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189 Cards in this Set

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Who and what year:
recognized that only those who had recovered from the plague could nurse the sick without becoming sick again.
430 BC- Thucydides
variolation
Fifteenth century- Chinese and Turks used dried crusts from smallpox pustules (inhaled or inserted into small cuts in the skin “variolation”) to induce immunity.
Who and what year:
realized milkmaids who had contracted cowpox (mild disease symptoms compared to smallpox) were not susceptible to smallpox.
1796 - Jenner

Dude got lucky
M. tuberculosis?
bacteria

mycobacterium tuberculosis
C. albicans?
candida albicans

fungus that causes thrush, systemic candiasis
T. Brucei
Parasitic protozoa that causes sleeping sickness

Trypanosoma Brucei
-gram positive bacterium that colonizes human skin, pimples & boils (other strains = food poisoning)
Staphylococcus aureus
The four kinds of pathogens that cause disease?
Bacteria, fungus, virus, protozoa
The GI tract is exterior or interior?
exterior
pH of vagina and skin?
acidic
Defensins general mechanism?

Associated with what epithelial cells?
"Poke holes in the pathogen"

All epithelial cells
Lymphocytes?
B, T, and NK cells
Granulocytes? In order from darkest staining to lightest
Basophils
Eosinophils
Neutrophils
Dendritic cell function?
Main function is the presentation of antigen to T cells
Hematopoiesis
The generation of the cellular elements of blood, including:
Red blood cells (RBC)
White blood cells (WBC) or leukocytes
Megakaryocyte - Platelets
These cells originate from __________ stem cells (HSC) whose progeny differentiate and divide under the influence of various hematopoietic _________
-pluripotent hematopoietic

-growth factors
Most abundant leukocytes are the _________
Followed by _________
-neutrophils

-lymphocytes
General term for WBC?
leukocyte

ALL LYMPHOCYTES ARE LEUKOCYTES
NK cells?
Large granular lymphocytes
Natural killer (NK) cells, lymphocytes of innate immunity
small lymphocytes are resting cells that have not interacted with antigen
Naïve lymphocytes
lymphocytes that have interacted with antigen and proliferate
Lymphoblasts
Lymphoblasts eventually differentiate into ________ or ________
effector cells or into memory cells
NK cells (large granular lymphocytes) are found throughout the tissues of the body but mainly in the
circulation

remain in blood until infection
NK cells are particularly important for?

secrete?
important for protection against viruses and some tumors
Secrete cytokines which prevent viral replication and helps to activate T cell-mediated immunity
main cause of pus?
neutrophils
Neutrophils granules?
Are phagocytic cells that contain toxic substances in intracellular granules (primary and secondary granules)
Employ oxygen-dependent and oxygen-independent pathways to destroy pathogens
_______ circulate in the blood for about _______, then mature and migrate into tissues, they are then referred to as _______.
-Monocytes

-8 hours

-macrophages
Function of dendritic cell folds
folds allow maximum interaction with other cells of the immune system
What molecules do dendritic cells use to present?
MHC-1

AND

MHC-2
Follicular dendritic cells (FDC) ?

Related to dendritic cells?
hold intact antigens in specialized areas of lymphoid tissues

not related
Mast cells are found ?
in the skin, connective tissue and mucosal epithelial tissue of the respiratory and digestive tracts
Basophil = ?
Eosinophil = ?
Basophil = allergic reactions
Eosinophil = parasitic worms
The nucleus of the megakaryocyte is very large and lobulated, which, under a light microscope?
can give the false impression that there are several nuclei
Megakaryocyte function is determined by a large number of cytokines, including _____
thrombopoietin
Thrombopoietin
glycoprotein hormone produced mainly by the liver and kidney that regulates the production of platelets by the bone marrow
Do erythrocytes have a role in immunology?
erythrocytes have an important immunological role in clearing immune complexes from the circulation in persistent infections and in some autoimmune diseases
Site if hematopoesis at the following:
embryo?
3-7 months fetus?
After 7 months?
yolk sac ->spleen & liver -> bone marrow
pH of the phagolysosome?
acidic
Binding to macrophage C3B = ?

