Immunology - Second Edition - Notes
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Early Immunology: Metchnikoff's observations of starfish cells coating foreign objects marked the beginning of immunology as a science.
Detailed observation of cellular defense mechanisms.
Modern Immunology: Rapid development in the last 40 years has made it crucial for research, diagnosis, and therapeutics.
Advanced techniques and applications.
Updated Content: The second edition includes updated material, more figures/tables, presentation modifications, and sections on Aging and Gender.
Comprehensive updates enhance understanding.
Book Structure:
Cellular and molecular components of the Immune System (Sections A–D).
Mechanisms involved in the development of Immunity (Sections E–G).
The Immune System in action (Section H–I).
Diseases and deficiencies of the Immune System (Sections J–L).
The Immune Response to tumors and transplants (Sections M, N).
The influence of Gender and Aging on the Immune Response (Sections O, P).
Additional Resources: Includes Appendices for CD molecules/Cytokines and a Glossary.
Useful reference materials.
A1 The Need
Microbial Existence: Microbes use digestive enzymes to survive on animal/plant products, grow on tissues, or infect cells to replicate within.
Survival strategies of microbes detailed.
Constant Battle: A constant battle happens between invading microbes and the immune system.
Immune system vs. microbes.
A2 External Defenses
Entrance: Microbes enter the body actively (skin penetration) or passively (ingestion/inhalation).
Entry methods of microbes.
Physical Barriers: The skin and epithelial cells provide barriers, with mucosal epithelial cells secreting mucus.
Anatomical barriers against microbes.
Mucociliary Escalator: Respiratory system cilia remove microorganisms during breathing.
Mechanism for clearing microbes.
Secretions: Sweat, tears, saliva, and gastric juices contain enzymes, peptides (defensins), fatty acids and antibodies.
Biochemical defenses.
Commensals: Nonpathogenic bacteria (commensals) prevent invasion by releasing toxic substances and occupying the microenvironment.
Role of commensal bacteria.
A3 Immune Defense
Immune System: Protects against microbes and worms using specialized organs and a mobile force of molecules/cells.
Overview of the immune system.
Innate Immunity: Rapid, acute inflammatory response with some specificity but no memory.
Characteristics of innate immunity.
Adaptive Immunity: Slower to develop, highly specific, with memory.
Characteristics of adaptive immunity.
Lymphocytes: Two major types: B cells (humoral immunity involving soluble molecules) and T cells (cellular immunity).
Key immune cells.
A4 Antigens
Definition: Antigens induce immune responses, including proteins, carbohydrates, lipids, and nucleic acids.
Types of antigens.
Antigenic Determinants: Antibodies or T cells bind to specific parts of the antigen molecule, determinants/epitopes.
Binding sites on antigens.
Antibody Binding: Antibodies bind to conformational determinants, T cell receptors to linear sequences.
Differences in binding preferences.
Immunogens vs. Haptens: Immunogens stimulate immune responses, while haptens react with antibodies but do not initiate immune responses unless attached to a carrier.
Distinctions between immunogens and haptens.
A5 Hemopoiesis
Common Stem Cell: Most immune system cells originate from a hemopoietic stem cell (HSC).
Origin of immune cells.
Location: HSC found in fetal liver/spleen, neonate, and adult bone marrow.
Location of HSC.
Differentiation: Requires contact with stromal cells and cytokines.
Requirements for cell differentiation.
Cytokines: Stromal cells produce cytokines like stem cell factor (SCF), monocyte colony-stimulating factor (M-CSF), and granulocyte-colony stimulating factor (G-CSF).
Role of cytokines in hemopoiesis.
B1 Cells of the Innate Immune System
Phagocytes: Neutrophils (PMNs) and macrophages ingest and kill microbes; opsonization enhances this.
Function of phagocytes.
Natural Killer (NK) Cells: Protect against viruses and some tumors by binding to and killing infected cells, releasing perforins, and inducing apoptosis. Secrete interferon gamma (IFN).
Role of NK cells.
Mast Cells/Basophils: Release pharmacological mediators causing vasodilation, increased vascular permeability, and leukocyte migration.
Involvement in inflammation.
Dendritic Cells: Recognize microbial antigens and present them to T cells activating adaptive responses.
Role in adaptive immunity.
B2 Molecules of the Innate Immune System
Innate Molecules: Molecules reacting with structures common to various microbes include Complement, Acute Phase Proteins and Cytokines (interferons and antimicrobial peptides).
Overview of innate molecules.
Complement System: Activated directly by the microbe (alternative pathway) or by antibodies (classical pathway); causes inflammation, chemotaxis, opsonization, and cell lysis.
Activation and function of complement.
Acute Phase Proteins: Produced in the liver, they maximize activation of complement and opsonization of microbes.
Role of acute phase proteins.
Cytokines: Small signaling molecules between cells including growth factors and chemical mediators.
Function of cytokines.
B3 Recognition of Microbes by the Innate Immune System
Pattern Recognition Receptors (PRR): Interact with and facilitate removal of groups of organisms with similar structures, recognize patterns associated with microbes.
Function of PRRs.
