Exam Format

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Exam Format

• 100 points - 60 pts mandatory 40 points where 4,
  10 point questions will be chosen
• Some open-ended questions, some short answer.
• Kuby question

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Cytokines

• Terminology
• How do cytokines achieve their effect?
• Radius of action
• Specific cytokines - also Th1 vs Th2 cytokines
• Receptor families
• Regulation of cytokine action

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granuloma formation
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Mucosal Immune System

• Components of the intestinal immune system
• Barrier system
• Innate immune system
• Adaptive immune system
• Antigen transport in the intestine
• IgA
• Commensal bacteria

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Primary ImmunodeficiencyDiseases
Matching
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lymphocytes monocytes DCs microglia
CCR5, CXCR4
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(No Transcript)
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Activated CD4 T cells
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Study Points for Ponzio Lectures

• Cell-mediated immunity
• ? Interactions between Antigen Presenting Cells
  (APC) and T cells, and the sites where these
  interactions occur
• ? Compare and contrast TH subsets and the types
  of immune responses in which they are involved,
  and the mechanisms by which they mediate these
  immune responses
• ? Interactions between TH1 cells and effector
  Cytotoxic T Lymphocytes (CTL)
• ? Interactions between TH1 cells and effector
  macrophages
• ? Mechanisms by which CTL and other cytotoxic
  effector cells kill target cells

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Ponzio, cont.

• Cancer immunology
• ? Various types of tumor-associated antigens, and
  different ways they can be detected to identify
  malignant cells in the body
• ? How T cells recognize tumor-associated antigens
  and are stimulated to become activated, clonally
  expand, and differentiate into effector cells
• ? Ways in which tumor cells avoid detection
  and/or rejection by the immune system
• ? Strategies for cancer immunotherapy that are
  based on our knowledge of how APC process and
  present antigens, and how T cells recognize and
  respond to antigens

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• Transplantation
• Transplantation is the process of transferring
  cells, tissues or organs, called a graft from one
  site to another or from one individual to a
  different individual.
• Graft rejection is an immunological response
  displaying specificity, memory and self-nonself
  recognition.
• Three major types of rejection
• Hyperacute rejection, mediated by preexisting
  recipient (host) antibodies to graft antigens.
• Acute graft rejection, in which TH cells and/or
  cytotoxic T cells mediate tissue damage.
• Chronic rejection, which involves both cellular
  and humoral immune components.
• The immune response to antigens encoded within
  the major histocompatibility complex is the major
  factor in rejection.
• Matching between a recipient and potential graft
  donors is determined by typing blood-group
  antigens and MHC class I and class II tissue
  antigens (tissue typing).
• Host T cells recognize allogeneic MHC molecules
  in two different ways termed direct and indirect
  presentation.
• Direct presentation occurs when host T cells bind
  directly to intact allogeneic MHC molecules on
  graft antigen presenting cells.
• Indirect presentation occurs when allogeneic MHC
  molecules from the graft cells are taken up,
  processed by host antigen presenting cells and
  presented as peptide fragments by self-MHC.

