Biochemistry & Biotechnology: Online Coaching in Delhi

Immunlogy Course


Immunology is a branch of biology and medicine that covers the study of immune systems (Defence system) in all organisms. Immunology is molecular & cellular in nature. It contextualizes the physiological functioning of the immune system in states of both health and diseases; malfunctions of the immune system in immunological disorders (such as auto-immune diseases, hypersensitivities, immune deficiency, and transplant rejection; and the physical, chemical, and physiological characteristics of the components of the immune system in vitro, in situ, and in vivo.


Immunology has applications in numerous disciplines of medicine, particularly in the fields of organ transplantation, oncology, rheumatology, virology, bacteriology, parasitology, psychiatry, and dermatology.


The immune system consists of functional thymus, bone marrow, and chief lymphatic tissues such as spleen, tonsils, lymph vessels, lymph nodes, adenoids, and liver. These components are cellular in nature, and embedded or circulating in various tissues located throughout the body.

Topics /Lesson Coverage – Immunology


Chapter 1

Overview of the Immune System                                   

A Historical Perspective of Immunology                                                

    Early vaccination studies led the way to immunology                         

    Vaccination is an ongoing, worldwide enterprise                                        

    Immunology is about more than just vaccines and

    Infectious disease                                                                          

    Immunity involves both humoral and cellular Components                  

    How are foreign substances recognized by the Immune system?        

Important Concepts for Understanding the Mammalian

Immune Response                                                                        

    Pathogens come in many forms and must firstbreach natural


    The Immune response quickly becomes tailored to suit

    the assault                                                                                    

    Pathogen recognition molecules can be conceded in the

    germline or randomly generated                                                      

    Tolerance ensures that the immune system avoids destroying

    the host                                                                                        


    The Immune response is composed of two interconnected

    arms: innate immunity and adaptive immunity                                  

    Adaptive immune responses typically generate memory                     

The Good, Bad, and Ugly of the immune system                           

    Inappropriate or dysfunctional immune responses can result in a

    range of disorders                                                                         

    The immune response renders tissue transplantation challenging                

    Cancer presents a unique challenge to the immune response             


Chapter 2

Cells, Organs and Micro-environments of the Immune


Cells of the Immune System                                                               

    Hematopoietic stem cells have the ability to differentiate into

    many types of blood cells                                                                       

    Hematopoiesis is the process by which hematopoietic stem cell

    Develop into mature blood cells                                                               

    Cells of the myeloid lineage are the first responder to infection            

    Cells of the lymphoid lineage regulate the adaptive immune response  

Primary Lymphoid Organs-

Where Immune Cells Develop                                                        

    The bone marrow provides niches for hematopoietic stem cell to

    self-renew and differentiate into myeloid cells and B lymphocytes               

    The thymus is a primary lymphoid organ where T cell mature             

Secondary Lymphoid Organs-

Where the Immune Response is initiated                                      

    Secondary lymphoid organs are distributed through-out the body

    and share some anatomical features                                                        

    Lymphoid organs are connected to each other and to infected tissue

    by two different circulatory systems blood and lymphatic                   

    The lymph node is a highly specialized secondary lymphoid organ              

    The Spleen organizes the immune response against blood-bone


    MALT organizes the response to antigen that enters mucosal tissues   

    The skin is an innate immune barrier and also includes lymphoid


    Tertiary lymphoid tissues also organize and maintain an immune


Chapter 3

Receptors and Signaling: B and T-Cell Receptors                          

Receptor- Ligand Interactions                                                               

    Receptor-ligand binding occurs via multiple noncovalent bonds           

    How do we quantitate the strength of receptor-ligand interactions?     

