Overview of the Immune System and Its Functions

What is immunology?

The study of the body's defense against infection or cells that threaten it.

What are the two main branches of the immune system?

Innate Immunity and Adaptive Immunity.

What are primary lymphoid organs and their functions?

Bone marrow (produces myeloid cells, NK cells, B and T lymphocytes) and thymus (where T lymphocytes mature and undergo selection).

What are secondary lymphoid organs?

Sites where naïve lymphocytes encounter antigens and become activated, including lymph nodes, spleen, and Mucosa-Associated Lymphoid Tissue (MALT).

What role do lymph nodes play in the immune system?

They filter excess extracellular fluid containing pathogens and facilitate interactions between dendritic cells and naïve lymphocytes.

What is the function of the spleen in the immune system?

It traps pathogens in the blood and activates naïve lymphocytes through resident macrophages and dendritic cells.

What is Mucosa-Associated Lymphoid Tissue (MALT)?

Includes tonsils, Peyer's patches, and the appendix, where dendritic cells activate naïve lymphocytes.

What characterizes the innate immune system?

It is the body's immediate, non-specific first line of defense against infection and does not generate immunological memory.

What are the types of barriers in the innate immune system?

Physical barriers (skin and mucous membranes), mechanical factors (mucous secretions, cilia), biochemical factors (lysozyme, HCl), and microbial factors (commensal bacteria).

What are phagocytes and their role in innate immunity?

Cells that engulf and degrade pathogens; includes macrophages, neutrophils, and eosinophils.

What are the functions of macrophages in the immune response?

They are phagocytic, act as Antigen Presenting Cells (APCs), secrete cytokines and chemokines, and recognize antigens through various receptors.

What is the role of neutrophils in the immune system?

They are the predominant cells that enter damaged tissue early after injury, phagocytose pathogens, and form Neutrophil Extracellular Traps (NETs).

How do eosinophils function in the immune response?

They primarily kill extracellular parasites (e.g., helminths) by releasing toxic granules and Reactive Oxygen Species (ROS) and are involved in allergic responses.

What are dendritic cells and their importance?

Professional Antigen Presenting Cells (APCs) that activate naïve T-cells and link the innate and adaptive immune systems.

What is the Major Histocompatibility Complex (MHC)?

A set of molecules displayed on cell surfaces that present antigens to T-cells, crucial for immune recognition.

What are the key signaling pathways involved in immune responses?

JAK-STAT and NF-κB pathways.

What are monoclonal antibodies used for?

They are used in diagnostics and therapeutics to target specific antigens.

What is the function of cytokines in the immune response?

They are signaling molecules that mediate and regulate immunity, inflammation, and hematopoiesis.

What is the role of chemokines in the immune system?

They are a subset of cytokines that specifically induce chemotaxis in nearby responsive cells.

What are the main types of adaptive immune cells?

T-cells and B-cells.

How do B-cells contribute to the immune response?

They produce antibodies that specifically target antigens.

What is the difference between innate and adaptive immunity?

Innate immunity is immediate and non-specific, while adaptive immunity is delayed and specific, involving memory.

What is the importance of antigen presentation in the immune response?

It is crucial for the activation of T-cells, which are essential for orchestrating the adaptive immune response.

What are basophils and their role in the immune response?

Basophils have receptors for IgE and release histamine and IL-4 upon activation, promoting Th2 development and involvement in allergic responses and inflammation.

What are mast cells and their functions?

Mast cells are sentinel cells present in skin, mucosal epithelium, and connective tissues. They express FcR for IgE antibodies and TLRs, releasing histamine and lipid mediators to promote acute inflammation and defend against helminths, also playing a role in allergic reactions.

What are Natural Killer (NK) cells and their role in innate immunity?

NK cells are lymphoid lineage cells important for killing cells infected with cytoplasmic pathogens and cancer cells. They recognize infected cells through stress receptors, lack of MHC I, or antibody coating (ADCC), inducing apoptosis via perforin and granzyme and secreting IFN-γ.

