1

VMUF
College of Medicine
Department of Microbiology and Parasitology

Immunology
The study of immunology, a broad fields encompassing both basic research and clinical applications,
deals with host defense reactions to foreign (nonself) entities known as antigens, antigen recognition
molecules, and cell-mediated host defense functions, especially as they relate to immunity to disease,
hypersensitivity (including allergy), autoimmunity, immunodeficiency, and transplantation.
IMMUNITY & THE IMMUNE RESPONSE
Immune response can be innate (nonadaptive) or adaptive (acquired).
Innate Immunity
Innate immunity is resistance that is not required through contact with a nonself (foreign) entity known
as an antigen. It is nonspecific and includes barriers to infectious agents, skin and mucous membranes,
phagocytic cells, inflammatory mediators, and complement components. It may vary with age and with
hormonal or metabolic activity.
Adaptive Immunity
Adaptive immunity, which occurs after exposure to an antigen (an infectious agent) is specific and is
mediated by either antibody or lymphoid cells. It can be passive or active.
A. Passive Immunity
Passive immunity is transmitted by antibodies or lymphocytes performed in another host. The
passive administration of antibody (in antisera) against certain viruses (hepatitis B) can be useful
during the incubation period to limit viral multiplication, after a needle-stick injury to someone
who has not been vaccinated. The main advantage of passive immunization with preformed
antibodies is the prompt availability of large amounts of antibody; disadvantages are the short
life span of these antibodies and possible hypersensitivity reactions if antibodies
(immunoglobulins) from another species are administered.
B. Active Immunity
Active immunity is induced after contact with foreign antigens (microorganisms or their
products). This contact may consist of clinical or subclinical infection, immunization with live or
killed infectious agents or their antigens, exposure to microbial products (toxins, toxoids), or
transplantation of foreign cells. In all these instances the host actively produces antibodies, and
lymphoid cells acquire the ability to respond to the antigens.



2

Advantages of active immunity include longterm resistance (based on memory of prior contact
with antigen and the capacity to respond faster and to a greater extent on subsequent contact
with the same antigen); disadvantages include the slow onset of rtesistance and the need for
prolonged or repeated contact with the antigen.
MECHANISMS OF INNATE IMMUNITY
Physiologic Barriers at the Portal of Entry
A. The Skin
Few microorganisms are capable of penetrating intact skin, but many can enter sweat or
sebaceous glands and hair follicles and establish themselves there. Sweat and sebaceous
secretions-by virtue of their acid pH and certain chemical substances (especially fatty acids)-
have antimicrobial properties that tend to eliminate pathogenic organisms. Lysozyme, an
enzyme that dissolves some bacteria cell walls, is present on the skin and can help provide
protection against some microorganisms. Lysozyme is also present in tears and in respiratory
and cervical secretions.
B. Mucous Membranes
In the respiratory tract, a film of mucus covers the surface and is constantly being driven upward
by ciliated cells toward the natural orifices. Bacteria tend to stick to this film. In addition, mucus
and tears contain lysozyme and other substances with antimicrobial properties. For some
microorganisms, the first step in infection is their attachment to surface epithelial cells by
means of adhesive bacterial surface proteins. If such cells have IgA antibody on their surfaces-a
host resistance mechanism-attachment may be prevented. When organisms enter the body via
mucous membranes, they tend to be taken up by phagocytes and are transported into regional
lymphatic channels that carry them to lymph nodes. The phagocytes act as barriers to further
spread of large numbers of bacteria. The mucociliary apparatus for removal of bacteria in the
respiratory tract is aided by pulmonary macrophages. This entire defense system can be
suppressed by alcohol, narcotics, cigarette smoke, hypoxia, acidosis, and other harmful
influences. Special protective mechanism in the respiratory tract include the hairs at the nares
and the cough reflexes, which prevents aspiration. In the gastrointestinal tract, several systems
function to inactive bacteria: Saliva contains numerous hydrolytic enzymes; the acidity of the
stomach kills many ingested bacteria (V cholerae ) and the small intestine contains many
proteolytic enzymes and active macrophages. Most mucous membranes of the body carry a
constant normal microbial flora that itself opposes establishment of pathogenic microorganisms
(bacterial interference) and has important physiologic functions. For example, in the adult
vagina, an acid pH is maintained by normal lactobacilli. Inhibiting establishment of yeasts,
anaerobes, and gram-negative bacteria.

