PHA 375- Immunology TBL #4

What is immunity?

Immunity is the ability of the immune system to protect the body from external invading pathogens by providing defensive mechanisms against infectious diseases.

What are the two main functions of the immune system?

To protect the body from external invading pathogens and to provide defensive mechanisms against infectious diseases.

What is the difference between self and non-self?

A healthy immune system recognizes self as the body's own tissues and non-self as foreign pathogens. Failure to distinguish between them can result in autoimmunity.

What is autoimmunity?

Autoimmunity occurs when the immune system attacks the body's own tissues because it cannot distinguish self from non-self, leading to autoimmune disease.

What is an immune response?

An immune response is the defense generated by the immune system against a potential pathogen.

How do innate and adaptive immunity differ?

Innate immunity is the first line of defense, nonspecific, rapidly mobilized, lacks immunologic memory, and does not produce specific antibodies. Adaptive immunity is the second line of defense, pathogen-specific, slower to respond initially, has immunologic memory, and produces specific antibodies.

How are white blood cells classified?

White blood cells are classified as granular leukocytes (eosinophils, neutrophils, basophils, NK cells) or agranular leukocytes (macrophages, dendritic cells, B cells, and T cells).

What is the major function of macrophages?

Macrophages engulf and destroy pathogens by phagocytosis.

What is the relationship between monocytes and macrophages?

Monocytes circulate in the blood and mature into macrophages after entering tissues.

What is the primary function of neutrophils?

Neutrophils destroy pathogens primarily through phagocytosis.

What is the primary function of basophils?

Basophils mediate inflammation and allergic reactions by releasing histamine and serotonin.

What is the primary function of eosinophils?

Eosinophils defend against worms and parasites and participate in allergic immune responses.

What are the functions of dendritic cells?

Dendritic cells perform phagocytosis, macropinocytosis, and antigen presentation as professional antigen-presenting cells (APCs).

Which immune cells are large granular lymphocytes that kill virus-infected cells and tumor cells?

Natural killer (NK) cells. They express pathogen-recognizing surface receptors, contain perforin and granzyme, and participate in antibody-dependent cellular cytotoxicity (ADCC) by binding the Fc region of antibodies.

What are the cellular components of the adaptive immune system?

B cells and T cells.

Where do B cells develop and mature?

B cells develop in the bone marrow and mature in secondary lymphoid organs such as the spleen, where they can become antibody-secreting cells after activation.

Where do T cells develop and mature?

T cells are produced in the bone marrow and mature in the thymus, where they become responsible for cell-mediated immunity.

What is an antigen?

An antigen is a foreign substance recognized by the immune system that may stimulate an immune response. Antigens may be organisms, molecules, or parts of molecules.

What is an epitope?

An epitope is the smallest region of an antigen recognized by immune cell receptors and/or antibodies.

What three properties determine whether an antigen is immunogenic?

Foreignness, size, and chemical/structural complexity. Large, complex, foreign molecules are the most immunogenic.

Why are small molecules (haptens) usually not immunogenic?

Haptens are too small to stimulate an immune response by themselves. They become immunogenic only after binding to a carrier protein.

What are immune receptors, and what is their function?

Immune receptors are receptors found on immune cells that recognize and bind pathogens, initiating an immune response.

What are the two major classes of immune receptors?

Preformed receptors of the innate immune system and somatically generated receptors of the adaptive immune system.

How do preformed receptors differ from somatically generated receptors?

Preformed receptors provide a rapid, nonspecific innate immune response, whereas somatically generated receptors are antigen-specific receptors produced by B and T cells during the adaptive immune response.

What are pattern recognition receptors (PRRs)?

PRRs are innate immune receptors that recognize broad molecular patterns (PAMPs) found on microbes but not normally found in the host.

Where are pattern recognition receptors (PRRs) found?

PRRs may be located on immune cell surfaces or exist in soluble forms, such as complement-related receptors.

Which receptors are examples of pattern recognition receptors (PRRs)?

Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs).

What are pathogen-associated molecular patterns (PAMPs)?

PAMPs are conserved molecular structures found on microbes that are recognized by pattern recognition receptors (PRRs).

What are the major somatically generated receptors of adaptive immunity?

B-cell receptors (BCRs) and T-cell receptors (TCRs).

How do B-cell receptors (BCRs) and T-cell receptors (TCRs) differ?

BCRs bind free antigens directly, whereas TCRs recognize peptide antigens only when presented on MHC molecules by antigen-presenting cells.

