Exam 2 Flashcards
Cell-mediated immunity: entirely associated with cell surfaces, T-cell receptors, that are unable ot “see” free antigens
T Cells: can regulate the immune responses of other cells (CD4) or indirectly kill cells (CD8) that carry specific antigens
- lymphocytes produced in red bone marow, migrate to thymus (primary lymphoid organ) where they mature (VDJ recombination of T cell receptor) and undergo selection
- T cell receptors must recognize self MHC proteins needed for activation, but not the self antigens (self tolerance) that the MHC presents (T-cell eliminated in thymus if criteria not met)
- “naïve” T cells recirculate only between the blood and lymphoid organs, do not enter other tissues; activated in secondary lymphoid organ
(Ex. Spleen, tonsils, or lymph nodes) - T-cell receptors are transmembrane proteins with constant and variable region, like antibodies; composed of 2 chains (alpha and beta)
- T-cell receptors recognize only a processed peptide fragment that the APC’s MHC presents to the T cell receptor, unlike B-cell receptors
- other transmembrane proteins closely linked to T-cell receptors serve as coreceptors, such as CD4 and CD8
- T cell activation occurs in secondary lymphoid tissue when antigen is displayed with self MHC on mature dendritic cells (DCs)
Cytotoxic Tcells - kill cells that are infected with viruses (or other pathogens)
- have CD8 coreceptor protein
- antigen-presenting cell (APC) often include dendritic cells (professional APC)
- activated by endogenous antigens bound to MHC class I proteins of dendritic cells
- activation results in the release of IL-2, TNF, and IFN-y; and they differentiate into memory cells and activated cells (clonal expansion)
- “altered-self” cells expresing the same combination of foreign peptide on MHC class I are targeted; may include tumor cells, virally infected cells, or cells with intracellular parasites
- release perforins, insert in membrane and make pores, granzymes enter infected cell and activate caspase enzymes that induce apoptosis
Helper Tcells
involved in activating and directing other immune cells;
their cytokines largely determine whether an immune response is humoral or cell-mediated; no killing ability
- have CD4 coreceptor protein
- 1st signal is initiated by exogenous antigens bound to MHC class Il proteins of macrophages, dendritic cells (phagocytosis or endocytosis), and Bcells (receptor-mediated endocytosis)
- 2nd signal is a verification step, naïve TH cells express the protein CD28 that must bind to costimulatory B7 protein on professional APCs; a protective measure to ensure TH cells are responding to a foreign antigen
- when 2nd activation signal is complete the originally undetermined T-helper null cell (TH0) releases a potent T cell growth factor called interleukin 2 (IL-2), which activates the T cells proliferation pathways
- TH0 cells differentiate into TH1 or TH2 cells depending cytokine environment
-Cellular Response- IL-12 &IFN-y induces TH1 differentiation; IFN-y inhibits TH2 cells
-Humoral Response- IL-4 drives TH2 differentiation, and inhibits TH1 cell production - both T helper cell groups are able to inhibit the activation of the other group using their own cytokines
- TH1 cells communicate attack against intracellular bacteria and protozoa
- TH2 cells communicate attack against extracellular parasites including helminths
TH1 cells mainly secrete:
IL-2: growth factor for Tand Bcells; natural killer cells become lymphokine- activated killer (LAK) cells
IFN-Y: inhibition of TH2 cells, strong macrophage-activating factor
TNF: major mediator of inflammation; high concentrations increase synthesis of prostaglandins, resulting in fever
GM-CSF: Granulocyte-Macrophage Colony Stimulating Factor
TH2 cells mainly secrete:
IL-4: growth factor for Bcells; suppresses TH1 cell production
IL-5: stimulates Bcells for growth, differentiation, and production of antibodies; activates eosinophils
IL-10: inhibits TH1 cells, cytotoxic Tcells, NK cells, ¯ophage cytokine synthesis
Humoral immunity: based on antibodies on cell surfaces and in body fluids (blood, lymph, etc.)
