3A Flashcards
What are the two types of hemocytoblasts?
-Myeloid line
- Lymphoid line
What is a hemocytoblast?
-multipotent stem cell
- all cells start here
What are the types of Blood parts in the Myeloid line?
-erythrocytes/ RBCs
- platelet cells
- granulocytes/ monocytes
How do erythrocytes form?
form in red bone marrow in erythropoiesis
How do platelets form?
Fragments form in red bone marrow from megakaryocytes in thrombosis
What are the types of granulocytes and monocytes?
- neutrophil
- basophil
- eosinophil
- monocyte
How do granulocytes/ monocytes form?
through leukopoiesis
What blood cells are part of the Lymphoid line?
- B-lymphocytes
- T-lymphocytes
- Natural killer cells
Where do lymphocytes mature?
In red bone marrow
Where do t-lymphocytes and pre-t-lymphocytes form?
-develop in the red bone marrow and then migrate to the thymus where they mature
What are t-lymphocytes comparable to?
special forces
Where do Natural Killer Cells form?
- this special type of lymphocyte matures in the red bone marrow
What are NK cells comparable to?
hit men
What part of immunity are natural killer cells?
innate immunity
What is innate immunity?
- immediate response to a wide array of substances?
What are the type of innate immunity?
1st defense
- physical and chemical barriers
2nd line of defense
- non -specific internal defense
- physiological response
What are the components of the 1st line of defense?
- physical and chemical barriers like skin, membranes, and secretions
- surface barriers and their secretions
What does the first line of defense do?
prevents entry of pathogens into the body
What is the second line of defense composed of?
- non-specific target cells and compounds that fight pathogens that have entered the body
- non-specific internal defense including cells and antimicrobial compounds
- physiological responses such as inflammation or fever.
Is the microbe identified in the first or second line of defense/ innate immunity?
NO
- just a broad defense against the bacteria but it doesn’t know what bacteria
What is adaptive immunity?
a delayed response to specific antigens with memory
What is included in adaptive immunity
cell-mediated and humoral branches
Why is adaptive immunity important
- it allows for a stronger secondary response due to memory cells produced against a specific antigen
What directs the cell-mediated branch of adaptive immunity?
t-lymphocytes
What directs the humoral branch of adaptive immunity?
-b-lymphocytes
What do first line of defense physical barriers include and do?
-includes mucous membranes and skin that protect our outer body (skin) and inner body surfaces (mucous membrane) these both prevent pathogens from entering the body
- the normal flora is on some surfaces that have commensal microbiota that helps prevent invading pathogens
- secretions from mucous membranes trap microbes allowing time for antimicrobial actions
- secretions are acidic interfering with bacteria growth
- lysosomes defensins, and dermcidin are secreting by skin and mucous membranes
Where are normal flora found?
on skin with commensal microbiota
What does skin and mucous do?
prevents pathogens from entering
What do secretions do?
-trap microbes allowing for antimicrobial actions
- secrete lysosomes, defensins, dermcidin
- have an acidic ph to deter bacteria growth
Do secretions kill bacteria?
No, just deter it
What cells form the second line of defense?
- phagocytic cells
- proinflammatory secreting cells
- apoptosis-initiating cells
- parasite-destroying cells
What do phagocytic cells do?
engulf pathogens to destroy them
What do proinflammatory secreting cells do?
secrete histamine, heparin, eicosanoids
What are eicosanoids?
local hormones
What is heparin?
an anticoagulant
What do histamines do?
stimulate vasodilation and increase permeability
What do apoptosis-initiating cells do?
trigger apoptosis in tells through the release of perforin which initates response and granzyme
What does perforin do?
-pokes holes in cell
What does granzyme do?
self-destruct button
What do parasite destroying cells do?
secrete a variety of substances that attack the surface of multicellular paracytes
What do parasite destroying cells do?
- secrete a variety of substances that attack the surface of multicellular parasites
-death by 1000 papercuts
-eosinophils go in like vultures
What is an example of a parasite destroying cells?
eosinophils
What is an example of an apoptosis-initiation cell?
NK (t-lymphocyte)
What are examples of proinflammatory secreting cells?
