Innate and Adaptive Immunity Flashcards
What are the steps for phagocyte mobilization?
- Leukocytosis ( release of neutrophils from bone marrow in response to leukocytosis-inducing factors from injured cells)
- Margination (neutrophils cling to the walls of capillaries in the inflamed area)
- Diapedesis of neutrophils
- Chemotaxis (inflammatory chemicals, chemotactic agent, promote postive chemotaxis of neutrophils)
What are the mechanisms buy which phagocytosis works to destroy pathogens? 3 ways
- Destruction of pathogens (acidification and digestion by lysosomal enzymes)
- Respiratory burst
- Oxidizing chemicals
What are the innate external defenses?
skin, mucous membranes and secretions, skin acidity, lipids in sebum, dermcidin in sweat, HCL in stomach, lysozyme in saliva, mucus, haris, cilia
What are the general innate internal defenses (cells and chemicals)? Meaning, what does the innate immune response do, what is it responsible for? As well as cells, and proteins.
- phagocytes
- NK
- Inflammatory response (macrophages, mast cells, WBC, inflammatory chemicals)
- Antimicrobial proteins (complement proteins and interferons)
- Fever
What are the functions and characteristics of NK cells?
- large granular lymphocytes
- target cells that lack “self” cell-surface receptors WITHOUT previous exposure to surface antigens
- induce apoptosis in cancer cells and virus infected cells
- secrete potent chemicals that enhance the inflammatory response
When is inflammation triggered? How does it help in the immune response?
- triggered whenever body tissues are injured or infected
- prevents the spread of damaging agents
- disposes of cell debris and pathogens
- sets stage for repair
cardinal signs of inflammation are?
redness swelling heat pain immobility (sometimes)
What FIRST needs to happen to start the process of inflammation? (what promotes it, and what causes the that promotion to occur?)
- macrophages and epithelial cells of boundary tissues bear TLRs
- TLRs actviated trigger the release of cytokines
- Cytokines promote inflammation
What are the inflammatory mediators?
What are they released by?
- –histamine (from mast cells), blood proteins, kinins, prostaglandins, leukotrienes and complement
- –released by injured tissues, phagocytes, lymphocytes, basophils and mast cells
What do inflammatory chemicals cause?
- dilation of arterioles, resulting in hyperemia
- increased permeability of local capillaries and edema =(leakage of exudate)
what is exudate? What does it contain?
- -exudate is a mass of cells and fluid that has seeped out of blood vessels or an organ, especially in inflammation
- -contains proteins, clotting factors and antibodies
What is the function of exudate?
- -moves foreign material into lymphatic vessels
- -delivers clotting proteins to form a scaffold for repair and to isolate the area (collagen and fibrin)
What are the steps of IFN production? Starting with virus entering cell.
- virus enters cell
- interferon gene inside cell turns on
- cell produces interferon molecules
- interferon is then secreted from that cell
- interferon enters neighboring cells–or binds to cell
- interferon stimulates cell to turn on genes for antiviral proteins
- antiviral proteins block viral reproduction in cell
What interferon do lymphocytes secrete?
gamma = immune interferon
p. 287 (also NK and macrophages)
What IFN do most WBCs secrete?
alpha
What IFN do fibroblasts secrete?
beta
What cells do IFNs activate?
macrophages and mobilize NK cells
What is the function of interferons?
- antiviral
- reduce inflammation
- activate macrophages and mobilize NK cells
What do genetically engineered INFs do?
- antiviral agent against hepatitis, genital warts
- MS treatment
What are the three phases of complement?
- Initiation or activation
- amplification of inflammation
- Membrane attack response (promotes phagocytosis and causes cell lysis)
What does C3a do?
triggers migration of neutrophils in the the tissues to enhance the inflammatory response
What does C3b do?
INITIATES the formation of a MAC and also opsinization
What does C5a do?
inflammation
What does MAC do?
cell lysis
What complement proteins are the mac made of?
C3b starts it, then C5b, C6, C7, C8, C9
What are the benefits of a moderate fever?
- -causes liver and spleen to sequester iron and zinc
- -increases metabolic rate which speeds up healing
What happens to self reactive B cells?
they undergo clonal deletion
or
they undergo receptor editing (rearrangement of their receptors)
What is positive and negative selection in T cells?
