Immunity | Human Health & Diseases

Immunity is the protection against diseases provided by the body‘s immune or defence system.
There are two parts of this system:

(i)The non-specific system

(ii)The specific system

Non-specific system

The defenses present from birth form the non-specific system.
This system does not distinguish between different pathogens and gives the same response each time the same pathogen attacks.

Specific Immune system

Gives a highly effective, long-lasting immunity to anything the body recognizes as foreign.
Specialised cells known as lymphocytes direct a defence against specific pathogens.
Although highly efficient, this immune response is slow, when it encounters a pathogen for the first time.
During the first encounter, some lymphocytes produce special protein molecules, called antibodies which are targeted specifically at the invading pathogen.
Although the capability of producing antibodies is present from before birth, they are only produced when the appropriate pathogen invades.
The specific immune system recognizes pathogens because their surfaces are covered in large molecules such as proteins, glycoproteins and polysaccharides.
The immune system also recognizes the toxins that are produced by pathogens as foreign particles.
Any molecule that the body recognizes as foreign is called an antigen.

Primary defence against disease

The defenses that prevent pathogens from entering the body:

Surface barriers

Defence mechanism	Function
Skin	Prevents entry of pathogens and foreign substances
Acid secretions	Inhibit bacterial growth on skin
Mucus	Prevents entry of pathogens, mucous membranes also produce defensins (small toxic peptides) that kill pathogens
Nasal hairs	Filter bacteria in the nasal passages
Cilia	Move mucus and trapped materials away from respiratory passages
Gastric juice	Concentrated HCl and proteases destroy pathogens in the stomach
Acid in vagina	Limits the growth of fungi and bacterial in female reproductive tract
Tears, saliva	Contain lysozyme which destroys bacteria

Other non-specific cellular, chemical and co-ordinated defenses

Defense mechanism	Function
Normal flora	Compete with pathogens, may produce substances toxic to pathogens
Defense mechanism	Function
Fever	Body wide response inhibits microbial reproduction and speeds body repair processes
Coughing and sneezing	Remove pathogens from respiratory tract
Inflammatory response	Involves leakage of blood plasma and phagocytes from capillaries. Limits spread of pathogens to neighboring tissues, concentrates defenses, digests pathogens and dead tissue cells, released chemical mediators attract phagocytes and lymphocytes to the site
Phagocytes (macrophages and neutrophils)	Engulf and destroy pathogens that enter the body

Cells of the immune system

Humoral Response

involves B-cells
B cells release antibodies into the blood plasma, tissue fluid and lymph. As the antibodies are released into fluids and the attack on the microorganisms takes place in the fluid this type of immunity is called humoral, humor means fluid.
Antibodies of B cells attack bacteria and some viruses
A non-activated B-cell has several antigen binding sites (antigen receptors) attached to its cell membrane whose shape is identical to the antibodies that the cell can make.
All the receptors in the membrane of one cell are identical, so a given cell can recognize only one type of antigen.
A complementary antigen attaches to it
When it binds to an antigen the cell is activated to clone itself, meaning that it multiplies to form many identical copies of itself.
Activation requires the presence of lymphokins secreted by T-helper cells as well as antigen.
Memory cells and effector cells (plasma proteins) are formed
These secrete large numbers of antibody into the blood, tissue fluid and lymph.
Effector cells live for a few days only
Memory cells survive for long periods of time and enable rapid response to be made to any future infection

Cell-Mediated Response

Involves T-cells
T cells attack the following:
- Cells that have become infected by a microorganism most commonly a virus
- Transplanted organs and tissues

(iii)Cancer-causing cells

The whole cell is involved in the attack thus cell-mediated immunity.
T cells do not release antibodies

The cell surface membrane of T cells contains specific receptors with particular shapes, similar to antibodies.

The receptors do not recognize the whole antigen molecules unlike antibodies
They bind only to fragments of antigens or other foreign molecules which are presented to them by other cells, often macrophages
Mature T cells possess a T4 molecule (T4 cells) or a T8 molecule (T8 cells) which give them different functions.
T4 cell are known as T helper cells. The HIV virus which causes AIDS infects mainly T-helper cells.
There are two types of T8 cells known as suppressor cells and killer cells (or cytotoxic cells).
Each type of T-cell produces a different type of lymphokine.
Lymphokins are small peptide nolecules with various functions.
T4 cells work in association with macrophages.
The macrophage first captures an antigen-carrying organism.
It then chops off a piece of the antigen an presents it at its cell surface where it is recognized as a foreign peptide by a T4 cell (one with a matching receptor) – The T cell then produces large amounts of lymphokines.
This have various functions which include;
stimulate T cells to multiply
promote inflammation
stimulate B cells to make antibodies
killer cells produce smaller amounts of lymphokines, but kill body cells which have become infected by viruses and cancer cells. This si done by a chemical attack or by punching holes in the cells.
They recognize e.g. a stray part of a virus on the outside of an infected cell or a mutant protein produced by a cancer cell.
They also attack and gradually destroy transplanted organs.
Suppressor cells secrete lymphokines that depress the activity of all the different types of white blood cells including phagocytes.
Helper cells secrete lymphokines which increase the activity of all the different types of white blood cells

