Week 3 - Immunology Flashcards
Who is Robert Koch?
1st person to identify microbes as causing disease
Koch’s Postulates
(used in disease identification)
- Pathogen must be found in every host + ever case
- Same pathogen must be isolated from the host and grown in pure culture
- When placed in a healthy host, that pathogen must cause the same disease
- When the pathogen is isolated from the new host, it has to be proven to be the original pathogen
Endemic Disease
normally found within the population
ex. common cold
Epidemic Disease
many people acquire disease over a short period of time
ex. COVID
Antibiotics
chemical subtances derived from mold or bacteria that cure infections
-pathogen causing disease must be bacterial in order for antibiotics to work
Immunity
the ability of a body to resist or eliminate potentially harmful, foreign materials or abnormal cells
immune system plays a key role in this
How does the immune system play a key role in immunity?
-defends against invading pathogens
-removes worn out cells
-identifies and destroys abnormal cells
Inappropriate immune responses lead to:
allergies + autoimmune diseases
Primary pathogens that activate the immune system:
-bacteria
-viruses: 94% of febrile illnesses; noncellular
Leukocytes
immune system effectors arising from stem cells in bone marrow
-neutrophils
-eosinophils
-basophils
-monocytes
-lymphocytes
(all destroy bacteria by phagocytosis)
Neutrophils
Leukocytes
highly mobile phagocytes engulf/destroy unwanted cells
Eosinophils
Leukocytes
secrete chemicals to fight parasites; also involved in allergic reactions
Basophils
Leukocytes
release histamine and heparin; also involved in allergic reactions
similar to mast cells
Monocytes
Leukocytes
are transformed into macrophages; tissue bound, phagocytic
B Lymphocytes
Adaptive Immunity
antibody-mediated immunity (adaptive)
-differentiate into plasma cells (stimulated by antigens to produce antibodies) + memory cells (lay dormant to prevent future infections)
stored/processed in bone marrow
Memory Cells
(B Lymphocytes)
Adaptive Immunity
lay dormant to prevent future infections
Plasma Cells
(B Lymphocytes)
Adaptive Immunity
stimulated by antigens to produce antibodies
T Lymphocytes
Adaptive Immunity
cell mediated immunity (adaptive)
-maintained by Thymosin
-antigen induces immune response against itself
-do not secrete antibodies; directly bind to target
-clonal/antigen specific
-slow response time
-two types: Cytotoxic + Helper
stored/processed in Thymus
Sites of Lymphoid Tissues
store, produce + process lymphocytes
-bone marrow (B lymphocytes)
-Thymus (T lymphocytes)
-lymph nodes
-spleen
-tonsils
-adenoids
-appendix
-Peyer’s patches (digestive tract)
Pathogens that enter the immune system are filtered by:
lymph nodes
What serve as macrophages within the lymph nodes?
lymphocytes
(spleen performs a similar role in the blood)
Innate (non-specific) Immunity Characteristics
Innate Immunity
1st line of defense from foreign pathogen
-cannot recognize a specific pathogen (non-selectively defends)
-natural killer cells, neutrophils, macrophages, dendritic cells, mast cells, basophils, eosinophils
-binds to pathogenic markers
-rapid but limited
-works immediately upon exposure to threatening agent
-respond to phagocytic cells by TLRs (toll-like receptors) - generic traits
4 Innate Immunity Defenses
Innate Immunity
- Interferon
- Natural T killer cells
- Complement system
- Inflammation
What is Inflammation?
Innate Immunity
non-specific response to tissue injury
-goal: bring phagocytes & plasma proteins to invaded or injured area
(same no matter what triggering event)
Characteristics of Inflammation
Innate Immunity
-defense by macrophages
-redness
-swelling
-interstitial clots
-immigration of leukocytes
-pus
-heat
Inflammation: Process
Innate Immunity
-Resident macrophages defend against bacteria (hour 1)
-Arterioles dilate (redness)
-Histamine is released to increase capillary permeability (swelling)
-Plasma proteins leave blood to enter inflamed area - leakage of plasma and fluid (edema)
-Fibrin walls off the area from surrounding tissues (interstitial clots)
-Neutrophils or monocytes emigrate from blood to area (adhere by margination, enter space by diapedesis, guided by chemotaxis)
-Within a few hours, leukocytes proliferate (pus)
-Increase in neutrophils 4/5x than normal
-Opsonins mark bacteria for destruction
-Antibody binds to foreign cells to make more susceptible to phagocytosis -> complement system activated
-Inflammatory process repairs tissue
Phagocyte Secreted Chemicals
(Inflammation)
Innate Immunity
-Nitric Oxide (macrophages)
-Lactoferrin (neutrophils)
-Histamine (increase capillary permeability)
-Kinins (from kininogens)
-Endogenous pyrogen (fever development)
-Leukocyte Endogenous Mediator (decreases plasma iron)
-Acute phase proteins (liver)
Margination
(Inflammation)
Innate Immunity
neutrphils/monocytes adhere to surface of capillaries
Diapedesis
(Inflammation)
Innate Immunity
neutrophils enter interstitial space
Chemotaxis
(Inflammation)
Innate Immunity
Neutrophils are guided to area in need
Opsonins
(Inflammation)
Innate Immunity
mark bacteria for destruction
(activated proteins of complement system)
Where does scar tissue form?