Innate Immunologic Mechanisms
Very early in the response to infection (first few hours), the engulfment of microorganisms by
macrophages (phagocytosis) and the activation of complement by the alternative pathway are
the important nonspecific host responses.

3

The next line of defense includes some responses that are still nonadaptive, release of cytokines
from macrophages and the release of other mediators that trigger the inflammatory response.

The inflammatory response occurs rapidly and generally adaptive response is initiated.
However, some microorganisms have found ways to evade these nonspecific host response for
example, bacteria (pneumococci) with polysaccharide-rich capsules can evade phagocytosis, and
some viruses (such as poxviruses) produce cytokine receptor homologs that function as
competitive antagonists of the cytokines. This slows the immune response long enough for the
microorganism to establish a niche.

A. Reticuloendothelial System
This system involves mononuclear phagocytic cells present in blood, lymphoid tissue, liver,
spleen, bone marrow, lung, and other tissues that are efficient in uptake and removal of
particulate matter from lymph channels and the bloodstream. It includes cells lining blood
and lymph sinuses (Kupffer cells in the liver) and histiocytes of tissues (macrophages). An
important function of the spleen, bone marrow, and other reticuloendothelial organs is
filtering microorganisms from the blood-stream. Phagocytosis by reticuloendothelial cells is
greatly enhanced by opsonins. When macrophages recognize microbial constituents, they
are stimulated to release cytokines that cause the recruitment of more phagocytic cells to
the site of infection.
B. Alternative Pathway of Complement Action
One pathway of complement activation, the alternative pathway, is very important as a first
line of defense against infection by microorganisms. The alternative complement pathway
can be activated by microbial surfaces and proceeds in the absence of antibody. There are
several antimicrobial properties of complement proteins that contribute to host defense,
including opsonisation, lysis of bacteria, and amplification of inflammatory responses
through the anaphylatoxins C5a, C4a, and C3a.
C. Phagocytosis
During bacterial infection, the number of circulating phagocytic cells often increases. The
main functions of phagocytic cells include migration, chemotaxis, ingestion, and microbial
killing. Microorganisms (and other particles) that enter the lymphatics, lung, bone marrow,
or bloodstream are engulfed by any of a variety of phagocytic cells. Among them are
polymorphonuclear leukocytes (granulocytes), phagocytic monocytes (macrophages), and
fixed macrophages of the reticuloendothelial system. Phagocytosis can occur in the absence
of serum antibodies, particularly if aided by the architecture of tissue.

1. Factors affecting phagocytosis
Phagocytosis is made more efficient by the presence of antibodies (opsonins) that coat surface
of bacteria and facilitate their ingestion by phagocytes. Opsonisation can occur by three
mechanisms: (1) Antibody alone can act as opsonin; (2) antibody plus antigen can activate
complement via the classic pathway to yield opsonin; and

4

(3) opsonin may be produced by a heat-labile system in which immunoglobulin or other factors
activate C3 via the alternative pathway.
2. Granulocytes (polymorphonuclear leukocytes or neutrophils)
Granulocytes contain granules composed of lysozyme, other hydrolytic enzymes, several
cationic proteins, the defensins (antimicrobial components), lactoferrin, and toxic nitrogen
oxides.
The functional mechanisms of intracellular killing of microorganisms in phagocytic granulocytes
are not fully known. They include nonoxidative mechanisms.
a. Increased oxidative activity results in accumulation of H
2
O
2
.
b. In normal granulocytes, superoxide anion (O
2
) is generated when paricles are
phagocytosed. When the bone marrow of patients is suppressed by disease, drugs, or
radiation, the number of functional granulocytes falls. If the granulocytes level drops below
500 polymorphonuclear neutrophils per microliter, the patient is highly susceptible to
opportunistic infection by bacteria.
3. Macrophages (circulating phagocytic monocytes)
Macrophages are derived from monocyte stem cells in bone marrow, have a longer life span
than circulating granulocytic phagocytes, and continue their activity at a lower pH. Macrophages
in blood can be activated by various stimulants, or activators, including microbes and their
products, antigen-antibody complexes, inflammation, sensitized T lymphocytes, cytokines, and
injury. Activated macrophages have an increased number of lysosomes and produce and release
interleukin-1 which has a wide range of activity in inflammation.
D. Inflammatory Response
Any injury to tissue, such as that following establishment and multiplication of
microorganisms, elicits an inflammatory response. The other mediators released from
activated macrophages include prostaglandins and leukotrienes. These inflammatory
mediators begin to alicit changes in local blood vessels. This begins with dilation of local
arterioles and capillaries, from which plasma escapes. Edema fluid accumulates in the area
of injury, and fibrin forms a network and occludes the lymphatic channels, limiting the
spread of organisms. A second effect of the mediators is to induce changes in expression of
various adhesion molecules on endothelial cells and on leukocytes. Cytokines and
derivatives of arachidonic acid, including prostaglandins and leukotrienes, are mediators of
the inflammatory response. Drugs that inhibit synthesis of prostaglandins (by blocking the
enzyme cyclooxygenase) act as anti-inflammatory agents.
E. Fever
Fever is the most common systemic manifestation of the inflammatory response and a
cardinal symptom of infectious disease.

