Immunology Flashcards
Four Classes of Pathogens
- Viruses
- Bacteria
- Fungi
- Protozoans and Worms
Immunogen
Molecule than can induce an immune response Foreign (not a shared self molecule) Large (>10 Kda), complex molecule Biodegradable (not inert) Can be allergens, microorganisms, etc.
Antigen
Molecule that can be recognized by immune system components
Immunogens and haptens
Innate vs. Adaptive Immunity
Innate- initial response to immunogen; epithelial barriers, phagocytes, dendritic cells, complement system, and NK cells; non specific and no memory
Adaptive Immunity- more specific with memory and turns on after innate; B cells to make Ab, T cells to effector T cells (CD8/cytotoxic cells that kill specifically, CD4 are directors of immune response for immune system to be more effective)
Neutrophil
phagocytosis and activation of bactericidal mechanisms
in circulation
Eosinophil
killing of Ab-coated parasites
in circulation
Basophil
promotion of allergic responses and augmentation of anti-parasitic immunity
in circulation
NK Cell
releases lytic granules that kill virus infected cells
in circulation
Monocytes
immature form of macrophages
in circulation
Lymphocytes
cells of adaptive immunity B and T cells B cells produce Ab T cells exert cytotoxic or regulatory functions in circulation
Macrophage
phagocytosis and activation of bactericidal mechanisms, antigen presentation, and wound healing
located in the tissues
Macrophage are pro-inflammatory and dedicated to destroying the bacteria
Once the infection is killed you must remove the neutrophils, so the macrophages then clean up the area
Produce factor to attract fibroblasts to secrete ECM to regeneration of tissue can occur
Inflammation – vessels become more leaky
produce IL-1 and TNF alpha to adhere leukocytes to endothelium as well as increase number of ICAM proteins on endothelium
Dendritic Cells
antigen uptake in peripheral sites
antigen presentation
in the tissues
Mast Cells
release of granules containing histamine and active agents
in tissues
Present near blood vessels and beneath surfaces exposed to the external environment.
They can release preformed inflammatory mediators from cytoplasmic granules, such as histamine.
In addition, they can start synthesizing inflammatory compounds such as such as prostaglandin D2, leukotriene C4, growth factors and chemokines
Upon interaction with its receptors, histamine can induce vasodilation favoring leukocyte infiltration to the tissues
Primary Lymphoid Organs
Thymus and Bone Marrow
where cells are produced
Secondary Lymphoid Organs
Adnoids, tonsils, lymph nodes, appendix, spleen, Peyer’s patches in ileum
Where cells go
Acute Inflammation: Macroscopic vs. Histologically
Macroscopic appearance (clinical manifestation) is defined by the presence of redness, heat, swelling, pain and loss of function. Histologically, it is defined as the presence of edema fluid and the infiltration of tissues by leukocytes
Characteristics of Acute Inflammation
It lasts from minutes to a few days after the infection is sensed and is characterized by:
- local environment changes
- microvasculature activation
- leukocyte accumulation (mostly neutrophils)
Pathogen Recognition Receptors
Immune cells carry “pathogen recognition receptors” (PRRs) that detect molecules shared by various microbes.
These microbial molecules are named “pathogen associated molecular patterns” or PAMPS.
Examples of PAMPS are lipopolysaccharide present in gram negative bacteria; double stranded RNA generated by viral replication; or flagellin, a constituent of bacterial flagella
PRRs such as toll-like receptors (TLRs) interact with PAMPS and induce immune responses; TLRs are located on the plasma membrane or endosome membrane
Upon contact with their ligand, signaling events ensue in the cells
IL-1beta
activates vascular endothelium, lymphocytes, local tissue destruction, and increases access of effector cells
TNF alpha
activates vascular endothelium and increases vascular permeability, which leads to increased entry of IgG, complement, and cells to tissues and increased fluid drainage to lymph nodes
IL-6
lymphocyte activation and increased Ab production
CXCL8
chemotactic factor recruits neutrophils, basophils, and T cells to site of infection
also called IL-8
IL-12
activated NK cells
induces differentiation of CD4 T cells into TH1 cells
Extravasation
The body must undergo changes locally through vasodilation and increased vascular permeability in the area of the agent inciting the inflammatory reaction to allow white blood cells to accumulate
The white blood cells must then leave the blood vessel, cross the basement membrane, and be drawn to the area where they are needed. This process is called extravasation
The process by which white blood cells are drawn to the area where they are needed is referred to as chemotaxis
Increased permeability of capillaries as a result of histamine, kinins, and prostaglandins allows PMNs to migrate through the capillary wall to reach the bacteria. This migration is called diapedesis and takes several minutes to occur.
PMNs
Polymorphonuclear leukocytes: granulocytes such as basophils, neutrophils, eosinophils, and mast cells
PMNs can phagocytose microbes and can produce radical oxygen species to kill microbes
Carry antimicrobial enzymes to kill them
Neutrophils expel chromatin to immobilize microbials
Fever Inducing Cytokines
IL-6- induces acute phase protein production
IL-1beta- production of IL-6
TNF alpha- mobilization of metabolites and shock
Acute Phase Proteins
These proteins are synthesized by the liver and are nonspecific responses to microorganisms and other forms of tissue injury.
