Immunology - Immunology Objectives Section 1 (Ch.1 ) Lecture Slides Handout

• Describe in general terms “host defense system” (immune system), why we need it, and what it does.
• Understand and be able to explain the difference between self and non-self.
• Explain the terms “tolerance” and “self-tolerance”.
  
• Describe the fundamental characteristics that distinguish an innate and an             adaptive immune response (specificity, diversity, memory, and regulation).
  
• List several examples of barriers to infection (e.g., skin, mucous, etc.).
  
• Cells: Describe, in general terms, the development of white blood cells from stem cells to progenitor cells to mature cells.
  
• List cells of the innate immunity and those of adaptive immunity.
  
• Define the terms clone, monoclonal, polyclonal as they apply to T cells and B cells.
• Tissues: Describe the role of the bone marrow and thymus (primary lymphoid tissues).
  
• Describe the role of the spleen and lymph nodes as organs (secondary lymphoid tissues) where primary immune responses occur. Recall the functions of different regions of the spleen and lymph nodes. Recall the location and function of specialized lymphoid tissues such as the mucosalassociated- lymphoid tissues (Peyer’s patches etc.)
  
• Antigens: List the chemical classes of antigens.
  
• Define antigen, antigenic determinant, determinant, and epitope.
  
• Define antigenicity and immunogenicity- classically- (and non classically).
  
• Define hapten and carrier and give examples of each
  
• Define the term mitogen. What cell populations do the following mitogens   activate: phytohemagglutin (PHA), Concanavalin A (Con A), Pokeweed mitogen (PWM), Lipopolysaccharide (LPS) at high concentrations?
  
• Describe the general structure of antibodies. List 5 isotypes.
  
• Define the terms cytokines and their role in general terms.
  
• Define the terms chemokines, and chemoattractant molecules. Describe their role in general terms.
  
• Describe in general terms the role of complement and mode of activation.
  
• List some of the proteolytic fragments generated during activation – C3b, C3a, C4a, C5a.

Phagocytes - Section 2

• Name the two cell types that function as phagocytes. List the various phagocytic   cells in the body and the tissue in which they are found. Describe phagocytes in        host defense with respect to
  • role,
  • receptors on their cell surface that play a role in their immunological      activation,
  • mode of interaction with antigen,
  • molecules that play a role in destruction of microbes,
  • the role of these molecules. Explain the term opsonization.
• Explain the role of the following in antigen recognition primitive pattern recognition receptor (PPRR), Fc receptor, complement receptor CR1, C-reactive protein (CRP)
• Describe the role of the following in host immunity, how they are produced,           where they are located. o phagosome, lysosomes (lactoferrin, defensins,         lysozyme, myeloperoxidase) and phagolysosome.
• NADPH oxidase, reactive oxygen intermediates (superoxide, hydrogen peroxide,
  hydroxyl radical, hydroxyl ion), and hypochlorite. Explain how hypochlorite is         formed.
• Inducible nitric oxide synthase and nitric oxide

Eosinophils

• Describe the role of the following in host immunity to helminths
  • FcR
  • Major basic protein
  • Eosinophil cationic protein

Natural Killer Cells

• Compare and contrast mode of interaction with antigen, and the mechanism of destroying infected cells. Explain the role of NK activating receptors versus that of the killer cell inhibitory receptors (KIR). What is perforin? granzymes? What is antibody dependent cell medidated cytotoxicity?

Mast Cells and Basophils

• List receptors for anaphylatoxins, for IgE. What is the signal for mast cell degranulation? List the products that are secreted. What is the role of histamine in inflammation?

Soluble Mediators

• Major topics include soluble mediators, cells of innate immunity, antigen     presenting cells,
• List the proteolytic fragments of the complement system that function as (a)          anaphylatoxins, (b) chemoattractants, and (c) opsonins.
• List the cytokines that are secreted by activated macrophages and dendritic cells (cells of innate immunity).
• Describe the role of IL-8 and MCP-1 (monocyte chemotactic factor), as well as    listing the source of these chemokines.

 

Antigen Presenting Molecules - Section 3

Major Histocompatibility Complex (MHC) Human Leukocyte Antigens(HLA)

• Describe the function of MHC molecules in antigen presentation
• Diagram the genetic organization of the human leukocyte antigen complex (HLA)/ major histocompatibility complex (MHC) for Class I and Class II MHC.
• Describe the murine system (H-2).
• Explain MHC polymorphism and the likely selective advantage of such a system.
• Explain codominant expression and the advantage of this.
  
• Explain the terms allele and linkage disequilibrium

MHC Class II – HLA-DP, HLA-DQ, HLA-DR (H2-IA, H2-IE)

• Identify the tissue distribution of class II MHC.
  
• List the major structural features of the Class II MHC

MHC Class I – HLA-A, HLA-B, HLA-C (H2-K, H2-D, H2-L)

• Identify the tissue distribution of class I MHC.
  
• List the major structural features of the Class I MHC

Antigen Processing and Presentation

• Diagram the pathway of processing of an exogenous protein antigen and list at     
• Explain the phrase CD4+ T cells are restricted by Class I MHC
  
• Diagram the pathway of processing of an endogenous protein antigen and list at least seven steps.
  
• Explain the phrase CD8+ T cells are restricted by Class I MHC
  
• Compare and contrast the presentation of exogenous and endogenous antigens to T lymphocytes.
  
• Identify the step(s) of antigen processing that are negatively affected by various herpes viruses.

Nonresponsiveness

• Determinant Selection

Molecular interactions between T cells and antigen presenting cells

• See summary sheet

 

Immunoglobulins (General) - Section 4

• Describe the basic structure of the immunoglobulin molecule.
• Describe the overall chain structure of the major classes and subclasses of immunoglobulins.
• List the major regions of the Ig molecule (e.g., constant, variable, hypervariable, complementary determining region (CDR) etc.) and describe their overall structure and function. Compare and contrast the structure of light and heavy chains.
• Recall the overall structure of the major Ig fragments (e.g., Fc) and describe the enzymatic digestion used to obtain these fragments.
• Name the two different types of light-chain constant regions
• Explain the following terms- allotype, isotype, and subclass.
• Explain the terms Am, Gm and Km (allotypes).
• Define the terms affinity and avidity.
• Explain the difference between monoclonal antibodies and polyclonal antibodies.

Immunoglobulin Isotypes

• List the different immunoglobulin isotypes.
• List the structural and biological properties (role/function) of the immunogloulin      isotypes.
  
