Exam 2 Flashcards
(70 cards)
1
Q
What is the difference between the innate and adaptive immunity?
A
Innate:
- 1st & 2nd line of defense
- Immediate (0-96hr)
- antigen independent
- Common PAMPs
- No memory
- NK, MO, DC, mast calls, neutrophils, basophils, eosinophils
Adaptive
- 3rd line defense
- Long (>96hr)
- Antigen dependent
- Unique epitopes
- Memory
- T & B lymphocytes
2
Q
What arethe first and second lines of defense in the innate immunity?
A
1) Physical/mechanical/biochemical barriers:
2) Inflammatory response
3
Q
What are examples of the physical, mechanical, and biochemical barriers of the innate immune system?
A
Physical:
- Tightly associated epithelium of skin, GI, GU, & resp
- Normal turnover of epithelium
- Low temp skin
- low pH of stomach & vagina
Mechanical:
- vomiting, defecation, urination
- mucociliary clearance –> cough sneeze
Biochemical
- Epithelial-derived chem: substances synthesized and secreted trap/destroy microorganism: Mucus, perspiration (antimicrob/fungal), saliva/tears - lysozyme, earwax
- Epithelial-derived proteins: antimicrob peptides, collectins, mannose-binding lectin
4
Q
How is the normal microbiome involved innate immunity?
A
- Normal microbiome: spectrum of microorganisms that colonize body’s surfaces (skin, MMB eyes, GI, urethra, vagina) unique to body location and individual
- Do not normally cause disease (colon, vagina (lactobacillus), skin (staphylococcus))
- Prolonged antibiotic treatment –> alters normal microbiome –> disease
5
Q
What is acute inflammation, the components, and the function?
A
- Response to cellular/tissue damage: septic/sterile (infection), nonspecific, rapid
- Components:
– vascular response
– plasma protein mediators
– cellular mediators - Functions:
– limit extent tissue damage
– destroy infectious microorganisms
– initiate adaptive immune response
– begin healing process
6
Q
What activates acute inflammation?
A
- Infection
- Necrosis: trauma, ischemia
- Oxygen/nutrient deprivation
- Genetic/immune defects
- Chemical injury
- Foreign bodies
- Temperature extremes
- Ionizing radiation
(Don’t need to memorize)
7
Q
What are the cardinal signs of acute inflammation?
A
- Redness (erythema)
- Heat
- Swelling (edema)
- Pain
- Loss of function
Morphologic patterns: serous (skin blister), fibrinous (heart), purulent/suppurative (lung), ulcer (duodenal)
8
Q
What is the vascular response aspect of acute immune response?
A
- Microcirculation near injury site: Arterioles, capillaries, venules
- 3 characteristic changes:
– vasodilation: dec velocity
– inc permeability: exudation & edema
– WBC adhere to vessel wall: diapedesis & cellular infiltration
9
Q
What are the plasma protein mediators of the acute inflammatory response?
A
- Three key systems: many plasma proteins in inactive form (proenzymes) sequentially activated (cascade)
1) Complement system/cascade
2) Clotting system/cascade
3) Kinin system/cascade - highly interactive (activate each other)
- tightly controlled by enzymes (inactivate & degrade)
10
Q
What are the aspects of the complement system?
A
- 10% serum proteins
- produced factors destroy pathogens directly & activate components innate/adaptive immune system
- activated by three pathways –> C3
1) Classical: antibodies bind antigens
2) Lectin: mannose-containing bacterial carbs
3) Alternative: gram- bacterial & fungal cell wall polysaccharides - C3a & C5a: anaphylatoxins –> mast cell degranulation (histamine), vasodilation, inc permeability
- C5a: maj chemotactic factor for neutrophil
- C3b: opsonin; surface pathogen label for neutrophil & MO
11
Q
What are the aspects and function of the clotting system?
A
- activated (primarily by platelets) proteins form blood clot (insoluble protein (fibrin) meshwork + platelets traps other cells)
- function:
– prevent spread of infection
– trap microorganisms & foreign bodies
– stop bleeding
– framework for repair - Activated: injury/infection: collagen, proteinases, kallikrein, plasmin, bacterial products (endotoxins)
- Dependent on Ca2+
- Forms on phospholipid membrane
12
Q
What are the aspects of the coagulation cascade?
