, granulocytes and immature thymocytes, in addition to red blood cells and platelets.

Question 10

Discuss the Spleen

Answer 10

Spleen
The spleen is an immunologic filter of the blood. It is made up of B cells, T cells, macrophages, dendritic cells, natural killer cells and red blood cells.

In addition to capturing foreign materials (antigens) from the blood that passes through the spleen, migratory macrophages and dendritic cells bring antigens to the spleen via the bloodstream.

An immune response is initiated when the macrophage or dendritic cells present the antigen to the appropriate B or T cells.

In the spleen, B cells become activated and produce large amounts of antibody.

Also, old red blood cells are destroyed in the spleen.

Question 11

Discuss the thymus

Answer 11

Thymus
The function of the thymus is to produce mature T cells.

Immature thymocytes, also known as prothymocytes, leave the bone marrow and migrate into the thymus.

Through a maturation process referred to as thymic education, T cells that are beneficial to the immune system are spared, while those T cells that might evoke a detrimental autoimmune response are eliminated.

The mature T cells are then released into the bloodstream.

Question 12

Discuss the Lymph Nodes

Answer 12

Lymph Nodes
The lymph nodes function as an immunologic filter for the bodily fluid known as lymph.

Lymph nodes are found throughout the body.

Composed mostly of T cells, B cells, dendritic cells and macrophages, the nodes drain fluid from most of our tissues.

Antigens are filtered out of the lymph in the lymph node before returning the lymph to the circulation.

In a similar fashion as the spleen, the macrophages and dendritic cells that capture antigens present these foreign materials to T and B cells, consequently initiating an immune response.

Question 13

What are The Cells of the adaptive Immune System?

Answer 13

The cells of the adaptive immune system are called lymphocytes.
B cells and T cells are the major types and are derived from hematopoietic stem cells in the bone marrow.
B cells are involved in the humoral immune response, whereas T cells are involved in cell-mediated immune response.

Question 14

What are the cells of the innate immune system?

Answer 14

The cells of the innate immune system include the phagocytes (macrophages, neutrophils, and dendritic cells), mast cells, eosinophils, basophils, and natural killer cells.
They identify and eliminate pathogens, either by attacking larger pathogens through contact or by engulfing and then killing microorganisms.
Innate cells are also important mediators in the activation of the adaptive immune system

Question 15

What are T-cells?

Answer 15

T-Cells
T cells recognize a “non-self” target, such as a pathogen, only after antigens (small fragments of the pathogen) have been processed and presented in combination with a “self” receptor called a major histocompatibility complex (MHC) molecule.

T lymphocytes are usually divided into two major subsets that are functionally and phenotypically different:
Killer/suppresor T cells
Helper T cells

Both T cells can be found throughout the body.

They often depend on the secondary lymphoid organs (the lymph nodes and spleen) as sites where activation occurs, but they are also found in other tissues of the body, most conspicuously the liver, lung, blood, and intestinal and reproductive tracts.

Question 16

What are Helper T-cells?

Answer 16

Helper T cell
The T helper subset, also called the CD4+ T cell, is a pertinent coordinator of immune regulation.

It only recognize antigens coupled to Class II MHC molecules.

Helper T cell activation also requires longer duration of engagement with an antigen-presenting cell.

The main function of the T helper cell is to augment or potentiate immune responses by the secretion of specialized factors called cytokines that activate other white blood cells to fight off infection.

Cytokine signals produced by helper T cells enhance the microbicidal function of macrophages and the activity of killer T cells.

In addition, helper T cell activation causes an upregulation of molecules expressed on the T cell’s surface, such as CD40 ligand (also called CD154), which provide extra stimulatory signals typically required to activate antibody-producing B cells.

Question 17

What are Killer/suppressor T cell?

Answer 17

The T killer/suppressor subset or CD8+ T cell. Killer T cells only recognize antigens coupled to Class I MHC molecules.
These cells are important in directly killing certain tumor cells, viral-infected cells and sometimes parasites.
The CD8+ T cells are also important in down-regulation of immune responses.
Killer T cells are activated when their T cell receptor (TCR) binds to this specific antigen in a complex with the MHC Class I receptor of another cell.
When an activated T cell contacts such cells, it releases cytotoxins, such as perforin, which form pores in the target cell’s plasma membrane, allowing ions, water and toxins to enter.
The entry of another toxin called granulysin (a protease) induces the target cell to undergo apoptosis.
T cell killing of host cells is particularly important in preventing the replication of viruses.

