Lecture 10-19 Flashcards
What is innate immunity?
It is present before any exposure to pathogens and is effective from the time of birth.
It involves nonspecific responses to pathogens
Consists of external barriers plus internal cellular and chemical defenses
What is acquired immunity?
Adaptive immunity, develops after exposure to agents such as microbes, toxins, or other foreign substances.
Specific response to pathogens
What are the chemical mediators in innate immunity?
Defensins, lysozymes, complement
Cells and tissues of the innate immune system are
Granulocytes, macrophages, dendritic and NK cells.
Acquired or specific immune systems involve what factors?
Cells, tissues
Memory
Discrimination, self/no self
Where do T cells mature?
Thymus
Where do B cells mature?
Bone marrow
What is the ultimate result of antigen presence?
B cell activation which leads to production of antibodies
What are some physical barriers involved in the innate immune system?
Epidermis Mucous membranes Mucous Lacrimal apparatus Saliva Hairs Cilia Epiglottis Urine Vaginal secretions Peristalsis, defecation, and vomiting
What are some chemical factors involved in innate immunity defense?
Sebum Lysozyme Saliva Gastric juice Urine Vaginal secretions
Why is skin an inhospitable environment for microbes?
Salty, acidic, and dry
Functions of lysozyme as an antimicrobial secretion
Hydrolyzes bond connecting sugars in peptidoglycan
Function of lactoferrin as an an antimicrobial secretion in mucous membranes
Secreted by activated macrophages and PMNs and sequesters iron from plasma
Function of lactoperoxidase as an antimicrobial secretion in mucous membranes
Produces superoxide radicals
What are two areas of the body that should be completely FREE of microbes?
The lower respiratory tract and the bladder
What are the innate functions of the respiratory immune system?
Mucociliary blanket, alveolar macrophages, and ciliary escalator
What are the innate functions of the gastrointestinal immune system?
Gastric acid in the stomach
Pancreatic enzymes, bile, GALT, normal microbiota, and peristalsis in the intestines
What makes the genitourinary tract an unfavorable environment for foreign microbes?
Acidity
What are some aspects of the innate immune system in the eye?
Lysozyme, lactoferrin, and secretory IgA in tears
Lacrimal apparatus for flushing, eyelashes as barrier
Bacteriocins
Antimicrobial peptides that are produced by normal flora; toxic proteins that are lethal to other strains of the same species in closely related bacteria
Three major activities of the complement system
Defend against bacterial infections
Bridging innate and adaptive immunity
Disposing of wastes
Opsonization
Microbes are coated by serum components (opsonins) in preparation for recognition/ingestion by phagocytic cells; binds to microbial cells, coating them for phagocyte recognition
Antibody and complement C3B together enhance phagocytosis
As a pathogen, which complement would you inactivate first in order to inactivate the complement system?
C3, followed by C5
What activates the classical pathway of complement system?
Antigen: antibody complexes (pathogen surfaces)
What activates the Lectin pathway of complement system?
Mannose-binding lectin binds mannose on pathogen surface
What activates the alternative pathway of complement system?
Pathogen surfaces - activation of C3 forms MAC
Name the three potential pathways for activation of the host complement system
Classical pathway, MB-Lectin pathway, and alternative pathway
How do bacteria evade the host complement system?
Capsules prevent C activation
Surface lipid-carbs prevent MAC formation
Enzymatic digestion of C5a
Soluble proteins or glycoproteins that are released by one cell population that act as intercellular mediators or signaling molecules. These must bind to specific receptors on target cells
Cytokines
Autocrine function of cytokines
Affect same cell responsible for their production
Paracrine function of cytokines
Affect nearby cells
Endocrine functions of cytokines
Spread by circulatory system to distant target cells
Chemokines
Specialized cytokines that stimulate chemotaxis and chemokinesis, thus directing cell movement
Monokines
Cytokines released from mononuclear phagocytes
Lymphokines
Cytokines released from T lymphocytes
Interleukins
Cytokines released from one leukocyte and act on another leukocyte
Colony Stimulating Factors (CSFs)
Type of cytokine that stimulates growth and differentiation of immature leukocytes in bone marrow
Which cytokine increases immunity to viral infection and upregulates cytolytic function?
IFN-alpha
Innate resistance
Which type of cytokine enhances differentiation, enhances antibody synthesis, activates phagocytic function, and enhances antigen processing and presentation?