A
- Extrinsic: tissue factor activation from damaged endothelial cells, reacts with factor VII
- Intrinsic: damage vessel wall activate Hageman factor (XII)
- Converge @ factor X –> activate fibrin –> polymerize fibrin –> clot
- Modulated by thrombin
– converts fibrinogen to fibrin: release fibrinopeptides A & B (chemotactic for neutrophils, permeability)
– activate plasminogen –> plasmin –> degrade fibrin - Produces fragments enhance inflammatory response
13
Q
What are the aspects of the kinin system?
A
- Activated by factor XIIa
- Primary product: bradykinin (vasodilation, permeability, pain)
– also produced by tissue kallikreins in saliva, sweat, tears, urine & feces
– modulated by kininase
14
Q
What are the cellular mediators of acute inflammation?
A
- Mast cells: most important
– histamine, prostaglandins (PGs), leukotrienes (LTs), cytokines, platelet activating factor (PAF) - Basophils: histamine
- Platelets: histamine
- Endothelial cells: cytokines
- Leukocytes: PGs, LTs, chemokines, PAF
- Macrophages: cytokines (TNF, IL-1, IL-6)
15
Q
What are the cellular receptors of the acute immune response?
A
Pattern recognition receptors: PRR
- found in interfaces (skin, reparatory tract, GI, GU)
- cellular (surface or intra) or secreted
- bind to pathogen-associated molecular patterns (PAMPs) & damage-AMPs (DAMPs)
(Toll-like receptors (TLR), complement receptors, scavenger receptors, NOD-like receptors (NLRs), glucan & mannose receptors)
(TLRs + PAMPs activate cell & release cytokines –> adaptive response)
16
Q
What are cytokines?
A
Large family of small-molecular weight soluble intercellular-signaling molecules
- secreted
- bind to specific cell membrane receptors
- regulate innate/adaptive immunity
- Pro or anti-inflammatory
- Pleiotropic: varied response depending on target cell
- Synergistic or antagoinistic
- Classified into several families: interleukins (lymphocytes & MO), interferons (viral infected), lymphokines, monokines, chemokines (chemotactic)
17
Q
What are interleukins?
A
Biochemical messengers produced many by MO & lymphocytes
- produced in response to PRRs or other cytokines
- alter adhesion
- chemotaxis (leukocytes)
- induce proliferation/maturation of leukocytes
- enhance/suppress inflammation
– pro: IL-1, IL-6 (TNF-a)
– anti: IL-4, IL-10 (TGF-B)
- Develop acquired immune response
18
Q
What are chemokines?
A
- Chemotactic cytokines: primarily attract leukocytes to site of inflammation
– from macrophages, fibroblasts, endothelial cells
(classified by amino acid arrangement)
19
Q
What are mast cells?
A
- most important cellular activator of inflammation
- near body surfaces
- Activated by: physical injury, chemical agents, immunologic means, TLRs
- Mediates: degranulation and synthesis
20
Q
How does inflammation affect endothelial cells and platelets?
A
- Nitric oxide and PGL2: inhibit platelet activation, vasodilate, suppress cytokines
- Endothelial cell damage is prothrombogenic which activated platelets (clot)
- Platelets: anucleate cytoplasmic fragments from megakaryocytes
– activated by collagen thrombin, thromboxane, PAF, Ag-Ab complexes
21
Q
What are phagocytes?
A
Two major: recruited to infection/cell death and phagocytose & destroy pathogen
- Neutrophil: rapid, first on site, short-lived, degranulate, neutrophil extracellular traps (NETs)
- Macrophage: slower, prolonged, cytokines
22
Q
What are natural killer cells?
A
- Lymphocyte driver of inflammation
- Recognize & eliminate virally infected & cancer cells
- TLR activation –> proinflammatory cytokines & toxic molecules
- Limit adaptive immune response (no excessive inflammation/autoimmunity)
- Protective & pathogenic roles in autoimmunity
23
Q
What are systemic manifestations of accute inflammation?
A
- Fever: endogenous pyrogens (IL-1, IL-6, TNF-a) & exogenous (pathogen)
- Leukocytosis: inc. # circulating WBCs, left shift (more immature)
- Plasma protein synthesis: mostly in liver, pro or anti-inflammatory
- Somnolence (drowsy), malaise, anorexia (dec. appetite), myalgia
24
Q
What are the outcomes of acute inflammation?
