Specific Acquired Immunity

Question 1

Discuss briefly the function of T cells

Answer 1

T cells themselves survey the surfaces of the body’s cells, looking for ones that have parasites within them or that are dangerously changed or mutated. (Cell-Mediated immunity)

Starting in lymphoid tissues, T cells can get things going by recognizing antigens (epitopes) with their surface receptors which bind antigens presented by dendritic cells.
Epitopes are regions on an antigen that can be recognized by an antibody or by T cell receptors. Epitopes are also called antigenic determinants.

The T cell is activated, proliferates, and the daughters travel throughout the body until they reach the place where antigen has invaded.

There they are restimulated by local antigen-presenting cells and release a family of short-range mediators called lymphokines (that is, cytokines made by a lymphocyte).

These mediators attract and activate monocytes and macrophages, which are specialized for phagocytosis, destruction, and eventual repair. Now you begin to get better.

Another type of T cells is specialized for killing any body cell that they recognize as containing abnormal molecules, which may be the result of damaging mutations, or the products of intracellular pathogens like viruses.

All T cells express CD3 and have T cell receptors that are created through DNA rearrangement.

T lymphocytes secrete short-range mediators called lymphokines, a subset of cytokines

Question 2

Discuss briefly the function of B cells

Answer 2

B cells protect the extracellular spaces of the body—the tissue fluids, blood, secretions—by releasing antibodies into these fluids. (Humoral immunity)
B cells also arrange for the phagocytosis and destruction of foreign materials.

Like T cells, they recognize antigens via surface receptors, and become activated and proliferate.

They then release soluble versions of their receptors, namely antibodies, which go out to do the work.

Although all resting lymphocytes look the same, you should now understand that there are two main types: T and B.

B lymphocytes secrete antibodies

B cell receptors see antigen alone, and do not require the simultaneous recognition of
an associated MHC molecule, or presentation, the way T cells do.

When a B cell binds antigen, it is activated to proliferate and differentiate (usually after help from a Tfh cell.)

A fully differentiated B cell is called a plasma cell, a protein-production factory. It releases soluble versions of its receptor, called antibodies. Antibodies bind to the corresponding antigen, and this may be enough to neutralize a toxin, or prevent a microorganism from binding to its target cell.

Question 3

Describe briefly the chief properties of IgG

Answer 3

IgG, short for Immunoglobulin G, is the most abundant antibody in blood.

Two adjacent IgG molecules, binding an antigen such as a bacterium, cooperate to activate complement, a system of proteins that enhances inflammation and pathogen destruction.

The complement system is very important in disease resistance, and its various components can do different things.

Some can lyse (burst) a bacterium by making holes in its membrane. Others
diffuse away from the site where antibody is interacting with antigen, and attract phagocytic cells, in this case predominantly polymorphonuclear neutrophils, or PMNs.

This is useful in disposing of many kinds of antigens.

IgG is the only class of antibody that passes the placenta from mother to fetus in humans, and so is very important in protecting the newborn until it can get its own IgG synthesis going.

Question 4

Describe briefly the chief properties of IgM

Answer 4

IgM is a large polymeric immunoglobulin. It’s even better at activating complement than is IgG and is the first antibody type to appear in the blood after exposure to a new antigen. It is replaced by IgG in a week or two.

Question 5

Describe briefly the chief properties of IgA

Answer 5

IgA is the most important class of antibody in the secretions like saliva, tears, genitourinary and intestinal fluids, and milk.

In these secretions it’s associated with another chain called Secretory Component, which it acquires from epithelial cells during the process of being secreted.

Secretory Component makes it resistant to digestive enzymes. IgA plays an important role as the first line of defense against microorganisms trying to gain access to the body through the mucous membranes.

Question 6

Describe briefly the chief properties of IgE

Answer 6

IgE is designed to attach to mast cells in tissues. Thus attached, when it encounters antigen, it will cause the mast cell to make prostaglandins, leukotrienes, and cytokines, and release its granules which contain powerful mediators of inflammation like histamine.

These mediators produce the symptoms of allergy, which range from hay fever and hives to asthma and anaphylactic shock, depending on the site of antigen entry and dose. All this is inconvenient; but the real role of IgE is in resistance to parasites, such as worms.