IFN-gamma
Adaptive immunity
Which type of cytokine upregulates coagulation response, stimulates production and release of acute-phase proteins, and activates phagocytic functions?
TNF
IFN-alpha and IFN-beta are interferons that do what?
Cause cells to produce antiviral proteins that inhibit VIRAL replication
IFN-gamma is an interferon that does what?
Causes neutrophils and macrophages to phagocytize BACTERIA
What innate immune defense kills infected target cells by releasing granules that contain perforin and granzymes? In other words, helps protect cells that have not been able to produce “self” tag?
Natural Killer (NK) cells
Phagocytes then kill the infected microbes
Neutrophils
Stain at neutral pH, lobed nuclei
Highly phagocytic
Basophils
Stain bluish-black or purple with basic dyes
Produce histamine
Eosinophils
Stain red with acidic dyes, may appear orange
Kills parasites using lytic factors and perforin
Monocytes
Phagocytosis
Later mature into dendritic cells or macrophages
Natural killer cells
Destroy target cells, large in size
T-cell function
Cell-mediated immunity (cell-mediated response)
B cell function
Produce antibodies (humoral response)
Have receptors for unique antigens
Platelet function
Blood clotting, small in size
Contains specialized cells including Langerhans cell and intraepidermal lymphocytes
Skin Associated Lymphoid Tissue (SALT)
Specialized immune barrier that have a “training ground” for immunity responses. Includes gut-associated lymphoid tissue, bronchial-associated lymphoid tissue, and urogenital system.
Mucosal-Associated Lymphoid Tissue (MALT)
Name the two mechanisms of phagocytosis
Opsonin-independent recognition
Opsonin-dependent recognition
Phagocytosis can be greatly increased by opsonization
Which phagocytosis mechanism involves non-specific pathogen component recognition, with a signaling mechanism involved. May recognize peptidoglycan, flagella, and other surface characteristics.
Opsonin independent mechanism
What are the four main forms of opsonin-independent mechanisms?
- Lectin-carbohydrate interactions
- Hydrophobic interactions
- Protein-protein interactions
- Detection of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRR)
What are PAMPs?
Pathogen-Associated Molecular Patterns
Unique to microbes, not present in host
Examples: LPS of gram-negative bacteria, peptidoglycan of gram-positive bacteria
Recognized by PRRs in phagocytic cells
What are Toll-Like receptors (TLRs)?
class of pattern recognition receptors that function exclusively as signaling receptors; recognize and bind unique PAMPs of viruses, bacteria, or fungi
The binding triggers signal which is then communicated to host cell nucleus, initiating host response
Autophagy
Highly conserved process that tags internal microbes for destruction using monoubiquitination
What might a PAMP (pathogen-associated molecular pattern) be in a virus?
Capsid proteins, viral RNA, etc.
During intracellular digestion, the phagosome fuses with lysosome to form ______ that will expose the bacteria to hydrolytic enzymes
Phagolysosome
How do Streptococcus pyogenes and Streptococcus pneumoniae evade phagocytosis?
Inhibition of adherence: M protein, capsules
How does Staphylococcus aureus evade phagocytosis?
Killing phagocytes: Leukocidins
How does Listeria monocytogenes evade phagocytosis?
Lysis of phagocytes via membrane attack complex (MAC)
How do Shigella and Rickettsia evade phagocytosis?
Escaping the phagosome
How do HIV and Mycobacterium tuberculosis evade phagocytosis?
Prevention of phagosome-lysosome fusion
Define inflammation
Innate, nonspecific response to tissue injury caused by pathogen or physical trauma; it is the immediate response of the body to injury or cell death
What are the cardinal signs of inflammation?
Redness Warmth Pain Swelling/edema Altered function
What chemical mediators are involved with acute inflammatory responses and what are their functions?
Selectins: cell adhesion molecules on activated capillary endothelial cells
Integrins: adhesion receptors on neutrophils
Chemotaxins: chemotactic factors released by injured cells
Describe an acute inflammatory response
Damaged tissue releases inflammatory chemicals called chemokines (kalikrein) - recruit macrophages
Dilation and increased permeability of capillaries brings blood to the area, may result in swelling
Various processes occur: margination, diapedesis, and extravasion
What are advantages of fever?
T-cell production increases due to increase in IL-1
Increase transferrins (iron scavenging)
Speeds up repair process
What are some disadvantages of fever?
