Immune Function Flashcards
what is immunity?
collective set of defenses against a wide variety of potential threats
what does immunity consist of?
pathogens
toxins
abnormal cells (cancer)
foreign cells (transplants)
innate immunity
present at birth
nonspecific-behaves same way regardless of threat
adaptive immunity
develops after exposure to threat
specifically identifies threat and maintains memory
where do most adaptive immune responses occur?
within lymphatic system
what percent of circulating WBCs are lymphocytes?
20-30%
lymphocytes
not phagocytic
most reside in lymphatic system
key players in adaptive immunity
lymphatic system components
lymph
lymphatic vessels
lymphatic tissues & organs
lymphatic cells-lymphocytes & others
lymphatic system functions
produces & “activates” lymphocytes
returns excess interstitial fluid to bloodstream
transports lipids from digestive tract
lymphatic system-produces & “activates” lymphocytes
red bond marrow & thymus
tonsils, MALT, lymph nodes & spleen
lymphatic system-returns excess interstitial fluid to bloodstream
maintain normal blood volume
lymphatics
carry interstitial fluid that has “leaked” from capillaries to venous system
converge & empty into two major collecting vessels
two main collecting vessels of lymphatic system
thoracic duct
right lymphatic duct
thoracic duct
receives 85% of body lymph
empties into left subclavian vein
right lymphatic duct
receives 15% of body lymph
empties into right subclavian vein
lymphoid tissues
lack connective tissue capsule
associated with systems possessing external opening(s)
respiratory lymphoid tissues
tonsils
digestive lymphoid tissues
MALT (mucosa-associated lymphoid tissue)
other lymphoid tissues
urinary and reproductive
lymphoid tissues contain
high concentration of lymphocytes
lymphoid tissues function
defend portals of entry for pathogens
lymphoid organs
possess a connective tissue capsule
thymus, lymph nodes and spleen
thymus location
superior mediastinum
thymus site of
site of T-cell programming and maturation
how long is thymus functional?
becomes nonfunctional after puberty
undergoes atrophy and replaced by fat
lymph nodes location
lie along courses of lymphatics
neck, axilla, groin
afferent/efferent lymphatics
cortex of lymph nodes
B lymphocytes
paracortex of lymph nodes
T lymphocytes
medulla of lymph nodes
efferent lymphatic and vasculature
what are lymph nodes the sites of?
antigen recognition by B and T lymphocytes
what do lymph nodes do in response to infection?
enlarge
what happens to lymph?
it is purified in lymph nodes before returned to blood
spleen function, location
multifunctional, nonessential
LUQ of abdomen
spleen-red pulp
removes, recycles old RBC
stores iron
stores platelets
spleen-white pulp
stores B and T lymphocytes
same arrangement as nodes
monitor circulating blood for antigen recognition
lymphoid cells-lymphocytes
all derived from red bone marrow
types of lymphocytes
T cells
B cells
NK cells
Macrophages and dendritic cells
T cells
80% of circulating lymphocytes
responsible for “cell-mediated” immunity
B cells
15% of circulating lymphocytes
responsible for “antibody-mediated” (humoral) immunity
NK cells
5% of circulating lymphocytes
role in innate immunity
macrophages and dendritic cells
important in “antigen presentation”
innate immunity characteristics
same response against any type of threat
no memory
mainly important in defense against pathogens
innate immunity levels
physical/chemical barriers phagocytosis immune surveillance complement inflammation fever
innate immunity-physical barriers
skin
epithelium of internal cavities and pathways
innate immunity-chemical barriers
some epithelium produce flushing secretions
-sweat, sebum, mucus
some produce secretions that kill/inhibit pathogens
-stomach acid, lysozyme in tears, antibodies in breast milk
phagocytic cells
neutrophils and eosinophils
monocytes/macrophages
-migrate towards chemotaxins
-phagocytosis enhanced by opsonins
monocytes/macrophages types and locations
free-circulate in blood/lymph
fixed-reside in tissues
-liver-kupffer cells
-CNS-microglia
what is the function of NK lymphocytes?
immune survelliance
what do NK cells do?
recognize and adhere to abnormal cell surface proteins
expressed by virally-infected cell or some tumor cells
“self” surface proteins prevent NK cell killing
what do NK cells secrete?