-basophils in circulation
-mast cells in tissues
What is the second line of defense?
antimicrobial components, physiological responses
What is an interferon?
a class of cytokines that nonspecifically impede viral spread
What are the components of the second line of defense?
Interferons like
-IFn alpha and beta
-IFN gamma
Complements
What do ifn alpha and beta do?
- bind to neighboring cells and prevent their infection by triggering the synthesis of enzymes that destroy viral nucleic acids and inhibit the synthesis of viral nucleic acids and proteins
- stimulate NK cells to destroy the virus-infected cells (basically call NK cells
Where is IFN alpha and beta produced?
produced by virus infected cells
What does IFN gamma do?
-stimulates the macrophages to destroy virus-infected cells
-serves as backup and cleans cell debris
What is a complement antimicrobial component?
- a group of plasma proteins that play a role in eliminating immune complex, cytolysis of pathogen cells, and opsonization
What is the difference between classical pathways and alternative pathways?
- alternative pathways do not require or involve antibodies and classical pathways do
What is a classical pathway?
when the plasma proteins bind directly to the antibody
What does the classical pathway do?
eliminates immune complexes
How does the classical pathway work?
the complement (C) cross-links (connects) immune (antigen-antibody) complexes to the erythrocyte, which transports to the liver and spleen
(acts like velcro that helps collect immune complexes and bring them to liver and spleen)
What does the alternative pathway do?
- the plasma proteins that bind directly to pathogen
- preforms cytolysis or opsonization
How does opsonization work?
- complement (C) binds to pathogen and acts as an opsonin
- enhances phagocytosis by flagging cells and enhancing inflammation
-enhances inflammation by activating mast cells and basophils attracting neutrophils and macrophages to site
How does cytolysis work?
-complement proteins create membrane attack complexes to lyse cell
- big holes allow in water leading to lysis.
What is inflammation?
an immediate, localized sequence of events that occurs in reaction to injury or immune stimulation
How does inflammation occur?
- pro-inflammatory compounds (histamine) is released by injured tissue, basophils, mast cells, and infectious organisms
- vascular changes triggered including vasodilation, increased capillary permeability, and increased cell adhesion molecules that support diapedesis of leukocytes
-(cams act as speed bumps in margination) - leukocytes are recruited by margination (bind to cams) and undergo diapedesis and chemotaxis
-plasma proteins exit the capillary decreasing capillary osmotic pressure and associated reabsorption - increased fluid and associated materials/cells picked up by lymphatic capillaries and delivered to lymph nodes for cleansing
What is chemotaxis?
following of chemical cues to the injury site
What is diapedesis?
exit capillary through endothelia
What is histamine?
a pro inflammatory compound
What do injured tissues release?
histamine
What is histamine released by?
-injured tissue,
-basophils
-mast cells
-infections organisms
What vascular changes occur during inflammation?
- vasodilation
-increased capillary permeability
-increased CAMS
What is a fever?
increase in body temp equal to or higher than 1 degree celsius from normal (37)
What are signs of inflammation?
-redness due to increased blood flow
- heat due to increased blood flow and metabolic activity
- swelling due to increased volume in interstitial fluid
- pain due to the stimulation of pain receptors in area (bc swelling pushes on them)
What first stimulates a fever?
pyrogens from immune cells and or infectious agents that circulate in the blood and trigger the hypothalamus to increase body temp
Hoe is a controlled fever beneficial?
-must be low grade
- inhibits bacterial and viral growth, promoting immune activity, accelerating tissue repair
What are the phases of fevers?
- onset: temps begin to rise
- stadium: elevated temp maintained
3: defervescence : temp returns to normal
What are the grades of fevers?
- low grade: 100-101
- intermidiate:102
- high grade: 103-104
- dangerous: over 104
What is an antigen?
- a molecule normally a protein or polysaccharide that is recognizable to immune cells through one or more of its epitopes
What is an epitope?
antigenic determinant
What does a self-antigen do?
recognizes the body’s tissues as self, allowing healthy tissue to be ignored by body’s immune system so no immune response is triggered
- also called immunotolerance
What does a foreign antigen do?
- stimulates an immune response (immunogenicity) by binding to either an antibody and or t-cell receptor located on t-lymphocytes
What is an antibody?