First step= positive selection
T cells must recognize self MHC proteins or they will die
Called MHC restriction (survivors are restricted to recognizing antigen on self-MHC)
second step = negative selection
T cells MUST NOT recognize self-antigen or will die = autoimmune diseases!
failure to recongize (bind tightly to) self antigen results in SURVIVAL and continued maturation
What is an antigen?
- substance that can mobilize the ADAPTIVE defense and provoke an immune response
- -most are large, complex molecules not normally found in the body (non self)
What is a complete antigen? What is does it mean that it is immunogenic and reactive? What are some examples?
Immunogenicity = ability to stimulate proliferation of specific lymphocytes and antibodies
Reactivity = ability to react with products of activated lymphocytes and antibodies released
examples: foreign protein, polysaccharides, lipids, nucleic acids (bacteria and viruses)
What is a hapten?
What does the hapten do?
What are some examples?
hapten = small molecules (peptides, nucleotides, hormones)
- -haptens are IMMUNOGENIC when attached to BODY PROTEINS
- cause immune system to mount a HARMFUL attack
ex. poison ivy, animal dander, detergents, cosmetics
What are the adaptive defenses?
- -specific, systemic, has memory!
- protects against infections agents and abnormal body cells
- amplifies inflammatory response
- activates complement
What is the humoral adaptive defense consist of and what is it mediated by and what does it defend against?
B-cells, antibodies, plasma cells
- mediated by B-cell activation and subsequent Ab production
- primary defense against EXTRAcellular microbes and toxins
What is the cell-mediated adaptive defense consist of and what is it mediated by and what does it defend against?
T-cells, Cytotoxic T-cells, Helper T-cells
- -mediated by activation of T-cells
- responsible for the bodies defenses against intracellular mnicrobes such as viruses
What molecule has little or no immunogenicity?
large, chemically simple molecules
plastics, valves, hips
What is an antigenic determinant?
- certain part of antigen that is immunogenic
- Ab and lymphocytes bind to them
- most have numerous antigenic determinants that: 1. mobilize several different lymphocyte pops and 2. form different Ab against it
Finish the sentence. Most naturally occurring antigens have numerous antigenic determinants that:
- mobilize several different lymphocyte populations
2. form different kinds of antibodies against it
What are the the examples of effector and regulatory cells and what do they do?
Regulatory cells = regulatory t, helper t(activate other lymphocytes and phagocytes)
Effector = cytotoxic t, macrophages, other leukocytes
In the adaptive immune response, what destroys antigens and what retain ability to target antigens in future?
effector cells target: cytotoxic t
memory b and memory t helper and t cytotoxic for future
Finish the sentence. Class I and II MHC genes are responsible for encoding HLAs (human leukocyte antigens) which are proteins found on the cell surface that?
Define the patients tissue type!
makes sense for checking these with transplant patients!
What are the APCs that are able to express both classes of MHC molecules?
DCs, monocytes, macrophages, B lymphocytes
** under certain conditions endothelial cells are also able to function as APCs
Discuss MHC I molecules and what cells they are found on and what they present.
present peptide fragments to Tc cells
found on all cells (except RBCs)
**may present degraded viral protein fragments from infected cells
Discuss MHC II molecules and what cells they are found on and what they present.
present peptide fragments to TH cells
found on APCs (DC, monocytes, macrophages, Bcells)
**bind fragments from pathogens that have been ENGULFED and digested during phagocytosis
What cell functions as the primary APC?
macrophages
What tissues and organs are the macrophages found?
Tissue macrophages are found: connective tissue lung (alveolar macrophages) liver (Kupffer cells) spleen lymph nodes peritoneum CNS (microglial cells) other areas
How do macrophages initiate the adaptive immune response?
They are activated during innate response when they engulf and antigen, break it down and the present it on MHC II for T cell (cell mediated response) to recognize, then activate B cells and Thelper cells
Where are DC located and how do they function?
Found through body in places where antigens can enter body:
langerhans cells (skin) –> transmit to nodes
follicular DCs (lymph nodes)
mucosal lining of bowel
Where do macrophages mostly remain?
fixed in lymphoid organs
What do dendritic cells do once they internalize pathogens?
enter lymphatics to present antigens to t cells in lymphoid organs
What do activated T cells do to macrophages?
release chemicals that make macrophages secrete bactericidal chemicals and become insatiable phagocytes
Why are DCs referred to as “professional” APCs?
because principal function of DCs is to present antigens and b/c DCs have the ability to induce a primary immune response in RESTING NAIVE T lymphocytes
What APC is CRITICAL in establishment of immunological memory?
Where does it display endogenous antigens?
