Download Notes on Acquired Immunity

Immunology: Acquired Immunity to Infection/Cell Mediated Immunity (Kong)
ACQUIRED IMMUNITY (GENERAL):

Need for Acquired Immunity:
Microorganisms can evade innate defenses
o Some fail to activate alternative complement pathway
o Capsules around some bacteria prevent phagocytosis
o Some produce toxins to kill phagocytic cells
o Some phagocytized microbes can evade lytic mechanisms, and go onto survive intracellularly
Innate defenses can become compromised
o Loss of skin (burn patient)
o Cilia in respiratory tracts ineffective (smokers)

Advantages of Acquired Immunity:
Specificity
Immunologic memory (quicker/stronger response on 2nd encounter)

Two Forms of Acquired Immunity:
1. Humoral: antibody mediated (produced by B cells); generally protect against extracellular microbes

Extracellular Microbes:
 Interstitial spaces, blood, lymph: complement, phagocytosis, Abs
 Epithelial surfaces (ie. Neisseria gonorrhoeae): antimicrobial peptides, Abs (IgA)
2. Cellular: T cell mediated ; generally protected against intracellular microbes

Intracellular Microbes:
 Cytoplasmic: NK cells, CD8+ T cells
 Vesicular (ie. mycobacteria, listeria): T cell and NK cell dependent macrophage
activation

Experiment to Determine Protective Mechanisms:
Protocol: mouse infected with nonlethal dose of tubercule bacilli; 6 weeks after infection the following is done to
mice of the same inbred strain:
o Mouse A receives serum from infected mouse
o Mouse B receives macrophages
o Mouse C receives lymphocytes
Each of the recipient mice is then infected with the same tubercule bacilli + listeria
Results:
o Mouse A and B become infected with both agents; Mouse C does not (immune to tubercule bacilli)
o Mouse C is also resistant to listeria because T cells specific for the tubercule bacilli activate
macrophages that mediate resistance to listeria as well (macrophage killing is NOT specific)
o However, if infected with listeria alone, Mouse C would become infected (as would Mouse A and B)
PROTECTIVE MECHANISMS OF ANTIBODIES (HUMORAL IMMUNITY):

Elimination of extracellular antigen

Steps:
B cell activation by antigen and helper T cells
Antibody secretion by plasma cells, leading to:
o Neutralization (antibody binds bacteria, preventing adherence)
o Opsonization (antibody promotes phagocytosis)
o Complement activation (antibody activates complement, which enhances opsonization and lyses some
bacteria)
PROTECTIVE MECHANISMS OF T CELL-MEDIATED IMMUNITY:

Active TH1 Cells:
Have high affinity IL-2 receptors and secrete IL-2 (autocrine driven proliferation)
Some activated TH1 cells become memory cells (long-lived)
Sensitized TH1 cells that activated by an infected APC release cytokines and express several markers:
o IFNγ and CD40L: activate macrophages to destroy engulfed bacteria ; IFNγ increases B7 expression and
class II MHC (increases capacity to present Ag to naïve CD4+ cells)
o Fas Ligand: kills chronically infected macrophages (Fas+), releasing bacteria to be destroyed by fresh
macrophages
o IL-2: cell proliferation
o IL-3 and GM-CSF: macrophage differentiation in bone marrow
o TNFα and TNFβ (Lymphotoxin): promotes diapedesis of fresh macrophages to site of infection
o CCL2 (MCP-1): migration of macrophages to site of infection

Activation of Macrophages:
Activation by TH1 cells also allows them to eliminate intracellular microbes efficiently
o Macrophage presents Ag to TH1 cell on MHC class II (binds TCR + CD4)
o CD40L on T cell binds CD40 on macrophage; IFNγ released from T cells binds its receptor on
macrophage

Upregulation of B7 and class II MHC (allows for presentation to more TH1 cells
o Activated macrophages produce free radicals (NO, superoxide), which are microbicidal and kill
intracellular organisms (non-specific)
Macrophage is not necessarily killed during this process (can return to resting stage)

Granulomas:
Form when intracellular organisms cannot be totally eliminated
Macrophages will fuse to form giant cells around infected macrophages; epithelial cells and T cells surround this
central core
Remain dormant for years with viable organisms inside (can be reactivated upon immunosuppression or trauma)
Can lead to loss of organ function (ie. mycobacteria in the lung)
PROTECTIVE MECHANISMS OF CD8+ CYTOTOXIC T CELLS:

Elimination of cells infected with intracellular viruses and bacteria.

Steps:
Specific C8+ T cell precursor encounters virally infected APC
Viral Ag presented on surface of APC with MHC class I (provides 1st signal by triggering TCR)
Costimulatory molecules on APC (B7) provide necessary 2nd signal for activation of naïve CD8+ T cell
Activated CD8+ T cell secretes IL-2, develops high affinity IL-2R, and promotes CD8 cell proliferation
Mature activated CD8 cells now encounter cells infected by the same virus, and only require 1 signal (recognition
of viral peptide-MHC class I) to induce lytic process

Lytic Process:
CD8 cells can kill virally infected cells/tumor cells with no effect on adjacent normal cells
Cytotoxic proteins store in granules a polarized fashion
o Perforin: aids in delivering contents of granules into target cell
o Granzymes: serine proteases; activate apoptosis in target cell
o Granulysin: antimicrobial actions; can induce apoptosis
Lysis primarily mediated by perforin (holes in target cell) and granzymes (apoptosis)
CD8 T cells engage target cells, align microtubules and Golgi, and then deliver lytic granules onto target cell
o Initial interactions held together by adhesion molecules present on all cells (nonspecific)
o Cytoskeletal/cytoplasmic rearrangement occurs next as a result of specific recognition
o Preformed granules then released onto target cell
INFECTIOUS ORGANISMS HAVE DEVELOPED WAYS TO EVADE CONTROL:

Anatomic Location: echinococcus (tapeworm) exists in hydatid cysts

Antigenic Change: influenza, HIV
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Immunosuppression and Antigenic Change: HIV