Intro to Immunology Flashcards
innate immunity
“Born with it” - Immunity that exists prior to exposure to a foreign
substance or pathogen (antigen) and is not improved by repeated
exposure to the same antigen. There is no/little immunological “memory”
Physical Barriers - epithelial surfaces:
-skin, lungs, GI tract, reproductive tract
- physical barriers with anti-microbial properties
Complement system:
- plasma proteins with anti-microbial properties, which are activated in
response to infection
Tissue-resident and circulating immune cells:
- macrophages, neutrophils, dendritic cells, etc., with capacity to kill
microbes and initiate an inflammatory response
adaptive immunity
State of immunity that is developed as a result of exposure to a foreign
substance or pathogen (antigen). It is specific for the particular antigen
and is enhanced following repeated exposure to the same antigen.
Immunological “memory”. This form is mediated primarily by
lymphocytes. Adaptive immunity will be explored in detail in subsequent
sessions.
properties of epithelial cells that contribute to innate immunity
Mechanical
- epithelial cells joined by tight junctions (skin, gut, respiratory tract, eyes)
- longitudinal flow of fluid (gut, urinary tract)
- mucociliary escalator (movement of mucus by cilia; airways)
- endothelial cells of the CNS (tight junctions)
Chemical
- low pH (gut)
- fatty acid secretions (skin)
- antimicrobial enzymes (lysozyme in tears, saliva, gut)
- antimicrobial peptides (defensins form pores in microbial membranes;
skin, gut, lungs)
Microbiological
- normal flora (skin, gut, respiratory tract)
complement system in innate immunity
Large number of circulating molecules that function in an enzymatic
cascade to:
i) induce inflammation - local increase in fluid (with plasma proteins
and white blood cells) to help combat infection
ii) opsonize pathogens - coat pathogen with molecules (fragments of
complement proteins) that promote uptake (phagocytosis) by
macrophages and neutrophils
iii) direct killing of microbes or infected cells - induce lysis
how is the complement system activated in innate immunity
The key points are that, regardless of the activation
mechanism, complement: i) Induces inflammation through the production of C3a,
C4a, and C5a. These diffusible factors can act on blood vessels and leukocytes
to induce inflammation. ii) C3b deposition (covalent attachment) on pathogen
surfaces can interact with complement receptors on leukocytes. This promotes
uptake and killing of the microbes. iii) The late steps of the complement cascade
can create the membrane attack complex (MAC) that leads to lysis of microbes.
This has been shown to be especially important in defense against Neiserria
species infections in humans.
neutrophils role in innate immunity
- often called polymorphonuclear (PMN) leukocytes
- short-lived (≈2-3 days), abundant cells of the circulation
- “flood” into sites of infection (inflammation), and engulf and kill microbes
macrophages role in innate immunity
- tissue-resident (derived from monocytes) in connective tissues,
mucosal tissues, liver, etc. - long-lived and present at the outset of infection; more can also be
recruited - initiate responses and serve many other roles, including direct killing
of microbes and facilitating adaptive immunity
acute inflammatory pathway
Cytokines and other mediators are
produced by macrophages, dendritic cells (not shown), mast cells, and
other cells in tissues in response to microbial products and damaged host
cells. These mediators increase the permeability of blood vessels, leading
to the entry of plasma proteins (e.g., complement proteins) into the
tissues and promote the movement of leukocytes from the blood into the
tissues, where the leukocytes destroy microbes, clear damaged cells, and
promote more inflammation and repair.
PRR
Pattern Recognition Receptors
recognize two general types of molecular patterns:
Pathogen-Associated Molecular Patterns (PAMPs) – molecules that
are unique to microbes. Example = components of the bacterial cell
wall.
- Damage-Associated Molecular Patterns (DAMPs) - “normal”
endogenous substances that are in the wrong place. Example = the
presence in the cytoplasm of proteins that normally reside in the cell
nucleus, indicative of cell damage.
