Chapter 21: Body Defenses Flashcards
What is the name of the germ cell that all WBCs originate from?
hemocytoblasts
Where are hemocytoblasts located?
in the red bone marrow
What are the two stem lines for WBC called?
MYELOID stem line
LYMPHOID stem line
What does the myeloid stem line produce?
forms granular WBCs and monocytes for NON-SPECIFIC defense
cells: basophils eosinophils neutrophils monocytes
What does the lymphoid stem line produce
forms 3 major types of cells: (generally for specific defense)
T cells and B cells in specific defense
Natural Killer cells (sub-category of t-cells) involved in non specific defense
What WBCs undergo further development in the tissues and what do they develop into?
Monocytes -> Macrophages
B-cells undergo maturation in the bone marrow then activation in secondary lymphoid organs
T-cells are produced in the red bone marrow, then migrate to the thymus where they become immunocompetent, and then must become activated in the secondary lymphoid organs or in the blood/lymph
What are the two different mechanisms by which foreign organisms or mutant cells can be destroyed?
PHAGOCYTOSIS: engulfed by a neutrophil or macrophage and undergoes intracellular digestion by lysosomes
LYSIS: cell membrane is attacked so that cell ruptures (ex. insertion of pore forming proteins)
all defense mechanisms are geared to making these two things happen more easily/efficiently
what are the two immune defense systems?
INNATE (nonspecific) defense system: defenses you are born with, active against any kind of invader
ADAPTIVE (specific) defense system: develop after birth upon exposure to specific foreign antigens
these two systems interact to collectively fight.
What are the categories and sub-categories of defense in the INNATE defense system?
SURFACE BARRIERS:
- physical
- chemical
INTERNAL DEFENSES:
- phagocytosis
- lysis by natural killer (NK) cells
- inflammation
- antimicrobial proteins
- fever
Describe the physical aspect of surface barrier defense.
intact SKIN: separates body from outside. Keratin resists: abrasion, tearing weak acids and bases, bacterial toxins etc.
intact MUCOSAE: protect internal cavities and openings
Describe the 4 chemical aspects of the surface barrier defense.
SKIN: acidic secretions inhibit bacterial growth
STOMACH: HCL and protein-digesting enzymes
SALIVA AND TEARS: lysozymes, defensins
MUCUS: traps organisms
What are the three types of cells that phagocytize?
MACROPHAGES
NEUTROPHILS
EOSINOPHILS
Describe macrophage’s role and function.
develop from monocytes
1) able to phagocytize repeatedly without damage
2) can also kill by releasing respiratory burst of oxidizing chems, acids, and others
considered the heavy hitters.
two types of mobility: FREE: wander through tissues -dendritic cells in epidermis -alveolar macrophages in lungs FIXED: ex kupffer cells in liver, microglia in CNS
Describe neutrophil’s role and function.
commonest WBC
1) first responders to infection
2) migrate from blood to infected tissue following chemical clues
3) SUICIDE KILLERS (are destroyed when phagocytize)
Describe eosinophil’s role and function.
pink staining granules
1) weak phagocytes
2) attack large parasites by surrounding them and releasing hydrolytic enzymes externally
Describe the 6 step process of phagocyte mobilization.
1) LEUKOCYTOSIS: inducing factors from dmgd cells stimulate release of WBCs from marrow to blood
2) MARGINATION: WBCs move along capillaries and cling to CAMs on capillary walls
3) CAMs: mark the sites of tissue dmg/infection
4) DIAPEDESIS: WBCs squeeze btwn endothelial cells and move towards site by amoeboid motion
5) POSITIVE CHEMOTAXIS: WBCs follow inc conc gradient of inflammatory chems toward site
6) NEUTROPHILS: are the 1st responders, followed by monocytes which develop into macrophages in the tissue
Explain the 5 step mechanism of phagocytosis.
