Immunology: 3 Flashcards
Which cell is this?
Macrophage
Explain innate immunity with the most important cells and receptors involved.
rapid, non specific, no memory
PAMPs and DAMPs –> pattern recognition receptors of macrophages, dendritic cells and mast cells
most important pathway: –> CD14/TLR on macrophages –> NFkB –> proinflammlatory cytokins:
- Il 1
- Il-6: increased production of acute phase proteins by hepatcytes, SAA, C-reactive Protein, complement proteins,…
- TNF-Alpha
- Platelet Derived Growth Factor
OR/AND binding of viral PAMPs to RIG-1->>generation of type I interferons in case of viral infections
What are opsonins?
antibodies or other substances binding to foreign microorganisms or cells makin gthem more susceptible to phagocytosis
Main products of mastcells?
histamine
leucotrines
prostaglandin
Where are leucocytes produced? Guyton 455
bone marrow: granulocytes and monocytes
lymph tissue: lymphocytes and plasma cells
Name the 6 types of leucocytes. Guyton 455
neutrophils (62%)
eosinophils (2.3)
basophils (0.4)
monocytes (5.3)
lymphocytes (30)
plasma cells
What are granulocytes?
What is their lifespan?
polymorphnuclear cells (neutros, eos, basos)
bone marrow –> 4-8hrs circulating in the blood –> 4-5 days in tissues –> death
Which two major lineages of WBC are formed?
myelocytic (myeloblast) –> granulocytes, monocytes, (megacaryocytes)
lymphocytic (lymphoblast) –> lymphocytes
What is the reticuloendothelial system?
monocyte-macrophage system
microbiome in the stomach and duodenum?
stomach: A dense population of gram-positive bacterial rods, primarily composed of Lactobacillus spp., colonizes the nonsquamous portion of the equine stomach.
duodenum: large population of proteolytic bacteria, and this colonization increases bytenfold in the ileum.
Physiologic skin inhabitants
Normal inhabitants include mixed populations of bacteria of species of Acinetobacter, Aerococcus, Aeromonas, Bacillus, Corynebacterium, Flavobacterium,
Micrococcus, Nocardia, coagulase-negative Staphylococcus, Staphylococcus aureus, Streptomyces, and nonhemolytic Streptococcus generae.
30 species of fungi can inhabit the skin and Alternaria, Aspergillus, Candida, Fusarium, Rhizopus, and Trichophyton spp., Malassezia are commonly present.
Bacterial flora in the large intestine
the predominant flora are the low guanine-cytosine (GC)-content bacteria, which include Cytophaga-Flexibacter-Bacteroides and Clostridium bacteria;
Standard microbiologic techniques specifically demonstrate Enterobacteriaceae,
Butyrivibrio spp., Streptococcus spp., Bacteroides spp., Lactobacillus spp., Selenomonas spp., Eubacterium spp., Propionibacterium spp., and Staphylococcus spp. in residence.
Rapid change from a roughage diet to concentrate results in ?
Rapid change from a roughage diet to concentrate results in
- increased anaerobes,
- decreased cellulolytic bacteria,
- decreased cecal protozoa diversity, and
- decreased pH in the equine cecum.
Which are the most frequent and prolific colonizers of the trachea after prolonged head elevation?
Pasteurella,
Actinobacillus, and
Streptococcus spp.
are the most frequent and prolific colonizers of the trachea after prolonged head elevation.
What are protein secretion systems?
Protein secretion systems (PSSs) are a structurally diverse complex of essential virulence factors for bacteria that allow specialized interactions among cells.
These main systems function to translocate various sized molecules and are important in the formation of adhesins on attachment to host cells.
Which are the most important PSS subgroups?
Fibrillar adhesins (FAs) and
nonfibrillar adhesins (NFAs)
What is the primary clinical significance of enveloped versus non-envelopped viruses?
The primary clinical significance of these features is that enveloped viruses, because of their fragile lipid membrane, are highly susceptible to inactivation by heat, desiccation, or detergents, and transmission typically requires direct exchange of body fluids, short distance aerosols, or arthropod vectors.
In contrast, nonenveloped viruses (e.g., equine rotavirus) are resistant to physical inactivation, and environmental contamination is more likely to be a significant factor in their transmission.
Basic structure of a virus?
DNA or RNA genome enclosed by a coat of protein called the capsid
For viruses that are enveloped, the capsid is enclosed further by a host cell–derived lipid membrane into which viral proteins have been incorporated.
What are retroviruses?
Retroviruses are a subset of single-stranded, positive-polarity RNA viruses that use their RNA genomes as templates to produce double-stranded DNA,
which in turn is used for the transcription of mRNA and new
viral genomes.
ssRNA enveloped viruses?
Coronaviridae Paramyxoviridae Bunyaviridae Toroviridae
Orthomyxoviridae Arenaviridae Togaviridae Flaviridae
Retroviridae Rhabdoviridae
Filoviridae
dsDNA enveloped viruses
Herpesviridae
Poxviridae, Chordopoxviridae
Hepadnaviridae
dsDNA non-enveloped viruses?