“perforins”
what do perforins do?
result in rupture of abnormal or infected cells
complement system components
over 30 plasma proteins
how does the complement system work?
plasma proteins react together in chain reactions or “pathways”
- similar to coagulation pathways
- some protein fragments have biological activity
classical pathway
activated by Ag-Ab complexes (adaptive immunity)
alternate pathway
activated by pathogen cell surface proteins (innate immunity)
lectin pathway
starts classical pathway in absence of Ag-Ab complexes
what is the endpoint of all complement pathways?
cleavage of C3 to C3a and C3b
C3b
powerful opsonin-enhances phagocytosis
cleaves C5 to C5a and C5b
C5a
chemotaxis-attracts neutrophils
C3a and C5a
anaphylatoxins-stimulate histamine release from mast cells and basophils
vasodilation, increased capillary permeability
C5b
joins C6-C9 to form membrane attack complex (MAC)
punches holes in pathogen membranes
inflammation
localized tissue response to injury or infection
inflammation characteristics
red, hot, swollen, painful, plus or minus loss of function
what happens in inflammation?
walls off area of injury/infection
removes offending agent and/or devitalized tissue
sets stage for permanent repair (regeneration)
fever
body temperature >37.2 C
what happens during fever?
accelerates WBC activity
inhibits some viruses and bacteria
fever-inducing agents
produced by some pathogens
endogenous pyrogens
interleukin-1 and tumor necrosis factor
treating fever
do not treat just to treat, ask why
adaptive immunity
AKA “immune response”
results from the coordinated activities of B & T lymphocytes
adaptive immunity-2 lines of defense
cell-mediated immunity
antibody-mediated (humoral) immunity
what is involved in cell-mediated immunity?
T cells
most important for intracellular pathogens & abnormal/foreign cells
what is involved in antibody-mediated (humoral) immunity?
B cells
most important for extracellular pathogens
what do both lines of defense (cell mediated and antibody mediated) in adaptive immunity do?
both recognize, respond to and remember threats based on specific antigens
T cells
80% of circulating lymphocytes
where do T cells mature
mature and acquire specificity for antigen in thymus
what dictates T cell specificity?
T cell receptor gene rearrangements before birth
what distinguishes T cell types?
cluster of differentiation (CD) markers on cell surface
general T cell markers
CD3, CD28
what marker denotes cytotoxic T cells or NK cells?
CD8 or T8
what do T8 cells do?
effector cells that directly attack foreign antigens
what marker denotes helper T cells?
CD4 or T4
what do helper T4 cells do?
helper T cells are the master regulatory cells of immune response
what marker denotes regulatory T cells?
CD4, CD25
what do regulatory T cells do?
suppress immune response
B cells
15% of circulating lymphocytes
where do B cells mature?
B cells mature and acquire specificity for antigen in bone marrow
what dictates B cell specificity?
specificity for antigen dictated by immunoglobulin gene rearrangements before birth
what do mature B cells express?
mature B cells express immunoglobulin on surface (B cell receptor)
what do B cells differentiate into?
B cells differentiate into plasma cells upon activation
what do plasma cells do?
produce immunoglobulins (antibodies)
antigens (foreign)
molecules that elicit an immune response
types of antigens
pathogen cell surface proteins
toxins
abnormal/foreign cell surface proteins
etc
where do T and B cells bind
a specific portion of an antigen known as epitope
specificity of T and B cells
each T or B cell is specific to one antigen only
haptens
atoms or small molecules that act as antigens only when bound to larger protein
examples of haptens
nickel atoms binding to skin keratin
poison ivy wax binding to skin keratin
most idiosyncratic drug reactions
what activates the cell?
antigen/hapten binding to T or B cell receptor
what do activated lymphocytes do?
multiply to form clones
four properties of adaptive immunity
specificity
versatility
memory
tolerance
specificity
each T or B cell responds to only one specific antigen
versatility
many different lymphocytes with limitless receptor specificities are produced
if activated will clone to combat a specific antigen
memory
some activated lymphocytes (memory cells) remain in circulation
provide more rapid defense against subsequent exposure
tolerance
immune system ignores “normal” antigens (self-antigens)
what are major histocompatibility complex (MHC) molecules?
“self” antigens encoded by MHC genes on chromosome 6
128 genes divided into 3 classes
class I and II MHCs
code for human leukocyte antigens (HLA)
class I MHCs code for _____
HLA-A, HLA-B, and HLA-C antigens
class II MHCs code for _____
HLA-DQ, HLA-DP, HLA-DR antigens
what determines tissue “type” used in transplantation matching?
6 antigens: HLA A, B, C, DQ, DP, DR
what can different HLA antigens also indicate?
predisposal to various diseases
what antigen is related to ankylosing spondylitis?
HLA-B27
what antigen is related to Graves’ disease?
HLA-DR3
what do MHC I and II proteins allow?
lymphocytes to distinguish between foreign and “self” antigens
MHC I proteins
MHC I proteins present on ALL nucleated cells function to transport foreign molecules (antigens) to cell surface
how do CD8 cytotoxic T cells see antigen?
only when complexed with MHC I
what happens after CD8 cytotoxic T cell sees antigen?
kills cell bearing foreign antigen
what kind of cells do cytotoxic T cells kill?
virally-infected cells
some cancer cells have MHC I that T cells “see” as foreign
MHC II proteins present on
only macrophages and B cells
function of MHC II proteins
transport fragments of engulfed molecules (antigens) to cell surface
function of MHC I proteins
transport foreign molecules (antigens) to cell surface
how do CD4 helper T cells see antigen?
only when complexed with MHC II
what does helper T cell do after it sees antigen?
secretes cytokines to activate immune response
cell mediated immunity cytotoxic T cells activated
inactive Tc cells activated by binding of TCR to MHC-I antigen complex
what happens after Tc cell activated?
