Lecture II Flashcards
A 72-yo male comes to the physician because of a 3-wk history of blisters and severe itching that did not improve with 1% hydrocortisone therapy. Physical examination shows several 2- to 6-cm tense blisters over the abdomen, groin, and flexor surfaces of the extremities. Severe blisters appear to have ruptured, resulting in the formation of surface erosions. A skin biopsy specimen shows subepidermal, nonacantholytic blistering with a mixed eosinophilic and lymphatic perivascular infiltrate in the superficial dermis. Immunofluorescent microscopy shows a linear deposition of IgG and C3 along the basement membrane. Which of the following epithelial structures most likely contains the antigen associated with the disease process? A. Adherens junction (zonula adherens) B. Desmosome (macula adherens) C. Gap junction D. Hemidesmosome E. Tight junction (zonula occludens)
D. Hemidesmosome Bullous pemphigoid (seen in this scenario) is mediated by autoantibodies that react with components of hemidesmosomes, disrupting the connection of epithelial cells to the underlying tissue and resulting in bulla formation. The immune mechanism of this condition can be regard-ed as a type II hypersensitivity reactions. Pemphigus vulgaris is mediated by autoantibodies that react with desmosomes, disrupting cell-cell connections in mucosa and skin. It starts with small vesicles, usually on the oral or nasal mucosa, and then spreads to other parts of the body. Bullae are delicate and flaccid. Nikolsky’s sign (production of blistering by light stroking or rubbing of the skin) is positive. Pemphigus is most common from ages 40 to 60.
In the small intestine, proteins localized in the basolateral surface of epithelial cells are prevented from migrating to the apical surface of the cell by the presence of which of the following labeled structures in the diagram?
A. Tight junctions (zonulae occludentes)
Blood is drawn from a 34-year-old male with bacterial meningitis for a complete blood count. The leukocyte count is elevated. Which of the following is released by the predominant type of white blood cell present?
A. Histamine
B. Leukotrienes
C. Lysozyme
D. Peroxidase
E. Vasoactive amines
C. Lysozyme
This question requires you to know that bacterial infections are associated with an elevated neutrophil count. These leukocytes represent ~60% of all leukocytes, have 3-5 nuclear lobes, and are filled with granules that contain bactericidal products, including lysozyme. Had the infection been viral, there would have been an increase in lymphocytes instead.
Histamine (choice A) is released by basophils and mast cells, along with other vasoactive amines (choice E). The “slow-reacting substance of anaphylaxis” (which consists of leukotrienes LTC4, LTD4, and LTE4 (choice B)) is also released by basophils, which possess large, dark blue/black spheroidal granules. Basophils and mast cells are basophilic (thus their name) and metachromatic, because of the presence of heparin, a glycosaminoglycan.
Eosinophils contain peroxidase (choice D). These white blood cells have a bilobed nucleus and possess red acidophilic granules in their cytoplasm. They also contain hydrolytic enzymes. Note that an increased eosinophil count is associated with parasitic infections, allergies, asthma, and some neoplasms.