Question 17

What are Natural Killer Cells?

Answer 17

Also referred to as NK cells, are similar to the killer T cell subset (CD8+ T cells). They are a component of the innate immune system which does not directly attack invading microbes.

They were named “natural killer” because of the initial notion that they do not require activation in order to kill cells that are “missing self.“

This term describes cells with low levels of a cell-surface marker called MHC I (major histocompatibility complex)– a situation that can arise in viral infections of host cells.

It is now known that the MHC makeup on the surface of those cells is altered and the NK cells become activated through recognition of “missing self”. Normal body cells are not recognized and attacked by NK cells because they express intact self MHC antigens

NK cells destroy compromised host cells, such as tumour cells (e.g. melanomas, lymphomas) or virus-infected cells (e.g. herpes virus, cytomegalovirus), recognizing such cells by a condition known as “missing self.”

NK cells that have been activated by secretions from CD4+ T cells will kill their tumor or viral-infected targets more effectively

Question 18

What are B cells?

Answer 18

B cells identifies pathogens when antibodies on its surface bind to a specific foreign antigen.

This antigen/antibody complex is taken up by the B cell and processed by proteolysis into peptides.

The B cell then displays these antigenic peptides on its surface MHC class II molecules.

This combination of MHC and antigen attracts a matching helper T cell, which releases lymphokines and activates the B cell.

As the activated B cell then begins to divide, its offspring (plasma cells) secretes millions of copies of the antibody that recognizes this antigen.

These antibodies circulate in blood plasma and lymph, bind to pathogens expressing the antigen and mark them for destruction by complement activation or for uptake and destruction by phagocytes.

Antibodies can also neutralize challenges directly, by binding to bacterial toxins or by interfering with the receptors that viruses and bacteria use to infect cells.

Question 19

What are Dendritic Cells?

Answer 19

Dendritic cells, also originate in the bone marrow, function as antigen presenting cells (APC); are more efficient than macrophages.

They are found in lymphoid organs such as the thymus, lymph nodes and spleen; also found in the bloodstream and other tissues of the body.

They capture antigen or bring it to the lymphoid organs where an immune response is initiated.

Dendritic cells are phagocytes in tissues that are in contact with the external environment; located mainly in the skin, nose, lungs, stomach, and intestines.

They are named for their resemblance to neuronal dendrites, as both have many spine-like projections, but dendritic cells are in no way connected to the nervous system.

Dendritic cells serve as a link between the bodily tissues and the innate and adaptive immune systems, as they present antigens to T cells

Question 20

What are Granulocytes or Polymorphonuclear (PMN) Leukocytes?

Answer 20

Granulocytes or Polymorphonuclear (PMN) Leukocytes
Another group of white blood cells is collectively referred to as granulocytes or polymorphonuclear leukocytes (PMNs).

Granulocytes are composed of three cell types identified as neutrophils, eosinophils and basophils, based on their staining characteristics with certain dyes.

These cells are predominantly important in the removal of bacteria and parasites from the body.

They engulf these foreign bodies and degrade them using their powerful enzymes.

Question 21

What are Macrophages?

Answer 21

Macrophages
Macrophages are important in the regulation of immune responses.
They are often referred to as scavengers or antigen-presenting cells (APC) because they pick up and ingest foreign materials and present these antigens to other cells of the immune system such as T cells and B cells.
This is one of the important first steps in the initiation of an immune response.
Stimulated macrophages exhibit increased levels of phagocytosis and are also secretory.
Macrophages are versatile cells that reside within tissues and produce a wide array of chemicals including enzymes, complement proteins, and regulatory factors such as interleukin 1
Also act as scavengers, ridding the body of worn-out cells and other debris, and as antigen-presenting cells that activate the adaptive immune system.

Question 21

What are other cells of the immune system?

Answer 21

OTHER CELLS
Mast cells reside in connective tissues and mucous membranes, and regulate the inflammatory response. They are most often associated with allergy and anaphylaxis.

Basophils and eosinophils are related to neutrophils. They secrete chemical mediators that are involved in defending against parasites and play a role in allergic reactions, such as asthma.

Question 22

What is Phagocytosis?

Answer 22

Phagocytosis is an important feature of cellular innate immunity performed by cells called ‘phagocytes’ that engulf, or eat, pathogens or particles.

Phagocytes generally patrol the body searching for pathogens, but can be called to specific locations by cytokines.