What are Pathogen Recognition Receptors (PRRs) and their function?

PRRs, such as Mannose Receptors and Toll-Like Receptors (TLRs), recognize Pathogen-Associated Molecular Patterns (PAMPs) like LPS, aiding in pathogen recognition.

What are Damage-Associated Molecular Patterns (DAMPs) and their significance?

DAMPs are recognized by NOD-like receptors (NLRs) released from dying or damaged cells, signaling tissue damage.

What are opsonin receptors and their role in phagocytosis?

Opsonin receptors, such as FcR (recognizing antibody Fc region) and CR (recognizing C3b), enhance phagocytosis by marking pathogens for engulfment.

Describe the process of phagocytosis.

Phagocytosis involves phagocytes engulfing pathogens, internalizing them into a phagosome that fuses with a lysosome to form a phagolysosome, where pathogens are killed.

What are the oxygen-dependent mechanisms in phagocytosis?

Oxygen-dependent mechanisms, or oxidative burst, involve the production of Reactive Oxygen Species (ROS) like superoxide ion and hydrogen peroxide to kill pathogens.

What are the oxygen-independent mechanisms in phagocytosis?

Oxygen-independent mechanisms utilize enzymes and toxic molecules such as lysozyme, nucleases, and proteases to kill pathogens.

What are acute phase proteins and their role in the immune response?

Acute phase proteins, produced by the liver in response to infection and inflammation (e.g., CRP, MBL), play roles in opsonization and recruitment of immune cells.

What is the complement system and its key functions?

The complement system consists of 30 plasma proteins that defend against microbes in extracellular spaces, acting as proteases, opsonins, or chemoattractants.

How does the complement system enhance phagocytosis?

Opsonization by C3b coating enhances phagocytosis of pathogens.

What is the Membrane Attack Complex (MAC) and its function?

The MAC, formed by C5b, C6, C7, C8, and multiple C9 copies, creates pores in microbial surfaces, leading to lysis of microbes/cells.

What role do C3a and C5a play in inflammation?

C3a and C5a act as chemoattractants, recruiting cells and inducing histamine release from mast cells, increasing endothelial permeability.

What are the pathways of complement activation?

The pathways include Classical (antibody-bound antigen), Lectin (MBL binding to microbial carbohydrates), and Alternative (spontaneous hydrolysis of C3 in plasma).

What is inflammation and its primary function?

Inflammation is a biological response to harmful stimuli aimed at eliminating the initial cause of cell injury, clearing out damaged cells, and initiating tissue repair.

What are the five cardinal signs of inflammation?

The five cardinal signs are calor (heat), dolor (pain), rubor (redness), tumor (swelling), and functio laesa (loss of function).

What initiates the inflammatory response?

The inflammatory response is initiated by injury or infection, with chemokines and cytokines causing vasodilation and increased vascular permeability.

What characterizes the adaptive immune response?

The adaptive immune response is characterized by specificity, delay, and the generation of immunological memory, leading to a stronger response upon re-exposure to a pathogen.

What are the components of adaptive immunity?

Adaptive immunity consists of T-cells, B-cells, and humoral components (antibodies).

Where do B-cells originate and develop?

B-cells originate from common lymphoid progenitors in the bone marrow, where they develop their B-Cell Receptor (BCR).

What happens to a B-cell if it cannot produce a B-cell receptor (BCR)?

The B-cell dies.

What is the process called when a B-cell binds to self in the bone marrow?

Negative selection, leading to apoptosis.

How many different B-cells can the body potentially have?

Up to 10 billion different B-cells.

What is the B-cell receptor (BCR) and its structure?

The BCR is the backbone marker of B-cells (CD19), consisting of two heavy chains and two light chains connected by disulphide bonds.

What is involved in heavy chain gene production for B-cells?

VDJ recombination, where Variable (V), Diversity (D), and Joining (J) gene segments combine with added nucleotides for junctional diversity.

What is the first step in light chain gene recombination?