Question 7

Define antigen

Answer 7

a

Question 8

Define epitope.

Answer 8

Only a small part an antigenic molecule, 10 to 20 amino acids, called an epitope, fits into the lymphocyte’s receptors. The fit is like a lock and key, and if it’s good, the lymphocyte can become activated.

A single lymphocyte may have a hundred thousand receptors on its surface, but all are identical, so each can only recognize one foreign shape.

Question 9

Discuss lymphocyte activation by antigen with respect to receptor binding, proliferation, and differentiation.

Answer 9

a

Question 10

Distinguish between ‘humoral’ (antibody-mediated) and cell-mediated immunity in terms of the types of lymphocytes involved, the nature of the molecules that they release when activated, and the types of inflammatory cells they preferentially involve. State which of these immunities can be transferred by serum.

Answer 10

a

Question 11

Discuss the common disorders associated with T cells.

Answer 11

Severe combined immunodeficiency syndrome (SCID)
Common γ chain lack of IL-7 signaling causes failure to mature

Purine nucleoside phosphorylase deficiency (causes severe combined immunodeficiency)

Adenosine deaminase deficiency (ADA) (causes severe combined immunodeficiency)

MHC class II deficiency

DiGeorge’s Syndrome (congenital thymic aplasia)

Wiscott-Aldrich Syndrome (x-linked, few platelets, cytotoxic T cell malfunction)

Ataxia-telangiectasia (wobbly gait, T cell deficiency)

Question 12

Discuss the common disorders associated with B cells.

Answer 12

Bruton’s agammaglobulinemia (x-linked agammaglobulinemia)

Transient hypogammaglobulinemia of infancy

Common variable immunodeficiency (defect in T cell signaling of B cell)

IgA and IgG subclass deficiencies

Question 13

timeline of adaptive immune response

Answer 13

So you get a specific response for each antigen but only a few T and B lymphocytes recognize any given antigenic sequence.

MUST BE INDUCED

Requires 7-10 days for activation because rare B and T lymphocytes with identical antigen recognition sequences must find each other.

Generates memory (1-5 additional days for the development of memory)

Question 14

The Two MHC Molecules

Answer 14

Class I = Antigens synthesized within the cell. Cell antigens of antigens from cell infections. Recognized by CD8+ killer T cells. Expressed on all cells except RBCs. Lack of expression on RBCs may playa role in the persistence of the malarial parasite – Plasmodium.

Class II = antigens are products of phagocytosis. Recognized by CD4+ helper T cells. Expressed on monocytes / macrophages, dendritic cells, B cells, and epithelial cells of the thymus.

Also known as HLA (human leukocyte antigens).

Question 15

Lymphoid Organs

Answer 15

B and T cells are produced in the bone marrow.

B cells are released from the bone marrow as mature cells, while T cells must pass through the thymus to become mature cells.

Mature B cells and T cells can be in the blood or resident in the lymph nodes and spleen.

Mature B cells and T cells can travel from one lymph node to another and to and from the spleen (trafficking or homing)

Question 16

Lymphocytes Markers

of T Cells

Answer 16

TCR receptor
CDs:
3
4
8
23

Question 17

Lymphocytes Markers

of B cells

Answer 17

Ig Receptor
CDs:
1
19
20
23
40
79 (a+b)

Question 18

Type 1 Helper T cells, Th1,

Answer 18

recognize antigen and make a lymphokine that attracts thousands of macrophages, the heavy-duty phagocytes, to the area where antigen has been recognized. This intense inflammation can wipe out a serious infection—or a transplanted kidney.
IL-12 and IFN-gamma differentiate this

have a molecular marker, called CD4, on their surface, which
increases their affinity for antigen, helps get them activated, and also serves us as a convenient tag for their identification.

Question 19

Th17 Helper T cells, Th17

Answer 19

are similar to Th1 in that their main role is to cause focused
inflammation, although they are more powerful than Th1. They have been implicated in many serious forms of autoimmunity.

TGFbeta and IL-6 differentiate this

have a molecular marker, called CD4, on their surface, which
increases their affinity for antigen, helps get them activated, and also serves us as a convenient tag for their identification.

