Immunology Flashcards
Basophils
Granulocyte Least common Mature in bone marrow Circulate in blood stream Release histamine and heparin (allergic and helminth response)
Eosinophils
Derived from bone marrow, 1-6% of WBCs Bloodstream and organs (GI &respiratory) Release H2O2 and oxygen radicals to kill viruses/parasites Release leukotrienes Active in allergic reactions, asthma Stimulate T-lymphocytes Antigen presenting Cell weakly phagocytic
Leukotriene
lipid signaling molecule that causes airway muscle contraction
Neutrophils
Most abundant granulocyte Circulates bloodstream "first responder" (bacteria and fungi) Releases cytokines Strongly phagocytic Neutrophil extracellular traps
Cytokines
Cell to cell communication proteins that control development, differentiation and movement to specific part of body
Interleukins, TNF, Chemokines, Interferons
Interleukin
13 cytokines that are regulators of immune response, inflammatory response and hematopoiesis
ILs 1&6-fever
IL 6-“acute phase” response
Tumor Necrosis Factor (TNF)
activates neutrophils, mediates septic shock, causes tumor necrosis
Chemokines
cytokine released by infected/injured cells-imitate immune response (signal neutrophils and macrophages) and warn neighboring cells of threat
Interferons
Block virus replication
Alpha, beta, gamma
Gamma is strongest-produced by Tcells, activates macro/NK/neutro
Mast Cells
Release histamine and heparin
Naive in bone marrow, mature in tissues
Degranulate (burst) if injured, encounter antigen/allergen, exposed to complement protein
Causes anaphylaxis
Monocyte
“Agranular”
Give rise to dendritic and macrophages
Develop in bone marrow>spleen and tissues
Differentiate in tissues
3 functions: phagocytosis, APC, cytokine production
Dendritic cell
Strongest of APCs Activate T-helper cells Capture antigen migrate to lymph node and present to T and B cells Langerhans cells
Macrophage
Large phagocyte release TNF and ILs Act as APCs to helper T cells Under skin, lungs, GI, respiratory 3 stages: resting-cleaners, Primed-active engulfing/APC, Hyperactivated-rapidly destroying pathogens
Kupffer Cell
Specialized macrophage within liver
destroy bacteria and old RBC
Chronic activation leads to overproduction of inflammatory cytokines
Causes liver damage/cancer
May become host for TB, Leishmania, Cikinguya
Natural Killer Cells
Cytotoxic lymphocytes against viruses and cancer cells
granules of destructive enzymes
Mature in bone marrow, lymph nodes, spleen, tonsils and thymus
enhanced by cytokines
Release performs and protease that lyse cell or trigger apoptosis
Can trigger apoptosis by surface contact
in bloodstream, liver and spleen
“kill or don’t kill”
Can kill during resting phase
Major Histocompatibility Complex (MHC) Proteins
AKA Human leukocyte antigen (HLA)
surface molecules that help determine if protein is “self” or “not self”
Bind antigen to cell surface and display for T-cell recognition
3 subgroups (I, II, III)
Determines organ donation compatibility
malfunction causes autoimmune diseases
T and B cell activation
Acute Phase Proteins
Produced by liver in response to release of IL-1, IL-6 and TNF
C-reactive protein, Mannose-binding lectin, lipopolysaccharide-binding protein
Mark pathogens/injured cells for destruction-activates complement
Complement system
Enhances ability of phagocytic cells to destroy pathogens
3 possible activation pathways: Classical (requires trigger), Alternative (continuously activated at low level), &Lectin pathway (requires very specific type of trigger)
ACTIVATED BY ANTIGENS
proteins made by liver
C3 most abundant in humans
Opsonization
enhancing phagocytosis of antigens by “marking” them for destruction
Chemotaxis
Attracting and activating macrophages and neutrophils; inducing mast cells and basophils to degranulate
Lysis
Rupturing pathogen cell-membranes by forming the Membrane Attack Complex (MAC)
Complement Fixation
Antigen combines with an antibody and it’s complement, causing the complement factor to become inactive or “fixed”
Membrane Attack Complex
C5b forms complex with C6, C7, C8 and C9 to form MAC
causes lysis of cell by disrupting osmotic balance (bringing water into cell), which causes the cell to swell and burst
Innate Immunity
Immediate response
Non-specific response (always the same)
Response doesn’t increase with repeat exposure
Adaptive Immunity
Antibodies recognize only ONE antigen, binds to specific site on invader