• Explain the difference between dimeric IgA and secretory IgA. Describe how dimeric IgA becomes secretory IgA.
  
• Identify cells that express receptor for Fc portion of IgG (FcR)

Complement - Section 5

• Describe the overall function of complement in host defense.
• Describe in general terms the source of complement proteins and the distribution of the soluble components in the body.
• Explain the CH50 test. Explain the rationale for using plasma CH50 levels in the assessment of disease processes. Explain the rationale for measuring C3, C4, and the conditions that would lead to a decrease in the serum levels of these two complement proteins.
• Compare and contrast the alternative and classical pathways with respect to activation, function, and components.
• List the complement receptors and the biological function(s) as a result of receptor-ligand interaction.

Alternative Pathway

• List the components of the alternative pathway of complement activation.
• Explain how the alternative complement pathway is activated.
  
• List the components of the C3 convertase AP, C5 convertase, AP
  
• Describe the role of the various components of the alternative complement pathway.
  
• Describe the role of each of the proteolytic fragments generated duringcomplement activation.
• Describe the various mechanisms by which the alternative complement pathway is regulated to minimize destruction of “self” (species specific proteins).

Classical Pathway

• List the components of the classical pathway of complement activation.
  
• Explain how the classical complement pathway is activated
  
• List the components of the C3 convertase CP, C5 convertase, CP
  
• Describe the role of the various components of the classical pathway.
  
• Describe the role of each of the proteolytic fragments generated during      complement activation.
  
• Describe the various mechanisms by which the classical complement pathway is regulated to minimize destruction of “self” (species specific proteins).

Terminal Pathway

• List the components of the terminal (common) complement pathway.
  
• Describe the role of the various components of the terminal (common) pathway.
  
• Describe the various mechanisms by which the terminal complement pathway is regulated to minimize destruction of “self” (species specific proteins).
  
• Describe the consequence of deficiencies in various components of the     complement system.

B cell Antigen Receptor and Antigen Independent Maturation/Differentiation/Ontogeny of B cells - Section 6 (Chapters 7a and 8)

B cell Antigen Receptor (Membrane immunoglobulin) (mIg)

• List the components of the B cell receptor complex

Somatic Recombination

• Describe and explain the molecular genetic mechanisms involved in the generation of antibody diversity (e.g., somatic recombination, combinatorial diversity, multiple germline genes, junctional diversity etc.).
  
• Describe the role of the products of the recombinase activating genes (RAG-1 and RAG-2), and the enzyme terminal deoxynucleotidyl transferase in somatic    recombination.
  
• Define the term “B cell repertoire” and recall how this is generated.

B cell maturation/development/differentiation (antigen independent); B cell Ontogeny

• Describe the sequence of events in the B cell developmental pathway from a        stem cell to a mature, naive cell. Explain how CD19 and CD20 can be used to      play a role in clinical practice.
  
• Diagram the order of rearrangement (somatic recombination) and expression of   Ig heavy chain and light chain genes during development of the B cell.
  
• Explain allelic exclusion with respect to immunoglobulin gene expression.
  
• Explain tolerance induction during B cell development. (apoptosis and anergy)
  
• Explain alternative splicing and its role in B cell development.

Part 2: “ B cells: Antigen-Induced Differentiation” - Chapter 8

• Describe the essential components of secondary lymphoid tissues.
• Compare and contrast the essential components (#1) of the peripheral lymph        nodes, the spleen, and the lamina propria.
  
• Explain why the initial site of a primary immune response depends on the route of antigen entry.
  
• Define the terms “T dependent antigens” and “T-independent antigens”. List several examples of T independent antigens and describe the typical characteristics of such antigens (e.g., polyclonal activators).
  
• Explain why T dependent antigens “must be” proteins. What is a hapten? A carrier protein? A mitogen? (See chapter 1)
  
• Diagram the steps in a humoral immune response to a protein antigen and-
• Explain crosslinking of antigen.
• Describe the fate of the antigen
• Describe the fate of the immunoglobulin.
• Describe the molecular interactions between the T cell and B cell.
• List the molecular interactions that are involved in adhesion.
• Explain clonal expansion and the clonal selection theory.
• Explain the role of the CD40-CD40L interaction (as determined by defects).
• Describe the various fates of the B cells that clonally expand.
• Describe the events that occur in the germinal center
• Describe isotype switching and the factors that influence it. .
• Explain somatic mutation/affinity maturation and how it contributes to
  generation of diversity.
• Describe the fate of activated B cells (apoptosis versus memory)
• Describe the role of the plasma cell, half life, localization.
• Explain the difference between transmembrane and secreted immunoglobulin
  
• Explain the consequence of a defect in the CD40-CD40L interaction.
  
• Explain how primary and secondary immune responses differ with respect to antibody titer, antibody isotype, lag phase, and site of the immune response.
  
• Understand the process of antibody feedback in negative regulation of B cells and the roles played by  FcRII.
  
• Explain E rosettes and their role in the clinical laboratory. Identify cells in the rosette formation.
  

For self study- not to be tested- List several examples of biochemical events triggered in B cells by antigen recognition. Understand the role of ITAMs (immunoreceptor tyrosine activation motifs), src homology domains, guanine exchange factor (GEF) and GTP activating protein (GAP), ras, various protein kinases, src family kinases, phospholipase C, CD45, Syk. (etc.)

T Cells - Section 7 (Chapters7b & 9)
T cell Antigen Receptor & Antigen Independent Maturation/Differentiation/Ontogeny of
T cells
T cell antigen receptor

• Describe the T cell receptor complex
  
• Describe the overall structure of the TCR (gamma/delta). Compare and contrast with the alpha/beta TCR.

Somatic recombination

• Describe and explain the molecular genetic mechanisms involved in the generation of T cell receptor diversity (e.g., somatic recombination, combinatorial diversity, multiple germline genes, junctional diversity etc.).
  
• Describe the role of the products of the recombinase activating genes (RAG-1 and RAG-2), and the enzyme terminal deoxynucleotidyl transferase in somatic recombination.
  
• Explain allelic exclusion.
  
• efine the term “T cell repertoire” and recall how this is generated.

T cell Maturation; T cell Differentiation (antigen independent); T cell Ontogeny

• Describe the sequence of events in T cell developmental pathway from a stem cell (bone marrow) to a mature, naive CD4+ or CD8+ T cell (thymus).
  
• Explain the processes of positive and negative selection in the thymus.(and death by neglect)
  
• Explain the terms lineage selection, double positive thymocytes, single positive thymocytes.
  
• Explain the term “interactive avidity”.
  
