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Immuno Flashcards

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1
Q

Innate immunity

A

Protection that relies on mechanisms that are present BEFORE infection occurs: first line of defense against infection

Physical barriers, macrophages, neutrophils, natural killer cells

Effector cells present and ready—immediate defense!

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2
Q

Adaptive immunity

A

Protection that is stimulated by exposure to infectious organism, effector cells have to be produced !

T cells, B cells

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3
Q

Antigen

A

Molecule/molecular fragment that can be recognized by a B or T cell

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4
Q

Effector cell

A

Any of various cell types of immune system that actively respond to stimulus and effect a change

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5
Q

3 Common phases between innate and adaptive systems

A
  1. Recognition (through receptors) of pathogen
  2. Activation of immune cells
  3. Effector function performed by activated cells to destroy the pathogen
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6
Q

Innate immunity features

A

Receptors are NOT specific for a particular pathogen—recognize BROAD classes
Limited specificity

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7
Q

Adaptive immunity features

A

Receptors are SPECIFIC for a particular pathogen
Recognize antigens specific to particular pathogens

HUMORAL response: B Cells, infection in body fluids

CELL MEDIATED response: T cells, cytotoxic . Infection in body cell s

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8
Q

Microbes express conserved macromolecules/molecular patterns NOT expressed by host cells

A

Pathogen associated molecular patterns (PAMPS) are structures of microbes that are conserved within a class of microbes, essential for their survival and specificity

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9
Q

Pathogen recognition receptors (PRRs)

A

PAMPS (pathogen associate molecular patterns) are recognized by cells of INNATE immune system in pathogen recognition receptors

Encoded in Germaine with fixed limited number of specificities
NONclonal expression: all cells of same lineage (neutrophils, macrophages) express an ARRAY of receptors of different molecular types
Each type of receptor is specific for a different PAMP

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10
Q

B and T cell receptors

A

Encoded by genes produced by rearrangement of gene segments, creating BILLIONS of receptor variants with many specificities
CLONAL expression: each lymphocyte expresses cell surface receptors of just ONE molecular type

Recognize antigens

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11
Q

PRR vs B/T cell receptor

A

Molecule specificity (Pattern recognizing receptor) vs antigen specificity

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12
Q

Toll-like receptors

A

Cells of innate immune system have these signaling receptors that deliver activation signals …leads to effector phase

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13
Q

Infection site/wound series of events

A

Surface wound introduces bacteria
Activation of resident effector cells to secrete CYTOKINES (engagement of signaling receptors like TLR expressed by macrophages triggers the synthesis of cytokines, which create state of inflammation)
Vasodilation and increased vascular permeability allow fluid, protein, and inflammatory cells to leave blood and enter tissue
Infected tissue becomes inflamed, causing redness, swelling, pain

ESSENTIALLY: secretion of pro inflammatory cytokines at infection site induces changes in vascular permeability that recruits inflammatory cells like neutrophils

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14
Q

All receptors expressed by a single B or T cell have the same…..

A

SPECIFICITY

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15
Q

Antibody

A

SOLUBLE form of B cell receptor

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16
Q

B and T cell receptor specificity is like what model ?

A

LOCK AND KEY concept
Dependent on chemical composition, physical forces, and molecular structure at receptor binding site
Depends on binding affinity between ligand and binding site on receptor

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17
Q

CLONAL selection and amplification of antigen-specific lymphocytes

A

The selection of a T or B lymphocyte “specific” for an antigen is based on recognition of antigen by the receptor, and this leads to an expansion of the reactive cell

CLONAL expansion results in a population of lymphocytes with IDENTICAL specificity

When antigen/pathogen is encountered, those cells whose surface receptors recognize or have specificity for that antigen with undergo activation, proliferation and differentiation to form CLONES
Clones of cells specifically equipped to eliminate that pathogen will be generated in this process
(Proliferation and differentiation of the lymphocytes give effector cells that terminate the infection)

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18
Q

B cell effector mechanisms

A

Relate to the properties of the antibodies (immunoglobulins) they produce: some antibodies cause lysis or killing pathogens while others neutralize pathogens or facilitate their uptake by phagocytes

