IMMUNO-SEROLOGY Essential Factors needed for an infxn to occur: - org in the GIT

1. Portal of Entry - inhabited by millions of microorg depending on

HOST-PARASITE RELATIONSHIP a. Nose the diff levels of the GIT
- through inhalation - colon has 10¹⁵ org
2 Opposing Factors - immune defenses in the body (cilia) prevents
1. Host- bigger the entry of parasites c. Respiratory discharges
2. Parasite - if parasites enter, pulmonary infxn occurs - coughing and sneezing
- lives on the host
• Ectoparasite b. Mouth d. Saliva
• Endoparasite - through ingestion - may be w/ sputum
- org capable of producing dis (pathogenic) - only strong bacteria can tolerate the immune
- may produce infxn when the host is immune- defenses of the mouth e. Extraction of Blood
compromised (opportunistic) - entry causes GI infxns
3. Mode of Transmission
Host-Parasite relationship involves 2 major factors: c. Skin
1. The properties of the parasite that enables them - through breaks or unbroken skin Nosocomial Infections
to produce dis - hospital acquired infxn
2. The mechanisms by which the host responds to d. Genito-Urinary Tract (GUT)
these parasites - org causing STD Not all infxns are communicable but all
- gonorrhea, veneral syphilis, soft chancre, communicable dis are infectious
 The most successful host-parasite relationship condyloma, (common before)
is the human body and its normal flora - now, there are 27 known STD’s Essential Factors for Infxn to occur:
 The normal flora can be pathogenic in cases 1. Microbial invasion
where in the body’s immune defenses are e. Blood - the entrance of microorg into the host via the diff
compromised - normally sterile portal of entry
- causes sepsis - respiratory tract by way of nose and mouth (TB,
 Unsuccessful host-parasite relationship leads
to infectious dis salmonellosis etc)
f. Placenta
- toxoplasma, plasmodium, schistosoma, 2. Virulence
Dynamic Balance
hookworm - as a rule, freshly discharged org from a person ill w/
- balance favors the host
the dis that it causes is the most virulence
Infection • If you are exposed to a parasite, you have - org harbored by carriers are less virulent
- is when there is colonization of org in or on the host to be exposed to billions of org for them to Virulence may be increased by rapid transfer of org
- the rxns in the body may or may not produce establish in your body through a series of susceptible animals
outward signs and symptoms of dis (carrier host) • Exposure → bloodstream → disseminated
to target organs to produce infxn 3. Establishment/ Colonization/ multiplication of the
Disease • Org are highly selective w/ their choice of org w/in the host
- caused by unsuccessful host-parasite relationship target organs - org are highly selective in their choice of tissues in
- if rxn has a series of signs and symptoms of an the host that they infect
illness 2. Portal of Exit - this is called Organotropism
a. Urine - this may be explained by:
Cardinal Manifestation - kidneys play an impt role • Metabolic requirement of certain org
- a distinct symptom that indicates the presence of a - S. haematobium eggs in urine • The protective characteristics that certain
certain dis tissues offer
b. Feces
 • Availability of essential receptor sites on host
cells
4. For the continued survival of the org there should
be:
a. Satisfactory Portal of Exit
b. Effective modes of Transmission to new host
• Direct
- droplet spray, sexual contact, kissing, blood
transfusion
• Indirect
- contaminated food and drinks, contaminated hands,
objects and instruments, flies and cockroaches
• Bites of insects and animals
Efficiency of modes of transmission of org
depends on:
• Adequate source
• Large enough inoculums
• Means of survival of org
• Susceptible host
PATTERNS OF DISEASE
Inapparent or Subclinical Infection
- pathogenic org are present but they do not cause
dis
2 Types are distinguished arbitrarily
1. Dormant Infection
- organ be recovered from the Px
- carrier is the Px who continues to pass out the org
2. Latent Infection
- when org cannot be recovered from the Px
- example:
• Herpes Virus
- oral virus
- produces lesions in the mouth
- org may be recovered w/ or w/out treatment
- may reoccur when triggered
- host may never recover
COURSE OF INFECTIOUS DISEASE
1. Incubation Period (Clinical)
- interval bet the time the infxn is received and the
appearance of signs and symptoms of the dis
• Ligand- lipid porion of lipoteichoic acid
2. Prodromal Period • Receptor- fibronectin (host cell receptor
- short interval (prodrome) that follow IP molecule)
characterized by ill-defined symptoms such as • M protein- acts as anti-phagocytic factor
headache, body malaise . .