Kappa (κ) chain recombination is attempted first, resulting in a higher prevalence of kappa light chains.

What initiates B-cell activation?

A BCR recognizing an antigen attached to follicular dendritic cells leads to binding.

What occurs after a B-cell binds to an antigen?

Endocytosis and degradation of the antigen into peptides, which are presented on MHCII on the B-cell surface.

What is required for T-cell dependent activation of B-cells?

An effector T follicular helper (Tfh) cell that recognizes the peptide-MHCII complex.

What are the outcomes of B-cell activation?

Proliferation, differentiation into plasma cells, and production of other antibody classes.

What is somatic hypermutation and its effect on B-cells?

It causes point mutations in the variable region of the BCR gene, increasing affinity for pathogens.

What is class switching in B-cells?

The process where a B-cell changes the constant region of its heavy chain gene to produce different antibody isotypes while maintaining antigen specificity.

What happens to activated B-cells after proliferation?

They differentiate into plasma cells or memory cells.

What are plasma cells and their function?

Plasma cells are non-dividing cells that secrete antibodies and die after about a week.

What is the general structure of antibodies (immunoglobulins)?

Antibodies consist of 2 heavy chains and 2 light chains, each with variable and constant regions.

What are the two fragments produced when antibodies are digested with papain?

Fab (fragment antigen binding) and Fc (fragment constant).

What is the role of the Fab fragment of an antibody?

It is responsible for antigen recognition.

What is the function of the Fc fragment of an antibody?

It determines the antibody's effector functions and binds to immune cell receptors.

What are the functional roles of antibodies?

Agglutination, opsonisation, complement activation, neutralisation, and antibody-dependent cell-mediated cytotoxicity (ADCC).

What is the role of IgM antibodies?

IgM is produced during infection, is a pentamer with 10 antigen binding sites, and acts as an opsonin.

What is known about the function of IgD antibodies?

IgD is co-expressed with IgM on the cell surface, but its function is not well understood.

What is the significance of somatic hypermutation in B-cells?

It allows B-cells with higher affinity BCRs to proliferate, while those with lower affinity undergo apoptosis.

What is the ratio of kappa to lambda light chain production in BCRs?

There is a 2:1 ratio, with more BCRs having kappa light chains.

What is the primary function of IgG?

IgG is the most important antibody in tissues and has the highest concentration in blood. It fixes complement, crosses the placenta for passive immunity of the fetus, and its Fc region is recognized by FcγR on phagocytes and NK cells.

What is the structure of IgA and its primary function?

IgA is primarily a dimer synthesized by plasma cells in mucosa-associated lymphoid tissue (MALT). It acts mainly as a neutralizing antibody on luminal surfaces and is secreted in breast milk for passive immunity to newborns.

How does IgE function in allergic responses?

IgE is a monomer that binds to FcεR receptors on mast cells and basophils. Upon re-exposure to a multivalent pathogen, it cross-links, leading to mast cell degranulation and allergic responses.

Where are T-cells produced and where do they complete their development?

T-cells are produced in the bone marrow but complete their development in the thymus.

What are the two main types of T-cells?

CD8 T-cells and CD4 T-cells.

What is the T-cell receptor (TCR) and its significance?

The TCR is the backbone marker of T-cells (CD3) and provides immense diversity through the recombination of gene segments in the variable regions of the α and β genes.

What is the process of positive selection in T-cell development?

In the thymus cortex, thymocytes whose TCRs bind MHC I become CD8 T-cells and those that bind MHC II become CD4 T-cells; those that do not bind die by neglect.

What occurs during negative selection of T-cells?

Thymocytes that bind self-antigens too strongly undergo apoptosis, ensuring self-tolerance.

What are naïve T-cells and their role after leaving the thymus?

Naïve T-cells are mature CD8 and CD4 T-cells that leave the thymus and circulate between blood and peripheral lymphoid tissue, awaiting activation by mature dendritic cells.

What is the immunological synapse?

The immunological synapse is the interface between an antigen-presenting cell (APC) or target cell and a naïve or effector lymphocyte, providing the two signals required for T-cell activation.