physical/mechanical barrier, chemical agents and normal flora are all
components of the skin immunity
keratinocytes
closely connected cells of the skin cross-linked with keratin, high turnover rate and prevents evaporation
the skins chemical agents
ph, and antimicrobial agents (cathelicidins, defensins, and dermicidins)
landergans cells
derived from bone marrow, dendritic cells located among keratinocytes, function as antigen presenting cells in immune responses to contact antigens and some skin gradts; contain birbeck granules
birbeck granula- unique to the skin and unknwon function
top arrow is pointing to the __________ and bottom arrow is pointing to the ______
langerhans cells and cytoplasmic process
langerhans cell
mucosa
epithelium, lamina propria (loose connective tissue with glands), and muscularis mucosae (smooth muscle)
submucosa
dense irregular connective tissue
muscularis externa
inner smooth muscle and outer smooth muscle
external layer
adventitia (loose CT) and serosa (loos CT)
- tight junction
- zonula adherens
- desmosome
H- hemidesmosome
tight junction
an occludens junction, composed of claudins and occludins (proteins); prevents leaking between cells and precents movement of membrane proteins
zonula adherens
an adherens junction, composed of cadherins, binds to actin of the terminal web (cytoskeleton)
desmosome
an adherens juntion, composed of desmoplakins and plakoglobins
gap junctions
a communicatin junction, composed of connexins
hemidesomosome
an adherns junction, connects the cell to the basement membrane so it is not an intracellular junction
IgA
resistant to proteolytic enzymes, so it can coexist with proteases in gut lumen
antigens in the gut are bound by ______ and undergo transcytosis into the intraepithelial pockets
M cells
__________ cells take up the antigen process it, and present it to the helper T lymphocytes
dendritic
_______ are then stimulated to differentiate into plasma cells which secrete IgA antibodies
B lymphocytes
______ is transported into the gut lymen where it binds its antigen on the surface of microorganisms, neutralizing potentially harmful invaders before they penetrate the mucosa
IgA
_______ bad bacterial species in the oral cavity
400
lamina propia in the mucosal immunity in oral cavity
contains macrophages, contains dendritic cells which project dendrites into the epithelium to uptake antigens and migrate to secondary lymphoid tissue and draining lymph nodes
saliva contains what 4 components that deal with immunity in the oral cavity
lysozyme, lactoferrin, histatins, and salivary IgA
lysozyme
found in oral cavity; cleaves bacteria cell walls
lactoferrin
part of oral immunity; complexes with iron and deprices microbe of nutrient
histatins
part of oral immunity; inhibits growth of candida albicans and streptococcus mutans
salivary IgA
part of oral immunity; aggregates oral bacteria, prevents formation of dental plaques
tonsils
lymphoid tissue
pemphigus vulgaris
acantholytic disorder in persons 30-60; formation of severe intraepidermal bullaw starting in oral cavity and spreading to skin; autoimmune attack of desmosomes; can be fatal
acantholytic
loss of cell connections like desmosomes ex. pemphigus vulgaris
bullous pemphigoid
resembles pemphigus vulgaris but is much less severe; features subepidermal bullae with characteristic inflammatory infiltarte of eosinophils; autoimmune attack on hemidesmosomes
two forms of diffuse lymphoid tissue
- loose cluster of lymphoid cells
- lymphoid nodules
located in the mucosa (unless senn in enlarged form in the submucosa like peyers patch)
GALT
gut associated lymphoid tissue
BALT
bronchus-associated lymphoid tissue
NALT
nose associated lymphoid tissue
VALT
vulvovaginal lymphoid tissue
lymphoid nodules
found in the lamina propria of the mucosa throughout the gut
in the ileum, these lymphoid nodules are especially large and press outward into the submucosa and are known as _________
peyers patches
tonsil lymphoid tissue
lymphoid tissue in trachea; BALT
lymphoid nodule in illeum (peyers patch); GALT
GALT, lymphoid nodule
left top: resting B cells
left bottom: newly formed B cells
right: germinal center of lymph node (or follicle)
in the respiratory tract humidifcation and turbbulent airflow cause large particles to land on the ________ surfaces
mucosal
vagina epithelium secretes _____ that normal flora convert into lactic acid, creating a acidic environment that in unfavorable for pathogenic microorganisms
glycogen
______ protein from kidney binds bacteria and prevents attachment to urinary tract lining
tamm-horsfall
longer male urethra
passive protection by creating longer route for bacteria to travel to bladder
eye immunity systems
blinking, lacrimal glands, meibomian glands, ciliary gland, bacteriostatic/cidal tear film
lacrimal gland
tears
meibomian glands
sebaceous glands on eyelids
ciliary gland
apocrine sweat glands on the eyelid
tears contain ____ and other antimicrobial substances
lysozymes
the generation of most bacteria is _______ to _____ minutes
20; 30 whereas the development of specific immunity response with antibodies could take days
phagocytic cells identify pathogens by recognizing _______ and ______