B Cells: bind specific to free (soluble) antigen or particulate antigen with its membrane bound antibody (B cell receptor); also serves as APC to TH cells
- B cells produced in red bone marrow; immunoglobulin (Ig) synthesis occurs
- tested for auto-reactivity by the immune system before leaving the bone marrow
- if highly reactive to self:
Clonal deletion- removal, usually by apoptosis
Receptor editing- opportunity to rearrange their conformation via RAG (recombination activating gene)
Anergy- B cells enter a state of permanent unresponsiveness and fail to respond ot their specific antigen - Ig is encoded by different segments of DNA, a V(variable) segment, a D(diversity) segment, a J (joining) segment, and a constant region; variable regions are shuffled by RAGs
- each Ig consists of 2 identical short polypeptides called light chains and 2 identical longer polypeptides chains called heavy chains; held together by disulfide bonds to form a Y-shaped molecule
- each “arm” is called Fab (fragment antigen-binding) region and the “stem” is called Fc (fragment crystallizable) region
- the heavy chain constant region is translated from 1of 5possible DNA sequences named u (mu), o (delta), y (gamma), a (alpha), E (epsilon), which give rise to a particular class of immunoglobulin
- immunoglobulins IgM (monomeric form) and IgD are present on mature “naïve” Bcells
- Bcells recirculate only between blood and lymphoid organs, activated in secondary lymphoid organ (Ex. lymph nodes, MALT, which includes tonsils and appendix)
- Bcells recognize their cognate antigen in its native form with its B-cell receptors (antibodies) ; each Ig can bind 2 identical epitopes
- binding of antigen to Ig on surface of appropriate Bcell is usually not sufficient to
activate the B cell to multiply; so, B cell (APC) internalizes antigen-antibody complex and incorporates portions of antigen (epitope) on MHC II - specific TH2 cell recognizes antigen displayed by B cell; cytokines such as IL-4 are released from TH2 cell to activate B cell; produces memory cels and plasma cells that secrete antibodies against the identical antigen
Complement
- consists of approx. 30 different proteins
- circulate freely in blood plasma, generally in inactive form (zymogen)
- complement can be activated by classical pathway (antigen-antibody complex) or alternative pathway (spontaneously) or lectin pathway (cell wall polysaccharides of certain bacteria and fungi)
- complement proteins (C3b) coat pathogen surface (opsonization), thus promoting phagocytosis and destruction by macrophages and neutrophils, which have receptors for C3b
- C5a is an important chemotatic protein, helping recruit inflammatory cells
- complement C5b initiates pathway for membrane attack complex (MAC) that forms pores in pathogens that have lipid membrane to induce lysis
Interferons (IFN-a, IFN-b, IFN-y)
- a class of proteins synthesized upon parasitic infection of a cell
- act as messengers to protect normal cells in vicinity from becoming infected
- IFN-a and IFN-b induce the degradation of RNA and block protein production
- IFN-y is produced by TH cells and natural killer cells to stimulate in the cellular response
Phylum: Platyhelminthes
Platyhelminthes (flatworms): phylum containing simplest bilateraly symmetrical animals
- most platyhelminthes are parasitic
- acoelomate body plan (no body cavity other than the gut); rarely has anus
- triploblastic (composed of three fundamental cell layers) Ex. mesoderm, ectoderm, and endoderm
- dorsoventrally flattened (greater surface area to respire by diffusion)
- tegument (surficial covering of a multicelular organism, an integument)
- parenchyma (loosely arranged mass of fibers and cells of several types)
Subclass: Digenea
Digenetic trematodes (flukes): a subclass within the class Trematoda
- digeneans parasitize all classes of vertebrates
- develops in at least two hosts
- first host is a mollusk (most often a gastropod) or very, rarely an annelid
Domain: Eukaryota
Kingdom: Animalia
Plylum: Platyhelminthes
Class: Turbellaria
Monogenea
Cestoidea
Trematoda
Subclass: Digenea
Aspidobothrea
Body Form
Most are dorsoventrally flattened and oval ni shape; others as thick as they are wide
- length ranges from 1.0 m to 6.0 cm
different suckers
Oral sucker: muscular sucker that surrounds the mouth
Acetabulum: ventral sucker of a fluke
Distome: fluke with two suckers, oral and ventral
Monostome: fluke that lacks a ventral sucker
Amphistome: fluke with the ventral sucker located at the posterior end
Tegument: surficial covering of a multicellular organism, an integument
- distal cytoplasm: anucleate layer of cytoplasm above a “sunken epidermis”
- cytons: cel bodies containing nuclei; lie beneath superficial muscle layer
- internuncial processes: channels that connect cytons ot distal cytoplasm
- syncytial: describes the continuous distal cytoplasm with no intervening cell membranes
- spines: consist of crystalline actin; often present in certain areas of the tegument
- spines lie above the basement membrane of distal cytoplasm
- most flukes can absorb small molecules including amino acids and hexoses
Muscular system
- circular muscles lies beneath the basal membrane of tegument
- longitudinal and diagonal layers underlying the circular muscles envelop body - muscle fibers are smooth, often in syncytial clusters
- myocyton: cell body of a muscle cell where nuclei occur; connect to fiber bundles
Nervous system: cerebral ganglia with orthogonal nervous system
orthogon: describes the ladderlike arrangement of nervous system in flatworms
- 3 main pairs of longitudinal trunks (dorsal, ventral, and lateral)
- cross-connected by a series of transverse commissures
- sensory endings extend from tegument; many types in cercaria and miracidium
tangoreceptors- receptors sensitive to touch
chemoreceptors- sensory receptor that responds ot chemical stimuli (some strikingly similar to olfactory receptors of vertebrate nasal epithelium)
eyespots: allows organism to distinguish light direction
Excretion: removal of waste takes place across tegument, epithelial lining of gut,
exocytosis of vesicles, and via excretory system
- removal of waste products of metabolism
- removal of unnecessary or harmful substances
- regulation of internal osmotic pressure
- regulation of internal ionic composition
Protonephridia
excretory system that is closed at the inner end by a flame cell and opens by a pore at the distal end
Flame bulb: specialized hollow excretory or osmoregulatory structure
- one or several small cells containing a tuft of flagella
- situated at the end of a minute tubule
- connected tubules ultimately open to the outside
- rod-like extensions of the flame cel form a filtering apparatus (weir)
- ductules of flame cells join collecting ducts that eventually feed into an excretory bladder that opens outside through a single pore
Flame cell formula: represents the number and arrangement of flame cells
used as a taxonomic character
Flame cell formula Steps:
1 Draw a vertical line down the center from anterior to posterior end. 2[( )+( )]
2. Draw a horizontal line where the main
collecting ducts bifurcate.
