innate Flashcards
What are the 3 main categories of microbial virulence factors?
- Structures involved in attachment, adherence, and invasion
- Toxins involved in cell or tissue damage
- Processes involved in immune avoidance
What is difference between chemokines and cytokines?
Cytokines are intracellular mediators, chemokines are chemo-attractant molecules
Associated with hypersensitivity and release histamine
Basophil
What organs are part secondary immune tissue?
Spleen, Lymph nodes, and MALT
The spleen is located:
upper left quadrant of abdoment, under diaphragm
What is the difference between endotoxins and exotoxins of bacteria?
Exotoxins- LPS or LOS in gram negative
Endotoxins- secreted toxins by gram positive or negative (not encoded in chromosome)
What are the 5 major lymphnode groups and the area of the body that they drain?
- Cervical- Scalp, face, nasal cavity, pharynx
- Axillary- Arm, chest wall, breast
- Inguinal- Genitalia, buttock, anus, abdominal wall, leg
- Mediastinal- Mid-chest, upper abdomen, lungs
- Mesenteric- Small and Large intestine, upper rectum
What is the significance of pnumonia in acute inflammation?
Pneumonia is inflammation where acute reaction is a significant cause of morbidity and mortality
What do you call lymphadenopathy with an active infection causing pain?
Lymphadenitis
What is an important bacteria for the nose?
Staphylococcus aureus
IL-12 functions
Ifng production, increased cytotoxicity (NK and T cells)
What are the structures of immune avoidance by microbial pathogens?
- Polysaccharide capsules
- Antigens that induce blocking antibodies
- Molecules inactivate antibodies
- Molecules mimic host structures
IL-6 functions
Synthesis of APRs (liver) and proliferation of antibody producing cells (B-cells)
What are the 3 main functions of the complement system?
- Oposonization (helps with phagocytosis)
- Inflammation _(_acute and dilate blood vessels)
- Lysis (generate proteins for lysis)
What are the processes of immune avoidance by microbial pathogens?
- Antigen variation
- Avoiding immune surveillance
- Supressing immune responses
What are the 5 stages in biofilm formation?
1) Reversible attachment 2) Irreversible attachment 3) Polysaccharide production 4) Growth and formation of 3D structure 5) Dispersal
What organs are part primary immune tissue?
Bone Marrow and Thymus
Endocrine
Acts a distance to stimulate cells
What is DAF and what disorder is associated with its deficiency?
Decay-accelerating Factor helps down regulate C3 convertase (prevents attack of the self). Deficiency causes paroxysmal nocturnal hemoglobinuria (PNH)- RBC lysis due to uncontrolled complement activation
What parts of the body drain into the left subclavien vein?
The entire lower body and left upper body
Which innate immune cell has oxidative burst?
Neutrophil (PMN)
Are catalase positive or catalase negative bacteria more dangerous to person with GCD?
Catalase Positive (can break down H2O2)
Catalase Negative cells still produce H2O2, but this activates the phagocytic cell to produce toxic substances that can kill the bacteria
What is the side of hematopoiesis and B-cell maturation?
Bone Marrow
How many lymph nodes are in the body?
500-600
What are the main components of the final phase of the complement system- formation of MAC?
C5b-C9 form the polymeric complex that creates perforations in cellular membranes of pathogens.
What are 3 useful diagnostic measures of the complement systems activity?
AH50- Alternative Pathway
MBL- Lectin Pathway
CH50 - Classic Pathway
Autocrine
Acts on the same cell that secretes it
What is the difference between red and white pulp of the spleen?
White- contain lymphocytes Red- RBC breakdown
What are the antimicrobial drugs that interfere with DNA?
- Quinolones/Fluoroquinolones
- Rifamycins
- Nitroimidazoles
IL-1 functions
Activation of inflammation and coagulation (endothelial), fever (hypothalamus), induce chemokine secretion to recruit WBCs
Which antibiotic drug should be reserved until the only option, due to disabling side effects in patients?
