Comprehensive Immunology: Innate, Adaptive, Cells, and Antibodies

Innate immunity

The ability to resist infection by means of normally present body functions.

Adaptive immunity

A type of resistance characterized by specificity for each pathogen, or microbial agent, and the ability to remember a prior exposure.

Chemotaxis

Immune cells move towards a chemical signal.

Diapedesis

White blood cells migrate from the bloodstream through an intact capillary wall to reach areas of infection or inflammation in the surrounding tissue.

Neutrophils

The most abundant type of white blood cell and a crucial component of the innate immune system.

Macrophages

Large, specialized white blood cells in the immune system that detect, engulf, and destroy foreign pathogens like bacteria.

Tissue cells

Act as the first responders to infection and injury by engulfing pathogens and damaged cells (phagocytosis) and signaling the broader immune system.

NK cells

Recognize and kill abnormal cells without prior sensitization.

T lymphocytes

Have adaptive immunity, which requires prior sensitization and antigen recognition by the T-cell receptor, and generally require MHC-I for activation.

Bone Marrow

The main source of hematopoietic stem cells, which develop erythrocytes, granulocytes, monocytes, platelets, and lymphocytes.

Thymus

Location for maturation of T lymphocytes.

Secondary lymphoid organs

Function as potential sites for contact with foreign antigens and increase the probability of an immune response.

Spleen

A secondary lymphoid organ that filters blood and helps initiate immune responses.

Lymph nodes

Central collecting points for lymph fluid that filter lymph fluid, trapping pathogens and initiating immune responses.

Mucosal-associated lymphoid tissue (MALT)

A secondary lymphoid organ that plays a role in immune responses at mucosal surfaces.

Primary follicles

Contain B cells not yet stimulated by antigens.

Secondary follicles

Form plasma cells and memory cells when exposed to an antigen.

B cells

Provide humoral immunity by producing antibodies that target pathogens in the bloodstream and other body fluids.

T cells

Responsible for cell-mediated immunity by directly killing infected cells, cancerous cells, and regulating the immune response.

Opsonins

Immune molecules that bind to pathogens like bacteria and viruses, essentially tagging them to make them more appealing and easier for phagocytes to destroy.

Eosinophils

Target and destroy parasites and play a significant role in allergic responses and the inflammatory process.

Basophils

Release histamine and other chemicals that cause inflammation and dilate blood vessels, most associated with allergic reactions and asthma.

Monocytes

Circulate in the blood and can migrate into tissues to become macrophages, powerful phagocytes that engulf bacteria, viruses, and cellular debris.

Antigen

Any molecule recognized as foreign by the immune system.

Immunogen

An antigen that is capable of inducing an immune response on its own.

Foreignness

The substance must be perceived as foreign by the host's immune system to stimulate an immune response.

High molecular weight

A substance needs a significant molecular weight to be recognized by the immune system.

Chemical Complexity

Large, complex molecules with diverse chemical structures are better immunogens because they present epitopes.

Degradeability

Must be capable of being processed and presented via Major Histocompatibility Complex molecules.

Hapten

Non-immunogenic materials that create new antigenic determinants when combined with a carrier.

Epitope

The precise region of an antigen that is recognized and bound by antibodies or T-cell receptors, triggering an immune response.

External defense systems

Act as a barrier and prevent pathogens from getting into the body.

Internal defense system

Fight pathogens and foreign substances that have already entered the body.

Pathogen-associated molecular pattern (PAMP)

The molecular structure of a microbe that is not found on host cells and is essential for the pathogen's survival.

Pathogen recognition receptors (PRRs)

Initiate both innate and adaptive immune responses by detecting PAMPS and DAMPS.

Toll-like receptors (TLRs)

Act as a pattern recognition receptor that recognize and bind to specific molecular structures on pathogens (PAMPs).

Acute-phase reactants

Liver-produced proteins that increase in the blood during inflammation, acting as key components of the innate immune system.