3. Starting anteriorly from the upper quadrant count the number of flame cells in a common
cluster. Add this number to other number of
flame cells in the remaining cluster. 2[ (3+3+3) +()]
4. Repeat with the lower quadrant working from anterior to posterior.
2[(3+3+3) + (3+3+3)]
Digestion- digestion in most flukes is predominantly extracellular in the ceca
waste is expelled through
- excretory system or tegument
- stored in worm tightly bound to protein
- periodically regurgitated
Cytokines
- cytokines are protein hormones utilized by immune cells to communicate
- can affect same cells that produce them, cells nearby, or cells distant in body
Ex. interferon, interleukin, growth factors, etc.
Cell Signaling
- ligand binds to a specific cell receptor protein, initiating intracellular signal cascades
- ligands may be located on cell surface of neighboring cells, dissolved in blood (cytokines) or on the surface of or secreted by pathogens
- cascades may activate transcription factors or proteins that control gene induction, phagocytosis, apoptosis, or secretion
Cell Signaling
Ex. JAK-STAT pathway: 3 main components include
- receptor
- Janus Kinase (JAK)
- Signal Transducer and Activators of Transcription (STAT)
- transmembrane receptor, activated by cytokine
- activates the JAK protein, which adds phosphate groups (P) to the receptor
-Kinases: are proteins that add phosphate groups to other proteins
-Phosphate groups: act as “on” and “of” switches on proteins - STAT is recruited and itself becomes phosphorylated, forms dimer, and moves into the cell nucleus, where it binds to DNA promoter region
Pattern Recognition Receptors- receptors with broad specificity that bind to molecules on the surface of pathogens; stimulated by PAMPs
- Pathogen-associated molecular patterns (PAMPs): small molecular motifs conserved within a class of pathogens
A. Scavenger receptors: bind lipoproteins and lipopolysaccharides from bacterial cells including Gram-positive bacteria (lipoteichoic acid) and Gram-negative
bacteria (lipopolysaccharide)
B. Complement receptors: integral membrane proteins that recognize fragments of complement and mediate various defense functions, including phagocytosis
C. Toll-like receptors (TLRs): single, membrane-spanning, receptors that recognize structurally conserved molecules of carbohydrates, nucleotides, and proteins derived from viruses, bacteria, protozoa, and helminthes parasites
Four important aspects of immune response include:
- nonself recognition: ability to distinguish self-antigens from nonself
- antigen-specific: recognizes and is directed against specific antigens
- systemic response: immunity is not restricted to initial infection site
- “memory”: recognizes and mounts stronger atack on previously encountered pathogens
Basis of self and nonself recognition
Major histocompatibility complex (MHC): cell surface glycoproteins, highly polymorphic
A. MHC class I proteins
- presents in every nucleated cell of the body (few exceptions)
-Cytotoxic T cells (CD8) respond to endogenous antigen bound to MHC class I proteins
B. MHC class II proteins
-found only on antigen presenting cells (macrophages, B cells, and dendritic cells)
-TH cells (CD4) respond to exogenous antigen bound to MHC class II proteins
Different Ig
IgM: pentamer, 1st antibody secreted during primary immune response; monomer, present on surfaces of B cells
IgG; monomer, major antibody secreted during the secondary response; 75% of plasma antibodies
IgD: monomer, present only on surfaces of Bcells; serves as antigen receptor
IgA: dimer, most abundant form of antibody in body secretions; high density of IgA-secreting plasma cels in MALT
IgE: Fc binds to mast cells, basophils, etc.; often secreted in response to helminth worms; low conc. in plasma
Plasma B cells: are large B cells that have been exposed to antigen
- produce and secrete large amounts of antibodies
- short lived cells and undergo apoptosis when the inciting agent that induced immune response is eliminated
Memory B cells: specific to antigen encountered during primary immune response
- can respond quickly following a second exposure to same antigen
- long lived cells
Human immunodeficiency virus (HIV): a retrovirus that attacks the body’s immune system; causes AIDS
A. HIV mounts direct attack on TH cells by binding to CD4 proteins on cell surface; monocytes are infected because they also express CD4
B. HIV kills TH cells, via apoptosis, faster than they can proliferate over time