Iridoviridae
Adenoviridae
Polyomaviridae
What are viral inclusion bodies?
RNA viruses typically replicate, transcribe mRNA, and translate viral proteins in the cytoplasm. These sites of replication account, respectively, for the location of viral inclusion bodies that are diagnostically useful in histopathologic sections.
Define virologic latency and give an example
Virologic latency is defined as the presence of a viral genome that is not producing infectious virus.
The genomes of latent viruses are transcriptionally suppressed and trans-
lationally silent so that no viral proteins are expressed that may identify the cell to the immune system as infected.
The classic latent infection is that of the herpesviruses. For the α-herpesviruses, such as EHV1 and EHV4, latent infections are established in the nuclei of
sensory neurons and can be maintained indefinitely, and infected animals serve as the reservoir of the virus. On reactivation viral nucleic acids are translocated across synapses to epithelial cells of the nasopharynx, which produce infectious virus. The stimuli that induce reactivation are poorly defined, but reactivation can be induced by immunosuppression (e.g., corticosteroids) and presumably by other stressors, such as pregnancy, transport, and social stress.
Meachanism of spread of EHV1 in the body
EHV1 infection is rhinopneumo- nitis caused by a localized infection of the nasopharyngeal mucosa.
In almost all cases, a cell-associated viremia alsooccurs in lymphocytes, but in most infected horses this does not result in disease.
However, in some cases, viremia is associated with infection of endothelial cells, and in the pregnant mare vascular damage to the uterus and placenta may lead to
abortion.Similarly, infection of the vascular endothelium in the central nervous system results in neurologic disease.
What is viral tropism?
ability of different viral strains to infect different cell typesand cause syncytia (fusion of an infected cell with neighboring cells leading to formation of multinucleate enlarged cells) formation
Which parasites infect the lung?
Several nematode parasites infect the equine lung. These include migrating stages of Strongyloides westeri and Parascaris spp. en route to the small intestine.
Migrating stages of aberrant parasites, such as Habronema sp., Draschia megas-
toma, and Strongylus spp., which induce granulomatous foci in the lung parenchyma, and adults and larvae of the lungworm Dictyocalus arnfieldi, which inhabit the bronchi, also occur.
Which parasites are stimulating intestinal smooth muscle hyperplasia?
A number of helminth parasites, including Parascaris
spp., stimulate intestinal smooth muscle hyperplasia.
Nematodes, particularly Cyathostomes, induce which type of inflammation?
a type 2 T-helper cell cytokine response consisting of interleukins (ILs) IL-4, IL-5, IL-9, and IL-13. IL-4 and
IL-13 induction of the Stat6 pathway is cen-tral to most of the resulting responses. There is a consistent mastocytosis and eosinophil infiltration of the intestine.
Which parasite is causing seasonal ventral midline dermatitis?
Onchocerca cervicalis infections (microfilariae in the skin)
vector: culicoides spp
Focal, alopecic, depigmented, pruritic lesions are often seen in infected horses
Lesion development is associated with immune-mediated killing of microfilariae in
the skin.
sensitive to macrocyclic lactone anthelmintics
[adults can be found in the nuchal ligament - normally asymptomatic - cannot be killed by Ivermectins]
Which parasites is transferred via mare’s milk?
Strongyloides westeri:
Mares remain infected with arrested third-stage larvae, which subsequent to foaling are transmitted to the foals in milk starting at 4 days postpartum.
What are PAMPs?
Which cells have them?
Which types are there?
The cell walls and membranes of bacteria contain various proteins and polysaccharides with characteristic, often repeating, molecular structures. These
pathogen-associated molecular patterns (PAMPs) include lipopolysaccharides (LPSs), peptidoglycans, lipoteichoic acid, and flagellins. Other PAMPs include viral nucleic acids and unmethylated bacterial cytosine-guanosine dinucleotides
(CpG).
PAMPs are recognized by pattern recognition receptors found on cells of the immune system, particularly those cells involved in the initial encounter with invading microbes. These “sentinel cells” include macrophages, dendritic cells, and mastcells, with macrophages being the most important for initiating
the inflammatory response.
- toll-like receptors (TLRs),
- retinoic acid–inducible gene–1 (RIG-1)–like receptors, and n
- ucleotide-binding oligomerization domain–like receptors.
How do injured cells provoke inflammation?
Injured cells release products collectively termed damage-associated molecular patterns (DAMPs) that bind TLRs on macrophages and other cells leading to the
production of proinflammatory cytokines that augment the inflammatory process.
Which are the cytokines initially release by the innate immune system?
Resident macrophages that encounter the invader initiate the inflammatory response through the production of proinflammatory cytokines such as interleukin- 1 (IL-1), IL-6, and tumor necrosis factor–alpha (TNF-α)
Main function of Il-1?