1. Possible mechanisms of fever production
The ultimate regulator of body temperature is the thermoregulatory center in the hypothalamus, which
is subject to physical and chemical stimuli. Direct mechanical injury or application of chemical
substances to these centers results in fever.

5

Among the substances capable of inducing fever (pyrogens) are endotoxins of gram-negative bacteria
and cytokines released from lymphoid cells, such as interleukin
Various activators can act upon mononuclear phagocytes and other cells and induce them to release
interleukin-1. Among these activators are microbes and their products; toxins, including endotoxins;
antigen-antibody complexes; inflammatory processes; and many others. Interleukin-1 is carried by the
bloodstream to the thermoregulatory center in the hypothalamus, where physiologic responses are
initiated that result in fever. Other effects of interleukin-1 are mentioned below. Cytokines are small
soluble proteins that are produced by one cell and influence other cells.
2. Beneficial effects of fever
Antibody production and T cell proliferation are more efficient at higher body temperatures than at
normal levels. Suppression of fever by drugs (aspirin) is not harmful during infections and often makes
febrile patients more comfortable.
3. Interferons
Viral infection induces the expression of antiviral proteins known as interferons. The alpha and beta
interferons help control viral replication by inhibiting proteins synthesis in cells.
4. Natural Killer (NK) Cells
Natural killer cells represent a district functional population of lymphocytes. They play a role in
antibody-dependent cellular cytotoxicity and have a role in the early phases of infection with
herpesviruses and other intracellular pathogens. They resemble large, granular lymphocytes
morphologically related to T cells. They do have two types of surface receptor, including an activating
receptor that recognizes carbohydrate ligands and an inhibitory receptor that recognizes MHC class I
molecules. They can kill certain virus-infected cells with altered levels of MHC class I molecules.
MECHANISMS OF SPECIFIC HOST DEFENSE
Adaptive Response
The adaptive response can be antibody-mediated (humoral), cell-mediated (cellular), or both. Upon
entry of a potential pathogen into the host and after interaction with the nonadaptive defense system
just described, it or its major antigens are taken up by antigen-presenting cells (APCs), macrophages. In
the antibody-mediated arm, helper lymphocytes recognize the pathogens antigens complexed with
class II MCH proteins on the surface of an antigen-presenting cell (macrophage or B cell) and produce
cytokines that activate B cells expressing antibodies that specifically match the antigen. In the cell-
mediated arm, the antigen-MCH class II complexes is recognized by helper (CD4) T lymphocytes, while
the antigen-MCH class I complex is recognized by cytotoxic (CD8) T lymphocytes. Helper T cell activity, in
addition to stimulating B cells to produce antibodies.

