Module 5-1 - Immune System Flashcards
Types of Blood Cell
Monocytes/Macrophages
Lymphocytes (B and T Cells)
Granulocytes (Polymorphonuclear leukocytes: Neutrophils, Eosinophils, Basophils, Mast Cells)
RBC
Platelet
Granulocytes
blood cells with granules like heparin and histamine in the cytoplasm
Neutrophils (bacteria), Eosinophils (parasites and algae), Basophils (become mast cells)
In what situation does Neutrophilia and Microcytosis occur?
Infection
In what situation does Eosinophilia occur?
Allergies
In what situation does Lymphocytosis occur?
Viral Infection
Hematopoietic Stem Cell
an undifferentiated cell that can go down a progenitor line to make a very differentiated cell
What are the Host Defense Systems?
- Physical and Chemical Barriers to Infection
- Inflammatory Response (Non Specific)
- Immune Response (Specific)
Physical and Chemical Barriers to Infection
Skin
Mucous Membranes and Secretions
Inflammatory Response
Non specific response
occurs after tissue injury or infection
causes fever and inflammation
phagocytic WBCs, antimicrobial substances, and natural killer cells accumulate
Immune Response
Specific Response
Identifies self from non self (host v foreign)
Recognizes and eliminates altered host cells
Antigen-Antibody response
What induces fever?
Prostaglandins
Classic Infection Signs
Redness
Swelling
Pain
Warmth
What sort of trauma can cause an inflammatory response
Mechanical
Thermal
Chemical
Antigen
Immunogen
A molecule that can stimulate and immune response
It is usually a protein or large CHO (NOT LIPIDS OR NUCLEIC ACIDS)
Epitope / Antigenic Determinant
Discrete immunologically active sites on antigens
A single antigen has several antigenic determinants on it
Each can stimulate a distinct clone of lymphocytes
Antibodies attach here
Hapten and Hapten Carrier complex
Low molecular weight compound - Basically Hapten is a small compound
Can combine with carrier protein molecules to act like an antigen
Ex: Penicillin cannot cause a reaction alone so by carrying it on a carrier protein it is then large enough to cause an immune response
Protein structure?
Long chains of amino acids
Partial or Incomplete Antigen
The situation in which hapten can only induce antibodies if bound to another carrier protein or molecule
How many epitopes are on an antigen?
Multiple
They stick out all over
Why is each epitope different on an antigen?
They have different amino acid patterns so the antibody must be specific
The amino acids have a variable and constant portion and each site has a different shape so antibodies need to be specific to just that site
Names of Immune Cell Lymphocytes are based on…
their location of maturation
T Cell = Thymus
B Cell = Bone
Regulatory Lymphocytes
Assist in the immune response
These are Helper T cells
They activate other immune cells
Effector Lymphocytes
Final stage cells of the immune response
These are killer T cells
They ensure removal of foreign invaders
B Lymphocytes
10-20%
Mature in bone marrow
Used in Humoral or Antibody Mediated Immunity
Secrete Antibodies
T Lymphocytes
60-70% (Predominant)
Mature in Thymus
Used in Cell Mediated Immunity
Do not involve antibody production - they do cell-to-cell killing
T4 Lymphocytes
The “Quarterback”
Helper T Cells
Secrete chemical messages that amplify or stimulate other things to happen, such as recruiting and activating cells to do things such as killing
Send Orders
Have CD4 Markers
Speed up or slow down the immune response, but do not do the direct killing
T8 Lymphocytes
Effector Cells
Natural Killer T Cells
Carry out the T4’s orders
The final immune response stage
There are a variety of them, but they all wait to seek and destroy until the T4 orders them to do so
Major Histocompatibility Complex (MHC)
These are the markers on the cells surface also known as Human Leukocyte Antigens (HLA)
They are four closely linked groups of genes (loci) on Chromosome 6 that code for specific cell surface molecules
MHC 1
HLA-A, HLA-B, HLA-C
On all NUCLEATED cells in the body and on platelets
Tells the immune system you are you
Present the processed antigen to cytotoxic T cells to tell which cells are “you”
MHC 2
