Chapter 45: The Immune System

immunological memory

The immune system's ability to remember a prior exposure to a foreign antigen; a portion of activated lymphocytes differentiate into long-lived memory B cells and memory T cells which remain inactive until same antigen appears; allows for faster response time

Can non-infectious substances trigger immune responses?

Yes, such as proteins, lipids, polysaccharides, or artificially synthesized molecules.

What is immunodeficiency?

Results from failure or absence of elements of the immune system.

What is the primary line of defense against pathogens?

Anatomical barriers like skin and mucus membranes.

What is Immunology?

study of the immune system, immune response, molecular mechanisms that help defend against microbial attacks or other foreign antigens.

What is the definition of immune response?

Collective and coordinated response to the introduction of foreign substances.

What is the immune system?

A complex network of organs, cells, and proteins that defends the body against infection and disease

Define antigen.

An antigen is any foreign molecule that triggers an adaptive immune response.

Define epitope.

The small specific part of the antigen that the antibody molecules bind to is called an antigenic determinant or an epitope.

Define paratope.

The corresponding site on the antibody that binds to an epitope is called a paratope.

What are the three ways antibody-bound antigens are processed to protect the host from infection?

a. Neutralization. b. Opsonization. c. Complement activation.

Describe the structure of antibody and T-Cell receptor.

Anitbody: Y-shaped, consists of four polypeptide chains: two identical heavy chains and two identical light chains, Each polypeptide chain has two main regions: a variable (V) region and a constant (C) region

T-cell receptor: Similar to antibody, cannot process antigens

What are the five classes (Isotypes) of antibodies?

IgM, IgG, IgD, IgA, and IgE.

How is IgM secreted?

IgM is secreted as a pentamer of immunoglobulin monomers.

What is the role of IgD?

IgD occurs with IgM as a receptor on the surfaces of B cells, its function is to enhance mucosal homeostasis and immune surveillance but also kinda unknown

What is the function of IgE related to mast cells and basophils?

IgE secreted by plasma cells of the skin and linings of the gastrointestinal and respiratory tract binds to basophils and mast cells, triggering release of histamine.

How is IgA secreted?

IgA is secreted as a dimer.

What is IgG?

IgG(γ) is the most abundant antibody circulating in the blood and lymphatic system – produced in large amounts when the body is exposed a second time to the same antigen.

What stimuli produce IgE antibodies?

IgE antibodies are produced in response to parasites and, in genetically susceptible individuals, to otherwise harmless environmental antigens (allergens), such as pollen, foods, and drugs.

What are the steps of antibody-mediated immunity?

1. Antigen Encounter and Engulfment by an Antigen-Presenting Cell

2. Antigen Degradation and Processing Within the phagocytic cell

3. Antigen Presentation on APC Surface

4. Interaction of APC with a Helper T cell

5. Activation and Proliferation of the Helper T cell

6. Antigen Encounter and Processing by a B cell

7. Antigen Presentation on B cell Surface

8. Interaction of B cell with a Helper T cell

9. Activation and Proliferation of the B cell

10. Differentiation into Plasma Cells and Memory B cells

11. Antibody Secretion by Plasma Cells

12. Antigen Clearance by Antibodies

What is Passive immunity?

Acquisition of antibodies from another person – including antibodies passed from mother to child through the placenta or in breast milk.

How are antibodies used in research?

a. Immunohistochemistry techniques – ELISA, Immunoblotting. b. Monoclonal antibody production – Hybridoma technology.

What can cause immune system malfunctioning?

a. Allergies and hypersensitivity. b. Autoimmune disorders.

What are the steps of cell-mediated immunity?

A. Presentation of antigens on cell surface. Viral proteins are degraded into fragments that act as antigens. The antigens are displayed on the cell surface bound to class I MHC proteins, making.

What happens to infected cells in cell-mediated immunity?

apoptosis and die.

What is the difference between immunoglobulins and antibodies?

Immunoglobulins are cell surface bound, whereas antibodies are secreted by plasma B cells.

What are immunoglobulin domain-like molecules?

A large class of molecules including antibodies, sharing similar protein folding domains.

What activates a naive B cell?

Binding to a foreign antigen.

What is the function of a plasma B cell?

Secretes antibodies.

Describe the basic structure of an antibody molecule.

Two identical heavy chains and two identical light chains.

What are the main regions of heavy and light chains?

Variable region and constant region.

What is the function of the variable region?

Contains the antigen binding site, contributes to high specificity.

What is the function of the constant region?

