Immune (addition to MCAT bio immune) Flashcards
Purpose of skin
- -innate immunity
- -pH is low in sweat so inhibits growth of microorganisms on skin
- -antibodies from in-body secretions move to surface to bind invaders
Mechanisms of protection for body openings
- Respiratory system - roaming macrophages, mucus traps invaders and moves it out by cilia
- Urogenital tract - maintains a level of acidity to protect against invaders
- Digestive tract - Peyer’s patches absorb bad agents
- Throat tonsils - surround the throat with organized immune cells that act as a lymphoid barrier to protect against invaders
Throat tonsil types
- Pharyngeal - located at back of throat, just past nasal opening
- Palatine - located on either side of throat/tongue (swollen with strep)
- Lingual - located at back of tongue
1st line of defense (innate, nonspecific)
- Skin
2. Protection of various openings
2nd line of defense (innate, nonspecific)
- Lymph system
- Spleen
- Blood stem cells
- Phagocytic cells
- Natural killer cells
- Interferons
- Pyrogens –> fever
- Complement system
- Inflammation
- Toll-like receptors
11, Non-specific ID-card model
Immune surveillance
- -the process of catching early cancers/issues
- -done by the lymph system
Lymph system
- -innate and nonspecific
- -removes excess fluid from tissues
- -acts as a checkpoint to catch invaders
lymphedema
–when you remove lymph nodes, water builds up in that area –> swelling
left subclavian vein
–the location where the fluid that passes through lymph is returned to blood circulation
spleen
- -innate and nonspecific
- -stores extra white and red blood cells
- -acts as a “checkpoint” to scan for invaders. Basically acts as a large lymph node.
blood stem cells
- -innate and nonspecific
- -RBCs and WBCs all made from bone marrow
granulocytes
- -eosinophils
- -basophils
EPO
–stimulates bone marrow to make RBCs and WBCs
aplastic anemia
–condition in which bone marrow stops working
erythrocytes
–red blood cells
leukocytes
- -white blood cells
- -includes all immune cells (basophils, lymphocytes, etc)
phagocytic cells
- -nonspecific cells
- -neutrophils
- -monocytes
- -macrophages
diapedesis
–the process of immune cells leaving the circulation to enter tissue spaces to combat invaders
neutrophils
- -part of nonspecific response
- -most common type of white blood cell
- -phagocytic
- -kills itself after eating bacteria
- -release their DNA to create nets when they die to trap more invaders
- -secrete cytokines as they die
- -secrete oxygen radicals as they die
monocytes
- -nonspecific
- -phagocytic
- -contains large horseshoe-shaped nucleus
- -turn into a macrophage once it gets into tissues
macrophage
- -nonspecific
- -phagocytic
- -Found only in tissues, not circulating in blood
Natural killer cells
- -nonspecific
- -recognizes a non-self and kills it
- -Releases protein perforin that pokes holes in invader cell membrane to kill it
- -Releases granzymes in the invader that target cell’s nucleus to reprogram DNA and cause invader cells to do apoptosis
Interferons
- -nonspecific response
- -proteins secreted by virally infected cells to warn other cells around it
- -Signal to produce more T-cells
- -A type of cytokine
- -Response of surrounding cells: reduce transcription and shorten half life to inhibit virus replication and proliferation
Temperature response
- -nonspecific response
- -Pyrogens cause fever –> body temperature increases
exogenous pyrogens
- -contained in bacterial cell wall
- -cause fever when ingested
endogenous pyrogens
- -hypothalamus controls body temp
- -internal pyrogens can reset body’s normal point so it maintains a higher body temp
Complement system
- -nonspecific response
- -proteins in the blood assemble into a “membrane attack complex” (MAC) that pierces a hole into membrane of invader
- -C3 protein is most important protein of the complex
Inflammation
- -nonspecific response
- -sign of warning cells and early immune cells on the scene
- -cytokines release histamines that cause redness, swelling
toll-like receptors
- -nonspecific
- -dont know how they work exactly
- -release cytokines to warn other cells of immune attack
3rd line of defense
- -All adaptive immunity, VERY specific
1. Lymphocytes
a. T-lymphocytes
b. B-lymphocytes
antibodies
- -proteins with binding sites for specific molecules called antigens
- -always Y-shaped with 2 antigen-combining sites
- -recognize a specific epitope
epitope
- -the part of the antigen to which the antibody attaches
- -a single antigen can have many different epitopes, so a single antigen can be recognized by many different antibodies
T-lymphocytes
- -These are responsible for “cell-mediated immunity” part of adaptive/specific immune response
- -educated in the thymus
- -like other lymphocytes, nucleus takes up most of cytoplasm
