Ch. 15 Immunology Flashcards
What are the physical barriers of the immune system?
Skin and mucosal membrane
Name the 4 infectious pathogens.
Parasites
Fungi
Bacteria
Viruses
Innate immune response
Nonspecific
Includes external and internal defenses, including inflammatory response
Adaptive immune response
Acquired, specific, learned
Ability to form immune “memory” from previous exposure
Function of immune system?
Defense against damaging molecules and foreign invaders
Primary lymphoid tissues
Thymus gland and bone marrow
Formation and maturation of immune cells
Secondary lymphoid tissues
Tonsils, lymph nodes in body, spleen
Interaction of mature immune cells with pathogens and initiation of immune responses
2 classes of cells in the immune system?
Adaptive
Innate
Adaptive cells
“Lymphocytes” (lymphoid stem cells)
B cells
- plasma cells
- memory cells
T cells
- Th cell
- Tc cell
Innate cells
“Granulocytes” (myeloid progenitor)
Natural killer cells
Neutrophil
Eosinophil
Basophil
Mast cell
Monocyte
- dendritic cell
- macrophage
Dendritic cells and macrophages are?
APCs (antigen presenting cells)
Macrophages are granulocyte and ____.
phagocytes
How are pathogens recognized?
Pathogen Associated Molecular Patterns (PAMP) recognized by Pattern Recognition Receptors (PRR) on the surface of macrophages
What is PAMP?
Pathogen Assoc. Molecular Patterns located on bacterium/foreign pathogen that a PRR on a macrophage will recognize
ex: LPS component of outer wall of G- bacteria (like E. coli)
What is PRR?
Pattern Recognition Receptors
Recognize PAMP; located on macrophages
Also located on most cells in body, but these notes are discussing macrophages
DAMPs
Danger/Damage Assoc. Molecule Patterns
PAMPs are just one type of DAMP
PRRs recognize molecules released by OUR own damaged or dying cells (DAMP)
Phagocytosis
- Macrophage comes into contact w/ pathogen
- Engulfment into phagosome
- Fusion w/ lysosomes
- Destruction
- Release of harmless molecules
Give a few examples of phagocytes and where they’re located in the body.
- Neutrophils (blood and all tissues)
- Monocytes (blood)
- Tissue macrophages (all tissues, including spleen, lymph nodes, bone marrow)
- Kupffer cells (liver)
- Alveolar macrophages (lungs)
- Microglia (CNS)
Macrophages have how many stages of activation?
3 stages of activation:
- resting/quiescent
- activated/primed
- hyperactivated
Macrophage Activation: Resting/quiescent
Stage 1
Clean up debris/garbage from cell death/turnover [dying cells release DAMPs too]
Macrophage Activation: Activated or Primed
Stage 2
In response to cytokines (IFN-gamma), macrophages take bigger “gulps,” express MCH-2 molecules for “antigen presenting”
Macrophage Activation: Hyperactivated
Stage 3
In response to DIRECT CONTACT with PAMPs (ex: LPS or mannose), becomes huge killing machine
Increase in:
-size, lysosomes, rate of phagocytosis, release of TNF, IL-1 (kill tumor cells, virus-infected cells, activates other immune cells) and oxidants (ex: H2O2)
Inflammation
Innate immunity - nonspecific response
Movement of neutrophils is tightly restricted to specific sites of injury
Circulating leukocytes interact with the vascular endothelium near the site of injury via specific molecular interactions with ____ ____.
Adhesion molecules
-these interactions are tightly regulated
What are 3 soluble factors which promote inflammatory response?
- Acute phase proteins
- Complement
- Opsonin function
Acute phase proteins
e.g. antibodies/other microbe binding proteins (opsonins), C-reactive protein; secreted by liver, circulate in plasma; some facilitate pathogen recognition by binding to “coated” bacteria, others are inhibitors of pathogen-secreted proteases
Complement
Plasma and membrane proteins
act as opsonins, cytotoxins (membrane attack complex [MAC]), stimulators of inflammatory cells
Opsonin function
An opsonin is a molecular “red flag’ which targets pathogens for attack/destruction
ex: antibodies, complement
How do antibodies also “opsonize” (decorate) pathogens?
