Exam 1 Flashcards
What are the 4 types of pathogens?
- bacteria
- viruses
- fungi
- parasites
What are 2 examples of the first line of defense?
- physical barriers
- mucous membranes
What are 4 examples of the second line of defense?
- phagocytic leukocytes
- antimicrobial proteins
- inflammation
- fever
What are 3 examples of the third line of defense?
- lymphocytes
- antibodies
- memory cells
What are granulocytes and what do they do?
cells that contain granules
involved in innate immunity
What are agranulocytes and what do they do?
cells that DONT contain granules
differentiate into B, T, NK, dendritic and macrophages
What 4 things does the innate immune system do?
- pattern recognition
- antimicrobial proteins
- inflammation
- fever
What is pattern recognition?
soluble proteins tag pathogens so receptors on innate cells can recognize them so NK cells or phagocytes can destroy them
What is the 2 benefits of a fever?
- lower replication of pathogen
- increases activity of adaptive immunity
What is an antigen?
substance that can stimulate an immune response
Are B or T cell involved in Humoral immunity?
B cells
Are B or T cell involved in Cell-Mediated immunity?
T cells
Do B or T cells present antigens on MHC molecules?
B cells
Do B or T cells recognize antigens presented on MHC molecules?
T cells
What do cytotoxic T cells do?
directly target and kill infected cells
What is clonal selection and expansion?
selection: T cells with receptors that recognize the specific pathogen are activated
expansion: T cell that can recognize the specific pathogen is proliferated
What is the difference between the intensity of the first exposure to pathogen v. the second exposure?
more intense and quicker (more antibody affinity)
What are 2 examples of primary lymphoid tissue and what happens there?
- bone marrow (B cells)
- Thymus (T cells)
cell maturation
What are 5 examples of primary lymphoid tissue and what happens there?
- lymph nodes
- tonsils
- spleen
- Peyer’s patch
- MALT
site for presenting antigens and lymphocyte activation
What type of secondary lymph tissue has no inflammation?
MALT
What is hypersensitivity?
immune reaction to something that is not a threat to the body (allergies)
What is autoimmunity?
disease driven by an immune response against self-antigen due to failure to eliminate auto reactive B/T cells
What is immunodeficiency?
lack of immune system function
What is the difference between primary and secondary immunodeficiency?
primary - inherited
secondary - aquired
What 4 ways can the immune system go wrong?
- autoimmunity
- hypersensitivity
- cancer
- immunodeficiency
What is an example of physical barriers?
- skin
- mucosal surfaces
What is an example of a organelle that contains antimicrobial protein and how does it work?
lysosome
cleaves polysaccharide of bacterial cell wall
How do antimicrobial proteins disrupt pathogen membranes?
their positive charge allows insertion into pathogen
How do cells of the innate immune system detect the presence of pathogens?
pattern recognition receptors
What do pattern recognition receptors recognize?
PAMPs
What are 5 examples of PRR?
- Toll-like receptors
- lectins
- scavenger receptors
- cytosolic innate receptor
- opsonin receptor
How do toll-like receptors work?
What do they bind to and what do they induce?
PAMPs bind to TLR inducing production of cytokines
How do Lectin receptors work?
What do they bind to and what do they induce?
bind to carbohydrates (glycans) on pathogens inducing phagocytosis
How do scavenger receptors work?
What do they bind to and what do they induce?
recognize negativity charged PAMPs inducing phagocytosis
How do cytosolic innate receptors work?
What do they bind to and what do they induce?
recognize intracellular PAMPs then inhibit pathogen growth and recruit WBC
Located cytosol
How do opsonic receptors work?
What do they bind to and what do they induce?
tag pathogens with opsonin as a target for phagocytosis
What are 2 examples of opsonic receptors?
Fc and CR1
Lectin, scavenger, and opsonin receptors are located ___________ and induce __________
innate cell surface
phagocytosis
TLRs and cytosolic innate receptors induce ____________ which signals _________
signaling pathways
cytokines
What are the 3 phagocytic cells?
- macrophages
- neutrophils
- dendritic cells
What is the first responding immune cell?
neutrophils
What is the purpose of cytokines?
“sound the alarm”
communicate among the immune cells
What are the 2 types of cytokines?
- inflammatory
- antiviral
What do inflammatory cytokines do?
stimulate inflammation at site of infection
What do antiviral cytokines do?
limit viral replication and activate NK cells
What is an example of antiviral cytokines?
alpha / beta INF
What are chemokines?
secreted proteins within the cytokine family who induce migration of WBC
What are the 4 major cells of the innate immune system?
- macrophages
- NK cells
- neutrophils
- dendritic cells
What is the function of macrophages?
phagocytosis and production of inflammatory cytokines via PRR signaling
What is the function of neutrophils?
granulocyte that kills pathogens
What 3 ways can neutrophils kill pathogens?
- phagocytosis
- degranulation
- NETosis
What is the most numerous WBC?
neutrophils
What is the primary component of pus?
neutrophils
What is neutrophil migration?
process that gets neutrophils to the site of infection
What are the 4 adhesion molecules in neutrophil migration?