1) ADHERENCE: must be able to attach itself to organism
2) engulfing into PHAGOSOME
3) fusion with lysome into PHAGOLYSOSOME
4) HYDROLYSIS by enzymes OR
- killing by burst of free radicals/oxidizing chems
- killing by defensins (in neutrophils)
5) EXOCYTOSIS of residual body
Explain the 5 step process of lysis by natural killer (NK) cells.
type of t-cell, but non-specific defense
1) crawl over surface of cells looking for abnormalities in marker proteins (lack of self proteins)
2) secrete PERFORIN and GRANZYMES to kill cancer and virus cells
3) perforins insert into the membrane, polymerize and forme pores
4) granzymes enter through pores and attack membranes, destroy nucleus, and triggers APOPTOSIS in the cell
5) NK cells also secrete chems that trigger the inflammatory response
What are the three roles of inflammation?
1) prevents the spread of infection
2) disposes of cell debris and pathogens
3) prepares for repair
What are the signs of inflammation?
R H S P sometimes I
Redness
Heat
Swelling
Pain
and sometimes
Immobilization
What are the three stimuli that trigger the inflammatory response?
HISTAMINES: released by mast cells (early warning system)
TOLL LIKE RECEPTORS (TLRs) - on macrophages in boundary epithelial tissues that recognize certain classes of microbes which trigger release of CYTOKINES (chem messengers)
INFLAMMITORY MEDIATORS: released by tissue, phagocytes, lymphocytes, basophils
Where are mast cells found?
in loose CT under skin and around blood vessels
What are some examples of inflammatory mediators?
kinins, prostaglandins, leukotrienes, and complement
describe the process of inflammation.
1) inflammatory chems released into extracellular fluid
2) dilation of arterioles -> hyperemia -> redness and heat
3) inc permeability of capillaries -> exudate leaks out -> swelling and pain
4) release of exudate: aids healing and
5) walls off area and provides framework for tissue repair
6) moves foreign materials into lymphatic system
7) more pain from bacterial toxins, lack of nutrition, prostaglandins and kinins
8) dmg to mucosa results in greater secretions of defensins
What is hyperemia?
congestion with blood
in inflammation, blood will accumulate in the area
What is pus evidence of?
phagocytic cells at work
What is an abscess
an area that is walled off by collagen fibers when an infection is not completely cleared
What are antimicrobial proteins?
proteins that enhance defense, attack microorganisms directly, or hinder their ability to reproduce
What are the two types of antimicrobial proteins involved in innate defense?
INTERFERONS
COMPLEMENT
Describe what interferons do.
When a cell becomes infected by a virus, it triggers the production and release of interferons
1) interferons exit the cell
2) bind to receptors on other cells and cause production of antiviral proteins which block viral reproduction
3) also activate macrophages and natural killer (NK) cells
4) reduce inflammation
are interferons specific or non-specific?
non-specific
each interferon will interfere with a variety of viruses
Explain the mechanism of complement proteins
20+ inactive proteins that act in a cascade
1) assist both specific and non-specific defense
2) major mechanism for destroying foreign antigens
2 pathways:
CLASSICAL pathway: C1 binds to antigen-antibody complex
ALTERNATIVE pathway: exposure of factors to bacterial cell wall
both pathways lead to cleavage of C3 into C3a and C3b - which causes lysis, enhanced phagocytosis and inflammation, and production of C reactive protein
Explain how complement proteins affect lysis of infected cells.
C3b binds to target cell
inserts membrane attack complex (MAC)
MAC forms and maintains a hole in the membrane resulting in rupturing
Explain how complement proteins affect phagocytosis. What is this method called?
OPSONIZATION
C3b coats microorganism with a protein that makes adhesion easier
Explain how complement proteins simulate inflammation.
C3a and others stimulate mast cells and basophils to release inflammatory chems
Explain what the C reactive compliment protein does.
produced by liver in response to inflammatory chems
acts as a target painter by binding to target cell
Describe the role of fever in our defense system.
thermostat in the hypothalamus is raised in response to PYROGENS secreted by leukocytes and macrophages
mild to moderate fever:
1) liver and spleen sequester iron and zinc (required for bacterial multiplication).
2) inc metabolic rate of tissue cells which inc rate of repair
Give some examples of inflammatory mediators.
kinins, prostaglandins, leukotrienes, and complement.
What can happen if you have a high fever?
denaturisation of the body’s enzymes
What are the four important aspects of the adaptive immune system?