    Interactions between receptors and ligand can be multivalent             

    Receptor and ligand expression can vary during the course of an

    immune response                                                                          

    Local concentrations of cytokines and other ligands may be

    extremely high                                                                              

Common strategies Used in many Signaling Pathways                 

    Ligand binding can induce conformational changes in and/or

    clustering of the receptor                                                                        

    Some receptors require receptor-associated molecules to

    signal cell activation                                                                       

    Ligand-induced receptor clustering can alter receptor location             

    Tyrosine phosphorylation is an early step in many signaling pathways 

    Adapter proteins gather members of signaling pathways                    

    Phosphorylation on serine and threonine residues is also a common

    step is signaling pathways                                                              

    Phosphorylation of membrane phospholipids recruits PH domain-

    containing proteins to the cell membrane                                         

    Signal-induced PIP2 breakdown by PLC causes an increase in

    cytoplasmic calcium ion concentration                                              

    Ubiquitination may inhibit or enhance signal transduction                   

Frequently Encountered Signaling Pathways                                 

    The PLC pathway induces calcium release and PKC activation             

    The Ras/Map kinase cascade activates transcription through AP-1               

        PKC activates the NF-kB transcription factor                                  

The Structure of Antibodies                                                           

    Antibodies are made up to multiple immunoglobulin domains              

    Antibodies share a common structure of two light chains and

    two heavy chains                                                                           

    There are two major classes of antibody light chains                          

    There are five major classes of antibody heave chains                               

    Antibodies and antibody fragments can serve as antigens                  

    Each of the domains of the antibody heavy and light chains

    mediate specific functions                                                               

    X-ray crystallography has been used to define the structural basis

    of antigen-antibody binding                                                            

Signal Transduction in B Cells                                                                

    Antigen binding results in docking of adapter molecules and enzymes

    into the BCR-lga/lgB membrane complex                                          

    B Cells use many of the downstream signaling pathways described


    B Cells also receive signals through co-receptor                                 

T-Cells Receptor and Signaling                                                      

    The T-cell receptor is a heterodimer with variable and constant regions       

    The T-cell signal transduction complex includes CD3                          

    The T-cell co-receptors CD4 and CD8 also bind the MHC                    


    Lck is the first tyrosine kinase activated in T cell signaling                  

    T cells use downstream signaling strategies similar to those of B cells  

Chapter 4

Receptors and Signaling: Cytokines and Chemokines                   

General properties of Cytokines and Chemokines                                   

Cytokines mediate the activation, proliferation and differentiation

of target cells                                                                                    

Cytokines have numerous biological functions                                       

Cytokines can elicit and support the activation of specific

T-cell subpopulations                                                                 

Cell activation may alter the expression of receptors and adhesion


Cytokines are concentrated between secreting and target cells               

Signaling through multiple receptors can fine tune a cellular response

Six Families of Cytokines and Associated Receptor Molecules              

Cytokines of the IL-1 family promote proinflammatory signals         

Hematopoietic (Class I) family cytokines share three-dimensional

structural motifs, but induce a diversity of functions in target cells          

The Interferon (Class II) cytokine family was the first to be discovered    

Members of the TNF cytokine family can signal development, activation,

or death                                                                                           

    The IL-17 family is a recently discovered, proinflammatory cytokine


    Chemokines direct the migration of leukocytes through the body        

Cytokine Antagonists                                                                     

    The IL-1 receptor antagonist blocks the IL-1 cytokine receptor            

    Cytokine antagonists can be derived from cleavage of the cytokine


    Some viruses have developed strategies to exploit cytokine activity     

Cytokine-Related Disease                                                              

    Septic shock is relatively common and potentially lethal                      

    Bacterial toxic shock is caused by superantigen induction of

    T-cell cytokine secretion                                                                 

    Cytokine activity is implicated in lymphoid and myeloid cancers           

    Cytokine storms may have caused many deaths in the 1918

    Spanish influenza                                                                          

Cytokine-Based Therapies                                                              

Chapter 5

Innate Immunity                                                                            

Anatomical Barriers to Infection                                                           

    Epithelial Barriers prevent pathogen entry into the body’s interior                

    Antimicrobial proteins and peptides kills would be invaders                 


    Microbes are recognized by receptors on phagocytic cells                   

    Phagocytized microbes are killed by multiple mechanisms                  

    Phagocytosis contributes to cell turnover and the clearance of

    dead cells                                                                                     

Induced Cellular Innate Responses                                               

    Cellular pattern recognition receptors activate responses to

    microbes and cell damage                                                                      

    Toll-like receptors recognize many types of Pathogen molecules          

    C-Type lectin receptors bind carbohydrates on the surfaces of

    extracellular pathogens                                                                  

    Retinoic acid inducible gene-I-like receptors bind viral RNA in the

    cytosol of Infected cells                                                                  

    Nod-like receptors are activated by a variety of PAMPs, DAMPS,