- glycoproteins
- integrin
- selectins
- immunoglobulin-like molecule
What are the 4 steps of neutrophil migration?
- rolling adhesion
- tight binding
- diapedsis
- migration
Describe the process of neutrophil migration?
- weak integration between selectins and glycoproteins allow neutrophils to slowly roll on endothelia surface
- IL-B and TNF-a (inflammatory cytokines) induce expression of binding integrins
- neutrophils move in between cells
- gradient directs neutrophils to infection
what are 2 examples of inflammatory cytokines?
- IL-1B
- TNF-a
What is the function of dendritic cells?
present peptides on MHC to T cells in lymphoid tissue
What is the function of NK cells?
kill cells infected with intracellular pathogens by making holes in the cell membrane
Cytokine INF-a/b induces NK cell proliferation via _________ signaling?
paracrine
Cytokine INF-a/b alter the expression of receptors on the infected cell that signal NK cells via ___________ signaling?
autocrine
NK cells also secret INF-g that recruits _____________
cytotoxic T cells
What is complement fixation?
attachment of proteins to pathogens marking them as non-self for phagocytosis
How does MAC kill microbes?
forms holes in extracelluar pathogens
What is an anaphylatoxin?
complement protein fragments that induce inflammation
What are the 3 complement pathways?
- alternative
- lectin
- classical
In all complement pathways, what is the key step?
cleavage of C3 into C3a and C3b
What is the order of activation of the complement pathways?
- alternative
- lectin
- classical
What does Factor B do in the alternative complement pathway?
binds to C3 and is cleaved by Factor D leaving Bb bound to C3
What does Factor D do in the alternative complement pathway?
cleaves Factor B into Bb (connected to C3)
Describe C3a and C3b
C3a: soluble anaphylatoxin
C3b: thioester bond that binds to pathogens
What happens to C3b when no pathogen is present?
remains soluble and is inactive
What happens in the alternative pathway once C3b binds to a pathogen’s surface?
more Factor B is bound then cleaved by Factor D creating the alternative C3 convertase
What is the alternative pathway C3 convertase?
C3bBb
How does opsonization occur in the complement system?
C3b binds to pathogen which is recognized by phagocytes CR1 (receptor) inducing phagocytosis
What are 2 methods of C3b regulation via PLAMA PROTEINS?
- Properdin (Factor P)
- Factor H and I
How does Properdin (Factor P) regulate C3b?
protects alternative C3 convertase on pathogen surface so it can cleave into C3b
How does Factor H and I regulate C3b?
cleaves bound C3b making it inactive
What are 2 methods of C3b regulation via MEMBRANE PROTEINS?
- Decay Accelerating Factor (DAF)
- Membrane Cofactor Protein (MCP)
How does Decay Accelerating Factor (DAF) regulate C3b?
disassembles alternative C3 convertase on human cells
How does Membrane Cofactor Protein (MCP) regulate C3b?
disassembles alternative C3 convertase and promotes Factor I (inactivation of C3b)
How is the C5 convertase of the alternative pathway made?
C3b binds to the C3 convertase C3bBb3b
What is the alternative C5 convertase?
C3bBb3b
__________ is cleaved into ______ which goes onto initiate the MAC
C5 convertase; C5b
Explain the building of the MAC?
- C5b, C6, C7 bind
- C7 hydrophobic site inserts into pathogen membrane
- C8 binds to unit allow C9 to bind and bore hole
How do PLASMA PROTEINS regulate MAC?
prevent C6 and C7 from associating with human cells
How do CELL-SURFACE PROTEIN regulate MAC?
prevent C9 recruitment on human cells
What are 2 examples of anaphylatoxins in the complement pathway?
C3a
C5a
What 3 places do anaphylatoxins bind after the complement pathway and why?
- Endothelial cells (increase vascular permeability)
- granulocytes (degranulation)
- phagocytes (attractant)
What 2 pathways in complement require acute phase inflammation to activate?
lectin and classical
(proteins required are not always in circulation)
______ causes liver cells to change proteins they secret leading to production of mannose-binding lectin and C-reactive protein
IL-6
What does MBL do in the lectin pathway?
binds to mannose on pathogens
What does MASP-1 & 2 do in the lectin pathway?
cleaves C4 and C2
What does C4b do in the lectin pathway?
binds to pathogen’s surface with thioester bond (similar to C3b)
What does C2b do in the lectin pathway?
binds to C4b (similar to Factor B) making the lectin C3 convertase
What is the C3 convertase of lectin pathway?
C4bC2b
What does C-reactive protein (CRP) do in the classical pathway?
binds to phosphocholine on pathogens via C1
What are the 3 complex of C1 in the classical pathway?
C1r
C1s
C1q
What do each of the C1 complexes do in the classical pathway?
C1q: binds to CRP and activates C1s and C1r
C1s: cleaves C4 and C2 to generate the classical C3 convertase
What is the C3 convertase of the classical pathway?
C4bC2b
How is C3b and C3a made for each complement pathway?
C3 convertase of each pathway is cleaved creating C3a and C3b
What do protease inhibitors do and what is an example?
inhibit bacterial proteases
a2-macroglobulin: traps protease like a trap
What do 3 things do defensins do?