Mannose Receptor: Binds mannosyl/fucosyl patterns, mediates phagocytosis and induces adaptive immune responses.
Role of mannose receptor.
Toll-like Receptors (TLRs): Recognize molecular patterns of pathogens, signal presence of pathogen, trigger expression of co-stimulatory cells.
Function of TLRs.
CD14: Binds lipopolysaccharide (LPS) on Gram-negative bacteria, facilitates destruction and induces cytokine secretion.
Role of CD14.
Scavenger Receptors: Recognize carbohydrates or lipids in cell walls.
Function of scavenger receptors.
B4 Innate Immunity and Inflammation
Inflammation: Deals with physical/chemical insults and microbes: leads to tissue repair.
Overview of inflammation.
Acute Inflammation: Short duration; neutrophils; release of inflammatory mediators.
Characteristics of acute inflammation.
Mediators: Produced by issues, microbes, mast cells, macrophages, include C3a, C4a, C5a, histamine, interleukins to cause vascular changes.
Mediators of inflammation.
Steps: Involve Neutrophil migration, fluid passage, and inhibitors to dampen response and tissue repair mechanisms.
Steps in the inflammatory process.
C1 Lymphocytes
Responsibility: Responsible for specificity and memory in the immune responses.
Role of lymphocytes.
Types: T and B cells with specific antigen receptors, communication is maintained through cell contact and secreted molecules.
Types of lymphocytes and their communication.
T Cells: Mature in the thymus, T cell selection dependent on binding and can be identified using monoclonal antibodies specific for characteristic molecules.
T cell maturation.
B Cells (Lymphocytes): Mature in bone marrow, two kinds of B cells identified producing IgG, IgA and IgE.
B cell maturation.
C2 Lymphoid Organs and Tissues
Primary Lymphoid Organs: Thymus and bone marrow where T and B cells mature.
Primary lymphoid organs location of maturation.
Secondary Lymphoid Tissues: Lymph nodes, spleen, and mucosa-associated lymphoid tissues (MALT).
Secondary lymphoid organs.
Lymph Nodes: Filter lymph, produce immune responses against foreign antigen.
Function of lymph nodes.
Spleen: Filters blood, producing immune responses against bloodborne microbes.
Function of the spleen.
C3 Mucosa-Associated Lymphoid Tissues
Predominance:
50% of lymphoid tissue in the human body, Respiratory, digestive, and genitourinary tracts.
Abundance and location of MALT.
NALT: Nasal-associated lymphoid tissue- tonsils
Example of NALT.
GALT: Gut-associated lymphoid tissue complexes - Peyers Patches.
Example of GALT.
M cells: Epithelial cells transport antigens and pass them to APC.
Function of M cells.
BALT: Bronchial aggregates of lymphocytes.
Example of BALT.
C4 Lymphocyte Traffic And Recirculation
Lymphocytes: migrate through the blood to secondary lymphoid organs to carry out their function.
Lymphocyte migration.
They enter lymph nodes via
high endothelial venules (HEV)Entry to lymph nodes.
Travel in blood to the spleen, then periarteriolar lymphoid sheath (PALS) and then re-enter the blood via red pulp (RP)
Traffic in the spleen.
Unique Traffic in MALT which lymphocytes stimulated at one site, can migrate to other mucosal immune sites to protect against antigens.
Lymphocyte migration in MALT.
C5 Adaptive Immunity at Birth
Newborn Lymphocytes: Have slight higher numbers of lymphocytes over adults that are fully functional.
Lymphocyte counts in newborns.
Maternal Protection:s Maternal IgG from placenta and IgA from colostrum provide passive immunity.- IgG synthesis occurs post birth.
Passive immunity from mother.
Immunity development depend on what their environment dictates ie when children respond to antigens.
Development of immunity in children.
D1 Antibody structure
Antibodies also called "immunoglobulins" that recognize antigens with high specificity and affinity and are glycoproteins.
Antibody definition.
The basic unit is two light (L) chains and 2 heavy (H) chains with 5 physical distinct classes: IgA, IgD, IgE, IgG, IgM.
Structure and classes of antibodies.
H- and L-chains divided into V and C regions, the V region being the location where the antigen- binding happens while the C region dictates the antigen's final destination.
V and C regions.
The greater the binding affinity to the binding site, the more likely the antibody will stay bound and not disassociate.
Binding affinity.
The antigen (which can have multiple binding sites) can dramatically increase the tightness of binding with multiple sites (Avidity).
Avidity in antigen-antibody binding.
D2 Antibody Class
Different antibody classes exist deal with the range of properties for different organisms and the entry sites found on the body (ie skin, genitourinary tract, etc).
Diversity of antibody classes.
IgG immunoglobulins are the bulk of the protection against foreign agents and cross the placenta for infant protection.
Role of IgG.
IgA is used in the first line of response for sites like the gastrointestinal tract and respiratory for microbes.
Function of IgA.
IgM is found in antigen B cells and part of an immune response.
Location and role of IgM.
In IgE stimulation and degranulation happens. These can be anaphylactic and involved in Type I responses.
Function of IgE.