    and other harmful substances                                                         

    Expression of innate immunity proteins is induced by PRR signaling    

Inflammatory Responses                                                               

    Inflammation results from innate responses triggered by infection,

    tissue damage or harmful substances                                              

    Proteins of the acute phase response contribute to innate immunity

    and inflammation                                                                           

Natural Killer Cells                                                                         

Regulation and Evasion of Innate and Inflammatory Responses  

    Innate and inflammatory responses can be harmful                           

    Innate and inflammatory responses are regulated both positively

    and negatively                                                                              

    Pathogens have evolved mechanisms to evade innate and

    inflammatory responses                                                                 

Interactions Between the Innate and Adaptive Immune Systems 

    The innate immune system activates and regulates adaptive

    immune responses                                                                        

    Adjuvants activate innate immune responses to increase the

    effectiveness of immunizations                                                                

    Some pathogen clearance mechanisms are common to both innate

    and adoptive immune responses                                                     

Ubiquity of Innate Immunity                                                         

    Plants rely and vertebrate immune responses to combat infections              

    Invertebrate and vertebrate innate immune responses show both

    similarities and differences                                                              


Chapter 6

The Complement System                                                                        Major Pathways of Complement Activation                                             

    The classical pathway is initiated by antibody binding                                

    The lectin pathway is initiated when soluble proteins recognize

    microbial antigens                                                                          

    The alternative pathway is initiated in three district ways                    

    The three complement pathways converge at the formation of the

    C5 convertase                                                                               

    C5 initiates the generation of the MAC                                              

The Diverse Functions of Complement                                           

    Complement receptors connect compliment-tagged pathogens

    to effector cells                                                                              

    Complement enhances host defense against infection                                

    Complement mediates the interface between innate and

    adaptive immunities                                                               

    Complement aids in the contraction phase of the immune


    Complement mediates CNS synapse elimination                        

The Regulation of Complement Activity                                

    Complement activity is passively regulated by protein stability

    and cell surface composition                                                   

    The C1 inhibitor, C1NH, promotes dissociation of C1 components

    Decay Accelerating Factors promote decay of C3 Convertases     

    Factor I degrade C3b and C4b                                                 

    Protectin inhibits the MAC attack                                              

    Carboxypeptidases can inactivate the anaphylatoxins C3a & C5a 

Complement Deficiencies                                                       

Microbial Complement Evasion Strategies                             

    Some pathogens interfere with the first step of immunoglobulin

    mediated complement activation                                              

    Microbial proteins bind and inactivate complement proteins                

    Microbial proteases destroy complement proteins                      

    Some microbes mimic or bind complement regulatory proteins    

The Evolutionary Origins of the Complement System           

Chapter 7

The Organization and Expression of Lymphocyte

Receptor  Genes                                                                                      The Puzzle of immunoglobulin Gene Structure                                              Investigators proposed two early theoretical models of antibody


    Breakthrough experiments revealed that multiple gene segments

    encode the light chain                                                                    

Multigene Organization of Ig Genes                                              

    Kappa light-chain genes include V,J, and C segments                                

    Lambda light-chain genes pair each J segment with a particular

    C segment                                                                                    

    Heavy-chain gene organization includes V, D, J and C, segments        

The Mechanism of V(D) J Recombination

    Recombination is directed by signal sequences

    Gene segments are joined by the RAG ½ recombinase combination

V(D)J recombination results in a functional lg variable regiongene

V(D)J recombination can occur between segments transcribed in either the same or opposite directions

Five mechanisms generate antibody diversity in naïve B cells.

T-Cell Receptor Genes and Expression

Understanding the protein structure of the TCR was critical to the process of discovering the genes

The B-chain in gene was discovered simultaneously in two different laboratories

A search for the a-chain gene led to the y-chain gene instead

TCR genes undergo a process of rearrangement very similar to that of lg genes

TCR expression is controlled by allelic exclusion

TCR gene expression is tightly regulated

Chapter 8

The Major Histocompatibility Complex and Antigen Presentation        

The Structure and Function of MHC Molecules

Class l molecules have a glycoprotein heavy chain and a small protein light chain

Class ll molecules have two non-identical glycoprotein chains

Class l and ll molecules exhibit polymorphism in the region that binds to peptides

General Organization and Inheritance of the MHC

The MHC locus encodes three major classes of molecules

The exon/Intron arrangement of class l and ll genes reflects their domain structure

Allelic forms of MHC genes are inherited in linked groups called haplotypes

MHC molecules are codominantly expressed

Class l and class ll molecules exhibit diversity at both the individual and species levels

MHC polymorphism has functional relevance

The Role of the MHC and Expression Patterns

MHC molecules present both intracellular and extracellular antigens

MHC class l expression is found throughout the body

Expression of MHC class ll molecules is primarily restricted to antigen-presenting cells

MHC expression can change with changing conditions

T cells are restricted to recognizing peptides presented in the context of self-MHC alleles

Evidence suggests different antigen processing and presentation pathways.