Ciproflaxcin (flouroquinolone)
What is the JAK-STAT Pathway?
A major immune regulation pathway
Major pro-inflammatory cytokines
TNF-alpha, IL1, IL6
What are the 3 main host barriers?
Anatomic, physiologic, and microbiological
Lymphadenopathy
enlargement of one or more lymph nodes
Which characteristics help with biofilm?
LPS, polysaccharide capsule, Exopolysaccharides
What is the difference between granulation tissue and granulomatous inflammation?
- Granulation Tissue (acute) and involved in tissue repair with increased vasculature
- Granulomatous inflammation (chronic) and cannot defeat the infection, the monocytes wall of inflmmation which forms granulomas.
What are the 4 TLRs located in the endosome?
- TLR3: viral dsRNA
- TLR7: viral ssRNA
- TLR8: viral ssRNA
- TLR9: unmethylated CpG DNA
What is lymphangitis?
inflammation or infection of lymph vessels
What is the main opsonization protein of the complement system?
C3b
What is Hot T-bone stEAK?
- IL1- fever (hot)
- IL2- stimulates T cells
- IL3- stimulates bone marrow
- IL4- stimulates IgE production
- IL5- stimulates IgA production
- IL6- Stimulates aKute phase protein production
What is the toxic moeity that all LPS endotoxins have?
Lipid A, a potent stimulator of innate immune responses (septic shock)
The _____ produces more antibodies than all other tissues together
MALT
What is an Nitro Tetrazolium Blue (NBT) test?
Measures oxidative burst activity of neutrophils to see if they are capable of phagocytosis.
This organ is the site of T-cell maturation and selection
Thymus
What is Nitroimidazoles MoA?
Activated drug forms toxic free radicals that damage DNA (very useful against anaerobic microbes)
What is the differenc between fibrinous exudate and fibrosis?
- Fibrinous Exudate (acute) characterized by fibrin
- Fibrosis (chronic) characterized by collagen
What disorder is associated with C1, C2, C4 deficiency?
Increased risk of immune complex disease, like SLE (lupus) because these are teh starting points of classical pathway
The 3 major antigent presenting cells
Macrophage, Dendritic Cells, & Follicular dendritic cells
Paracrine
Acting on an adjacent or nearby cell
What causes Cholera?
- Vibrio cholerae (A+B mediated toxin) Gram Negative Rod
- One A subunit and 5 B subunits
- A subunit activates adenylate cyclase; increases cAMP; promotes secretion of electrolytes and fluid by intraepithelial cells
- Profuse watery diarrhea
What are the secreted proteins of the innate immune system?
Lysozymes, complement, C-reactive proteins (CRP), and defensins
Biofilm bacteria cause ___% of infections
80%
What are the two antimicrobial drugs that interefere with folate synthesis?
Sulfanomides and trimethoprim
What are the main causes of chronic inflammation?
- Persistent tissue injury and acute inflammation
- Microorganisms resistant to phagocytosis or intracellular killing (Mycobacteria, virus, fungi, parasites)
- Foreign bodies
- Autoimmune disorders
- Primary granulomatous diseases
Defense against viruses is mediated by
NK cells
What are sessile bacteria?
Bacteria growing in a biofilm
In the thymus, cells enter via ____ and leave via ____
blood & lymph
What are the main causes of Chronic Granulomatous Disease (GCD)?
Inherited disorder of phagocytic cells, inability to produce bactericidal superoxide anions. Defect in NADPH oxidase enzyme.
(typically X-linked recessive)
Granules contain vasoactive amines like histamine, proteases kill bacteria
Mast Cell
What is the convergence point of all 3 pathways of the complement system?
C3 Convertase (C3 cleavage into C3a and C3b)
C3b goes onto activate C5 convertase
What are the 3 pathways of the complement system and their starting factors?
