Non-specific immunity Flashcards
What defines and constitutes the first line of defense?
1st line - chemical and mechanical barriers
- surface membrane barriers
- skin and mucous membranes and their secretions
mechanical
- stratified squamous ET (stratum corneum) of skin
- mucous membranes lining body cavity
Chemical
- acidity of skin secretions
- HCl and digestive enzymes of stomach/small intestine
- bactericidal enzymes of saliva and tears
- mucous traps of digestive and respiratory tracts
What are some components of the 2nd line of defense?
phagocytosis, natural killer cells, fever, inflammatory response
how does phagocytosis contribute to nonspecific immunity? what cells are responsible?
macrophages and neutrophils and eosinophils
- none require specific receptors on surface
- ingest any foreign cells
intracellular digestion
release of free radicals, defenses
opsonization - coating of complement protein and antibodies to enable phagocytosis of foreign cells/particles
how do natural killer cells contribute to nonspecific immunity? what do they develop from? what do they have receptors for?
develops from same line as T ells - non specific form of lymphocyte
- does have receptors for constant region of antibody, but does not require recognition
kills cancer cells/virus infected cell before activation of immune system
- similar to killer T cell: releases perforin and granzyme B
- perforin pokes holes in cell membrane, granzyme ruptures inside of the cell
how do fevers contribute to nonspecific immunity? what organ is in charge of regulation body temperature?
leukocytes and macrophages release pyrogens
- pyrogens - reset body temperature by causing hypothalamus to increase temperature
increased temperature inactivates bacterial enzymes
- sequesters ion and zinc needed by bacterial enzymes into liver and spleen
- increases metabolic rate of cells
how does the inflammatory response contribute to nonspecific immunity?
inflammation brings increased number of phagocytic ells and plasma proteins to the invaded area
- help isolate, destroy or inactivate the foreign cells/virues
- remove debris
- prepare for healing or repair
begins with flood of cytokines (inflammatory chemicals) released into the ECF by injured tissue
- 5HT and histamine in crease permeability
describe the role of the following chemicals in the inflammatory response: prostaglandins, plasma bradykinin, histamine and heparin
what affect do steroids have on inflammation?
prostaglandins - vasodilation, increase capillary permeability
plasma bradykinin - vasodilation, increase permeability
histamine - vasodilation and increased permeability
heparin - prevents clotting and injury site
steroids decrease inflammatory response and decrease healing
what if interferon? what releases it? what are its functions?
anti-microbial protein synthesized in cells that are infected by a virus
- also released by activated lymphocytes, macrophages
function - simulate neighboring cells to make antiviral proteins which prevent replication of the virus
- does not protect infected cells
- autocrine/paracrine: travels short distance to warn other cells
- antiviral effects: activation of macrophages and mobilization of NK
what is complement? what are the two pathways?
anti-microbial proteins - similar to clotting proteins
- produced by liver
- activated in cascade
classical pathway - involves activation by Fc fragment of antibody
- rapid - linked to immune system (specific)
alternate pathway - does not need antibody (nonspecific)
- triggered by complement activation
- triggered by polysaccharides of bacterial coat
what are the first steps of the classical and alternative pathway? describe the following steps
classical - antibody exposure activates C3
alternate - complement/sugar interaction activates C3
- C3b binds to target cell surface
- triggers insertion of membrane attack complexes (MAC)
4, form and stabilizes opening in target cell membrane - interferes with target cells ability to release Ca
- provides binding sites for macrophages/neutrophils
- stimulates basophils/mast cells to release histamine
- attracts neutrophils
Describe the 3 ways complement destroys pathogens: enhanced inflammation, opsonization, cytolysis
enhanced inflammation - complement C3a stimulates mast cells/basophils to release inflammatory chemicals
opsonization - complement C3b makes bacteria easier to phagocytose by coating surface
- serve as binding sites for macrophages and neutrophils
cytolysis - complement C3b leads to rupture of target cells
- triggers insertion of MAC proteins which allows cytoplasm to leak out
Describe what C3a/b and C5a/b do in the complement pathway
C3/5a - triggers mast cells/basophils to release histamine and increase inflammatory response
C3b - binds to surface of bacteria for opsonization - increases changes of phagocytosis
- OR can bind to C5 and split it
C5b - binds with C6-9 and makes donut like opening - MAC
- causes cytolysis
describe specificity and memory of the specific immune response
specificity - immunity directed against particular pathogen
- immune system has ability to recognize particular substance
memory - ability of immune system to recognize the repetition of previous event
- provides more rapid response
what is an antigen? define the following: hapten, antigenic determinant, antigenic receptor, and epitope
antigen - substance that stimulated the immune response
- typically large molecule - protein, polysaccharide, lipids
hapten - molecules of low molecular weight that are too small to be antigenic on their own, but can become antigenic by binding larger molecule
antigenic determinant - immunogenic site on the antigen that antibodies or T lymphocytes can bind
antigenic receptor - molecules on the surface of B/T lymphocytes which recognize and combine with particular antigenic determinants
epitope - specific sequence of AA/polysaccharides on antigen surface that would fit variable component of an antibody
do T cells make antibodies
no, but they have receptors on their surface that function similarly to antigens
- receptor specific to antigen epitope
- can get multiple responses to same antigen due to different epitopes on surface
what is a polyclonal response? how is this possible?
