38 terms

MICRO 1.05a - Humoral Immunity

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humoral immunity
• Aspect of immunity which is:
o Mediated by B-cell component of the immune response
o Involves the binding of antibodies to specific antigens


• Characterized by:
o Recognition of antigens associated with microorganisms or foreign bodies
o This recognition is coupled with the ability to initiate an appropriate action
Active Immunity
• Induced after contact with foreign antigens (e.g. microorganisms or their products)

• In all these instances, the host actively produces antibodies, and lymphoid cells acquire the ability to respond to the antigens

• Capable of recognizing antigens and amplifying antigen-recognizing cells

• Protection is delayed until antibody production reaches an effective level

• The ability to recognize and respond to an antigen consequently increases with exposure (usually 5-7 days)

• The cells that are amplified are those which produce antibody - plasma cells (B cells)

• May lead to organ dysfunction through deposition of immune complexes
May consist of:
1. Clinical or subclinical infection
2. Immunization with live or killed infectious agents or antigens
3. Exposure to microbial products (toxins, toxoids)
4. Transplantation of foreign cells
active immunity may consists of
Passive Immunity
• Transfer of active immunity from one individual to another
o Mother to child (transplacental)
o Powerful but temporary
o Antitoxin and antiserum play important roles in fighting disease


• The passive administration of antibody (in antisera) against certain viruses (e.g. hepatitis B)

• Can be useful during the incubation period to limit viral multiplication (e.g. after a needle stick injury to someone who has not been vaccinated)

• Short-lived immunity; powerful but temporary

• Anti-toxin and anti-serum play important roles in disease fighting
Advantages

Active Immunity -
Long-term 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)


Passive Immunity

Prompt availability of large amounts of antibody
advantage of active vs passive
Disadvantages

Active Immunity

•Slow onset of resistance
• Requires prolonged or repeated contact with the antigen (Protection is delayed until antibody production reaches an effective level)


Passive Immunity

• Short life span of these antibodies (Short-lived immunity)
• Possible hypersensitivity reactions if antibodies (immunoglobulins) from another species are administered
disadvantage of active vs passive
HUMORAL IMMUNE RESPONSE
• Primary molecular component: Antibodies
• Synthesized by B cells and Plasma cells in response to challenge by antigen
• Antibodies - provide protection from re-challenge by infectious agent, block spread and facilitate elimination of infectious agent
• Must be available to recognize the infectious agents and interact with host systems and cells (e.g. complement and macrophages) promote clearance of antigen and activation of subsequent immune response
• Serve as cell surface receptors that stimulate appropriate B cell antibody factories to grow and produce more antibodies
• Helper CD4+ T lymphocytes recognize pathogen's antigens complexed with class II MHC proteins on surface of APCs (macrophage and B cells) expressing antibodies that specifically match the antigen
• B cells undergo clonal proliferation and differentiate to form plasma cells, which then produce specific immunoglobulins (antibodies)
HUMORAL IMMUNE RESPONSE
• Primary molecular component: _______

• Synthesized by ________s in response to challenge by antigen

• ________- provide protection from re-challenge by infectious agent, block spread and facilitate elimination of infectious agent

• Must be available to recognize the infectious agents and interact with host systems and cells (e.g. complement and macrophages) ________________

• Serve as cell surface receptors that stimulate appropriate __________________ to grow and produce more antibodies

• ______________ recognize pathogen's antigens complexed with class II MHC proteins on surface of APCs (macrophage and B cells) expressing antibodies that specifically match the antigen

• ___________undergo clonal proliferation and differentiate to form plasma cells, which then produce specific immunoglobulins (antibodies)
1. Neutralization of toxins and viruses
2. Opsonization of pathogen, which aids its uptake by phagocytic cells
HUMORAL IMMUNE RESPONSE

• Major host defense functions of antibodies include:
o Important against pathogens that:
Produce toxins
Have polysaccharide capsules that interfere with phagocytosis

o Applies mainly to extracellular pathogens and their toxins
• Antibody-mediated defense is;
ANTIGENS

immunogen
• A substance that can react with an antibody

• Everything that is foreign

• Can become an __________if it causes a response:
o Serve astarget of an immune response
o Substance that provoke production of antibody or initiate immune response
• All immunogens are antigens but not all antigens are immunogens
• All ________are ________but not all _________are _______
• Substances recognized by the body as "foreign":
o Proteins (best immunogens)
o Carbohydrates (weak immunogens)
o Lipids (poor immunogens)
o Nucleic acids (poor immunogens)
o Large polysaccharides
o Any substance from microorganisms, transplanted cells, serum, egg white and pollens