Role of lymphocytes in cell mediated and humoral response

cell mediated/cellular involves T-cells;
humoral involves B-cells
clonal selection
receptors on T/B cell membranes for recognition of antigen
divide/mitosis to form clones
T cells to form effector cells
B cells to form plasma cells
B cells/plasma cells release antibodies (into blood/plasma)
different types of antibodies IgM/IgG
to structure of antibodies
to modes of action
T-helper cells activate B-cells
activate macrophages
secretion of lymphokins
T-cytotoxic cells destroy virus infected cells
T-suppressor cells control immune response
memory cells
slow primary response/fast secondary response (Idea –could be shown on a graph)

Memory Cells

memory cells are important if a second infection of an antigen occurs
the population of memory cells is much larger than the original population of B cells from which they came from.
Therefore the response to the second infection called secondary response is much more rapid and is also greater than the primary response to the original infection as shown in the graph below.
The primary response may not be rapid enough to prevent a person suffering from an infection but if that person survives, they will rarely suffer from it again because of the greater secondary response.
With each exposure, the response gets more efficient.
This is the basis of vaccination (booster doses).

Explain the role of memory cells in long-term immunity

produced by both T and B lymphocytes/cells
survive for long periods
remain in lymphoid system and circulate in blood and in lymph
constantly checking for return of pathogen with same antigen
go fewer divisions before differentiating into plasma cells
Second response called secondary response
greater than primary response to original infection
Antigen presenting cells/APCs continue to expose
antigen to memory cells to maintain memory

Immunological Memory

Primary immune response – cellular differentiation and proliferation, which occurs on the first exposure to a specific antigen
Lag period: 3 to 6 days after antigen challenge
Peak levels of plasma antibody are achieved in 10 days
Antibody levels then decline
Secondary immune response – re-exposure to the same antigen
Sensitized memory cells respond within hours
Antibody levels peak in 2 to 3 days at much higher levels than in the primary response
Antibodies bind with greater affinity, and their levels in the blood can remain high for weeks to months

Describe the role of lymphocytes in cell mediated and humoral response

cell mediated/cellular involves T-cells;
humoral involves B-cells
clonal selection
receptors on T/B cell membranes for recognition of antigen
divide/mitosis to form clones
T cells to form effector cells
B cells to form plasma cells
B cells/plasma cells release antibodies (into blood/plasma)
different types of antibodies IgM/IgG
to structure of antibodies
to modes of action
T-helper cells activate B-cells
activate macrophages
secretion of lymphokins
T-cytotoxic cells destroy virus infected cells
T-suppressor cells control immune response
memory cells
slow primary response/fast secondary response (Idea –could be shown on a graph)

Relate the molecular structure of antibodies to their functions;

An antibody is a molecule synthesized by an animal in response to the presence of foreign substances called antigens
Each antibody is a globular protein molecule called immunoglobulin.
Structure consists of four polypeptide chains
Two heavy chains and two light chains
The chains are held together by disulphide bridges
It has a constant and a variable region
The variable part is specific to each type of antibody produced
There are different classes of antibodies e.g. IgS, IgM, IgA, IgE and IgD
Its structure consists of two heavy chains (H-chains) and two light chains (L-chains)
It has a constant and variable part, the variable acts like a key which specifically fits into a lock
The body van produce an estimated 100 million different antibodies recognizing all kinds of foreign substances, including many the body has never met.
It does this by shuffling different sections of parts of the genes on which produce the variable region.

Antigen

An antigen is a molecule which can cause antibody formation
All cells possess antigens in their cell surface membranes which acts as markers, enabling cells to recognize each other.
Antigens are usually glycoproteins
The body can distinguish its own antigens (self) from foreign antigens (non-self) and normally makes antibodies against non-self antigens.
Microorganisms carry antigens on their surface
They are proteins that are utilized by the immune system to detect and neutralize foreign objects.
They consist of light chains (the two smaller ones) and the heavy chains (the two central ones) which both have a variable region (specific to every different type of antibody) at the tips with an antigen-binding site (shown in yellow).
The heavier chains and the heavy and light chains are linked together by disulfide linkages which are a type of covalent bonds that are formed upon the oxidation of thiol groups [-SH2] that are left over from the cysteine
They are very important to the functioning of the antibody because most of its functions are carried out in an extracellular aqueous environment which attacks both the other available alternatives, ionic bonds and hydrogen bonding so the preservation of an antibody’s structure is critical to its proper functioning and the disulfide linkages ensure just that.

Functions of antibodies

Opsonization – the stimulation of other immune cells (like Macrophages) to engulf a foreign particle.
Agglutination – the clumping together or precipitation of antigen-bearing material.

Lysis – breakdown of an antigen bearing particle.
Detoxification – the neutralization of harmful substances produced by foreign particles.

Explain what is meant by monoclonal antibodies and describe how they may be used to diagnose diseases

antibodies developed from a single cell/clone;
they have a defined specificity;
reactive with a single epitome/antigen;
early diagnosis – couple to fluorescent markers to locate antigens;
g. Chlamydia/streptococcal throat infections/gonorrhea/STDs;
Chlamydia difficult to distinguish from gonorrhea/difficult to diagnose;
used to diagnose lung/breast/colon//rectal cancer;
classification of type of leukemia by specific markers on white blood cells;
ensures correct treatment (for leukemia) given;
distinguish between leukemias and lymphomas (both types of cancer of white blood cells);
distinguish between closely related herpes viruses 1 (cold sores on lips and 20% of genital herpes) and herpes virus 2 (genital infections);
recommended treatment is different for two viruses;
therefore important to distinguish between them;
monitors spread of malaria by identifying stages in infected mosquitoes;