Immunology Lec 5 - Innate-Adaptive Immunity Interface Flashcards
1
Q
failure of the innate immune system and what happens as a result
A
- In many circumstances, innate immune responses are sufficient to clear an infection
- When these fail, more potent, adaptive immune responses are required
- The triggers for an adaptive immune response are antigens
2
Q
antigens; triggers of the adaptive immunity
-what are antigens
-receptor construction
-what can antigens be
-derivation
A
- Antigens are macromolecules that induce adaptive immune responses via recognition by specialized receptors on lymphocytes
- Receptors for antigens are constructed in such a way that the
immune system is potentially capable of recognizing the so‐called “antigenic universe” - Antigens can be any macromolecules, including proteins (recognized by B and T cells), lipids or carbohydrates (recognized by B cells only)
- Although usually derived from pathogens, they can also be from
other sources such as food, dust, pollen and transplanted tissue; if
self‐derived macromolecules are inappropriately perceived as
dangerous (these are called autoantigens), autoimmune disease may develop; in contrast, a positive form of autoimmunity would be
elimination of cancerous cells by targeting tumor‐derived antigens
3
Q
antigenicity; what is it, correlation, proteins, lipids, carbs
A
- Antigenicity = ability to act as an antigen (induce an adaptive immune response)
- Antigenicity tends to correlate with:
‐the size of the molecule
‐the degree of foreigness: (xenoantigen 1 > alloantigen 2 > autoantigen) - Polysaccharides can be poor antigens because they can degrade quickly ; glycoproteins (oligosaccharides bound to proteins) tend to be more antigenic
- Lipids are relatively conserved; therefore, tend to be poor antigens (too much like self); glycolipids and lipoproteins are more antigenic
- Proteins are the best antigens (the immune system is optimized to process and present protein‐derived antigens)
- The adaptive immune system must be able to recognize the shape of an antigen (i.e., its conformation); so, molecules that are structurally unstable are not good antigens (e.g., gelatin)
- Polymers that cannot be degraded by cells cannot be presented to the adaptive immune system; therefore, stainless steel bone pins and plastic heart valves are non‐antigenic
4
Q
antigen vs epitope; what are they, antibody, T cell
A
Antigen:
* A molecule in its native form that
is recognized by a B or T cell
Antibodies:
* Recognize molecules (antigens) in
their native form but bind to only a portion of the molecule (the epitope; in its native 3‐D form)
* Can recognize proteins, polysaccharides and lipids
Epitope:
* The small portion of an antigen that
directly binds to a B or T cell receptor
T cells:
* Recognize linear peptide fragments
(epitopes), derived from processed antigens, that are presented by MHC class I or II
* Recognize only protein‐derived epitopes
5
Q
hapten; what is it, what can it contribute to, why does it matter
A
- A molecule that is too small on its own to function as an antigen
- However, if coupled to a larger carrier molecule, it can contribute to the formation of a novel epitope that wasn’t present originally
Why does this matter?
* One important reason is that haptens can have important clinical
implications (two molecules that the immune system usually ignores become immunogenic)
6
Q
clinical relevance of haptens; penicillin allergies
A
- The case of penicillin allergies
- The antibiotic penicillin is a hapten because it is too small to be recognized by the adaptive immune system
- In the body, penicillin gets broken down
- One component, penicillanic acid, can bind to otherwise inert proteins like albumin
- This can potentially create a new
epitope that otherwise is not present on the albumin - If an epitope is formed by the
“penicilloyl‐protein complex”, it can
induce an acquired immune response - Sometimes these responses manifest as allergic reactions
7
Q
clinical relevance of haptens; allergic contact dermatitis
A
Why is contact with poison ivy a problem?