Mostly on antigen presenting cells like B Cells, Macrophages, and APCs
Present processed antigen to helper T Cells to give orders (so it can get antibodies made and tell cytotoxic T cells what to attack and what not to attack)
The antibody will then go onto the antigens on cells that need to be destroyed and “lock up” so a macrophage can come get it
Types of Immunity
Cell mediated immunity
Humoral or Immunoglobulin mediated immunity
Which type of immunity involves the production of antibodies?`
Humoral or Immunoglobulin mediated immunity
T8 Suppressor Cell
tells when the immune response it over and no longer needed
Reduces the humoral response
Memory T Cell
Does not forget the antigen and response to the specific antigen in cell mediated immunity - since there are no antibodies made, this cell remembers and can launch an attack faster if the same invader enters the body
Remains dormant until second exposure
Cell Mediated Immunity
T Cells respond directly to antigens (helper, killer, suppressor, memory)
Involves destruction of target cells through secretion of lymphokines rather than antibodies
Humoral or Immunoglobulin Mediated Immunity
B cells mature into plasma cells and produce specific antibodies that mark things for destruction
Provides for elimination of bacteria, neutralization of bacterial toxins, and prevention of viral infection
Which type of immunity is fastest? Slowest?
Fast - Cell Mediated
Slow - Humoral (can take months to make antibodies)
Why is specific immune response special?
the antigens can allow responses from infected cells and viral cells (inside) - unlike just neutrophil response - and T cells can do surveillance for cancer cells and mutated cells
Do cell mediated and humoral responses occur at the same time?
Often they do
What sort of immune response is launched regarding a transplanted organ?
Cell Mediated Response
It is recognized as non self and is attacked
What do T lymphocytes function in?
Activating other T cells and B cells
Controlling viral infections
Rejecting foreign tissue graft
Delayed hypersensitivity reactions (ex: poison ivy)
Regulating and amplifying T and B cell response
High Lymphocyte count indicates what?
A viral infection
Cytotoxic (CD8+) T Lymphocytes
T8 Killer Cells
They bind to the surface of an invading cell, disrupt the membrane, and release toxic chemicals
They have the CD8+ markers
Helper (CD4+) T Lymphocytes
Helper T4 Cells - Quarterback
Have CD4+ marker
Secrete cytokines to direct cells
Facilitate cell mediated response
Stimulates B cells to proliferate and mature into plasma cells for humoral response
Natural Killer (NK) Cells
Large granular lymphocytes with CD16 and CD56 markers
Non specific effector cells that kill tumor cells and virus infected cells
Its programmed killing is inhibited by contact with MHC I (Self Molecules)
It pokes holes in cells so cytotoxic enzymes can destroy it
What determines the activity of NK cells? What enhances NK cell activity?
Determined by:
Perforins
Enzymes
Toxic Cytokines
Enhanced By:
IL-2 (from T4 helper)
What are the main communicators between WBCs?
Interleukins
Macrophages
Phagocytic Effector cells in both humoral and cell mediated responses
Do not have surface receptors for specific antigens, but can ingest an antigen to put on its surface to present to a T4 cell to activate the T Lymphocyte Response
They do have the Fc region antigens and for the constant complement portion of an antibody tough
Non specific response role in bacterial infection
secretes Cytokines
Variable versus Constant Portion
Variable Portion is the unique portion of an antigen while the constant is the same on every antigen
Macrophages can only read the constant portion, and activation of this portion by antibodies gets them to come over and eat it
Antigen Presenting Cells
APCs
B Cells
Macrophages
Cytokines
small hormone like polypeptides
“Interleukins”
Act on immune cells to regulate inflammatory responses including movement, proliferation and differentiation of leukocytes and other cells (the T4’s messages)
They end up enhancing the production and maturation of B Lymphocytes into Plasma Cells
Usually have multiple jobs or mult kinds can do one job
How are Cytokines named?