A
- Complete resolution
- Healing by scarring/fibrosis
- Chronic inflammation
25
What causes chronic inflammation?
- Persistent infection: mycobacteria, certain viruses/fungi/parasites
- Hypersensitivity diseases: excessive/inappropriate activation immune system, autoimmune disease
- Prolonged toxin exposure: exogenous (silica), endogenous (lipids - atherosclerosis)
26
What are the cell mediators of chronic inflammation?
- Macrophages: phagocytosis, cytokines, display antigens & activate T cells, repair
- Lymphocytes
- Eosinophils
- Mast cells
Example: granulomatous inflammation (TB) - collections of activated MO often with T cells and sometimes necrosis
27
What are the aspects of wound healing?
- Repair/healing: architecture & function
- Regeneration: replacement with healthy (epithelia skin/intestine, stem cells)
- Scar formation: too severe/cannot regenerate, function (usually) retained,
28
What are the types of tissue regeneration?
Determined by type of cell & presence of stem cells
- Labile: continuously dividing, contain stem cells, (hematopoietic, stratified squamous/cuboidal/columnar/transitional epithelia)
- Stabile: normally minimal, divide response to injury (parenchyma solid organs, endothelial cells/fibroblasts/smooth muscle cells)
- Permanent tissues: Non-proliferative postnatal (neurons, cardiac, skeletal (but have stem cells)
29
What are the types of wound healing?
- fills in, seals (epithelization), shrink (contraction)
- Primary intention: minimal tissue loss, close apposition of wound edges
-- 24hr: neutrophils migration, basal cell activation
-- 3-7d: neutrophils replaced by MO; granulation tissue
-- Wks: fibroblast proliferation, collagen accumulation
- Mo: scar no inflammatory cells, no contraction
- Secondary intention: > tissue replacement, scar formation, **contraction**
-- 24h: fibrin clot larger, more exudate & necrotic debris
-- 3-7 >granulation
-- wks: collagen replaces matrix, dermal appendages destroyed
-- mo: contraction
30
What are the phases of wound healing?
- Phase I: inflammation
-- coagulation, fibrin mesh, cell scaffold
-- cellular infiltration: platelets, neutrophils, MO
- Phase II: Proliferation & reconstruction
-- 3-4days post injury to 2 wks
-- MO invasion, angiogenesis & fibroblast proliferation (granulation tissue), collagen sythesis, epithelialization, contraction, differentiation
- Phase III: remodeling & maturation
-- ++ wks post injury - 2 yrs
-- continued differentiation, scar formation & remodeling
31
What affects tissue repair?
- Infection
- Diabetes
- Nutrition
- Drugs, glucocorticoids
- Mechanical factors
- Foreign bodies
- Type/extent/location injury
- Obesity, tobacco smoke
32
What is dehiscence?
When a surgical incision reopens internally or externally
- mostly 5-12 days after suturing
- Risk factors: *infection, obesity, malnutrition, vascular insufficiency, movement
33
What are abnormalities in tissue repair?
- Defects in healing: ischemia --> venous leg, arterial, diabetic ulcers, & pressure sores
- Excessive formation of repair components: hypertrophic (excessive collagen, regress after months, affected dermis) keloid (not regress, familial - African-Amer)
- Exuberant granulation: blocks re-epithelialization, surgery
- formation of contractures: excessive --> deformities (burns palms, soles, anterior thorax) compromise ROM
- Peds & elderly dec. immunity & inflammation & repair
34
What is the difference between humoral and cell-mediated immunity?
- Humoral: against extracellular microbes and their toxins, B cells & Ab
- Cell-mediated immunity: against intracellular microbes & cancers, T cells
35
What is the difference between active and passive immunity?
- Active: involved host's immune response, long lived
-- Natural: natural exposure to Ag
-- Artificial: immunization
- Passive: Not involve host's immune response, temporary
-- Natural: Ab through placenta/breastmilk
-- Artificial: immunotherapy
36
What is the definition of antigen, immunogen, epitope, paratope, self-antigen, hapten, allergen, and antibody?