6

Promotes the development of delayed hypersensitivity and thereby also serves in the defense against
intracellular agents, including intracellular bacteria (mycobacteria), fungi, protozoa, and viruses.
Cytotoxic T cell activity is aimed mainly at the destruction of cells in tissue grafts, tumor cells, or cells
infected by some viruses.
Antigens
A. Foreignness (Difference From Self)
In general, molecules recognized as self are not immunogenic; for immunogenicity, molecules must be
recognized as nonself.
B. Molecular Size
The most potent immunogens are usually proteins. Generally, molecules with a molecular weight less
than 10,000 are weakly immunogenic, and very small ones (amino acids) are nonimmunogenic.
C. Chemical and Structural Complexity
D. Antigenic Determinants (Epitopes)
The smallest unit of a complex antigen that is capable of binding to an antibody is known as an antigenic
determinant, or epitope.
E. Genetic Constitution of the Host
Two strains of the same species of animal may respond differently to the same antigen because of a
different composition of immune response genes.
F. Dosage, Route, and Timing of Antigen Administration
The immune response can be optimized by carefully defining the dosage (including number of doses),
route of administration, and timing of administration )including intervals between doses). It is possible
to enhance the immunogenicity of a substance by mixing it with an adjuvant. Adjuvants are substances
that stimulate the immune response.
Cellular Basis of the Immune Response
The capacity to respond to immunologic stimuli resides mainly in lymphoid cells.
A. B Cells
B cells are lymphocytes that develop in the bone marrow in mammals.
B. T Cells
T cells are lymphocytes that require maturations in the thymus and form several subclasses with specific
functions. They are the source of cell-mediated immunity.

7

ANTIGEN RECOGNITION MOLECULES
ANTIBODIES
Antibodies (immunoglobulins) are formed by B lymphocytes. Each individual has a large pool of
different B lymphocytes (about 10
11
) that have a life span of days or weeks and are found in the bone
marrow, lymph nodes, and gut-associatted lymphoid tissues (tonsils or appendix). B cells display
immunoglobin molecules on their surface. These immunoglobins serve as receptors for a specific
antigen, soi that each B cell can respond toonly one anytigen or a closely related group of antigens. An
antigen interacts with the B lymphocyte that shows the best fit by virtue of its immunoglobulin
surface receptor. The initial step in antibody formation is phagocytosis of the antigen, usually by
antigen-presenting cells (chieftly macrophages or B cells) that process and present the antigen to T cells.
Antibody Structure & Function
Antibodies are immunoglobulins which react specifically with the antigen that stimulated their
production. They make up about 20% of plasma proteins. Antibodies that arise in an animal in response
to a single complex antigen are heterogeneous. These antibodies are said to be polyclonal. Antibodies
that aries from a single clone of cells, are referred to as monoclonal.
Immunoglobulin Classes
A. IgG
Each IgG molecule consist of two L chains and two H chains linked by disulfide bonds (molecular formula
H
2
L
2
). Because it has two identical antigen-binding sites, it is said to be divalent. There are four
subclasses (IgGI to IgG4). IgG is the predominant antibody insecondary response and constitutes an
important defense against bacteria and viruses. It is the only antibody to pass the placenta and is
therefore the most abundant immunoglobulin in newborns.
B. IgM
IgM is the main immunoglobulin produced early in the primary immune response. IgM is present on the
surface of virtually all uncommitted B cells. It is the most efficient immunoglobulin in agglutination,
complement fixation, and other antigen-antibody reactions and is important also in defense against
bacteria and viruses. It can be produced by a fetus undergoing an infection.
C. IgA
IgA is the main immunoglobulin in secretios such as milk, saliva, and tears and in secretions of the
respiratory, intestinal, and genital tracts. It protects mucous membranes from attack by bacteria and
viruses.



8

D. IgE
The Fc region of IgE binds to a receptor on the surface of mast cells and eosinophils. This bound IgE acts
as a receptor for the antigen that stimulated its production, and the resulting antigen-antibody complex
triggers allergic responses of the immediate (anaphylactic) type through the release of mediators.
E. IgD
IgD acts as an antigen receptor when present on the surface of certain B lymphocytes. In serum it is
present only in trace amounts.
Immunoglobulin Genes & Generation of Diversity
Special genetic mechanisms have evolved to produce the very large number of immunoglobulin
molecules (about 10
11
) that develop in the host in response to antigenic stimulation without requiring
excessive numbers of genes.
Immunoglobulin Class Switching
Initially, all B cells matched to an antigen carry IgM specific for that antigen and produce IgM in
response to this exposure to antigen. In class switching, the same assembled V
H
gene can sequentially
associate with different C
H
genes, so that the immunoglobulin produced later (IgG, IgA, or IgE) has the
same specificity as the original IgM but different biologic characteristics.