The Endogenous Pathway of Antigen Processing and Presentation

Peptides are generated by protease complexes called proteasomes

Peptides are transported from the cytosol to the RER

Chaperones aid peptide assembly with MHC class l molecules.

The exogenous Pathway of Antigen Processing and Presentation

Peptides are generated from internalized molecules in endocytic vesicles

The invariant chain guides transport of class ll MHC molecules to endocytic vesicles

Peptides assemble with class ll MHC molecules by displacing CLIP

Cross-Presentation of Exogenous Antigens

Dendritic cells appear to be the primary cross-presentation cell type

Mechanisms and Functions of Cross-Presentation

Presentation of Nonpeptide Antigens


Chapter 9

T-Cell Development                                                                                

Early Thymocyte Development

Thymocytes progress through four double-negative stages

Thymocytes can express either TCRαβ or TCRyδ receptors

DN thymocytes undergo β-selection, which results in proliferation and differentiation

Positive and Negative Selection

Thymocytes “learn” MHC restriction in the thymus

T Cells undergo positive and negative selection

Positive selection ensures MHC restriction

Negative selection (central tolerance) ensures self-tolerance

The selection paradox: Why don’t we delete all cells we positively select?

An alternative model can explain the thymic selection paradox.

Do positive and negative selection occur at the same stage of development, or in sequence?

Lineage Commitment

Several models have been proposed to explain lineage commitment

Double-positive thymocytes may commit to other types of lymphocytes

Exit from the Thymus and Final Maturation

Other Mechanisms That Maintain Self-Tolerance

TREG cells negatively regulate Immune responses

Peripheral mechanisms of tolerance also protect against auto reactive thymocytes


Apoptosis allows cells to die without triggering an inflammatory response

Different stimuli initiate apoptosis, but all activate caspases

Apoptosis of peripheral T cells is mediated by the extrinsic (Fas) pathway

TCR-mediated negative selection in the thymus induces the intrinsic (mitochondria-mediated) apoptotic pathway

Bcl-2 family members can inhibit or induce apoptosis

Chapter 10

B-Cell Development                                                                                

The Site of Hematopoiesis

The site of B-cell generation changes during gestation

Hematopoiesis in the fetal liver differs from that in the adult bone marrow

B-Cell Development in the Bone Marrow

The stages of hematopoiesis are defined by cell-surface markers, transcription-factor expression, and immunoglobulin gene rearrangements

The earliest steps in lymphocyte differentiation culminate in the generation of a common lymphoid progenitor

The later steps of B-cell development result in commitment to the B-cell phenotype

Immature B cells in the bone marrow are exquisitely sensitive to tolerance induction

Many, but not all, self-reactive B cells are deleted within the bone marrow

B cells exported from the bone marrow are still functionally immature

Mature, primary B-2B cells migrate to the lymphoid follicles

The Development of B-1 and Marginal-Zone B Cells

B-1 Cells are derived from a separate developmental lineage

Marginal-zone cells share phenotypic and functional characteristics with B-1B cells and arise at the T2 stage

Comparison of B-and T-Cell Development

Chapter 11

T-Cell Activation, Differentiation, and Memory

T-Cell Activation and the Two-Signal Hypothesis

Costimulatory signals are required for optional T-cell activation and proliferation

Clonal anergy results if a costimulatory signal is absent

Cytokines provide Signal 3

Antigen-presenting cells have characteristic costimulatory properties

Superantigens are special class of T-cell activators

T-Cell Differentiation

Helper T cells can be divided into district subsets

The differentiation of T helper cell subsets is regulated by polarizing cytokines

Effector T helper cell subsets are distinguished by three properties

Helper T cells may not be irrevocably committed to a lineage

Helper T-Cell subsets play critical roles in immune health and disease

T-Cell Memory

Naïve, effector, and memory T cells display broad differences in surface protein expression

TCM and TEM  are distinguished by their locale and commitment to effector function

How and when do memory cells arise?
What signals induce memory cell commitment?