Binding to macrophage TLR = ?
C3B = phagocytosis
TLR engagement = cytokine secretion
Primary lymphoid organs?
Thymus and bone marrow are primary organs

Where maturation of lymphocytes takes place
Secondary lymphoid organs?
Lymph nodes, spleen and mucosal-associated tissues are secondary organs

Which trap antigen and promote lymphocyte activation
Lymphocytes recirculate at a rate of ?
Lymphocytes recirculate at a rate of 5 X 10^6 cells/min
Lymphocytes arrive at lymph nodes in __________; then they ________
Lymphocytes arrive at lymph nodes in arterial blood; extravasate from capillaries
Expansion of the lymph nodes occurs in ________
lymphoid follicles
cells in the spleen that take-up antigen and stimulate T an B-cells
Spleenic macrophages and dendritic cells
White pulp of spleen consists of sheath of lymphocytes called the ?
periarteriolar lymphoid sheath (PALS)
The gut associated lymphoid tissues, GALT include
tonsils, adenoids, appendix and Peyer’s patches that line the gut
BALT?
Bronchial-associated lymphoid tissues
Most secondary lymphoid tissue is associated with?
the gut
Pathogens arrive through direct delivery across mucosa mediated by specialized cells called
M cells
frequency of inherible innate immune disease?
rare
What infects the interstitial spaces, blood, and lymph?

Defense mechanism?
-Everything

-complement, macrophages, neutrophils
What infects epithelial surfaces?

Defense?
-neisseria gonorrhoeae and candida albicans

-Antimicrobial peptides
What infects the cytoplasm?

Defense mechanism?
-viruses, listeria, and protozoa

-NK cells
What infects the vesicles?

Defense mechanism?
-mycobacteria, trypanosomes

-Activated macrophages
Intracellular pathogens in nucleus or cytosol attacked by ?
killing the infected host cell
____ is by far the most important molecule in the complement cascade
C3
The quickest of the 3 complement pathways is the
alternative pathway
The Classical pathway is part of both the innate and adaptive immune response and can be activated by _______ or _______
C-reactive protein (innate) or antibody (adaptive) binding to the pathogen.

Always assume antibodies
______ is the product of C3 hydrolysis
iC3
alternative pathway soluble C3 convertase?

Bound C3 convertase?
iC3Bb

C3bBb
Pathogen bound C3b fragments (Bb is absent) can perform what function?
They can bind to Complement Receptor 1, CR1, on macrophages to optimize phagocytosis
What is the alternative C5 convertase?
Binding of C3b to existing C3bBb complexes at pathogens surface forms the alternative C5 convertase = (C3b)2+Bb
Classical C5 Convertase?
C4b2a3b
C5 convertase function?
Cleaves C5 into C5a and C5b
C5b function?
C6 and C7 bind and exposes the hydrophobic sites of C7 allowing it to insert into the lipid bilayer.
What happens when C8 binds C5b?
hydrophobic sites on C8 are exposed and it is inserted into the membrane with C6+C5b+C7
C8 function?
C8's exposed hydrophobic site once in the membrane initiates the polymerization of C9 forming the pores
C5a function? notable feature?
recruits neutrophils to infection site

Most potent anaphylatoxin
Factor P function? aka?
Up-regulates C3bBb and prevents inhibition by factor H.