Tachycardia
Acidosis due to increased metabolic rate
Dehydration
Death above 44-46 celsius (112-114 F)
What is the result of histamine release by damaged cells?
Vasodilation, increased permeability of blood vessels
What is the result of kinins release by damaged cells?
Vasodilation, increased permeability of blood vessels
What is the result of prostaglandins release by damaged cells?
Intensify histamine and kinin effect (vasodilation and increased permeability of blood vessels)
What is the result of leukotrienes release by damaged cells?
Increased permeability of blood vessels, phagocytic attachment
What are the two types of adaptive immunity?
Humoral: antibody-mediated
Cell-mediated: based on action of T lymphocytes
Naturally acquired active immunity
Type of specific immunity a host develops after exposure to a foreign substance (consequence of prior infection)
Naturally acquired passive immunity
Transfer of antibodies, e.g., mother to fetus across placenta, or through breastfeeding
Artificially acquired active immunity
Intentional exposure to a foreign material (vaccination)
Goal is to stimulate antibody production
Artificially acquired passive immunity
Preformed antibodies or lymphocytes produced by one host are introduced into another host
Goal is to give antibodies directly
For example: immune globulin therapy
What is a hapten and when is it used?
Antigen combined with carrier molecules; used when the antigen is too small to illicit an immune response on its own, but when combined with a carrier molecule the body will recognize it
Where are MHC-I molecules found and what type of processing do they use?
MHC class I are found on almost all types of nucleated cells (so not RBCs because they don’t have nucleus)
Utilize endogenous antigen processing
Where are MHC-II molecules found and what type of processing do they use?
MHC class II molecules are found only on Antigen Presenting Cells (APCs) which are macrophages, dendritic cells, and B-cells
Utilize exogenous antigen processing
MHC class I molecules utilize endogenous antigen processing, meaning what?
Class I bind to antigen peptides that originate in the cytoplasm. They then present the antigen to CD8+ T cells (cytotoxic T lymphocytes)
MHC class II molecules utilize exogenous antigen processing, meaning what?
Class II binds to antigen fragments that come from outside the cell and present them to CD4+ T cells (Helper T cells)
Identify the cells that can function as APCs (antigen presenting cells)
Macrophages
Dendritic cells
B cells
What type granular leukocytes destroys cells that don’t express MHC I?
Natural killer cells
These also kill virus infected and tumor cells, as well as attack parasites
In terms of Cluster of Differentiation Molecules (CDs), what is the MHC class II coreceptor on T cells, monocytes, and macrophages?
CD4
In terms of Cluster of Differentiation Molecules (CDs), what is the MHC class I coreceptor on cytotoxic T cells?
CD8
Describe T cell receptor structure and function
TCRs are found in plasma membrane surface and contain an antigen binding site
They recognize and bind fragments of antigens presented by APCs
Describe B cell receptors structure and function
BCRs are immunoglobulin receptors for specific antigen that will activate that particular B cell
Consist of two light chains and two heavy chains connected with disulfide bonds
Explain molecular events resulting in Helper T cell activation
- APC encounters and ingests microorganism. Antigen is enzymatically processed into short peptides, which combine with MHC class II molecules and are displayed on the surface of APC
- A receptor on helper T cell binds to the MHC-antigen complex. If this includes a Toll-like receptor (TLR), APC releases costimulatory molecules. These two signals activate helper T cell which produces cytokines
- Cytokines cause helper T cell to proliferate and develop its effector functions
Explain molecular events resulting in cytotoxic T cell activation
- Response is triggered by abnormal cell (cancer, virus infected, etc.)
- Abnormal antigen is presented on cell surface in association with MHC-I molecules. CD8+ T cells with receptors for the antigen are transformed into cytotoxic T lymphocytes
- CTL induces destruction of virus infected cell by apoptosis
Explain molecular events resulting in B cell activation through the T dependent pathway
T dependent requires 2 signals before B cell differentiates into plasma cell and memory cell:
Antigen-BCR specific interaction
Activated T helper 2 binds B cell presented antigen and secretes B cell growth factors
Explain molecular events resulting in B cell activation through T independent pathway
T independent involves polymeric antigens with large number of identical epitopes (i.e., LPS)
Less effective than T dependent pathway
Antibodies produced have low affinity for antigen
No memory cells are formed; overall weaker immune response
Antibodies are also known as immunoglobulin, which are made by activated B cells (plasma cells). What are the 5 immunoglobulin classes?