Tc cell divides
what do Tc cells divide into?
Tc cells specific to same antigen
memory Tc cells
regulatory T cells (later)
how to Tc cells kill infected/cancerous cell?
secretion of toxins
what toxins do T3 cells secrete?
perforin
lymphotoxin
cytokines that trigger apoptosis
memory Tc cells
produced with cytotoxic T cells
stay in circulation
immediately form cytotoxic T cells if same antigen reencountered
regulatory T cells
produced late
secrete suppression factors
inhibit responses of T and B cells
limit immune response to single stimulus
T helper cell activation
Inactive Th cells activated by binding of TCR to MHC II-antigen complex
what does T helper cell activation require?
antigen-presenting cell
what happens after T helper cell is activated?
Th cell divides
what do Th cells divide into?
Th cells specific to same antigen
memory Th cells
what do Th cells secrete?
cytokines that stimulate both cell-mediated and antibody-mediated immune responses
cytokines
signaling molecules used by immune cells
how can cytokines act?
locally and/or systematically
approx 20 are well characterized
perennial research targets for biological therapies
cytokines worth knowing
interleukin 1 (IL-1) interleukin 2 (IL-2, T cell growth factor) interleukin 5 interleukin 8 interferons tumor necrosis factor (TNF, cachectin)
what is interleukin 1 IL-1 produced by?
produced by macrophages that are eating
what does interleukin 1 IL-1 do?
causes T cell division
causes increase in circulating neutrophils
causes the acute phase reaction
acts on the hypothalamus to cause fever and fatigue
attracts macrophages for granuloma formation
what is interleukin 2 (IL-2, T cell growth factor) produced by?
activated Th cells
what does interleukin 2 (IL-2, T cell growth factor) do?
causes T cell division
what is interleukin 5 produced by?
activated Th cells
what does interleukin 5 do?
causes increase in eosinophils-important in allergies and parasitic infestations
what is interleukin 8 produced by?
macrophages
what does interleukin 8 do?
chemotactic for neutrophils
what are interferons produced by?
some are produced by T cells
what do interferons do?
“interfere” with viruses and many other activities
what does beta interferon do?
transforms B cells into plasma cells
what does gamma interferon do?
activates macrophages and increases MHC II expression
what is tumor necrosis factor (TNF, cachectin) produced by?
produced by T cells, macrophages
what does tumor necrosis factor (TNF, cachectin) do?
causes inflammation
causes the acute phase reaction
acts on the hypothalamus to cause fever
induces apoptosis
what happens in B cell sensitization in antibody mediated immunity?
inactive B cells “sensitized” by binding of BCR to antigen
antigen taken into B cell
antigen expressed on B cell surface with MHC II
now recognizable by Th cell
what happens when Th cell binds in antibody mediated immunity?
Th cell binds to MHC-II-antigen complex
secrete cytokines that “activate” B cell
what happens once B cell is activated?
activated B cell clones
what does an activated B cell clone into?
plasma cells
memory B cells
what do plasma cells do?
produce and secrete antibodies
what do memory B cells do?
stay in circulation
immediately form plasma cells if same antigen reencountered
what are antibodies (immunoglobulins)?
soluble proteins in plasma
what are antibodies (immunoglobulins) made of?
two pairs of amino acid chains
heavy and light
what does each chain on an antibody consist of?
constant and variable segments
antibody (immunoglobulin) constant segments
determine Ig class 5 classes
antibody (immunoglobulin) variable segments
determine Ig specificity to antigen
Antigen-binding site
IgM
first antibody secreted after B cell activation
short-lived
circulate as five-antibody starburst (pentamer)
responsible for rapid destruction of incompatible blood types
IgG
second antibody secreted after B cell activation
80% of plasma antibodies
long-lasting, monomer
responsible for resistance against many pathogens and toxins
can IgG cross placenta?
yes
maternal IgG provies passive immunity to fetus and newborn
IgA
produced as dimer
found primarily in glandular secretions
glandular cells absorb from plasma and secrete them onto apical surface
bind pathogens before they enter body
what kinds of glandular secretions are IgA found in?
mucus, tears, saliva, breast milk
IgD
acts as B cell receptor
binding of antigen sensitizes B cell
IgE
on surfaces of basophils and mast cells
Ag binding stimulates release of histamine to initiate inflammation
also important in allergic response
actions of antibodies
precipitation and agglutination -formation of immune complexes activation of complement system stimulation of phagocytes -opsonization inciting inflammation prevention of bacterial and viral adhesion
first antigen exposure
produces primary response develops slowly, transient -illness occurs -antigens activate B cells to form plasma cells -antibody production slow
subsequent antigen exposures
produces secondary response
more rapid, extensive and prolonged
no illness
memory cells already primed