Directly block binding of invader cells, Inactivate viruses/neutralize toxins, Mark pathogen for destruction by phagocytes
Requires days to develop
Responce enhanced by repeated exposure (develops memory for quicker/more intense response)
Antibody
2 light chains, 2 heavy chains, antigen binding sites, FAB region, Fc region
IgM, IgG, IgE
IgM
Primary immune response
Half life of ~10 days
usually in intravascular space
increased levels=RECENT exposure to antigen
IgG
4 subclasses
Found in Blood, lymph, CSF, peritoneal fluid
Evenly distributed in intra/extravascular space
Only class that crosses placenta-Rh antigen, but gives baby moms immunity
Helps NK find their target (opsonization), immobilize bacteria by binding to cilia/flagella, activates complement, neutralizes toxins and some viruses by binding
Late in primary response
IgA
Primarily in external secretions (including breast milk)
Protects infant, prevents viruses from entering cell, prevent pathogens from attaching to/penetratin epithelial surfaces
IgE
Low amounts in serum
2 day half life
Binds to mast cells and basophils
Triggers degranulation, releasing histamin/leukotrienes/heparin from granulocytes
Increased in atopic people & in presence of parasites
IgD
Present on surface of naive B cells
low amounts in serum
unknown function
Primary Lymphoid organs
Thymus and Bone Marrow
where immature lymphocytes go to mature/proliferate
Secondary Lymphoid Organs
Spleen, lymph nodes, tonsils/adenoids, appendix
Where antigens presented to mature B & T lymphocytes to imitate adaptive immune response
B-Cell
Elliminates extracellular pathogens
Antigen-presenting cell w/ MHC
Produces antibodies (immunoglobulins, Ig) to neutralize pathogen
Has membrane-bound antibodies, recognizes antigen by B-cell receptor coupled with T-helper, prompts B-cell to divide into effector cells which produce antibodies
Produce memory B cells
T-Cell
Destroy intracellular pathogens (viruses/intracellular bacteria)
Directly kill infected cells
CD8 cells
Killer t-cells/cytotoxic
specialize in identifying and killing cells infected with virus
CD4
Helper t-cells
doesn’t directly kill pathogen, sounds alarm with cytokines
Assists in activation of CD8
Signal B cells to start secreting antibodies
Activated cell differentiates into effector and memory cells
Hypersensitivity Reactions
exaggerated, inappropriate immunologic reaction thats harmful to host
What are the 4 types of Hypersensitive reactions?
Type I: allergy/anaphylaxis
Type II: Cytotoxic, antibody dependent
Type III: Immune complex
Type VI: Delayed, cell mediated
Type I
Anaphylactic
First exposure: IgE binds to mast cells
Repeated: antigen binds to IgE bound mast cell, degranulates releasing histamine/heparin
5-30 minutes
Antigens-food, pollen, drugs
Vasodilation, broncho-constriction, edema, itching
Type II
Cytotoxic Antigens on cells or in extracellular matrix leads to complement-mediated lysis IgG hours-days hemolytic anemia
Type III
Immune complex
IgG
antigen-antibody complex forms and deposits in tissue inducing inflammatory response
complement activated, lysosomes released, tissue damage
2-3 weeks
lupus, rheumatoid arthritis
Type VI
Delayed cell-mediated
T-lymphocytes, lymphokines
2-3days
macrophage ingests antigen, process and presents with MHC, helper T cell activated and produces gamma interferon activating macrophages
contact dermatitis, poison oak/ivy, TB test reaction, erythema multiforme (target lesions)
Hereditory Angioedema
deficiency of C1 protease inhibitor (leads to excess C3a, C4a, C5a)
autosomal dominant
larygeal edema, capillary permeability
Epitope
area on an antigen that triggers a response
Autoimmune Disease
A trigger interferes with normal mechanisms protecting auto-antigens against an immunologic response causing tissue injury
Criteria: autoantibodies, self-reactive T-lymphocytes, imbalance between T and B cell factors
Types of triggers: exogenous, endogenous, molecular mimicry
Graves’ Disease
Environmental and genetic factors: stress, smoking, postpartum, increased iodine intake
Autoantibodies: thyroid stimulating immunoglobulin (TSI)
Rheumatic Fever
Molecular mimicry (reaction to infection with Streppyogenes) Rheumatic heart disease (valve damage)
Myasthenia Gravis
Autoantibody blocking/inactivation of alpha chain of Ash receipts
Thymus abnormalities in 70%
Anti-AChR antibodies (damage post synaptic membrane, blocks AChR active binding site, increase receptor turnover)
Systemic Lupus Erythematosus (SLE)
Type III
