Chapter 9
host response to
infection
Definition of terms
IMMUNOLOGY
• The study of immune system and the immune response.
IMMUNOGEN
• is any substance that is capable of inducing an immune response, whether humoral or cellular.
ANTIGEN
• Is a substance that is recognized by a antibody or T cell and serves as the target of the
immune response.
PROPERTIES OF IMMUNOGENS
1. FOREIGNNESS
• Antigens or immunogens are genetically foreign to the
host, or recognized by the body as non-self.
4. IMMUNOGENICITY
• Of a substance also increases with chemical complexity.
The more structurally complex a substance is, the more
immunogenic it becomes.
2. CHEMICAL COMPOSITION
• Most organic substances can be antigenic, except for pure 5. ABILITY TO RESPOND
lipids and nucleic acids.
• To a particular immunogen is predetermined by the
• Proteins serve as the most antigenic or most immunogenic. genetic constitution of the host animal.
6. ANTIGENICITY
3. MOLECULAR SIZE
• Molecules with molecular weights below 10,000 Daltons • Also depends on the method of administration. The dose
of the antigen introduced and the mode of administration
are only weakly immunogenic or not immunogenic at all.
should be taken into account as well, as it varies among
• Molecular weights greater than 100,000 Daltons are very
immunogens.
potent immunogens.
LINES OF DEFENSE
Our body is equipped with defense mechanisms that aim to prevent the occurrence of infection.
FIRST LINE OF DEFENSE
• Serves to prevent the entry of microorganisms into the body.
• Major first line of defense: skin and mucous membranes.
• KERATIN LAYER OF THE SKIN
- a mechanical barrier that prevents the entry of the organisms.
SECOND LINE OF DEFENSE
• The innate arm of the immune system.
• Main factor involved: inflammatory response.
• Other factors: killer cells, neutrophils and macrophages; and substances release by activated cells such as
interferons.
THIRD LINE OF DEFENSE
• The adaptive arm of the immune system
• Major players: B cells and T cells.
THE IMMUNE SYSTEM
The immune systems main function
• To defend the host against infection caused by viruses, bacteria, fungi, and parasites.
• Most important cells that are involves in the immune system: B lymphocytes or B cells and T lymphocytes or T cells – derived from the
bone marrow.
PRIMARY(OR CENTRAL) LYMPHOID ORGANS
• Where lymphocytes are produced.
• lymphoid organs: thymus and the bone marrow.
• B cells and T cell
- originated in the bone marrow.
- only B cells remains in the bone marrow to reach maturity.
- T cells need to migrate to the thymus, where they mature.
- upon maturation: B and T cells enter bloodstream and migrate to secondary (or peripheral) lymphoid organs
SECONDARY (OR PERIPHERAL) LYMPHOID ORGANS
• are the sites where antigens from organisms entering the body or present on the body surfaces are trapped. Its is in these lymphoid
tissues where B cells and T cells encounter antigens through their receptors.
• Lymphoid organs: lymph nodes, spleen, and mucosa-associated lymphoid tissue(tonsils, appendix, peyer's patches of the small intestine.)
THE IMMUNE SYSTEM
T LYMPHOCYTES (T CELLS)
• Consist of 2 main subsets: the T helper cells
(CD4+ T cells) and the cytotoxic T cells (or
cytolytic T cells or CD8+ T cells).
• T cells make up of 60-80% of circulating
lymphocytes in the blood.
• T helper cells
- promote inflammation and antibody
production.
• Cytotoxic T cells
- recognize and kill virus-infected cells, tumor
cells and foreign cells.
- also possess immunologic memory.
B LYMPHOCYTES (B CELLS)
• Primary function of the B cell is to
produce antibodies.
• Also function as antigen presenting cells.
• B cells possess immunologic memory –
allows them to have an accelerated
response upon re-exposure upon reexposure to the same organism or antigen.
• B cells are the only cells in the body with 2
immunoglobulins on its surface (IgM and
IgD)
INNATE IMMUNITY
INNATE IMMUNITY
• Also known as natural immunity.
• it is non-specific and includes the host barriers (first line of defense)
• Also involved the processes such as phagocytosis and inflammation (second line of defense)
• Activated within minutes following exposure to the antigen, but does not improve after exposure.
