Intro Host Defenses 1/5/15 Flashcards
What are the functions of the immune system?
- Distinguish self from nonself
2. Protect the body from invading infectious organisms (parasites, bacteria, fungi, virus)
Components of immunes system
microbes, innate, adaptive, barriers
characteristics of innate immunity
- it is preformed
- nonspecific
- no immunological memory
- does not improve overtime
(often unsuccessful in killing infection; adaptive kicks in)
components of innate immunity
- barriers like skin and mucous
- cells of innate defense (neutrophils, monocytes, macrophages, dendritic cells, natural killer cells)
- animicrobial peptides and proteins like complement and c- reactive poteins
characteristics of adaptive immunity
- very specific
- slow onset
- highly effective
- has immunonlogical memory
- improves overtime
B Lymphocytes
lymphocytes that undergo differentiation in the bone marrow
produce antibodies and immunoglobins (IG)
What are antibodies?
Antibodies are protein molecules that bind to antigens
Antigens derived from microbes
T lymphocytes
lymphocytes that differentiate in the thymus
produce cytokines and interleukins (IL)
cytokines do not bind to antigen, they sstimulate or suppress cells of the innate and adaptive immunity
Neutrophils (PMN)
- multilobed nuclei
- phagocytize and kill organisms internally
- short life (live for a day; die; new ones are created from bone marrow)
Monocytes
- kidney shaped nucleus
- phagocytize internally
- more effecient in controlling internal pathogens
- leave circulatory system and migrate to organs become macrophages
Macrophages
- differentiated monocytes
- live longer than monocytes (months to years)
Dendritic Cells
- also differentiated (similar to macrophages)
- found in tissues
- have long membrane extensions
- capable of both phagocytosis and pinocytosis
- can (along with macrophages) present antigens (CD14) with t lymphocytes to initiate the adaptive immunity response
most efficient antigen presenting cells
What is antigen presentation?
The protein antigens produced or secreted by the microbes are usually complex in nature and are of high-molecular weight.
T cells cannot recognize the protein antigens in their native state.
The complex protein antigens should be internalized by dendritic cells and macrophages and within the intracellular compartment, the protein antigen is broken into a simple antigenic peptide.
The antigenic peptide is then conjugated with major histocompatibility class molecule (MHC) and then presented on the cell surface for recognition by T cells.
MHC molecules
self antigens
well tolerated by immune system
expressed on cell surface of nucleated cells
classes of MHC molecules
MHC class I, II and III. T cells can only recognize processed antigenic peptides expressed in conjunction with either MHC class I or II molecules on the cell surface of dendritic cells.
Why do neutrophils only participate in innate immunity?
neutrophils exclusively participate in innate defenses because they cannot present the antigens.
Lactoferrin
antimicrobial peptide
- present in neutrophils and macrophages
- major iron-sequestering protein.
- limits availability of free iron which starves pathogen and kills it
Defensins
- α-defensin is produced by neutrophils and panneth cells. - β-defensin is produced by epithelial cells in the lungs. Defensins are positively charged molecules and hence they are cationic proteins and they bind to negatively charged bacterial surface and induce lysis of the bacterial cell.
complement
- 30 or more
- Proteins include C1 through C9, factors B, D, and P, andregulatory proteins
- get activated when there is an antigen- antibody reaction
- infection in gram negatie releases LPS
- infection in gram posistive or fungus releases mannose
- complete activation causes lysis of bacteria
Complement activation pathways
- Classical pathway: activation of C1 followed by C4, C2= C142 activates C3; which activates C5, (6,7,8, 9) (membrane attack complex)
- Alternate Pathway activation of C3 by LPS activates C5,6,7,8,9 and lysis of bacteria
- In mannose lectin pathway, mannose than binds to the host protein lectin. This complex activates C4 followed by C2. The C42 complex activates C3.
C3 activation result in subsequent activation of other complement factors and formation of membrane attack complex. Complement thereby contributes to innate immunity.
- Alternate Pathway activation of C3 by LPS activates C5,6,7,8,9 and lysis of bacteria
Complement as opsonins
Complement along with antibodies enhances the phagocytic ability of the neutrophils and monocytes. Phagocytic cells have receptors for complement and antibodies on their cell surface. When the bacterial surface is coated with complement (or antibodies), then the complement on the bacterial cell surface binds to the corresponding receptors on the macrophage cell surface resulting in easy and enhanced uptake of the bacteria. This process is called opsonisation. In this case complement and antibodies are called opsonins.
C- reactive proteins
proteins produced by the liver cells can bind to cell surface of Staphylococcus and inactivate the bacteria
Natural Killer Cells
These are large granular lymphocytes that usually do not phagocytose the bacteria but lyse the abnormal cells such as cancer cells and microbe-infected cells.
MHC classes on leukocytes
MHC class II, expressed on the surface of leukocytes. Down-regulation of MHC Class I molecules on leukocyte cell surface will activate NK cells to induce lysis of target cells such as cancer cells or infected cells.
Cancer cells and virus-infected cells down-regulate the expression of MHC-Class I molecules leading to lysis by NK cells.
Perforin and Granulysin
One of the well understood mechanism by which NK cells induce lysis of target cells will be by producing antimicrobial peptides such as perforin and granulysin. Perforin creates pores on the cell surface of the target cells thereby facilitating the entry of granulysin into the target cells. Granulysin kills the target cells and the intracellular microbe.