IgG IgM IgA IgD IgE
Describe IgG in terms of its valence, abundance, where it is found, and function
Monomer - bivalent (2 binding sites)
80% of serum antibodies
Capable of complement fixation and crossing the placenta
Found in blood, lymph, and intestine
Enhances phagocytosis, neutralizes toxins and viruses, and protects fetus and newborn
**second antibody to appear in response to infection (M is first)
Describe IgM in terms of its valence, abundance, where it is found, and function
Pentamer - (10 binding sites) 5-10% of serum antibodies Capable of complement fixation Found in blood, lymph, and on B cells Agglutinates microbes, first antibody introduced in response to infection
Describe IgA in terms of its valence, abundance, where it is found, and function
Dimer (4 binding sites)
10-15% of serum antibodies
Found in secretions
Functions in mucosal protection
Describe IgD in terms of its valence, abundance, where it is found, and function
Monomer (2 binding sites)
0.2% of serum antibodies
Found in blood, lymph, and B cells
Functions in initiation of immune response on B cells
Describe IgE in terms of its abundance, where it is found, and function
0.002% of serum antibodies
Found on mast cells, on basophils (histamine), and in blood
Functions in allergic reactions; lysis of parasitic worms, opsonization
What is “class switching” in terms of antibody kinetics?
Change in antibody class secreted by plasma cells under the influence of T helper cells (i.e., may switch from IgM to IgG); event unfolds with time
During primary antibody response, there is a lag period of several days to weeks where there is no antibody detectable in blood. After B cell differentiation into plasma cells, the antibody is secreted. How is an antibody titer calculated?
The titer is the measure of serum antibody concentration
It is the reciprocal of highest dilution of antiserum that gives positive reaction
What are the characteristics of a secondary antibody response
B cells mount a heightened memory response:
Shorter lag phase
More rapid log phase
Longer persistence
Higher IgG titer and production of antibodies with higher affinity for the antigen
What is combinatorial joining?
The segments clustered separately on same chromosomes have exons that code for constant regions and exons that code for variable regions.
Exons for constant region are joined to one segment of the variable region via RAG-1 and RAG-2 recombination enzymes
What is the clonal selection theory?
States that each lymphocyte has membrane-bound immunoglobulin receptors specific for particular antigen and after the receptor is engaged, proliferation of the cell occurs such that a clone of antibody producing cells is produced
What is the clonal deletion theory?
The elimination of certain T cell populations in the thymus that have specificity for self-antigens (forbidden clones)
Name the 5 consequences of antibody binding of an antigen
Agglutination Opsonization Complement activation Neutralization Antibody-dependent cell-mediated cytotoxicity
Define agglutination, one of the consequences of antibody binding of antigen
Agglutination reduces number of infectious units to be dealt with by sticking together
Define opsonization, one of the consequences of antibody binding of antigen
Coating antigen with antibody, enhancing phagocytosis
Define complement fixation, one of the consequences of antibody binding of antigen
Addition of complement causes inflammation and cell lysis
Define antibody-dependent cell-mediated immunity, one of the consequences of antibody binding of antigen
Antibodies attached to target cell cause destruction by macrophages, eosinophils, and NK cells
Define neutralization, one of the consequences of antibody binding of antigen
Blocks adhesion/attachment of bacteria, viruses, or toxins to mucosa
Describe the function of cytotoxic T lymphocyte (CTL)
Destroys target cells on contact; generated from T cytotoxic (Tc) cell
Describe the function of an activated macrophage
Enhanced phagocytic activity; attacks cancer cells
Describe the function of Natural Killer (NK) cell
Attacks and destroys target cells; participates in antibody-dependent cell-mediated cytotoxicity
Which of the cytokines promotes inflammation?
TNF-alpha
Which of the cytokines inhibits humoral immunity and activates TH1 cellular immunity?
Interleukin-12 (IL-12)
Which of the cytokines responds to viral infection and interferes with protein synthesis?
IFN-alpha and IFN-beta
Which of the cytokines stimulates macrophage activity?
IFN-gamma
How does Coxiella burnetti escape phagocytosis?
By surviving in the phagolysosome
What processes occur in the acute inflammatory response?
Margination
Diapedesis
Extravasion
What are the chemicals that are released by damaged cells?
Histamine
Kinins
Prostaglandins
Leukotrienes
What are the two types of acquired immunity?