CELL SURFACE RECEPTORS FOR ANTIGEN
1. B Cell Receptor for Antigen
B cells express a form of gM that is located on the cell surface. Cell surface IgM has the same antigen
specificity as the secreted IgM antibody molecule.
2. T Cell for Antigen
The T cell receptor is a transmembrane heterodimetric protein composed of two disulfide-linked chains.
This receptor resembles a membrane-bound Fab fragment of immunoglobulin.
3. The major Histocompatibility Complex
The major histocompatibility complex (MHC) was first detected as the genetic locus encoding the
glycoprotein molecules (transplantation antigens) responsible for the rapid rejection of tissue grafts
transplanted between genetically nonidentical individuals.
4. The Immunoglobulin Supergene Family
All the molecules discussed-antibodies, the T cell receptor, and MHC proteins-have structural features in
common.

9

5. Antigen Processing & Presentation
Antigen processing and presentation are the means by which antigens become associated with self MCH
molecules for presentation to T cells with appropriate receptors.
ANTIBODY-MEDIATED (HUMORAL) IMMUNITY
The Primary Response
When an individual encounters an antigen for the first time, antibody to that antigen is detectable in the
serum within days or weeks depending on the nature and dose of the antigen and the route of
administration (oral, parenteral). The serum antibody concentration continues to rise for several weeks
and then declines; it may drop to very low levels. The first antibodies formed are IgM, followed by IgG,
IgA, or both. IgM levels tend to decline sooner than IgG level.
The Secondary Response
In the event of a second encounter with the same antigen (or a closely related cross-reacting one)
months or years after the primary response, the antibody response is more rapid and rises to higher
levels than during the primary response. This changes in response is attributed to the persistence of
antigen-sensitive memory cells following the first immune response. In the secondary response, the
amount of IgM produced is qualitatively similar to that produced after the first contact with the antigen.
Protective functions of Antibodies
Because of the close structural complementarity between antibodies and the antigen that elicited them,
the two tend to blind to each other whenever they meet, in vitro or in vivo. Antibodies can produce
resistance to infection by opsonising (coating) organisms, which makes them more readily ingested by
phagocytes; antibodies can bind to viruses and reduce their ability to blind to cellular receptor
molecules and invade host cells; and most importantly, antibodies can neutralize toxins of
microorganisms (diphtheria, tetanus, and botulism) and inactive their harmful effects. Antibodies can be
induced actively in the host by administering appropriate antigens or preparations containing them
(toxoids of diphtheria, tetanus), but protection is delayed until the antibodies reach helpful
concentrations. In antibodies can be administered passively (preformed in another host), which makes
them immediately available for preventive or therapeutic purposes. Antibody-mediated immunity
against bacteria is most effective when directed against microbial infections in which virulence is related
to polysaccharide capsules (pneumococcus, haemophilus, neisseria). In such infections, antibodies
complex with the capsular antigens and make the organisms susceptible to ingestion by phagocytic cells
and destruction within the cells.




10

THE COMPLEMENT SYSTEM
The complement system includes serum and membrane-bound proteins that function in both adaptive
and innate host defense system. These proteins are highly regulated and interact via a series of
proteolytic cascades. The term complement refers to the ability of these proteins to complement
(augment) the effects of other components of the immune system (antibody). Complement has several
main effects: (1) lysis of cells (bacteria and tumor cells), (2) production of mediators that participate in
inflammation and attract phagocytes, (3) opsonisation of organisms and immune complexes for
clearance by phagocytis, and (4) enhancement of antibody-mediated immune responses. Complement
proteins are synthezised mainly by the liver and by phagocytic cells.
Complement Activation
Several complement components are proenzymes, which must be cleaved to form active enzymes.
A. The Classic Pathway
Only IgM and IgG activate or fix complement via the classic pathway.
B. The Alternative PathwAy
Many unrelated substances, from complex chemicals (endotoxin) to infectious agents (parasites),
activate a different pathway.
Regulation of the Complemen t System
Major Biologic Effects
A. Opsonization
Cells, antigen-antibody complexes, and other particles are pphagocytosed much more efficiently in the
presence of C3b because of the presence of C3b receptors on the surface of many phagocytes.
B. Chemotaxis
C5a stimulates movement of neutrophils and monocytes toward sites of antigen deposition.
C. Anaphylatoxins
C3a, C4a, and C5a can produce in creased vascular permeability and smooth muscle contraction. C3a
and C5a also stimulate mast cells to release histamine.
D. Cytolysis
Insertion of the C5b6789 complex into the cell surface leads to killing or lysis of many types of cells,
including erythrocytes, bacteria, and tumor cells.