• Does not possess memory.
• THE INMATE ARM OF IMMUNE SYSTEM
- major function: kills invading microorganisms, activating acquired or adaptive immune responses.
- often successful in eliminating microbes and preventing infectious diseases.
IMPORTANT COMPONENT
INNATE IMMUNITY
FACTORS THAT LIMIT ENTRY OF MICROORGANISMS
MODE OF ACTION
• Keratin layer of intact skin
• Acts as a mechanical barrier
• Lysozyme in tears and other secretions
• Degrades the bacterial cell wall
• Respiration cilia
• Directs organisms trapped in mucus out of the
respiratory passageways.
• Low ph in stomach and vagina; fatty acids in skin
• Surface phagocytes
• Normal flora of throat, colon, and vagina.
• Natural killer cells
• neutrophils
• Retards the growth of microbes
• Ingest and destroy microbes
• Prevents colonization by pathogens
• Kill virus-infected cells
• Ingest and destroy microbes
FACTORS THAT LIMIT ENTRY OF MICROORGANISMS
• Macrophages and dendritic cells
• Interferons
• Complement system
• Fever
• Inflammatory response
MODE OF ACTION
• Ingest and destroy microbes; present antigens to
helper T cells
• Inhibit viral replication
• Membrane attack complex creates holes in bacterial
cell membrane
• Retards bacterial growth
• Limits spread of microbes
ACQUIRED (ADAPTIVE) IMMUNITY
ACQUIRED IMMUNITY
• occurs after exposure to an antigen, improves upon repeated exposure, and is specific.
• Responsible for conferring lifetime protective immunity to re-infection with the same pathogen.
• May be active or passive.
• Active immunity
- resistance-induced after contact with foreign antigens.
- advantage is that resistance is long term
- disadvantage is its slow onset.
• Passive immunity
- resistance based on antibodies preformed in another host.
- advantage is that large amount of antibody are promptly available.
- disadvantages include short lifespan of antibodies and possible hypersensitivity reactions that can occur.
HUMORAL IMMUNITY
HUMORAL IMMUNITY OR ANTIBODY-MEDIATED IMMUNITY
• Directed primarily against
(1)Toxin-induced diseases
(2)Infections in caused by encapsulated organisms. (ex: pneumococci, meningococci,
haemophilus, influenzae)
(3)Certain viral infections.
• Involved mainly the activities of the different antibodies and involves both a primary and
secondary response.
ANTIBODIES
• Are globulin proteins (immunoglobulins) that react specifically with the antigen that stimulated their
production.
MOST IMPORTANT FUNCTION OF ANTIBODIES
(1) To neutralize toxins and viruses.
(2) To opsonize microbes so that they will be readily recognized and more easily phagocytosed
(3) To activate complement
(4) To prevent the attachment of microbes to mucosal surfaces.
FIVE MAIN CLASSES OF ANTIBODIES
IgG
• Predominant antibody in the secondary response
• Major defense against bacteria and viruses
• Only antibody can cross the placenta
• Therefore, the most abundant antibody in newborns
• Together with IgM; can activate complement
• Only immunoglobulin that acts as an opsonin, thus
enhancing phagocytosis.
• Main immunoglobulin in chronic infections
IgM
• Largest among the immunoglobulin
• Main immunoglobulin produced early in the primary
response.
• Predominant immunoglobulin in acute infections
• Most efficient activator of complement owing to its
large size
• Present on the surface of B cells
• Important in defense against bacteria and viruses
IgA
• Main in immunoglobulin in secretions
• Prevents the attachment of organisms (bacteria and
viruses) to mucous membranes
IgD
• Has no antibody function
• Found in the surface of many B cells
• Serves as the surface marker for B cells, but may function
as an antigen receptor
• Present in small amount of serum.
IgE
• Medically important
(1)Mediates immediate (anaphylactic) hypersensitivity
reaction
(2)Provides defense against certain parasites such as
helminths
• It binds to the surface of mast cells and basophils, after
binding, serves as an antigen receptor for the antigen
(allergen)
ANTIBODIES
PRIMARY RESPONSE
• Involved in the first encounter with the antigen.