1) antigen specific
2) systematic - whole body response
3) has memory: memory cells
4) amplifies inflammatory response and carries out complement fixation
What are the two components to the adaptive immune system
Humoral component (antibody mediated): antibodies released by B cells into fluids immobilize bacteria, toxins, free viruses, and mark for destruction
Cellular component (cell mediated):
- T cells act directly against cancer, infected, or foreign cells.
- NK directly attack by lysing
- indirect attack via chems that stimulate inflammation, lymphocytes and macrophages
What are antigens?
substances that can mobilize the immune system and provoke an immune response
usually large complex molecules
What are complete antigens?
can by themselves provoke the immune response
They are:
antigenic - stimulate antibody production
reactive - react with activated lymphocytes and antibodies released in response
What is an incomplete antigen?
called HAPTENS
1) are reactive but not antigenic on their own
2) can become antigenic/immunogenic when they attach to body proteins
3) often cause immune system to attack the body (allergic reaction)
What are antigenic determinants?
refer to the parts of a molecule that cause antibody formation or activation of lymphocytes
most antigens are large proteins:
therefore many antigenic determinants that dictate what type of antibodies and lymphocytes will respond and how many (more sites, larger response)
What type of molecules are typically not antigenic?
large repetitive (simple) polymers like plastics
What are self antigens?
MHC proteins on the cell surface that identify the cell as self
two types:
Class I MHC - found on nearly all cells
Class II MHC - only on some cells acting in immune response
Explain how class 1 MHCs are formed in a normal healthy cell and in an infected cell.
both types are a result of the recycling of proteins within the cell.
healthy celss result in a peptide protein
in infected, there are fragments of foreign antigens that come from within the cell
What are class II MHCs formed of?
proteins that are outside the cell
What are the three crucial cells of the adaptive immune system?
B lymphocytes - produce antibodies (humoral)
T lymphocytes - kill directly (cell-mediated)
Antigen presenting cells (APCs) - alert other defense cells
Where are lymphocytes formed?
red bone marrow
When lymphocytes are newly formed, what can be said about their structure?
they are nearly identical with each other
What happens to the lymphocytes after they are formed in the red bone marrow?
they travel in the blood/lymph to the lymphoid organ where type will be determined and development take place.
Where do T cells develop?
in the Thymus
Where do B cells develop?
in the Bone marrow
Explain how lymphocytes are processed (developed) in the thymus and red-bone marrow.
two hormones: thymosin and thymopoietin
T lymphocytes divide and are exposed to antigens
Then undergo two selection processes:
POSITIVE selection: suitable cells are stimulated for growth/maturation
NEGATIVE selection: unsuitable are stimulated to undergo apoptosis
Results in immunocompetence and self tolerance
What are the characteristics of immunocompetence?
1) can respond to antigens that are most likely to be in the environment
2) genes determine which antigen receptors are on a T or B cell
3) each cell has only one type of receptor, but many receptors per cell
4) receptors develop prior to exposure
5) after processing in the thymus and the bone marrow, these cells are still immature and are called naïve cells
What happens to the lymphocytes after they go through the sorting process?
they are called naïve cells at this point
1) naïve cells move to secondary lymphoid organs
2) if they encounter their specific antigen, they bind to it and finish maturation to mature and functional cells
3) they then begin making clones of identical cells
Discuss how B-cells and T-cells differ in their ability to react to antigens
B-cells can react to antigens directly
T-cells depend on APCs (antigen presenting cells) to capture and display antigen fragments to them
What are the three types of APCs (antigen presenting cells)
DENDRITIC cells: most common, capture and carry antigens to lymph organs
MACROPHAGES: wait in tissue for antigens to come to them
Activated B cells: B-cells migrate looking for CAMs (sign of inflammation and possible antigens)
How are antigens processed by APCs (antigen presenting cells)
1) APC phagocytizes antigen
2) hydrolysis of antigen and presents fragment in a cleft attached to its MHC protein
3) T-cells detect these fragments and become activated (activate immune response)
4) T-cells then release chems that increase the number of APCs and macrophages
What is the antigen challenge?
refers to the first encounter of naïve B-cell and its specific antigen
Where is the most common place for the antigen challenge to occur?
the spleen
What are the steps to the process of humoral (antibody mediated) response?
