Immunology and Immnosuppression

• Overview of the immune system
• Immune system components
• Barriers: Skin. Gut and respiratory tract
• Innate/ Natural
• Adaptive/ Acquired
• Innate immunity
• Acute-phase response
• Cytokines: IL. TNF
• Proteins: C3. Serum amyloid P component, CRP, Mannose-binding lectin, Lysozyme, Soluble CD14
• Autoimmune diseases
• Toll-like receptors (TLR)
• Bacterial: Lipopeptides, flagellin, hypomethylated DNA.
• Fungal: Zymozan
• Viral: Single-stranded or double stranded viral RNA)
• Local inflammatory response
• Dilatation & increased permeability of microscopic vessels
• Endothelial activation ￫ Adhesion of white blood cells
• Atraction & activation of phagocytic cells: Neutrophils & mononuclear cells
• Adaptive immunity
• Humoral immunity: Complement system, antibodies
• Cellular immunity: T-Lymphocytes
• Anatomy of the adaptive immune system
• Stem cells of bone marrow ￫ red cells, leucocytes, B cells 
• Thymus ￫ T cells
• Lymph nodes, Spleen, Mucosal-associated lymphoid tissue (MALT)
• B cells
• Antigen ￫ B cells + T helper cells ￫ Immune response ￫ Immunoglobulin production IgM IgG
• T cells
• Receptors + HLA
• Impaired regulation of the immune response: clinical examples
• Clonal disorder
• Multiple myeloma
• Paroxyamal nosturnal haemoglobinuria (PNH): DAF, CD59
• Autoimmunity
• Autoantibodies
• The major histocompatibility complex, antigen presentation and transplantation
• Major histocompatibility complex (MHC)
• Class I & II molecules encoded in HLA region present antigen to T cells
• In mice
• MHC
• Chromosomal region. Encode molecules for foreign tissue rejection
• In human
• Chromosome 6. Human leucocyte antigen (HLA)
• Classes I & II important in 
• Antigen presentation to T cells
• Tissue compatibility for transplantation
• Class III
• Complement proteins. GEnes for tumour necrosis factor (TNF)
• MHC and associated diseases
• Class I
• HLA-B27
• Ankylosing spondylosis, reactive arthitis, psoriatic arthropathy, reiter's syndrome
• HLA-CW6
• Psoriasis
• Class II
• HLA-B8-DR3
• Systemic lpus erythematosus, Addison's disease, Graves' disease, coeliac disease, type 1 diabetes
• HLA-DR4
• Rheumatoid arthritis
• HLA-DR2
• Multiple sclerosis
• Antigen presentation
• B cells recognises soluble antigen
• T cells
• Antigen ￫ Peptides presented by Class I or II on APC
• Class I + peptides from endogenous protein + CD8-positive cytotoxic T cells
• Class II + peptides from exogenous protein + CD4-positive T-helper cells
• Transplantation
• Pathways of immune recognition after transplantation
• Direct pathway: Donor MHC molecules and peptides
• Indirect recognition: MHC on host APC. Exogenous antigen from transplant
• Effector mechanisms of rejection
• Humoral machanisms
• Antibody. Complement activation. Thrombosis. Ischaemia
• Avoided by vitro cross-match
• Cell-mediated mechanisms
• Delayed-type hypersensitivity. CD4. Macrophages. Cytotoxic effects CD8 T cells, natural killer (NK) cells
• Inhibit T cell mediated rejection: Ciclosporin. Tacrolimus
• Chronic rejection
• Obliterative vascular changes
• Immunosuppression
• Xenotransplantation
• Pig kidneys.
• Hyperacute rejection. Complement-dependent. Antibodies to galactose-[1,3]-galactose
• Porcine infectious agents
• T Cells
• T cell receptors
• T cell functions
• T helper cells
• Cytotoxic T cells
• Natural killer T cells
• Regulatory T cells
• Gamm Delta T cells
• Helper cell differentiation
• T-cell development
• Activation of T cells
• Memory cells
• T cell immunodeficiencies: clinical example
• B cells
• Antibody structure and function
• Early development
• T cell dependent and T cell independent responses
• Primary response
• Antibody production and class switching
• Affinity maturation
• Generation of memory cells
• Regulation of B cell activation
• B cell immunodeficiency disorders: clinical examples
• x-linked agammaglobulinaemia 
• Selective IgA deficiency
• Tolerance and autoimmunity
• Mechanisms that maintain tolerance
• Mechanisms of loss of tolerance
• Polyclonal B-cell activation
• Cross-reactivity
• Exposure to previously sequestrated antigens
• Modification of self-antigen
• Autoimmune diseases: clinical examples
• Systemic diseases
• Organ specific diseases
• Complement
• Complement system
• Activation of the complement system
• Functions and regulation of the complement system
• Complement deficiencies: clinical examples
• Inflammation
• Mast cells
• Cell migration
• Adhesion molecules
• Chemokines
• Phagocyte effector functions
• Opsonisation
• Intracellular killing
• Neutrophils
• Macrophages
• Inflammation: clinical examples 
• Increased inflammation
• Familial Mediterranean fever
• Secondary amyloid
• Defective inflammation
• Leucocyte adhesion deficiency
• Chronic granulomatous disease
• Anti-inflammatory therapy
• Non-steroidal anti-inflammatory drugs
• Corticosteroids
• Novel agents
• Immunosuppressive therapy
• Corticosteroids
• Effect on neutrophils
• Effect on lymphocytes and monocytes
• Efects on NF-kB
• Corticosteroid use
• Cytotoxic drugs
• Cytotoxic drug use
• Inhibition of primary response
• Differentiated effect on lymphocytes
• Non-specificity
• Ciclosporin and related compounds
• Therapeutic antibodies or soluble ligands/ receptors
• Agents acting on lymphocytes 
• Anticytokine agents
• Therapeutic antibodies in oncology
• Drug combinations
• The future