(Inflammation)
Innate Immunity
non-regenerative tissues (ex. nerve + muscle)
Drugs that suppress inflammatory process:
Innate Immunity
-NSAIDS (aspirin - inhibits histamine release; ibuprofen)
-Glucocorticoids (suppress all aspects to resist infection)
-Infliximab (Remicade)/Humira (autoimmune diseases)
-Chemotherapy (methotrexate, azathioprine, 6-mercaptourine) -> decreases WBCs
-Interferon (inhibits multiplication of viruses)
Interferon
Innate Immunity
triggers production of virus blocking enzymes
-enzymes inactive unless attacked by virus
-released nonspecifically from any cell when virus attacks
-induces immunity to many viruses
-warns other cells of viral attack
-slows cell division
-anticancer effects
Natural Killer Cells
Innate Immunity
naturally occuring lymphocyte cells
-lyse membranes
-1st line of defense against cancer
-destory cancer and virus infected cells
-provide an immediate non-specific defense
-release chemicals to destroy target cells
Complement System
Innate Immunity
non-specific response consisting of plasma proteins produced by the liver
-activated by exposure to carbohydrate chains (identification markers) on microbial surface + antibodies produced by foreign invaders
-cascade (C1-C4) reinforces general inflammatory tactics
(forms membrane attack complex C5-C9 to form holes in victim cells)
Membrane Attack Complex
(MAC)
Innate Immunity
-C5 starts the membrane attack complex
-forms pore in membrane of the invader
-foreign particle is recognized by antibody
-complex attaches to foreign body & causes lysis
-formed by C5-C9
occurs towards the outer end of complement cascade
Membrane Attack Complex: Process
(MAC)
Innate Immunity
- Antibody molecules attach to the antigens on the pathogen’s membrane
- Complement proteins link two antibody molecules
- Activated complement proteins attach to the pathogen’s membrane in step by step sequence, forming membrane attack complex (MAC)
- MAC pores in the membrane cause lysis
Membrane Attack Complex: C5-C9
(MAC)
Innate Immunity
- C5 binds with C6 and C7
- C567 complex binds to membrane via C7
- C8 binds to complex and inserts into cell membrane
- C9 molecules bind to complex and polymerize
- 1-16 molecules of C9 bind to form a pore in the membrane
Adaptive (Specific) Immunity
Adaptive Immunity
2nd line of defense
-learn from exposure (ex. vaccine or familiar pathogen)
-fast and strong but takes more time (prepares for attack)
-two types: cell mediated and antibody mediated (humoral)
Antibody Mediated (Humoral) Immunity
Adaptive Immunity
production of antibodies by B-Lymphocytes -> plasma cells -> antibodies
Cell Mediated Immunity
Adaptive Immunity
production of T-Lymphocytes to directly attack unwanted cells
What allows T + B cells to recognize invaders?
(distinguish between antigenic and normal cells)
Adaptive Immunity
Ag (antigen ) presence
-surface receptors for binding with one possible type of antigen
Recognition of an antigen stimulates…
Adaptive Immunity
B cells to convert to plasma cells, then into antibodies
All antibodies eventually enter where?
blood or lymph
What are antibodies?