- -Gets a lot more cytoplasm when it gets activated
Types of T-lymphocytes
- Helper T-cells
- Inducer T-cells
- Cytotoxic T-cells
- Suppressor T-cells
Helper T-cells
- -work with other cells to make the immune response more efficient
- -Has CD4 marker
Inducer T-cells
- -stimulate replication of more T-cells
- -CD4 marker
Cytotoxic T-cells
- -these are the killing cells of the cell-mediated immunity
- -CD8 marker
Suppressor T-cells
- -turn down immune response
- -Unknown whether CD4 or CD8
B-lymphocytes
- -associated with “humoral” or “antibody” specific response
- -make and secrete antibodies
- -educated in the periphery (i.e. no particular organ associated with education)
- -See a huge increase in rough ER when they are activated (in order to make lots of proteins/antibodies)
- -Called a plasma cell when activated
MHC markers
- -set of cell surface proteins essential for the immune system to recognize self vs. foreign molecules
- -These are hugely polymorphic and they can present all sorts of things in their groove
- -Vary a lot between individuals but not within an individual - this makes it difficult to find an exact donor match
- -coded for on chromosome 6
Class 3 MHC markers
–complement proteins
Class 2 MHC markers
- -found on macrophages, B-cells, some T-cells
- -structure: 1 alpha and 1 beta component side by side in lipid bilayer
- -groove at top to “present an antigen”
- -Known as APC’s - antigen presenting cells
–these present external antigen in immune response
Class 1 MHC markers
- -found on all nucleated cells, including immune cells
- -NOT found on RBCs (b/c RBCs not nucleated)
- -structure: 1 large segment is called the “heavy chain” and the smaller segment is called the “beta-2-microglobulin”
- -heavy chain is embedded in cell membrane and beta-2 segment is attached just to heavy chain
- -these present internally synthesized molecules in their groove
- -Normally these would be presenting “self” antigens in their groove, but if cell has been infected by a virus and is replicating the viral genome, the MHC1 markers will be presenting “viral” antigens in their groove, to which immune system responds
Types of transplants
- Autologous
- Heterologous
- Allogenetic
Autologous transplant
- -Get your own tissue
- -No issue w/ matching MHC markers
Heterologous transplant
- -get someone else’s tissue with matched MHC markers
- -usually from family members
Allogenetic
- -someone else’s tissue with unmatched MHC markers
- -success depends on what type of transplant
what type of transplant does not need a match b/w donor and recipient?
cornea
graft vs. host disease
- -new bone marrow will make immune cells that don’t match the rest of the body cells
- -new immune cells attack the body
- -This can be fatal
Initial response to infection
- Phagocyte mobilization
- -immune cells squeeze between cells (extravasation) and move from bloodstream into tissue (diapedesis)
- -inflammatory chemicals act as positive chemotactic agents, telling immune cells to come toward that location
- -neutrophils begin eating up invader
Second step in response to infection
- Monocytes move into tissue, convert to macrophages, phagocytize invader
- -Macrophage fuses the invader with a lysosome and digests invader
- -Puts a small peptide fragment from invader into the groove of macrophage’s MHC2 marker
- -macrophage acts as antigen presenting cell
Third step in response to infection
- More nonspecific responses
- -Interferons released - alpha and gamma
- -secrete other cytokines including interleukin-1
interferon types
- alpha interferon: warning signal and stimulates NK cells
2. gamma interferon: stimulates monocytes to make more macrophages
interleukin-1
–an endogenous pyrogen
Fourth step in response to infection
- T-cell recognition and actions
- -Helper T cell is MHC2 restricted, meaning it only can recognize the antigen when it is presented in the MHC2 groove
- -Helper T cell recognizes antigen in MHC2 marker and attaches to it macrophage with the help of the CD4 protein as a co-receptor
- -Helper T cell can now secrete macrophage inhibition factor, interleukin-2, inducer T-cells
macrophage inhibition factor
- -traps macrophages at the scene of the invader
- -secreted by helper T cells after they have recognized antigen in MHC2 groove
interleukin-2
- -T-cell growth factor - stimulates replication of bound T cells
- -secreted by helper T cells after they recognize antigen in MHC2 groove
inducer T-cells
- -signal for more T-cells
- -activated by helper T-cells in response to recognizes antigen in MHC2 groove
clonal selection
- -the mechanism by which only T-cells that attack foreign substances proliferate
- -the process of “educating” lymphocytes
5th step in immune response
