[DISCUSSION] MODULE 1 UNIT 2 Flashcards by Arriane Camacho

•Refers to a substance that reacts with antibody or
sensitized T cells

ANTIGEN

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•May not be able to evoke an immune response in
the first pla

ANTIGEN

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•Macromolecules capable of triggering an
adaptive immune response by inducing the
formation of antibodies or sensitized T cells

•IMMUNOGENS:

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“ALL (?) ARE ANTIGENS, BUT NOT ALL
(?) ARE IMMUNOGENS.”

IMMUNOGENSANTIGENS

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• Induce detectable specific immune responses

IMMUGENECITY

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• Results to formation of antibodies (humoral
immune response) and activation of T
lymphocytes (cellular/cell-mediated immune
response)

IMMUNOGENICITY

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• Ability to react with the specific antibodies or
activated T cells that it induces

SPECIFIC REACTIVITY/ ANTIGENICITY

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•Partial or incomplete antigen

HAPTENS

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•Small, chemically defined substances which
are not immunogenic but can react with
antibodies of appropriate specificity

HAPTENS

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•Usually a small molecule; thus cannot be
immunogenic

HAPTENS

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•If it is conjugated with protein, it becomes a
bigger molecule, and it becomes
immunogenic

HAPTENS

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• Immunologically active portions of an antigen
which can react with antibodies and T-cell
antigen receptors (after antigen processing)

EPITOPE (ANTIGENIC DETERMINANT)

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• Involved with actual binding

EPITOPE (ANTIGENIC DETERMINANT)

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• Can be linear or conformational

EPITOPE (ANTIGENIC DETERMINANT)

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→ consist of sequential amino acids on
a single polypeptide chain

• Linear

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→ result from the folding of a
polypeptide chain/s, and nonsequential amino
acids are brought into close proximity

.• Conformational

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• Provides bulk or molecular mass to the antigen (Ag)
molecule

CARRIER /SCHLEPPER MOLECULE

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• May be albumin, globulin or synthetic polypeptide

CARRIER /SCHLEPPER MOLECULE

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CARRIER /SCHLEPPER MOLECULE SIGNIFICANCE:

Adds bulk so it becomes immunogenic
Important in regulation of humoral immune
response to the Ag

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HBsAg added with carrier molecule (yeast)
→

vaccine

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→ recognize the carrier portion

• T cells

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→ recognize the haptenic portion

• B cells

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•ANTIGEN MOLECULES MAY BE:

Univalent and unideterminant
Multivalent and unideterminant
Multivalent and multideterminant

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•Nonself component of the host ; alien to the host

FOREIGNESS

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•Generally, only foreign substance is immunogenic

FOREIGNESS

• Substances that are altered from what is normal to the host may become immunogenic →

autoantigen

Foreigness • E.g., in cancer cells →

production of tumor specific antigen

• Heterogeneity in the building blocks that make up the antigen

CHEMICAL COMPLEXITY

• Chemically complex • Most immunogenic

PROTEINS

• Building blocks are repeating monosaccharide units

POLYSACCHARIDES

• Weak and partial immunogens

POLYSACCHARIDES

do not possess sufficient chemical diversity

POLYSACCHARIDES

- rapidly degraded

POLYSACCHARIDES

•Immunogenic forms of polysaccharides

1. Pure polysaccharides 2. Lipopolysaccharides

1. Pure polysaccharides

• Pneumococcal capsule

2. Lipopolysaccharides

• Endotoxins of gram-negative bacteria

• Strong immunogens

GLYCOPROTEINS

• ABO blood group antigens

GLYCOPROTEINS

•Usually weak immunogens

•POLYPEPTIDES

•POLYPEPTIDES examples

hormones: insulin and growth hormone

•in the form of DNA and RNA

•NUCLEIC ACIDS

•Usually not immunogenic, unless coupled to a protein

•NUCLEIC ACIDS

•In some autoimmune disorders like SLE, tjese are are immunogenic (anti-ds-DNA are formed)