Humoral response
Cell mediated response
Define the humoral response
Antibodies defend against infection in body fluids
Define cell-mediated response:
Cytotoxic lymphocytes defend against infection in body cells
Compare and contrast innate and acquired immunity
Innate: recognition of trait shared by broad ranges of pathogens using a small set of receptors. Rapid response
Acquired: recognition of traits specific to particular pathogens, using a vast array of receptors. Slower response
All of the following are involved in keeping the lower respiratory tract free of microorganisms except: A. Ciliary escalator B. Epiglottis C. Alveolar macrophages D. Lacrimal apparatus
D. Lacrimal apparatus
Which of the following pathways for complement activation is generally dependent upon the formation of antigen-antibody complexes? A. The classical pathway B. The alternative pathway C. The lectin pathway D. All of the above
A. The classical pathway
Which leukocytes function to produce toxins against certain parasites? A. Lymphocytes B. Basophils C. Eosinophils D. Neutrophils
C. Eosinophils
Which host defense is more effective against gram positive bacteria than gram negative bacteria? A. Mucus B. Sebum C. Gastric juice D. Lysozyme
D. Lysozyme
Because of thicker layer of peptidoglycan, it will have a greater impact – gram negative are protected by outer membrane
Natural killer cells specifically kill which of the following?
A. Gram positive
B. Gram negative
C. Fungi protozoa
D. Tumor cells and cells infected by microorganisms
D. Tumor cells and cells infected by microorganisms
Each of the following is an effect of complement activation, except: A. Opsonization B. Increased phagocytic activity C. Interference with viral replication D. Increased blood vessel permeability
C. Interference with viral replication
Eosinophils defend against protist and helminth parasites by: A. Phagocytosis B. Complement activation C. Antibody production D. Releasing perforin and lytic enzymes
D. Releasing perforin and lytic enzymes
Which of the following is INCORRECTLY matched?
A. PAMP - peptidoglycan
B. TLR - stimulation of the inflammatory response
C. Histamine - vasodilation
D. None of the above
D. None of the above
Class II major histocompatibility complex molecules are found on all of the following except:
A. B cells
B. T cells
C. Dendritic cells
D. None of the above, all have MHC class II molecules
B. T cells
What is the difference between normal microbiota and transient microbiota?
Normal microbiota permanently colonize the host
Transient microbiota may only be present for days, weeks, or months
Define the symbiotic relationship: Commensalism and give an example
One organism benefits while the other is unaffected/unharmed
Example: Staph Aureus in your nose
Define the symbiotic relationship: Mutualism and give and example
Both organisms benefit
Example: E. Coli in the gut benefit from rich nutrients, while they produce vitamins B & K for host benefit
Define the symbiotic relationship: Parasitism and give an example
One organism benefits at the expense of the other (host is harmed)
Example: H1N1
Define microbial antagonism
Competition between microbes
What are 3 ways that normal microbiota protect the host?
Occupying niches that pathogens might occupy
Producing acids
Producing bacteriocins
What are opportunistic pathogens?
Members of normal microbiota that produce disease under certain circumstances, such as when they are misplaced to an area they are not normally found
Where might you find the following normal microbiota:
Staphylococci (S. epidermidis)
Micrococci (M. luteus)
Diphtheroids (aerobic Corynebacterium xerosis and anaerobic Propionibacterium acnes)
Acinetobacter
Malassezia furfur
Skin
What is the predominant bacterium found on the conjunctiva of the eye?
Staphylococcus epidermidis
What normal flora might you find in the external ear?
Similar to skin flora as well as fungi
Where might you find the following normal microbiota:
S. mutans
Lactobacillus
Mouth
How do oral bacteria remain in place and what purpose do they serve as normal microbiota?
Oral bacteria such as S. mutans and Lactobacillus are very sticky, so they adhere to gums and teeth
They suppress pathogens by competitive inhibition in the upper respiratory system
What are the predominant normal microbiota in the nostrils?
Staphylococcus aureus and S. epidermidis
Where might you find the following gram positive normal microbiota:
Staphylococci (S. epidermidis)
Micrococci (M. luteus)
Diphtheroids
Streptococci (both alpha and beta-hemolytic)
Pharynx and trachea
Where might you find the following potentially pathogenic microbiota in low numbers:
Streptococcus pneumoniae
Neisseria meningitidis
Haemophilus influenzae
Mycoplasmas
Nasopharynx
