L11 Flashcards
Defense against pathogens is the
principal physiologic function of the immune system
Involves both the innate and adaptive immune response
Different pathogens trigger
distinct immune responses and effector mechanisms
Pathogens have mechanisms to
evade the immune response
INNATE IMMUNITY
MACROPHAGES
NEUTROPHILS
COMPLEMENT SYSTEM
ADAPTIVE IMMUNITY
B cells and Antibody (IgG) T cells (indirect help by helper CD4+ T cells)
Neutrophils and Macrophages will
remove particulate antigen by phagocytosis
HIGH AFFINITY RECEPTORS: Mannose receptor
- binds mannose on microbial cell wall mediating cell-microbe binding and initiating phagocytosis
HIGH AFFINITY RECEPTORS: Mac-1 Integrin-
Binds microbes opsonized with complement proteins
HIGH AFFINITY RECEPTORS: Scavenger receptor-
binds microbes in a non-mannose specific manner
Opsonin –
derived from a Greek word meaning “to prepare for eating”.
Antibodies
Complement Proteins
Lectin
OPSONIZATION of a microbe occurs when it is
coated/bound by an opsonin to target it for phagocytosis (mediates binding to phagocyte receptors).
More efficient than mannose receptor mediated phagocytosis
Enhances inflammation and antimicrobicidal activity
RNI=
REACTIVE NITROGEN INTERMEDIATES Nitric Oxide (NO)
Exaggerated/strong activation of macrophages and neutrophils can
injure normal host tissue by release of lysosomal enzymes ROS and NO
Microbicidal products do not distinguish between self tissue and microbes or normal tissue and infected tissue
CD8 +T cell role in
immunity against intracellular microbes
CD8+T Recognize
antigen in a MHC I restricted manner
CD8+T called
CALLED CYTOTOXIC T CELLS as they secrete perforin and granzymes which will directly lyse/kill infected cells
Very important for anti-viral immunity
CD8+T Secrete
cytokines such as IFN-g and TNF-a
CD8+ T cells also
kill phagocytes which have engulfed microbes
Macrophage: Remove
particulate Antigen by phagocytosis
Followed by production of ROS and RNI
Macrophage: Take up soluble antigen, process and present antigen to
T cells
Macrophage secrete
pro-inflammatory cytokines (IL-1, IL-6, TNF-a) and chemokines (CCL2, CXCL1, etc) that induce inflammation and immune chemotaxis
Induced through the recognition of microbial byproducts by Toll-like receptors (TLRs) and Nod-like receptors (NLRs)
Which Th cell would be needed against intracellular infections?
Th 1
Neutrophil: Migrate toward the site of
inflammation within an hour of tissue injury in response to chemotactic factors
IL-8
IFN-g
C5a
Neutrophil Effectively phagocytose
microbes
Can eliminate microbes via ROS and RNI
Neutrophils Can also kill microbes by
oxygen independent mechanisms DEGRANULATION (release of granuoles) Defensins Myeloperoxidase Neutrophil extracellular traps (NETs)
Role of COMPLEMENT in Immunity against Extracellular Microbes:
Serves as an opsonin and enhances phagocytosis by phagocytes
Serves as a chemokine and recruits and activates leukocytes to the site of inflammation
Forms the membrane attack complex (MAC) and mediates lysis of the microbe
B cells produce
antibody
Neutralization
Opsonization
Memory
B cells express
MHC II and can present antigen to T cells
Bacterial products can directly
activate B cells in a T cell independent manner
CD4+ T cells can also make
inflammatory cytokines (IFN-g and TNF-a)
These cytokines activate macrophages and promote phagocytosis, bacterial killing and inflammation
Called Th1 cells when they make these inflammatory cytokines
CD4+ T cells (helper T cells) produce
cytokines (IL-4, IL-5 and IL-10)
These cytokines are B cell growth factors which activate B cells and promote antibody production
Called Th2 cells when they make these B cell promoting cytokines
Which Th response is more important during extracellular defense?
Th 2
Mechanisms of Immune Evasion by extracellular bacteria
Antigenic variation
Inhibition of complement activation (many bacteria)
Resistance to phagocytosis (e.g. Pneumococcus)
Scavenging of ROS (e.g. catalase-positive Staphylococci
Facultative intracellular pathogen can
survive inside host cells to evade the immune system
Obligate intracellular pathogen MUST
INFECT HOST to survive
Injury caused by
host immune response
Deleterious effects on host immune system
IMMUNITY TO INTRACELLULAR PATHOGENS
Both innate and adaptive immune response are involved
Cell mediated immune response is dominant rather than antibody response
Pathogens have mechanisms in place to survive and replicate within host cells (e.g. phagocytes)
Disease and resulting pathology are a consequence of the host’s immune response to the infectious agent
INNATE
Dendritic Cells (APC) Natural Killer (NK) cells Macrophage/Neutrophils
ADAPTIVE
CD4+ T cells (helper T cells)
CD8+ T cells (cytotoxic T cells)
DENDRITIC CELL
Professional APCs that present Ag to T cells
Carry Ag from site of infection to lymph node where they will present Ag to naïve T cells
Produce cytokines such as IL-12 that regulate the differentiation of CD4+ T cells (promote either Th1 generation or Th2 generation)
NK CELL
Main function is to kill virus infected cells (and tumor cells)
Secrete cytokines (IFN-g) required for macrophage and Th1 development
Activation of NK is regulated between signals from activating and inhibitory receptors
CD4 +T cell role in immunity against intracellular microbes
Recognize Antigen in a MHC II restricted manner
CALLED HELPER T CELLS as their main role is to help coordinate the responses of other immune cells
Differentiate into Th1 or Th2 subsets producing distinct cytokines with distinct biological activity
Th1 CD4+ T cells produce IFN-g and TNF-a and promote cell mediated immunity
PROVIDE HELP TO CD8+ T CELLS AND MACROPHAGES
Th2 CD4+ T cells produce IL-4 and promote antibody mediated immunity
PROVIDE HELP TO B CELLS