The liver synthesizes these proteins in response to certain cytokines, namely, IL-1, IL-6, and TNF, produced by the macrophage after exposure to microorganisms
Functions of Acute Phase Proteins
Some acute-phase proteins can act as opsonins, attaching to the surface of microbes and making them easier targets for phagocytosis
Other acute-phase proteins bind to the surface of bacteria and activate complement, which can directly kill bacteria and also promote inflammation
Complement Cascade
Proteolytic cascade that exerts antimicrobial activities by:
- increasing vascular permeability
- attracting phagocytes
- enhancing phagocytosis
- lysing microbes
Acute Inflammation Overview
Acute inflammation occurs before immune response
Vascular stage – arterioles and venules constriction then dilate; capillary permeability allows (redness, swelling, heat, pain, and loss of function) and as fluid leaves the capillary the blood becomes more viscous and clotting occurs
Cellular stage: phagocytic WBC and adhere to vessel wall and emigration occurs to blood and guided by chemotactic agents to infection; leukocytes phagocytose the bacteria
Products of phagocytosis and plasma and blood cells = exudates (serous fluid, WBC breakdown products, and debris)
Mediators are derived from cells or plasma; histamine are fond in mast cells, basophils, and platelets and released to cause dilation and increase permeability of vessels
Serotonin produces similar reactions
Precursors forms are always present by proteolytic enzymes activate them when necessary
Complement cascade: leukocytes chemotaxis, and phagocytosis
These responses lay the ground work before immune response really kicks in
Chronic Inflammation
If inflammation is over or signals continue = chronic inflammation can occur on joints, blood vessels, etc. and linked to MS, rheumatoid arthritis, cancer, heart attack, Alzheimer’s, etc.
If the offending stimulus cannot be rapidly removed, the inflammation tends to become chronic
Cellular infiltrates include primarily lymphocytes and monocytes/macrophages
Chronic bacterial infections may lead to the formation of granulomas (collections of macrophages surrounded by T cells)
Chronic viral infections lead to more diffuse inflammation, although macrophages and T cells are still present; response can be towards infectious antigens or even self antigens causing autoimmune issues
TLR-1 and TLR-2 vs. TLR-6 and TLR-2 Heterodimers
TLR1 and 2 recognizes triacyllipopeptides
TLR2 and 6 recognizes diacyllipopeptides
Both:
Ligands- mycobacteria (lipomannans), lipoproteins, lipoteichoic acids (gram positive), cell wall beta glucans (bacteria and fungi), and zymosan (fungus)
Cellular Distribution: monocytes, dendritic, mast, eosinophils, and basophils
TLR-3
on endocytic vesicles and recognizes double stranded RNA
Cellular distribution: NK cells
TLR-4
Recognizes LPS and lipoteichoic acids (Gram negative and positive respectively)
Cellular distribution: macrophages, dendritic, mast, and eosinophils
TLR-5
Recognizes flagellin from bacterial flagella
Cellular distribution: intestinal epithelium
TLR-7
Recognizes single stranded RNA and located on endocytic vesicles
Cellular distribution: plasmacytoid dendritic cells, NK, eosinophils, and B cells
TLR-8
Recognize single stranded RNA
Cellular distribution: NK cells
TLR-9
Recognizes unmethylated CpG oligonucleotides (bacteria and herpes virus) from bacterial genomes once degraded in the endosome
Located on endocytic vesicles
Cellular distribution: plasmacytoid dendritic cells, basophils, eosinophils, and B cells
TLR-10
Do not know what ligand it recognizes
Cellular distribution: plasmacytoid dendritic cells, basophils, eosinophils, and B cells
Macrophages: M1 vs. M2
M1 = inflammatory; example: CD68+
M2 = resolving or anti-inflammatory or healing; example: CD163+
M1 activity inhibits cell proliferation and causes tissue damage, while M2 activity promotes cell proliferation and tissue repair
Acute vs. Chronic Inflammation: Cell Involvement
Macrophages are involved in BOTH acute and chronic inflammation and is the MAJOR leukocyte involved in orchestrating inflammatory response
PMNs, basophils, and eosinophils play a key role acute inflammation
Lymphocytes are the players in chronic inflammation
Steps to Healing Process
- Within minutes after injury, coagulation occurs and the fibrin clot is formed.
- Inflammation is induced, characterized by early entry of neutrophils and subsequent macrophage accumulation, responsible for debris engulfment, bacterial killing, and trophic support.
- Fibroblasts invade the established fibrotic scar and produce a matrix.
- Granulation tissue is established and angiogenesis occurs.
- In the final step, re-epithelialization takes place, the extracellular matrix undergoes remodeling and contraction, while cellular components undergo apoptosis.
Morphology of Necrosis
Karyolysis: shrinkage of nucleus
Pyknosis: is the irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis
Kayorrhexis: breakdown/fragmentation of nucleus
Steps of Apoptosis
- commitment to cell death induced by extra/ intracellular factors.
- cell killing by activation of intracellular proteases(caspases).
- phagocytosis of apoptotic bodies.
- lysosomal degradation of apoptotic bodies