CRP

Increases rapidly within 4 to 6 hours of an inflammatory or infectious event.

C3

Increases not as rapidly within 48-72 hours of an inflammatory or infectious event.

Significance of abnormal levels of acute-phase reactants

Signifies the presence of inflammation in the body, indicating an underlying condition like infection, trauma, autoimmune disease, or cancer.

Major function of CRP

Recognizing and binding to foreign pathogens (bacteria) and damaged cells, activating the complement system to enhance phagocytosis by immune cells.

Defense mechanism of NK cells

Directly killing virus-infected and tumor cells through the release of perforin and granzymes, and also by producing cytokines.

Granzymes

Trigger cell death in target cells, such as those infected by viruses or that have become cancerous.

Process of inflammation - Initiation

Damaged cells release chemicals, such as histamine and cytokines.

Process of inflammation - Vasodilation and Increased Permeability

Blood vessels become wider, increasing blood flow to the injured area; Increased permeability allows fluid, proteins, and white blood cells to leak out of the capillaries.

Process of inflammation - Recruitment of Immune Cells

White blood cells are attracted to the injured area; Engulf and destroy damaged cells, bacteria, and other foreign substances.

Process of inflammation - Tissue Repair

Once the threat is removed, the inflammatory process begins to resolve; Fibroblasts produce collagen to repair damaged tissue.

Steps in the process of phagocytosis - Chemotaxis and Adherence

Phagocytic cells are drawn to the target particle through chemical signals; The cell adheres to the particles.

Steps in the process of phagocytosis - Ingestion and Phagosome Formation

The cell membrane extends to surround the particles, forming pseudopods that meet and fuse.

Steps in the process of phagocytosis - Phagolysosome formation

The newly formed phagosome then fuses with one or more lysosomes.

Steps in the process of phagocytosis - Digestion and Elimination

The digestive enzymes from the lysosome break down and destroy the ingested particle.

Main pathogen-recognition receptors

Toll-like receptors: proteins that act as sentinels of the innate immune system, recognizing molecular patterns found on pathogens like bacteria, viruses, fungi, and parasites.

Intracellular mechanism for the destruction of foreign particles during phagocytosis

Destruction occurs through: Oxygen-dependent mechanisms, like the production of reactive oxygen species, and oxygen-independent mechanisms.

Importance of phagocytosis in innate immunity

Pathogen clearance: Phagocytes engulf and digest bacteria, fungi, and viruses, directly eliminating them before causing a full-blown infection.

Importance of phagocytosis in adaptive immunity

Antigen presentation: Specialized phagocytes present processed fragments of the pathogens they have engulfed to lymphocytes.

Perforin

Create pores in the cell membranes of target cells, leading to their destruction.

How NK cells recognize target cells

Recognize target cells by balancing signals from two types of receptors that bind to MHC class I molecules.

Methods NK cells use to target cells - Perforin/Granzyme-Mediated Cytotoxicity

When an NK cell encounters a stressed or infected target cell, it forms an immunological synapse.

Methods NK cells use to target cells - Death Receptor-Mediated Apoptosis

NK cells express death ligands, while target cells express corresponding death receptors.

Structure of a typical immunoglobulin

Y-shaped structure formed by two identical heavy chains and two identical light chains, linked by disulfide bonds.

Isotypes

Distinct classes and subclasses of antibodies that exist within a species.

Allotypes

Subtle, genetically determined variations in amino acid sequences within a specific isotype.

Idiotypes

Unique antigenic determinant formed by a specific amino acid sequence and arrangement of the variable regions of an individual antibody molecule.

Immunoglobulin types - IgG

Serum %: 75%; Structure: Monomer; Primary location: Blood and extracellular fluid.

Immunoglobulin types - IgA

Serum %: 15%; Structure: Monomer in blood, dimer in secretions; Primary location: Mucosal surfaces and secretions.