• List the four factors on which interactive avidity depends.

Naive Lymphocyte Recirculation

• List the selectins and integrins expressed on a naive lymphocyte. List their counter molecules present on the post capillary venules (high endothelial venules) in peripheral lymph nodes and in the mucosal lymph nodes. Compare and contrast the counter molecules in these two sites.
  
• Explain the role of matrix metalloproteinases in the extravasation of lymphocytes from the blood to a tissue.

Primary Immune Response CD4+ T cells - Section 7 (Chapter 9) continued

Site-

• Where does a primary immune response take place. Compare and contrast the essential components (#1) of the peripheral lymph nodes, the spleen, and the lamina propria
  
• Explain how the route of entry determines the site of the initial immune response.
  
• Describe two ways in which the antigen may get to the site of the immune response
  Recognition of antigen- antigen presenting cells
  
• Explain the role of antigen presenting cells in the activation of a Thp
  
• Diagram the role of the TCR in recognition of antigen that is displayed by an antigen presenting cell. Show molecular interactions- adhesion, regulatory costimulatory (See Chart) .
  
• List the cytokines secreted by an activated antigen presenting cell. Thp cell Activation (Antigen dependent)
  
• Explain the role of CD80/CD86-CD28 interaction in clonal expansion of T cells
  
• Explain what is meant by a “two signal” (or more) requirement for T cell activation.
  
• Name the cytokine secreted by the activated Thp and its role.
  
• Name the receptors expressed de novo in T cell activation –leading to clonal expansion when the cytokine for the receptor is available.
• Explain clonal expansion
  
• Define mechanisms leading to anergy in the regulation of T cells Th0 in T cell Differentiation (Antigen-dependent)
  
• Name the cytokines secreted by the Th0 cells
  
• Name the cytokine that contributes to the generation of Th1 cells: Explain the cell sources of that cytokine and the factors that lead to its secretion.
  
• Name the cytokine that contributes to the generation of Th2 cells; Name the presumed cell sources for that cytokine Th1 and T2 cells in T cell Differentiation
  
• List the Type 1 cytokines
  
• List the Type 2 cytokines
  
• Describe reciprocal regulation by Type 1 and Type 2 cytokines
  
• Describe the mechanism by which IL-10 downregulates the production of Type 2 cytokines
  
• Explain the role of CD80/CD86 -CTLA4 (CD152) in regulation of T cell responses.
  
• List the immunological roles of Type 1 cytokines, (ii) of Type 2 cytokines.
  
• Recall that unlike for Ig genes, somatic mutation is not a mechanism used to generate diversity in the TCR genes. Memory CD4+ T cell Responses
  
• Explain the role of CD95-CD95 ligand interaction on activated T cells.
  
• Describe the fate of activated T cells (apoptosis versus memory)
  
• Explain how primary and secondary immune responses of CD4+ T cells differ with respect to antigen presenting cell, lag time and site of the immune response.
  

Immunology Objectives - 11

Primary Immune Response CD8+ T cells (Continued- Chapter 9) Section 7

CD8+ T cell Activation (antigen dependent differentiation)

• Site of initial response (why is it different from CD4+ T cells)
  
• Explain the role of target cells in the activation of a naive CD8+ T cell.
  
• Name the receptors expressed de novo in T cell activation –leading to clonal expansion when the cytokine for the receptor is available.
  
• Explain what is meant by “helper independent” naive CTLs.
  
• Explain what is meant by a “two signal” (or more) requirement for T cell activation.
  
• Describe the events that lead to delivery of a ‘lethal hit” by CTLs.
  
• Explain why CTLs are not destroyed when they deliver “the lethal hit”.
  
• Describe the fate of activated T cells (apoptosis versus memory)
  

Memory CD8+ T cell Responses

• Explain how primary and secondary immune responses of CD8+ T cells differ with respect to lag time and site of the immune response.
  
• Describe the properties of memory lymphocytes.

Superantigens

• Diagram the mechanism of superantigen recognition of T cells. Compare with nominal antigen recognition. What would superantigens activate so many T cells?

E Rosettes

• Explain E rosettes and their role in the clinical laboratory.

Gamma-Delta T cells (If covered in class)

• Differentiate between the two types of TCR (alpha/beta, gamma/delta) and distinguish their subsets.
  
• Compare and contrast antigen recognition by gamma/delta T cells versus alpha/beta T cells.
  
• Discuss the role of gamma/delta T cells versus alpha/beta T cells
  Signal Transduction – NOT ON EXAM
  
• List several examples of biochemical events triggered in T cells by antigen? MHC recognition.
• Understand the role of ITAMs (immunoreceptor tyrosine activation motifs), src homology domains, guanine exchange factor (GEF) and GTP activating protein (GAP), ras, various protein kinases, src family kinases, phospholipase C, CD45, ZAP 70. (etc.)

Immunology Objectives: 12

Inflammation - Section 8 (Chapter 10)

Inflammation

• List the 5 hallmarks of inflammation explain how each is brought about.
  
• Relevant cells in tissues and in circulation prior to inflammation
  
• Relevant proteins in tissues and in circulating prior to inflammation
  
• Role of tissue damage in activating intrinsic coagulation pathway

Activation of Intrinsic Coagulation Pathway and Consequences

• Explain role of kallikrein
  
• Explain how tissue damage leads to the production of C5a, bradykinin, and neutrophil activation.
  
• What is the stimulus for histamine release from mast cells?
  
• Explain the role of histamine on the expression of P-selectin on the endothelial cells?
  
• Describe the role of P-selectin in acute inflammation.
  
• Describe other effects of histamine on the endothelium and the role that this plays in acute inflammation.

Activation of Tissue Macrophages

• Tissue macrophages play an important role in acute inflammation. List at least six actions of activated macrophages.
  
• List other local effects of TNF.
  
• List the systemic effects of IL-1 and TNF.
  
• Explain how IL-6 secretion is induced and the source of IL-6. Explain why levels of C-reactive protein increase in patients with heart disease.

Activated Endothelium

• What is the stimulus for E-selectin expression on the endothelial cell surface. Compare and contrast the role and stimulus for cell surface expression of E-selectin and P-selectin.
  
• Describe the effects of IL-1 and TNF on the vascular endothelium
  
• List the integrins that are present on both neutrophils and monocytes. List also their counter molecules and which one(s) are upregulated in acute inflammation. VLA-4 is another integrin present on monocytes (not neutrophils). Name the counter molecule for VLA-4 and the effect of IL-1 and TNF on its expression. What is CD18?
  
