Immunology

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Immunology

• Wednesday, August 13

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Host Defense

• The immune system fights against
• Invading pathogens
• Viruses and bacteria
• Foreign substances
• Abnormal cells
• Cancer
• Failure of the immune system
• Autoimmunity
• Allergy and hypersensitivity

Figure 43.0 Specialized lymphocytes attacking a
cancer cell
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Figure 43.1 An overview of the body's defenses
Innate immune responses
Adaptive immune responses
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Figure 43.2 First-line respiratory defenses
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Figure 43.4 The human lymphatic system
Lymph passes through lymphnodes where it
encounters immune cells
Lymph flows from tissues through lymphatic
vessels returning to the blood
Green immune cell development Pink trap
pathogens
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Cells of the Immune System

• Innate immune cells
• Phagocytes
• Macrophages and neutrophils
• Natural killer cells
• Eosinophils and basophils
• Mast cells
• Adaptive immune cells
• Lymphocytes
• B cells and T cells

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Cell Development
Bone marrow
Stem cell
Lymphoid progenitor
Myeloid progenitor
Megakaryocyte
Erythroblast
Blood
RBC
Platelets
B cell
T cell
Neutrophil Eosinophil Basophil Monocyte
Macrophage
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Innate Immunity

• Phagocytes
• Macrophages and neutrophils
• Bind to bacterial surface proteins
• Engulf bacteria
• Secrete cytokines
• Initiates inflammation
• Inflammatory Response
• Heat, pain, redness, and swelling
• Attracts immune cells to the site of infection

Figure 43.3 Phagocytosis by a macrophage
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Figure 43.5 A simplified view of the
inflammatory response

• Infection by bacteria release of chemical
  signals
• Blood vessels dilate, increasing blood flow
• Chemokines attract phagocytic cells
• Phagocytes consume pathogens and cell debris

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Cell Functions
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Figure 43.17 Classical complement pathway

• Complement set of 20 serum proteins involved in
  a cascade that leads to the lysis of a target
  cell
• Complement binds to antibody bound pathogen
• Form a membrane attack complex (MAC)
• MAC pores in the pathogens membrane causes cell
  lysis

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Adaptive Immunity

• Lymphocytes provide efficient and selective
  defense against specific pathogens
• Specificity lymphocytes respond to particular
  foreign molecules
• Diversity lymphocytes can responds to many
  different foreign molecules
• Antigens bacteria, virus, fungi, protozoa, worms

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Lymphocytes

• Lymphocytes types
• B cells
• produce antibodies (Ab) bind and target antigen
  for destruction
• T cells
• CD4 cells helper T cells
• Provide help to B cells
• CD8 cells cytotoxic T cells
• Lysis of infected target cells

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Figure 43.8x B lymphocyte
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Antigen Recognition

• Lymphocytes recognize specific antigen through
  receptor on their surface
• B cell receptor (BCR) membrane bound Ab
• T cell receptor (TCR)
• Many different receptor are produced by genetic
  recombination giving lymphocytes the capacity to
  respond to millions of different antigen molecules

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Figure 43.8 The development of lymphocytes

• How do lymphocyte receptors develop that only
  recognition foreign antigen (nonself) and not
  react to self components
• Self-tolerance as lymphocyte development, cells
  that are reactive to self are deleted leaving
  only cells that react to foreign antigen
• Failure of this mechanims results in autoimmunity
• Attack by the immune system of self tissues

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Antigen Presentation

• Lymphocyte receptors recognize antigen fragments
  presented by cells on MHC (major
  histocompatibility complex) molecules
• MHC class I found on all nucleated cells
• presents foreign antigen within infected cells
• Recognized by CD8 T cells
• MHC II found on antigen presenting cells
• Macrophages and B cells are professional APCs
  that take up foreign antigen in the environment
  and present it to lymphocytes
• Recognized by CD4 T cells

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Figure 43.9 The interaction of T cells with MHC
molecules
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Antigen Response

• Interaction of lymphocyte with the specific
  antigen it recognizes stimulates it to divide and
  differentiate
• Effector cells production of many short lived
  cells with identical specificity that fight the
  antigen
• Memory cells production of long lived cells
  with the same specific receptor that allow for
  faster, more efficient response if the antigen is
  encountered again
• Property that is the basis of vaccines

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Figure 43.6 Clonal selection
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Figure 43.7 Immunological memory
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Immune Reponses