D3 Generation of Diversity
3 different unlinked gene groups encode immunoglobulins that include proteins, carbohydrates, lipids, and nucleic acids that induce an immune response. These 3 groups are: the 𝜅, 𝜆 L-chains and 𝐻 chains.
Gene groups encoding immunoglobulins.
V, D, and J segments translocate along the genome to create a final polypeptide chain.
Translocation of gene segments.
Antibody (Ig) formation is first initiated, by the stem cell (SC), to create a unique sequence which triggers the formation of cell factories and memory cell to generate copies and faster immunity processes when stimulated.
Initiation of antibody formation.
D4 Allotypes and Idiotopes
Genetic variants that are present in some individuals and are absent from others are called
allotropes.Definition of allotropes.
The idiotype is the set of unique antigenic determinants formed by the variable (V) regions of the antibody and the number of different idiotypes in an individual is at least as numerous as the number of specificities.
Definition of idiotype.
D5 Monoclonal Antibodies
Using immortal myeloma tumor cells which fuse with antibody-producing cells, mass produced antibodies called hybridomas are tested and used to target specific cells.
Production of monoclonal antibodies.
Fully human antibodies are made from fusing human B cells with myeloma cells.
Generation of fully human antibodies.
D6 Antigen/Antibody complexes
Formation of a matrix by combining antibody to antigen in order to lead to eventual lysing of active attacking force.
Formation and outcome of antigen-antibody complexes.
Complement activation attracts neutrophils and phagocytes which begin opsonization.
Consequences of complement activation.
D7 Immunoassay
A biochemical test that measures the presence or concentration of a substance in a biological solution is called
_innunoassay.Definition of immunoassay.
This method is used to look for high levels of infections agents and toxins.
Uses antibodies that trigger an output signal.
Applications of immunoassay.
D8 Antibody Functions
The key functions of an antibody are activating and helping the removal of foreign complexes along with acting as a binding surface before other cells remove as well.
Primary functions of antibodies.
E1 The B Cell Receptor Complex, Co-Receptors, and Signaling
Activation of B cells is crucial in order to carry out their function.
Importance of B cell activation.
There are two signals: 1st is binding of the lymphocyte to an antigen and 2nd relies on the aid accessory and co-stimulatory molecules for cell interaction and the signal.
Signals for B cell activation.
E2 B Cell Activation
There are two types of B cell activation, T-dependent and T-independent (help). Most cases of activation with proteins/antigens is reliant on T cell help and interactions via cytokines.
Types of B cell activation.
T-independent B cells mature to create IgG, activate other cells, or for memory purposes.
Outcome of T-independent B cell activation.
E3 The Cellular Basis Of The Antibody Response
All antibodies are coded by B and T cell receptors, so that they can have the necessary responses to the foreign body invasion.
Coding of antibodies.
Clonal selection allows the creation of B and T cells with more high-affinity regions that are stimulated by high binding in order to better defend.
Clonal selection process.
E4 Antibody response in different tissues
After the activation of b cells, depending on the part of the body will dictate which path the helper T cells take ( e.g GALT,BLAT etc .), and what is going to happen with the tissue itself ( B cell population, stimulation).
Antibody response variation in different tissues.
F1 Cellular Immunity and The Role of T Cells In Immune Responses
Cytotoxic immunity is dictated by the recognition of helper and virgin or memory T cells that are activated by specific receptors on T and B cells.
Cytotoxic immunity mechanism.
This happens mostly with specific protein (Ag).
Specificity of cytotoxic immunity.
F2 T cell recognition of antigen
the antigen from the cell then binds to 1 of the T cells to create either memory T, a clone, or be killed by a T cell that identifies with specificity if they are in proximity.
Outcomes of T cell recognition.
there are T helpers 1 (for helper functions) and T helpers 2 as a result (T-cell mediated).
Types of T helper cells.
F3 Shaping the T cell repertoire
The key roles of alpha cells and beta cell are to kill and signal a positive confirmation of a target that needs to be eliminated.
Both need receptors for specificity.
MHC are used for class types I and II.Role of alpha and beta T cells, MHC class types.
F4 T cell activation
After an insult on T and B cells from T1 bacteria the following actions take place: cells need help getting to various areas, cytokines can be used to suppress, stimulate, or regulate killing . After initial recognition by what is captured, molecules do more and initiate expression on what cells are targeted.
Events following T cell activation.
F5 Clonal Expansion And Development Of Effector Function
After activation has occurred in specific groups (types 1,2) , this activation is responsible for the type of cytokines induced and the growth of the Th ( T helper cells). This is a result of CD8 and CD4.
Cytokine induction and T helper cell growth.
F6 Cell-mediated Immunity in Context
Helper Th or H cells will need a class II MHC that is activated by the cells themselves. The CD8 will require that they see if there are MHC to allow or disallow their ability to recognize targets, but they do not express it themselves
This activation is often for immune deficiencies.MHC requirements for T helper and CD8 cells.
G1 Regulation Of The Immune Response Overview
The role of the immunity is a series of actions, as the process begins and is identified actions must be done correctly and in a safe manner to the correct stimulus from an outside or inside invader.
Overview of immune response regulation.
There are a series of