Do memory cells reflect the heterogeneity of effector cells generated during a primary response?

Are there differences between CD4* and CD8* memory T cells?

How are memory cells maintained over many years?

Chapter 12

B-Cell Activation, Differentiation, and Memory Generation

T-Dependent B-Cell Responses

T-dependent antigens require T-cell help to generate an antibody response

Antigen recognition by mature B cells provides a survival signal

B cells encounter antigen in the lymph nodes and spleen

B-cell recognition of cell-bound antigen results in membrane spreading

What causes the clustering of the B-cell receptors upon antigen binding?

Antigen receptor clustering induces internalization and antigen presentation by the B cell

Activated B cells migrate to find antigen-specific T cells

Activated B cells move either into the extra-follicular space or into the follicles to form germinal centers

Plasma cells form with in the primary focus

Other activated B cells move into the follicles and initiate a germinal center response

Somatic hypermutation and affinity selection occur within the germinal center

Class switch recombination occurs within the germinal center after antigen contact

Most newly generated B cells are lost at the end of the primary immune response

Some germinal center cells complete their maturation as plasma cells

B-cell memory provides a rapid and strong response to secondary infection

T-Independent B-Cell Responses

T-Independent antigen stimulate antibody production without the need for T-cells help

Two novel subclasses of B cells mediate the response to T-Independent antigens

Negative Regulation of B Cells

Negative signaling through CD22 shuts down unnecessary BCR signaling

Negative signaling through the FcyRllb receptor inhibits B-cell activation

B-10B cells act as negative regulator by secreting lL-10

Chapter 13

Effector Responses: Cell-and Antibody-Mediated Immunity

Antibody-Mediated Effector Functions

Antibodies mediate the clearance and destruction of pathogen in a variety of ways

Antibody isotypes mediate different effector functions

Fc receptors mediate many effector functions of antibodies

Cell-Mediated Effector Responses

Cytotoxic T lymphocytes recognize and kill infected or tumor cells via T-cell receptor activation

Natural killer cells recognize and kill infected cells and tumor cells by their absence of MHC class l

NKT cells bridge the innate and adaptive immune systems

Experimental Assessment of Cell-Medicated Cytotoxicity

Co-culturing T cells with foreign cells stimulates the mixed-lymphocyte reaction

CTL activity can be demonstrated by cell-mediated lympholysis

The graft-versus-host reaction is an in vivo indication of cell-mediated cytotoxicity

Chapter 14

The Immune Response in Space and Time

Immune Cell Behavior before Antigen Is Introduced

Naïve lymphocytes Circulate between secondary and tertiary lymphoid tissues

Naïve lymphocytes sample stromal cells in the lymph nodes

Naïve lymphocytes browse for antigen along reticula networks in the lymph node

Immune Cell Behavior during the Innate Immune Response

Antigen-presenting cells travel to lymph nodes and present processed antigen to T cells

Unprocessed antigen also gains access to lymph-node B cells

Immune Cell Behavior during Adaptive Immune Response

Naïve C4+T Cells arrest their movements after engaging antigens

B cells seek help from CD4+ T cells at the border between the follicle and paracortex of the Lymph Node

Dynamic imaging approaches have been used to address a controversy about B-cells behavior in germinal centers

CDB+ T cells are activated in the lymph node via a multicellular interaction

Activated lymphocytes exit the lymph node and recirculate

A summary of our current understanding

The immune response contracts with 10 to 14 days

Immune Cell Behavior in Peripheral Tissues

Chemokine receptors and Integrins regulate homing of effector lymphocytes to peripheral tissues

Effector lymphocytes respond to antigen in multiple tissues 

Chapter 15

Allergy, Hypersensitivities, and Chronic Inflammation

Allergy: A Type l Hypersensitivity Reaction

lgE antibody are responsible for type l hypersensitivity

Many allergens can elicit a type l response

IgE antibodies act by cross-lining FCE receptors on the surfaces of innate immune cells

IgE receptor signaling is tightly regulated

Innate immune cells produce molecules responsible for type I hypersensitivity symptoms

Type l hypersensitivities are characterized by both early and late responses

There are several categories of type l hypersensitivity reactions

There is genetic basis for type l hypersensitivity

Diagnostic tests and treatments are available for type I hypersensitivity reactions