2. Cell surface Lectin
3. Invasion Period - in Chlamydia
- dis reaching its full development and maximum -host cell receptor → N-acetyl-D-glucosamine
intensity
• Acute- rapid onset of a few hours 3. Protein Adhesin
• Chronic- insidious, days or weeks - in Mycoplasma
...
4. Fastigium or acme II. Virulence Factors that promote pathogen survival
- disease at its height and host injury
1. Anti-phagocytic Factors
5. Defervescence or decline - promote invasiveness
- manifestation will start to subside a. Slime layer or Capsule
• Lysis - covers surface components to w/c phagocytes
• Crisis attach
- example: polysaccharide capsule of
6. Stage of Convalescence meningococcus, Hib, Klebs, Pneumococcus,
Cryptococcus; Polypeptide of B. anthracis
b. Protein A
PARASITE - binds to Fc portion of IgG
- S. aureus (pathogenic)
Pathogenicity c. M protein
- is the dis producing ability of the org - acts as antiphagocytic molecule
- component of the cell wall of S. pyogenes
Virulence d. Leukocidin
- is the degree of pathogenicity of a give org - destroys phagocytic leukocytes
- this is measured by the number of org or -streptococcus and staphylococcus
microgram of toxins required to kill 50% of the e. Coagulase
members of a particular animal spp (LD₅₀ or - triggers clotting in plasma producing fibrin coat
lethal dose) around S. aureus org
- also produces fibrin walls around staph lesions w/c
PATHOGENIC PROPERTIES OF MICROORGANISMS becomes impenetrable to phagocytic cells
I. Adherence - marker for pathogenicity of S. aureus org (versatile)
- ability of microorg to attach to epithelial cells of but
the skin and mucous membranes is not responsible for its pathogenicity
- attachment is cell specific f. Proteases
- hydrolyze Ig particularly IgA → preventing
1. Pili or Fimbriae adherence opsonization and phagocytosis
Ex. Enterobacteriaciae (ETEC, V. cholera, S. - Neisseria and Strep
dysenteriae), N. gonorrhea, S. pyogenes
- fimbriae contains lipoteichoic acid and M protein 2. Spreading Factors
→ causes adherence of strep to buccal EP cells - promote invasiveness
- pathogenic bacteria may discharge enzymes that - can elicit host rxn that damage tissues such as Bacterial Cytolysins
dissolve host tissues and destroy physical hypersensitivity rxns stability relatively heat unstable; toxicity is dest
barriers Examples: enzymes
- promote the spread of org Diphtheria specificity more specific in their axn (target organs
a. Collagenase E. coli A-B Exotoxin toxicity highly toxic to animal tissues
- destroys collagen of fibrous CT → promotes the P. aeruginosa antigenicity Weakly antigenic
spread of infxn Tetanus - H–Bind action do not induce fever and inflammatory re
b. Fibrinolysin Botulinum - L–Bind
- dissolves fibrin clots
... Conversion to Can be altered and converted to non-to
c. Lecithinase (alpha-toxin) toxoid formaldehyde, heat or acid
- enzyme that depolymerizes host cell membrane Biologic effects - Cytotoxic effects
d. Hyaluronidase - Inhibition of protein synthesis
- dissolves hyaluronic acid, the cement subs in bet - Interference with neuronal transmissti
cells - Effects on the transport of ions and flu
III. Toxic Factors
- produced by both Gram (+) and Gram (-) bacteria CHARACTERISTICS OF EXOTOXINS AND ENDOTOXINS
2 Types of Toxins bases
• Exotoxins Component and protein in nature commonly produced by gram (+) bacteria; secreted into their
• Endotoxins release surroundings
- have the capacity for genetic change (ability of Toxic component Two-component protein toxin
certain microorg to undergo mutation  Binding Component
periodically)  Toxic Component
Mechanisms of Fever - strat. Squamous EP of the skin w/ its superficial
Activators Factors that affect the Host responses to cornified layer
Endotoxins, viruses, bacteria, Ag-Ab complexes, Infectious agents: - most effective simple mechanical barrier
steroid, sensitized T cells 1. Age - org can gain access to the underlying tissue only
↓ 2. Nutritional Status by:
Cells 3. Psychological Status • Breaks in the EP (burns)
Granulocytes, monocytes, macrophages, tumor cells: 4. Genetic Predisposition • By way of hair follicles, sebaceous glands,
