Host defense Flashcards
What are the five types of pathogens that can invade the body?
- Extracellular bacteria
- Intracellular bacteria
- viruses
- Fungi
- Parasites
In addition to invading the host, causing damage, and colonizing, what must a microbe do to cause disease?
Evade the immune system
Why would an antibody response to an intravellular bacteria be ineffective?
Antibodies cannot penetrate cells
What are the two major mechanisms by which extracellular bacteria mediate tissue damage?
Generate inflammation
Release toxins
What is the first line of defense against invading microbes
Phagocytosis
What are the two ways in which complement can act to aid in the destruction of microbes?
Opsonize
Directly lyse
What is the component of the bacteria cell wall in gram positive bacteria? Gram negative?
Gram positive = peptidoglycan
Gram negative = lipopolysaccharide
What is the principle protective response (protects against developing the disease at all)?
Humoral immunity
Which class of antibodies opsonize microbes?
IgG
What are the two types of antibodies that can activate the complement pathway?
IgM and IgG
Which is the antibody that is found in the primary reaction? Secondary?
Primary = IgM Secondary = IgG
What is the chemical secreted by helper T cells that assist in B cell-mediated humoral immunity, and is the most potent activator of macrophages?
interferon-gamma.
What is the effect of the bacteria polysaccharide capsule that some bacteria are able to produce?
Resist phagocytosis and may inhibit complement activation
What is the effect of genetic variation seen in the surface antigens of bacteria?
Constantly change targets
What is the bacteria type that mediates septic shock?
Gram negative
What are the cytokines release by the body that induce septic shock?
IL-1 and TNF
What are superantigens?
Toxins that bind to class II MHC proteins, and activate T cells to produce TNF
What are the genes that an individual must express in order to be susceptible to superantigens?
V[alpha] or V[beta] regions in the variable chain of the TCR
What causes the carditis seen in rheumatic fever?
Cross reactive antibodies
What else besides carditis can rheumatic fever cause? What causes this?
Poststreptococcal glomerulo-nephritis, caused by immune complexes lodging in the kidneys
What are the two types of bacteria discussed in class that thrive in phagocytic cells?
Listeria and mycobacteria
What is the mechanism by which listeria evades death in phagocytes?
Disrupts phagosome and escapes into the cytoplasm
What is the mechanism by which mycobacterium escapes death in the phagosome?
Inhibits the fusion of phagosome and lysosomes
What happens when listeria escapes into the cytoplasm of a phagosome?
CTLs will kill when seen through MHC class I
If the innate immunity is ineffective agaisnt intracellular bacteria, what cells will get rid of these bacteria?
NK cells
Macrophages need NK cells to stimulate them to get rid of persistent bacteria in their cytoplasm. What chemical do they release to activate NK cells? What do the NK cells release in return?
IL-12 release by macrophages
NK cells produce interferion gamma
How effective is interferon gamma at inducing macrophages to kill microorganisms in their cytoplasm?
Only partially
What is a granuloma?
A clump of macrophages surrounded by fibroblasts and Th cells
What is the mechanism whereby microorganisms in the cytoplasm of phagosomes induce CTLs to kill the macrophage? What happens if the microorgamism down regulates this?
MHC class I expression
If down regulated, then NK cells will kill d/t lack of self antigen
What is the cytopathic effect?
The process by which viruses destroy an infected cell once through with using it to reproduce
Most viruses down-regulate the production of class I MHC expression. What is the effect of this?
NK cells are released from their normal state of inhibition by the absence of class I MHC proteins (also helped by interferon)
When is humoral immunity important EARLY in a viral infection?
i.f.f. the host has pre-existing antibodies
What are the three routes by which antibodies help to rid the body of microorganisms?
- Bind to virus and neutralize
- Bind an opsonize
- Activate complement
When are antibodies not useful?
When the microorganism is inside a cell. Only after virus lyses cell.
What are the principal protective immune components/cells during ESTABLISHED virus infections? Why?
Cytotoxic T lymphocytes because they can lyse virus infected cells before the virus has a chance to complete its replicative process
What is the mechanism by which CTLs are induced to kill cells?
When virus bits presented on MHC class I proteins
What are the three ways in which viruses can evade the immune system?
- Alter their antigens
- prevent class I MHC
- Kill CD4+ T cells (HIV)
If a virus downregulates MHC class I presentation, what will still kill the cell? Why?
NK cells, because they need to see MHC class I self peptides to not kill
What are the two processes through which viruses indirectly cause damage through the response they effect?
CTLs cause pathological lesions (hep B in liver)
Molecular mimicry
What is molecular mimicry?
Theoretical instance whereby a virus expresses proteins similar to that of its host, causing a deleterious immune response on self tissues
What are the two effects of type 1 IFN (interferion-alpha)?
- Upregulates MHC class I
2. Activates NK cells
Why are fungal infections on the rise?
Increased number of immunosuppressed patients (chemotherapy, HIV etc).
Where do fungi proliferate?
Inside phagocytic cells and in EC tissue
What are the principle mediators of the innate immune response against fungi?
Neutrophils
Which is more effective at eliminating fungi, Th1 or Th2 responses?
Th1
What feature of the outer layer of helminths confers resistance to the innate immune system?
Will bind complement, but is resistant to its effects
Also resistant to PMNs and mcrophages d/t thick teguments
Parasites that survive in phagocytes activate what immune response?
Th1
Helminthic (or other worm) infestations induce what type of response?
IgE + eosinophils (Th2).
[IgE binds to parasite, ADCC doneby eosinophils]
What is the immune response to plasmodium?
TH1 mediate CTLs
What is the immune response to protazoa that survive withi macrophages?
CD4+ to interferon gamma to activate macrophages