•NUCLEIC ACIDS

•Include triglycerides and other fatty substances

LIPIDS

•Not immunogenic unless coupled to proteins

LIPIDS

• E.g., cardiolipin used in the RPR tes

LIPIDS

• The larger the molecule the better immunogen

HIGH MOLECULAR MASS/ SIZE

• Molecules less than 1 kD →

non immunogenic

• Molecules > 1 kD but <6kD →

weakly immunogenic

• Molecules > 10kD →

more immunogenic

•Reasons why size/mass is important in immunogenicity:

•Number of epitopes increases proportionately with size • Large size of molecules become easily phagocytosed and processed by macrophages to become more attractive to T cells

Tertiary conformational structure of the protein molecule

SPATIAL ACCESSIBILITY OF DETERMINANT GROUPS

•Must be exposed and accessible to the receptors of immunoglobulins or the T cell receptors (TCRs)

SPATIAL ACCESSIBILITY OF DETERMINANT GROUPS

•Must be exposed and accessible to the receptors of immunoglobulins or the T cell receptors (TCRs) →

so the antigen can be bound

•Hidden (internally located) determinant groups →

NOT REACTED UPON

• Maintenance of the conformational structure of the protein antigen

RIGIDITY

• Loss/alteration/ denaturation of conformational structure leads to

loss of reactivity

• Physical state of the antigen molecule

INSOLUBILITY

• Ag must be (?) to be immunogenic

particulate and insoluble

•Intermolecular cross-linking, aggregation due to heat, attachment of hapten to

insoluble carrier substance

•Antigen is taken up and processed by macrophage

ABILITY TO BE PROCESSED AND PRESENTED WITH MHC MOLECULES

•Immunogenic components are coupled to

MHC Class II molecules

•Ag is then presented at the surface of the (?), to be recognized by the

macrophage lymphocytes

• Substances mixed with antigen before injection

ADJUVANTS

•MECHANISMS OF ACTION OF ADJUVANTS

1. Increased phagocytic uptake and local delayed release of antigen 2. Delayed destruction and elimination of antigen 3. Lengthened contact of antigen with immunocompetent cells 4. Local granuloma formation → migration of leukocytes;increased number of leukocytes involved

PROPERTIES OF ANTIGEN

1. IMMUNOGENICITY 2. SPECIFIC REACTIVITY/ ANTIGENICITY

PARTS OF THE ANTIGEN

1. EPITOPE (ANTIGENIC DETERMINANT) 2. CARRIER /SCHLEPPER MOLECULE

PROPERTIES/PREREQUISITES FOR IMMUNOGENICITY

1. FOREIGNESS 2. CHEMICAL COMPLEXITY 3. HIGH MOLECULAR MASS/ SIZE 4. SPATIAL ACCESSIBILITY OF DETERMINANT GROUPS 5. RIGIDITY 6. INSOLUBILITY 7. ABILITY TO BE PROCESSED AND PRESENTED WITH MHC MOLECULE

Biochemical cpds

• PROTEINS • POLYSACCHARIDES • GLYCOPROTEINS •POLYPEPTIDES •NUCLEIC ACIDS • LIPIDS

EXAMPLES OF ADJUVANTS:

•Alum precipitate • Squalene • Freund’s adjuvant

• Suspension of aluminum hydroxide mixed with antigen

•Alum precipitate

•A long hydrocarbon molecule present in human sebaceous gland secretions and shark liver oil

• Squalene

→ water in oil emulsion and killed M. tuberculosis → without M. tuberculosis

• Freund’s adjuvant •Complete •Incomplete

ANTIGENS

• Monoclonal activators • T-dependent antigens • T-independent antigens

• Activates B cells in the absence of T cells

• T-independent antigens

• Activates B cells only in the presence of T cells and the proteins they secrete (cytokines)

• T-dependent antigens

• E.g., proteins

• T-dependent antigens

• E.g., polysaccharides

• T-independent antigens

•Molecules that are typically derived from bacteria

SUPERANTIGENS

•Oligoclonal activators

SUPERANTIGENS

•Activate only a subset of T cells, and not all T cells

•Oligoclonal activators

• Polyclonal activators

MITOGENS

• Typically plant proteins that bind to molecules present on virtually all T cells and/ or B cells