release interleukin 5. Hormonal Balance sweat glands (staph traverse the stratified layer)
↓ 6. Environmental Status - most pathogenic org are not capable of penetrating
Endogenous pyrogens intact EP cells
↓ Mechanisms by which the host defends itself - skin continuously desquamates → shed
Stimulate thermoregulatory fever center of the against invasion of organisms: contaminating organisms → colonize again after 8
hypothalamus 1. Nonspecific hrs
2. Specific • Vaginal EP- protected during child-bearing
Pathogenic Org can either be: • Humoral years by:
1. Extracellular parasites • Cellular  Low pH
2. Intracellular parasites NON-SPECIFIC HOST-DEFENSE MECHANISM  Exclusionary effect of normal bacterial flora
• Facultative intracellular I. Mechanical Defenses
• Obligate intracellular 2. Respiratory Tract EP
A. Epithelial Barriers - less effective mechanical barrier
1. Skin and Mucous Membranes
HOST
- protected by a viscous mucous covering → trap the
microorg → sweep away before reaching EP
surface
- secretory IgA lysozyme and lactoferrin secreted into
the mucous
3. Gastrointestinal Tract
- sloughs off EP cells regularly and the entire EP is
replaced w/in 36 hrs
- defecation eliminates 10¹² bacteria/day
4. Urinary Tract
- multilayered transitional EP
B. Flushing action of the urine, tears, saliva
- these eliminates potential pathogens
- urination w/in 30 min after coitus prevents cystitis
in females
C. Coughing, sneezing, and epiglottic reflex
- eliminates irritants in the respiratory tract
- epiglottic reflex prevents aspiration pneumonia
D. Hairs in the anterior nares
E. Cilia of the respiratory tract
II. Chemical Defenses
1. Mucin of mucous secretions of the respiratory and
GIT
2. Lysozyme (muramidase)
- destroys cell walls of many gram(+) bacteria
- found in mucous secretions, tears, saliva, nasal
secretions and sweat
3. Fatty acids
- in sweat and ear wax
4.low pH of the skin
- acid pH of gastric secretions, the urine, secretions
of the adult vagina have bactericidal effect
5. Spermine
- found in semen
- have bactericidal effect
6. Lipase
- in human milk
- has activity against E. histolytica and G. lamblia
trophs
7. bile potential antiviral
8. interferon agents
III. Microbial Defenses: Microbial Interferences or
Antagonism by microbial flora
- suppress the colonization of potential pathogens
- competition for essential nutrients
- production of inhibitory subs
- example: Colicin
IV. Tissue Factors and Cellular Defenses
1. Inflammation
- body’s attempt to localize and destroy infectious
microorg and repair damaged tissues
- it protects the host by:
• Promoting phagocytosis
• Localizing infection by forming walls of
clotted plasma
• Producing exudates (pus) which in some
cases allowed direct drainage of microorg and
tissues out of the body
2. Phagocytosis
- an essential component of inflammation
Immuno Compromised Host
- depression of host defense mechanisms either
non-specific, specific or both
- high risk age groups are the very young and the
very old
- prone to opportunistic infections w/c are caused
by microorg that are not ordinarily considered
pathogenic or virulent but become so if the
immunologic capacity of the host is impaired
Opportunistic Organisms
• Bacteria- Pseudomonas, Mycobacterium
avium-intracellulare
• Viruses- Herpes simplex, Herpes zoster,
Cytomegalovirus
• Fungi- Candida albicans, Cryptococcus
neoformans, Histoplasma capsulatum
• Protozoa- Pneumocystis carinii,
Cryptosporidium, Isospora, Toxoplasma
• Helminths- Strongyloides
Factors that Contribute to the Depression of Host
Defense Leading to Infection
1. Alteration of physical barriers such as break in the
integrity of the EP
2. Diseases
• Inherited and acquired immune deficiencies
• Disease involving hematopoietic system like
lymphomas and leukemia
• Carcinoma
• Certain viral infxn like measles (anergy)
• Diabetes mellitus
- increase in glucose level impairs phagocytosis and
decrease inflammatory responses
3. Use of immunosuppressive agents like steroids,
cytotoxic drugs, irradiation, antilymphocytic
serum can cause a decrease in circulating
phagocytes, interfere w/ Ab production, impair