* Urushiol is a component of sap produced by the poison ivy plant
- It is a hapten (non‐antigenic on its own)
- When skin comes in contact with poison ivy, urushiol is transferred
- Urushiol binds to proteins in the skin
- This causes skin proteins to be perceived as foreign and dangerous
- The immune system responds to the skin proteins the same way it
would respond to a skin graft - The result is what is known as
“allergic contact dermatitis”, which
causes an uncomfortable skin rash
8
Q
antigens; cross reactivity
A
- Sometimes different proteins have identical/similar epitopes
- This can lead to an adaptive response against one antigen cross‐
reacting with a different one
———————————————-
Example #1: blood typing - Gut microbes often express glycoproteins that are similar to those expressed on red blood cells
- Antibodies produced against the microbial antigens can cross‐react with blood group antigens
- ## This is often the cause of transfusion reactions (rejection of mismatched bloodExample #2: Brucellosis
- In cattle, antibodies against Yersinia enterocolitica can sometimes cross‐react with Brucella abortis; the former is non‐problematic, latter is a reportable disease
- Brucella testing is via detection of antibodies in serum
- Cross‐reactive antibodies could result in false positives and erroneous culling of cattle
9
Q
dendritic cells; examples, APCs, important for what
A
- Antigens trigger adaptive immunity but they must be presented to B and T cells
- Macrophages, B and dendritic cells can process and present antigens in the context of major histocompatibility complex (MHC) molecules, which are required for the activation of T cells
- These three cell types are known as professional antigen‐ presenting cells (APCs)
- All three cell types can re‐activate antigen‐experienced (i.e. previously activated) T cells
- However, dendritic cells are, by far, the most efficient at activating
naïve T cells - Therefore, dendritic cells are the most important APCs in the induction of a primary immune response
10
Q
kinetics of an immune response
A
- Remember that in addition to being APCs, dendritic cells are also sentinel cells
- This means that the initiation of an adaptive immune response can occur in parallel with innate responses
- This is important because it takes longer for adaptive effector functions to become operational
11
Q
the origin of dendritic cells
A
- The so‐called “classical” dendritic cells (cDCs) are derived from the myeloid lineage; hence, they are sometimes called myeloid (or myeloid‐derived) DCs or monocyte‐derived DCs or type 1 DCs (DC1 cells)
- Similar to macrophages, cDCs are sometimes given unique names, depending on their anatomical location (e.g., follicular DCs are in B cell follicles of lymphoid tissues; Langerhans cells are DCs located in the skin)
- Plasmacytoid DCs (pDCs) are
derived from the lymphoid lineage and are sometimes called type 2 DCs (DC2 cells) - pDCs specialize in responding to viruses by producing large quantities of type I interferons (initiate anti‐viral programs in cells)
12
Q
immature dendritic cells
A
- DCs in an immature state are distributed throughout the body and
specialize in capturing and processing antigens - If capturing non‐dangerous antigens, DCs remain immature
- Immature DCs promote immunological tolerance
- T cells that recognize antigens presented by immature DCs are typically rendered tolerant or die; this prevents responses against self‐antigens
- If antigens are acquired in the context of danger signals (PAMPs/DAMPs), DCs will mature into potent APCs by upregulating expression of molecules required for activation of T cells
13
Q
dendritic cell trafficking
A
- DCs survey tissues throughout the body
- If they encounter antigens in a dangerous context, they need to present antigen‐derived epitopes to T cells to initiate an adaptive immune response
- Lymphoid tissues, such as lymph nodes, are specialized antigen‐
presenting areas - Tissue‐resident DCs traffic to lymphoid tissues where naïve T cells
concentrate - The co‐localization of DCs and T cells facilitates efficient antigen
presentation
14
Q
dendritic cell maturation
A
- En route to secondary lymphoid tissues, DCs undergo a maturation process
- Maturation involves the upregulation of molecules that are required to activate naïve T cells
-start with DC precursor in bone maarow, immature DC in tissue, mature DC in lymphoid organs
-IL1, TNF-a and especially HMGB1 are key mediators of DC maturation **
-DCs acquire antigens and present them to T cells
15
Q
histiocytomas
A
- Histiocytomas are benign tumours that are sometimes seen in dogs
- They are caused by excessive proliferation of macrophages or
dendritic cells in connective tissues
(collectively, these cells are also known as histiocytes) - Langerhans cells (specialized DCs in the skin) are often a cause