1) antigen challenge occurs
2) activation of the B cell
3) B cell grows and multiplies to form clone
4) most of cloned cells become plasma cells and begin secreting large amounts of antibodies
5) after destruction of antigen, thousand of B-cells remain as memory cells
What happens on a molecular level to activate a B cell?
- antigen binds to receptor and cross links adjacent receptors together
- cross-linked receptor-antigen complex taken in by endocytosis
- interaction with helper T cells stimulates activation of B cell
What is the rate of antibody secretion in a primary response (first exposure to antigen)?
2000/molecules per second
How long does response last in a primary response (first exposure to antigen)?
plasma cells produce antibodies for 4-5 days then die by apoptosis
How does second exposure to an antibody differ from primary?
memory cells help provide a faster response
just a few days after infection the antibody conc. is massively higher than in primary (primary may not have had a chance to respond yet)
plasma cells live longer the second time
What are the 2 types of humoral immunity?
ACTIVE humoral immunity
PASSIVE humoral immunity
Describe active humoral immunity.
Natural and artificial
Natural:
- B-cells exposed to antigen naturally
- clone and produce antibodies
- memory cells remain after
Artificial:
- use vaccine of dead/weakened pathogen/component
- stimulates antibody and memory production
Describe passive humoral activity
it is when antibodies produced elsewhere are introduced into the body providing FAST and SHORT-TERM relief since B-cells not stimulated.
Natural:
placenta/milk
Artificial:
injection for immediate protection, but ends with degradation
What is another name for an antibody?
an immunoglobulin (Ig)
Describe the basic structure of an antibody (Ig)
4 polypeptide chains:
- 2 heavy with flexible hinge
- 2 light chains
- held together by disulfide bridges
it is Y shaped
variable region at the v top
constant region at the I bottom
What does the stem (constant) region of an antibody do?
dictates the cells/chems that the antibody can bind to
and how it functions in fighting antigens
it is also the part that determines its class
What are the 5 classes of Igs (antibodies)?
remember MADGE:
IgM IgA IgD IgG IgE
Describe IgM antibodies
first antibody released by plasma cells in primary response
- contains many antigen binding sites (potent agglutinator)
- readily fixes and activates complement
Describe IgA antibodies
very small amounts in plasma
mainly found in secretions on body surfaces (mucus, saliva, milk, sweat)
prevents attachment of pathogens to epithelial cells
Describe IgD antibodies
are bound to surface of B cells
acts as the antigen receptor; binds antigen and activates B cell
Describe IgG antibodies
Most abundant 75-85% of circulating antibodies
Reacts with: bacteria, viruses, and toxins in blood/lymph
fixes complement
can cross placenta
Main antibody of 1st and 2nd response
Describe IgE antibodies
secreted by plasma cells in skin, tonsils, GI and resp tracts
- very little in plasma, but rises with severe allergic reactions and chronic parasitic infections
- stem binds to mast cell and basophil receptors to trigger release of histamine
triggers INFLAMMATORY & ALLERGIC responses
What antibody is the first antibody released by plasma cells in the primary response?
IgM
What antibody is found in secretions on the body surfaces
IgA
What antibody is bound to the surface of B cells?
IgD
What is the most abundant antibody?
IgG
What is the antibody that triggers the inflammatory and allergic response?
IgE
What are the 4 ways that antibodies work?
Remember PLAN
P recipitation
L ysis by complement
A gglutination
N eutralization
How do antibodies stimulate complement fixation and activation?
1) formation of antibody-antigen complex triggers complement fixation
2) leads to lysis, stimulates inflammation and phagocytosis
Primary defense against cellular antigens (bacteria, incompatible RBCs)
Explain how antibodies act by neutralization.
it is the simplest mechanism of antibodies
1) antibody blocks sites on viruses so they can’t bind to target cell
2) antibody binds on to bacterial exotoxin and inactivates it
3) complexes eventually destroyed by phagocytosis
How do antibodies act by agglutination?
antibodies bind up antigens together to form clumps and then are phagocytized
How do antibodies act by precipitation?
soluble molecules are cross-linked into large complexes that settle out of solution and are then phagocytized
What are monoclonal antibodies and what are they used for?
they are prepared by fusing a b-cell with a tumor cell (can then replicate indefinitely in culture)
these antibodies react with a single antigen, 2 uses:
1) diagnosis (ex pregnancy, STIs, and some cancers)
2) used as treatment for circulatory cancers (leukemia, lymphomas)
Compare humoral response, with cell-mediated response.