- immunoglobulin
- a protein produced y specialized immune cells capable of recognizing, and binding to one or more epitopes on an antigen
What is a major histocompatibility complex?
-MHC
- a group of genes responsible for forming MHC molecules
- genetically deteremined so they are unique to each person
What are the MHC groups?
Class one and two
What do class one MHC’s do?
-display endogenous proteins located inside the cell membrane of all nucleated cells
- in healthy cells these are self-antigens which should be ignored by the immune system
- in an infected cell these include foreign antigens which stimulates an immune response
-healthy cells have self-antigens on MHC1
- infected cells have foreign antigens on MHC1
What do class two MHCs do?
- produced in antigen-presenting cells only
- phagocytic
- APCs display exogenous proteins that originated outside the cell on MHC class two molecules
- these exogenous proteins (antigenic) come from processed phagocytic molecules engulfed by APCs
- essential in t-lymphocyte activation
-basically rallies all the troops, shows and tells antigens it finds, but doesn’t kill it (don’t shoot the messenger)
How do proteins get displayed on MHC cells?
-MHC1 cells are found on all nucleated cells
- self-antigens displayed on MHC1 are ignored/tolerated by the immune system
- MCH1 molecules are synthesized in the rER
-Self-antigen (peptide fragments of the cell) randomly bind to MHC1
- MHCI/self-antigen complex displayed at the membrane signaling to the immune system “all is well” and cell is ignored
- Infectious agents (viral particles or other microbes) enter the cell and are digested into fragments
-MHC1 molecules and processed foreign antigens combine and are transported to the plasma membrane
- MHC1 molecules are synthesized in the rER
-Processed foreign antigens bind to MHC 1
- MHC1/self-antigen complex is displayed at the cell membrane signaling to the immune system that “I’m sick” resulting in the apoptosis of the infected cell
-Only APCs synthesize MHCII molecules
APCs phagocytize an exogenous antigen (from an engulfed pathogen)
- secretory vesicles containing MHCII complex forms
- the complex is embedded in the cell membrane and communicates to the immune system that “this is what we should be looking for
What does the APC and MHCII complex say?
this is what we should be looking for
What synthesizes MHCII molecules?
APCs
What do self antigen-mhc1 complexes say before an infectious agent is ingested?
I’m ok
What do self antigen-mhc1 complexes say after an infectious agent is ingested?
I’m sick
How many t-cell receptors are on a single cell?
multiple, identical antigenic t-cell receptors on a single cell
How are t-lymphocyte classes shown?
-specific cell docking proteins are associated with the t-lymphocytes
- each lymphocyte has a specific CD
How do Helper t-lymphocytes work?
- display CD4 along the t-cell receptor
- foreign antigens are processed by APCs and displayed on MHC2
- TCR had specific genetically determined antigen binding sites
- Helper t-cells are activated with binding
What is CD4 on?
only helper t0lymphocytes and interacting with MHC2
What are the types of t-lymphocytes
helper t-lymphocytes
cytotoxic t-lymphocytes
How do cytotoxic t-lymphocytes work?
-displays CD8 along the side
-endogenous antigens are displayed on MHC1 of all nucleated cells
- TCR has specific genetically determined antigen binding sites as well
CD8 interacts with MHC1
- CTC activated with binding
What is CD8 associated with
-MHC1
-Cytotoxic T-cells
What are the two types of adaptive immunity?
- cell-mediated
-humoral immunity
What is cell mediated immunity directed by?
-t-lymphocytes
What is cell-mediated immunity effective against?
antigens within the cell
How do Cytotoxic t-lymphocytes help with cell-mediated adaptive immunity
- become activated by binding to foreign Antigens displayed on the infected cell
- effector response is to trigger apoptosis of the infected cell through the release of perforin and granzyme y activated cytotoxic t-lymphocytes
- activated cytotoxic t-cells CD8 target infected/ unhealthy cells stimulating them to undergo apoptosis
How do helper t-cells help with cell-mediated adaptive immunity?
- activated helper t-lymphocytes stimulate the proliferation of activated t-lymphocytes (cytotoxic and helper) and lymphocytes through the release of interleukins (IL2 + IL4)
- basically helps humoral and cell mediated
What is humoral immunity directed by?
b-lymphocytes
What is humoral immunity effective against?
antigens outside of the cell
How does humoral immunity work?