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19
Q

T cell effector mechanisms

A

Include direct killing of pathogens and the production of cytokines, which act directly on pathogens or activate other cells to mediate an effector function (inflammation)

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20
Q

Adaptive immune memory

A

Immunological memory is the ability to respond more rapidly with a greater magnitude and quality to pathogens that have been encountered fore and reflected preexistence of a CLONAL expanded population of antigen-specific lymphocytes

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21
Q

Naive T cells can differentiate into three types of effector T cells…

A
  1. TH1, type 1: INTRAcellular bacteria and Protozoa, viruses: inflammation/autoimmunity
  2. TH2, type 2: Defense against helminths and venoms: allergy/asthma
  3. TH17, type 3: Extracellular bacteria and fungi: inflammation/autoimmunity
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22
Q

Antimicrobial peptides: defending and cathelicidins, innate immunity

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A

Defensins are amphipathic peptides that disrupt the membrane of microbes!

23
Q

Soluble factors of innate immune system present in serum

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A

Plasma proteins:
1. Complement: series of plasma proteins involved in destruction of extracellular pathogens
2. Mannose binding lectin
3. C-reactive protein
4. Coagulation factors and the Kinin system

24
Q

Mannose binding lectin

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A

Binds to patterns of carbohydrate groups present in bacterial cell-wall polysaccharides in the correct spatial orientation

When bound to surface of pathogen, MBL triggers the activation of the lectin pathway of complement activation
LOW levels of MBL in newborn is risk for sepsis