- Alternative (spontaneous and microbial surfaces)
- Lectin (Microbial surfaces, mannose)
- Classic (Antigen-antibody complexes)
What are the main chemoattractant proteins of the complement system?
C3a and C5a (attract neutrophils and monocytes)
Which immune organ is the major site of immune response to pathogens?
Spleen
What is measured to identify acute phase response?
APR- acute phase reactants (plasma proteins)
What is the arrangment of LPS/LPO on bacteria’s cell membrane?
True or False: in Latent disease there is no replication
False, if viral there is no replication but in bacteria. there needs to be some small amount of replication
What causes Anthrax?
- Bacillus Anthracis (A+B mediated toxin) Gram Positive
- 2 A subunits- Edema Factor (EF) and Lethal Factor (LF)
- ED activates adenylate cyclase
- LF cleaves cellular kinases and leads to altered cell signaling and cell death
What is the most common cause of secondary lymphedema?
- Filariasis- due to infection by nematode Wuchereia bancrofti, transmitted by mosquitoes.
- Adult worms reside in lymphatic vessels and nodes, especially in legs; scrotum top site in post-pubertal males.
- Main goal of treatment is to kill the adult worm
What are the products of oxidative burst and their enzymes?
Hydrogen Peroxide (Super Oxide Dismutase, SOD)
Hypochlorous Acid “bleach” (myeloperoxidase)
What are the two major phyla in human flora?
Baceroidetes & Firmicutes
What disorder is associated with decreased C3 protein?
Increased risk of encaspulated bacteria infection (no opsonization)
How do naked viruses and enveloped viruses attach to cell?
Naked- attach via capsid proteins, enter via endocytosis
Enveloped- attach via glycoprotein spikes, enter via fusion/endocytosis
What is the MoA for Trimethoprim (tmp)?
Inhibits DHFR (reducing enzyme that generates THF)
What do PRRs do?
Pattern Recognition Receptors promote rapid expression of pro-inflammatory cytokines/chemokines (to clear pathogens)
What are the main functions of NK cells?
- Use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells
- Induced to kill when exposed to activation signal or absence of MHC 1 on target cell surface
- Can also kill via antibody-dependent cell-mediated cytotoxicity (CD16 binds Fc region of Ig)
What is the difference between pili and flagella?
- Pili are shorter, thinner, and more numerous (attachment)
- Flagella are longer, thicker, and fewer in number (locomotion)
What are the two mechanisms of vancomycin resistance?
Consitutive resistance (VanA locus) and Inducible resistance (VanB locus). Both result from expression of D-Ala, D-Lac in peptide sidechain of PG
What is the first lymphoid structure to encounter foreign agents?
Lymph Nodes
What parts of the body drain into right lymphatic duct and right subclavian vein?
Right side of body above the diaphragm
Chylothorax
accumulation of lymph in the thorax
What is C1-INH and what disorder is associated with its deficiency?
C1- inhibitor down regulates C1r and C1s (classical pathway). Deficiency causes excessive vasoactive peptides (bradykinins) and hereditary angioedema.
Phagocytic cells recognize____ & _____
PAMPs and DAMPs
What is an important bacteria for the vagina?
Lactobacillus species
Type of cancer associated with cells of immune system
Lymphoma
What does MALT stand for?
Mucosal-associated Lymphoid Tissue
The 3 main phagocytic cells are:
Macrophage, Dendritic Cells, and PMNs
What is lymphedema?
Interstitial collection of lymph due to disruption of flow
DAMPs are associated with
necrotic cell death
What are bacterial pili and their signifcance?
Filamentous structures extending from bacterial surface, help with initla adherence to host cells or EC matrix.
Can be multifunctional
What causes Pertussis (whooping cough)?
- Bordetella pertussis (A+B mediated toxin) & Gram Negative
- A subunit activates adenylate cyclase; increases cAMP in neutrophils and macrophages; decreases phagocytosis
What is Rifamycins MoA?