Question 20

Type 2 Helper T cells, Th2

Answer 20

stimulate macrophages to become ‘alternatively activated,’ able to function in walling-off pathogens and promoting healing, a process that usually takes place after the pathogen-killing Th1 response. They are very important in parasite immunity.

IL-4 differentiates this

have a molecular marker, called CD4, on their surface, which
increases their affinity for antigen, helps get them activated, and also serves us as a convenient tag for their identification.

Question 21

Follicular Helper T cells, Tfh

Answer 21

are stimulated by antigen and migrate from T cell areas of lymph nodes into the B cell follicles, where they help B cells get activated and make the IgM, IgG, IgE and IgA antibody subclasses.

have a molecular marker, called CD4, on their surface, which
increases their affinity for antigen, helps get them activated, and also serves us as a convenient tag for their identification.

Question 22

Regulatory T cells, Treg

Answer 22

make cytokines that suppress the activation and function of Th1,
Th17, and Th2 cells, so they keep the immune response in check. They are part of the Th family.

have a molecular marker, called CD4, on their surface, which
increases their affinity for antigen, helps get them activated, and also serves us as a convenient tag for their identification.

Question 23

Cytotoxic or killer T cells, CTL

Answer 23

destroy any body cell they identify as bearing a
foreign or abnormal antigen on its surface.

CD8.

Cytotoxic T cells also examine the surfaces of incoming dendritic cells for presented antigenic fragments; in this case, they are looking for fragments on a different class of
antigen-presenting molecule, called MHC Class I, which is not only on dendritic cells, but on all cells. 

The clone of CTL gets expanded and the daughters circulate in large numbers throughout
the body. When one of the daughters of a stimulated CTL binds a cell showing the same peptide, it delivers a ‘lethal hit,’ signaling the target cell to commit suicide by activating an internal self destruction process (apoptosis). The target cell’s nucleus disintegrates and the cell dies. The activated killer T cell then is free to find more targets. This is a great way to eliminate infected cells.

Kill by FAS – FAS ligand interaction.
T cells expressing the FAS ligand bind to FAS, a protein on a target cell to induce caspase activation and apoptosis.

Kill by secreting toxic agents as well.
TNF, a cytokine, can also induce apoptosis. Perforin is a pore-forming protein. Granzymes also induce apoptosis.

Question 24

Activation of Helper T cells

Answer 24

Signal 1
Requires T cell receptor recognition of HLA bound antigen.
Requires CD4+ binding to Class II or CD8+ binding to class I
Signal 2
B7-1 or B7-2 on the APC binds to the T cell surface protein CD28
Other co-stimulation
CD2 binding to leukocyte functional antigen-3, ICAM binding to LFA-1, Cytokine signals

Question 25

IL-2 and IL-15

Answer 25

are general activators of T cells.

Question 26

IL-12 and IFN-γ

Answer 26

drive T helper cells to Th1 helper cell subtypes

Question 27

IL-4

Answer 27

drives T helper cells to Th2 helper cell subtypes.

Question 28

IL-10

Answer 28

down-regulates Th1 and TGF-β down-regulates Th1 and Th2 subtypes

Question 29

Functions of the Thymus

Answer 29

Immature T cells migrate from the bone marrow to the thymus.

T cells become either CD4+ helper T cells or CD8+ killer T cells.

During the maturation process, selection occurs.
	Positive selection – T cells must recognize MHC class I or MHC class II molecules 	in order to be stimulated to mature (self-restricted).

Negative selection – T cells that recognize self-antigens bound to MHC class II on 	the thymus epithelial cells are driven to apoptosis (tolerant to self-antigens).

Mature T cells that are self-MHC restricted and tolerant to self-antigens leave the thymus to settle in lymph nodes or the spleen.

Question 30

IgD

Answer 30

IgD is the main form of antibody inserted into B cell membranes as their antigen receptor, which seems to be its only biological role.

Question 31

Antibody Function in Disease

Answer 31

The first time an antigen enters the body at the mucous membranes, it may penetrate to the local lymphoid tissues where there are T and B cells. The environment there favors the production of IgA and, in certain people, IgE too.