Many of the effects of IL-1 are mediated through its capacity to increase the production of other cytokines, such as granulocyte colony-stimulating factor (G-CSF), TNF-α, IL-6, and platelet-derived growth factor (PDGF). IL-6 is responsible for the increased production of acute phase proteins by hepatocytes, including complement proteins, C-reactive protein, and serum amyloid A (SAA).
Activates T cells, Chemotactic for neutrophils, Activates neutrophils
Induces fever, Activates B cells,
Enhances NK cell killing
Fibroblast growth factor Stimulates collagen production
Stimulates PGE synthesis Stimulates keratinocyte growth
Stimulates bone resorption
Activates osteoclasts Induces IL-6 production
Describe the immunologic pathway happening in the cell after a viral infection
During viral infections, intracellular pattern recognition receptors (such as RIG-1) bind to viral PAMPs and induce the production of type I interferons (IFNs), including IFN-α and IFN-β. These are produced in virus-infected cells within hours
and inhibit viral replication through various mechanisms. In addition, natural killer (NK) cells are capable of lysing virus infected cells via recognition of different types of receptors on the surface of infected cells, as well as recognizing cells expressing fewer major histocompatibility complex molecules, the expression of which can be downregulated by viral infection. Finally, NK cells have surface Fc receptors that can bind the Fc portion of antibodies bound to the surface of infected cells and subsequently kill the infected cell through the process of antibodydependent cellular cytotoxicity
what is the complement system?
The complement system (part of innate response) consists of over 30 different plasma proteins that are produced primarily in the liver. This complex interacting series of proteases and their substrates results in the production of physiologically active intermediaries that can damage membranes, attract neutrophils and other cells, increase blood flow and vascular permeability, and opsonize bacteria and other particles for phagocytosis
Describe the pathways initiating the complement system
lectin pathway is initiated when soluble carbohydrate-binding proteins bind to carbohydratestructures on microbial surfaces. Proteases associated with these carbohydrate binding lectins then initiate the cleavage of complement components and activate the pathway.
The classical pathway involves the binding of C1q to antibodies already bound to the surface of a microbe. Bound C1q is proteolytic and cleaves other complement components activating the pathway.
The activation of complement via the alternate pathway does not involve antibodies. Instead, certain microbial products stimulate the association of factor D, a proteolytic enzyme, with the complex of factor B and C3b leading to the
formation of C3 convertase and its deposition on the microbial surface.
All three pathways converge with the generation of C3 convertase and the cleavage of C3. Soluble C3a, producedby the cleavage of C3 by the C3 convertases, can bind to mast cells causing them to degranulate and is thus referred to as an anaphylatoxin, as is C4a. C3b serves as an opsonin for C3b receptor-bearing phagocytic cells. C3b is also required for the formation of the membrane attack complex by the terminal complement components, C5 through C9. In this process C5 is cleaved and C5a is generated, which, along with C3a, is a chemoattractive factor for neutrophils and monocytes. C5b forms a complex with C6, C7, and C8 on cell surfaces. This leads to the insertion and polymerization of C9 that forms a pore in the membrane leading to cell lysis.
Lipid mediators of the immune system?
Where do they come from?
Prostanoids are lipid mediators that regulate the inflammatory response.The prostanoids include the prostaglandins (PGs), leukotrienes (LTs), and prostacyclin (PGI2), and they are the
product of cyclooxygenase cleavage of arachidonic acid followed by endoperoxidation.
The major sources of prostanoids in acute inflammation are the phagocytes, endothelial cells, and platelets.
Prostanoid production depends on?
Prostanoid production depends on the activity of the two isoforms of the cyclooxygenase(COX) enzymes within cells:
- *COX-1,** which is present in most cells and its expression is generally constitutive, and
- *COX-2,** for which expression is low or undetectable in most cells but its expression increases dramatically on stimulation, particularly in cells of the immune system.
Proinflammatory and anti-inflammatory effects of PGE2?
PGE2 is considered proinflammatory because it promotes
- vasodilation by activating receptors on vascular smooth muscle and
- increases vascular permeability indirectly by enhancing the release of histamine and other mediators from tissue leukocytes such as mast cells.
- responsible for fever production.
However, as inflammation progresses, PGE2 synthesis by macrophages is enhanced as a result of increased expression of COX-2 and PGE-synthase, and the resulting increased levels of PGE2
- inhibit leukocyte activation,
- inhibit mast cell degranulation, and
- relax smooth muscle contractions
- In the lung, PGE2 promotes bronchodilation.
Thus in these situations PGE2 may be considered antiinflammatory.
what are chemokines?
Which one plays a central role?
Chemokines are chemotactic cytokines. These are soluble proteins produced by host cells that induce the directional migration and activation of leukocytes, as well as other somatic cell types, and thus play major roles in the inflammatory response.
The chemokine CXCL8 (previously known as IL-8) plays a central role in the
migration of neutrophils, including equine neutrophils.