• IL-1 and TNF induce endothelial cells to express MCP-1 and IL-8. Explain the role of these molecules and why circulating leukocytes move toward the region in which these molecules are present in highest concentration.
  
• Explain what is meant by “IL-1 and TNF act synergistically”. Rolling, Margination, Diapedesis
  
• Explain the role of P-selectin, E-selectin, LFA-1, Mac-1, VLA-4, PE-CAM with respect to rolling, margination, and diapedesis. On what cells are they expressed? On what cell(s) is/are the relevant ligand expressed. Name the ligand in each case.
  

 

Immunology Objectives: 13
Degradation of Basement membrane and tissue matrix

• Explain the role of matrix metalloproteinases (MMPs) in the recruitment of cells from the circulation to the site of infection within a tissue. Name the cell source and their properties.
  
• Explain how this facilitates acute inflammation. Consider why cancer patients might be administered MMP inhibitors.
• Dampening Inflammation
  
• Describe the role of TIMPs, TGF, apoptosis in dampening inflammation.

Chronic Inflammation

• In chronic inflammation, the inflammatory response is sustained. Often this will occur when antigen is always present as occurs in autoimmune disorders. What cells of the adaptive immune system would play a role in chronic inflammation in autoimmune disorders?
  
• List the Type 1 cytokines secreted by Th1 CD4+ T cells. Note that TNF is secreted by both activated macrophages and by CD4+ Th1 cells. Describe IL-17 with respect to cell source, and role in inflammation.
  
• Follow the steps in the delayed hypersensitivity reaction. Note the sequence of events and the role of antigen presenting cells, inflammatory mediators secreted by activated macrophages, etc. Note that the early steps are exactly the same as that described for acute inflammation.
• Describe where the Th1 cells were activated and the processes by which they were able to enter the site of inflammation. Name the pro-inflammatory cytokines and the anti-inflammatory cytokines.
  
• Explain the reciprocal regulatory nature of Type 1 and Type 2 cytokines.
  
• Recall the differences in the requirement for activation of naive CD4+ T cells and memory T cells.
  
• Recall the molecular interactions between activated or memory T cells and endothelial cells that allow the T cells to leave the blood vessel and enter the site of inflammation.
  
• Explain how products of Th1 cells (i.e. interferon gamma and tumor necrosis factor)
  perpetuate the inflammatory response.
  
• Clinical Relevance (See Lectures- Basic Science Perspective on Autoimmunity and
  Immunodeficiency Disorders as well as Novel therapies- a Basic Science Approach)

Immunology Objectives: 14
Cytokines & Chemokines - Immunology Objectives: Section 9: Ch 6

• Cytokine Sources (Cells secreting the cytokine or chemokine)
• Target (cells expressing receptors)
• Effect and role in immune responses
• IL-1
• IL-2
• IL-3
• IL-4
• IL-5
• IL-6
• IL-7
• IL-10
  
• IL-12
• IFN
• Type 1 interferons
• Upregulates 2’-5’ oligoadenylate synthethase; Increases Class I MHC

Immunology Objectives: 15

• IFN
• Type 2 interferon
• TNF
• TGF
• ckit ligand
• GM-CSF
• G-CSF
• M-CSF

Chemokines

• IL-8 (CXCL8)
• MCP-1 (CCL2)
• Eotaxin (CCL11)

Chemoattractant

• C5a
• List Type 1 cytokines and their role in immune responses
• List Type 2 cytokines and their role in immune responses

Immunology Objectives: 16
Sections 10 and 11 available only in Class Slides
Basic Science Component: Tumor Immunology - Ch 15- Section 12

Tumor Immunology (See Class Slides)

• Illustrate how destruction of tumors may occur by phagocytes, natural killer cells, and cytotoxic T cells.

Tumor Evasion of the Immune System

• Tumors may escape immunosurveillance by the immune system by affecting various aspects
  
• Describe evasive techniques listed below and explain how each would affect the T cell response to tumors.
  
  • Hole in the T cell repertoire
    
  • Determinant selection
    
  • Lack of costimulatory molecules
    
  • Lack of Type 1 cytokines
    
• Describe evasive techniques listed below and explain how each would affect the T cell or B cell response to tumors.
  
  • Shedding of tumor antigens
    
  • Antigenic modulation
    
  • Loss of antigenicity
    
  • Loss of class I MHC expression
    
  • Antigen masking

Immunology Objectives: 17
Basic Science Component: DNA vaccines - Ch 12- Section 12
Objectives: DNA vaccines (See Class Slides)

• Compare and contrast the immunological processes that are activated during
  immunization with a recombinant protein, toxoids, attenuated bacteria, inactivated
  viruses, and DNA vaccines.
  
• What is the rationale for choosing to develop a DNA vaccine?

Immunology Objectives: 18
Immunology Objectives: Immunodiagnostics: Dr. Lennon

• Recall the various antibody isotypes and specify those that are commonly used in clinical laboratory tests.
  
• Diagram the basic structure of the IgM antibody and explain the significance of this.
  
• Review the terms affinity and avidity. Recall the types of intermolecular interactions between antigen and antibody.
  
• Describe the formation of antigen-antibody complexes and the theory of lattice formation.
  
• Compare and contrast the three zones that comprise a precipitation curve.
  
• Compare and contrast the precipitation based assays (i ) one dimensional (ii) radial immunodiffusion, (iii) ouchterlony double diffusion.
  
• Explain “pattern of identity”; pattern of non identity”; and “pattern of partial identity”.
  
• Describe the difference between soluble and insoluble immune complexes.
  
• Explain the principles of agglutination and the list the factors that affect agglutination.
  
• Describe how antibody titer is determined and how it is reported.
  
• Describe the basic principles of the following: (i) direct and indirect agglutination, (ii) latex agglutination, (iii) hemagglutination.
  
• Explain “zeta potential” and why this phenomenon poses a problem for agglutination of antigenantibody complexes.
  
• List several application of the agglutination test.
  
• Compare and contrast the direct and indirect Coombs’ tests. Give relevant clinical scenarios that use these tests.
  
• Describe in overall terms the general principles and technique of the ELISA test.
• Explain how antigen-antibody interaction is detected.
• Describe the CH50 complement test to detect overall deficiencies in the classical pathway of complement.

Immunology Objectives: 19

Infectious Agents that Thrive Outside Cells - Immunology Objectives: Infections Chapter 11, Section 13

Innate Immunity

• Describe the role of each of the following in a host response to infection. Include the recognition aspects as well as the mode of action. Various products are secreted by cells- explain the effect of each.
  