25
C reactive protein
Triggers the classical pathway of complement activation
26
Two major effector functions of INNATE immune cells:
1. Phagocytosis 2. Cytokines secretion
27
Neutrophil phagocytosis
Neutrophil phagocytosis of bacterium, phagosome fuses with specific granules, bacterium is killed, neutrophil dies by APOPTOSIS and is phagocytosed by macrophage : EFFEROCYTOSIS
28
What are the first effector cells recruited to sites of infection?
NEUTROPHILS
29
What promotes the phagocytosis of bacteria?
SERUM
30
Macrophages express …
Phagocytic and signaling receptors The signaling receptors are located on cell surface, endosomes, or cytoplasm
31
Signaling cascade of TLRs (receptors on macrophages) drives production of cytokines
Activation of TLR by ligand, TIR domains recruit cytoplasmic adaptor proteins MyD88 and TRIF. These proteins associate with kinases and trigger activation of Transcription factors like NF-kB and IRF These TFs promote gene expression and result in synthesis of pro-inflammatory cytokines and type 1 interferons The effector function is acute inflammation, stimulation of adaptive immunity
32
Cytoplasmic PRR (Patern recognition receptors)
ONLY innate immune cells These receptors recognize PAMPS present in cytoplasm 1. NOD-like receptors: detect BACTERIAL components derived from intracellular degradation of bacteria 2. Rig-I-Like receptors: detect viral RNAs RESULT? Secretion of inflammatory cytokines!
33
Secretion of IL-6
Bacteria induce macrophages to produce IL-6, which acts on hepatocytes to induce synthesis of acute-phase proteins C-reactive protein or mannose-inking lectin act as complement activators to destroy pathogen
34
Innate immune response to viral infection
Many cell types—macrophages, epithelial cells, fibroblasts, endothelial cells, lymphocytes—produce type 1 INTERFERON 1. This induces resistance to viral replication in all cells 2. Increase expression of ligand for receptors on NK cells 3. Activates NK cells to kill virus infected cells
35
Natural killer cells
Kill virus infected cells and are early component of the host response to VIRAL infections
36
TWo pathways of intracellular virus that give interferon response
These pathways are present in NK cells and macrophages mediated by TLR8 and TLR3 Type 1 interferon induces proliferation of NK cells and their differentiation into CYTOTOXIC cells, NK cells induce virus infected cells to undergo apoptosis
37
Macrophage and NK cell relationship
1. Macrophage secretes inflammatory cytokines that recruit and stimulate NK cells 2. NK cell and macrophage form a pair 3. NK cells proliferate and differentiate into effector NK cells secreting interferon 4. Interferon binds to receptor on macrophage and activates them to increase phagocytosis and secretion of inflammatory cytokines
38
Hematopoietic stem cells
All types of blood cells are derived from these stem cells in the bone marrow
39
Blood cell normal ranges
RBC: 6-8*10^6 Platelets 2-5*10^5 Leukocytes 5-17*10^3
40
Cell types of innate vs adaptive
Innate: neutrophil, eosinophils, basophilic, monocytes Adaptive: lymphocyte, B and T MOST ABUNDANT: Neutrophils
41
INNATE SYSTEM CELLS
1. Granulocytes/PMN leukocytes: neutrophil, eosinophils, basophils 2. Monocytes and macrophages 3. Mast cell 4. Dendritic cell
42
NEUTROPHIL
Most prevalent granulocyte Greates percentage 60% o hematopoietic is for neutrophil production 100 billion neutrophils produced by humans daily SHORT life span Located during normal conditions, not just inflammatory FIRST CELLS that do arrive to inflammation sites Acts by PHAGOCYTOSIS and degranulating (release proteolytic enzymes) and forms neutrophil extracellular traps (NETS)
43
Neutrophil extracellular traps
One way for neutrophils to kill pathogens ! Net like structures composed of dna-histories complexes and proteins released by activated neutrophils They allow neutrophils to kill extracellular pathogens while minimizing damage to HOST cell Can cause pathology:
44
Basophils
Have basophilic granules Lifespan of days Located in blood Recruited to infection sites following exposure to HELMINTHS and TICKS Involved in inflammation Immunomodulatory function by secreting IL4 and 13 Associated with allergies and asthma
45
Eosinophils
Eosinophilic granules Life span of days to weeks Located in blood and tissues lining the GI tract and airways Involved in ALLERGIC inflammation Functions by degranulation, release eosinophilic granules content can damage membrane of parasites
46
Monocytes
Large, round to kidney shaped nucleus, diffuse pale blue gray staining cytoplasm commonly having vacuoles Life span is days Located in blood, travels to tissues to give rise to macrophages Phagocytic, innate defense against bacteria Precursor of tissue macrophages and dendritic cells in tissues Limited antimicrobial function in blood
47
Macrophage
Round nucleus, vacuolated cytoplasm, irregular shape Life span is MONTHS Located in many peripheral tissues as RESIDENT phagocytic cell Phagocytosis, release of inflammatory cytokines, immune surveillance and some antigen presentation Can change function—pro inflammatory or anti inflammatory based on cytokines environment If activated by interferon gamma, can become a killer of bacteria resistant to lyric activity of phagosome
48
Effector function of macrophages
Binding of bacteria to phagocytic receptors on macrophages induces their engulfment and degradation Binding of bacteria components to SIGNALING RECEPTORS on macrophages induces the synthesis of inflammatory cytokines : effector function
49
Dendritic cells
Round nucleus, clear cytoplasm, star shaped In primary and secondary lymphoid don’t tissue and peripheral tissues Lifespan is months Regulate adaptive immune response via antigen processing and presentation to T cells to initiate the adaptive immune response PROFESSIONAL antigen presenting cells (APC) Secrete cytokines that modulate adaptive response
50
Mast cells
Round nucleus, cytoplasms densely packed with granules that stain purple Located in tissues, mostly connective tissues surrounding vasculature, nerves, lamina proprietary of mucosa Life span: weeks to months Act by releasing inflammatory mediators via degranulation and synthesis of lipid mediators Involved in innate defense against parasites and allergic responses Express Fc epsilon receptors, bind IgE
51
Natural killer cells : lymphoid cells
Large cell, round nucleus, azure Philip cytoplasmic granules In blood and SPLEEN Life span weeks to months Located in blood in normal conditions too Function is to destroy virally infected or abnormal host cells ; tumor cells Acts by targeted release of cytotoxic granules
52
ADCC: effector function of NK cells
Anti CD20 antibody binds to CD20 on surface of B cell lymphoma cell Receptors on NK cell recognize bound anti CD20 antibody Cross linked receptors signal NK cell to kill Lymphoma cell and that cell dies by apoptosis ADCC: antibody dependent cell mediated cytotoxicity
53
Primary lymphoid organs
1. Bone marrow: B cells are matured here but not T cells 2. Thymus : where T cells mature

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