Dendritic cells
MHC I AND MHC II
Humoral immunity is more important than cellular immunity in defending against what? Why?
microbes with capsules rich in polysaccharides and lipid toxins
Why?because ONLY THE B lymphocytes are capable of responding to and producing antibodies specific for many types of these molecules.
T cells, mediators of cellular immunity, primarily respond to?
surface protein antigens
What are the two things that a B cell clone turns into?
- most clone cells become plasma cells
2. memory cells
When does the primary immune response occur? What is the time frame to mount a response? When are the peak levels for plasma Ab reached?
- -occurs on 1st exposure to Ag
- –3-6 days = lag period
- -peak levels in 10 days then decline
When does a secondary immune response occur? What is the time frame to mount a response? When are peak Ab levels reached? How long do Ab levels stay high?
- -occurs on re-exposure to same Ag
- -sensitized memory cells mount response in few hours
- -peak levels reached in 2-3 days and much higher levels than primary
- -Ab levels stay high for weeks to months
- Ab bind with much greater affinity
Discuss the composition of the classic structure of an antibody.
- -compromised of 4 polypeptide chains with at least 2 identical antigen binding sites
- -two identical light chains
- -two identical heavy chains (forms the “Y”)
- -Variable (V) regions of each arm combine to for identical antigen-binding sites
- Constant (C) region
What does the constant (C) region of the antibody structure determine?
- the antibody class(M, A, D , G, E)
- -cells and chemicals the Ab can bind to
- how Ab class functions in Ag elimination
- **Determine the EFFECTOR part of the antibody
What is significance of V (variable) region on antibody?
It is where Ag-Ab binding occurs and differ from antibody to antibody
What are properties of IgG?
- -most abundant
- -large molecule
- -possess anti: viral, bacterial, toxin properties
- -present in ALL body fluids
- -readily enters tissues
- -capable of crossing placenta(passive immunity to fetus)
What are properties of IgA?
- -primarily in secretory: sweat, saliva, tears, colostrum(milk), bronchial, gastro, prostatic, vaginal
- -primary function is in local immunity on mucosal surfaces
- -prevents attachment of viruses and bacteria to epithelial cells
What are properties of IgM?
- -pentamer
- -first Ab released by plasma cells during primary response
- -effective agglutinating agent because of numerous ag-binding sites
- -readily fixes and activates complement
- -first Ab to be produced by developing fetus and immature B lymphocytes
What do high levels of IgM in the blood signify?
Acute infection
What are the properties of IgD?
- -monomer
- -primarily on B cell membranes where functions as receptor
- -function is unknown
What are the properties of IgE?
–least common, binds very tightly to basophils and mast cells
–secreted by plasma cells in skin, mucosae of go and respiratory tracts, tonsils
–involved in inflammation and allergic responses by:
causing mast cell degranulation and release of chemical mediators including histamine
–essential for combating parasitic infections
–abdominal pain with increase =may want to thing worms
What determines which foreign substances our immune system will recognize and resist?
GENES not antigens
What are the forms the ab-ag complex can take on?
** are most important
Precipitation of ab-ag complex
**Agglutination of pathogens
**Neutralization of toxins
complement activation (classical pathway)
[leads to cell lysis and phagocytosis]
What occurs in neutralization?
- simplest mechanism
- -ab block specific sites on viruses or bacterial endotoxins
- -prevent ag from binding to receptors on tissue cells
- -ab-ag complexes undergo phagocytosis
What occurs in agglutination?
–ab bind same determinant on more than one cell-bound ag
–cross-linked ag-ab complexes agglutinate
ex= clumping of mismatched blood
What occurs in precipitation?
- soluble molecules are cross-linked
- -makes precipitate and subject to phagocytosis
What is the main defense against cellular antigens???
Compliment fixation and activation!!!
How does complement fixation and activation occur? What are the steps? (Think classical pathway).
- ab bind close together on cellular antigen
- complement binding sites trigger complement fixation on cells surface
- complement triggers cell lysis (MAC puts hole in cell, influx of fluid)
What are the activated complement functions?
- -amplifies inflammatory response
- -opsonization
- -enlists more and more defensive agents
what are monoclonal antibodies?
- -commercially prepared pure Ab
- -produced by hybridomas
- proliferate forever and produce single kind of ab
- -used in research, clinical testing and **cancer treatment
After antigen binding stimulates T cell, proliferation cannot occur until?
co-stimulation must occur
T-cell must bind to antigen on MHC II with CD4 or MHC i with CD8 and then also have TCR bind as well.