In membrane-bound immunoglobulins (BCRs), it contains the transmembrane domain that anchors to the plasma membrane. Determines antibody isotype.

Are antibodies soluble or membrane-bound?

Antibodies are soluble, lacking the membrane anchoring domain.

What are epitopes?

Small, specific parts of antigens that antibodies bind to.

What kind of chemical structures can epitopes have?

Diverse, including carbohydrate residues, amino acid residues, toxin molecules.

How do T-cell receptors recognize antigens?

They bind to peptides that are processed by antigen-presenting cells (APCs) and presented in the context of MHC molecules.

What are professional antigen presenting cells (APCs)?

Cells that process and present antigens to T cells, including dendritic cells, macrophages, and B cells.

What are MHC molecules?

Major Histocompatibility Complex molecules, self-identifying proteins on cell surfaces. T cells recognize antigens only in the presence of MHC.

What are the five major isotypes of immunoglobulin molecules?

IgG, IgM, IgD, IgA, IgE.

What determines the isotype of an immunoglobulin?

Differences in the heavy chain constant region.

What are the Greek letters for the heavy chains of each isotype?

Gamma (γ) for IgG, Mu (μ) for IgM, Delta (δ) for IgD, Alpha (α) for IgA, Epsilon (ε) for IgE.

What are the light chain isotypes (classes)?

Kappa (κ) and Lambda (λ) chains.

Is there a functional difference between Kappa and Lambda light chains?

No functional difference found.

In humans, what is the proportion of antibody molecules carrying Kappa vs Lambda chains?

Two-thirds carry Kappa, one-third carry Lambda.

What structural differences exist between antibody isotypes?

Differences in heavy chain C region length, disulfide bond locations, hinge regions, and glycosylation.

Which isotypes have a hinge region?

IgG, IgA, IgD.

Which isotypes lack a hinge region?

IgM, IgE.

How do secreted IgD, IgE, and IgG exist?

Always as monomers.

How does secreted IgA exist?

Forms monomers and dimers.

How does secreted IgM exist?

Forms only pentamers.

What joins the antibody molecules in IgA dimers and IgM pentamers?

A joining chain or J chain.

What antibody isotypes are antigen receptors on circulating B cells?

IgM and IgD.

What is the first antibody class secreted in any immune response?

IgM.

What are the main antibodies found in blood, lymph, and connective tissues?

IgM, IgA, and IgG.

Which immunoglobulin isotypes provide bulk of specific adaptive immunity against bacteria and viruses in ECF?

IgM and IgG.

Where is secreted IgA found?

Lining GI, respiratory, GU tracts, in tears, saliva, breast milk.

What is the function of IgA in saliva?

Keeps the mouth free of pathogens.

What kind of immunity does IgA in mother's milk provide?

Passive immunity to babies.

What is IgE important for?

Responding to parasites and mediating allergic responses.

How does IgE mediate allergic responses?

Binds receptors on mast cells and basophils, sensitizing them to allergens and triggering histamine release.

What is the function of IgD?

Occurs with IgM on B cell surface, may be important for B cell activation; exact role is still unclear.

What is somatic gene recombination (or rearrangement)?

A process where DNA segments encoding antibody (and TCR) regions are recombined in different ways to generate diversity. Occurs in somatic cells (lymphocytes) during maturation.

What is VDJ recombination?

The basic process of somatic recombination that generates antibody and T cell receptor diversity. Involves V, D, J gene segments for heavy chains and V, J segments for light chains.

Who discovered the process of VDJ recombination?

Susumu Tonegawa, awarded the 1987 Nobel Prize in Physiology or Medicine.

What enzyme catalyzes VDJ recombination?

VDJ recombinase.

VDJ recombination process (Heavy chain)?

First, a D segment joins a J segment (DJ recombination). Second, a V segment joins the combined DJ segment (V-DJ recombination).

VDJ recombination process (Light chain)?

A V segment joins a J segment (VJ recombination); no D segment is involved.

Number of combinations for Kappa light chain VJ recombination?

Approx. 40 Vκ segments and 5 Jκ segments recombine in ~200 ways.

Number of combinations for Lambda light chain VJ recombination?

Approx. 30 Vλ segments and 4 Jλ segments recombine in ~120 ways.

Number of combinations for Heavy chain VDJ recombination?

Approx. 65 VH, 27 D, and 6 JH segments can produce 10,530 combinations.

Light Chain Gene Rearrangement and Expression Process?