pathogen associated molecular patterns (PAMPs) and damage/necrotic self, damage-associated molecular patterns (DAMPS)
Coagulase negative streptococci on the skin can inhibit
staph aureus
Neutrophils are also known as
polymorphonuclear leukocytes
Neutrophils typically last
2 days
Neutrophils kill engulfed substances in vesicles called ________ where the microbe is killed and degraded
phagolysosome
Macrophages are derived from _________ once they move into the connective tissue
Monocytes
Macrophages serve to kill and to degrade antigens and also to _____ peptides from those antigens
Present
Macrophages are professional antigen ________ cells
Presenting
Conventional dendritic cells are important in ______________ because they are very efficient at presenting antigen to ____________
Immunosurvelliance; T cells
________ are specialized stromal cells in lymph nodes and spleen. They are adept at trapping antigen and presenting to B cells
Follicular dendritic cells
Natural kill cells arise and mature in the ___________
Bone marrow
Natural killer cells contain _______ and __________
Granzyme and perforin
Natural killer cells contain cell surface receptors for ___________
IgG
The microbial molecules that stimulate innate immunity are called _____________
PAMPS (pathogen-associated molecular patterns)
Innate immune responses are mediated by proteins that recognize and interact with components specific to microbes they are called ______________
Pattern recognition receptors
Pattern recognition receptors are divided into two groups _________ and __________
Secreted and circulating
pattern recognition receptors definition
the innnate immune system recognizes structures that are sharded by various classes of microbes and are not present on normal host cells
examples of things pattern recognition receptors will recognize
- endotoxin, LPS
- GC rich oligonucleotides
- double stranded DNA
- mannose residues on bacterial glycoproteins
lectin
can bind polysaccharides specific to pathogen
pattern recognition receptor family
toll-like receptors
toll-like receptors
recognize microbrial proteins, lipids and polusaccharides (on cell surface) and nucelic acids (in endosomoes)
Toll like receptors (TLR) located on cell surface recognize
lipids, polysaccarhides and proteins
toll like receptors (TLR) on the membrane of endosomes recognize
nucleic acids
TLR-2 recognizes
several bacterial and parasitic glycolipids and peptidoglycans
TLR-3,7, and 8 are specific for
viral single stranded and double straned RNAs
TLR-4 is specific for
bacterial LPS (endotoxin)
TLR-5 is specific for
a bacterial flagellar protein flagellin
TLR-9 recognizes
unmethylated CpG DNA that is abundant in microbial genomes
type I interferons
IFN alpha and beta
type II interferons
IFN gamma
primary reactions of the innate immune system are ___________ and ____________
acute inflammation and antiviral defense
innate immune defense against intracellular viruses is mediated mainly by the help of the ________ system
interferon
pattern recognition receptors on macrophages and dendritic cells detect a virus attack and secret what warning proteins _________ making them type I/type II interferon cells
interferon alpha and beta; type I
innate immunity cells use TLR 7 to detect RNA/DNA and TLR 9 to detect RNA/DNA
RNA;DNA
most human cells ahve type I/type II interferon cells
type I
interferons can lead to
cell death
macrophages secrete hormones called ________ that attract immune system cells to the site and activate cells involved in tissue repair
cytokines
Natural killer cells are type I/type II interferon cells becuase they secrete interferon alpha and beta/gamma which stimulates/inhibits macrophages which in return secrete IL-2/IL-5 which inhibits/stimulates natural killer cells
type II; gamma; stimulates; IL-2; stimulates
natural killer cells can destory some ________ cells
cancer
the four main cytokines of innate immunity
tumor necrosis factor; IL-1; Interferon gamma; IL-6
_______ is the chief stimulator of the production of most acute phase proteins, wheras the other implicated cytokines influence subgorups of acute phase proteins
IL-6
an acute phase protein has been defined as
a protein whose plasma concentration increase (positive acute phase proteins) or decreases (negative acute phase proteins) by at least 25 % during inflammatory disorders
the changes in concentrations of acute-phase proteins are due largelyto changes in their production by _________
hepatocytes in the liver
c reactive proteins
can promote the recognition and elmination of pathogens and enhance the clearance of necrotic and apoptic cells
serum amyloid A proteins influence ______ _______ during niflammatory states
cholesterol metabolism
haptoglobin Nd hemopexin are __________ that protect against reactive oxygen species by removing iron-containing cell-free hemoglobin and heme from circulation
antioxidants
hepcidin can contribute to increases/decreases in serum iron
decreases
red line- lacking innate immunity
green line- lacking adaptive immunity
yellow- normal immunity
the inteferon system is involved in eliminating ______ infevted cells
viral