What is an autograph?
transplant from one body site to another in the SAME PERSON (skin graft)
What is an isograft?
transplant between identical twins
MHC should be identical
(ex: renal transplant)
What is an allograft?
transplant between two individuals who are not identical twins (may be related like siblings or parent to child, etc.)
What is a xenograft?
transplant from one species to another
(pig liver to human)
(heart transplants from baboons and chimps)
What does the lymph fluid transport?
acellular fluid and cells of the immune system
What are the two functions of the lymph system?
- Fluid handling (2-4L/24hours)
2. Immune surveillance
What are the central (primary) lymphoid organs?
Bone marrow
Thymus
What are the peripheral (secondary) lymphoid organs?
Lymph nodes, spleen, MALT =tonsils, Peyers patches in intestine, appendix, and respiratory, GI and reproductive systems
What are the two ways that adaptive immunity can be acquired?
Active: develops by getting the vaccine (passive) or disease (active)
Passive: host receives antibodies or immune cells from another source
What processes lymph from a discrete, adjacent anatomic site?
lymph nodes
Compare and contrast lymph and serum.
- Electrolytes are pretty equal (Na, K, Cl, Ca)
- Creatinine is pretty equal
- Glucose is pretty equal, little higher in serum
- More cholesterol in serum
- More Total protein in serum
- More albumin in serum
- Urea is higher in serum
- IgG is higher in serum
What are the three main determinants for filtration (lymph)?
- Net hydrostatic pressure
- Net oncotic pressure
- Capillary permeability
What can change capillary permeability (think in terms of filtration to lymph system)?
Sepsis causes ARDS (adult respiratory distress syndrome)
Fever
Infection
Inflammation
Burns (destroy CT)
Toxic damage (sepsis, pancreatitis, inhalation)
What is capillary oncotic pressure?
colloid osmotic pressure contributed by plasma proteins, mainly albumin
What is interstitial oncotic pressure?
colloid osmotic pressure contributed by active proteins in the interstitium
The capillary lumen has significatnly higher oncotic pressure than that of the interstitum and most blood proteins remain within capillary lumen. This means? And what is the difference and where is it favoring?
This leads to drawing fluid from the interstitium INTO the lumen.
Difference is about 20mmHg favoring resorption into capillary lumen.
What can increased intravascular hydrostatic pressure cause? How?
Edema = from fluid overload and localized obstruction
- -heart failure causes pulmonary edema and lower leg edema
- -cirrhotic liver disease causes obstruction of flow from destruction of cells=portal htn=ascites
What can decreased intravascular oncotic pressure cause? How?
Edema = protein loss
- -malnutrition (intake issue or malabsorption in GI issue)
- -liver failure (not making proteins)
- -nephrotic syndrome (pee out proteins)
What diseases cause lymphatic obstruction? Where will the edema occur?
Lymphoma
Metastatic cancers
Edema occurs DISTAL to the obstruction
Where do neutrophils reside? What do they attack? Can they move?
Attack and destroy bacteria in the blood, they also go into the tissues as needed
Where are lymphocytes stored and how long do they live?
Stored primarily in lymph nodes
–live weeks to months
Where are leukocytes stored? How long do they live?
- -formed in bone marrow, stored there until needed
- granulocytes live 4-8 hours in blood, 4-5 days in tissues (life span shortened if infection)
- -monocytes live 10-20 hours in blood, live for MONTHS in TISSUES as macrophages
What three factors determine if phagocytosis will occur?
- Rough surface= increase phagocytosis
- Protective protein coat = less likely to be phagocytize
- Tagged with Ab or marker = increase phagocytosis
What is in exudate?
combo of varying portions of necrotic tissues, dead neutrophils, dead macrophages, and tissue fluid
What do basophils and mast cells secrete? Where are they located? What Ab has special propensity to become attached to these cells?
Secrete: histamine, bradykinin, serotonin
Basophils = blood
Mast cells = tissues
IgE
What do interferons do? (IFNs)
- -activated IFNs interact with specific cellular receptors, causing the expression of antivirus and immune modulatory genes.
- -activated macrophages
- induce B cells to switch Ig type
- alter T-helper response
- -inhibit cell growth
- promote apoptosis
- -induce an antiviral state in unaffected cells
What cells release what interferons?
Alpha and beta secreted by virus infected cells
gamma is mainly secreted by T-cells, NK cells, macrophages