Humoral:
- b-cells produce antibodies
- targets: bacteria and molecules in extracellular environments
Cell-mediated response:
- t-cells recognize and respond only to processed fragments of antigen displayed on the surface of body cells, but destroy directly
- targets: infected body cells and foreign cells
B-cells need to recognize non-self to become activated (encounter antigen), what do T-cells require to become activated?
need to simultaneously come into contact with self receptor on a cell and non-self (antigen) that is on the MHC protein and with a third variable of cytokines
What are the three types of t-cells?
Helper t-cells (also called T4 or T with a sub h, or CD4)
Cytotoxic (killer) T cells (T sub c, T8, CD8)
Memory helper and cytotoxic T cells
Regulatory T cells
T sub dh - delayed hypersensitivity helper T cells
Gamma delta T cells
What are T4 cells (helper t-cells)?
1) have CD4 cell recognition protein on cell membrane
2) bind to foreign antigen attached to a MHC II peptide on an APC
3) stimulate both specific and non specific defense
Different methods of stimulation for different types
What are cytotoxic cells?
1) have CD8 protein on surface
2) bind to foreign antigen attached to MHC 1
3) destroy invaders by lysing infected and foreign cells - use perforin and other methods
How do natural killer (NK) cells differ from cytotoxic t-cells
cytotoxic t-cells look for antigens bound to MHC I peptide.
NK cells look for other signs of abnormality, including lack of MHC I which would not be seen by normal cytotoxic t-cells
also NK cells are part of the innate system and cytotoxic t-cells are part of the adaptive immune system
What do memory helper and memory cytotoxic t-cells do?
these are the cells that remain after destroying an antigen infection. Function in much the same way as memory b-cells
b/c of their experience, they provide a faster and stronger response to second exposure
What do regulatory t-cells do?
t-cells that inhibit action of other t-cells to end immune responses
What do Gamma Delta T-cells do?
live in the intestine and are adapted to fighting cancer
What are the 4 types of proteins that are found on the surface of t-cells?
1) TCR - t-cell antigen receptors (variable region binds to antigen fragment, constant region binds to MHC)
2) CD4, CD8 - adhesion molecules, help t-cells stick to other cells during recognition
3) Costimulant receptors
4) Other receptors: some activate, some inhibit
What is the crucial costimulant to helper t-cells?
CD 28 on helper t-cells binding with B7 protein produced by macrophages and dendritic cells and put on their surface
What is costimulation?
the process which requires three signals in order to activate t-cell response
1) binding to foreign antigen
2) binding to self antigen (MHC protein)
3) costimulant
What are the three types of costimulation?
1) t-cell binds to specific proteins on APC surface (eg CD28 on t-cell to B7 protein on macrophage/dendritic cell)
2) t cell binds to signal molecules ex cytokine or interleukins
3) t-cell binds to other cells ex activated b cell
What is anergy?
it is what occurs if their is no costimulation:
t-cells become tolerant to that antigen, are unable to divide, and do not secrete cytokines
What are cytokines?
chemical messengers in the immune system that allow the cells to communicate
either inhibit or activate immune responses
all t-cells secrete at least one cytokine when active to amplify effect
What are 4 roles of cytokines?
1) costimulation of t-cells
2) cell toxins
3) enhance killing by macrophages
4) enhance inflammation
What are some examples of cytokines?
interleukin 1 and 2, gamma interferon
What cytokine stimulates acceleration of t-cell division?
interleukin 2
Go through the process of how t-cells are activated
1) APCs display fragment of foreign antigen on MHC protein
2) t-cells bind to foreign antigen and MHC complex
3) CD4, CD8 proteins adhere to target during recognition
4) Costimulant binds to t-cell
5) t-cell enlarges and forms clones
6) cells carry out actions according to their class
&) some cells are kept as memory cells
What do helper t-cells do (T sub h, T4, CD4 cells)?