Tages pathogen for destruction - “kill/eat”
Serves as molecular bridge between invader and phagocytic cell
Engagement w/ Fc receptor triggers activation of macrophage
Can block viral entry/post-entry replication
What are the 2 regions of an antibody?
Fc region
Variable region
Antibody defense is ____ is virus gains entry to host cell.
inadequate
Do plasma cells (subtype of B cell) have memory?
NO
Antibodies
Immunity is conferred by antibodies - immunoglobulin (Ig) proteins produced and released by B-lymphocytes (plasma B cells) - a given B cell “clone” produces antibody against a single, specific antigen
Antibody diversity generated by mixing and matching of several different types of DNA segments –> molecular design
–can create over 100 million different possible combinations
IgG composes __% of all antibodies
75%
The __ ___ ____ is a cell surface-resident version of the antibody molecule.
B cell receptor
____ region of the receptor linked by accessory proteins to signaling pathways which trigger B cell activation.
Cytoplasmic
What determines whether a B cell becomes a plasma or memory cell?
The way it’s activated
–if there’s a second signal requiring a T cell, the B cell becomes a memory cell
Memory cells require __ ____ dependent activation
T cell
Effector cells are known as?
Plasma cells
What are the 2 simultaneous signals B cell activation requires?
- clustering (“crosslinking”) of B cell receptors
2. binding to an activated helper T cell (T cell dependent activation) or by recognition of “danger molecules”
T/F: T cell dependent activation is required for B cell –> memory cell.
true
Acquired immunity and memory cells
Acquired immunity is specific, antibody dependent response
“memory cells” respond faster than naive cells - second exposure to antigen is faster and more robust than after first exposure
–this is why vaccines are useful
T cells: similarities w/ B cells
Surface receptors (TCR [T cell receptor]) - antibody like
Like BCR (B cell receptor), TCR also results from modular construction via gene shuffling/recombination
Like B cells, T cells also undergo clonal selection in response to specific antigen recognition
T cells: differences from B cells
B cells mature in bone marrow, T cells in thymus
BCR/antibody recognize any organic molecule, TCR recognize ONLY protein antigens
B cells can export (secrete) its BCR’s in form of antibodies, but TCR’s are restricted to surface of T cells
B cell can recognize an antigen “by itself” but T cells ONLY recognize antigens that are properly presented by another cell (antigen presenting)
TCR Proteins
Antigen recognition dependent on “presentation”
Antigen recognition proteins on membranes of T cells:
- 1) cannot bind directly to antigens
- 2) APCs, such as dendritic cells and macrophages, help T cells bind to antigens by processing and presenting them
Dendritic Cells
Originate in marrow and migrate to most tissue (esp. where pathogens might enter body)
Engulf protein antigens, partially digest them, and display polypeptide fragments on their surface for T cells to “see”
- a) antigen fragments assoc. w/ histocompatibility antigens
- b) secrete cytokines to attract T lymphocytes in secondary lymphoid organs
Once activated, T cells divide to form effector T cells and memory T cells
What are the classes of MHC molecules?
Class 1
Class 2
MHC molecules: Class 1
made by all cells except RBCs
Class 1 MHC molecules and foreign antigens presented together to activate cytotoxic T cells
Activate Killer T cells
MHC molecules: Class 2
Made by APCs and B cells
Class 2 MHC molecules and foreign antigens presented TOGETHER to helper T lymphocytes
Rule of 8s
Killer T cells have CD8 for MHC-1
Helper T cells have CD4 for MHC-2
Viruses
undergo constant mutation and gene shuffling, so immune memory of a given infection is no guarantee against future infections
–this is why flu shot is a yearly thing
Viral surface antigens contain Hemagglutinin (H) and Neuraminidase (N)
–ex: H1N1 (common human “A” flu strain) and H5N1 (“bird flu”)
How do viruses undergo mutations?
Occurs from antigenic shift (genetic shuffling) and antigenic drift (random mutation)
