Lect 5 & 6 - Immunopathology Flashcards
What systems make up the adaptive immune system?
Humoral and cellular parts
What systems make up the Innate immune system?
Barrier and Chemical Mechanisms, PRR, and cellular (Phagocyte and Natural killer response)
what antimicrobial peptides are there?
-Defensins, cathelin, protegrin, granulsyin, histatin, probiotics, secretory leukoprotease inhibitor
what are the different pathways of the compement system?
classic, alternative and MB-Lectin
what pattern recognition receptors (PRR) are there?
TLRs, NLRs, RLRs, CLR’s, and scavenger receptors.
NOTE PRR is like a primitive version of antibodies that evolved first and allowed recognition of DAMPS ( damage-associated molecular patterns) and PAMPS ( pathogen-associated molecular patterns ).
Each healthy immune cell carries identical receptor of a given type
what different types of PRRs are there?
Cell surface (transmembrane) and intracellular receptors – TLRs, NLRs, RLR’s and CLR’s Fluid-phase soluble molecules (Mannose receptors)
What role do Mannose receptors fill?
primarily present on the surface of macrophages and dendritic cells.
It provides a link between innate and adaptive immunity.
It recognizes and binds to repeated mannose units on the surfaces of infectious agents and its activation triggers endocytosis and phagocytosis of the microbe via the complement system.
remember to look up and remember the complement system.
DO IT
what pathway in the complement pathway is triggered by Antigen antibody complexes?
classical
what pathway in the complement pathway is triggered by Mannose binding lectin?
MB - lectin
what pathway in the complement pathway is triggered by pathogen surfaces?
It can be triggered by foreign materials and damaged tissues. Also by C3b, therefore kicks in when other pathways are triggered too.
What are the final products of the complement system?
MAC lysis of pathogens.
C3b also causes the Opsonization of pathogens
C3a and C5a mediate inflammation and cause phagocyte recruitment.
what does the cytokine IL1 do?
comes from macrophages/epithilia and causes coagulation, acute phase proteins, inflammation along with fever.
what does the cytokine TNF do?
comes from macrophages and T LYMPHOCYTES. causes coagulation, inflammation, acute phase proteins, fever
AND ACTIVATES NEUTROPHILS
what does the cytokine IL6 do?
comes from macrophages endothelia and T LYMPHOCYTES.
causes acute phase proteins, and PROLIFERATION OF B LYMPHOCYTES. This is one of very few cytokines of innate immunity which affect B cells. most of the B cell affecting cytokines are cytokines of adaptive immunity.
what does the cytokine IL23 do?
released from macrophages and dendritic cells.
Targets T Lymphocytes and induces CD8+ memory T cells to proliferate. also
CAUSES RELEASE OF IL17. this cytokine causes release of many others and also prostaglandins - important in inflammation.
what term is used for lymphocyte replication
clonal expansion
where do B cells and T cells develop
B - Bone marrow
T - Thymus
where do mature lymphocytes go? (the secondary lymphoid organs)
White pulp of the spleen
Lymph Nodes
Mucosal Surfaces
what is the range of antigentic variability?
10 to the 9.
what is the name for a antigen receptor?
Immunoglobulin
describe the mechanism of antigen presentation
Antigens are internalised
Broken down to peptides
Peptides associate with newly synthesised Class 2 molecules and are brought to the cell surface.
If the peptides are foreign they are recognised by helper T cells which are then activated.
Helper T cells produce cytokines needed by B cells, T cells , etc.
what do class 1 and class 2 MHCs do?
MHC class 1 proteins present peptides to cytotoxic T cells MHC Class 2 proteins present peptides to helper T cells
why do we have MHC?
T cells will only see antigens in association with MHC Proteins. essential part of how their receptors work. the antigens are bundled with the MHC on the surface of APCs.
what parts of the T cell helper receptor are there that bind on to the B cell?
T cell CD40L -> B cell’s CD40
TCR + CD4 -> B cell’s MHCII
IL2/4/5 released also recognised by B cells ILR.
what are the functions of Killer or cytotoxic T lymphocytes?
Killer or cytotoxic T lymphocytes are able to kill. Cellular immunity
what are the functions of Helper T lymphocytes
secrete growth factors (cytokines) which control immune response: Help B lymphocytes and T lymphocytes
what do suppressor T lymphocytes do?
damp down immune response
what do B lymphocytes?
develop potential to secrete antibodies: humoral immunity
what does the binding of antibodies to antigens do to them/
neutralizes them (eg. blocking viral binding sites) Agglutination - causes them to clump together, and Precipitation out of their solutions. also activates compliment system all of these aspects HELP PHAGOCYTOSIS
how do cytotoxic cells kill their targets?