• *Immunogens: Proteins > carbohydrates > nucleic acids
• Substances recognized by the body as "foreign":
• Epitope
o Antigenic Determinant
o Site where the antigen is recognized by the antibody
o Portion of an antigen that combines with the products of a specific immune response
Hapten

o Low molecular weight substance that is non-immunogenic but which can react with the products of a specific immune response and antibodies
o Recognized as foreign but not enough to stimulate the immune response (too small to initiate an immune response)
o Can be an immunogen if it binds to another protein (Hapten-Carrier Conjugate)
Antibody

o Specific protein which is produced by B cells and plasma cells in response to antigens
o Protein that has the ability to combine with the antigen that stimulated its production
o Antibodies must also interact with the host system and cells such as the complement and macrophages to promote clearance of the antigen and activation of subsequent immune system
o Serve as cell surface receptors that will stimulate appropriate antibody factories to counteract the leak channels of the pathogenic cell
composition
size
number
ANTIGENIC DETERMINANTS
1. COMPOSITION
o Antigenic determinants recognized by B cells and the antibodies secreted by B cells are created by:
Primary sequence of residues in the polymer (linear or sequence determinants)
Secondary, tertiary or quaternary structure of the molecule (conformational determinants)
DETERMINANTS RECOGNIZED BY B CELLS AND ANTIBODIES

1.
o Antigenic determinants recognized by ____and the antibodies secreted by B cells are created by:

Primary sequence of residues in the _______(linear or sequence determinants)

Secondary, tertiary or quaternary structure of the molecule (___________)
2. SIZE
o Number of epitopes is limited
o In general antigenic determinants are small and are limited to approximately 4-8 residues (amino acids and or sugars)
Located at the external surface of the antigen and accessible by the antibodies
DETERMINANTS RECOGNIZED BY B CELLS AND ANTIBODIES

2.
o Number of epitopes is _______
o In general antigenic determinants are small and are limited to approximately _________
Located at the ________surface of the antigen and accessible by the antibodies
3. NUMBER
o In theory, each 4-8 residues can constitute a separate antigenic determinant.
o In practice, the number of antigenic determinants per antigen is much lower than what would theoretically be possible.
o Usually the antigenic determinants are limited to those portions of the antigen that are accessible to antibodies
DETERMINANTS RECOGNIZED BY B CELLS AND ANTIBODIES

3.
o In theory, each _______ can constitute a separate antigenic determinant.
o In practice, the number of antigenic determinants per antigen is much _____than what would theoretically be possible.
o Usually the antigenic determinants are l____________
COMPOSITION
o Antigenic determinants recognized by T cells are created by the primary sequence of amino acids in proteins.
o T cells do not recognize polysaccharide or nucleic acid antigens.
o The determinants need not be located on the exposed surface of the antigen since recognition of the determinant by T cells requires that the antigen be proteolytically degraded into smaller peptides.
o Free peptides are not recognized by T cells; rather the peptides associate with molecules coded for by the MHC and it is the complex of MHC molecules + peptide that is recognized by T cells.
o Polysaccharides (T-independent antigens)
o Proteins (T-dependent antigens)
DETERMINANTS RECOGNIZED BY T CELLS
1. COMPOSITION
o Antigenic determinants recognized by_____ are created by the primary sequence of amino acids in proteins.

o T cells do not recognize _____

o The determinants need not be located on the exposed surface of the antigen since recognition of the determinant by T cells requires that the antigen be _______

o ___________; rather the peptides associate with molecules coded for by the MHC and it is the complex of MHC molecules + peptide that is recognized by T cells.

o ________(T-independent antigens)

o _________(T-dependent antigens)
8-15 amino acids
DETERMINANTS RECOGNIZED BY T CELLS

2. SIZE
o Small and are limited to approximately ________
3. NUMBER
o In theory, each 8-15 residues can constitute a separate antigenic determinant.
o In practice, the number of antigenic determinants per antigen is much less than what would theoretically be possible.
o The antigenic determinants are limited to those portions of the antigen that can bind to MHC molecules.
o This is why there can by differences in the responses of different individuals.
DETERMINANTS RECOGNIZED BY T CELLS

3. NUMBER
o In theory, each 8-15 residues can constitute a separate antigenic determinant.
o In practice, the number of antigenic determinants per antigen is much _________what would theoretically be possible.
o The antigenic determinants are li________________molecules.
o This is why there can by differences in the responses of different individuals.
B Cell
- Primary sequence of residues in the polymer
- Secondary, tertiary or quaternary structure of the molecule


T Cell
- Primary sequence of amino acids in proteins
- MHC molecules + peptide complex
Composition B cell vs T cell
B cell
4-8 residues

Tcell
8-15 amino acids
size B cell vs T cell
B cell
No. of antigenic determinants per antigen LESSER than theoretical (4-8 residues)