What is the primary function of innate immunity?

Innate immunity provides the body's immediate, nonspecific defense against pathogens through rapid cellular and soluble defense mechanisms.

What is phagocytosis?

Phagocytosis is the multistep process in which phagocytic cells (macrophages, neutrophils, and dendritic cells) recognize, engulf, and destroy pathogens.

Which immune cells are the primary phagocytes?

Macrophages, neutrophils, and dendritic cells are the primary phagocytic cells.

What are the four stages of phagocytosis?

1. Chemotaxis and migration 2. Recognition of pathogens by surface receptors 3. Engulfment 4. Digestion.

What occurs during chemotaxis and migration?

Chemotaxis is the movement of phagocytes toward chemoattractants released by injured tissue. Phagocytes leave the bloodstream by diapedesis, squeezing between endothelial cells to enter infected tissues.

What is diapedesis?

Diapedesis is the amoeboid movement of phagocytes through endothelial cells to leave the bloodstream and enter surrounding tissues.

How do phagocytes recognize pathogens?

Phagocytes recognize pathogens through pattern recognition receptors (PRRs), complement receptors that bind C3b-coated pathogens, and Fc receptors that bind antibody-coated pathogens.

Which receptors are involved in pathogen recognition during phagocytosis?

Pattern recognition receptors (PRRs), complement receptors, and Fc receptors.

What happens after pathogens bind to phagocyte receptors?

Binding activates the phagocyte, causing it to secrete cytokines and chemokines that recruit and activate other immune cells.

Which cytokines are released by activated phagocytes, and what are their functions?

IL-1 and IL-6 cause fever, TNF-α increases vascular permeability, and IL-8 and IL-12 recruit and activate neutrophils and natural killer cells.

What occurs during the engulfment stage of phagocytosis?

Pseudopods extend around the pathogen, which is internalized by endocytosis into a membrane-bound vesicle called a phagosome.

What is a phagosome?

A phagosome is the intracellular vesicle formed after a pathogen is engulfed by endocytosis.

What occurs during the digestion stage of phagocytosis?

The phagosome fuses with a lysosome to form a phagolysosome, where the pathogen is destroyed.

What is a phagolysosome?

A phagolysosome is the vesicle formed by fusion of a phagosome and a lysosome, where pathogens are digested and killed.

How are pathogens destroyed inside the phagolysosome?

Pathogens are destroyed by lysosomal hydrolytic enzymes, reactive oxygen species (superoxide, hydrogen peroxide, and hydroxyl radicals), nitric oxide (NO), and an acidic pH.

What are the cellular components of adaptive immunity?

The cellular components of adaptive immunity are B cells and T cells.

What is the function of B-cell receptors (BCRs)?

B-cell receptors (BCRs) recognize specific antigens. Each B cell responds to one antigen or a closely related group of antigens. Antigen binding stimulates the B cell to divide, proliferate, and secrete antibodies.

How are B-cell receptors (BCRs) different from T-cell receptors (TCRs)?

BCRs bind free antigens directly, whereas TCRs recognize peptide antigens only when presented on MHC molecules by antigen-presenting cells.

What is the structure of an antibody?

An antibody consists of two identical heavy chains and two identical light chains. The variable regions form two identical antigen-binding (Fab) sites, while the Fc region binds Fc receptors on immune cells.

Why can antibodies recognize so many different antigens?

The variability of the heavy and light chain variable regions and their random pairing create a large number of unique antigen-binding sites capable of recognizing many different epitopes.

What are the five major functions of antibodies?

1. Agglutination 2. Neutralization 3. Opsonization 4. Complement-mediated lysis 5. Antibody-dependent cellular cytotoxicity (ADCC).

What is agglutination?

Agglutination is the cross-linking of pathogens by antibodies, trapping them in aggregates that limit their spread and make them easier for immune cells to destroy.

What is neutralization?

Neutralization occurs when antibodies bind microbes or toxins, preventing them from attaching to host cells and causing infection or damage.

What is opsonization?

Opsonization is the coating of pathogens with antibodies (opsonins), making them easier for macrophages, dendritic cells, and neutrophils to recognize and phagocytose through Fc receptors.

How does complement-mediated lysis destroy pathogens?

Antibody binding activates the classical complement pathway, leading to formation of the membrane attack complex (MAC), C3b-mediated opsonization, and production of the anaphylatoxins C3a, C4a, and C5a.