The hygiene hypothesis has been advanced to explain increases in allergy incidence

Antibody-Mediated (Type ll) Hypersensitivity Reactions

Transfusion reactions are an example of type ll hypersensitivity

Hemolytic disease of the newborn is caused by type ll reactions

Hemolytic anemia can be drug induced

Immune complex-Mediated (Type lll) Hypersensitivity

Immune complexs can damage various tissues

Immune complex-mediated hypersensitivity can resolve spontaneously

Autoantigens can be involved in immune complex-mediated reactions

Arthus reactions are localized type lll hypersensitivity reactions

Delayed-Type (Type lV) Hypersensitivity (DTH)

The initiation of a type lV DTH response involves sensitization by antigen

The effector phase of a classical DTH response is induced by second exposure to a sensitizing antigen

The DTH reaction can be detected by a skin test

Contact dermatitis is a type lV hypersensitivity response

Chronic Inflammation

Infections can cause chronic inflammation

There are noninfectious causes of chronic inflammation

Obesity is associated with chronic inflammation

Chronic inflammation can cause systemic disease

Chapter 16

Tolerance, Autoimmunity, and Transplantation 

Establishment and Maintenance of Tolerance

Antigen sequestration is one to protect self-antigens from attack

Central tolerance limits development of autoreactive T cells and B cells

Peripheral tolerance regulates autoreactive cells in the circulation


Some autoimmune diseases target specific organs

Some autoimmune diseases are systemic

Both intrinsic and extrinsic factors can favour susceptibility to autoimmune disease

Several possible mechanisms have been proposed for the induction of autoimmunity

Autoimmune diseases can be treated by general or pathway-specific immunosuppression

Transplantation Immunology

Graft rejected occurs based on immunologic principals

Graft rejection follows a predictable clinical course

Immunosuppressive therapy can be either general or target-specific

Immune tolerance to allografts is favored in certain instances

Some organs are more amenable to clinical transplantation than others

Chapter 17

Infectious Diseases and Vaccines

The importance of Barriers to Infection and the Innate Response

Many viruses are neutralized by antibodies

Cell-mediated immunity is important for viral control and clearance

Viruses employ several different strategies to evade host defense mechanism

Influenza has been responsible for some of the worst pandemics in history

Bacterial Infections

Immune responses to extracellular and intracellular bacteria can differ

Bacteria can evade host defense mechanism at several different stages

Tuberculosis is primarily controlled by CD4* T cells

Diphtheria can be controlled by immunization with inactivated toxoid

Parasitic Infections

Protozoan parasites account for huge worldwide disease burdens

A variety of diseases are caused by parasitic worms (helminthes)

Fungal Infections

Innate immunity controls most fungal infections

Immunity against fungal pathogens can be acquired

Emerging and Re-emerging Infectious Diseases

Some noteworthy new infectious diseases have appeared recently

Diseases may re-emerge for various reasons


Protective immunity can be achieved by active or passive immunization

There are several vaccine strategies, each with unique advantages and challenges

Conjugate or multivalent vaccines can improve immunogenicity and outcome

Adjuvants are included to enhance the immune response to a vaccine

Chapter 18

Immunodeficiency Disorders

Primary Immunodeficiencies

Combined immunodeficiencies disrupt adaptive immunity

B-cell immunodeficiencies exhibit depressed production of one or more antibody isotypes

Disruptions to innate components may also impact adaptive responses

Complement deficiencies are relatively common

Immunodeficiencies that disrupts Immune regulation can manifest as autoimmunity

Immunodeficiency disorders are treated by replacement therapy

Animal models of immunodeficiency have been used to study basic immune function

Secondary Immunodeficiencies

HIV/AIDS has claimed millions of lives worldwide

The retrovirus HIV-1 is the causative agent of AIDS

HIV-1 is spread by intimate contact with infected body fluids

In vitro studies have revealed the structure and life cycle of HIV-1

Infection with HIV-1 leads to gradual impairment of immune function

Active research investigates the mechanism of progression to AIDS

Therapeutic agents inhibit retrovirus replication

A vaccine may be the only way to stop the HIV/AIDS epidemic

Chapter 19

Cancer and the Immune System

Terminology and Common Types of Cancer Malignant Transformation of cells

DNA alterations can induce malignant transformation

The discovery of oncogenes paved the way for our understanding of cancer induction