- Antigen: molecule that binds with Ab or TCR/BCR (exogenous/endogenous)
- Immunogen: Ag capable inducing immune response
- Epitope: Ag portion for recognition & binding (Ag may >1, defined by shape & makeup)
- Paratope: (aka Fab) Ab/BCR/TCR recognition site for Ag
- Self-antigen: non-foreign antigen
- Hapten: small molecules only immunogenic when bound to larger molecules
- Allergen: antigen that elicits an allergy
- Antibody: serum glycoprotein from plasma cells responding to immunogen
37
What are the five antibody classes, structure, major properties and functions?
- IgG: most abundant (80-85%), crosses placenta, 4 subclasses, Complement activation, Fc binds to phagocytes, mast cells, and platelets, toxin neutralization
- IgA: 2 subclasses, in blood & secretions (slgA, dimer), toxin & bacterial neutralization
- IgM: first Ab produced, largest Ig, pentamer, complement activation, agglutination,
- IgE: allergic & parasitic infection mediator, binds to Mast cells
- IgD: Ag receptor on early B cells
38
What are the tissues of the immune system?
- Primary (generative/central) lymphoid organs: location of T & B cell maturation to competency (Thymus, Bone marrow)
- Secondary (peripheral) lymphoid organs: location of adaptive immune response - antigens, naive lymphocytes, B and T cell interactions (Lymph nodes, Spleen, Mucosal & cutaneous lymphoid tissues)
39
What is Clonal Diversity and Selection?
- Diversity: lymphocytes specific for a large number of antigens before exposure "mature/naive"
- Selection: in secondary tissue Ag exposure selects Ag-specific cells producing "effector" (**activated differentiate for specific function**) & memory lymphocytes (live on, heightened awareness, react rapidly & strongly)
1) Ag processed & presented
2) Th induction (proliferate & differentiate, highly specialized)
3) B cell induction --> plasma cells, CD8+ T cell induction --> Tc cells: destroy cell-mediated MHC I positive (tumor & viral infection)
-- sometimes B-cell selection --> Class-switch (change in Ab production class) or Affinity maturation (higher affinity Abs)
40
What are the cells of the adaptive immune system?
- B cells: plasma cells- produce Ab, Memory B cell
- T cells: CD4+ helper (Th1&2), regulatory (Treg), CD8+ cytotoxic (CTL), memory
- Dendritic cells (DCs): translate b/w innate & adaptive, most important antigen-presenting cell (APC)
- Macrophages (MO): pt mononuclear phagocyte system, phagocytize then APC to T cells, important in: innate, adaptive, humoral, cell-mediated
41
What increases antigen immunogenicity?
- Foreign to host
- Molecular size
- Chemical complexity
- Quantity
- Adjuvants (vaccine- substance stimulate immune response)
- Genes, age, nutrition, reproductive status, diseases, immunosuppressive med
(May not need to know)
42
What are the aspects of Ag tolerance?
- Def: ability to distinguish self from nonself
- Central Tolerance: immature w/ receptors against self eliminated (primary lymphoid organs)
- Peripheral Tolerance: mature that recognize self, eliminated
(May not need to know)
43
What is the structure of an antibody?
- 4 poly peptide chains: light chins (2), heavy chains (2), constant & variable regions (in both chains)
- Crystaline fragment (Fc): responsible for most biologic function (complement activation, opsonization)
- Antigen-binding fragment (Fab): receptor for Ag (Antigen-binding site/paratope, complementary determining regions (CDRs), frame work regions (FRs)
44
What determines antibody specificity?
- Chemical nature of AA in CDRs
- Shape of binding site
- Lock and key
- Valence: number of functional Ag-binding sites (most 2, IgA - 4, IgM - 10 [typ. only 5 at a time])
(Plasma cell only produce one type at a time)
45
What are BCRs and TCRs?
- BCR: B Cell Receptor - Ab & other molecule complex on cell surface for intracellular signaling
-- **recognize Ag & communicate to nucleus**
-- Immunocompetent have IgM w/ or w/o IgD
- TCR: T Cell Receptor - Ab-like & accessory protein complex for intracellular signaling
-- **recognize Ag & communicate to nucleus**
-- Several severe defects in T cell response related to mutations in this complex
46
What is the role of MHC in immunity and transplantation?
- Major Histocompatibility Complex: that which presents Ags of APCs
- aka Human leukocyte antigens (HLAs)
- Class I: all cells but RBCs
- Class II: limited cells (MO, DC, B cells, activated T cells, some epithelial cells)
- Most genetically diverse human genetic loci
- **Haplotype:** group genes inherited as single unit (one copy from each parent, codominant)
- Transplant rejected if MHC Ags are too different
47
What is antigen processing and presentation?