T cell
No. of antigenic determinants per antigen LESSER than theoretical (8-15 amino acids)
number B cell vs T cell
contribution of immunogen (foreigness, size, chemical composition, degradability)

contribution of biological system (age, genetic constitution)


method of administration
(adjuvant, dose, route)

chemical nature of immunogen
(protein, polysaccharides, nucleic acids, lipids, physical form)
Factors affecting immunity
Contribution of the Immunogen


FOREIGNNESS
• Molecules must be recognized as "non-self"
• Discrimination between self and non-self

o Self = not immunogenic
o Non-self = immunogenic
• Only foreign cells are immunogenic


SIZE
• The bigger, the better
• In most cases, molecules with <10,000 MW are weakly immunogenic.
• Haptens (small molecules) become immunogenic only if linked to a carrier protein (become larger) Hapten-Carrier Conjugate


CHEMICAL COMPOSITION/COMPLEXITY
• Certain level of complexity is required.
o Ex. Amino acid homopolymers < amino acid heteropolymers (2-3 AA)
• The more complex the substance is chemically, the more immunogenic it will be.


DEGRADABILITY
• Antigens that are easily phagocytized are generally more immunogenic.
• For T- dependent antigens, the development of an immune response requires that the antigen be phagocytized, processed, and presented to helper T cells by an antigen presenting cell (APC).
Contribution of the Immunogen


____________
• Molecules must be recognized as "____________

• Discrimination between self and non-self

o ______= not immunogenic
o ____________ = immunogenic
• Only foreign cells are immunogenic


____________
• The ____________, the better
• In most cases, molecules with <10,000 MW are ____________
• ____________(small molecules) become immunogenic only if linked to a carrier protein (become larger) Hapten-Carrier Conjugate


CHEMICAL COMPOSITION/COMPLEXITY
• Certain level of ____________is required.
o Ex. Amino acid homopolymers < amino acid heteropolymers (2-3 AA)
• The more ____________the substance is chemically, the more ____________it will be.


DEGRADABILITY
• Antigens that are easily phagocytized are generally more ____________
.
• For ____________, the development of an immune response requires that the antigen be phagocytized, processed, and presented to helper T cells by an antigen presenting cell (APC).
Contribution of Biological System


AGE

• Very young and very old (extreme ages) have decreased ability to mount an immune response to an antigen




GENETIC CONSTITUTION OF HOST

• Species - some are immunogenic to one species and not in another
• Individual - some substances are immunogenic in one individual (responders) but not in others (non-responders)
• Different stain of the same species different genes for immune response different response
• Species or individuals may lack or have altered genes that code for the receptors for antigen on B cells and T cells
• Species or individuals may not have the appropriate genes needed for the APC to present antigen to helper T cells
Contribution of Biological System


_________

• Very young and very old (extreme ages) have _________ability to mount an immune response to an antigen




_________

• Species - some are _________

• Individual - some substances are immunogenic in _________

• Different stain of the same species -> different genes for immune response ->different response

• Species or individuals may lack or have altered genes that code for the receptors for antigen on B cells and T cells

• Species or individuals may not have the appropriate genes needed for the APC to present antigen to helper T cells
Method of Administration


ADJUVANT
o Substances that can enhance the immune response to an immunogen
o Prolongs the effect of the immune response
o May result to undesirable side effects (fever and inflammation)
o May illicit allergic reactions


DOSE
o Amount of antigen for optimal response
o There is a dose of antigen above or below which the immune response will not be optimal
o The dose of administration of an immunogen can influence its immunogenicity


ROUTE
o Subcutaneous > Intravenous > Intragastric
o Can alter the nature of response
Method of Administration


_________
o Substances that can enhance the immune response to an immunogen
o _________the effect of the immune response
o May result to _________
o May illicit _________reactions


_________
o Amount of antigen for optimal response
o There is a dose of antigen above or below which the immune response will _________
o The dose of administration of an immunogen can _________


_________
o Subcutaneous _________ Intravenous _________ Intragastric
o Can alter the nature of response
Chemical Nature of Immunogen


PROTEIN
o Usually very good immunogens
o Vast majority of immunogens are proteins
o May be pure proteins, glycoproteins, or lipoproteins


POLYSACCHARIDES
o Pure polysaccharides = good immunogens
o Lipopolysaccharides = good immunogens


NUCLEIC ACIDS
o Usually poor immunogens
o Single stranded or complexed with proteins may become immunogenic


LIPIDS
o Non-immunogenic but may be haptens if conjugated with protein
o Some glycolipids and phospholipids are immunogenic for T cells and illicit a cell-mediated immune response