- b-lymphocytes are activated when antigens bind to its b-cell receptors and the antigen BCR complex is engulfed, processed, and displayed
- helper t-lymphocytes interact with this complex stimulating the proliferation of activated lymphocytes resulting in the formation of memory cells and plasma cells
- effector response is the release of antibodies into the body fluids by newly produced plasma cells
- activated b-cells release antibodies which act in a variety of ways to support the immune system
What response does humoral immunity have?
- the release of antibodies into the body fluids by newly produced plasma cells
- activated B-cells release antibodies that act in a variety of ways to support the immune system
How does co-stimulation of helper t-lymphocytes work?
- during first stimulation CD4 on helper t-lymphocyte binds with MHC2 molecule on APC and TCR on helper t-lymphocytes interacts with antigen within the MHC2 molecule
-during the second stimulation interleukin 2 (IL2) self-stimulates cloning of helper t-lymphocytes - this creates the effector response of activated t-lymphocytes releasing interleukin that acts to regulate immune cells
How does the co-stimulation of B-lymphocytes work?
-1st stimulation the free antigen binds to BCR and B-lymphocyte engulfs (phagocytosis) complex and presents antigen to helper t-cell
- 2nd the stimulation the b cells act as an antigen-presenting cells and the helper t-lymphocytes bind to these cells and release IL-4 which triggers b-cell proliferation forming memory and plasma cells
-this has the effector response of antibodies being capable of recognizing the initial antigens and are secreted from plasma cells and circulating through the lymph and blood
What happens when Antigens bond to the FAB site (f antigen binding site)
- neutralization
-aggulation
=precipitation
What is neutralization?
when the antibody binds to the fab site and covers the biologically active portion of the microbe or toxin
-binds to and blocks antigen to prevent it from becoming active
-
What is aggulation?
when the antibody binds to the FAB site and cross-links cells like bacteria to form a clump
What is precipitation?
- when an antibody binds to the FAB site and cross-links circulating particles like toxins forming an insoluble antigen-antibody complex
- particles are harder to identify when soluble so this makes them easier to identify
What happens when a bacteria enters the body?
aggulation
What is the F(C) site
constant region
What happens when an antigen binds to the F(c) site
-complement fixation
- opsonization
- activation of NK cells
What is complement fixation?
when an antibody binds to the FC region and complement proteins so that the complement is then activated
What is opsonization
when the FC region of an antibody binds to receptors of phagocytic cells triggering and enhancing phagocytosis
What is the activation of NK cells?
- when the FC region of the antibody binds to an NK cell triggering the release of cytotoxic chemicals
- antigens bind to antibodies, NK Cell binds to the constant region
What is primary response?
the immunologic response to a first exposure
What is a lag phase?
the initial period of no detectable antibodies
What does exposure lead to in immunity?
the production of antibodies
How soon does the production of antibodies happen?
- within 1-2 weeks before antibodies peak and then it declines over time
How does the production of antibodies start?
with plasma cells producing IGM and IGG
What are the two types of acquired immunity?
passive and acive
How is passive immunity acquired?
- the transfer/ receiving of antibodies from another source
- naturally acquired or artificially acquired
How is natural passive immunity acquired?
- transfer of maternal antibodies across the placenta or breast milk
- short term protection
How is artificial passive immunity acquired?
- transfer of direct administration of collected antibodies
- not quick or efficient
- typically antitoxins or antivenoms
-used when body doesn’t stand a chance of making it on its own - most people won’t ever need
How is active immunity acquired?
-develops in response to antigen exposure
- we make antibodies
How does naturally acquired active immunity happen?
- develops after exposure to antigens in environment
How does artificially acquired active immunity happen?
- develops after administration of an antigen (usually through vaccination)
-this stimulates an active immune response and promotes immunity to that particular antigen
How do vaccines work?
vaccines stimulate the first exposure to build memory cells so the first real exposure looks like the second exposure would
What is the difference between first and second exposure?
- in first exposure igm is produced first than igg and the levels slowly rise
- in second exposure antibody levels rise rapidly to a higher titer and last longer, predominantly igg, igg is now produced at the same time as IGM
