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Immunology lecture 15 16 Immune response to infectious agents


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Why are viruses inaccessible to antibodies and other soluble mediators such as complement
Because they reside within the cytoplasm of infected cells
What is the only way to eliminate a virus from the body
Eliminate the infected cell
Name some important viruses
Hepatitis B, Influenza, Herpes simplex, Cytomegalovirus, Epstein-Barr, Human immunodeficiency
What are the two main innate effector mechanisms that defend the body against viruses
Type 1 interferons; NK cell-mediated killing of infected cells
What cells produce IFN-alpha
mononuclear phagocytes (leukocyte interferon)
What cells produce Interferon-beta
Many cells, including fibroblasts (fibroblast interferon)
When is interferon produced
When viral double-stranded RNA (PAMP) is recognized by a Toll-like receptor
What is the mode of action of interferon
Paracrine. It induces MHC class 1 expression to enhance presentation of viral antigens to CD8 cells. It also induces IL-12 receptor expression by CD4 T cells
How do NK cells mediate killing of infected cells
Many viruses attempt to inhibit MHC class 1 expression by the infected cells. Using inhibitory receptors that recognize MHC class 1, NK cells detect the loss of MHC class 1 expression and become activated
Who are the two main players in adaptive immunity to viruses
Cytotoxic T lymphocytes and Antibodies
What is required for a robust CD8 T cell response
CD4 T cell help
How do cytotoxic T lymphocytes mediate killing of infected cells
They secrete perforin and granzyme and express FasL. They can also cause pathology, as with Hepatitis B
During what viral stage are antibodies effective
Extracellular stages
Which immunoglobulin plays an important role in blocking viral entry at mucosal surfaces
Secretory IgA
How do viruses evade the immune system
Antigenic variation; Inhibition of antigen presentation by MHC class 1; Production of proteins which antagonize immune responses; Target immune system cells
What are some example of intracellular bacteria
Mycobacterium tuberculosis, Mycobacterium leprae, Leigonella pneumophila, Listeria monocytogenes
Who are the three important players in innate immunity to intracellular bacteria
Phagocytes (neutrophils and macrophages); NK cells (important source of IFN-gamma); Cytokines (IL-12, which stimulates production of IFN-gamma by NK cells and development of CD4 Th1)
What role do CD4 T cells play in adaptive immunity to intracellular bacteria
Stimulated to become Th1 by IL-12. Express CD40L and IFN-gamma.
What type of hypersensitivity does macrophage activation by CD4 T cells cause
Delayed type (IV) hypersensitivity
Histologically, what is extensive macrophage activation by CD4 T cells described as
Granulomatous inflammation
What role do Cytotoxic T lymphocytes play in adaptive immunity to intracellular bacteria
Crucial for controlling some intracellular bacterial infections (Listeria monocytogenes) which readily escape from the phagolysosome into the cytoplasm
In humoral immunity to intracellular bacteria, what stimulates B cells to class switch
IFN-gamma produced by CD4 T cells (Th1)
What are some methods of immune evasion by intracellular bacteria
Inhibition of phagolysosome function (M. tuberculosis, L. pneumophila)
Neutralization of ROI (M. leprae)
Escape into cytoplasm (L. monocytogenes)
Who are the important players in adaptive immunity to intracellular bacteria
CD4 T cells (activate macrophages)
CTL (kill the escapees from the phagolysosome)
Humoral immunity (B cell class switching)
How do extracellular bacteria mediate pathology
By inducing inflammation and directly producing toxins that damage host cells and tissues
What are some examples of extracellular bacteria
Meisseria spp.; Eschericia coli; Staphylococcus aureus; Streptococcus pyogenes
What are some common players in innate immunity to extracellular bacteria
Complement, phagocytes, innate response to LPS, Fever/pyrexia, Acute phase reactants
How does complement aid in innate immunity to extracellular bacteria
The alternative pathway of complement activation is directly activated by components of bacterial cell walls, as well as the mannose-binding lectin (MBL) pathway. Complement enhances phagocytosis of bacteria through opsonization, directly mediates bacterial cell lysis by formation of MACs, and generates inflammatory mediators that attract and activate phagocytes
How do phagocytes aid in innate immunity to extracellular bacteria
They express scavenger receptors, complement receptors, and Toll-like receptors that allow them to phagocytose bacteria and become activated to kill
What are the innate responses to LPS
LPS binds to TLR-4, and induces inflammation that both enhances bacterial killing and mediates pathology. LPS has potent effets on macrophage activation, as well as other phagocytes. It can induce cytokine production and the respiratory burst, and cause the "left shift"
What role does fever play in innate immunity to extracellular bacteria
Fever can be helpful in limiting bacteria replication. Pyrogens can be derived from bacteria or may be synthesized by the body
What are acute phase reactants
Serum plasma proteins that serve to protect the body from bacterial infection. They include C-reactive protein, fibrinogen, and serum amyloid A. They are stimulated by cytokines such as TNF, IL-1, and IL-6
In adaptive immunity to extracellular bacteria, what role does humoral immunity play
Antibodies produced by B cells are the primary mechanism of adaptive immunity to extracellular bacteria
What are some complications of immune response to extracellular bacteria
Septic Shock (respiratory distress and decreased liver function); Toxic Shock Syndrome (massive polyclonal activation of CD4 T cells); Rheumatic fever (Type II hypersensitivity); Poststreptococcal glomerulonephritis (antigen deposit in glomeruli)
What are some tactics used by extracellular bacteria to evade the immune system
Antigenic variation; Inhibition of complement activation; Resistance to phagocytosis; Inactivation of ROI
What is unique about fungi
They are opportunistic pathogens, usually causing infections in the immunocompromised
What is the innate immune system response to fungi
Phagocytes, such as neutrophils and macrophages
What is the adaptive immune system response to fungi
Cell mediated immunity, such as granulomatous inflammation
What is the adaptive immune response to protozoa
Cell mediated immunity (Th1 responses) and Humoral immunity (in the extracellular stages)
What is the innate immune response to helminths
There is none
What is the adaptive immune response to helminths
Th2 responses primarily. IL-4 (class switching to IgE) and Il-5 (stimulates eosinophils). Eosinophils use FceR1 to recongize IgE, and release major basic protein. Mast cells and basophils also express FceR1
How do parasites evade the immune system
Antigenic variation and resistant surface coats
What are some complications of immune responses to parasites
Delayed-type hypersensitivity and immune complex deposition

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