C. HIV-encoded proteins also cause a decrease in the expression of MHC class I on infected cells, so these cells are less likely to be recognized and are killed by NK cells
D. when CD4+ Tcell numbers decline below a critical level of 200 cells per uL, cell-mediated immunity is lost
Acquisition of nutrients:
Feeding and digestion- varies with nutrient type and habitat within the host
Ex. flukes of lungs, intestine, urinary bladder, rectum, and bile ducts draw a plug of tissue into their oral sucker and use pharynx as a pump to erode tissue
Ex. flukes living in blood vessels are immersed in its semifluid blood food, so has no necessity ot breach host tissue
Reproductive system:
- most trematodes are hermaphrodites, and some can self-fertilize
- always cross-fertilize if 2 or more digeneans are in the same host
- exception are schistosomes that are dioecious
- ectolecithal system: yolk is contributed by vitelline cells, yolk not stored in female gamete
Male Reproductive system:
testes: usually 2, number varies with species
- each testis has a vas efferens that ultimately connects to vas deferens
- internal seminal vesicle: located within cirrus pouch, stores sperm
cirrus: male copulatory organ; cirrus pouch encloses the cirrus
Digenea: Form and Function
Female Reproductive system:
ovicapt: sphincter muscle that controls the release of oocyte from the ovary
Laurer’s canal: vestigial vagina
Mehlis’ gland: unicellular mucous and serous glands surrounding the ootype
ootype: a slightly expanded area of the oviduct that is surrounded by Mehlis’ gland
vitellaria: a group of vitelline glands that produce vitelline cells
- vitelline cells produce the bulk of the shell material and yolk of the egg
oogenotop: “egg forming apparatus”
Development
Polyembryony: development of a single zygote into more than one offspring
- Somatic cell: contributes to body tissue of the embryo
- Propagatory cell: stem cells
- they are germinal cells in reproducing forms
Ex. additional embryo in miracidium, sporocyst, or redia - give rise to germ cells in sexual adults
Ex. sperm and egg
- they are germinal cells in reproducing forms
Pathogen: any organism or substance that produces a disease state
Pathogenicity: encompasses the total sum of consequences regarding the presence of a foreign species in the host
- a parasite is pathogenic if it causes changes in hte anatomy, physiology or behavior of the host
Virulence: deals with the consequences of the presence of the foreign species on the transmission of the hosts genes
- a parasite is virulent if it reduces host reproductive success
Digenean: Leucochloridium variae
- definitive hosts include warblers
- embryonated eggs are ingested by the terrestrial snail (Succinea ovalis)
- sporocyst divided into 3 parts:
1. central body in snail’s hepatopancreas
2. tube connecting the central body to the broodsac
3. broodsac in the head-foot of the snail and enters its tentacles - brightly colored broodsac pulses in enlarged snail tentacle
- tailless cercariae develop in branched sporocysts; metacercaria encyst in broodsac
Digenean: Alaria americana
Parasite of wolves, foxes, coyotes, and the domestic dog (humans are accidental hosts)
- miracidia hatch out of egg and penetrate snail
- sporocysts shed cercariae - cercaria penetrate tadpole
- mesocercaria develop in tadpole
(infective to next host, either paratenic or definitive host) - water snake (paratenic host) eats infected tadpole or frog
- canid eats infected snake and mesocercariae are freed by digestion
- mesocercariae penetrate gut, move to diaphragm & then lungs (metacercaria)
- (after 5 weeks) they migrate up the trachea and then to the small intestine
Alaria americana Pathology:
- mature Alaria sp. very pathogenic causing severe enteritis
- often kills host in severe infections
- can be fatal in humans when accumulated in large numbers
Alaria americana Epidemiology:
- found in various species of Canidae in northern North America
- mesocercariae are pathogenic to human
- acquired by eating undercooked frogs’ legs
- transmammary transmission of mesocercariae to offspring via milk
Population structure:
set of quantitative descriptors of a host population, including prevalence of infection, incidence, abundance or density, intensity, variance of a frequency distribution, and curve of best fit
prevalence
percentage in individuals of a single host species infected at a given time
incidence
the number of new infections per unit time divided by the number of uninfected hosts at the beginning of the measured time
