Immune System: Innate Resistance

Immune System Overview

• The immune system evolved as a dual defense mechanism to prevent, limit, and resolve infections from disease-causing organisms and neoplasms.
• It limits the scope of immunology to humoral immunity and serology due to the topic's vastness.

Innate Resistance

• Innate, or non-specific, resistance serves as the body's first line of defense, aimed at preventing or limiting pathogen and neoplasm invasions.
• Anatomical defenses like skin, mucous membranes, and normal flora provide a physical barrier.
• Mechanical defenses such as urination and the mucociliary escalator physically expel invaders.
• Chemical defenses like pH, lysozyme, interferon, and complement damage or kill invaders.
• Cellular defenses, including neutrophils, eosinophils, basophils, monocytes, and lymphocytes, carry out various functions.
• Key characteristics include being present at birth, ready for immediate use, non-specific, lacking memory, unable to differentiate self from non-self, and unable to resolve established infections.

Leukocytes

• Includes both a white blood cell count (WBC) and a white blood cell differential count (DIFF).
• WBC (White Blood cell Count) provides an absolute count of total leukocytes per unit of blood volume; increased counts often indicate infection.
• A WBC result of less than 4.5 x10³/μL indicates leukopenia, which is also defined as bone marrow failure and increased destruction.
• Results greater than 11.0 x103/μL indicate leukocytosis which can be caused by infection or leukemia.

Differential Count (DIFF)

• Calculates the count of each type of WBC, aiding in understanding innate resistance.
• Results can be expressed as a percentage (relative count) or as an absolute count (thousands of cells per microliter).
• An increase in specific populations can help identify the type of pathogen.
• < 40% or < 1.8 x103/μL of Neutrophils (Neu/NeuA) indicates Neutropenia, typically caused by bone marrow failure.

• 80% or >7.0 x10³/μL of Neutrophils (Neu/NeuA) indicates Neutrophilia, which typically caused by bacterial infection.

• < 25% or < 1.0 x103/μL of Lymphocytes (Lym/LymA) result indicates Lymphopenia resulting in bone marrow failure.

• 35% or > 4.8 x103/μL of Lymphocytes (Lym/LymA) result indicates Lymphocytosis resulting in viral infections.

• 10% or > 0.8 x103/μL Monocytes (Mon/MonA) result indicates Monocytosis resulting in inflammation or with infection.

• 5% or > 0.4 x103/μL Eosinophils (Eos/EosA) result indicates Eosinophilia resulting in parasitic infection.

• 1% or > 0.2 x103/μL Basophils (Bas/BasA) result indicates Basophilia resulting in leukemia

Acquired Resistance

• Mechanisms function only after innate defenses fail and a successful invasion by pathogenic organisms occurs.
• It serves as a second line of defense, intended to clear or resolve infections, characterized by not being present at birth, having a 3-day response delay, high specificity, memory, the ability to differentiate self from non-self, and the ability to resolve established infections.

Humoral and Cell-Mediated Immunity

• Resistance divides into humoral and cell-mediated compartments.
• T lymphocytes include TH1, TH2, Ts, and TC (cytotoxic T lymphocytes (CTL)), where only TC cells are non-regulatory, killing infected/neoplastic cells in an antigen-specific manner.
• B lymphocytes are responsible for humoral (soluble) immunity.
• B cells create humoral immunity by producing and secreting immunoglobulins (Ig) or antibodies (Ab), which recognize and clear antigens.
• By definition, any substance capable of generating an antibody response is an antigen.

Anatomy of Immunity

• B cells originate and develop fully in the bone (red) marrow, a primary lymphoid organ.
• T cells originate in the bone marrow but mature in the thymus gland, learning to differentiate self from non-self.
• Both B and T cells populate secondary lymphoid organs, such as lymph nodes and spleen.
• Within the secondary lymphoid organs, specific associations between B and T cells exist.

Physiology of Immunoglobulins (Ig)

• There are five types of Ig : IgM, IgD, IgG, IgA, and IgE, each with different characteristics and functions, they all share a basic structure and are produced similarly.
• Ig are glycoproteins with two identical heavy (H) chains and two identical light (L) chains, represented as H₂L₂.
• The variable (V) and constant (C) domains in H and L chains form the antigen-binding site (paratope), with each monomer carrying two paratopes.
• The CH domain determines the Ig type and how antigens are cleared.
• IgM, functioning as an antigen receptor on B cells and secreted as a pentamer during initial immune responses, marks acute infections and often reacts optimally with carbohydrate antigens at room temperature naturally occurring.
• IgG is secreted as a monomer for convalescence and secondary immune responses, marking chronic infection and can cross the placenta.
• IgG optimally reacts with protein antigens at body temperature.

Serology

• It is the scientific study or diagnostic examination of blood serum, especially regarding the immune system.
• Antibodies are specific to given antigens, similar to a lock and key, which makes antibodies useful laboratory tools.

Precipitation and Agglutination Reactions

• Precipitation involves the reaction between an antibody and a soluble antigen.
• As the immune complex forms and precipitates, it becomes visible to the naked eye.
• Celiac disease results in a gluten immune reaction and avoidance of gluten is critical.
• The double diffusion assay is performed to identify which cereal grains have gluten.
• In an Ouchterlony double diffusion assay, antibody is placed in the center well and antigens surrounding.

Agglutination

• It involves the reaction between an antibody and particulate antigen, becoming visible to the naked eye.
• Agglutination reactions are used for red blood cell phenotyping using specific antibodies to identify RBC antigens.

Agglutination Assay

• A solution of antibody is mixed with an antigen solution.
• After stirring, the antibody binds the antigen and when concentrations reach equivalence the agglutinate forms,
• Blood types are determined by agglutination assay.
• Factors such as ABO(H) and Rh(D) systems classify RBCs, dependent on the antigens present.
• A and B antigens are carbohydrates, leading individuals to produce IgM antibodies against antigens they lack.
• Rh(D), being a protein antigen, induces IgM antibodies only in multiply transfused or pregnant individuals with feto-maternal bleeds.
• anti Anti-Rh(D) antibodies are invariably IgG.

Blood Types and Transfusions

• Blood type depends of the blood type antigens
• O= blood types have both Anti-A and anti-B antibodies
• O+blood types have both Anti-A and anti-B antibodies
• A= blood types have Anti-B antibody
• A+ blood types have Anti-B antibody
• B= blood types have Anti-A antibody
• B+ blood types have Anti-A antibody
• AB= blood types have niether anti-A nor anti-B antibodies
• AB+ blood types have niether anti-A nor anti-B antibodies

Blood Sample Interpretation

• A person's blood type can be easily determined by mixing a drop of RBCs with an antibody of known specificity and watching for agglutination.

Blood Transfusions

• In transfusions, recipients receive "like" RBCs in minimal plasma, though other types may be given based on availability.
• Compatible blood is critical due to the destruction of incompatible cells and risk of death.
• Type O- RBCs suit any transfusion due to O= is a "universal" donor.
• Type AB+ can receive any types so AB+ is a "universal" recipient.
• Anti-B antibodies attack the donated type B cells in an A recipient.
• Hgb and membrane release from transfusions can cause renal failure.
• The recipient can die after only 3–5 mL of incompatible blood.