For the cell type that makes them (ex: Lymphokines)
International nomenclature - ex: interleukin 1 through 17
the biologic property first ascribed to them - ex: interferon
ILs
Interleukins
Cytokine
Involved in fever, inflammation, and regulation of immune cell response
IF
Interferons
Cytokine
Augments natural killer cell activity and exerts antiviral activity to boost immune system response (when given as an IV)
TNF
Tumor Necrosis Factor
Cytokine
Destroys things by directing cytotoxins toward tumors
CSF
Colony Stimulating Factor
Cytokine
Stimulates different colonies of WBC to be produced
Reticuloendothelial System
RES
Tissue Macrophages - localized to different regions and tissues and given different names based on their area
Wherever the macrophages are migrating to with the system they may stay their entire life
Alveolar Macrophages
Lung Macrophage
Kupffer’s Cells
Liver macrophage
Peyer’s Patches
Intestine Macrophage
Microglial Cells
CNS Macrophage
Langerhan’s Cells
Skin macrophage
Histiocytes
Connective tissue macrophage
Where are macrophages most abundant?
Lymph fluid and lymph nodes
If the macrophage count is high…
you probably have an infection
Lymph Nodes
Distributed along lymphatic vessels
an immune system structure
Filters lymph fluid and removes bacteria and toxins from circulation
Crucial in the proliferation of immune cells
Thymus
Located in the mediastinum
Produces T lymphocytes
Spleen
Largest lymph organ
reservoir for blood
macrophages clear cellular debris and process hemoglobin here
Tonsils
produce lymphocytes
guards against airborne and ingested pathogens
immune system structure
very important, especially in those <2 y/o
Thoracic Duct drains…
the left side of the body while the right lymphatic duct drains the top right quarter
What is not in lymph that is in plasma
RBC
Lymph flows back to the ___
heart
Afferent Lymph Vessels
carries lymph into nodes
What does a warm, tender, enlarged, and maybe red lymph node indicate?
That the lymph is working at phagocytizing foreign particles because that is inflammation
What does a non painful, enlarged, fixed lymph node mean?
Indicates cancer
Especially if you cannot feel the edges of it
If a node is enlarged than where is the infection occurring?
Distal to the lymph node
this is because lymph nodes drain from distal areas back toward the heart
B Lymphocytes
Basis of humoral immunity
When an antigen binds with a receptor it will differentiate into a plasma cell and secrete immunoglobulins/antibodies
What is an action B lymphocytes can do other than make antibodies once they differentiate into plasma cells?
They can act as Antigen Presenting Cells (APCs) by ingesting and depositing an antigen onto its own surface to activate T lymphocytes (T4) to secrete cytokines and initiate a response
What regulates B lymphocyte activity?
T Lymphocytes (T4) and Cytokines
Memory B Cells
B lymphocytes that circulate indefinitely and become active and remember how to make a specific antibody if there is a repeat exposure
They can be induced to make the antibody when told by cytokines from T cells
Structure of an Antibody
- Fc (Constant Fragment)
- Fab (Antigen Binding Fragment)
Heavy Chain and Light Chain
Fc
Constant fragment / Heavy chain of an antigen
It is a non specific activator site for inflammation
It is identical for all antibodies of a single class (IgE, IgG, etc)
Fab
Antigen Binding Fragment / Light Chain of an antigen
Is specific for each individual antibody
Contains a specific antigen binding site
An antigen binds to this site and which activates the constant portion to attract macrophages
Binding to the Fab portion –> ?
Binding to Fab –> Activates Fc portion –> Destruction of microorganism
What are the major class of Immunoglobulins (antibodies)?
