12 Integration of Immune response Flashcards
Immune responses to Cytosolic infection
processed and presented on MHC1
Immune responses Vesicular infection
(deliberately taken into cell by phagocytosis) – processed and presented on MHC2
why are there different immune responses to different types of infection
So the right T cells (CD4/CD8 activated)
Anatomic barriers
- Skin
- Oral mucosa
- Respiratory epithelium
- intestine
Complement/antimicrobial proteins (first thing activated-lectin pathway)
- C3
- Defensins
- Reg-3-gamma
Innate immune cells
- Macrophages
- Granulocytes
- NK cells
Adaptive immune cells
- B cells/antibodies
- T cells
Physical barriers
Skin
gut
lungs
eyes/nose/oral cavity
Skin - mechanical
longitudinal flow of air or fluid
mechanical – epithelia cells joined by tight junctions
skin - chemical
> fatty acids
> beta-defensins, Lamellar bodies, Cathelicidin
skin - microbiological
> normal microbiota
gut - mechanical
longitudinal flow of air or fluid
mechanical – epithelia cells joined by tight junctions
gut - chemical
low pH
> enzymes (pepsin)
> alpha-defensins, Reg3, Cathelicidin
gut - microbiological
> normal microbiota
lungs - mechanical
mechanical – epithelia cells joined by tight junctions
movement of mucus by cilia
lungs - chemical
> pulmonary surfactant
> alpha-defensins, cathelicidin
lungs - microbiological
> normal microbiota
eyes/nose/oral cavity -mechanical
> tears
nasal cilia
mechanical – epithelia cells joined by tight junctions
eyes/nose/oral cavity - chemical
> enzymes in tears and saliva (lysozyme)
> histatins, beta-defensins
eyes/nose/oral cavity - microbiological
normal microbiota
Innate Immunity -primary immune response stages
- epithelial barrier
- immediate local response (innate):
- complement proteins
- macrophages
phagocytes
- macrophage:
> phagocytosis and activation of bactericidal mechanisms
> APC - neutrophil:
> phagocytosis and activation of bactericidal mechanisms
Phagocyte recognition
- toll-like receptors
- C-type lectin receptors
- other PRRs: NOD-like receptors scavenger receptors, Fc receptors
Macrophage function
Activated macrophages produce numerous cytokines and chemokines
TNF
activation of local endothelium initiation of cytokine production; upregulation of adhesion molecules
IL-6
triggers production of acute phase proteins from liver, enhances antibody production from B cells; induces T-cell proliferation
IL-8
triggers neutrophil chemotaxis; chemotactic for basophils and T cells; activation of neutrophils promotes angiogenesis
IL-12
activates NK cells; polarization of T cells to T helper
Early induced response
innate and inflammatory
- inflammatory mediators from complement, macrophages, mast cells
- attract leucocytes and serum proteins (more complement)
Adaptive immune response
later adaptive response
- antigen carriage by dendritic cells to lymphoid tissue
- activation of specific T and B lymphocytes and antibody production
- recirculation to site of infection
Lymphocytes and Pathogens meet
Coordinated way for pathogens and cells to meet in the lymph node to activate the adaptive immune response
transport of antigen to lymphoid organs
Dendritic cells take up bacterial antigens in the skin and then move to enter a draining lymphatic vessel
Dendritic cells bearing antigen enter draining lymph node where they settle in the T cell areas
During migrating the dendritic cell changes it function from uptake to presentation, it starts to mature
T cell homing adhesion molecules
L selectin on surface
To leave blood circulation the express L selectin
Sit and wait in the lymph node
Naïve T cell and B cell homing
Circulating lymphocyte enters the high endothelial enters high endothelial venule in lymph node
Binding of L-selectin to GlyCAM-1 and CD34 allows rolling interaction
LFA-1 is activated by chemokines bound to extracellular matrix
Activated LFA-1 binds tightly to ICAM-1
what is the third signal for in T cell interaction with DCs
what T cell it becomes
Paracortex function
activation of specific T and B cells
- Activation of antigen-specific T cells by dendritic cells
- Activation of antigen-specific B cells by T cells
what is lymph node structure made of
paracortex
germinal centre
Germinal centre function
maturation of activated B cells
- Division
- Somatic mutation
- Class switching
- Formation of plasma cells and memory cells
what does class switching cause
increases defence effector functions
what does division cause
increases size of response
what does somatic mutation cause
increases affinity of the response
what is somatic mutation
immunoglobulin variable domains involves point mutations, resulting in amino acid changes that effectively increase or decrease the affinity of interaction with the antigen epitope
Tissue homing
Tissue homing of activated lymphocytes is determined by their expression of particular adhesion molecules (eg. integrins) and chemokine receptors
Leucocyte adhesion molecules involved in
Adhesion molecules involved in the selective homing of T cells to different tissues
Inducers of inflammation (amplifying events)
- C3a and C5a (anaphylatoxins)
- Mast cell products (e.g. histamine - immediate release, leukotrienes - delayed release)
- Prostaglandins (e.g. from macrophages and mast cells)
- Cytokines (e.g. from macrophages and T cells)
- Chemokines
