Host Defenses Flashcards
Innate Response
functions in normal host without prior exposure to invading microbes
Adaptive Response
consists of antibody response, and lymphocyte-mediated response, tailored to particular microbial infection and characterized by memory
Constitutional Factors
of Innate Immunity
- makes one species innately susceptible and another resistant to certain infections
- genetics
- age
- metabolic factors
- neuroendocrine factors
- environment
Interferon
- type 1 produced by cells of the innate immune response or infected cells
- type 2 part of adaptive response
- play a role in anti-virus infections
Interferon-α/β
- type 1 interferons
- part of innate immune response
- antiviral action
- induce resistance to viral replication
- increase MHC class 1 expression and antigen presentation
- activate NK cells to kill virus infected cells
Phagocytic Cell Types
- neutrophils
- monocytes
- macrophages
- eosinophils
Lymphocytic Cell Types
- B and T cells
- NK cells
- plasma cells
Phagocytosis
1) bacterium becomes attached to membrane evaginations called pseudopodia
2) bacterium is ingested, forming phagosome
3) phagosome fuses with lysosome
4) lysosomal enzymes digest captured material
5) digestion products are released from cell
Neutrophils
- first responders in innate immunity
- primary function to phagocytize and kill extracellular bacterial and yeast pathogens
- involved in acute inflammation
- live 1 day in tissues
- bind and engulf bacteria, and destroy them with toxic contents of granules
Eosinophils
effective defense against helminths
NK Cells
- lymphocytes
- involved in viral infection
- stimulated by IFNs released from infected cells and dendritic cells
- on binding, release cytokines
- kill cells by releasing perforins and granzymes
NK Recognition of Infected Cells
- two receptor binding interactions
- activating receptor: binds to virus infection associated ligand
- blocking receptor binds to MHC 1 molecule to inhibit immune response
Classical Pathway
Activation Factors
- C1 binding to C-reactive protein on pathogen surface
- binding of antibody to antigen
Classical Pathway Steps
- Ab-Ag complex binds C1 qrs
- C1s cleaves C4 into C4a & C4b
- C4b attaches to target surface, C2 attaches to C4b
- Cls cleaves C2 into C2a & C2b
- results in C4bC2b = C3 convertase
- cleaves C3 into C3a & C3b
- C3b binds to C3 convertase
- forms C4bC2bC3b = C5 convertase
Lectin Pathway
Activation Factors
- mannose binding protein/lectin
- mannose binding lectin associated serine protease-2 (MASP-2)
Alternative Pathway
Activation Factors
- contact of microbial cell wall with C3
Alternative Pathway Steps
- C3b binds to microbial cell wall
- C3b bound by Factor B
- Factor B cleaved by Factor D to Ba &Bb
- results in C3bBb = C3 convertase
- C3 convertase stabilized by properdin
- C3 convertase binds to and cleaves C3 to C3a &C3b
- results in C3bBbC3b = C5 convertase
Terminal Pathway
- same for all pathways
- forms the MAC
- C5b binds to C6
- complex binds to C7
- complex binds to C8
- C5bC6C7C8 binds to a poly-C9 complex and completes the MAC
MAC
- membrane attack complex
- forms pores in the membrane of the target cells, allowing free movement of ions and water
- results in cell lysis and death
Results of Complement Activation
- lysis of target cell
- opsonization
- activation of inflammatory response
- clearance of immune complexes
Humoral Immunity
- part of adaptive immunity
- mediated by antibodies secreted by antigen activated B cells and their progeny plasma cells
- primary and secondary responses
Primary Humoral Response
- long inductive period/lag phase
- weaker response/magnitude
- utilizes IgM
Secondary Humoral Response
- shorter inductive period
- greater magnitude
- class switched IgM to IgG
Cell-Mediated Immunity
- part of adaptive immunity
- mediated by antigen activated T cells and the cytokines they secrete
- CD8+ T cells = cytotoxic T cells
- CD4+ T cells = helper T cells
Antibodies/Immunoglobulins
- two short and two longer chains joined by disulfide bonds
- react with specific antigens to form specific immune responses
- pepsin cleaves to 1 Fab’2 and 1 Fc
- pepain cleaves to 2 Fab and 1 Fc
Epitope
antigen determinant binding site on antigen
Paratope
antigen binding site on the Fab region of the antibody
B cells
- APC
- can recognize antigen without presentation by MHC
- creates clones to either fight specific antigen or serve as memory
MHC Class 1
- in all nucleated cells
- cytoplasmic intracellular infections
- present to CD8+ T cells (MHC restricted)
- also recognized by NK cells
MHC Class 2
- only in antigen presenting cells
- extracellular and intracellular vesicular infections
- present to CD4+ T cells (MHC 2 restricted)
Th1 Cells
- in cell-mediated immune response
- produce cytokines
- activate macrophages and neutrophils
Th2 Cells
- in humoral immune response
- recognize antigens presented by B-lymphocytes
- produce cytokines that promote antibody production
ADCC
- antibody dependent cell-mediated cytotoxicity
- cell-mediated immune response
- an effector cell lyses a target cell if it has been bound by a specific antibody
- NK cells, macrophages, neutrophils, eosinophils