IgG
IgM
IgA
IgD
IgE
IgG
Most abundant antibody in the blood (75%)
Appears in all body fluids and can cross placenta
Major antibacterial and antiviral antibody
2nd Antibody produced during an immune response; greater on second exposure or with booster shots
IgM
10% of immunoglobulins in blood
1st immunoglobulin produced during an immune response
Too large to cross membranes, only in vascular system
Activates complements and is responsible for natural immunity in species
M = Mostly in blood
IgA
15% of all immunoglobulins
Mostly in body secretions like saliva, tears, mucus, bile, etc
Defends against pathogens on body surfaces, especially respiratory and GI tracts - acts locally in GI tract but can act systemic
IgD
<1% of all immunoglobulins
Present in plasma and is easily broken down
Rare
Predominant antibody on the surface of B cells and is mainly and antigen receptor
Needed for the maturation of B Lymphocytes
IgE
<1% of all immunoglobulins
Antibody involved in immediate hypersensitivity reactions or allergic reactions occurring in minutes of exposure to an antigen
Binds to mast cells and basophils
Stimulates release of mast cell granules (histamine and heparin)
Also involved in parasitic infection
What immunoglobulin is the reason we do not normally get zoonoses?
IgM
Which is the largest type / structure of immunoglobulins?
IgM
Which immunoglobulin has a booster effect where it increases dramatically upon second exposure?
IgG
Types of Immunity
Natural
Active
Passive
Natural Immunity
Innate Resistance
Factors: heredity, age, health, species, sex
Occurs due to IgM
Active Immunity
Acquired through immunization (all or part of a microorganism) OR from actually having the disease
Passive Immunity
Immunity transferred from another source
Sources: breast milk, anti serum, pooled gamma globulin, immune serum
Short Term Protection is offered
Inactivated Vaccines
Killed viruses providing active immunity
not capable of replicating in the host - present little risk to recipient
Maintenance of lifelong immunity requires multiple doses
Live Vaccines (Attenuated)
Mostly involves use of live virus with altered virulence
Does not require use of multiple doses
Give active immunity
Active Immunization
Use of a modified product of an organism such as a toxoid is given
gives active immunity
Maintenance of protective titers requires periodic boosters
Examples of Active Immunity Vaccinations
Hepatitis B vaccine
Diphtheria Pertussis & Tetanus (DPT)
Haemophilus influenzae B vaccine
Poliovirus vaccine
Rotavirus vaccine
Measles, Mumps, and Rubella vaccine (MMR)
Varicella virus vaccine
Influenza virus vaccine
Pneumococcal polysaccharide vaccine
Why is active immunity not guaranteed by a vaccine?
You have to make the antibodies in response
Titer
a test to check for antibodies or if we are making antibodies
Often used with immunizations
Booster
A booster immunization to make sure you can continue to have a strong immune response with antibodies
How does passive immunity occur?
When antibodies from a human or animal are given to people who do not have immunity to the organism
Can either be naturally through placenta and breast feeding or by injection of gamma globulins
What are the components of a passive immunity vaccination?
- Immunizing Agent - active component
- Suspending Fluid - sterile water, saline, complex tissue culture fluid
- Preservatives - stabilizers or antibiotics to prevent bacterial overgrowth
- Adjuvants - aluminum based compound to enhance immunogenicity and prolong stimulatory effects
What kind of immunity does a Rabies Vaccine offer?
Passive Immunity because you need immediate protection - not the time to make your own antibodies
Same applies to snake antivenom
Examples of Passive Immunity Globulins
Hepatitis B immune globulin
Diphtheria antitoxin
Tetanus immune globulin
Varicella zoster immune globulin
Rabies immune globulin
Humoral Immunity depends on …
maturation of B cells into plasma cells and secretion of antibodies
What are the effector responses of humoral immunity?
Precipitation of antigen antibody complexes
Agglutination or clumping of cells
Neutralization of bacterial toxins and viruses
Lysis and destruction of pathogens or cells
Adherence of antigen to immune cells
Facilitation of phagocytosis
Activation of complement
There is a primary and secondary response in humoral immunity
Serum Sickness
Immune response (like an allergic reaction) occurs when falsely identifying a protein in medicine or antiserum
Causes hives, itching, joint, pain, swollen lymph nodes, pain
Can occur up to 25 days after exposure to the drug the first time and only 3 the next time
What are the stages that occur in a humoral response?