cell mediated immunity (CMI) activity
4. Prolonged use of antimicrobial agents can lead to
overgrowth of Candida albicans
5. Nutritional deficiency
6. Alcoholism
7. Smoking
8. Overexposure to cold
9. Physical and emotional stress
IMMUNITY
- the capacity of the animal to recognize what is self
or non-self
- there are molecules on the surface of cells that your
immune system will recognize as self or non-self
- resistance to infection
- Immunity was introduced in medicine to refer to
those people who did not get small pox or plague
once they had the diseases
- refers to the resistance of a host org to invasive
pathogens or their toxic products
 - refers to all mechanisms used by the body as
protection against environmental agents 3. Individual Immunity Property Innate Adaptive
(microorg or their toxic products, foods, - person to person differences in susceptibility 1. Physical Skin and none
chemicals, drugs, proteins, animal hair, dander) - genetic factors play a role in this, each one is barrier mucous
that are foreign to the body genetically diff from each other, each one will membranes
have a did degree of resistance 2. Soluble Enzymes (ex. Lymphokines
SUSCEPTIBILITY factors lysozymes are Ab
-when one has no protection against a disease Acquired Immunity (specific, adaptive) and made
- refers to the immunity a person develops during his complement possible by
Kinds of Immunity lifetime. This may be done to active participation ), acute B-
1. Natural Immunity of the host in passive acquisition of the protection phase lymphocyte
• Species Immunity from another host proteins, α s
• Racial Immunity - more specialized than innate immunity and it and β -collectively
• Individual Immunity supplements the protection by provided by innate interferons known as
immunity cytokines
2. Acquired Immunity - immunity is acquired by contact w/ an invader and -usually
• Active the body produce Ab against the invader produced by
- it is induced by immunized individuals to non T-cells
 Natural
immunized individuals (contact w/ foreign agent) -enhance any
 Artificial
- adaptive transfer (immunization) refers to the response to
• Passive transfer of immunity by the transfer of immune foreign
 Natural cells invaders
 Artificial 3. Cells NK cells (T- T and B-
- has several generalized features that characterize it lymphocyte lymphocyte
Natural Immunity (innate, non-specific, non-adaptive) and serve to distinguish it from other pathologic s) s
- inherent, innate and genetically determined agents: 4. Self or Non yes yes
- induces the diff barriers of the body such as the 1. Specificity Self
mechanical barriers, the macrophages, phagocytic - the antibody will respond only to the particular Ag 5. Specificity no Yes
cells, monocytes, and subs that the cells secrete to 2. Adaptiveness 6. Memory no Yes
destroy invaders - the ability to respond to foreign subs even those
that the body hasn’t encountered yet, and Actively Acquired
3 Types of Natural Immunity activate the T-lymphocytes and produce Ab - when a foreign subs is encountered 1 of 2
1. Species Immunity against the foreign subs responses is observed. Most commonly there is
- a given org is capable of producing in one animal spp - the immune system’s ability to adapt to the an immune response w/ the production of specific
and not in another changes brought about by those foreign subs Ab
- dis limited to lower animals that you won’t find in 3. Responsiveness
higher animals or v/v -discrimination bet self and non-self
4. Memory Natural Immunity
2. Racial Immunity - a property shared w/ the nervous system is the - subclinical infection – one does not manifest clinical
- possessed by a race, among one animal spp ability to recall previous contact w/ a foreign symptoms of the infection but one has the
- there may be a diff in susceptibility molecule infecting org in small amt; they can still stimulate
Example: - the response is highly specific for a particular the immune system to produce the necessary
Blacks are more susceptible to TB than whites; or the pathogen, it improves w/ each successive protection.
