Parasitology Exam #2 Flashcards
what type of cell are Natural Killer Cells (NK)?
lymphocytes (second line of defense, nonspecific immunity, innate immunity)
Target own infected cell it can be cancer cells or cells that has inside of them extracellular parasites (parasites living within the actual cells)
Natural killer (NK) cells:
- Do not kill pathogen directly, but induce apoptosis of infected cells(cancer and viral)
- Release perforins, insert in membrane and make pores, granzymes enter infected cell and activate caspase enzymes that induce apoptosis
- Big player in immune surveillance and the bodies defense against cancer
- Do not have T-cell receptors, but do express Fc receptor molecules for lgE
Natural Killer only target cells that does not have what class receptor?
MHC class 1 Even thought the NK cell is activated it does not mean that it will release the perforins. If its able to make contact with MHC class 1, with the inhibitory receptor, then it will not do degranulation, no release of perforins. On the other hand if the target cell does not have MHC class 1 then the NK cell will be activated and it will release the perforins
if a target cell have a MHC class 1, what happen to the NK cell
The inhibitory receptor of NK react with MHC class 1 and it will inhibit the release of the granule (Cytotoxicity)
Mast Cells:
- Primarily located under mucosal surfaces
- Release chemical mediator such as histamine to promote inflammation
- Triggered during allergic responses express Fc receptor molecules for lgE
- Important component of the inflammatory response
The IgE primed mast cells release granules and powerful chemical mediators into the environment. What are the powerful chemical mediators?
Histamine and Cytokines
what does vasodilation does to the skin
Redness
what does endothelial gaping and fluid leakage does to the skin during a allergy
Swelling
What does anti-Histamine treat ?
Allergic reaction
How long can an Acute inflammation occurs
over seconds, minutes, hours, and days
Chemical signals:
are released by infected or injured during initial response to tissue damage (acute Phase).
Ex. (histamine, prostaglandins, & bradykinins)
Acute inflammation:
- dilation of local blood vessels increases blood flow at site (red & warm)
- increased permeability of capillaries causing edema (tissue swelling)
- tissue swelling puts pressure on nerve endings (pain & potential loss of function)
- macrophages and neutrophils release cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF) which acts on hypothalamus to raise body temp. (fever)
A. fever is one of the most common symptoms of infection
B. fever stimulates phagocytosis and causes liver and spleen to store iron and zinc needed by bacteria
C. fever may destabilize certain viruses and bacteria - cell death (necrosis) always occurs to some degree during inflammation
What element helps bacteria to grow?
Zinc and Iron
Delayed type hypersensitivity (DTH):
Type of acute inflamation, occurs.
Type of cell mediated immunity in which the ultimate effectors are activated macrophages
- a period of 24 hours or more elapses between the time of antigen introduction and the response to it in an immunized subject
- Delay occurs because TH1 cells with receptors for that particular antigen require time to arrive at antigen site, recognize the epitopes on APCs, and become activated and secrete IL-2, TNF, and IFN-y
how long could DTH takes to activates?
hours to days to activate because its cell mediated
What analog did Dr. Sharp gave for the DTH?
Weed wacker reaction when cutting in shorts, poison ivy
Examples of DTH
- Poison ivy plant with urushiol. Urushiol is a hapten: does not illicit an immune response unless it is coupled to another molecule
- Tuberculin skin test (montoux) reaction
how to know if you previously exposed to a allergic reaction, what will happens to you?
Swell/indurate
Immediate Hypersensitivity (definition)
a type of antibody mediated immunity which involves degranulation of basophils and mast cells in the area
Allergy and asthma related
Immediate Hypersensitivity:
- Basophils and mast cells have receptors that bind the Fc portions of antibody (lgE)
- When exposed to the same allergen a 2nd time, degranulation occurs
- Results in dilation of local blood vessel and increased permeability; edema
- Immediate hypersensitivity is important in some parasitic infections
- Immediate hypersensitivity in humans is the basis of allergies and asthma
What example did Dr. Sharp gave for immediate hypersensitivity?
- if you are asthmatic and you go to a dirty house
- if someone is allergic to cat, and goes to a cat home and have their nose running and/or sneezing
Anaphylaxis:
(systemic immediate hypersensitivity): hypersensitivity produced by exposure to further doses of the same protein, usually when exposure is within less than 2 weeks
Ex. Bee stings
What is happening during Anaphylaxis?