(Ab)
Adaptive Immunity
immunoglobulins
-globular proteins found in blood serum (Ig)
-“arms” attach to antigens by agglutination
-amplify immune response to promote antigen destruction
-mark and identify foreign material for destruction
-activate MAC (membrane attack complex)
Types of Antibodies
(G. A. M. E. D)
Adaptive Immunity
-IgG
-IgA
-IgM
-IgE
-IgD
IgM
(Antibody)
Adaptive immunity
B cell surface receptor for antigen attachment
IgG
(Antibody)
Adaptive Immunity
most abundant
produced in large amounts
IgE
(Antibody)
Adaptive Immunity
protection against parasitic worms/allergies
IgA
(Antibody)
Adaptive Immunity
found in G.I., G.U., respiratory secretions
IgD
(Antibody)
Adaptive Immunity
uncertain function; found on many B cell surfaces
Toll-Like Receptors (TLRs)
Adaptive + Innate Immunity
act as a bridge between adaptive and innate immunity by mediating activation of pathogen specific T Lymphocytes
-activate signaling pathways, inducing overlap of inflammation
dual functioning
TLRs: role in adaptive immunity
recognize generic traits of all microbes
TLRs: role in innate immunity
TLRs recognize pathogens + generate an immediate defense by producing pro-inflammatory cytokines (destroy or limit invading pathogens)
Antibody: Composition
(tail + arms)
Adaptive Immunity
composed of 5 interlinked polypeptide chains
-2 long chains
-2 short chains
-arranged in “Y” shape
-tail = classification region (determine function) + binding sites for mediators
-arms = determine specificity of antibody with antigen binding sites present (unique)
Antibody attachment to antigen identifies foreign material for destruction, leading to:
cascade leads to formation of membrane attack complex
by phagocytosis + stimulation of killer cells
Polyclonal Antibodies
mixed antibody group, each bind to a separate epitope
usually made within our bodies
Monoclonal Antibodies
recognizes and binds to only one epitope of an antigen
commonly made in lab using mice or cell cultures
Immune Complex Disease
Acitivation of Complement System
overzealous antigen-antibody response causes damage to normal and invading foreign cell
-occasionally exaggerated response -> tissue damage
-bacterial, viral or parasitic infections
-damage to kidneys, joints, brain (ex. Glomerulonephritis following strep infection or Rheumatoid Arthritis)
(Ag-Ab-Complexes)
Differentiation of B Cells: Plasma Cells
produce and secrete IgG antibodies (Ab) and each antibody combines with antigen (Ag) marking it for destruction
-Ab response delayed during initial contact with Ag (plasma cells formed during delay)
-peak = a couple weeks after primary response when Ab concentration decreases
Differentiation of B Cells: Memory Cells
small percentage of B lymphocytes that become a specific cell
- remain dormant and expand a specific clone
-secondary response is faster, more potent and longer lasting
-re-exposed to same antigen = memory cells ready for immune response (adaptive immunity)
can be induced by a disease or vaccine
Active v. Passive Immunity
active: results from exposure to Ag (antigen)
passive: from transfer of preformed Ab (antibodies) - ex. from mother to fetus (borrowed immunity)
Blood Groups are named by….
the presence of antigens on the surface of erythrocytes
(type of passive immunity)
Blood Type A
A antigen, B antibody
(anti-B antibody)
Blood Type B
B antigen, A antibody
(anti-A antibody)
Blood Type AB
A + B antigens, No antibodies
universal recipient / no antibodies
Blood Type O
No antigens, anti-A and anti-B antibodies
universal donor
Agglutination
(Transfusion Reaction)
If Ag of the donor and Ab of recipient match by letter, the donated RBCs can agglutinate in recipient’s blood
-cells burst
result of transfusion reaction
RH +
individual with RH factor
85% of population
RH -
individual without RH factor
-produce anti-RH antibodies when first exposed to RH factor
-mother receives Rho-gam if pregnant and RH -
Erythroblastosis Fetalis
mother’s blood exchanges with 1st fetus during childbirth, producing anti-RH antibodies
-affects second pregnancy/childbirth
-results in ischemia + agglutination
(hemolytic disease of the newborn - HDN)
Antigen
(Ag)
foreign proteins that initiate the immune response
-found on: viruses, bacteria, parasitic worms, fungi, etc.