Binds to bacterial DNA-dependent RNA polymerase and prevens mRNA synthesis
What are the 5 general steps of the complement system?
- Initiation of complement activation
- C3a: inflammation
- C3b: opsonization
- C5a: inflammation
- Lysis of microbe (MAC)
What are the main functions of the lymphatic system?
Collect/Drain excess fluid, absorb fat, conduit for immune cells
What is the difference between normal antigen presentation and superantigens?
Normal Antigens- highly specific and stimulates relatively small number of Tcells
Superantigens- Nonspecific and massive polyclonal expansion of many Tcells (cytokine storm)
Dendritic cells are
The major antigen-presenting cells
Compare Pathogenicity, Virulence, and Infectivity
- Pathogenicity is the organism’s ability to cause disease
- Virulence is the degree of damage or disease resulting from infection
- Infectivity is the likelihood of infection/disease with exposure to a particular dose
What is the MoA for sulfanomide?
Inibits folate precursor synthesis
What is biofilm?
The adherence of bacteria to eachother and a surface
What causes tetanus?
- Clostridium tetani (A+ B mediated toxin) Gram Positive
- A subunit inhibits gylcine NT release from inhibitory neurons in CNS (paralysis)
What are the main causes of acute inflammation?
- Microbial infections
- Tissue necrosis
- Physical Agents
- Chemical irritants
- Immune-mediated hypersensitivity
What are the main vasoactive mediator proteins (anaphylatoxins) of the complement system?
C3a, C4a, C5a
Which commensal bacteria will take over and become pathogenic when gut bacteria is wiped out?
C. difficile
What is the chief stimulator of APRs?
IL-6
Associated with allergic response and parasitic infection
Eosinophil
What are the important bacteria for the skin?
Staphylococcus epidermidis
Staphylococcus aureus
Streptococcus pyogenes
What disorder is associated with C1-INH deficiency?
Increased vasoactive peptides (bradykinins) causes hereditary angiodema
What are the 4 TLRs located on the plasma membrane?
- TLR2: Bacterial and parasitic glycolipids and peptidoglycans
- TLR4: Bacterial LPS
- TLR5: Bacterial flagellar protein (flagellin)
- TLR6: Bacterial lipopeptides
What is Quinolones MoA?
Inhibit DNA gyrase and topoisomerase
What are the hallmark components of chronic inflammation?
- Persistent
- Slow response
- Cell-mediated immunity
- Mononuclear cells (lymphocytes, plasma, macrophages)
- Weeks to years
What is an important bacteria for the GI tract?
E. coli & clostridium spp.
What are the hallmark components of acute inflammation?
- Immediate repsonse
- Rapid onset
- Innate immunity
- Neutrophils
- Short Duration (hours to weeks)
- Prominent vascular response
What are polysaccharide capsules?
Extracellular, attached to G+/- bacteria surface. Avoids phagocytosis and immune recognition. Common in pathogens that can enter CNS
What are the 3 main mechanisms of antibiotic resistance?
- Enzmatically Modify or Inactivate Drug (ex. B-lactamase)
- Alter Drug Target (de novo mutation, spread via horizontal exchange)
- Alter Drug Exposure (decreased uptake G-, increased efflux)
What disorder is associated with deficiency of C5b-C9 proteins?
Increased suscepitbility to Neisseria spp. infections (cannot assemble MAC)
Tumor Necrosis Factor functions
Activate neutrophils, inflammation and cogulation (endothelial), fever (hypothalamus), catabolism (muscle, fat), and apoptosis
Which immune cells is derived from monocytes?
Macrophage
What causes Diptheria?
- Cornybacterium diphtheriae (A+B toxin mediated disease), Gram Positive
- A subunit inhibits protein synthesis
What are planktonic bacteria?
Free-floating bacteria
Signs of acute inflammation
- Rubor (redness)
- Tumor (swelling)
- Calor (heat)
- Dolor (pain)
- Functio Laesa (loss of function)