- Basophils and mast cells release pharmacologically active substances
- Widespread rapid inflammatory response that may be fatal if not treated rapidly
- Tremendous drop in blood pressure
- Swelling of epiglottis can block trachea, and bronchial constriction
Chronic inflammation
acute inflammation that fails to heal; occurs over longer times and is disease related
Fibrosis:
arises from abnormal and continuous wound repair processes that fails to terminate resulting in elevated levels of collagen and scarring
Granulomas:
nodules of inflammatory tissues that may accumulate around persistent antigen
Abscess:
when necrotic debris confined to a localized area forms pus that may cause an increase in hydrostatic pressure
Ex: Schistosoma
Ulcers:
an area of inflammation that opens out of the skin or mucous surface
Schistosoma infection can result______
in liver fibrosis
what can Dracunculus do on human?
infection and abscess
Leishmaniasis effect on human?
Skin Ulcer
Complement
- consists of approx. 30 different proteins, along with factors, B, D, and P.
- 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 with factors, B, D, and P.)
- Complement proteins (C3b) coat pathogen surface (Opsonization), Thus promoting phagocytosis and destruction of pathogen by macrophages and neutrophils, which have receptors for C3b
- C5a is an important chemotactic protein, helping inflammatory cells
- complement C5b initiates pathway for membrane attack complex (MAC) that form pores in pathogens that have lipid membrane to induce lysis
What analog did Dr. Sharp used for C3b ?
If you play paintball and got shot with a fluorescent color, you be taking out every next time.
Alternative pathway is also considered as
domino effect
What are three ways complements can be activated?
- classical pathway (antigen-antibody complex)
- alternative pathway (spontaneously)
- lectin pathway (cell wall polysaccharides of certain bacteria and fungi)
What are the three interferons ? and also are Cytokines*
IFN- α
IFN- β
IFN- γ
Interferons:
- A class of proteins synthesized upon parasitic infection of a cell
- Act as messengers to protect normal cells in vicinity from becoming infected
- IFN-α and IFN-β induce the degradation of RNA and block protein production
- IFN-y is produced by TH cells and natural killer cells to stimulate cells in the cellular response
Cytokines:
- cytokines are protein hormones utilized by immune cells to communicate
- can effect same cells that produce them, cells nearby, or cells distant from the body
Ex. Interferon, interleukin, growth factors, etc.
What are the two functions of interleukin?
- Activator
2. Grow cell
Cell signaling:
- Ligand binds to a specific cell receptor protein, initiating intracellular signal cascades
- Ligands may be located on cell surface or neighboring cells, dissolved in blood (cytokines) or on the surface of or secreted by pathogens
- Cascade may activate transcription factors or protein that control gene induction, phagocytosis, apoptosis or secretion
Ex: JAK-STAT pathway
What is JAK ?
Janus Kinase
What is STAT?
Signal Transducer and Activator or Transcription
JAK-STAT pathway, what are the 3 main components ?
- receptor
- Janus Kinase
- Signal Transducer and Activator or Transcription
What are Kinases?
are proteins that add phosphate groups to other proteins
What are Phosphate groups?
Act as “on” and “off” switches on proteins
Signal Transducer and Activator or Transcription (STAT):
- Transmembrane receptor, activated by cytokine
- activates the JAK protein, which adds phosphate groups (P) to the receptor
- STAT is recruited and itself becomes phosphorylated (dimerized), forms dimer, and moves into the cell nucleus, where it binds to DNA promoter region
specific immunity-adaptive immunity is which line of defense?
the third line
What are the four important aspects of specific immunity response? (third line of defense)
- Nonself recognition: ability to distinguish self-antigen from nonself
- Antigen-specific: recognizes and is directed against specific antigens
- Systemic response: immunity is not restricted to initial infection site
- “memory”: recognizes and mount stronger attack on previously encountered pathogens
*soldier that attck the castle with amory, and archers hit the soldier in the eye hole
what is Pattern Recognition receptor ?
receptors with broad specificity that binds to molecules on the surface of pathogens; stimulated by PAMPs -Pathogen-associated molecular patterns (PAMPs): small molecular motifs conserved within a class of pathogens
what are three Receptor of (PAMPs)?
A. Scavenger receptors
B. Complement receptors
C. Toll-like Receptors (TLRs)
Scavenger receptors:
bind lipoproteins and lipoproteins and lipopolysaccharides from bacterial cells including Gram-positive bacteria (lipoteichoic acid) and Gram-negative bacteria (lipopolysaccharide)
*bacteria
Complement receptors:
integral membrane proteins that recognize fragments of complement and mediate various defense function, including phagocytes
Toll-like receptors (TLRs):
single, membrane-spanning, receptors that recognize structurally conserved molecule of carbohydrate, nucleotides, and proteins derived from viruses, bacteria, protozoa, and helminthes parasites
*antimicrobial proteins
Major Histocompatibility complex (MHC):
Basis of self and nonself recognition
Cell surface glycoproteins, highly polymorphic
What analog did Dr. Sharp used about what are MHC 1?