PHYSICAL FORM
o Particulate antigens are more immunogenic than soluble ones
o Denatured antigens are more immunogenic than the native form
Chemical Nature of Immunogen


_________
o Usually_________
o Vast _________of immunogens are proteins
o May be pure proteins, glycoproteins, or lipoproteins


POLYSACCHARIDES
o Pure polysaccharides = _________
o Lipopolysaccharides = _________


NUCLEIC ACIDS
o Usually _________
o Single stranded or complexed with proteins
may become _________


LIPIDS
o _________ but may be _________if conjugated with protein
o Some glycolipids and phospholipids are immunogenic for _________ and illicit a cell-mediated immune response


PHYSICAL FORM
o Particulate antigens are more immunogenic than soluble ones
o Denatured antigens are _________than the native form
T-independent antigens
T-dependent antigens
Hapten carrier conjugate
Types of antigen
T-Independent Antigens
• Antigens which can directly stimulate the B cells to produce antibody without the requirement for T cell help
• Polysaccharides are T-independent antigens
• The responses to these antigens differ from the responses to other antigens


Properties:

o Polymeric structure
Characterized by the same antigenic determinant repeated many times


o Polyclonal B cell activation
Can activate B cell clones specific for other antigens (Polyclonal activation)
T-independent antigens can be subdivided into Type 1 and Type 2 based on their ability to polyclonally activate B cells:
1. Type 1 T-independent antigens are polyclonal activators
2. Type 2 T-independent antigens are not


o Resistance to degradation
T-independent antigens are generally more resistant to degradation
Persist for longer periods of time and continue to stimulate the immune system


• Examples: Pneumococcal polysaccharide, lipopolysaccharide, flagella
_________
• Antigens which can directly stimulate the B cells to produce antibody without the requirement for T cell help
• _________are T-independent antigens
• The responses to these antigens differ from the responses to other antigens


Properties:

o Polymeric structure
Characterized by the _________


o Polyclonal B cell activation
Can activate _________
T-independent antigens can be subdivided into Type 1 and Type 2 based on their ability to _________

1. _________ are polyclonal activators
2. _________are not


o Resistance to degradation
T-independent antigens are generally _________
Persist for _________ of time and continue to stimulate the immune system


• Examples: _________
T-Dependent Antigens
• Antigens that do not directly stimulate the production of antibody without the help of T cells
• Proteins are T-dependent antigens
• Structurally, these antigens are characterized by a few copies of many different antigenic determinant



• Examples: Microbial proteins, non-self or altered-self proteins
_________
• Antigens that _________stimulate the production of antibody without the help of T cells
• _________are T-dependent antigens
• Structurally, these antigens are characterized by a _________


• Examples: _________
Hapten Carrier Conjugate
• Haptens become immunogenic when attached to molecules called carrier
• Immunogenic molecules to which haptens have been covalently attached
• The immunogenic molecule is called the carrier
• Structurally these conjugates are characterized by having native antigenic determinants of the carrier as well as new determinants created by the hapten (haptenic determinants).
• The actual determinant created by the hapten consists of the hapten and a few of the adjacent residues, although the antibody produced to the determinant will also react with free hapten.
• In such conjugates the type of carrier determines whether the response will be T-independent or T-dependent.
_________
• Haptens become immunogenic when attached to molecules called _________
• Immunogenic molecules to which haptens have been _________attached
• The immunogenic molecule is called the _________
• Structurally these conjugates are characterized by having_________

• The actual determinant created by the hapten consists of the _________and a ________ although the antibody produced to the determinant will also react with free hapten.
• In such conjugates the type of carrier determines whether the response will be _________
IMMUNOGLOBULINS (IG)
• Aka Antibodies (Ab)/Agglutinins
• Glycoprotein molecules that are produced by plasma cells (B cells) in response to an immunogen
• Function as antibodies which react specifically with the antigen that stimulated their production
• Ig derive their name from the finding that they migrate with globular proteins when antibody-containing serum is placed in an electrical field
_________
• Aka Antibodies (Ab)/Agglutinins

• Glycoprotein molecules that are produced by _________ in response to an immunogen

• Function as _________which react specifically with the antigen that stimulated their production

• derive their name from the finding that they migrate with _________when antibody-containing serum is placed in an electrical field
• Polyclonal Antibodies
o Antibodies that arise in an animal in response to a single complex antigen are heterogeneous because they are formed by several different clones of cells, each expressing an antibody capable of reacting with a different antigenic determinant on the complex antigen
Monoclonal Antibodies

o Antibodies that arise from a single clone of cells, eg, in a plasma cell tumor (myeloma), are homogeneous
o Produced by fusing a myeloma cell with an antibody-producing lymphocyte
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