Immunology: Memory B-Cells

Memory B-Cells

• A few activated clone cells develop into moderate numbers of Memory B-cells, similar to the original clone.
• These cells do not become plasma cells, but instead circulate throughout the body and populate lymphatic tissue, remaining dormant until re-exposure.
• Upon re-exposure to the same antigen, they greatly enhance the population of the clone line for the specific antigen.

Antibody Formation and Response

• Response time: Faster
• Potency: Stronger
• Duration: Longer

Antibody Structure

• Immunoglobulin: a class of protein with a molecular weight of 160,000 to 970,000, present in serum (20% of all plasma proteins), and functions as antibodies.
• Each Heavy Chain is paralleled by a Light Chain.
• Variable portion of the chain pair is different for each specific antibody and binds to its specific antigen.
• Constant Portion determines other properties, such as diffusability, adherence to tissues, or complement.

Antibody Function

• Antibodies are the antigen-recognition molecules of B cells, made both as:
  • Membrane-bound receptors for antigen, the B-cell receptor.
  • Secreted (unbound, free) antibodies that bind antigens and elicit humoral effector functions.
• Functions of Antibodies:
  • Agglutination: Clump antigens together to be more easily destroyed by phagocytes.
  • Precipitation: Soluble antigens are precipitated and destroyed by phagocytes.

T-Cell Function

• Activated T-Cells circulate into lymph and blood and throughout the body.
• Activated T-Cells continue to circulate for months or years.
• Memory T-Cells: Some remain as new T cells similar to the original clone.
• Subsequent exposure results in a more rapid and powerful response than the first exposure, due to memory T-Cells spread throughout the body.

Major Histocompatibility Complex (MHC) Proteins

• MHC is a set of genes that code for cell surface MHC proteins (in humans, aka HLA).
• Autorecognition: MHC allows the immune system to bind to, recognize, and tolerate itself.
• Determines the compatibility of organ donors.
• Main function is to bind to Antigens from pathogens and display them on the cell surface for recognition by T-Cells.
• MHC I: present on all nucleated cells, presenting processed Antigens to Cytotoxic T-Cells who express CD8 Receptors.
• MHC II: present on Antigen Presenting Cells (Macrophages, Dendritic Cells, and B-cells), presenting processed Antigens to Helper T-Cells who express CD4 Receptors.

Immunity

• Active immunity: the person's own body develops the antibodies or activated T-Cells in response to foreign Antigen.
• Passive immunity: transfusion of antibodies or T lymphocytes to confer immunity, lasting only for a few weeks.

Alterations in Immunity

• Hypersensitivity reactions:
  • Exaggerated immune response to a foreign substance, resulting in inflammation or destruction of normal tissue.
  • 4 types (I, II, III, IV).
• Autoimmune reactions: mistakes self as non-self.

Type I Hypersensitivity

• Involved allergens are normally harmless, but re-exposure in certain individuals causes an allergic reaction.
• Acquired, predictable, rapid in onset, localized or systemic.
• Allergen binds with IgE (bound to) mast cells and basophils, causing anaphylactic degranulation.

Type II Hypersensitivity

• Also known as cytotoxic hypersensitivity, killing cells.
• Mediated by IgG or IgM and the complement system.
• Ab (IgM, IgG) binds to antigen on the patient's own cells, recognized by macrophages and dendritic cells (phagocytes).

Type III Hypersensitivity

• Immune complex-mediated, involving IgG, antigen, and complement.
• Circulating dissolved antigen binds with IgG antibody, creating Ag/Ab complexes of varying size.
• Large complexes are removed by macrophages, while smaller complexes are deposited in tissue, triggering inflammation and tissue destruction.

Type IV Hypersensitivity

• Delayed hypersensitivity reaction, not antibody-mediated.
• Cell-mediated, CD4+ and CD8+, helper T-Cells and cytotoxic T-Cells.
• Both T-Cell types recognize antigen:MHC (I&II) complex, activating tissue destruction.

Severe Combined Immunodeficiency (SCID)

• Severe defect in both the T and B lymphocyte systems.
• Serious, life-threatening infections in the first few months of life.
• Many forms, most common is X-linked recessive (hence, "bubble-boy").

RAA System

• Renin is released by the kidney in response to underperfusion or decreased NaCl delivery.
• Renin converts Angiotensinogen to Angiotensin I.
• ACE-1 converts Angiotensin I to Angiotensin II.
• Angiotensin II causes vasoconstriction and Aldosterone secretion.
• Aldosterone saves sodium and water, increasing blood pressure.
• ACE-2 converts Angiotensin II to Angiotensin (1-7), which is a vasodilator, anti-inflammatory, and antioxidant.
• Blockage of the ACE-2 enzyme receptor by Covid-19 is therefore pro-inflammatory and vasoconstrictive.

Diagnostic Tests

• Molecular Tests and Antigen Tests: show if you have an active coronavirus infection.
• Antibody Tests: look for antibodies made by the immune system in response to a specific virus, but should not be used to diagnose COVID-19 due to the time it takes for antibodies to develop.