different components react to different epitopes on the same antigen
most naturally occurring antigens have many sites that:
- activate several different lymphocyte populations
- bind different kinds of antibodies
describe the role of the t lymphocyte in the immune system
originates in red bone marrow, mature and multiply in the thymus
- each cell recognizes only one antigenic determinant
- selection occurs in thymus
competent lymphocytes reside in diffuse lymphatic tissue, spleen, lymphatic nodules, and in the paricortical and medullary areas of lymph nodes
describe the role of B lymphocytes in the immune system. what happens when they are activated?
originate and mature in red bone marrow
- one lymphocyte produces antibodies which recognize only one antigen
reside in diffuse lymphatic tissue, spleen, germinal centers of lymphatic nodules
when activated - increase ribosomal ER and golgi apparatus
- increases amount of cytoplasm
describe the role of macrophages in the immune system. what do they arise from?
arise from monocytes in the blood
secrete chemicals which activate T/B cells
T cells secrete chemicals that activate
act as antigen presenting cella
reside in loose CT, lymph node sinuses, lung, liver sinusoids
what is an APC? what dose a helper T cell do?
antigen presenting cell - must be phagocytic
- lysosome breaks down antigen into protein components and present them on the surface
T helper cells - undergoes cellular changes that recognize specific epitope of specific antigen
- cellular changes allow T helper cells to release molecules that activate T/B cells - causes them to multiply
what is an MHC class I molecule? what is its function? what is the purpose of TAP channels on ER
found on any nucleated cell in the body
function - present antigens produced internally on the external surface of plasma membrane - endogenous proteins
- MHC I /antigen complex can bind to a T cell receptor to activate the T cell
- T cell can destroy the cell demonstrating MHC I/antigen complex
TAP channel - allows molecules into lumen of ER
- binding site of MHC I on inside of lumen, need to let molecule in
- TAP: transporter associated antigen processing
once the MHCI receptor/antigen is presented, what happens next?
T killer (cytotoxic) cells interacts with MHC I
- CD8: specific binding site on T cytotoxic that recognized MHCI
- intermolecular binding - activates T cells, stabilizes activity
what is the MHC class II molecule? What is its function>
found only on antigen-presenting cells - exogenous antigen
- macrophages, B lymphocytes, monocytes, dendritic cells
engulf foreign antigen - binds with protease enzymes to degrade antigen into antigenic components
- vesicle binds with golgi or ER
MHCII on the golgi or ER leaves and presents antigen
What happens after MHCII receptor/antigen is presented?
T helper interacts with MHCII
- CD4: specific binding site on T helper that interacts with MHCII
- intermolecular binding - activates T cells, stabilizes activity
what are cytokines? what are they involved in? describe interferon gamma, interleukin-1 and 2
cytokines - proteins/peptides secreted by one cell that regulates another
- involved in costimulation
interferon gamma - increases expression of MHC I/II molecules
- secreted by helper T, cytotoxic T and NK cells
interleukin-1: costimulation of B and T cells
- secreted by macrophages, B cells and fibroblasts
- need CD4 of T helper to help activate
Inerleukin-2: costimulation of B and T cells
- secreted by helper T
describe the following T cells: delayed hypersensitivity, memory, suppressor
delayed hypersensitivity - respond to antigens by releasing cytokines
- promote phagocytosis and inflammation in allergic reaction
memory - responsible for memory in cellular immunity
suppressor - limit the attack and the immune system functions
possess CD8 receptors
describe helper T cell activation
- macrophage processes antigen and displays via MCHII on its surface
- T helper cells interacts with molecule via TCR
- costimulation occurs as the macrophage releases interleukin 1 - which activated the T helper cells
- intermolecular-binding occurs via the CD4 molecule
can fascinate the activation of B cells or killer T cells
proliferated into more T helper and T memory cells
describe cytotoxic T cell activation
- MHCI displays antigen on surface of target cell
- activation of cytotoxic T cell begins when T cell receptor binds to MHCI/antigen complex
- costimulation occurs when CD8 molecule binds to MHCI
- more costimulation occurs due to cytokines (interleukin-2) released by helper T - goes to T killer cells that recognize same antigen
- activated cytotoxic T cell divides exponentially
can lyse cells via perforin
describe the proliferation of B lymphocytes
- before B cell can be activated by helper T, must process the same antigen that activated the T helper cell
- antigen binds to B cell receptor and both taken in via endocytosis - B cells uses MHCII to present antigen to T helper
- T helper releases interleukin-2 that stimulate B cell to divide
- B cell proliferates and gets converted to plasma cells - produce antibodies
also can create memory cell for subsequent exposures to the virus
describe antibodies. what is the constant and variable regions? what are they heavy and light chains?