Alternative pathway of complement

• Phagocytes
  
• Mast cells
  
• Antigen presenting cells
  
• Describe the role of the activated macrophage (list 7) and how each contributes to the innate immune response (including inflammation).

Adaptive Immunity

• Describe the role of innate immunity in recruiting adaptive immunity.
  
• Explain the role of CD4+ T cells
  
• Explain how Th1 cytokines enhance innate immunity.
  
• Describe the role of B cells

Interaction of Innate and Adaptive Immunity

• Explain how cytokines secreted by Th1 cells enhance innate immunity, but how cytokines secreted by Th2 cells down regulate innate immunity.
  
• Explain how antibodies secreted by plasma cells enhance innate immunity, including activation of the classical pathway.

Fungi

• When fungi are too large to be phagocytosed, the phagocyte can contribute to the destruction of the fungi by a process referred to as the “frustrated phagocyte effect’. Explain.
  
• Explain the term “hole in the repertoire” and the infectious agent to which individuals
  with this defect are susceptible.

INFECTIOUS AGENTS THAT THRIVE INSIDE PHAGOSOMES

• Describe the role of macrophage, CD4+ T cells, and Type 1 cytokines in host defense to infectious agents that thrive inside the phagosome.
  
• Explain why individuals who are on immunosuppressive therapy or those who have AIDS are particularly at risk for serious complications when infected with Mycobacterium tuberculosis.
• Describe the role of CD4+ T cells, Type 1 cytokines, pCTL, and CTL in host defense to infectious agents that thrive inside cytosol but are not contained within a vacuole.
  
• Explain why a defect or a mutation in indolameamine-2,3-dioxygenase (IDO) affects the regulation of an immune response.

Immunology Objectives: 20

• Why must some of the antigen of an infectious agent that thrives in the phagosome, be degraded and presented on the cell surface in context of Class I MHC.
  
• Explain how natural killer cells influence the course of the infection –in the absence of a viral infection.
• Explain how nitric oxide might play a role in this type of infection.
  
• Name the two cell types that play the most significant role in host defense to infectious agents that thrive inside phagosomes. Understand that microorganisms that thrive within phagosomes or in the cytosol can (at some time) be found outside the cell. At this time, these microorganisms will activate many of the same mechanisms as do extracellular bacteria. However, this is NOT the predominate mechanism by which these organisms are eliminated.

INFECTIOUS AGENTS THAT INFECT THE CELL CYTOSOL
When this Agent is Outside the Cell

• For a brief period of time, infectious agents that will infect the cell cytosol are found
  outside the cell. Describe the processes that act on the infectious agent when they are outside the cell. Explain why it is necessary to activate CD4+ Th cells during this type of infection.
  
• Explain the need for dendritic cells in peripheral non lymphoid tissues as well as in
  secondary lymphoid tissues. Describe the two processes by which antigen that is in a peripheral non lymphoid tissue is transported to a secondary lymphoid tissue.

Role of CD4+ T cells

• In a model of HIV infection, chemokine receptors function as coreceptors. Name two
  coreceptors and name the primary receptor for infection of CD4+ T cells.
  
• Explain why individuals with HIV eventually develop AIDS (acquired immunodeficiency
  syndrome).

Role of Natural Killer Cell

• Describe the role of natural killer cells in viral innate immunity (a) prior to recruitment of adaptive immunity, (b) after recruitment of innate immunity. Compare the modes of cell destruction in these two scenarios.

Cytotoxic T cells

• Viruses are an example of infectious agents that will be sequestered within the cell
  cytosol during most of the infection.
• Describe the process by which a segment of a protein in the cytosol eventually becomes displayed on the cell surface in context of Class I MHC.
  
• Explain how pCTL differentiates to a mature CTL, capable of delivering “the lethal hit”.
• Explain the process of “the lethal hit”

Immunology Objectives: 21
Role of B cells

• Explain how B cell activation can possible occur to an agent that thrives within the cell cytosol.
  
• Explain how antibodies produced at this stage helps to (a) reduce the numbers of
  infectious agents outside the cell, (b) destroy infected cells.

Viral Evasive Strategies

• Epstein Barr Virus (HHV-4) produces a viral protein that is an IL-10 homolog. Explain why this would help the virus thwart the immune system.
  
• Review how human herpes simplex virus (HHV-1 and HHV-2) hinders the immune
  response.
  
• Review how cytomegalovirus (HHV-5) hinders the immune response.
  
• Neisseria spp. Resist opsonization by complement protein C3b. Explain how the alternative and the classical pathways of complement can still be effective in host defense against this infectious agent.
  
• Rickettsia rickettsii avoids destruction in the cell cytosol by escaping to the cell cytosol. As such, how would the immune system attempt to eliminate the infection?
  
• Patients with leprosy may have either a mild form or a more severe form of the disease.
• Explain why the type of cytokines (Type 1 or Type 2) that predominates in the infection, determines the course of the infection.
  
• Explain how Shigella dysenteriae hinders the immune response.
  
• Explain the term antigenic variation as it relates to Borrelia burgdorferi.
  
• Explain why Mycobacterium tuberculosis is not readily destroyed in the phagosome.
  Overall 16. Compare and contrast the relative contribution of various cells of the innate and adaptive immune systems that predominate in response to infection with extracellular bacteria, intracellular bacteria, and viruses.

Basic Science Component- Novel Therapies - Section 14 -
Objectives only available in Class Slides
Immunology Objectives: 22

Clinical Immunology Objectives
Immunology Objectives: 23
Immunology Objectives: Immunization - Chapter 12

Vaccination Hazards

• List several immunization hazards. Explain “herd immunity”.

Passive Immunization

• Explain in general terms the difference between passive natural and passive artificial
• Give at least two examples of natural passive immunization.
  
• Explain the term gamma globulins and how the administration of gamma globulins provides artificial passive immunization.
  
• Describe situations in which a patient should be administered gamma globulin therapy.

Active Immunization

• Define the terms “intentional immunization” and “unintentional immunization”.
  
• List several different forms of intentional immunization.

Types of Active Immunization

• List at least three examples of inactivated/killed vaccines and their properties.
  
• List several vaccines that consist of attenuated organisms.
  
• Give two examples of toxoid vaccines. (Define the term “toxoids)
  
• Describe the properties of recombinant vaccines and give two examples. Explain why these are safe even for patients that are immunocompromised.
  
• Explain the term conjugated vaccine. Provide two examples.
  
• DNA vaccines- later lecture.
  