11

Clinical Consequences of Complement Deficiencies
Deficiency in components of the membrane attack complex greatly enhances susceptibility to neisserial
infections. Deficiencies in components of the alternative pathway are also known properdin deficiency is
associated with greater susceptibility to meningococcal disease.
CELL-MEDIATED IMMUNITY
Antibody-mediated immunity is most important in toxin-induced disorders, in most microbial infections,
it is cell-medaited immunity that imparts resistance and aids in recovery, through the cooperation of
antibodies may be required. Furthermore, cell-mediated immunity is central in host defense against
intracellular pathogens such as viruses and in combating tumor cells. The important role of cell-
mediated immunity is underlined in clinical situations in which its suppression (AIDS) results in
overwhelming infections or tumors.

Development of T Cells
Within the thymus, T cell progenitor cells undergo differentiation (under the influence of thymic
hormones) into T cell subpopulations.
T Cell Proliferation & Differentiation
T cell proliferation depends on a variety of events. Resting T cells must receive two signals for activating
to occur. One signal comes from the T cell receptor interacting with an MCH-antigen complex presented
on another cell.
T Cell Functions
T cell have both effector and regulatory functions.
A. Effector Functions
Cell-mediated immunity and delayed hypersensitivity reactions are produced mainly against antigens of
intracellular parasites, including viruses, fungi, some protozoa, and bacteria (mycobacteria). A deficiency
in cell-mediated immunity manifests itself primarily as marked susceptibility to infection by such
microorganisms and to certain tumors.
B. Regulatory Functions
T cells play a central role in regulating both humoral (antibody-mediated) and cellular (cell-mediated)
immunity. Antibody production by B cells usually requires the participation of T helper cells (T cell-
dependent response), but antibodies to some antigens (polymerized macromolecules such as bacterial
capsular polysaccharide) are the result of a T cell-independent response.


12

HYPERSENSITIVITY
The term hypersensitivity or allergy, denotes a condition in which an immune response results in
exaggerated or inappropriate reactions that are harmful to the host. In a given individual, such reactions
typically occur after the second contact with a specific antigen (allergen). The first contact is a necessary
preliminary event that induces sensitization to that allergen. There are four main types of
hypersensitivity reactions. Types I, II, and III are antibody-mediated; type IV is cell-mediated.
Type I: Immediate (Anaphylactic)
Hypersensitivity
Type I hypersensitivity manifests itself in tissue reactions occurring within 5 minutes after the antigen
combines with the matching antibody. It may take place as a systemic anaphylaxis (after administration
of heterologous proteins) or as a local reaction (an atopic allergy such as hey fever). The general
mechanism of immediate hypersensitivity involves the following steps. An antigen induces the
formation of IgE antibody, which binds firmly by its Fc portion to receptor on mast cells and eosinophils.
A. Type 1 Hypersensitivity Mediators
1. Histamine exists in a preformed state in platelets and in granules of mast cells and eosinophils.
Its release causes vasodilation, increased capillary permeability, and smooth muscle contraction
(bronchospasm). Antihistamine drugs can block histamine receptor sites and are relatively
effective in allergic rhinitis. Histamine is one of the primary mediators of a type I reaction.
2. Prostalandins and thromxanes Related to leukotrienes, prostaglandins and thromboxanes are
derived from arachiodic acid via the cyclooxygenase pathway. Prostaglandins produce
bronchoconstriction and dilation and increased permeability of capillaries. Thromboxanes
aggregate platelets.
B. Treatment and Prevention of Anaphylactic
Treatment aims to reverse the action of mediators by maintaining the aiway, providing artificial
ventilation if necessary, and supporting cardiac function. Epinephrine, antihistamines, and
corticosteroids.
C. Atopy
Atopic hypersensitivity disorders exhibit a strong familial predisposition and are associated with
elevated IgE levels. Predisposition to atopy is clearly genetic, but symptoms are induced by
exposure to specific allergens. These antigens are typically environmental (respiratory allergy to
pollens, ragweed, or house dust) or foods (intestinal allergy to shellfish). Common clinical
manifestations include hay fever, asthma, eczema, and urticaria.
Type II: Hypersensitivity
Type II hypersensitivity involves the binding of antibodies (IgG or IgM) to cell surface antigens or
extracellular matrix molecules. Antibody directed at cell surface antigens can activate complement (or
other effectors) to damage the cells. The antibody (IgM or IgM) attaches to the antigen via the Fab
region and acts as a bridge to complement via the Fc region.