Antigen invades –> attaches to something (MCII) –> Macrophage engulfs and presents the antigen on its surface –>T4 cells then are stimulate from the presence of that MCII antigen –> T4 then activates B cells and differentiation into plasma cells to make antigens/immunoglobulins –> attach to invaders and allows destruction and an attack
Proliferation of B and T then occurs allowing Memory cell creation
How does HIV prevent the humoral response?
HIV destroys the CD4 marker on the T4 cells which means it can no longer direct destruction
How do IgG and IgM levels differ between induced immunity through a primary vaccination and a booster dose?
In the primary vaccination the IgM level will be the first main responder with a slow and slight increase in IgG over time
In the booster dose, the IgM level raises the same immediately like in the first dose, but the IgG has been raising since the first dose and immediately grows higher and higher (way above IgM)
IgM was metabolized after the first dose, but IgG remained
Cell Mediated Immunity
Protection against viruses and cancer cells
Action of T Lymphocytes and Macrophages predominate this response
Macrophages processes the antigen and presents it to T Cells
No antibodies, but protects against viruses and cancer
What type of immunity allows for constant cancer screening?
Cell Mediated Immunity
What are the stages of a cell-mediated immune response?
Antigen –> Macrophage engulfs antigen –> Antigen MHC II expression –> Release of cytokines by T4 to stimulate T8 –> T8 Production of cytotoxic cells
Complement and the Complement Cascade
Consists of 20 proteins circulating as functionally inactive molecules that cause inflammation in response to an invader
They “complement” the immune system by helping make an inflammatory response to draw WBC in to the area to phagocytize foreign bodies and lyse it
What is usually required for the complement cascade to work?
The antigen-antibody (IgG or IgM) reaction to activate the complement system
Chemotaxis
Draws WBC to foreign bodies
Potential Pathways for Complement Cascade
Classic Pathway
Alternative (Properdin) Pathway
Classic Pathway of Complement Cascade
initial step with activation of C1 (complement 1 protein)
Fc portion (constant) of IgG and IgM antibody is turned on after the antigen binds to the Fab portion
Alternative (Properdin Pathway) of Complement Cascade
Initial step with activation of C3
Activation is done by pieces of bacterial or fungal cell walls being released during phagocytosis
Does NOT involve antibodies
Debris activates complements for its destruction
What do Complement Proteins 1 through 5 do?
Stimulates mast cell degranulation, WBC chemotaxis, and opsonization of bacteria
What do Complement Proteins 6 through 20 do?
Bacterial cell lysis by making cell wall “leaky”
Pokes holes for enzyme injection
Complement Mediated Immune Responses
Cytolysis
Adherence of Immune Cells
Chemotaxis
Anaphylaxis
Opsonization
Cytolysis
Destruction of cell membranes (body cells or pathogens)
Adherence of Immune Cells
Adhesion of Ag-Ab complexes to surfaces of cells or tissues (phagocytes)
Chemotaxis
Chemical attraction of phagocytic cells to foreign agents
Anaphylaxis
Degranulation of mast cells with release of histamine and other chemical mediators
Opsonization
Targeting of antigen so it can be easily engulfed and digested by macrophages
Not marked by antibodies, another molecule
What are the main things complements do?