Random V and J segments recombine. The VJ segment recombines with the C segment. DNA is transcribed to pre-mRNA. RNA processing (splicing, etc.) produces mature mRNA. mRNA is translated to the light chain polypeptide.

Antigen Presentation Process?

APC engulfs pathogen/antigen. Antigen is degraded into peptides. Peptides bind to MHC molecule (Class I or II). Peptide-MHC complex moves to cell surface and is displayed.

What is MHC Class I?

MHC molecules that present peptides from intracellular pathogens to cytotoxic T cells (CD8+). Found on most nucleated cells.

What is MHC Class II?

MHC molecules that present peptides from extracellular pathogens to helper T cells (CD4+). Found on professional APCs.

What are CD4+ T cells?

Helper T cells, recognize antigens presented by MHC Class II, activate macrophages and B cells.

What are CD8+ T cells?

Cytotoxic T cells, recognize antigens presented by MHC Class I, kill infected cells.

What happens during a primary immune response?

First exposure to antigen. Naive lymphocytes activated. Clonal expansion. Differentiation into plasma cells and memory cells. Antibodies appear in blood in 3-14 days. Response ends by week 4.

What happens during a secondary immune response?

Second exposure to the same antigen. Rapid activation of memory cells. Faster and stronger response than primary. Less antigen needed. Many more antibodies produced.

What is Immunological Memory?

The adaptive immune system remembers prior exposure to an antigen, allowing for a faster and stronger response upon re-exposure.

What is Active Immunity?

Immunity acquired by exposing an individual to antigens, generating an adaptive immune response and immunological memory.

What is Passive Immunity?

Acquisition of antibodies from another person or animal (e.g., maternal antibodies, antitoxins). It is short-lived and produces no memory.

What is the complement system?

A group of blood proteins that aid the innate immune response, can be activated by antibodies, form membrane attack complexes (MAC) to lyse cells.

Complement Activation Process leading to lysis?

Complement proteins activated (e.g., by antibody binding). Subunits assemble on pathogen surface. Form pores (MAC) in membrane. Cell lysis and death.

How do antibodies neutralize pathogens?

By binding to them, inhibiting their toxic effects or infectivity.

How do antibodies opsonize pathogens?

By coating pathogens, making them easier for phagocytic cells to ingest and kill.

What are the two types of adaptive immune responses?

Humoral immunity and Cell-mediated immunity.

What is Humoral Immunity mediated by?

B lymphocytes secreting antibodies, primarily eliminates extracellular microbes.

What is Cell-Mediated Immunity mediated by?

Different types of T lymphocytes (Helper and Cytotoxic), recruits phagocytes, kills infected cells, primarily eliminates intracellular pathogens.

What is Clonal Selection?

The process where a specific lymphocyte (B or T cell) with a receptor that recognizes a foreign antigen is selected from a diverse pool and proliferates.

Clonal Expansion Process?

Selected lymphocytes undergo multiple cycles of cell division to produce a clone of cells with the same specificity.

Simplified Antibody-Mediated Immune Response Process?

Naive B cell recognizes antigen via surface Ig (BCR). B cell processes antigen and presents on MHC II. Helper T cell recognizes antigen on B cell. Helper T cell activates B cell. Activated B cell proliferates (clonal expansion). B cells differentiate into plasma cells and memory cells. Plasma cells secrete antibodies. Antibodies clear antigen by neutralization, opsonization, or complement activation.

Simplified Cell-Mediated Immune Response Process?

Infected host cell degrades intracellular pathogen into antigens. Antigen fragments bind to MHC Class I. Peptide-MHC I complex presented on cell surface. Cytotoxic T cell recognizes complex. Cytotoxic T cell activated and kills infected cell (e.g., by inducing apoptosis).

What is the defining feature of adaptive immunity created by V(D)J recombination?

Antibody and TCR diversity.

Where does V(D)J recombination occur?

In developing lymphocytes during T- and B-cell maturation in primary lymphoid organs (bone marrow and thymus).

What are lymphocytes?

Cells involved in adaptive immunity (B cells, T cells) and some innate immunity (NK cells), derived from lymphoid lineage stem cells.

What are the primary lymphoid organs?

Bone marrow and thymus.

What are the secondary lymphoid organs?

Lymph nodes, spleen, mucosal-associated lymphoid tissue (MALT).

What kind of immunity is provided by IgG in mammals?

Provides bulk of specific adaptive immunity against bacteria and viruses in ECF.

What kind of immunity is provided by IgA in secretions?

Protects mucosal surfaces by binding to antigens and blocking attachment of pathogens.