13

Type III: Immune Complex Hypersensitivity
When antibody combines with its specific antigen, immune complexes are formed. Normally, they are
promptly removed by the reticuloendothelial system, butr occasionally they persist and are deposited in
tissues, resulting in several disorders. In persistent microbial or viral infections, immune complexes may
be deposited in organs (the kidneys), resulting in dysfunction. Wherever immune complexes are
deposited, they activate the complement system, and macrophages and neutrophils are attracted to the
site, where they cause inflammation and tissue injury. There are two major forms of immune complex-
mediated hypersensitivity. One is local (Arthus reaction) and typically elicited in the skin when a low
dose of antigen is injected and immune complexes form locally. A second form of type III
hypersensitivity involves systemic immune complex disease. Acute poststreptococcal
glomerulonephritis is a well-known immune complex disease. Its onset occurs several weeks after a
group A -hemolytic streptococcal infection, particularly of the skin, and often occurs with infection due
to nephritogenic types of streptococci.
Type IV: Cell-Mediated (Delayed) hypersensitivity
Cell-mediated hypersensitivity is a function not of antibody but of specially sensitized T lymphocytes
that activate macrophages to cause an inflammatory response. The response is delayed, it usually starts
2-3 days after contact with the antigen and often lasts for days.
A. Contact Hypersensitivity
Contact hypersensitivity occurs after sensitization with simple chemicals (nickel, formaldehyde), plant
materials (poison ivy, poison oak), topically applied drugs (sufonamides, neomycin), some cosmetics,
soaps, and other substances. In all cases, small molecules enter the skin and then, acting as haptens,
attach to body proteins to serve as complete antigen. Cell-mediated hypersensitivity is induced,
particularly in skin. When the skin again comes in contact with the offending agent, the sensitized
person develops erythema, itching, vesication, eczema, or necrosis of skin within 12-48 hours. Patch
testing on a small area of skin can sometimes identify the offending antigen. Subsequent avoidance of
the material will prevent recurrences.
B. Tuberculin-Type Hypersensitivity
Delayed hypersensitivity to antigens of microorganisms occur in many infectious diseases and has been
used as an aid diagnosis. It is typified by the tuberculin reaction. When a small amount of tuberculin is
injected into the epidermis of a patient previously exposed to Mycobacterium tuberculosis, there is little
immediate resaction. A positive skin test indicates that the person has been infected with the agent but
does not imply the presence of current disease. However, a recent change of skin test response from
negative to positive suggests recent infection and possible current activity. A positive skin test response
assists in diagnosis. For example, in leprosy, a positive lepromin skin test indicates tuberculoid disease,
with active cell-mediated immunity, whereas a negative test suggests lepromatous leprosy, with weak
cell-mediated immunity.

14

INADEQUATE IMMUNE RESPONSES TO INFECTIOUS AGENTS
There are a considerable number of inherited immune deficiency diseases that can effect the host
response to infection. In some cases, the pathogen ultimately causes immune suppression.
IMMUNOLOGIC DIAGNOSTIC TESTS
An antigen will react only with antibody elicited by that antigen or by a closely related antigen.
Enzyme-Linked Immunosorbent Assay (ELISA)
Enzyme immunoassay, which has many variations, depends on the conjugation of an enzyme to an
antibody. To measure antibody, known antigens are fixed to a solid phase (plastic microdilution plate),
incubated with test antibody dilutions, washed, and reincubated with an anti-immunoglobulin labelled
with an enzyme (horseradish peroxidise).
Immunofluorescence
Fluorescence dyes (fluorescein, rhodamine) can be covalently attached to antibody molecules and made
visible by ultraviolet light in the fluorescence microscope. A direct immunofluorescence reaction occurs
when known labelled antibody interacts directly with unknown antigen. An indirect
immunofluorescence reaction occurs when a two-stage process is used. Another use of fluorescent-
tagged antibody molecules is to count and classify cells by flow cytometry using a fluorescence-
activated cell sorter (FACS).
Immunoblotting
Immunoblotting (sometimes called Western blotting) is a method for identifying a particular antigen in a
complex mixture of proteins. The complex mixture of proteins is subjected to sodium dodecyl sulphate
(SDS)-polyacrylamide gel electrophoresis (PAGE). This separates the proteins according to molecular
size.