1) stimulate and regulate whole defense (innate and adaptive)
2) stimulate other t-cells to multiply and differentiate
3) costimulate activated b-cells to clone and multiply
4) stimulate b-cell antibody production and release
5) stimulates macrophages and NK cells to become more active
6) attract WBCs to area and strengthen non-specific defense
What would happen to our immune system if there were no helper t-cells?
we would have no immune response
What is the mechanism for how helper t-cells act?
1) bind to APC
2) CD28 binds to B7 (costimulant)
3) stimulates APC to produce IL-1
4) IL - 1 stimulates helper cell to produce IL - 2
5) IL - 2 stimulates: b-cell multiplication, production of antibodies, helper t cells to multiply, activation of NK cells (pos feedback loop)
What is the normal costimulus for cytotoxic t-cells?
IL - 2 (interleukin 2)
Explain the mechanism for activation of cytotoxic t-cells
1) bind to target containing both MHC and antigen fragment
2) CD 8 helps bind t-cell to target cell
3) costimulant binds to t-cell
4) t-cell activates, enlarges and forms clones
5) clones search out and attack target cells with the same antigen
6) remain active for 1 week after 1st exposure and die by apoptosis
7) many memory cells are kept
What are the 4 mechanisms for killing by cytotoxic t-cells?
1) lysis of target cell: T8 cell binds to target then releases perforin and granzymes
2) T8 cell binds and secretes lymphotoxin
3) T8 cell releases tumour necrosis factor (triggers apoptosis in cancer cells)
4) T8 cell secretes gamma interferon which stimulates macrophages
What does the success of an organ transplant depend on?
the similarity of MHCs in the organ to that of the person’s own cells
if incompatible, t-cells and b-cells attack tissues
What is the minimum match when testing for an organ donor?
75%
What treatments are used in an organ transplant, what is the AE of this?
drugs to suppress immune system:
cytotoxic drugs, radiation, anti lymphocyte globulins, corticosteroids, cyclosporine
results in a suppressed immune system and there is an increased risk of infection
What are the 2 types of immunodeficencies?
Congenital
Acquired
explain what congenital immunodeficiencies are.
it is a genetic defect that causes:
- dec number of t and b cells
- defective cytokine receptors
- defective enzymes that normally destroy metabolites toxic to t-cells
Children have little to no defense and is fatal if not treated soon after birth
What are the two types of acquired immunodeficiencies?
Hodgkin’s disease: cancer of b-cells suppress function of lymph nodes
Immunosuppressive drugs used for transplants
How are congenital immunodeficiencies treated?
treated by:
- transplants of normal donor stem cells
- using viruses to insert normal genes into own stem cells
Give an example of a congenital immunodeficiency
SCIDS: severe combined immunodeficiency syndromes
Explain how the HIV virus interferes with t-cells to result in AIDS.
HIV virus has surface proteins that fit into CD4 receptors of t-cells (blocks it from working)
functions as a normal virus, but primary target is helper t-cells
What are the symptoms of AIDS?
severe weight loss, night sweats, swollen lymph nodes
Is there a cure for AIDS?
not yet, but drug cocktails have been shown to extend survival time
What is an autoimmune disease?
when the immune system can’t tell self from non-self resulting in attacking own tissues
What does the immune system attack in multiple sclerosis?
the myelin sheaths
What does the immune system attack in Grave’s disease?
thyroid
What does the immune system attack in type I diabetes
destroys beta cells in the pancreas
What does the immune system attack in systemic lupus erythrematosus
many body organs
What does the immune system attack in myasthenia gravis
communication between nerves and skeletal muscles
What does the immune system attack in rheumatoid arthritis?
joints
What does the immune system attack in glomerular nephritis?
kidneys
What are some possible causes of autoimmune diseases?
lymphocytes not properly selected
new self antigens appearing by mutation
cross reaction between self antigins and antibodies
What are hypersensitivities?
immune system causes tissue dmg as it fights off a perceived, but unreal threat
rarely cause death
anaphylactic shock: a systemic response to entry of an allergen directly into the blood
- bronchiole constriction
- vasodilation
- treat with epinephrine