  

Tetanus Toxoid

• What are the advantages of using toxoids as vaccines?
  
• Define tetanus toxin, tetanus toxoid, heterologous antiserum, homologous antiserum.
  
• Explain why natural immunity to tetanus is not possible.
  
• Describe the causative agent of tetanus, the mechanism of infection, and the mode of action of the toxin.
• Explain how “neonatal tetanus” can occur.
• Explain the various clinical approaches to treat a patient that has been infected (or thought to be infected) with C. tetani spores.

Polio Vaccine

• Explain the difference between the Sabin polio virus and the Salk polio virus with respect to mode of administration, type of immunity which follows, as well as the advantages and disadvantages of each. Under what conditions does the CDC recommend that Sabin oral polio vaccine be administered instead of the SALK injected polio vaccine? Why?

Adjuvants

• Explain in general terms the role of adjuvants in vaccine administration.
  
• Provide examples and the hypothesized mechanism of most adjuvants.

Immunology Objectives: 24
Immunology Objectives: Hypersensitivity Reactions - Ch. 13

• List the Gell and Coomb’s classification.
  
• Which of the Gell and Coombs classifications deal with (a) antibody mediated immunity? (b) cellular immunity?

Type I Hypersensitivity Reactions

• Re: Type I hypersensitivity reaction. What is the (a) sensitization phase? (b) the effector phase?
  
• Explain why Type I hypersensitivity reactions can occur so rapidly following contact with antigen when the production of IgE antibodies requires 10-14 days.
  
• What is the stimulus for mast cell degranulation?
  
• List the primary effector mediators released by mast cells
  
• Explain the principle of the skin test, RAST (radioallergosorbent test).
  
• Explain the principle of the ELISA test for IgE.
  
• List the clinical manifestations (locally and systemically) categorized as Type I hypersensitivity.
  
  • Allergic Rhinitis: Describe the symptoms and stimulus.
    
  • Asthma: Describe the symptoms and the potential stimuli, both immunological and non immunological.
    
  • Anaphylaxis: Describe the clinical manifestations and the stimuli.
    
  • List the three categories of intervention for patients susceptible to Type I
    hypersensitivity reactions; Also, explain how each of the following pharmacological interventions mediate their effects and when each is used for intervention.
    
    • Sodium cromoglycate (cromolyn sodium)
      
    • Epinephrine
      
    • Steroids
      
    • Anti-histamines
      
• Explain the principle underlying desensitization therapy.
  
• Explain the mechanism of drug induced hypersensitivity (Type I – see also Type II below).

Immunology Objectives: 25
Type 2 Hypersensitivity Reactions: Antibody mediated (antigen on cells)

• Describe the (a) sensitization, and (b) effector phase of a Type II hypersensitivity reaction. Note that when antigen is an intrinsic component of the cell, destruction is ongoing.
  
• Note that IgE antibodies play an important role in the Type I hypersensitivity reaction, yet IgM and IgG antibodies play an important role in Type II hypersensitivity reactions. This leads to very different biological consequences. Explain.
  
• Explain the role of phagocytes, natural killer cells and the complement system in a Type II hypersensitivity reaction. Compare complement mediated lysis and ADCC.
  
• List several Type II hypersensitivity reactions.
  
• Explain the transfusion reaction in terms of ABO blood type, isohemagglutinins, and red blood cell destruction.
  
• Explain the hemolytic disease of the newborn (erythroblastosis fetalis) in terms of Rh blood group incompatibility between the mother and the fetus, placental transfer of IgG antibodies, and mechanism of fetal red blood cell destruction.
  
• Describe the mechanism and specific tissue (cells) damage in Goodpasture’s syndrome and insulin dependent diabetes.
  
• List the diagnostic techniques used (e.g. immunofluorescence and EM techniques) to evaluate Type II hypersensitivity tissue injuries.
  
• List the therapies used for the diseases that involve Type II hypersensitivity reactions.
  
• Compare drug induced Type II hypersensitivity reactions with Type I induced hypersensitivity reactions.

Immunology Objectives: 26
Type 3 Hypersensitivity Reactions: Antibody mediated (soluble antigen immune complexes)

• Describe the (a) sensitization, and (b) effector phase of a Type III hypersensitivity reaction.
  
• Note that IgG and IgM antibodies play an important role in both Type II and Type III
  hypersensitivity reaction. Yet, these are classed as different reactions. Explain.
  
• Explain the role of phagocytes and the complement system in a Type III hypersensitivity reaction.
• Compare the mechanism of action of these in a Type II hypersensitivity reaction and a Type III hypersensitivity reaction.
  
• List several examples of Type III hypersensitivity reactions.
  
• Explain the clinical manifestations of SLE in terms of immune complex deposition and the consequence of this. Consider the effects of persistent antigenic challenge.
  
• Explain the clinical manifestation of Farmer’s lung in terms of immune complex deposition and the consequence of this.
  
• Explain the clinical manifestations of serum sickness and the mechanism by which pathology occurs. Also, explain why a second injection of the horse serum could lead to anaphylaxis and death.
  
• Name one clinically useful heterologous antibody preparation used in North America and the potential benefit and harm to the patient.
  
• List the diagnostic techniques used (e.g. immunofluorescence and EM techniques) to evaluate Type III hypersensitivity tissue injuries.
  
• List the therapies used for the diseases that involve Type III hypersensitivity reactions.
  
• Compare drug induced Type II hypersensitivity reactions with drug induced Type I hypersensitivity reactions.

Immunology Objectives: 27

Type IV Hypersensitivity Reactions: Cell Mediated

• Describe the (a) sensitization phase, (b) effector phase of a Type IV hypersensitivity reaction.
• Describe the cell types and the cytokines that predominate in a Type IV hypersensitivity reaction.
  
• Explain, in general terms, the different effects of Type 1 and Type 2 cytokines on a Type IV hypersensitivity reaction
  
• List 3 subclasses of Type IV hypersensitivity reactions.
  
• How is the Type IV hypersensitivity reaction normally regulated?
  
• Describe the predominant cytokines in a patient with tuberculoid leprosy versus that of a patient with lepromatous leprosy. Explain why the presence of different cytokines leads to different outcomes.
  
• Granuloma formation is associated with chronic and persistent antigen. Explain the formation of a granuloma and where these localize in lung tuberculosis, in sarcoidosis, and in Crohn’s colitis. What is the suspected pathogenic agent?
  
• List step by step the effector phase of a Type IV hypersensitivity reaction.
  