What are the two signals required for T-cell activation?

Signal 1 is TCR recognition of a specific peptide presented on an MHC molecule; Signal 2 is co-stimulation, typically via CD28 on the T-cell binding to B7 (CD80 or CD86) on the mature dendritic cell.

What happens to T-cells without the second signal during activation?

Without the second signal, T-cells may become anergic or die.

What are effector CD8 T-cells also known as?

Effector CD8 T-cells are known as Cytotoxic T Lymphocytes (CTLs).

How do effector CD8 T-cells kill infected cells?

They kill infected cells by signaling them to undergo apoptosis through either linking death ligands to death receptors (extrinsic pathway) or secreting perforin and granzyme.

What is the primary role of effector CD4 T-cells?

Effector CD4 T-cells mediate the immune response through direct interaction with other immune cells or secretion of cytokines.

What determines the development of naïve CD4 T-cells upon activation?

The cytokines present during activation by dendritic cells determine what the naïve CD4 T-cell develops into.

What cytokines do Th1 cells secrete and their function?

Th1 cells secrete IFN-γ and IL-12 to activate macrophages, increasing MHCI and II expression, and efficiently destroy intracellular pathogens.

What is the role of Th2 cells in the immune response?

Th2 cells secrete IL-4 and IL-5 to recruit and activate eosinophils, mast cells, and basophils, primarily to destroy extracellular parasites.

What cytokines do Th17 cells secrete and their significance?

Th17 cells secrete IL-17, which induces fibroblasts and epithelial cells to secrete IL-6, CXCL8, and G-CSF, leading to recruitment of neutrophils and amplifying acute inflammatory responses.

What is the consequence of inappropriate activation of Th2 cells?

Inappropriate activation of Th2 cells can lead to allergic reactions.

What is the estimated diversity of T-cell receptors due to gene recombination?

The estimated diversity of T-cell receptors is about 10^15 (one quadrillion).

What are Tfh cells and their primary function?

Tfh cells (IL-6) stay in the follicles of secondary lymphoid organs and activate B-cells by secreting cytokines (IFN-γ, IL-4, TGF-β) and promoting proliferation, somatic hypermutation, and class switching.

What is the role of Treg cells in the immune system?

Treg cells (TGF-β, IL-2) inhibit T cell proliferation, prevent dendritic cells from secreting IL-12, and secrete IL-10 and TGF-β, suppressing the immune system and preventing Th1 differentiation.

What can result from a lack of Treg cells?

A lack of Treg cells can lead to autoimmune disease.

What are MHC molecules and their primary function?

MHC molecules (Human Leukocyte Antigen - HLA) are glycoproteins that bind and present peptide antigens to T-cells.

What is the significance of MHC polymorphism?

MHC molecules are highly polymorphic, which is advantageous for populations but a main cause of rejection in transplantation.

Where are MHC Class I molecules expressed?

MHC Class I molecules are present on all nucleated body cells except erythrocytes (RBCs).

What is the structure of MHC Class I molecules?

MHC Class I consists of three α subunits and a β2-microglobulin.

What type of peptides do MHC Class I molecules present?

MHC Class I presents peptides derived from intracellular proteins, either normal cellular proteins or pathogen proteins (antigens) to CD8 T-cells.

What is the processing pathway for MHC Class I?

Intracellular antigens are degraded by proteasomes into peptides, transported into the ER by TAP, bind to newly synthesized MHC I molecules, and are then transported to the cell surface.

Where are MHC Class II molecules expressed?

MHC Class II molecules are present on the cell surfaces of antigen-presenting cells (APCs) such as macrophages, dendritic cells, and B-cells.

What is the structure of MHC Class II molecules?

MHC Class II consists of α and β chains.

What type of peptides do MHC Class II molecules present?

MHC Class II presents peptides derived from extracellular pathogens that have been phagocytosed or endocytosed and degraded in phagolysosomes or acidic endosomes to CD4 T-cells.