What is antibody-dependent cellular cytotoxicity (ADCC)?

ADCC occurs when antibodies coat infected or abnormal cells and immune cells bind the Fc region of those antibodies to kill the target cell. NK cells, macrophages, and neutrophils mediate ADCC, while eosinophils kill IgE-coated helminths by degranulation.

What is the difference between MHC class I and MHC class II molecules?

MHC class I is expressed on all nucleated cells, presents intracellular antigens, and is recognized by CD8+ cytotoxic T cells. MHC class II is expressed on dendritic cells, macrophages, and B cells, presents extracellular/phagocytosed antigens, and is recognized by CD4+ helper T cells.

Why are MHC molecules important?

MHC molecules present peptide antigens to T cells, allowing the adaptive immune system to recognize infected or abnormal cells and initiate an immune response.

What is the difference between CD4+ and CD8+ T cells?

CD4+ T cells (helper T cells) make up about two-thirds of mature T cells, recognize antigens presented on MHC II, and coordinate immune responses by releasing cytokines. CD8+ T cells (cytotoxic T cells) make up about one-third of mature T cells, recognize antigens presented on MHC I, and directly kill virus-infected and abnormal cells.

Why can't T-cell receptors (TCRs) bind free antigens?

TCRs recognize peptide antigens only when they are presented on MHC molecules by antigen-presenting cells (APCs). Unlike antibodies and BCRs, TCRs cannot bind free antigens directly.

What is antigen presentation?

Antigen presentation is the process of loading peptide fragments onto MHC molecules so they can be recognized by T cells. Extracellular antigens are presented on MHC II, whereas intracellular antigens are presented on MHC I.

How are extracellular antigens presented on MHC class II?

Phagocytes recognize pathogens through PRRs binding PAMPs, engulf them by phagocytosis, digest them within phagolysosomes, load peptide fragments onto MHC II in the endoplasmic reticulum, and transport the peptide-MHC II complex to the cell surface for recognition by CD4+ T cells.

How are intracellular antigens presented on MHC class I?

Intracellular proteins are tagged with ubiquitin, degraded by the proteasome, transported into the endoplasmic reticulum, loaded onto MHC I, and transported to the cell surface for recognition by CD8+ T cells.

Why do MHC I and MHC II normally not trigger autoimmune responses?

Both MHC I and MHC II present self and non-self peptides, but self-reactive T cells are eliminated during negative selection (thymic selection), preventing immune responses against normal body tissues.

What is the immunologic synapse?

The immunologic synapse is the junction between an antigen-presenting cell (APC) and a naïve T cell where antigen recognition and T-cell activation occur.

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

Signal 1: TCR binds the peptide-MHC complex through the CD3 complex. Signal 2: CD28 on the T cell binds CD80 or CD86 on the antigen-presenting cell. Both signals are required for full T-cell activation.

What happens if a T cell receives only the first activation signal?

Without the second (costimulatory) signal, the T cell is not activated and instead becomes anergic (unresponsive) or undergoes apoptosis.

How do B-cell receptors (BCRs) initiate B-cell activation?

BCRs bind free or cell-bound antigens directly and transmit signals through the associated Igα and Igβ proteins, whose ITAMs initiate intracellular signaling.

How do B cells function as antigen-presenting cells?

After binding an antigen, the B cell internalizes it, degrades it into peptides, loads the peptides onto MHC II, and displays the peptide-MHC II complex on its surface for recognition by CD4+ helper T cells.

How does T-dependent B-cell activation occur?

A CD4+ helper T cell recognizes peptide-MHC II on the B cell and releases IL-4, IL-5, and IL-6. These cytokines stimulate the B cell to proliferate, differentiate, and become an antibody-secreting plasma cell.

What is the structure of an antibody?

An antibody consists of two identical heavy chains and two identical light chains. A variable light-chain domain and variable heavy-chain domain form each antigen-binding site within the Fab region, while the Fc region binds Fc receptors on immune cells.

How are extracellular antigens presented on MHC class II?

Phagocytes recognize pathogens through PRRs binding PAMPs, engulf them by phagocytosis, and digest them within phagolysosomes. MHC II molecules are synthesized in the ER and transported in vesicles that fuse with the phagolysosome, where peptides are loaded. The peptide-MHC II complex is then transported to the surface for recognition by CD4+ T cells.

What happens to some activated T cells after an immune response?

Some activated T cells become memory T cells, which respond more rapidly and strongly if the same antigen is encountered again.