aka properdin
Factor H function
Factor H plasma protein reduces complement reactions by making C3b susceptible to cleavage by factor I creating a iC3b fragment that is incapable of forming a C3 convertase
Factor I function
cleaves C3b into iC3b
DAF function? Aka?
leans over and binds to C3bBb and displaces Bb fragment

aka decay-accelerating factor
MCP function? aka?
leans over and binds to C3bBb and allows factor I to inactivate it

membrane co-factor protein
CR2
B-cell co-receptor and recognizes C3d
CR3 & CR4
recognize iC3b

iC3b can be recognized by phagocytic cells
C3a and C5a contribute to _________
Also referred to as ________
____ is more stable and potent than____
C3a and C5a contribute to acute inflammation
Also referred to as anaphylatoxins
C5a is more stable and potent than C3a
alpha-2-macroglobulins
inhibit potentially damaging proteases
alpha-2-macroglobulins mechanism
first trap the protease with a “bait” region -> protease cleaves the bait -> alpha-2-macroglobulin binds covalently through activation of thioester group -> surrounds the protease (still active) but cannot access other protein substrates
_______ and alpha-2-macroglobulin inhibit potentially damaging proteases
Serpins
Amphipathic
both hydrophobic and hydorphilic
alpha-defensins produced by?
Produced mainly by neutrophils and Paneth cells
Paneth cells ?
specialized epithelial cells of the small intestine
beta-defensins
Expressed mainly by epithelial cells of the respiratory tract the urogenital tract and the skin.
Macrophage receptor for C3b?

receptor for iC3b?
-CR1

-CR3, CR4
CR3 and CR4 recognize iC3b and other ligands such as:
LPS, lipopolysaccharide (Gram negative bacteria)
Lipophosphoglycan
Filamentous hemagglutinin
Cell-surface structures on yeast
Carbohydrate-binding proteins = ?

examples?
-lectins

-mannose and glucan
Scavenger receptors = ?
Scavenger receptors = preference for molecules that are negatively charged.
Examples of things scavenger receptors bind?
Nucleic acids and phosphate-containing lipoteichoic acids (Gram positive bacteria)
TLR-3
Ligands?
Microorganisms recognized?
Cells carrying receptor?
Cellular Location?
Ligands = double stranded RNA
Microorganisms recognized = viruses
Cells carrying receptor = NK cells
Cellular Location = Endosomes
TLR-4
Ligands?
Microorganisms recognized?
Cells carrying receptor?
Cellular Location?
Ligands = LPS
Microorganisms recognized = Gram negative
Cells carrying receptor = macrophages, dendritic cells, mast cells, eosinophils
Cellular Location = plasma membrane
TLR-5
Ligands?
Microorganisms recognized?
Cells carrying receptor?
Cellular Location?
Ligands = Flagellin
Microorganisms recognized = bacteria with flagella
Cells carrying receptor = intestinal epithelium
Cellular Location = cell membrane
TLR-7:
Ligands?
Microorganisms recognized?
Cells carrying receptor?
Cellular Location?
Ligands = single stranded viral RNA
Microorganisms recognized = viruses
Cells carrying receptor = NK cells, eosinophils, B-cells
Cellular Location =
Translocation of NFkB to macrophage nucleus initiates
transcription of proinflammatory cytokines -> IL-1, IL-6, CXCL8, IL-12 and TNF-alpha
IL-1 local effects? systemic effects?
activates endothelium and lymphocytes

fever/production of IL6
IL-6?
systemic effects of fever and acute phase protein production by hepatocytes
CXCL-8 aka? Local effects?
aka IL8

chemokine - recruits neutrophils and basophils
IL-12
activates NK cells
TNF-alpha local? system?
local = activates endothelium and increases permeability leading to increased entry and drainage

systemic = shock
Polymorphonuclear leukocytes
granulocytes = BEN
Are neutrophils in healthy tissue?
nope
The four structural classes of adhesion molecule present on white blood cells and the cells with which they interact are:
Selectins
Vascular addressins
Integrins
Immunoglobulin superfamily
Selectins ?
are carbohydrate-binding lectins
Vascular addressins
contain carbohydrate groups to which selectins bind
Integrins
typically bind to Ig superfamily proteins
Macrophage secretes TNF-alpha, CXCL8, IL6 -> causes
neutrophil release
In healthy tissue endothelial cells contain granules known as ________ which contain _________
-weibel-palade bodies

