Immunoglobulins: IgG & IgA

• Antibodies are also known as Immunoglobulins

IgG Immunoglobulin

• IgG Immunoglobulin is the most common antibody
• It serves as "opsonin"
• It activates the Complement Pathway
• It is part of "Antibody Dependent Cell-Mediated Cytotoxicity”
• IgG kills cells infected with viruses
• Fab region is the antigen binding site
• IgG structure includes Light (L) chains, Heavy (H) chains, Disulfide bonds, and Hinge region
• In chemical structure C stands for constant, and V stands for variable

Opsonization

• Opsonization involves the pathogen being "coated” with IgG
• Opsonization helps phagocytes target the pathogen

Antibody-Dependent Cell-Mediated Cytotoxicity

• When 2 CD-16 receptors on NK Cells have bound to IgG antibodies, the NK cells releases its granzymes and perforin molecules
• Which then kills the pathogen

IgA Immunoglobulin

• IgA Immunoglobulin is found in Mucosal Membranes
• This membrane lines cavities that are in contact with the “outside world"
• IgA has a Dimer structure consisting of two immunoglobulins bound at the Fc region by a J chain
• IgA functions as an opsonization
• Prevents the attachment and invasion of viruses and bacteria into the mucosa
• Inhibits pathogen's motility, causes aggregation of pathogens, masks pathogen adhesion sites which prevents ability to adhere to epithelium

IgE Immunoglobulin

• IgE Immunoglobulin Binds to IgE Receptors on Mast Cells, Basophils, and Eosinophils
• This triggers granule release from the cell
• Mast cell granules contain histamine and heparin
• Basophil granules contain histamine, cytokines, and substances that stimulate mucus production and smooth muscle cell
• Eosinophil granules contain major basic protein, eosinophilic cationic protein, and eosinophil peroxidase, and eosinophil-derived neurotoxin
• These granules kill large extracellular pathogens that cannot be ingested

IgM Immunoglobulin

• IgM Immunoglobulin is the B-cell receptor
• It's the first antibody produced in all immune responses
• It can be produced without influence from a T-cell
• It activates the complement

Complement Pathway

• A membrane Attack Complex is created in membranes of pathogens
• This leads to pathogen destruction

Case Study: Alyssa

• Alyssa is a 19-year-old female, who presents to the clinic with complaints of a sore throat and fatigue
• Alyssa presented to clinic almost 2 weeks ago after her symptoms started
• A Rapid Strep test was negative and a Mono-spot test was also negative
• Her symptoms have persisted and she presents with a sore throat and not eating well
• Physical exam confirmed she has bilateral tender anterior cervical lymphadenopathy
• On her oral exam, she has bilateral enlarged tonsils that are coated with a white exudate
• Infectious mononucleosis is suspected
• Alyssa's Mono-Spot test was negative last week, however, it is suspected that it was falsely negative
• Serologic testing is pursued
• Levels of antibodies IgG VCA and IgM VCA were present against the Epstein-Barr Virus (EBV)
• Antibodies target the Epstein-Barr Virus antigens

Viral capsid

• Viral capsid contains Envelope proteins
• Includes the viral envelope
• The viral genome is present
• Nucleocapsid
• The viral tegument

Viral Infections

• In a viral infection, IgM is the first antibody produced in all immune responses
• IgM can be produced without influence from a T-cell
• IgM activates the complement pathway
• IgG is the most common antibody
• IgG serves as an “opsonin”
• IgG activates the Complement Pathway
• Evolution of antibody and blood EBV DNA markers during EBV infection in an immunocompetent host.
• DNA deoxyribonucleic acid
• EA early antigen
• EBNA Epstein-Barr virus nuclear antigen
• EBY: Epstein-Barr virus
• Ig: immunoglobulin
• VCA

Complement system pathway

• C1 cleaves C2 and C4
• C3 Convertase cleaves C3
• C5 Convertase Cleaves C5

Components of the Immune System

• The Immune System is split into two parts, Adaptive and Innate
• Adaptive Immunity includes T-Cells and B-Cells for targeting, and Cytotoxic T-Cells and Antibodies
• Innate Immunity includes Chemcial and Physical Barriers, Phagocytes such as Neutrophils, Macrophages and Dendritic cells, and the Complement System

Lymphoid Organs

• Lymphoid Organs have Lymphocytes
• Lymphoid Organs include Lymphoid organs, T-Cells, B-Cells, Bone marrow, Lymph nodes, Spleen, Thymus, Lymphatic vessels, Mucosa-associated lymphatic tissue, Tonsils and Peyer patches
• The Lymphatic system contains lymphatic nodules or diffuse lymphatic tissue
• Primary Lymphoid Organs are bone marrow and the thymus
• Secondary Lymphoid Organs are where the immune response takes place.
• Secondary Lymphoid organs include the lymph nodes, spleen, and mucosa-associated lymphoid tissue (MALT)
• T Lymphocytes originate in the bone marrow
• B Lymphocytes originate and become naïve B-cells in the bone marrow
• Pro-T lymphocytes travel to the thymus where they become naïve T-cells
• Naive B-cells migrate from bone marrow to secondary lymphoid organs to encounter foreign antigens

T-Cells

• The naive T cell differentiates into its subtype, which then undergoes clonal expansion
• Memory T-cells rapidly produce cytokines when re-exposed to their pathogen

CD8+ T-Cells

• Naïve CD8+ T-Cells recognize antigens presented on MHC Class I
• Once activated, CD8+ T-Cells undergo clonal expansion to form effector cells
• Bulk of effector cells are short-lived and die after clearance of the infection
• The Memory cell's 2nd exposure to the antigen will trigger immediate effector

B-Cells

• Naïve B-cells exposed to their antigen will differentiate into plasma cells and memory B-cells
• A second exposure to its antigen will trigger the Memory B-Cell to quickly change into plasma cells and secrete antibodies

Immune Response

• In a primary immune response, a small number of naïve cells require activation before responding to a pathogen
• Activation requires a high pathogen burden
• Primary immune responses take days to weeks
• In a secondary immune response, memory cells are already made
• Antibodies are already made
• Requires a low pathogen burden to re-engage the immune system
• Innate and Adaptive Immune Systems work together at the same time