• Antibodies become detectable in the serum after a period of 7-10 days.
• Serum level of antibodies continues to rise for several weeks, then declines and may drop to very low levels.
• First antibodies to appear: IgM, followed by IgG or IgA
SECONDARY RESPONSE
• Occurs after re-exposure to the same antigen.
• Second encounter with the same antigen or closely related one occurring months or years after the primary response
leads to a rapid antibody response of a much higher intensity than the primary response.
• During the secondary response, the amount of IgM produced is similar to that after the first contact with the antigen,.
• The IgG levels tend to persist much longer than the primary response.
CELL-MEDIATED IMMUNITY
• Is also important in defense against fungi, parasites, and tumors and in the rejection of organ transplants.
• Individuals with competent cellular immunity, opportunistic pathogens rarely or never cause disease, and the spread of
other agents, such as certain viruses or tumors.
• Bacterial intracellular infections such as tuberculosis and viral infections, is primarily cell-mediated immunity that imparts
resistance and aids in recovery.
COMPONENTS OF THE CELL-MEDIATED IMMUNITY
(1)Macrophages - which present the antigen to T cells, as well as ingest and destroy microbes.
(2)Helper T cells – which participate in antigen recognition and in the regulation of B cells and cytotoxic T cells functions.
(3)Natural killer cells (NK) – which can inactivate pathogens.
(4)Cytotoxic T cells - which can kill virus-infected cells, with or without antibodies.
- macrophages and helper T cells produce substances called cytokines, which can activate further other helper T cells
cytotoxic T cells.
CELL-MEDIATED IMMUNITY
PRIMARY RESPONSE
• After initial exposure to the antigen, the specific T cell proliferates and produces a small clones of cells.
SECONDARY RESPONSE
• On subsequent exposure to the antigen, the small clones expand and many more specific T cells are produced.
HYPERSENSITIVITY REACTIONS
HYPERSENSITIVITY
• Is used when an immune response results in exaggerated or inappropriate reactions that are harmful to the host.
HYPERSENSITIVITY REACTIONS
FOUR MAIN TYPES
TYPE 1 : IMMEDIATE ANAPHYLACTIC HYPERSENSITIVITY
• What we know as “allergy”.
• The process begins when an allergen induces the formation of IgE, which binds to mast cells and basophils of certain
chemicals (especially histamine).
• The first contact with the antigen sensitizes, that is, induces, the antibody.
• Subsequent contacts elicit the allergic response. (ex: pollens, animal fur, foods, and various drugs.)
• Clinical manifestations are typical in a given individual. These can take the form of urticaria (hives), eczema, rhinitis and
conjunctivitis (also known as hay fever), and asthma.
• The most severe form is systemic anaphylaxis, in which severe bronchoconstriction and hypotension or shock can be
fatal. The most common causes are food (such as peanuts and shellfish), venom, and drugs (e.g, penicillin).
TYPE 2: CYTOTOXIC/CYTOLYTIC HYPERSENSITIVITY
• Involves 3 possible mechanisms
FIRST MECHANISM
• involves the natural killer cells in a process called antibody-dependent cellular cytotoxicity (ADCC).
• Entry of antigen stimulate formation of IgG, which binds to the antigen. This binding causes activation of the natural killer
cells (responsible for the destruction of the antigen).
SECOND MECHANISM
• Known as antibody-complement mediated lysis.
• Occurs when antibodies directed at antigens of the cell membrane activate complement. This generates a membrane attack
complex, which damages the cell membrane.
THIRD MECHANISM
• Involves formation of antibodies directed against receptors. This is exemplified by the condition myasthenia gravis, in which
antibodies (autoantibodies) are produced against acetylcholine receptors, preventing the binding of acetylcholine. This leads
to the inability to transmit nerve impulse to the muscles, resulting in paralysis of the muscles.
TYPE 3: IMMUNE COMPLEX HYPERSENSITIVITY
• Occurs when antigen-antibody complexes activate complement and induce an inflammatory reaction in tissues.
• Activate the complement system, whenever immune complexes are deposited.
• Neutrophils are attracted to the site, and inflammation and tissue injury occur. In persistent bacterial or viral infections, immune
complexes may be deposited in organs (e.g., the kidneys), resulting in damage.