Once a pathogen has been engulfed by a phagocyte, it becomes trapped in an intracellular vesicle called a phagosome, which subsequently fuses with another vesicle called a lysosome to form a phagolysosome.

The pathogen is killed by the activity of digestive enzymes or following a respiratory burst that releases free radicals into the phagolysosome.

Phagocytosis evolved as a means of acquiring nutrients, but this role was extended in phagocytes to include engulfment of pathogens as a defense mechanism.

Phagocytosis probably represents the oldest form of host defense, as phagocytes have been identified in both vertebrate and invertebrate animals.

Question 23

What is Immunological memory?

Answer 23

When B cells and T cells are activated and begin to replicate, some of their offspring become long-lived memory cells.

Throughout the lifetime of an animal, these memory cells remember each specific pathogen encountered and can mount a strong response if the pathogen is detected again.

This is “adaptive” because it occurs during the lifetime of an individual as an adaptation to infection with that pathogen and prepares the immune system for future challenges.

Immunological memory can be in the form of either passive short-term memory or active long-term memory.

Question 24

What is passive memory?

Answer 24

Newborn infants have no prior exposure to microbes and are particularly vulnerable to infection.

During pregnancy IgG, is transported from mother to baby directly across the placenta, so human babies have high levels of antibodies even at birth, with the same range of antigen specificities as their mother.

Breast milk or colostrum also contains antibodies that are transferred to the gut of the infant and protect against bacterial infections until the newborn can synthesize its own antibodies.

This passive immunity is usually short-term, lasting from a few days up to several months.

In medicine, protective passive immunity can also be transferred artificially from one individual to another via antibody-rich serum

Question 25

What is active memory and immunization?

Answer 25

ACTIVE MEMORY AND IMMUNIZATION
Long-term active memory is acquired following infection by activation of B and T cells.

Active immunity can also be generated artificially, through vaccination.

The principle behind vaccination (also called immunization) is to introduce an antigen from a pathogen in order to stimulate the immune system and develop specific immunity against that particular pathogen without causing disease associated with that organism.

This deliberate induction of an immune response is successful because it exploits the natural specificity of the immune system, as well as its inducibility.

Question 26

Difference between Live attenuated and inactivated vaccines

Answer 26

Live attenuated vaccines

Produced by modifying a disease-producing (“wild”) virus or bacterium in a laboratory.
The resulting vaccine organism retains the ability to replicate (grow) and produce immunity, but usually does not cause illness.
The majority of live attenuated vaccines available contain live viruses.
Live attenuated bacterial vaccine are available.

Inactivated vaccines

Composed of either whole viruses or bacteria, or fractions of either.
Inactivated vaccines are either protein-based or polysaccharide-based.
Protein-based vaccines include toxoids (inactivated bacterial toxin) and subunit or subvirion products.
Most polysaccharide-based vaccines are composed of pure cell wall polysaccharide from bacteria.
Conjugate polysaccharide vaccines contain polysaccharide that is chemically linked to a protein. This linkage makes the polysaccharide a more potent vaccine.

Question 26

What is a major characteristic of antigens derived from acellular vaccines?

Answer 26

Many antigens derived from acellular vaccines do not strongly induce the adaptive response, most bacterial vaccines are provided with additional adjuvants that activate the antigen-presenting cells of the innate immune system and maximize immunogenicity

Question 27

What are viral and bacterial viruses based on?

Answer 27

Most viral vaccines are based on live attenuated viruses, while many bacterial vaccines are based on acellular components of micro-organisms, including harmless toxin components.

Question 28

Examples of live attenuated vaccines

Answer 28

• Viral: measles, mumps, rubella, vaccinia. zoster, yellow fever, rotavirus, intranasal influenza, oral polio
• Bacterial: BCG, oral typhoid

Question 29

Examples of inactivated vaccines

Answer 29

WHOLE-CELL VACCINES

• Viral: polio. hepatitis A, rabies and influenza
• Bacterial: pertussis, typhoid, cholera, plague

FRACTIONAL

Subunit:
Hepatitis B, influenza, acellular pertussis, HPV and anthrax

Toxoid:
Diptheria, tetanus

Question 30

Examples of polysaccharide vaccines

Answer 30

Pure polysaccharide
*pneumococcal
* meningococcal
* salmonella typhi (vi)

Conjugate polysaccharide
*haemophilus influenzae type b
*pneumococcal
*meningococcal