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• Neuroimmunology
• Neuroimmunology is the biomedical discipline that
  centers on the bidirectional communication
  between the central nervous system (CNS) and the
  immune system.
• CNS can affect the immune system via the
  autonomic outflow or the neuroendocrine outflow.
• Autonomic nervous system controls independent
  activities such as blood circulation, eyelid
  blinking and one component is the sympathetic
  (noradrenergic) system.
• Sympathetic nerve fibers innervate primary
  (thymus bone marrow) and secondary (lymph node
  spleen) lymphoid organs.
• Norepinephrine is the neurotransmitter released
  by the sympathetic nerve fibers and receptors for
  norephinephrine are found on various cells of the
  immune system.
• Norepinephrine has numerous effects on the immune
  system.
• Hypothalamic-pituitary-adrenal (HPA) axis- brain
  stimulation results in increased IL-1 that
  triigers releae of corticotrophin releasing
  hormone that acts on the anterior lobe of the
  pituitary gland. Adrenocorticotropin (ACTH) is
  released by the pituitary and induces the release
  from the adrenal gland of corticosteroids which
  suppress the immune system.
• Cytokines such as IL-1, IL-2, TGF-ß and IFNs
  exert various affects on the central nervous
  system such as induce fever, stimulate
  proliferation of astrocytes, and foster neural
  differentiation.
• Brain is an immunologically privileged site.
  Immune privilege is an active process associated
  with antigen-specific suppression of
  cell-mediated and humoral immunity.
• An important aspect of the neuroimmune axis is
  its relationship to diseases.
• Immune system is involved in the pathogenesis of
  numerous diseases of the central and peripheral
  nervous system, such as multiple sclerosis,
  Guilllain-Barre syndrome, myasthenia gravis.
• Multiple sclerosis (MS) is an inflammatory,
  demyelinating disease affecting the myelin
  sheaths surrounding nerve fibers and nerve axons.
  Genetic, environmental and autoimmune factors
  play a role in the pathogenesis of this disease.
  Studies from the animal model experimental
  autoimmune encephalomyelitis (EAE) suggest that
  Th1 and Th17 cytokines are critical mediators of
  the inflammation and that antibodies also play a
  role. The class II HLA alleles, DR15, DQ1 are
  the most consistently identified genes.
  Interferon-ß is one FDA approved therapy for MS.
• Myastenia gravis is a disease that affects the
  neuromuscular junction causing weakness of
  voluntary muscles eye closure, face, chewing,
  swallowing. The target autoantigen is the
  nicotinic acetylcholine receptor (AChR) and
  antibodies to this receptor are found in about
  90 of patients.
• Guillian-Barre syndrome is an acute demyelinating
  disease of the peripheral nervous system.
  Numerous viruses and bacteria are implicated with
  the onset of disease. This disease is believed to
  be primarily antibody mediated.

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Fitzgerald-Bocarsly - Immunity to Infectious
Diseases

• Mechanisms of host defense to different pathogens
• Bacteria, viruses, parasites be fluent with the
  mechanisms if I stressed them
• Pathways to get CD4 activation vs. CD8
• Cytosolic vs. endosome-expressed antigens
• The presence of an immune response does not
  always protection
• Th1 vs. Th2 responses
• What are Th1 vs. Th2 cells? What do they do and
  what do they make? In what systems is one more
  important than the others?
• Host evasion strategies
• Infectious organisms put a lot of their energy
  into evading the immune response
• Antigenic variation - examples
• Immunosuppressive cytokines
• Inhibition of antigen presentation to CD8s (many
  viruses)
• Decoy receptors
• Immunopathology what is it and when does it
  occur?

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Vaccines and Immunotherapy

• Distinguish passive and active therapy
• Passive immunotherapy (mostly Ab, but could be
  cells) is given for immediate protection
• Quick acting
• Short-lived
• May be used acutely for known exposure or a
  prophylaxis (e.g. to patients with a known Ig
  immunodeficiency)
• Active immunization
• Immunize to get to a primary, then secondary
  response and memory
• Type of vaccine can determine type of immune
  response
• Immunotherapy
• Cytokines
• Antibodies to block function of cytokines,
  receptors

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Types of Vaccines

• Do we want CTL?
• Then we have to get the antigen into the
  endogenous processing pathway (cytoplasm to
  proteasome to TAP to ER to MHC I to surface)
• Live vaccine that can infect cells - attentuation
• Viral vectors
• DNA vaccine that gets genes products expressed in
  the cytoplasm
• Other strategies such as liposomes, ISCOMs
• Do we want CD4 help and antibody?
• Then we need to get antigen into the endosomal
  pathway and processed and presented with MHC
  Class II
• Subunit vaccines
• Recombinant protein vaccines
• Killed vaccines
• Toxoids
• Conjugate vaccines

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Other vaccine issues

• What diseases is it reasonable to hope to
  eradicate?
• Role of non-human hosts, whether the virus
  integrates,relative infectivity (higher
  infectivity means more of the herd needs to be
  immunized)
• Adjuvants
• Compliance
• Can we make therapeutic vaccines?
• KUBY QUESTION from chapters assigned to my
  lectures (Chapters 18,19)

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Mechanisms Leading to Autoimmunity
No Central Tolerance
Self-reactive TH
Infectious Agent
Decreased Tregs