Immunoglobulin types - IgM

Serum %: 5-10%; Structure: Pentamer in blood, monomer on B cells; Primary location: Blood lymph.

Immunoglobulin types - IgD

Serum %: <1% (0.2%); Structure: Monomer; Primary location: B cell surface.

Immunoglobulin types - IgE

Serum %: <1% (0.002%); Structure: Monomer; Primary location: Bound to mast cells and basophils.

Light chains of immunoglobulins

Smaller, composed of a single variable domain and a single constant domain.

Heavy chains of immunoglobulins

Larger, consisting of one variable and multiple constant domains.

Structure of IgG

Has a Y-shape and is composed of two identical heavy chains and two identical light chains held together by disulfide bonds.

Differences in IgG subclasses

Differ in their structural variations, particularly in the Fc region and hinge, which dictate their functional capabilities.

Structure of IgM vs IgG

IgM is a pentameric structure, made of five Y-shaped subunits linked by disulfide bonds and a J-chain.

Function of IgG

The most abundant class in the blood, it can diffuse into tissues and bind to pathogens and toxins, neutralizing them.

Function of IgA

Found in mucosal secretions, protects mucosal surfaces by preventing pathogen adherence and invasion.

Function of IgM

The first antibody produced in response to a new antigen allows for efficient binding to pathogens and activation of the complement system.

Function of IgE

Plays a role in defense against parasitic worms and is involved in allergic and inflammatory responses.

Function of IgD

Primarily found on the surface of B cells, where it acts as a B cell receptor, signaling for activation of B cells.

Secretory component of IgA

A protein fragment of the polymeric immunoglobulin receptor that remains attached to dimeric IgA.

Differences of IgD

Largely a cell-bound receptor on mature B cells, rather than a freely circulating antibody.

Cells that IgE binds to in allergic reactions

Mast cells and basophils.

Significance of the gamma band in SPE

Primarily containing immunoglobulins (antibodies).

Hypervariable region of the antibody

Specific segment of the antibody's variable region that has a high degree of amino acid variation and directly contacts an antigen.

Bence-Jones proteins

Abnormal proteins found in the urine that are produced by plasma cells.

J chain

A protein that forms a disulfide bond to link individual immunoglobulin subunits into polymers.

Primary immune response - Lag phase

After the first encounter with an antigen, there is a delay of several days to weeks before antibodies begin to appear.

Primary immune response - Log Phase

Activated B cells undergo clonal expansion, differentiating into short-lived plasma cells that secrete antibodies.

Primary immune response - Peak Phase

The antibody levels in the blood reach a peak.

Primary immune response - Decline Phase

Antibody levels decrease but may remain at a detectable level.

Secondary immune response - Lag Phase

Due to the presence of memory B cells generated during the primary response, the latent period is much shorter.

Secondary immune response - Log Phase

Memory B cells rapidly differentiate into plasma cells, producing a large quantity of high-affinity antibodies.

Secondary immune response - Peak Phase

Antibody levels reach a much higher peak concentration compared to the primary response.

Secondary immune response - Decline Phase

Antibody levels drop but remain at a higher level than after the primary response.

Monoclonal antibody production - Antigen Selection and Preparation

The specific molecule to be targeted is identified, synthesized, or purchased.

Monoclonal antibody production - Immunization

A host animal is injected with the antigen along with an adjuvant to stimulate an immune response.

Monoclonal antibody production - B-cell Isolation

After repeated injections, antigen-specific B lymphocytes are extracted from the animal's spleen.

Monoclonal antibody production - Hybridoma Formation

B cells are fused with cancerous myeloma cells, which are immortal and can grow indefinitely in culture.

Monoclonal antibody production - Selection and Screening

Fused cells are grown in a selective culture medium that only allows the hybridomas to survive.

Monoclonal antibody production - Antibody Expression and Purification

Selected hybridomas are cultured in large bioreactors to produce a high quantity of the specific mAb.