The IgA is secreted and local immunity is established. Oral polio vaccine, for example, favors the formation of mucosal IgA antibodies to polio virus, which trap viruses before they can even enter the body.

If the antigen penetrates further into the body, it reaches local lymph nodes or the spleen, and there the environment favors first IgM production, and then IgG, which bind up pathogens as they circulate.

When most antigens enter the body, there will be both T and B cell responses to them. Some will be more important than others for that particular antigen.

Antibody is important for combating extracellular pathogens like the bacteria Staphylococcus, Streptococcus, and Hemophilus. It is also important for neutralizing toxins like tetanus toxin, and will block the spread of virus in the blood (but once the virus gets into cells, killer T cells will be needed to get rid of it.)

Question 32

Type I Hypersensitivity

Answer 32

Seen in patients who make too much IgE to an environmental antigen, which is often innocuous like a pollen or food.
IgE bound to mast cells and to basophils causes degranulation. Results in the release of histamine which leads to the synthesis of prostaglandins and leukotrienes. Ultimately you get recruitment of Th1 cells and basophils (late phase).

More than 10% of the population have allergic symptoms.

Although usually a nuisance, asthma can be life-threatening, and several people die each year of anaphylactic shock, in which the mast cells throughout the body are suddenly degranulated and release their histamine. A bee sting or certain foods can do it.

We don’t know why some people are allergic; it is partly genetic, and if both your parents are allergic your risk of developing allergies goes up to over 60%.

Question 33

Type II Hypersensitivity

Answer 33

Autoimmunity due to antibodies which can react against self.

There are a number of ways this can come about: For example, if a foreign antigen happens to look like a self molecule, the response to the antigen may accidentally ‘cross-react’ with self.

If an antigen sticks to certain cells in the body, the immune response may destroy the cells
as innocent bystanders. The mechanism is what we observed in normal antibody immunity:
antibody binds, complement is activated, phagocytes are attracted, and they attempt to eat the antigen.

Examples:
Hemolytic disease of the newborn (maternal antibodies to fetal blood group antigens cross the placenta to destroy the fetal RBCs)
Myasthenia gravis (antibodies to acetylcholine receptors cause problems with nerve conduction)
Good pasture’s syndrome (antibodies to basement membranes causes nephritis)

Question 34

Type III Hypersensitivity

Answer 34

Can occur whenever someone makes antibody against a soluble antigen.

Immune complexes of antigen and antibody are usually eaten by phagocytes, but if they
are a bit too small for that, they may instead get trapped in the basement membranes of
capillaries they circulate through. This will happen mostly where there is net outward movement of fluid from blood to tissues, such as in the kidneys, joints, pleura and skin.

The trapped complexes activate complement and the usual inflammatory response occurs, with the tissue damaged as an innocent bystander. No matter what the antigen is, the symptoms tend to be the same: arthritis, glomerulonephritis, pleurisy, rash.

Foreign antigens that cause Type III include drugs like penicillin when given in large doses, and foreign serum, such as horse antiserum to rattlesnake venom (in fact, the syndrome is often called serum sickness.)

More troublesome is when the antigen is internal, as part of an autoimmune process. Thus people with systemic lupus erythematosus, SLE, make antibody to their own DNA, some of which can always be found free in blood, and people with rheumatoid arthritis make antibody… to antibody.

Question 35

Type IV Hypersensitivity

Answer 35

Cell-mediated hypersensitivity caused by activated CD4+ T cells. Can be autoimmune, or more commonly innocent bystander injury.

For example, in tuberculosis most of the destruction in lungs is T cell mediated,
not bacterium-mediated. In acute viral hepatitis, most of the liver destruction is by
killer T cells, just doing their job.

Examples:
Contact hypersensitivity such as a reaction to nickel.
Dendritic Langerhans cells react recruiting CD4+ cells that ultimately mediate this hypersensitivity.
Tuberculin reaction
Macrophages react recruiting CD4+ cells and CD8+ cells that ultimately mediate the hypersensitivity.
Granulomatous hypersensitivity
Macrophages wall off mycobacterium, undergo changes to become epitheliod and recruit CD4+ cells.
Crohn’s disease = granulomas containing macrophages and CD4+ cells in the ileum and colon.