• Describe the Mantoux reaction with respect to antigen, cells, cytokines, and time of maximum induration.
  
• The Mantoux reaction involves memory T cells. What characteristic of the Mantoux reaction makes this “obvious”? Why is this reaction referred to as a delayed hypersensitivity reaction?
  
• Describe poison ivy dermatitis in terms of a contact hypersensitivity with respect to hapten, cells, cytokines, sensitization phase and effector phase.

Immunology Objectives: 28
Immunology Objectives Chapter 14

• Define the following terms: central tolerance, peripheral tolerance, anergy, suppression, sequestration.
  
• Autoimmunity occurs when there is a loss of self tolerance. List three ways in which self tolerance can be lost.
  
• Explain what is meant by “loss of sequestration” and why this leads to activation of non tolerized T cells. Provide at least two examples of loss of sequestration.
  
• Autoimmune disorders can be classified by the manner in which the immunopathology is initiated. List five different ways by which the immunopathology (leading to autoimmunity) can be initiated.
  
• Study chart – list of autoimmune disorders- mode of pathology- For each learn autoantibodies and autoantigens.

Immune Complex Mediated

• Three autoimmune disorders in which the immunopathology is initiated by immune complexes are described in your handout: systemic lupus erythematosus (SLE), Wegener’s granulomatosis, and rheumatoid arthritis.
  
• Review the Type III hypersensitivity reaction and the mechanism of tissue destruction. Explain how activation of complement on immune complexes can cause tissue damage.

Systemic Lupus Erythematosus

• What is the major autoantibody that forms immune complexes and hence immunopathology. (What are the auto antigens? autoantibodies?)
  
• What antibody is associated with spontaneous abortions?
  
• Name the HLA alleles that predispose to SLE. What is the female/male ratio susceptibility?
  
• Consider the significance of polyclonal B cell activation?
  
• Name the tissues in which immune complexes are trapped and this correlates with pathology.

Rheumatoid Arthritis (RA)

• Note that rheumatoid arthritis pathology involves both immune complex and cell associated pathology.
  
• Name the HLA disease association and female-male ratio for susceptibility to RA.
  
• Describe rheumatoid factor and its role in RA immunopathology.
  
• Name the tissues in which pathology occurs.
  
• Name the two main cytokines that are present in excess in RA and are targeted in approved immunotherapy of RA.

Antibodies to Cell Surface Antigens

• Name three autoimmune disorders in which immunopathology is initiated by antibodies to cell surface antigens.
  
• Antibodies that are targeted to cell surface antigens cause damage by a hypersensitivity reaction- name the hypersensitivity type (Chapter 13).
  
• Review Type II hypersensitivity reactions and the mechanism of tissue damage.

Immunology Objectives: 29
Pernicious Anemia

• Name the autoantibody that initiates pathology and explain why this leads to
  malabsorption of vitamin B12 and defective red blood cells and megablastic anemia.
  
• Note that pernicious anemia can also be caused by blocking antibodies. See section blocking antibodies.

Goodpasture’s Syndrome

• Name the autoantibody that initiates immunopathology in Goodpasture’s Syndrome.
  
• Name the tissues (cells) that are targeted in this autoimmune disorder.
• Name the HLA association and the female-male ratio, and age for susceptibility to this autoimmune disease.
  
• Explain how the linear deposition of IgG and complement can play a role in diagnosis.

Cold Agglutinin Disease

• Name the autoantibody that initiates immunopathology in cold agglutinin disease.
  
• Name the tissues (cells) that are targeted in this autoimmune disorder.
  
• Explain why this disease is called “cold” agglutinin disease and the treatment for this
  disease.

Blocking Antibodies

• Name two autoimmune disorders in which immunopathology is initiated by BLOCKING antibodies.

Myasthenia gravis

• Explain the role of acetylcholine at the neuromuscular junction in the absence of
  pathology.
  
• Explain how anti-acetylcholine receptor antibodies that cause endocytosis and
  degradation of the acetylcholine receptor can cause pathology. Describe how this
  manifests clinically. Explain why this is referred to as a “blocking antibody”.

Pernicious Anemia

• Name the antibody that prevents the binding of intrinsic factor to vitamin B12.
  
• Explain why this is referred to as a blocking antibody. (See also antibodies to cell surface antigens).

Stimulating Antibodies
Grave’s Disease

• Name the autoantibody that initiates pathology in Graves disease.
  
• Explain the role and source of thyroid stimulating hormone (TSH) on the thyroid gland in normal physiology. Explain how the production of TSH is down regulated.
  
• Explain how the normal physiology (#2) is altered in the presence of the autoantibody- thyroid stimulating immunoglobulin.
  
• Describe the clinical manifestations of Grave’s disease and why this is the outcome of #3.

Immunology Objectives: 30
Cell Mediated Pathology

• Name three autoimmune disorders in which the primary pathology is initiated by cell damage.

Hashimoto’s Thyroiditis

• Hashimoto’s thyroiditis is an autoimmune disorder resulting from cell damage (tissue- thyroid gland).
• Describe how this manifests clinically.
  
• What is the female-male ratio and the age for disease susceptibility?
  
• Laboratory tests that detect autoantibodies can be used for diagnosis. Yet, these antibodies are not the initiating factor in this disease. Explain.

Multiple Sclerosis

• Multiple sclerosis is an autoimmune disorder resulting from cell damage (tissue- brain and spinal cord). Yet, antibodies to myelin basic protein are present even though they are not the initiating factor in the disease. Explain
  
• Oligoclonal antibodies are present in cerebral spinal fluid. They are diagnostic, but are not the initiating factor in the disease. Explain.
  
• Describe the susceptibility to this disease with respect to ethnicity, HLA association, and region from equator.

Ankylosing Spondylitis

• Joints (tissue) are affected. But, this disease differs from rheumatoid arthritis. Describe susceptibility with respect to female-male ratio and HLA association.
  
• Note that there is NO rheumatoid factor!!=

Immunotherapy

• Non-antigen specific: List five non antigen specific immunotherapies and provide specific examples.
  
• Antigen specific: List four antigen-specific immunotherapies and provide specific examples for each.

Immunology Objectives: 31
Immunology Objectives: Immunodeficiency Disorders - Chapter 15

• Explain the difference between primary and secondary immunodeficiency disorders.
  See attached Tables. Learn names of disorders as well as defect and immunological manifestations.

Severe Combined Immunodeficiency Disorder (SCID)

• Explain the defect in (a) SCID and (b) X-SCID. Also explain why these defects lad to dysfunction in both T cell and B cell immunity.