• Other infectious process: malaria, dengue and hepatitis B infection.
TYPE 4: DELAYED (CELL-MEDIATED) HYPERSENSIVITY
• Involves T lymphocytes, not antibody.
• “delayed”, it starts hours or days after contact with the antigen, and often lasts for days.
• It involves either helper T cells or cytotoxic T cells.
• Cytotoxic T cells
- Contact hypersensitivity is an example of condition that involves reaction of cytotoxic T cells.
- occurs after sensitization with simple chemical (e.g., nickel), plant materials (e.g., poison ivy), topically applied drugs, some cosmetics, soap
and other substances.
- Attack skin cells and the sensitized skin develops erythema, itching, vesicle, eczema, or necrosis within 12-48 hours.
• Helper T cells
- Is seen in granulomatous conditions such as tuberculosis or systemi fungal infections.
- Also involved in the tuberculin skin test (PPD).
VACCINES
• A great number of infectious diseases can be prevented by giving vaccines that induces either active or passive.
IMMUNIZATION PROGRAMS HAVE ACHIEVED THE FOLLOWING GOALS:
1. Protection of population groups from the development of pertussis, diphtheria, tetanus, and rabies.
2. Control of the spread of measles, mumps, and rubella
3. Elimination of smallpox in the world
TYPES OF IMMUNIZATION
PASSIVE IMMUNIZATION
• Involves the injection of purified antibody in preparations called immune globulins or antibody-containing serum for rapid,
temporary protection or treatment of a person.
• Immune serum globulin preparations are derived from infected humans or animals and are available as prophylaxis for
several bacterial and viral diseases. (e.g., human rabies immune globulin and immune globulins against hepatitis A or B,
measles, chickenpox, and diphtheria).
ACTIVE IMMUNIZATION
• Involves the injection of vaccines prepared from organisms or their products.
• Vaccines can divided into 2 groups on the basis of whether they infect the person (live vaccines) or not (inactivated/subunit/killed
vaccines).
LIVE VACCINES
- Prepared using organisms with limited ability to cause disease (avirulent or attenuated).
- Useful for protection against infections caused by enveloped viruses..
Dr Edward Jenner
• Developed the first vaccine for smallpox.
Dr Albert Sabin
• Developed the first live oral polio vaccine.
2 PROBLEMS WITH THE USE OF LIVE VACCINES
(1)The organism, although rendered avirulent or weakened, may still revert to a virulent form.
(2)The vaccine may be dangerous for immunosuppressed patients or pregnant women.
INACTIVATED OR KILLED VACCINES
• Provide a large amount of antigen to produce a protective response without the risk of infection by the agent.
• Are used to provide protection against most bacteria and viruses that cannot be attenuated, may cause recurrent infection, or have
oncogenic (cancer causing) potential.
• Generally safe, except in people with allergies to components of the vaccine.
DISADVANTAGES OF USING KILLED VACCINES
(1) Immunity is not lifelong
(2) Immunity may be only humoral and not cell-mediated
(3) The vaccine does not elicit a local IgA response
(4) Larger doses must be used
3 MAJOR TYPES OF INACTVATED VACCINES
TOXOID
• Are inactivated toxic (e.g., those for diphtheria, tetanus, and pertussis)
INACTIVATED BACTERIA
• Are available for polio (salk vaccine), hepatitis A, rabies, influenza, and other viruses
SUBUNIT VACCINES
• Are developed after identification of the bacterial or viral components that elicit a protective immune response.
• For example, the hepatitis B virus vaccine was prepared from the surface antigen of the virus from chronic carriers of the
infection.
PROBLEMS WITH VACCINES USE
• Live vaccines can occasionally revert to virulent forms and may be life-threatening
when given to immunocompromised patients and pregnant women.
• The side effects that develops in association with vaccination. (hypersensitivity and
allergic reactions to the antigen in the vaccine)
• Fever develops as a response to the vaccine.
• Organisms with many serotypes are difficult to control with vaccination. For
example, there is no vaccine yet developed against the dengue virus. There is also no
vaccine available to prevent the common cold because the virus which commonly
causes it has more than 30 serotypes.
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