Genes associated with cancer control cell proliferation and survival

Malignant transformation involves multiple steps

Tumor Antigens

Tumor-specific antigens are unique to tumor cells

Tumor-associated antigens are normal cellular proteins with unique expression patterns

The Immune Response to Cancer

Immunoediting both protects against and promotes tumor growth

Key immunologic pathways mediating tumor eradication have been identified

Some inflammatory responses can promote cancer

Some tumor cells evade immune recognition and activation

Cancer Immunotherapy

Monoclonal antibodies can be targeted to tumor cells

Cytokines can be used to augment the immune response to tumors

Tumor-specific T cells can be expanded and reintroduced into patients

New therapeutic vaccines may enhance the anti-tumor immune response

Manipulation of costimulatory signals can improve cancer immunity

Combination cancer therapies are yielding surprising results

Chapter 20

Experimental Systems and Methods

Antibody Generation

Polyclonal antibodies are secreted by multiple clones of antigen-specific B cells

A monoclonal antibody is the product of a single stimulated B cell

Monoclonal antibodies can be modified for use in the laboratory or the clinic

Immunoprecipitation- Based Techniques

Immunoprecipitation can be performed in solution

Immunoprecipitation of soluble antigens can be performed in gel matrices

Immunoprecipitation allows characterization of cell-bound molecules

Agglutination Reactions

Hemagglutination reactions can used to detect antigen conjugated to the surface of red blood cells

Hemagglutination inhibition reactions are used to detect the presence of viruses and of antiviral antibodies

Bacterial agglutination can be used to detect antibodies to bacteria

Antibody Assays Based on Antigen Binding to Solid-Phase Supports

Radioimmunoassay are used to measure the concentrations of biologically relevant proteins and hormones in bodily fluids

ELISA assays used antibodies or antigens covalently bound to enzymes

The design of an ELISA assay must consider various methodological options

ELISPOT assays measure molecules secreted by individual cells

Western blotting can identify a specific protein in a complex protein mixture

Methods to Determine the Affinity of Antigen-Antibody Interactions

Equilibrium dialysis can be used to measure antibody affinity for antigen

Surface plasmon resonance is commonly used for measurements of antibody affinity

Microscopic Visualization of Cells and Subcellular Structures

Immunocytochemistry and immunohistochemistry used enzyme-conjugated antibodies to create images of fixed tissues

Immunoelectron microscopy used gold beads to visualize antibody-bound antigens

Immunofluorescence-Based imaging Techniques

Fluorescence can be used to visualize cells and molecules

Immunofluorescence microscopy used antibodies conjugated with fluorescent dyes

Confocal fluorescence microscopy provides three dimensional images of extraordinary clarity

Multiphoton fluorescence microscopy is a variation of confocal microscopy

Intravital imaging allows observation of immune responses in vivo

Flow Cytometry

Magnetic Activated Cell Sorting

Cell Cycle Analysis

Tritiated (H) thymidine uptake was one of the first methods used to assess cells division

Colorimetric assays for cell division are rapid and eliminate the use of radioactive isotopes

Bromodeoxyuridine-based assays for cells division used antibodies to detect newly synthesized DNA

Propidium iodide enables analysis of the cells cycle status of cell populations

Carboxy-fluorescein succinimidyl ester can be used to follow cell division

Assays of Cell Death

The 51Cr Release assay was the first assay used to measure cell death

Fluorescently labeled annexin V measures phosphatidyl serine in the outer lipid envelope of apoptotic cells

The TUNEL assay measure apoptotically generated DNA fragmentation

Caspase assays measure the activity of enzymes involved in apoptosis

Biochemical Approaches Used to Elucidate Signal Transduction Pathways

Biochemical inhibitors are often used to identify intermediates in signaling pathways

Many methods are used to identify proteins that interact with molecules of interest

Whole Animal Experimental Systems

Animal research is subject to federal guidelines that protect nonhuman research subjects

Inbred stains can reduce experimental variation

Congenic resistant strains are used to study the effects of particular gene loci on immune responses

Adoptive transfer experiments allow in vivo examination of isolated cells populations

Transgenic animals carry genes that have been artificially introduced

Knock-in and knockout technologies replace an endogenous with a nonfunctional or engineered gene copy

The cre/lox system enables inducible gene deletion in selected tissues


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