- MHC I: display peptides from cytoplasmic proteins (normal, virus, tumor) (proteosomes --> ER) *recognized by CTLs
- MHC II: present Ag from extracellular microbes & proteins (endolysosome), *recognized Th
- APCs: B cells, MO, DC
48
What do Natural Killer Cells do?
- Cell-mediated destruction of MHC negative cells (Tumor & virally infected)
- Like Tc but not selected in thymus and no TCRs
- NK-T cells: produced in thymus and very limited TCRs (like Tc)
49
What are the regulatory lymphocytes?
Treg & Breg - similar function
- regulate the immune response
- mostly via suppression
(tolerance, immunosuppressive cytokines, limit response, homeostasis)
50
What are superantigens?
- Ag not digested/processed but bind to TCR & MHC II outside normal binding site
- Result: Out of control immune response, cytokine storm, toxic shock, (polyclonal Th-cell activation regardless of TCR specificity)
51
What is the difference between primary and secondary immune responses?
- Primary:
-- lag phase: 5-7 days, IgM production
-- IgG produced similar levels to IgM
- Secondary:
-- Rapid both IgM and IgG
-- IgM lev similar to primary, IgG produced in larger quantities for longer time
52
What are the mechanisms of effector B cells?
- Direct:
-- Neutralization: block/inactivate binding of Ag to receptor
-- Agglutination: clumping suspended insoluble fibers
-- Precipitation: make soluble Ag into insoluble principate
- Indirect:
-- Ab activates components of innate immunity: complement & phagocytes
53
What is the difference between systemic and mucosal immunity?
- Systemic: immunocompetent lymphocytes migrate among secondary lymph organs
-- final defense, systemic & internal
- Mucosal: partially independent, protect external surfaces
-- lacrimal/salivary glands, breast lymphoid tissue, bronchi, intestines, GU tracts, MALT
-- IgA predominant, IgM & G present
-- first line, local & external
(may not need to know)
54
How is the acquired immune response over the lifespan?
- Infants: immunologically immature (phagocytic, Ab, C' deficient, IgG from mother but declines 5-6 mo. old)
- Elderly: decreased function dec B & T cell production, dec. function mature WBC (dec. thymus activity, specific Ab production & circulating memory B cells)
55
What are the four mechanisms/types of hypersensitivity?
Type I: IgE mediated
Type II: tissue-specific
Type III: immune complex-mediated
Type IV: cell-mediated
*how immune response causes tissue injury and disease*
- seldom is a disease associated with only a single mechanism
55
What is the difference between hypersensitivity, allergy, autoimmunity, and alloimmunity?
- Hypersensitivity: Altered immunologic response to an Ag that results in disease or damage to the host. (*imbalance b/w effector & control mechanisms*)
Three sources:
1) Allergy: deleterious affects of hypersensitivity to environmental Ag
2) Autoimmunity: disturbance in immunologic tolerance to self-Ag
3) Alloimmunity: immune system of one individual produces reaction against tissue of another individual
56
What is sensitization?
- Exposure to Ag creating primary and secondary immune response
- Can be rapid (one exposure) or require multiple (yrs)
- Post sensitization reactions can be immediate or delayed
57
What is the mechanism, main cellular components, and clinical example of a type I hypersensitization?
- IgE-Mediated Hypersensitivity
- Rapid, previously sensitized
- Ag binds to IgE on Mast cell
- "allergies"
- Mostly against environmental Ag
- Most common
- Local (vary depending on portal of entry) or systemic (usually injection may be ingestion - may shock, fatal)
- Sensitization: Activate Th2, B cell switch (to IgE), IgE --> mast cell
- Re exposure: IgE activate mast cell release **histamine** + (other vasoactive amines), enzymes, proteoglycans (heparin)
- Genetic factors: atopy (genetic propensity to immediate, hypersensitivity reactions)
- Environmental factors: pollutants, viral infection, nonatropic allergy (temp extremes, exercise
- Anaphylaxis, bronchial asthma, allergic rhinitis, sinusitis, food allergies
58
What are the characteristics of anaphylaxis?