Surface Cell Proteins
Lymphocytes
present on all cells, ex. bacteria, fungi, yeast
-cell to cell recognition
-facilitated diffusion
-active transport
Major Histocompatability Complex (MHC)
Lymphocytes
cell surface molecules that bind to peptide fragments derived from pathogens + display them on cell surface for recognition by appropriate T cells
-no two people will have the same type of MHC glycoproteins on cell surface -> rejection after organ transplant
-mature lymphocytes bear receptors specific to different MHC (undergo apoptosis to keep the body safe from its own defense mechanism)
human leukocyte antigens controlling major part of immune system
MHC: Class 1 Glycoproteins
(Human Leukocyte Antigens)
Lymphocytes
found on all nucleated cells; non-professional antigen presenting cells
-help Cytotoxic T Cells respond to foreign antigens
genes found on Chromosome 6
MHC: Class 2 Glycoproteins
(Human Leukocyte Antigens)
Lymphocytes
found on macrophages, B + T cells; professional antigen presenting
-recognized by Helper T cells & are confined to surfaces of special types of immune cells
-make up the interior of Thymus
genes found on Chromosome 6
MHC Molecule Function
present antigens that cells may be housing due to an infection or intrusion by foreign tissues to T cells
-plasma membrane glycoproteins that block T cell binding
Epitopes
Lymphocytes
specific shape/size/sub-shape on an antigen (Ag)
antibodies recognize epitopes for antigen binding
Lymphocytes only respond to antigens presented to them by:
Lymphocytes
ANTIGEN PRESENTING CELLS
-Macrophages: cluster around B cell clone; each bind to MHC molecule; engulfs microbe into antigenic peptides; MHC transports bound antigen to cell surface
-Phagocytosis: process and present antigen & expose on macrophage surface
Interleukin Secretion
Lymphocytes
secreted by antigen presenting cells (macrophages + dendritic cells)
-chemical mediator enhances the differentiation + proliferation of the now activated B cell clone
Antigen Presenting Cells
Dendritic Cells + Macrophages
Cytotoxic T Cells
Cell Mediated Immune Response
secrete chemicals (perforin) to destroy targets before virus can enter the nucelus and replicate
-bind to foreign antigens only, not MHC self-antigens (protection from self immune attack)
-respond in association with Class 1 MHC glycoproteins when combined with foreign peptide
-protect against virus-induced cancer
create Memory T Cells
Helper T Cells
secrete chemicals that amplify the activity of other immune cells w/ cytokines
-recognize MHC Class 2 glycoproteins
-release Cytokines
create Memory Helper T Cells
Cytokines
chemicals secreted by Helper T Cells that message other immune cells to ward off invaders
-B cell growth factor
-interleukin 2
-chemotaxins
-macrophage-migration inhibition factor
amplify or reduce the activity of other immune cells
Primary v. Secondary Immune Response
-Primary: B or T cells activate 1st time + produce memory cells
-Secondary: same antigen encountered again; memory cells produce a faster response and long lasting
Immune System is regulated by Endocrine + Nervous Systems by…
negative feedback loops
ex. cortisol mobilizes storage of metabolic fuel
Cancer Cells
have counter productive blocking antibodies that interfere with T Cell function
Immune System Tolerance
preventing the immune system from attacking its own tissues
-dysfunction may result in autoimmune disease
normally tolerant of self-antigens
Clonal Deletion
Immune System Tolerance
self antigens seen in early development
-apoptosis prevents from interaction with body’s own proteins
(major mechanism)
Clonal Allergy
Immune System Tolerance
single signal will turn off compatible T cell so it does not attack itself
-lymphocyte must receive two specific signals at the same time for activation
Receptor Editing
Immune System Tolerance
B cell with a receptor for one of the body’s own antigens changes its receptor to a non-self version if it encounters a self-antigen
makes sure B and T cells do not attack each other
B Ag Sequestering
Immune System Tolerance
self molecules are hidden from the immune system
seen with eyes and testes
Autoimmune Disease
arise from the loss of tolerance of self-antigens or exposure to a foreign antigen almost structurally identical to a self-antigen
-result of abnormal functioning immune system
-may be related to pregnancy - arising from lingering fetal cells post pregnancy
What cells are lacking in severe immunodeficiency?
B and T cells
HIV
virus invades and incapacitates helper T cells
Allergies
acquisition of inappropriate specific immune reactivity (hypersensitivity) to a normally harmless substance
-immediate or delayed
-antibody mediated
Chemical Mediators of Allergic Reactions
-histamines
-slow reactive substance of anaphalaxis (SRS-A) - leukotriene similar to prostaglandins
-eosinophil chemotactic factor
Allergens bind to and ellicit synthesis of…
IgE antibodies
-tail portions attached to mast cells and basophils
-these cells produce and store inflammatory chemicals (histamine)