DiGeorge’s Syndrome

• Describe the defect in DiGeorge’s Syndrome. Explain why these individuals are particularly prone to viral and fungal infections.
  
• Explain the treatment for individuals with DiGeorge’s Syndrome.
  
• Under what conditions do patients with DiGeorge’s Syndrome improve with age.

Chronic Granulomatous Disease

• Describe the defect, the cells in which this manifests, and increased susceptibility to microbes.
  
• Describe the immunological and clinical manifestations.

Transient Hypogammaglobulinemia of Infancy

• Describe the clinical manifestations and treatment.
  
• Describe the female/male susceptibility, treatment, and age at which the disorder presents.
  
• Explain why this defect manifests at six months of age and why it improves with age when individuals with XLA do not.

Common Variable Immunodeficiency

• Explain the defect, age of onset, male/female susceptibility, treatments, and clinical manifestations.
  
• Complete the following table.
  • XLA Transient hypogammoglobulinemia of infancy
  • CVI
  • Age onset
  • Defect
  • Male/female susceptibility
  • Clinical manifestation

Immunology Objectives: 32
Selective IgA Dficiency

• Describe the immunological and clinical manifestation and population susceptibility.

Hyper IgM Syndrome

• Explain the genetic defect as well as immunological and clinical manifestations.

Phagocytic Immunodeficiency Disorder

• List 2 primary immunodeficiency disorders that affect phagocytosis. Describe the defect, consequence, and treatment.

Other leukocyte Disorders

• Describe the defect in LAD 1; in LAD2. What is the consequence?

Complement

• Describe the consequences and clinical manifestation of a defect in
  
  • C3
    
  • C5-C9
    
• Explain why a dysfunction in C3 nephritic factor results in unregulated consumption of C3. Describe the clinical manifestation and cause.
  
• Describe the defect in Hereditary Angioneurotic Edema (HANE)/ Hereditary Angioedema (HAE), effect on complement function, and clinical manifestations.
  
• Describe the defect in paroxsymal nocturnal hemoglobulinemia, effect on complement function, and clinical manifestation.

Secondary Immunodeficiency Disorders

• List 4 extrinsic factors that can result in secondary immunodeficiency disorders. Give one or two examples of each category.
  
• Describe multiple myeloma with respect to defect, consequences of serum protein manifestation, and method of detection.
  
• Explain the term “monoclonal gammopathy” and provide an example.
  
• Describe the defect in Waldenstrom’s macroglobulinemia and clinical manifestation.

Immunology Objectives: 33
Human Immunodeficiency Virus

• Describe cells affected, and how the virus is spread.
  
• Name the receptor/coreceptor to which HIV binds.
  
• Explain why this secondary immunodeficiency disorder leads to an increased susceptibility to so many types of infections.

Immunology Objectives: 34
Immunology Objectives Tumor Immunology- Clinical section

Tumor Recognition

• Explain the difference between a tumor specific antigen and a tumor associated antigen.

Tumor Specific Antigens

• List 5 tumor specific antigens and the tumor(s) with which each is associated.

Tumor Associated Antigens

• List three tumor associated antigens and specify the type of tumors each is associated.
  
• List also the normal conditions as well as pathological conditions (aside from tumors) with which each of the tumor associated antigens is linked.
  
• Describe the role of tumor associated antigens in either diagnosis or in monitoring efficacy of treatment or recurrence of tumors.

Immunology in Diagnosis or in Monitoring Prognosis

• Role of tumor specific antigens
  
• Role of Bence Jones Proteins

Novel Therapies for Tumors:

• Role of Chemokines and chemokine receptors
  
• Role of dendritic cells as adjuvants
  
• Fusion of dendritic cells with tumor cells
  
• Role of cytokines-- GM-CSF, IL-2, IFNγ, IL-12
  
• Enhancing expression of Class I MHC
  
• Tumor infiltrating lymphocytes (TILS)
  
• Radiolabeled (or toxin) monoclonal antibodies (purging, idiotypic, modified)

Neoplasms

• Differentiate between Waldenstrom’s macroglobulinemia and multiple myeloma.

Immunology Objectives: 35
Immunology Objectives: Transplantation Chapter 17

• Define; recipient, donor, rejection, host, “host versus graft”disease and “graft versus host” disease.
• Review MHC, HLA, polymorphism, and codominant expression.
• Define “minor histocompatibility proteins” and their potential role in transplant rejection.
• Review the MHC gene locus
• Explain what is meant by tissue compatibility (and incompatibility).
• Explain the principle of each of the following approaches used to determine tissue compatibility.
  • serological
  • mixed lymphocyte reaction
    
  • restriction length polymorphism
    
  • polymerase chain reaction
• Define the following: isograft/autograft, allograft, xenograft.
• Describe 3 types of graft rejection with respect to
  
  • length of time following transplant
    
  • immunological aspects
    
  • treatment
    
  • mechanism of graft destruction
• Describe graft versus host disorder with respect to clinical manifestations and role of immunology.
• Explain what is meant by “ graft rejection displays immunological memory”.
• Surgical and ischemic perfusion occurs when the host receives a transplanted organ.
  
• Explain how this initiates graft rejection.
  
• Describe how chemokines and cytokines alter the vascular endothelial cells.
  
• Review the role of IL-8 and monocyte chemotactic protein.
  
• Describe the role of neutrophils and monocyte in graft rejection.
  
• Explain how chemokines and cytokine in circulation affect circulating leukocytes.
  
• Explain why an increase in vascular permeability is necessary for extravasation of
  neutrophils, monocytes, and T cells into the tissue graft.
• List various types of grafts, their prognosis, and type of complication associated with each.
• Explain- for which grafts is graft versus host a problem. Why?
• Explain the role of T cells in bone marrow transplantation with respect to how they can “help” the engraftment and how they can “hinder’ the engraftment.
• Describe the role of IL-3 and GM-CSF in bone marrow transplant.
• List non specific treatments for immunosuppression in clinical transplantation cases.
• Describe HOW each mediates immunosuppression.
• List complications that often arise from immunosuppressive therapy.
• Describe the role of IL-2 and IFN(Type 1 cytokines) in the differentiation of pre-cytotoxic T cells to mature cytotoxic T cells (CD8+)
• Describe the role of IFNand TNF (Type 1 cytokines) in the activation of phagocytes.
• Describe the role of IL-2 on natural killer cell cytotoxicity.
• Describe the role of CD4+ T cells in B cell activation.
• Describe the role of antibodies in complement activation and the role of complement in graft rejection.