- Rapid & severe immediate hypersensitivity
- W/i min. re-exposure (hospital/communal)
- **Vascular shock, widespread edema, & difficulty breathing**
*itching, hives, erythema, bronchiole contraction, respiratory distress, laryngeal edema, vomiting, cramps, diarrhea, shock, death*
59
What is the mechanism, main cellular components, and clinical example of a type II hypersensitization?
- Tissue Specific Hypersensitivity
- Ab react with Ag on cell surface or ECM
- Destroy cell: opsonization & phagocytosis
*transfusion, autoimmune hemolytic anemia, drug reactions (penicillin)*
- Trigger inflammation: C' & FcR-mediated
*Glomerulonephritis, graft rejection, Pemphigus vulgaris*
- Cellular dysfunction (interfere w/ normal cell function)
*Myasthenia gravis, Grave's disease*
60
What is the mechanism, main cellular components, and clinical example of a type III hypersensitization?
- Formation Ab-ag complex, deposit in tissue --> inflammation & tissue damage
- Systemic diseases:
-- Kidney: glomerulonephritis
-- Joints: arthritis
-- Small blood vessels: vasculitis
*Lupus, poststreptococcal glomerulonephritis, polyarteritis nodosa, reactive arthritis, serum sickness, arthus reaction)
61
What is the mechanism, main cellular components, and clinical example of a type IV hypersensitization?
- CD4+ mediated inflammation: cytokines, inflammation, tissue injury
-- delayed (TB test), inflammation chronic & destructive
- CD8+ mediated inflammation: cell killing, tissue injury
-- Ag-expressing target cells
*Rheumatoid arthritis, MS, T1DM, IBD, psoriasis, contact sensitivity*
62
What are autoimmune diseases?
- Immune reaction against self-Ags
- Failure to tolerance
- Genetics may contribute to breakdown of self tolerance
- Environmental triggers: infections, tissue damage, microbe molecular mimicry
- 5-10% US pop, chronic & progressive
- Reaction is not pathogenic or due to tissue damage, no other disease
- Can be organ specific, or systemic
63
What is Systemic Lupus Erythematosus?
- Autoimmune disease involving multiple organs (1:2500, higher blacks & Hispanics)
- Mostly women (9:1) childbearing (17-55)
- Acute or inscidious
- Chronic, remitting, relapsing
- Skin, joints, kidneys, serosal membranes
- Failure self-tolerance
-- Genetic: MHC & non-MHC genes --> predisposition
-- Immunologic: persistence & uncontrolled activation self-reactive lymphocytes
-- Environmental: UV light & some drugs
- Various autoAb --> Type III
64
What is transient neonatal alloimmunity:
Maternal immune system sensitized against fetus Ags
- fetal Ags cross placenta --> mother immune response --> maternal alloAb cross placenta --> bind fetal cells --> alloimmune disease
- In urtero or after birth, may be fatal if untreated
65
What is transplant rejection?
- Immune system of recipient of an organ transplant reacts against Ag on donor cells
- MHC major target
- Direct to T cells or indirect through APCs
- Allograft (same species), Xenograft (different species)
1) Hyperacute: immediate, Ab & Ag
2) Acute rejection: #1 cause early graft failure, days to weeks, T cells & Ab
3) Chronic rejection: principal cause of graft failure, mo-yrs T cells
66
What are transfusion reactions?
- immune system of recipient reacts against donor cell Ags
- >80 Ags, ABO & Rh strongest response
- Universal donor: type O
- Universal recipient: type AB
*A has A Ag, B Ab*
67
What is the transplantation of HSC?
- Hematopoietic Stem Cell transplants
- Treat: hematologic malignancies, BM failure syndromes (aplastic anemia), inherited BM disorders (sickle cell anemia, immunodeficiency states)
- Recipient's cells destroyed (irradiation or chemotherapy)
- Problems: Graft-versus-host disease (GVHD) & immunodeficiency
68
What is primary immunodeficiency diseases?
- (congenital): genetically determined - inherited
- usually detected infancy (6mo-2yr)
- clinical: increased susceptibility to recurrent infections
- Severe combined immunodeficiency (SCID)
-- genetically distinct syndromes, defects both humoral & cell-mediated immune responses
69
What is secondary immunodeficiency?
- acquired
- from complications cancer, infections, malnutrition, DM, stress, physical trauma, medical treatments: immunosuppression/irradiation/ chemotherapy
- newly acquired or reactivation of latent infection)
- more common than primary