MITOGENS

• → • T cells

Phytohemagglutinin (PHA) & Concanavalin A

• (?)→ B cells

Lipopolysaccharide (LPS)

• (?) → both B and T cells

Pokeweed mitogen

ACTIVATORS OF LYMPHOCYTES

1. ANTIGENS 2. SUPERANTIGENS 3. MITOGENS

A. According to its relation to the host

1. Autologous 2. Syngeneic 3. Allogeneic or homologous ; Isoantigen/alloantigen 4. Xenogeneic /heterologous * Heterogenetic/heterophil

•ACCORDING TO PRESENCE IN THE HOST

1. Sequestered antigen 2. Tissue-type antigens 3. Tissue-specific antigens 4. Blood group antigen

•ACCORDING TO ITS ABILITY TO STIMULATE IMMUNE RESPONSE

1. Thymus-dependent antigen 2. Thymus-independent antigen

ACCORDING TO THEIR SEROLOGIC BEHAVIOR

1. Agglutinogen • Hemagglutinogen 2. Precipitinogen

CLASSIFICATION OF ANTIGENS

A. According to its relation to the host •ACCORDING TO PRESENCE IN THE HOST •ACCORDING TO ITS ABILITY TO STIMULATE IMMUNE RESPONSE • ACCORDING TO THEIR SEROLOGIC BEHAVIOR

EXAMPLES OF GOOD IMMUNOGENS USED AS VACCINES

1. Killed organisms 2. Attenuated or altered bacteria 3. Detoxified toxins 4. Artificially assembled microbial components

FACTORS CONTRIBUTING TO THEIMMUNE RESPONSIVENESS OF A HOST AGAINST AN ANTIGEN

1. Dosage of the antigen 2. Frequency of encounter with the antigen 3. Route of introduction into the host 4. Age and gender of the host 5. Genetic endowment 6. Underlying disease; medication

Oil in water emulsion

Incomplete Freud's Adjuvant

Oil in water emulsion with dead mycobacteria

Complete Freud's Adjuvant

Oil in water emulsion with muramyl dipeptide, a constituent of bacteria

Freud's Adjuvant with MDP

Aluminum hydroxide gel

Alum (aluminum hydroxide)

Aluminum hydroxide gel with killed B. pertussis

Alum plus B. pertussis

Matrix of Quil A containing viral proteins

Immune Stimulatory Complexes

Delayed release of antigen: enhanced uptake by macrophages

Alum (aluminum hydroxide) Incomplete Freud's Adjuvant

Delayed release of antigen: enhanced uptake by macrophages with induction of co-stimulators in macrophages

Complete Freud's Adjuvant Freud's Adjuvant with MDP Alum plus Bordetella pertussis

Delivers antigen to cytosol: allows induction of CTLs

Immune Stimulatory Complexes

Source of Con A

Jack beans

Tetramer

Con A PHA

Ligan of Con A

A-D-mannose & A-D-Glucose

Target cells are T cells

Con A PHA

Target cells: T cells and B cells

PWM

Ligand of PHA:

N-acetylgalactosamine

Ligand of PWM

Di-N-acetylchitobiose

Polymeric

PWM

Source of PWM

Pokeweed

Source of PHA

Kidney beans

Structural Property of Thymus-dependent

Complex

Structural Property of Thymus-independent

Simple

Chemistry of Thymus-dependent

Proteins; protein-nucleoprotein conjugates; glycoprotein; lipoproteins

Chemistry of Thymus-independent

Polysaccharide of pneumococcus: dextran polyvinyl pyrolidone; bacterial lipopolysaccharide

Antibody class induced by Thymus-dependent

IgG, IgM, IgA, (+IgD and IgE)

Antibody class induced by Thymus-independent

IgM

Immunological memory response

Thymus-dependent

FREE PASS FOR HIGH SCORE

Presence in most pathogenic microbes

Thymus-dependent

Antibody-generating

Antigens

Trigger immune response

Immunogens

Coined haptens

Landsteiner

Antogens can be classified depending on their

Valency

Immune tolerance =/ Autoimmune Disease

Nonself

Cancer cells = tumor-specific antigen

Nonself