- poke holes in microbe membranes
- neutralize toxins
- chemoattractants
What tissues express a-defensins?
neutrophils and Paneth cells
What tissues express B-defensins?
epithelial cells, respiratory, and urogenital track
What is the difference between primary and secondary immunodeficiencies?
primary: inherited
secondary: aquired
The type of organism helps identify the __________ in an immunodeficiency
defect/mutation
What are the 5 categories of innate immunodeficiencies?
- physical/microbial
- complement
- PRR/cytokine
- phagocytic
- NK cells
What are 2 examples of physical/microbial immunodeficiencies?
- Cystic Fibrosis
- Crohn’s Disease
What are 3 examples of complement immunodeficiencies?
- regulatory proteins (Factor H&I)
- MAC deficiency
- HANES
What is an example of PRR/cytokine immunodeficiency?
recurrent HSE (herpes)
What are 3 examples of phagocytic immunodeficiencies?
- Leukocyte adhesion deficiency (LAD)
- Chediak-Higashi syndrome (CHS)
- Chronic granulomatous disease (CGD)
What are 2 examples of NK cell immunodeficiencies?
- classical
- functional
How is Cystic Fibrosis an immunodeficiency?
CFTR is mutated causes thick sticky mucus causing biofilms that prevent immune cells and antibiotics
How is Crohn’s Disease an immunodeficiency?
Paneth cells lack a-defensins causing increased microflora
How is loss of Factor H and I an immunodeficiency?
Factor H and I down regulate complement by inactivating C3b
so if they’re missing C3 is depleted in serum causing increased bacterial infections
How is improper formation of MAC an immunodeficiency?
defects in any subunit of MAC causes recurrent infections
How is HANE (complement) an immunodeficiency?
Loss of C1INH (C1 inhibitor) leads to non specific cleavage of C4 and C2 causing unwanted inflammation that doesn’t respond to meds
What is pyogenic bacteria?
induces neutrophilic inflammation and pus
How is recurrent HSE an immunodeficiency?
TRAF3 (induces INF-a/b antiviral cytokine) expression is decreased causing increased viral replication and decreased NK cells activation
How is leukocyte adhesion deficiency (LAD) an immunodeficiency?
defect in B2-integrin affects tight binding because LFA-1 which induced tight binding of neutrophils on the surface of epithelial cells is defective
no opsonization and phagocytosis
recurrent skin and muscoa infections
How is Chediak-Higashi Syndrome (CHS) an immunodeficiency? And what’s made because of this
inability to merge lysosome and phagosome because of giant granules and defective NK cells
recurrent bacterial infections that phagocytes normally can control
How is Chronic Granulomatous Disease (CGD) an immunodeficiency? And what is caused by the deficiency?
NADH does not produce superoxide and hydrogen peroxide to lower pH
no break down
build up of neutrophils
recurrent bacterial and fungal infections
How is classical NK cell deficiency an immunodeficiency?
absence or very low numbers of NK cells
How is functional NK cell deficiency an immunodeficiency?
Fc-gamma receptor on NK cells that participate in ADCC (interaction of NK cells with infected cell surface receptors) are mutated
no cytotoxic granules released
What is antibody dependent cell-mediated cytotoxicity (ADCC)?
Fc-gamma receptors on NK cells engage antibody-bound infected cells and induce death via cytotoxic granules
What is the purpose of antimicrobial peptides?
Form pores in cells
What are mast cells important for?
Inflammation
NK cells don’t recognize PAMPs, What do they recognize on infected cells?
Receptors that are meant to be inactive. If they are activated on the infected cell the NK cell will kill the host cell
What does histamine cause?
Swelling
What causes the heat from a fever?
Increased metabolism
Antibodies are easier to deal with intra or extracellular pathogens?
Extracellular
Where does the colonel process occur?
Secondary lymph tissue
What occurs in the lymph nodes?
Dendritic cell presentation and cleaning on lymphatic fluid
What allows transportation in MALT since no inflammation can occur here?
M cells
What is inside lysosomes that destroy pathogens?
Antimicrobial peptides
What cell cleans up neutrophils?
Macrophages
What signals the release of mannose binding lectin and c reactive protein in the liver?
IL-6
What cells do antiviral cytokines signal for?
NK cells
What kind of TLRs target Intracellular pathogens by looking for viral DNA and RNA?
Endosomal TLRs
Where are TLRs located for extracellular pathogens?
Cell surface
What are the only PRR that are not located on cell surface?
Cytosol-innate receptors
Endosomal TLRs
What cell type is important for Intracellular pathogens?
NK cells
What does iC3b bind to?
CR3 and CR4
C4 and C2 are involved in what 2 pathways?
Classical
Lectin
What is LFA-1 important for?
Tight binding of neutrophils
What is selectin important for?
Rolling adhesion of neutrophils
What is LFA-1 important for?
Tight binding of neutrophils
What happens if NK cells are deficient in FC-gamma?
Cannot do ADCC
What introduced the expression of integrins for tight binding in neutrophil migration?
IL-B
TNF-a
(Inflammatory cytokines)