-p-selectin
Upon exposure to the inflammatory mediators ____, _____, and _____ the p-selectin in the weibel-palade bodies is transported to the cell surface
-Leukotriene LTB4
-C5a
-histamine
______ is also expressed on endothelial surfaces after exposure to TNFalpha or LPS
E-selectin
Diapedisis?
squeezing through endothelial cells
extravasation?
the process by which neutrophils migrate out of blood capalaries and into tissues
Neutrophil receptors for phagocytosis?
Fc
scavenger
CR3
N-formyl-met (not human)
mannose
CD14 (LPS receptor)
CR4
glycan
Fc receptor?
binds to Fc region on antibodies
respiratory burst?
Respiratory burst = Transient increase in oxygen consumption = purpose is to raise the pH of the phagosome so the granule contents can become active to kill pathogen
C-reactive protein Binds to ________ component of LPS of bacterial and fungal cell walls but not in human cells
phosphorylcholine
C-reactive protein can bind _____ to initiate classical pathway of complement fixation in absence of antibodies
C1q
mannose binding lectin binds
Binds mannose-containing carbohydrates of bacteria and yeast
Mannose containing carbohydrates on human cells do not bind MBL because ?
their geometry does not permit multipoint attachment to MBL
Do monocytes express macrophage mannose receptor?
no
Monocytes do not express the macrophage mannose receptor but have receptors that can bind to ________ coating a bacterial surface
MBL molecules
Type I interferon function?
Interfere with viral replication by infected cells

Alert immune system cells that infection is present

Make virus-infected cells more vulnerable to killer lymphocyte attack
Interferon type 1 mechanism
viral material enters cell -> transctiption factor IRF3 + NFkb + AP-1 turn on IFN-beta gene -> IFN-b is secreted -> IFN-b binds in autocrine to cell -> IFN-b causes IRF7 to cause expression of IFN-alpha
Does IFN-alpha expression depend on NFkB?
no
Type _______ interferon induce proliferation of NK. In addition, NK cells are also activated by ____ and _____
-type 1

-IL-12 (macrophages) and TNF-a (macrophages)
Stimulation of NK cells with IFN-a and IFN-b favors?

Stimulation of NK cells IL-12, IF-gamma release favors ?
-favors the development of cytotoxic effector function

-the production of cytokines
NK cells provide an early response to virus infection and ___________ take over to finish the job
effector T cells
Effector T cells enter the site of infection -> become major source of _____ and cell-mediated cytotoxicity -> secrete inhibitory cytokine _____.
-IFN-gamma

-IL-10
Function of IL-10?
turns off NK cells
NK cells are analagous to what adaptive immune cell?
CD8 T-cells
two terms for the part of the antigen bound by Ig or TCR
Epitope or antigenic determinant
(MHC) is a cluster of genes on the short arm of human chromosome __
chromosome 6
The genes for immunoglobulin heavy chain and T-cell receptor B-chain have arrays of _______ segments
V, D, and J segments
Genes for the immunoglobulin light chain and the T-cell receptor alpha chain have ______ segments
D and J
Cytotoxic t-cells are know as ______ and are presented antigens by ______.
-CD8 t-cells

-MHC class 1
What is CD8?
The coreceptor that ensures cytotoxic t-cells only bind MHC1.
How many subunits of MHC1 are membrane bound?

MHC 2?
MHC1 = 1 anchor

MHC2 = 2 anchors
Helper T-cells are called _____ and have antigens presented to them via _________
-CD4 T-cells

-MHC-2
Coreceptor for MHC2 molecules?
CD4
MHC class 2 molecules are found on
macrophages, dendridic cells, and b-cells
MHC class I presents antigens derived from the _______
cytosol
The TCR recognizes both the _______ and ________
antigen and MHC molecule
Why type of pathogens do CD8 T-cells mainly kill?
viruses
TH1 cells mainly activate ?