relative resistance to plasmodium vivax malaria of encounter w/ the same pathogen. In effect,
west Africans and their descendants compared to the adaptive immune system remembers and Artificial Immunity
American whites stimulates again the T-cells to produce the Ab
- immunization utilizing vaccines containing either
live org, live attenuated (nonpath but still
antigenic), killed or inactivated org, or Ag in the
form of modified toxins (toxoids- toxins treated w
formaldehyde and have lost their toxicity but not
their antigenicity)
Passively Acquired
- immunization utilizing vaccines containing
preformed Ab
-the body’s immune system does not participate in
the formation of Ab
Natural Immunity
- it results from the transfer of Ab or immune cells to
one individual from another individual who has
already acquired the dis and has produced the
specific Ab
- example: Ab pass thru the placenta from mother to
fetus; also thru breast feeding
Artificial Immunity
- administration of pre-formed Ab, immune-
competent cells (sensitized lymphocytes,
lymphokines)
Heterologous vs. Homologous Antibodies
Heterologous Antibodies
- produced by lower animals
- undergoes dilution, catabolism, immune complex
formation and immune elimination
- example: heterologous Ab such as that from the
horse can cause at least 2 kinds of
hypersensitivity rxn:
• Type I (immediate, anaphylaxis)
• Type II (serum sickness from immune
complex)
Homologous Antibodies
- produced from the same spp
- example: man reaches a peak level in the serum
about 2 days after subcutaneous injection,
undergoes dilution and catabolism
-stays longer in the circulation
IMMUNIZATION
- protection against infectious dis
- protection generated prior to possible exposure
to an infectious agent is the objective in the usual
active immunization in childhood
- protection thru passive immunization is the
objective by injections of Ig to protect traveler
against HAV in countries where the dis is common
- protection against development of dis can also
be afforded by post-exposure w/ immunization
- example: by administration of rabies vaccine
and Ig against the rabies virus, toxoid and anti-
toxin against diphtheria
Active Immunization
1. Live Organisms
• Vaccinia vaccine against smallpox
- in the late 15th century, milkmaids where
noted to be exposed to cowpox (vaccinia)
appeared to escape infxn w/ smallpox. It was
then that Jenner showed that deliberate
administration to humans of lymph from a
cow with vaccinia led to protection against
smallpox
2. Live Attenuated Organisms
Advantage:
 has the advantage of acting like a
natural infection and stimulate longer
lasting protection
Disadvantage:
 risk of reversion to greater
virulence during multiplication in the
vaccine
• Oral Polio Vaccine (OPV) or Sabin
- very easy to administer, oral drops
• Bacillus of Calmette and Guerin (BCG)
- attenuated M. bovis, not an assurance that
one will not get TB. One may get it but in a
milder form
• Measles, mumps and Rubella (MMR)
3. Killed Organisms
• Parenteral Polio Vaccine (Salk)
- no lifelong immunity
• Rabies
- nervous tissue (goats- 25); ducks embryo (14-
21); cell culture (5)
• Japanese B. encephalitis Vaccine
• Influenza Virus
- flu virus undergoes antigenic shift so that one
will only be protected against one type of flu
antigen and not the other type
Active immunization with living organisms is
generally superior to immunization using killed
organisms in inducing long lived immune response
4. Toxoids
• Tetanus Toxoid
• Diphtheria Toxoid
- the above toxoids have been used in
combination w/ killed B. pertrussis bacilli
- it was demonstrated that treatment of these