TLR
a type of PRR - “toll like receptors”
Stimulation of these receptors on cells of
the immune system leads to activation of those cells. Effects include:
↑ microbe-killing capacity of phagocytes
↑ cytokine secretion (usually pro-inflammatory)
- Induction of a virus-resistant state (type I interferons)
- Enhance ability to activate adaptive immunity
NLR
a type of PRR - “NOD like receptors”- cytosolic pattern recognition receptors
>20 genes in humans
- activation by interaction with microbe-derived ligands (PAMPs) or
DAMPS produces multiple downstream signals - typically proinflammatory
- some family members activate the “inflammasome”, an enzyme complex
that activates IL-1beta. This cytokine produces a robust inflammatory
response
Outline the path of lymph flow, including the major lymph vessels and the
regions they drain. Explain a major clinical implication of the asymmetric
pattern of lymph drainage.
Explain the special anatomic features that reflect the function of lymph
nodes as filters of lymph, and spleen as filter of blood. Apply this
information to understanding causes of lymphadenopathy and
splenomegaly.
Describe the pathways that lymphocytes use to travel between blood and
tissues, and compare to pathways used by other WBCs.
White blood cells originate in bone marrow and circulate in blood,
but they function in tissues. WBCs leave blood and enter tissues
by passing through the walls of post-capillary venules in a
process called diapedesis. Post-capillary venules are the most
leaky part of the blood vascular system (even more leaky than
most capillaries). Diapedesis occurs in response to chemotactic
factors (inflammatory mediators) produced in tissues: gaps form
between endothelial cells lining post-capillary venules and postcapillary venule endothelial cells express surface receptors that
bind to white blood cells and promote their transfer across the
endothelium and into connective tissue.White blood cells originate in bone marrow and circulate in blood,
but they function in tissues. WBCs leave blood and enter tissues
by passing through the walls of post-capillary venules in a
process called diapedesis. Post-capillary venules are the most
leaky part of the blood vascular system (even more leaky than
most capillaries). Diapedesis occurs in response to chemotactic
factors (inflammatory mediators) produced in tissues: gaps form
between endothelial cells lining post-capillary venules and postcapillary venule endothelial cells express surface receptors that
bind to white blood cells and promote their transfer across the
endothelium and into connective tissue.White blood cells originate in bone marrow and circulate in blood,
but they function in tissues. WBCs leave blood and enter tissues
by passing through the walls of post-capillary venules in a
process called diapedesis. Post-capillary venules are the most
leaky part of the blood vascular system (even more leaky than
most capillaries). Diapedesis occurs in response to chemotactic
factors (inflammatory mediators) produced in tissues: gaps form
between endothelial cells lining post-capillary venules and postcapillary venule endothelial cells express surface receptors that
bind to white blood cells and promote their transfer across the
endothelium and into connective tissue.Like other white blood cells, both naïve and memory lymphocytes
leave the blood to enter loose connective tissues throughout the
body by passing through the walls of post-capillary venules.
Unlike other wbc’s, lymphocytes can then leave connective
tissues and re-enter the blood circulation. They do this by
entering lymphatic capillaries and traveling in lymphatic
vessels back to the blood.
Explain the difference between primary and secondary lymphoid organs.
Like other white blood cells, both naïve and memory lymphocytes
leave the blood to enter loose connective tissues throughout the
body by passing through the walls of post-capillary venules.
Unlike other wbc’s, lymphocytes can then leave connective
tissues and re-enter the blood circulation. They do this by
entering lymphatic capillaries and traveling in lymphatic
vessels back to the blood.
Distinguish lymphoid follicles from thymic lobules, both structurally and
functionally
The thymus, like the bone marrow, is not involved in the
generation of immune responses against foreign antigen. It is the
site of proliferation and maturation of T lymphocytes: In the
thymus, T lymphocytes acquire markers characteristic of distinct T
cell subsets (ie. helper, cytotoxic, suppressor), and T cells “learn”
discrimination between self and non-self, through deletion of cells
recognizing self antigens. (Note not all T cells recognizing self
antigen are deleted in the thymus; some enter the circulation and
are deleted peripherally – more on this with Immune Path and in
I&I).
Regardless of category, all of the secondary lymphoid tissues
have as a fundamental unit of organization the lymphoid follicle
(= lymphoid nodule).
An active lymphoid follicle has a germinal center and a
surrounding peripheral zone called the mantle. B and T
lymphocytes have a characteristic distribution with respect to
these two regions:B cells are concentrated in germinal centers and in the inner
region of the mantle. (B cells surrounding, but not in, germinal
centers tend to be memory cells). T cells predominate in the outer
mantle of lymphoid follicles.