They launch an inflammatory response and mark a virus for a macrophage to find
This is a non specific response
Types of Immune Disorders
Hypersensitivity Disorders
Autoimmune Disorders
Immunodeficiency Disorders
Type I Hypersensitivity Disorders
IgE Mediated allergic reaction (basically allergic mast cell reaction)
Anaphylactic - immediate, mediated by IgE
IgE antibodies bind with antigens on the surface of Mast cells –> release of allergic mediators that cause vasodilation, increased capillary permeability, smooth muscle contraction, and eosinophilia
ex: anaphylaxis, allergy, hay fever, asthma, rhinitis, anaphylaxis, insect reactions
Type II Hypersensitivity Disorders
Cytotoxic reaction (cytolytic, complement-dependent)
IgG or IgM antibodies bind to cellular or exogenous antigens causing activation of the complement cascade –> this causes phagocytosis or cytolysis
ex: Blood transfusion reaction, Goodpasture’s syndrome, erythroblastosis fetalis, autoimmune anemia
Type III Hypersensitivity Disorders
Immune complex reactions / antigen and antibodies keep grouping together (d/t PMNs) and clump together and are deposited somewhere causing inflammation reaction
ex: Post streptococcal, serum sickness, autoimmune vasculitis
Type IV Hypersensitivity Disorders
Cell mediated reactions (immediately activates T4 cascade)
Delayed reaction
APC presents antigen to T cells in association with MHC –> T cells release lymphokines that stim macrophages (NO ANTIBODIES) –> Lysozymes released and damage surrounding tissue (an inflammation reaction causing damage)
ex: Contact dermatitis, Tb test, transplant rejection, poison ivy, allograft rejection, HVGD and GVHD
Which Hypersensitivity Disorder types are humoral/antibody mediated and which are cell mediated?
Humoral/Antibody - I II III
Cell Mediated - IV
Autoimmune Disorders
Immune response against self / T celsl get hyperactive and destroy healthy “you” cells
ex: rheumatoid arthritis and SLE, can cause Diabetes type I or Pernicious Anemia
Anaphylactic Shock
A systemic response from a type I hypersensitivity reaction
Anaphylaxis
Systemic response to the inflammatory mediators released in type I hypersensitivity
ex: Histamine, acetylcholine, kinins,, leukotrienes, and prostaglandins all cause VASODILATION (less circulating volume, could lead to shock)
ex: acetylcholine, kinins, leukotrienes, and prostaglandins all can cause BRONCHOCONSTRICTION
Goodpasture’s Syndrome
Type II Hypersens. Rxn
Inflammation in glomerulus from exposure to an antigen similar to the lining of the glomerulus
Erythroblastosis Fetalis
Hemolytic Disease of the Newborn
Type II Hypersens. Rxn
If the mom is rH negative and dad is rH positive and the baby is rH positive, during delivery the babies blood, if exposed to the mom, can cause the mom to develop antibodies in response to rH antigens
Nothing occurs in the first pregnancy, but in the second if the baby is rH+ then the IgG will cross the placenta (not IgM since its too big) and bind to rH and kill fetal RBC –> leads to anemia and cyanosis
This is why we give Rhogam twice during pregnancy
Agglutination
Blood clumping that occurs if the opposite antibody hits the antigen on an opposite blood type
ex: If you give B blood transfusion to an A blood person, the anti A antibodies in the donor B blood will connect with the A antigen on the recipients normal blood and destroy it, while the recipients anti b antibodies will hook to the b antigen and destroy those cells
Hemolytic Anemia
Type II reaction
This is the agglutination when the donor blood antibodies kill an opposite recipient blood type if given to the wrong person
What antigen and antibodies are present in A, B, O, and AB Blood?
A - Antigen A; Anti B Antibody
B - Antigen B; Anti A Antibody
O - No Antigens; Anti A and Anti B Antibodies
AB - A and B Antigens; No Antibodies
What is the mechanism of a type III hypersensitivity reaction?
Immune complexes deposit on the walls of blood vessels and activate complements
Blood vessels are then damaged
Inflammatory response at the vessel level causes damage in type III
HVGD
Host v Graft Disease
Type IV Hypersens Rxn
Tissue Transplant Rejection
If the MHC I are not similar enough (still need autoimmune drugs even if they are) the autoimmune system activates in a delayed reaction to the new organ
GVHD
Graft v Host Disease
Type IV Hypersens Rxn
Organ transplanted attacks the host
We can suppress the T cells in the person, but T cells in the organ will attack the person and are not suppressed
How is Tb testing a Type IV Hypersen Rxn?
Tb is a huge bacteria so we dont have antibodies or a titer for it
If we put an antigen under the skin and look for a cell mediated response indicating Tb exposure