(protein) exotoxins w/ formaldehyde and other
chemicals eliminated their toxicity but left their
antigenic properties unaffected. Formaldehyde
appears to effect this change by providing methyl
w/ derivatives at the amino groups
5. Recombinant Vaccines
- recombinant DNA technology
- recombinant DNA segment w/c may be exposed to
another living cell (yeast, E. coli)
• Yeast derived Hepatitis B Vaccine
- production of vaccine against hep B from yeast
by recombinant DNA technology simplifies the
production of greater quantities of safer vaccines
than the vaccine prepared from blood plasma of
humans
6. Synthetic Vaccine
- bec of their greater purity, synthetic peptide
vaccines may afford protection that is associated w/
fewer side effects. The design of the specific peptide
vaccine is based on knowledge on AA sequence of
the protein Ag
7. Anti-idiotypic vaccine
- an antibody (idiotype) induced to a specific epitope
of an Ag has a combining site that structurally fits
the epitope. If Ab in turn, is used as an
immunogen to induce an Ab (an anti-idiotype)
that reacts w the Ag combining site of the
idiotype, the anti-idiotype may structurally mimic
the epitope. This structural mimicry is referred to
as an Internal Image. Bec of the resemblance of
the anti-idiotype and the original Ag epitope, its
internal image (anti-idiotypic Ab) can be used as
an immunogen to induce Ab against the original
epitope
Passive Immunization
- administration of preformed Ab and other
preformed subs from another individual or animal
1. Injection of Non-human Serum
- usually horse serum
• Anti-tetanus serum (ATS)
• Anti-diphtheria serum (ADS)
- both are anti-toxins
• Anti-rabies serum (ARS)
- anti-viral
2. Injection of Convalescent serum or Hyperimmune
Serum
- taken from human recovering from infectious dis
- may be used against measles and rabies
3. Human Pooled γ-globulin Infection
- pooled over from over 1000 donors
- 95% IgG, traces of IgM and IgA
- should be given w/in 72 hrs of exposure to limit
viral multiplication w/c may prevent or modify
the dis
4. Transfer of Immuno-Competent Cells
- T and B cells (that will produce the Ab) from
immune-competent to immune deficient host
- known as Adoptive Immunity
5. Administration of Lymphokines and Monokines
a. γ- Intereron
- when secreted as a lymphokine or by the
activated macrophages, it is called Immune
Interferon
- enhances natural killer cell activity
- inhibits viral replication of neighboring
uninfected cells thru specified receptors on
the cells, w/o interfering w/ their normal
metabolic process
b. Transfer Factor
- a non-IgG, low molecular weight material from T-
lymphocytes
- 2 forms: Ag- specific and non-specific
Major Function of the Immune System
1. Defense
a. Hypofunction
- increased susceptibility of infxn
b. Hyperfunction
- allergy or hypersensitivity rxn
2. Homeostasis
- removal of worn-out cells or damaged cells
a. Hyperactivity
- autoimmune dis
- an impt form of regulation concerns the prevention
of immune response against self Ag. For various
reasons, this regulation may be defective and an
immune response against self is mounted. This
type of immune response is termed
autoimmunity, and is the cause of dis. Such as
some form of arthritis, thyroiditis and diabetes
that are very difficult to treat
3. Surveillance
- recognition and removal of abnormal or mutant
cells
- role of CMI (cell mediated immunity) T-lymphocytes
- failure of function will result to tumor or malignancy
(cancer)
DEVELOPMENT OF IMMUNE SYSTEM IN MAN
(refer to p.8 of book)
GENETIC CONTROL OF IMMUNE RESPONSE
(refer to p.9 of book)
DENISE 