Genetic susceptibility and environmental factors
immune complex formation targets double-stranded DNA
Antibodies: Anti-dsDNA, anti-Smith
Type I Diabetes
Genetic susceptibility (MHC class II)
Insulin and Islet cell Autoantibodies
t-cell cytokine production and cellular toxicity
Rheumatoid Arthrititis
Type III
Genetic & environmental factors (tobacco smoke)
Autoantibodies: Rheumatoid factor, anti-CCP
Multiple Sclerosis
Genetic
pro-inflammatory autoimmune respinse causes myelin destruction
Both T and B cells
Active Immunity
Artificial antigens administered to elicit controlled immune response
Mediators: antibody and T cells
long duration, slow onset
*most typical vaccines
Passive Immunity
Antibody transferred from immune individual to non immune individual (immunoglobulins or transferred through placenta)
Immediate, but short duration
Live Attenuated Vaccines
Active Immunity Weakened form of virus Antigen stimulates immune response Must be refrigerated Not for immunocompromised/pregnant MMR, Varicalla, Flu
Inactivated Vaccine
Active Immunity Pathogens killed to inactivate so we can isolate antigenic material freeze-dried weaker immune response, multiple doses Polio, Hep A, Japanese encephalitis
Subunit
Active Immunity
Use component of pathogen as vaccine to mimic exposure
Toxoid
inactivated/killed toxins used to elicit immune response resulting in antibodies that can neutralize toxins (diphtheria)
Surface protein Subunit
uses purified protein from pathogen
Polysaccharide Subunit Vaccine
uses polysaccharide antigens (meningococcal, pneumococcal)
Recombinant Subunit Vaccine
antigens made w/ recombinant DNA tech
Conjugate Subunit Vaccine
Polysaccharide from bacterial capsule bound to carrier protein
induces long-term protection
Hib, pneumococcal, meningococcal
Types of Leukocytes
Lymphocytes, granulocytes, monocytes and macrophages
Antigen
anything that causes an immune response
Hematopoiesis
Formation and development of cells that make up blood
Fetus: liver/spleen/thymus
Birth^: bone marrow and lymph tissue
Primary Immune Response
IgM formed early, first exposure to antigen, typically acute infection
IgG formed late
Secondary Immune Response
IgG high, old infection
Adhesion Molecules
Membrane proteins that connect cells to other cells or extracellular matrix
Major role in recruitment of neutrophils to inflammation
Chronic inflammation>chronic cytokines release and leukocyte infiltration>release of lysozyme/free radicals>tissue damage
Function of Plasma Cells
AKA effector cells
produce antibodies
Most abundant isotope of antibody in serum?
IgD
Monoclonal Antibodies
Antibodies produced the lab, bind to only one site on antigen
Polyclonal Antibodies
Prepared from immunized animals, can bind to multiple sites on an antigen
T-Cell and B-Cell Location
Immature: Thymus (T only) and bone marrow
Mature: Spleen, lymph nodes, tonsils/adenoids, appendix
Granulocytes
Basophils, Eosinophils, Neutrophils, Mast cells
Type I interferons
Includes alpha and beta, function is to induce viral resistance in cells; can be produced by any cell in body
Type II Interferons
Secreted only by natural killer cells and t lymphocytes; signals immune system to respond to infectious agents or cancerous growth
What does blood type testing look for?
agglutination (antibody binding to antigen causing clumping)
Type A Blood
A antigens, anti-B antibodies
Type B Blood
B antigens, anti-A antibodies
Type AB Blood
A and B antigens, no antibodies
AB+ is universal recipient
AB- least common (1%)
Type O blood
no antigens, Anti-A and anti-B antibodies
O- is universal donor
O+ most common (38%)
RH Blood
if present blood is + if absent blood is -
Rh- antibodies are not always present button develop upon exposure (Rh- mom and Rh+ fetus-hemolytic disease in newborn)
Indirect Coombs Test
Mom’s blood drawn mixed with Rh+ RBCs, combo’s serum added-causes agglutination if antibodies present (Rh-)
Test initially and at 28-30 weeks and 36 weeks
mother given RhoGAM immediately after delivery
Radioallergosorbent test (RAST)
blood test to detect specific IgE antibody to allergen in serum
Positive Antigen test
pathogen is currently in body
detectable before antibodies on first infection
Positive antibody test
patient has been exposed to pathogen, may or may not be currently infected
Titer
measures the concentration of an antibody, determined by finding highest dilution at which it still causes agglutination-higher titer=more antibody present
RPR most commonly used