They attach to the non self antigens on the cell surface, and then release PERFORIN, an enzyme which makes holes in the cell’s membrane.
at the same time, the T cell releases enzymes which promote apoptosis in the target cell, and these enzymes cross the target’s membranes through these newly created holes.
describe the receptors between an APC and a helper T cell
APC MHC II -> t cell TCR and CD4
APC CD80 -> T cell CD28
what type of cell has CD4 and what type has CD8? what do they bind to?
CD8 is found on killer cells. CD8 binds onto MHC CLASS 1
CD4 is on helper cells. it binds to MHC CLASS 2 being presented, either by the APC or B cells.
what do dendritic cells do?
similar to macrophages. can activate helper (CD4) T cells by acting as a APC with their MHCII.
what do IL2,4,5,13,17 and INF gamma have in common?
they are cytokines of ADAPTIVE IMMUNITY. these all have effects on B cells such as isotype (immunoglobilin) switching or proliferation.
What is Hypersensitivity
Undesirable, damaging, discomfort-producing and sometimes fatal reactions produced by the normal immune system (directed against innocuous antigens) in a pre-sensitized (immune) host.
how many types of hypersensitivity are there and what are they?
TYPES I - IV
I - IgE MEDIATED REACTION (anaphylactic)
II - CYTOTOXIC REACTION
III - IMMUNE COMPLEX REACTION
IV - CELL MEDIATED REACTION (DTH)
what happens in a type one (anaphylactic) hypersensitivity reaction?
IgE Ab mediated mast cell and basophil degranulation- release of lots of inflammatory mediators.
Common antigens are:
Pollen, bee venom, animal dander
Associated diseases
Hay fever, allergic asthma
what is a severe type 1 hypersensitivity reaction called?
ANAPHYLAXIS
what parts of the body are affected in type 1 hypersensitivity reactions?
smooth muscle, blood vessels, mucous glands, platelets, sensory nerve endings, eosinophils.
what causes release of IMMUNOGLOBULIN E?
Produced by plasma cells from class-switched B cells under the control of IL-4 and CD40L - CD40 interaction
what preformed mediators are released in a type 1 hypersensitivity reaction
HISTAMINE
Stimulation of irritant nerve receptors
Smooth muscle contraction
Increase in vascular permeability
KALLIKREIN
Activates bradykinin - similar actions to histamine
note that type 1 hypersensitivity reactions also release lipid mediators. what does this in turn cause?
release of LEUKOTRIENES
and PROSTAGLANDINS
what do basophils and eosinophils do?
in hypersensitivity,
BASOPHILS
Similar properties to mast cells over longer time scale
EOSINOPHILS
GRANULES contain cytotoxic proteins (e.g. Eosinophil Cationic Protein)
Attracted to sites of allergic inflammation by CHEMOKINES (e.g. Eotaxin 1/2)
In tissues, RELEASE CONTENTS OF GRANULES - major source of tissue damage in allergic response
what do T cells do in a type 1 hypersensitivity reaction?
Involved in both EARLY and LATE response to allergen
Cytokine production by activated T cells critical in ongoing response
what examples of allergic diseases are there that cause type 1 hypersensitivity reactions?
ASTHMA
RHINITIS
DERMATITIS
FOOD ALLERGY
what is a hypersensitivity type 2 reaction?
cytotoxic reactions
Activation of the complement cascade resulting in cell lysis
immunoglobulin/C3b results in opsonisation and phagocytosis of healthy cells
what initiates a type 2 reaction?
Initiated by IgM (WHICH CAN BIND TO COMPLEMENT SYSTEM) or complement-binding IgG
What diseases or problems cause a type 2 hypersensitivity reaction?
Blood group incompatibility
Autoimmune haemolytic anaemias
Affecting neutrophils
Affecting platelets
describe HYPERSENSITIVITY - TYPE III
similar to type 2
IgG binds to an antigen, and the complex kicks off the complement fragments.
these cause neutophils to come and also causes Opsonisation.
ATTEMPTED PHAGOCYTOSIS OF COMPLEX CASUES RELEASE OF ENZYMES + OXYGEN RADICALS.
this causes necrosis and tissue damage of otherwise healthy cells.
what OTHER ANTIBODY-MEDIATED IMMUNOPATHOLOGY is there?
Direct inactivation
e.g. to Intrinsic factor - B12 deficiency
Indirect inactivation
binding to e.g. hormone results in clearance of AgAb complex
Receptor blockade inactivation
e.g. To AChR in Myasthenia Gravis
describe HYPERSENSITIVITY - TYPE IV
T cell mediated - CD4+ cells (MHC class II)
Activates macrophages which cause tissue damage.
Requires previous exposure to antigen.