- Activation of 2 arms of the immune system: cell-mediated immunity (T-cell) and humoral/antibody immunity (B-cell)
Cell-mediated immunity
- -carried out by cytotoxic T-cells
- -When helper T-cells release IL-2, it stimulates cytotoxic T-cells to replicate
- -Tc cells have a receptor fitting the specific antigen presented by the APC, allows Tc cells to bind more MHC-antigen complexes and attack
- -memory Tc cells also made for future responses
Antibody immunity
- -carried out by B-cells
- -B-cell binds antigen, chews it up, displays it on surface of MHC2
- -IL-2 signal is what triggers B-cells to divide/proliferate and turn into plasma cells (IL-2 is released by helper T-cells when they bind MHC2-antigen complex)
- -Plasma cells are the antibody producing cells
- -memory B-cells are made for future response
T-cells versus B-cells
- -B-cells can pick up free antigens floating around
- -T-cells can only see the MHC-antigen complex
Helper T-cells are crucial because
–they activate both arms of the adaptive immune system: cell-mediated and antibody response
Antibody functions
- increase rate of phagocytosis
- increase attack by complement system
- increase attack (lysis) by NK cells
Opsonization
–the process of enhancing phagocytosis by marking it with an antibody
Secondary response
–much quicker and stronger response to exposure as a result of memory B-cells and T-cells
HIV
–targets CD4 Helper T-cells, which knocks out cell-mediated and antibody immune responses
Fab
- -antigen binding faction
- -There are 2 antigen binding sites per antibody
- -Each Fab is made of 1 heavy chain and 1 light chain
Fc
- -constant fraction
- -similar sequence from one antibody to the other
Hypervariable regions
–where there is the most variation and where specificity is most important for binding of that specific antibody
5 classes of antibodies
–This is based on the slight variations in the “constant” regions
- IgM
- IgG
- IgD
- IgA
- IgE
IgM
- -pentamer shape
- -Can bind many more things and agglutinate whatever it binds to
- -get enhanced phagocytosis due to agglutination
- -Usually first antibody to respond to invader
IgG
- -second main actor after IgM
- -most common Ab
IgD
–on surface of B-cells
IgA
- -dimer held together
- -most common Ab in bodily secretions (breast milk, tears, saliva, mucus)
IgE
–promotes the release of histamine, which triggers allergic reactions
Allergic response
- -hypersensitivity response
- -atypical b/c mostly IgE class antibodies are secreted
- -B cell binds antigen –> B cell turns to plasma cell –> plasma cell secretes IgE –> these bind to mast cells’ (granulocytes) surfaces
- -When allergen binds antibodies on mast cell’s surface, the mast cell releases histamine and other chemicals
Anaphylaxis
- -an ACUTE allergic reaction
- -rapid
Type IV - delayed hypersensitivity
- Poison ivy
- -takes 2-3 days to develop
- -cell-mediated response
- -CD8 T cells kill affected cells - Mantoux tuberculin skin test
- -inject small amounts of tuberculin peptides
- -feel for induration - hardened and raised skin as part of inflammation response
Somatic recombination
- -The way we create so many B-cell receptors to recognize possible invaders
- -As B-cells are being produced in bone marrow, each B-cell mixes and matches from its genome the genes that will code for its surface receptor - this is basically DNA splicing
- -V,D, J genes contribute to antibody binding ability
- -C genes contribute to constant region
- -This happens only in B-cells
Methods of adding diversity to B-cells even after somatic recombination
- As B-cell proliferates as plasma cells, there are random mutations that add more variation
- Splicing mechanism isn’t very “clean” so can leave a nucleotide hanging or cut an extra one off
Heavy chain genes
Vh
D1-D12
Jh1-Jh4
constant region genes
Light chain genes
V
J
Constant region
**Notice there are no D region genes in light chains
anergy
- -The process by which T-cells require co-stimulation to be activated
- -Can only occur when there is an additional coreceptor
tolerance
- -When you are a newborn and your immune system isn’t working very well yet, you can accept a range of tissue types
- -this is called tolerance
autoimmune mimicry
–occurs when the foreign antigen and the self antigen are so similar that the T-cell is stimulated to attack both
Graves disease
–causes exophthalmia (bug eyes)
Diabetes
–beta cells of pancreas attacked by body’s immune system
Lupus
–causes butterfly rash
Myasthenia Gravis
- -with ptosis (droopy eye)
- -targets neuromuscular junctions - acetylcholine receptors
- -thymus abnormalities
Scleroderma
- -“hard skin”
- -overproduction of collagen and other possible organ damage
- -alopecia (hair loss)
- -produce auto-antibodies that target centromeres
Inflammatory Bowel Disease
–autoimmune
Inflammatory bowel syndrome
–not autoimmune