Flag hole, they are used as an identification, information for other cell.
purple flag = marine life in Ocean
What are the two type of MHC ?
MHC Class 1 protein and MHC class 2 protein
MHC class 1 protein:
- Present on every nucleated cell of the body (few exception)
- Cytotoxic T cells (CD8) respond to ENDOGENOUS ANTIGEN bound to MHC class 1 protein
“if you have a nucleus, you have MHC class 1”
what happened if T-cell don’t see a living cell but a cell present?
It release perforin and enzyme to kill cell (in MHC class 1)
MHC class 2 proteins:
- found only on antigen presenting cells (macrophages, B cells, and dendritic cells)
- TH cells (CD4) responds to EXOGENOUS ANTIGEN bound to MHC class 2 protein
- Th cells are Helper cell
- MHC class 2 protein also have MHC class 1 protein
Macrophages
Agranulocytes (mononuclear leukocytes)
1. Monocytes mature into active macrophages at site of infection
2. Intracellular killing and digest pathogens via phagocytosis
3. Phagosome fuses with lysosome, (oxygen-containing and nitrogen containing free radicals)
4. roam continuously in the extracellular fluid bathing tissue
5. antigen-presenting cell (APC) for helper T cells (TH)
6. respiratory burst for additional cell-killing ability (liberates deluge of free radicals)
7. express Fc receptor molecules for igG to trap antigen-antibody complexes
Ex. –Kupffer cells of liver
- Dendritic cells in blood
- Microglial cells in CNS,
Neutrophils
Granulocytes (polymorphonuclear leukocytes)
- Most abundant circulating leukocytes (50-70% of peripheral blood leukocytes)
- First cell on site of tissue damage or infection
- Intracellular killing via phagocytosis, greater range of reactive oxygen radicals
- Large numbers in blood until attracted to tissues during inflammation
- Roam in the extracellular fluid bathing tissues
- Express Fc receptor molecules for lgE
Eosinophils
Granulocytes (polymorphonuclear leukocytes)
- 2%-5% of the total leukocytes in blood
- important in the elimination of parasites
- degranulation, next to parasite, releases extremely potent mediators (enzymes & toxins)
- high blood count is often associated with parasitic infection & allergic diseases
- express Fc receptor molecules for lgE
Basophilis
Granulocytes (polymorphonuclear leukocytes)
- circulating cells, least numerous at about 0.5%
- not important as phagocytes
- release mediators such as histamine to promote inflammation
- express Fc receptor molecules for lgE
Lymphocytes
Natural Killer (NK) Cells
- Do not kill pathogen directly, but induce apoptosis of infected cells(cancer and viral)
- Release perforins, insert in membrane and make pores, granzymes enter infected cell and activate caspase enzymes that induce apoptosis
- Big player in immune surveillance and the bodies defense against cancer
- Do not have T-cell receptors, but do express Fc receptor molecules for lgE
Bradykinins
Are known to cause endothelial gaping. Very potent vasodilator
Cell-mediated immunity :
entirely associated with cell surfaces, T-cell receptors, that are unable to “see” free antigens
T-cells (definition)
can regulate the immune responses of other cells (CD4) or indirectly kills cells (CD8) that carry specific antigens
Specific immunity (Adaptive immunity) , T-cell:
- Lymphocytes produced in red bone marrow, migrate to thymus (primary lymphoid organ) where they mature (VDJ recombination of T cell receptor) and undergo selection
- T cells must recognize self MHC proteins needed for activation but not the self anitgens (self tolerance) that the MHC presents (T-cell eliminated in thymus if criteria not met)
- “Naïve” T cells recirculate only between the blood and secondary lymphoid organ
(Ex. Spleen, tonsils, or lymph nodes) ++ Do not enter the tissues; activated in secondary lymphoid organs - T-cells 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)
What was the analog of Dr. Sharp on CD4 and CD8 figurative
What do CD4 do, they are generals, they give order and CD8 are hand-to-hand combat soldier
What was the analog of Dr. Sharp of T-cell maturing in Thymus
They goes to University of thymus where only 2 % pass,
If the graduate fail to attack the wrong cells but start attacking the good one, then it is an autoimmune
what is CD stands for?
