Immune System Components and HLA

Components of the Immune System

• The immune system defends the body against foreign entities.
• "Self" refers to the body's own cells and components, whereas "non-self" refers to foreign entities that the immune system targets.
• MHC (Major Histocompatibility Complex) molecules are crucial for immune recognition.
• The Human Leukocyte Antigen (HLA) is the MHC in humans, functioning as a "self-marker."
• Each individual has a unique HLA, much like a "biological identity."
• Identical twins are the exception, typically sharing the same HLA.

HLA Genes and Function

• HLA is coded by 6 genes: HLA-A, HLA-B, HLA-C, HLA-DP, HLA-DR, and HLA-DQ.
• HLA plays a role in binding clefts that hold antigen proteins.
• MHC Class I molecules (HLA-I) are found on nearly all cells, excluding red blood cells, and includes skin, bone and nerve cells.
• MHC Class II molecules (HLA-II) are found on antigen-presenting cells and immune cells like macrophages.

Grafts and Transplants

• Grafting involves the transfer of tissue (skin) or an entire organ between individuals.
• Autograft: Donor and recipient are the same individual, meaning the graft occurs within the same body.
• Isograft: Donor and recipient are genetically identical, such as identical twins.
• Allograft: Donor and recipient are genetically different but of the same species.
• Xenograft: Donor and recipient are genetically different and belong to different species.

HLA Coding

• HLA is coded by 6 genes.
• HLA Class I is coded by the A, B, and C genes.
• HLA Class II is coded by the DP, DQ, and DR genes.

Non-Self

• Non-self refers to any foreign body not considered part of the body's own system.
• The modified cell is considered non-self.
• HLA presents non-self such as a viral peptide, or self-peptide like a mutant or viral peptide.

Immunological Self

• Immunological self is when the immune system recognizes something as part of the body.
• All nucleated body cells break down proteins into peptides presented on the cell membrane, associated with HLA-I molecules.
• Immunological self = HLA-I + self-peptide.

Pathogens

• Pathogens are infectious agents that cause infection in living organisms by invasion and growth.
• Types include non-microscopic pathogens (worms) and microscopic pathogens (bacteria, viruses, fungi, protozoa).

Antigens

• An antigen is a large molecule (protein or complex carbohydrate) that triggers an immune response.
• Antigens can be free, like bacterial toxins, snake venom and vaccines.
• Antigens can be carried by a cell as in the case of allografts in MHC.
• Some antigens are from a modified self such as a cancer/tumor cell or infected by bacteria, carrying self MHC + non self peptide,
• Antigens can be carried by particles, such as viruses, dust or pollen, causing allergies.

Graft Acceptance and Rejection

• Graft acceptance or rejection depends on the compatibility of MHC between the donor and recipient.
• It's nearly impossible for unrelated individuals to have the same HLA because of the high gene allele combination.
• Modified cells are considered non-self because HLA presents non self-peptides like mutant or viral peptides.

Blood Components

• Blood is composed of red blood cells, white blood cells, platelets and plasma.
• Red blood cells transport oxygen and carbon dioxide.
• Platelets aid in blood coagulation.
• Leukocytes are immune cells.

Immune Cell Origins and Types

• Immune cells originate in bone marrow.
• The myeloid stem cells evolve into monocytes, granulocytes, and mast cells.
• There are categories of stem cells that stem from lymphoid or myeloid.
• The Lymphoid family of cells product B cells and T cells.

Granulocytes

• Have a multi-lobed nucleus.
• Neutrophils perform phagocytosis.
• Eosinophils help with phagocytosis.
• Basophils are related to allergic reactions.

Monocytes

• Have a horseshoe-shaped nucleus.
• Responsible for phagocytosis of antigens or non-self cells.

Lymphocytes

• There are two types of lymphocytes: B Lymphocytes and T Lymphocytes.

B Lymphocytes

• B cells differentiate, which leads to activation of plasma cells that produce antibodies specific to an antigen.
• B cells have antibody receptors known as surface antibodies.

T Lymphocytes

• T-helper cells (Th or T4) activate B cells.
• T-killer cells (Tc or T8) destroy infected cells.

Lymphoid Organs

• Lymphoid organs include primary and secondary organs.

Primary Lymphoid Organs

• Bone marrow: production site for all leukocytes and maturation of B-lymphocytes.
• Thymus: site of T-lymphocyte maturation.

Secondary Lymphoid Organs

• Interaction site between leukocytes and antigens.
• Spleen: filters antigens in the blood.
• Lymph nodes: filters antigens in the lymph.

Maturation of Immune Cells

B Lymphocytes

• B lymphocyte maturation happens in bone marrow.
• B lymphocytes that have receptors against self-antigens are eliminated, while cells that don't recognize "self" are preserved.

T Lymphocytes

• T-lymphocyte maturation goes through double selection.
• Mature T lymphocytes should recognize self-HLA molecules but not react to self-peptides.
• T lymphocytes are selected in two steps: the ones that can bind to the HLA molecule and those that bind to self-peptide after which the others are preserved.

Secondary Lymphoid Organs Details

Lymph Nodes

• Lymph nodes are distributed around lymphatic vessels and contain lymph which collects fluid between cells.
• Play the role of triggering specific immune responses against antigens brought by the lymph.

Spleen

• Secondary lymphoid organ connected to blood vessels.
• Functions to trigger immune reactions against antigens in the blood circulation.