y shaped protein produced by B lymphocytes in response to antigen
constant - non-specific component
- activated NK killer, complement, mast cells and basophils
variable region - specific component
heavy chain - large interior
light chain - small exterior
both heavy and light chain have constant and variable regions
Describe IgG antibodies
activated complement and functions as an opsonin to increase phagocytosis
- an cross the placenta to provide limited immune protection to the fetus/newborn
main antibody in primary and secondary responses - vaccines
active in Rh transfusion rxns
describe IgD antibodies
antigen binding receptor on the surface of B lymphocytes
describe IgM antibodies
pentamer - activates complement
- antigen binding receptor on the surface of B lymphocytes
active in ABO-induced transfusion reactions - agglutination
describe IgA antibodies
dimer
secreted into saliva, tears, and onto surface of mucous membranes
found in breast milk to provide limited immune protection to the newborn
describe IgE antibodies
binds to mast cells and basophils via constant region
- stimulates inflammatory response - causes hypersensitivities
- mast cells and basophils respond by releasing heparin/histamine
describe the following actions of antibodies: neutralization, opsonization, agglutination, complement fixation
neutralization - inactivates small antigens
- toxins released by bacteria binds to antibody
- ingested by macrophage - cell dies or releases chemicals
opsonization - triggers classical pathway of complement
- coating can be complement protein or antibody
- increases likelihood of endocytosis by macrophage
agglutination - precipitation occurs when multiple cells are bound to antibody
- binds antigens together
- easier for macrophages to break down
complement fixation - activates complement cascade (classical)
describe the primary and secondary immune response
primary - 1st exposure
- latent period (5-7 days): T helper must become activated before activating other lymphocytes
- activated lymphocytes begin to make antibodies - few, do not last long
- antibody levels peak at day 20
secondary - 2nd exposure to antigen
- no latent period
- antibody levels ride in minutes/hours
- plateau rather than peak may last for 6 weeks: stays high for longer period of time to protect body
describe passive natural immunity
passive - another body produces the antibodies
- fetus/infant not exposed to antigen, but gets antibodies from mother
IgG - crosses placenta
IgA - breastfeeding
describe passive acquired immunity
passive - another body produces the antibodies
- not natural, raised in commercial product and injected
Rhogam - Rh negative mom
- contains antibodies against D antigen - prevents mother’s primary immune response to D antigen
anti-snake venom - contains antibodies against venom toxin
- neutralizes or precipitates toxin
- prevents damage to tissue
describe active natural immunity
getting sick - develop memory cells via primary response
- when secondary response comes around, high amounts of antibody are produced to protect the body from getting sick again
describe active acquired immunity
acquired - commercial way of getting exposure
- do not actually get sick
T helper and B lymphocytes are activated and produce antibodies when exposed to antigen again
hepatitis, polio vaccines
what are hypersensitivities?
excessive immune reaction against antigens that most people tolerate
ex. mold, dust, pollen, vaccines, bee toxins etc
describe type I hypersensitivity. what antibody is involved?
allergies - IgE antibody - immediate hypersensitivity
1. initial presentation of allergen results in no symptoms but results in sensitivity
- APC present antigen fragments to T helper cells
- high # T helper cells differentiate into T helper 2 cells - released IL-4
- IL-4 stimulates B cells to secrete IgE
- IgE binds to mast/basophils
- later exposure to allergen results in alleged binding/crosslinking the antibodies bound to mast/basophils
- mast cells and basophils degranulate and release large amounts of histamine
- systemic reaction (anaphylactic shock) usually require that allergen enters bloodstream/distributed systemwide
describe type II hypersensitivity. what antibodies are involved?
immediate hypersensitivity - IgG and IgM
- blood transfusion reactions
- glomerulonephritis
- systemic lupus erythematosus
- Rheumatoid arthritis
describe delayed hypersensitivities. What cells are involved?
t lymphocyte cytokine release
- allergic contact dermatitis
- tuberculin skin test reaction