cluster and differ
Cytotoxic T cell (definition)
kills cells that are infected with viruses (or other pathogens)
*macrophage
Cytotoxic T cells (characteristics)
- 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 expressing the same combination of foreign peptide on MHC class I are targeted; may include tumor cells, virally infected cells, or intracellular parasites
- Release perforins, insert in membrane and make pores, granzymes enter infected cell and activate caspase enzymes that induce apoptosis
Helper T cells (definition):
involved in activating and directing other immune cells; their cytokines largely determine whether an immune response is humoral or cell mediated; no killing ability
Helper T cells (characteristic):
- have CD4 coreceptor protein
- 1st signal is initiated by exogenous antigens bound to MHC class II proteins of macrophages, dendritic cells (phagocytosis or endocytosis), and B cells (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 Respone- 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 T and B cells; 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 concentration increase synthesis of prostaglandins, resulting in fever
- GM-CSF: Granulocyte-macrophage Colony Stimulating Factor
TH2 cells mainly secrete:
- IL-4: growth factor for B cells; suppress TH1 cell production
- IL-5: stimulates B cells for growth, differentiation, and production of antibodies; activates eosinophils
- IL-10: inhibits TH1 cells, cytotoxic T cells, NK cells, & macrophage cytokine synthesis
Humoral immunity (definition) :
Based on antibodies on cell surfaces and body fluids (blood, lymph, etc.)
B Cells (definition) :
-bind specific to free (soluble) antigen or particulate antigen with its membrane bound antibody (B cell receptor); also serves as APC to TH cells.
If B cells is 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 to their specific antigen
Clonal deletion definition:
removal, usually by apoptosis
Receptor editing definition:
opportunity to rearrange their conformation via RAG (Recombination Activating Gene)
Anergy definition:
B cells enter a state of permanent unresponsiveness and fail to respond to their specific antigen
B cells (characteristics):
- B Cells produced in red bone marrow; immunoglobulin (lg) synthesis occurs
- lg is encoded by different segments of DNA, a V (variable) segment, a D (diversity) segment, a J (joining) segment, and a constant region; variable are reshuffled by RAGs
- Each lg consists of 2 identical short polypeptides called light chains and 2 identical longer polypeptide 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 1 of 5 possible DNA sequences named u (mu), 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” B cells
- B cells recirculate only between blood and lymphoid organs, activated in secondary lymphoid organ (Ex. Lymph nodes, MALT, which includes tonsils and appendix)
- B cells recognize their cognate antigen in its native form with its B-cell receptors (antibodies); each Ig can bind identical epitopes
- Binding of antigen to Ig on surface of appropriate B cell 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 cells and plasma cells that secrete antibodies against the identical antigen
What are all Ig and their function:
IgM: pentamer, 1st antibody secreted during primary immune response monomer, present on surfaces of B cells
*chinese star
IgG: monomer, major antibody secreted during secondary response; 75% of plasma antibodies
IgD: monomer, present only on surfaces of B cells; serves as antigen receptor
IgA: dimer, most abundant form of antibody in body secretions; high density of IgA-secreting plasma cells in MALT
IgE: Fc binds to mast cells, basophils, etc.; often secreted in response to helminth worms; low conc. In plasma
*Neutrophils, Basophils…
B cells are divided into two type of cells, what are they ?
Plasma B cells and Memory B cells
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
*Archers
Memory B cells:
specific to antigen 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+ T cell numbers decline below a critical level of 200 cells per uL. Cell-mediated immunity is lost (*cold/atletic foot/ deadly)
Phylum- Platyhelminthes (Flatworms):
phylum containing simplest bilaterally 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 multicellular organism, an integument)
- parenchyma (loosely arranged mass of fibers and cells of several types
What is the differences between Acoelomate, Pseudocoelomate and coelomate?
Acoelomate : ecto,meso,endoderm on the outside and lumen in the middle
Pseudocoelomate: Ecto and mesoderm on the outside, pseudocoelom (space between mesoderm and endoderm– not consider true lumen) endoderm and lumen
Coelomate: Ecto, meso and mesentery on the outside, coelom (space between 2 mesoderm), and endoderm and then lumen
Pathogen-associated molecular patterns (PAMPs)
small molecular motifs conserved within a class of pathogens
Phylum: Platyhelminthes
“Flatworms”: Phylum containing simplest bilaterally 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 multicellular organism, an integument)
- Parenchyma (loosely arranged mass of fibers and cells of several types