• Cell Mediated Immune Repsonse
• Cells involved
• CD8 CTLs target and lysis infected cells
• CD4 T cells help to activate CTLs
• Antigens involved
• Intracellular bacteria and viruses
• Fungi, protozoa and parasitic worms
• Humoral Immune Response
• Cells involved
• B cell production of antibodies
• CD4 T cell help to activate B cells
• Antigens involved
• Extracellular bacteria, toxins, viruses in body
  fluids

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Figure 43.10 An overview of the immune responses
An APC (macrophage) presents engulf antigen to
CD4 helper cells via MHC II molecules Helper T
cells are central in connect the two arms of the
immune response
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Figure 43.10 An overview of the immune responses
Humoral response results from the activation of B
cells directly by free antigen and indirectly by
stimulating cytokines secreted by helper T
cells B cells develop into plasma cells which
secrete antibody
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Figure 43.10 An overview of the immune responses
Cell mediated immunity results from the
activation of CTLs directly through antigen
displayed on infected cells via MHC I and
indirectly by helper T cells Activated CTLs lyse
infected cells
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Figure 43.10 An overview of the immune responses
Secondary response occurs faster through memory
cells
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Figure 43.11 The central role of helper T cells
a closer look
CD4 cell is activated by binding antigen display
by MHC II on an APC that has engulfed a pathogen
Cytokines further stimulate CD4 cells and help
activate B cell and CTLs
Activated CD4 secretes cytokines
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Figure 43.12a The functioning of cytotoxic T
cells
Activated CTL discharges perforin which create
pores in the infected cell membrane
CTL is activated by binding antigen display by
MHC I on an infected cell
Water flows into the cell through the pore and
the cell is lysed
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Figure 43.12b A cytotoxic T cell has lysed a
cancer cell
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Figure 43.13 Humoral response to a T-dependent
antigen
An APC engulf a pathogen and displays antigen
bound by MHC II molecules that are transported to
the cell surface
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Figure 43.13 Humoral response to a T-dependent
antigen
A helper T cell with a receptor specific for the
antigen-MHC II complex is activated to
proliferate and secrete cytokines
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Figure 43.13 Humoral response to a T-dependent
antigen
A B cell APC also engulfs a pathogen and displays
antigen bound by MHC II Activated helper T cells
recognize and bind this B cell and secretes
cytokines to activated it
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Figure 43.13 Humoral response to a T-dependent
antigen
Activated B cell proliferates into plasma cells
that secrete antibody specific for pathogen and
memory cells
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Figure 43.14 Epitopes (antigenic determinants)
Different antibody molecules react with different
epitopes on the same large antigen molecules
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Figure 43.15a,b The structure of a typical
antibody molecule
Diversity in antibody molecules allowing response
to many different pathogens results from genetic
recombination for form the variable regions
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Figure 43.15c Antibody molecule
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Table 43.1 The Five Classes of Immunoglobulins
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Figure 43.16 Effector mechanisms of humoral
immunity
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Immunity in Health

• Active immunity
• Naturally acquired chicken pox
• Artificially acquired vaccination
• Passive immunity
• Transfer of Abs pregnancy (IgA)
• Transplantation blood transfusion, tissue
  grafts, and organ transplants
• Ability of the immune system to recognize nonself
  results in destruction of incompatible cells from
  other individuals

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Immunity in Disease

• Abnormal immune function can lead to disease
• Allergy hypersensitive reactions to certain
  environmental antigens
• Autoimmunity loss of tolerance to self results
  in response against self molecules
• Lupus (SLE) Ab are generated that react against
  self
• Immunodeficiency
• Innate genetic disorders SCID
• Acquired disorders cancers, AIDS

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Figure 43.18 Mast cells, IgE, and the allergic
response

• A B cell encounters an allergen and is activated
  to secrete IgE specific for the allergen
• IgE bind to mast cell
• Allergen binds to IgE on mast cells triggering
  degranulation
• Granules release histamine and other inflammatory
  agents

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Immunity in Disease

• Abnormal immune function can lead to disease
• Allergy hypersensitive reactions to certain
  environmental antigens
• Autoimmunity loss of tolerance to self results
  in response against self molecules
• Lupus (SLE) Ab are generated that react against
  self
• Immunodeficiency
• Innate genetic disorders SCID
• Acquired disorders cancers, AIDS