TH2 cells ?
TH1 cells mainly activate macrophages

TH2 cells chiefly help B cells
antibody isotypes are named according to their?
heavy chain
IgE?
binds to mast cells -> allergic reactions
First antibody produced in primary adaptive immune response?
IgM
IgM structural component?
pentameric -> 10 bind sites
Highest quantity antibody in the body?
IgA

the body includes mucosal surfaces
Highest quantity in the blood?
IgG
________ are the antibody isotypes found mainly in the blood, lymph and extracellular spaces
IgM, IgG and IgA
_____ region of IgE binds to mast cells.
constant region
Tissue rejection caused by
extensive polymorphism of MHC class I and II genes
Memory b-cells are activated and what antibodies are used?
IgG
Positive selection?
T-cells that bind too poorly to MHC are eliminated. Those that bind tight move on to the next step
Negative Selection?
T-cells that survive positive selection are tested again. If they bind TOO strongly to MHC they will be eliminated
1st immune system components to be activated = ?
complement
1st Step in the alternative pathway involves
spontaneous hydrolysis and activation of complement component C3
_____ is the product of C3 hydrolysis
iC3
iC3 binds to _____ in the blood or ECF making it susceptible to cleavage by ______
factor B

factor D
What activates C5 in the alternative pathway? What is it called?
Alternative C5 convertase = C3b2Bb
What activates C5 in the classical pathway? What is it called?
Classical C5 convertase = C4b2a3b
Difference between DAF and MAP mechanism
DAF -> DAF binds and Bb is released

MAP -> MAP binds, Bb is released, and then Factor I cleaves C3b to iC3b
What do C3a and C5a do?
bind mast cells, phagocytes and endothelial cells -> release of histamine -> Histamine increases blood vessel permeability and blood flow
Activate endothelial cells -> direct phagocytes to site of infection
C5a Increases the adherence of monocytes and neutrophils to blood vessel walls and acts as a powerful __________ factor
chemotactic
what is alpha-2-macroglobulin?
a protease inhibitor
Rolling Adhesion:

What binds to selectin?
sialyl-Lewis X
Rolling Adhesion:

Where is LFA-1? What does it bind to
LFA-1 is on the neutrophil and binds to ICAM-1
Rolling Adhesion:

Where is ICAM-1? What does it bind to?
ICAM-1 is on the epithelial cells and binds to LFA-1
Rolling Adhesion:

What is CXCL8 and where does it bind?
A chemokine that will bind to CXCL8 receptor and help the macrophage enter thru the basement membrane
Rolling Adhesion:

What is CD31?
Protein between epithlial cells that macrophage slips through
azurophilic granules?
proteins and peptides that can distrupt and digest microbes
specific granules?
competes with the microbe from metals (iron and copper)
______ cleaves C4 and C2
MASP-2
C3 convertases:
Alternative?
Classical?
C3 convertases:
Alternative – C3bBb
Classical – C4bC2a (C4b2a)
C5 Convertases:
Alternative?
Classical?
C5 Convertases:
Alternative = C3b2Bb
Classical = C4b2a3b
Alternative C5 Convertase
Alternative = C3b2Bb
Classical C5 Convertase
Classical = C4b2a3b
When any human cell becomes infected it responds by making cytokines called type 1___
interferons
Type two interferons are made by
NK cells, CD8 T cells and CD4 TH1 cells
Which type 1 interferon is multiform? single form?
single form = type beta

multi = type alpha
Which lymphocytes have a well developed cytoplasm? which dont?
B and T dont -> all nucleus

NKs have well developed cytoplasm
Two effector functions of NK cells
Cell killing
Secretion of cytokines
MIC ligand is expressed by/on?

receptor for ?
-virus infected cells

-receptor for NKG2D on NKs
Will a B-cell have somatic recombination of TCR genes?
no - false
IgE ________ region binds to ______ cells
IgE constant region binds to mast cells
If IgE variable region catches an antigen what happens?
Causes the mast cell to degranulate
Tissue rejection caused by extensive polymorphism of
MHC class I and II genes
What can Work in the anaerobic conditions found in damaged tissue
Neutrophils
Responsible for puss?
neutrophils